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Autism: It's on the Rise and Linked to Many Health Problems

Learn How Heavy Metals Play a Role

April brings the bliss of warm days, blue skies, emerald trees and apple blossoms. It also ushers in autism awareness month—that time of the year when we turn our attention to the growing epidemic of neurodevelopmental disabilities striking children across America.

Autism rates are rising. One in every forty-one U.S. children—2.41 percent—are afflicted with autism spectrum disorder, according to new data from the U.S. National Institutes of Health (NIH). "The prevalence of autism spectrum disorder is much higher than previously thought," Dr. Wei Bao, lead author of the new study, told CBS News. That's up from 1 in 68 in 2010. But Bao said in the 1970's, only 1 in 1000 children suffered from autism.

Boys are three times more likely to have autism than girls, although now researchers believe that girls' rates are underestimated because the disorder manifests differently in females, and because girls may be more adept at hiding autism. Girls may in fact be suffering in silence. One Australian study of 50 girls from the Bond University Center for Autism Spectrum Disorder in Brisbane, Australia, found that the girls were teased, bullied, often highly anxious, and could develop eating disorders or self-injurious behavior.

Whatever the final count, each child suffering from autism can cost up to $2.4 million over a lifetime, according to a landmark study by the organization Autism Speaks.

Though every child with autism is unique, autism spectrum disorders (ASD) can lead to difficulties with social interaction and communication, anxiety and rage, a tendency to engage in repetitive behaviors (such as rocking, spinning, finger play or fluttering the hands), problems with coordination or balance, an increased need for order, obsessive and narrow preoccupations, and many other symptoms. Some children with autism are nonverbal. Though autism is a neurodevelopmental disorder, one that essentially impacts brain function, it is also associated with many other health issues including poor sleep, digestive distress, bipolar disorder, depression, anxiety, and attention deficit and hyperactivity disorder (ADHD).

This suggests that autism is a body-wide phenomenon affecting the entire immune and nervous systems. In fact, specific immune abnormalities have been found in 30 to 70 percent of autistic children, according to Jane El Dahr, M.D., is the Chief of Pediatric Allergy, Immunology, and Rheumatology at Tulane University Health Sciences Center. Inflammation may be impacting the entire body, including the brain; and some researchers contend that by reducing brain inflammation, the destructive effects of chronic inflammation on the nervous system can be reduced, allowing for improvement in autism.[1]

The Link Between Heavy Metals and Autism

Nobody knows for sure why autism is on the rise, but one good guess supported by abundant research is the increasing toxicity of the modern world. There are over 80,000 chemicals registered for use in the U.S. and every year 2000 more are added—so many that if the Environmental Protection Agency were to test them all it would take centuries. Every day we encounter environmental toxins such as particulates from pollution; heavy metals, pesticides and herbicides in food and water, endocrine disrupters from plastics and other modern chemicals. Chemicals are abundant in everyday items such as computers, smart phones, furniture, cosmetics, cleaners, toys, carpet and more.

Heavy metals appear to play a role in autism spectrum disorders (ASD). One recent study found that mothers of children with ASD have more mercury dental amalgam restorations than mothers of healthy children not suffering from the disorder, suggesting exposure to mercury during pregnancy and possibly breastfeeding.[2] Other studies have correlated mercury toxicity with autism as well.[3] A 2015 study of 100 children with autism and 100 healthy children not suffering from the disorder, found significantly higher levels of mercury, lead and aluminum in the children with autism group.[4] The researchers concluded that "environmental exposure to these toxic metals at key times in development may play a causal role in autism."

In order to determine whether heavy metals are playing a role in symptoms, a whole blood elemental metals analysis is useful and safe. Not only can such tests measure levels of toxic metals along with beneficial nutrients (such as zinc or magnesium), it can measure imbalanced mineral pairs. Such a screen can indicate elevated exposure to toxic metals or imbalances of nutrient metals in whole blood.

The Irreplaceable Role of Glutathione

Our ability to excrete mercury and other toxic metals is dependent on the presence of abundant glutathione, our most important endogenous antioxidant. Glutathione is essential to detoxification, quenching free-radicals, helping modulate immune function, and removing mercury safely from the cell. Glutathione binds to mercury and allows it to be safely carried out of the body into the bile.[5] Biliary secretion of mercury is in large part dependent on the presence and transport of glutathione in the bile.[6] [7]

The severity of autism has indeed been correlated with toxic metals and low glutathione, particularly red blood cell glutathione levels.[8]

Typical oral supplementation of glutathione, however, has low bioavailability while liposomal formulations protect glutathione from being broken down by digestive acids and enzymes, allowing it to be taken up into the cells where it is needed.

Can Chelation Therapy Help Autism?

Numerous studies have documented actual improvements in symptoms of autism after chelation therapy for heavy metals. The word chelation comes from the Greek word chele that means claw of a lobster, thus depicting the concept of holding with a strong grip; molecules that chelate 'claw' metals loose from the cells, and hold onto them. In one study, after six months of chelation therapy, verbal and nonverbal communication of ASD children improved, as did ability to adapt to change and relate to other people.[9] Another impressive study documented significant improvements in autism symptoms after a mere six months of oral chelation therapy.[10]

However, there is a hidden dark side to typical oral and intravenous chelation therapy: toxins such as methylmercury, cadmium, arsenic, can be reabsorbed after excretion into the bile. This reabsorption and redistribution can put stress on the organs of detoxification, such as the liver and kidney, and further damage a delicate system already under stress.

Intestinal Metal Detox for Autism?

Thiolated resins are unique substances with metal-binding groups that tightly bind metals like mercury, and were first used in the 1970s to address a mass methylmercury poisoning incident in Iraq. Grain treated with a methylmercury fungicide that was never meant for human consumption was imported into Iraq as seed grain.[11] Tragically, the poison grain was eating by rural Iraqis, and thousands died while many more were left disabled. It was found that thiolated resins could significantly reduce the half-life of the methylmercury, improving some of the devastating symptoms.[12],[13],[14]Today, thiol-functionalized silica can safely intercept mercury and other metals in the gut, binding them tightly while avoiding redistribution and subsequent toxicity to the liver and kidneys. Because this type of binder acts locally in the gastrointestinal tract, it can allow metals to safely drain at a natural rate.

Though autism spectrum disorders can be challenging and difficult, the good news is that there are many approaches to improving symptoms. In fact, as children grow into adults, autism naturally tends to improve. Autistic children can grow into inspiring and remarkable adults with unique gifts. One such person is Temple Grandin, who holds a PhD in animal science, teaches at Colorado State University, runs her own business, and gives talks around the world. First immortalized in a profile for The New Yorker Magazine by the late Oliver Sacks, she described herself in her own biography, Emergence, as unable to tolerate normal contact, living in a world of excruciating and heightened sensation, subject to violent rages, still without language by age three, yet able to sit on the beach sifting sand in fascination for hours. Today, as autism awareness grows, there is increasing acceptance of human neurodiversity, and hope for families dealing with autism spectrum disorders.


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https://www.quicksilverscientific.com/resource-center/the-blog/mercury-a-potent-toxin-with-widespread-health-impact

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[1] Rodriguez JI, Kern JK. Evidence of microglial activation in autism and its possible role in brain underconnectivity. Neuron Glia Biol. 2011 May;7(2-4):205-13. View Full Paper

[2] Khaled, E.M., Meguid, N.A., Bjørklund, G. et al. Metab Brain Dis (2016) 31: 1419. View Abstract

[3] Kern JK, Geier DA, Adams JB, Toxicity biomarkers in autism spectrum disorder: a blinded study of urinary porphyrins. ediatr Int. 2011 Apr;53(2):147-53. View Abstract

[4] Mohamed F, Zaky EA, El-Sayed AB Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism. Behav Neurol. 2015. View Abstract

[5] Ballatori N, Clarkson TW. Biliary secretion of glutathione and of glutathione-metal complexes. Fundam Appl Toxicol. 1985;5:816–31. doi: 10.1016/0272-0590(85)90165-4. View Abstract

[6] Ballatori N, Clarkson TW. Dependence of biliary secretion of inorganic mercury on the biliary transport of glutathione. Biochem Pharmacol. 1984;33:1093–8. doi: 10.1016/0006-2952(84)90519-7. View Abstract

[7] ArticlePubReaderPDF–728KCitation

Select item 3317707

7. Jozefczak M, Remans T, Vangronsveld J et al. Glutathione Is a Key Player in Metal-Induced Oxidative Stress Defenses. Int J Mol Sci. 2012; 13(3): 3145–3175. View Full Paper

[8] Adams JB, Baral M, Geis E The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol. 2009:532-640.

[9] Blaucok-Busch E, Amin OR, Dessoki HH et al. Efficacy of DMSA Therapy in a Sample of Arab Children with Autistic Spectrum Disorder. Maedica (Buchar). 2012 Sep;7(3):214-21. View Abstract

[10] Adams JB, Baral M, Geis E et al Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A--medical results. BMC Clin Pharmacol. 2009 Oct 23;9:16. View Full Paper

[11] Bakir F, Damluji SF, Amin-Zaki L. Methylmercury poisoning in Iraq. Science. 1973 Jul 20;181(4096):230-41. View Abstract

[12] Saha B, Iglesias M, Dimming IW, Streat M. Sorption of trace heavy metals by thiol containing chelating resins. Solv Extract Ion Exch. 2000 Jan 1;18(1):133-67.

[13] Sangvanich T, Morry J, Fox C, et al. Novel oral detoxification of mercury, cadmium, and lead with thiol-modified nanoporous silica. ACS Appl Mater Interfaces. 2014 Apr 23;6(8):5483-93. View Abstract

[14] Clarkson TW, Small H, Norseth T. Excretion and Absorption of Methyl Mercury After Polythiol Resin Treatment. Arch Enviro Health: Int J. 1973 Apr 1;26(4):173-6. View Abstract 

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Four Essential Tips for Boosting Your Energy Naturally

Worn Out, Weary, Sapped & Spent

Remember the immense and boundless energy of childhood? That full-throttle-jump-on-the-bed-run-in-circles-and-yell-at-the-top-of-your-lungs Vesuvius of energy? Delight and curiosity about everything, and then the sweet plunge into deep, restorative sleep at nap-time or nighttime…waking up with nary an ache or pain…

If that kind of energy feels long gone—if you drag through the day depending on red bull, coke, and various energy products—you may need a different kind of reboot. Here are four essential and effective tips for a natural and sustained energy boost.

Make Sure to Get Restorative Sleep

Do you have an unpaid sleep debt? Sleep is a foundation of health and a source of abundant energy. Chronic lack of sleep raises risk of many health problems, including heart disease, diabetes, obesity, depression and anxiety.[1]

Yet sleep is the first thing people cut down on when work and family pressures mount. Nearly a third of Americans are sleep deprived. That has serious consequences beyond being tired. Many inflammatory molecules and hormones are impacted by sleep.[2],[3]

Meditation, yoga and guided relaxation have been proven to improve sleep, and many youtube videos, tapes and apps are available.[4] But that may not be enough when you're wired and tired. One effective sleep re-set comes in the form of supplemental melatonin. Melatonin is a natural hormone that regulates the body's circadian rhythm—it is suppressed by bright light or daylight, and surges as night falls. Melatonin levels begin increasing in the late evening, reaching their peak between 2:00 and 4:00 a.m.[5] When the body's sleep cycle becomes dysregulated, supplemental melatonin can help restore normal, healthy sleep patterns.[6] Night time melatonin levels are reduced in primary insomnia.[7] Normal melatonin secretion also declines with age.

Melatonin offers additional benefits beyond sleep, because it can function as a potent antioxidant. It can, for instance, reduce oxidative stress in high-intensity athletes during training.[8]

When standard over-the-counter supplements containing melatonin are taken, only 15% of the melatonin is absorbed. A liquid liposomal formulation may offer more rapid distribution and better uptake to the blood stream. In addition, for those highly sensitive to melatonin, a liquid format can be easily titrated to a very low dose.

A good night's deep sleep literally helps our brain cells replenish the energy stores they spent during the day. Sleep recharges the brain and the body.

Exercise Regularly

There's a funny paradox to energy—you have to spend it to get it. One way of combating exhaustion is regular exercise. Consistent aerobic exercise—even as little as 20 minutes three times a week—can boost energy levels in fatigued individuals. In one study, low intensity or moderate intensity exercise increased energy levels 20% after six weeks, and dropped feelings of fatigue by as much as 65%, and the researchers suggest that exercise acts directly on the central nervous system to increase energy and reduce fatigue.[9]

Even moderate exercise, however, can deplete vitamins and minerals—often through sweating. A broad-spectrum vitamin and mineral supplement can be the best multivitamin for energy. It will include a panoply of necessary nutrients to offer a natural energy boost. For instance, B complex vitamins are important for energy metabolism in the body, and athletes with low levels perform more poorly during high-intensity exercise. Adequate levels of calcium and vitamin D are necessary for skeletal strength and even for skeletal muscle function, which is important for high-impact exercise.

Calm the Mind and Soothe Anxiety

Chronic anxiety and worry are consequences of the so-called "monkey mind", as it's called in Buddhist thought—a mind seemingly filled with innumerable drunken monkeys jumping, chattering, screeching endlessly. It's hard not to worry in today's high-octane, always-connected, ever-demanding world.

Both anxiety and worry are known to deplete energy levels and lead to a kind of wired-and-tired exhaustion. Excessive worry will shift you into a constant fight-or-flight state, triggering your sympathetic nervous system to release stress hormones such as cortisol. Chronically elevated cortisol levels raise blood sugar and triglycerides to meet the demands of increased stress. Chronic fatigue can be one outcome. To calm the overactive monkey mind, well-known supplements such as Gamma-aminobutyric acid (GABA) and L-theanine can offer natural assistance in achieving relaxation. Some individuals suffering from chronic anxiety and insomnia do not naturally make sufficient levels of GABA. In turn, L-theanine, an amino acid found in green tea. L-theanine competes in the brain with the most important excitatory neurotransmitter, glutamate. By inhibiting the action of glutamate, it produces a calm, relaxed state.[10]

Turn to Adaptogenic Herbs

Adaptogenic herbs are healing plants that bring the body back into balance, especially its ability to handle stress. These healing botanicals help your entire body cope with fatigue, increasing non-specific resistance to stress. In the words of herbalist Dan Moriarty, founder of Sun Horse Energy, "They balance physiology at a cellular level for stress accommodation, and help the body achieve homeostasis. Think of a violin. If tuned too tightly the stress will break the strings. If tuned too loosely, the strings will be floppy. Either way, you won't have music. Adaptogens tune your body to the right pitch and tension." Adaptogens with a long record of safety, that have been used for hundreds or thousands of years, include Schisandra berry,Ginseng, Chinese licorice root, Lycium (the goji berry), and many others.


[1] Fernandez-Mendoza J, Vgontzas AN Insomnia and its impact on physical and mental health. Curr Psychiatry Rep. 2013 Dec;15(12):418. View Full Paper

[2] Kim TW, Jeong JH, Hong SC. The impact of sleep and circadian disturbance on hormones and metabolism. Int J Endocrinol. 2015;2015:591729. View Full Paper

[3] Meier-Ewert HK, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004 Feb 18;43(4):678-83. View Abstract

[4] Neuendorf R, Wahbeh H, Chamine I et al. The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review.

Evid Based Complement Alternat Med. 2015;2015:902708. View Abstract

[5]Peuhkuri K, Sihvol N, Korpel R Dietary factors and fluctuating levels of melatonin Food Nutr Res. 2012; 56. View Full Paper

[6] Sack RL. Use of melatonin for sleep and circadian rhythm disorders. Review article.Ann Med. 1998. View Abstract

[7] Riemann D, Klein T, Rodenbeck A, et al. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res. 2002; 113: 17-27. View Abstract

[8] Ortiz-Franco M, et al. Effect of Melatonin Supplementation on Antioxidant Status and DNA Damage in High Intensity Trained Athletes.

Randomized controlled trial. Int J Sports Med. 2017 View Abstract

[9] Puetz TW, Flowers SS, O'Connor PJ. A randomized controlled trial of the effect of aerobic exercise training on feelings of energy and fatigue in sedentary young adults with persistent fatigue. Psychother Psychosom. 2008;77(3):167-74. View Abstract

[10] Nathan PJ, Lu K, Gray M, et al. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21-30. View Abstract 

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The Mother of All Antioxidants

How Glutathione Promotes Health, Energy and Longevity

It seems like everywhere you turn today you hear about the astonishing health benefits of antioxidants, phytonutrients, and nutraceuticals. From the eye-catching news that an antioxidant in beets might stave off Alzheimer's disease, to man-made super-antioxidants that can prevent cells from dying, to the good news that antioxidant-rich foods like dark chocolate, tea, walnuts, prunes, blueberries, strawberries, hazelnuts and more can lower the risk of Type 2 diabetes, it appears indisputable that the phytonutrients packed into plants are good for us.

It's hard to deny the benefits of antioxidants. We just need to eat right, right?

It's not quite that simple. Even if we consciously eat as colorful and healthy a diet as we can, we might need to proactively boost our defenses with antioxidant supplements.The nutrient, vitamin and mineral levels in food have been steadily declining for many decades.[1] At the same time, the prevalence of toxins and chemicals has soared: there are now more than 80,000 chemicals in use in the United States, many of which have never been tested and may be harmful to health. They lurk in everything from furniture to household cleaners, cosmetics, cars, toys, water and food.

Comprehensive antioxidant protection entails promoting our own internal antioxidant defenses. In particular, this means protecting and replenishing levels of our most critical endogenous antioxidants, the versatile metabolic gems that our own body makes all the time.

The Free Radical Theory of Aging and Health

Sixty years ago a brilliant cardiologist and chemist named Denham Harman came up with the free radical theory of aging, and it forever changed the way we think about health and longevity.[2] He proposed that free radicals, generated by normal cellular metabolism as well as by toxins from the environment, are highly reactive and damaging, and contribute to poor health and aging. Later, in 1972, Harman extended his theory and proposed that mitochondria, the energy powerhouses inside our cells, generate (and are damaged by) the free radicals they create when they produce energy. Energy is like a metabolic fire, and it can singe us.[3],[4]

In the simplest terms, the theory suggests that free radicals generate what is known as "oxidative stress", and this needs to be "quenched" or repaired by antioxidants. When more antioxidant is made available, cells can safely undertake a higher level of metabolic activity.

Science has since confirmed that aging, and the degenerative diseases associated with aging, are indeed in part due to our decreasing ability to defend ourselves against free radical damage and oxidative stress.[5] But nature is wise: our bodies have evolved sophisticated, natural detoxification systems that work on a deep cellular level to protect us and quench the fire of free radicals.[6] Every day our detoxification systems work heroically to fend off toxic insults, but the marvels our bodies perform are rarely even thought about until our system becomes overwhelmed and breaks down. Efficient detoxification depends on a series of seamless reactions that bind toxins to shuttle damaging free radical molecules out of the body.

Glutathione, the Mother of All Antioxidants, to the Rescue

Our quintessential antioxidant defense is the glutathione system, which includes glutathione itself, along with the enzymes and other proteins that enable glutathione to do its work. Glutathione is actually a very simple molecule—our body makes it from three amino acids—cysteine, glycine and glutamine. Yet it is incredibly versatile—a universal toxin-binder. Glutathione is extremely important for maintaining intracellular health.

There have been more than 94,000 peer-review medical articles exploring glutathione and its impact on health. The entire glutathione system contains multiple molecules and enzymes that function to quench oxidative stress, repair damaged proteins, and detoxify or remove both internal and external toxins. Glutathione S-Transferase (GST) is a critical enzyme that catalyzes the transfer of a metal onto the glutathione so it can be safely bound and excreted.A well-functioning glutathione system also contains proteins and enzymes that can safely bind and move toxins and heavy metals out of the body.[7] Glutathione is present in every single cell of our bodies, and concentrations are particularly high in the liver, where glutathione binds to toxins to ensure they're removed or excreted.

Glutathione not only scavenges free radicals, it helps regenerate other critical antioxidants, such as Vitamin C and Vitamin E.[8] It helps regulate immune responses, and is critically important in inflammatory conditions.[9] It regulates molecules that play a key part in inflammation, such as NF-κB, molecules called "inflammasomes", immune cells involved in fighting infections such as T cells and phagocytes, and more.[10] It plays a role in regulating autoimmune diseases, where there is an increased level of oxidative stress associated with immune activation and inflammation.[11]

Glutathione plays a key role in defending us from mercury toxicity. Mercury is the most harmful naturally occurring substance we know of. It is a far more powerful biological toxin than either lead or arsenic. We can be exposed to mercury through auto pollution, consumption of fish, and Hypersensitivity to low-dose mercury exposure from dental amalgam fillings has been demonstrated, with exquisite sensitivity to amalgam-derived Hg in sensitized individuals.[12]

How to Support Your Glutathione Levels

Glutathione is continually recycled in the body — but all too often the system is overwhelmed by too many toxins or stressors. Glutathione production also declines with age. The 'mother' of all antioxidants can be severely depleted during serious illness. According to Jeremy Appleton, ND, Chairman of the Department of Nutrition at the National College of Naturopathic Medicine in Portland, Ore., glutathione is inevitably depleted in those who are severely ill.

One might think the easy answer is to simply supplement with glutathione, but oral supplementation is unreliable, since glutathione is degraded by stomach acids and enzymes in the GI tract. Glutathione production can be supported by other supplements, including Vitamins C and E, selenium, alpha-lipoic acid, n-acetyl cysteine, B vitamins, and key botanicals such as milk thistle.

Liposomal delivery systems can protect glutathione from breakdown in the digestive system. In addition to greatly improving bioavailability, the liposomal delivery format enables intracellular delivery of glutathione. In cell cultures, liposomal glutathione has been demonstrated to be 100 times more efficiency for intracellular delivery than non-liposomal glutathione.[13]


[1] Davis DR, Epp MD, Riordan HD Changes in USDA food composition data for 43 garden crops, 1950 to 1999. J Am Coll Nutr. 2004 Dec;23(6):669-82. View Abstract

[2] Viña J, Borras C, Abdelaziz K. The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging. Antioxid Redox Signal. 2013 Sep 10; 19(8): 779–787. View Full Paper

[3] Harman, D (1956). Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology 11 (3): 298–300. View Abstract

[4] Harman, D (1972). The biologic clock: the mitochondria? Journal of the American Geriatrics Society 20 (4): 145–147. View Abstract

[5] Matés JM, Pérez-Gómez C, Núñez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem. 1999 Nov;32(8):595-603 View Abstract

[6] McCall MR, Frei B Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med. 1999 Apr; 26(7-8):1034-53 View Abstract

[7] Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. View Abstract

[8]Dixon DP, Sgteel PG, Edwards R. Roles for glutathione transferases in antioxidant recycling. Plant Signal Behav. 2011 Aug; 6(8): 1223–1227. View Abstract

[9] Rahman, W. MacNee, Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches, Free Radic. Biol. Med. 28 (9) (2000) 1405–1420. View Abstract

[10] M. Suthanthiran, M.E. Anderson, V.K. Sharma, A. Meister, Glutathione regulates activation-dependent DNA-synthesis in highly purified normal human lymphocytes-T stimulated via the Cd2-antigen and Cd3-antigen, Proc. Natl. Acad. Sci. USA 87 (9) (1990) 3343–3347. View Abstract

[11] Perricone C, et al. Glutathione: a key player in autoimmunity. Autoimmun Rev. 2009 Jul;8(8):697-701.

[12] Rocha JBT, Aschner M, Dórea JG Mercury Toxiity. J Biomed Biotechnol. 2012; 2012: 831890 View Full Paper

[13] Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010 Oct;35(10):1575-87. View Abstract 

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Boost Brain Health and Gain Your Cognitive Edge

Be Smart About Brain Health: Know the Top Phytonutrients and Supplements for Mental Clarity

Most of us know about the foods and nutrients that help protect our hearts—from fish high in Omega 3 fatty acids, to generous helpings of leafy greens, brightly colored vegetables and fruits, and particularly the lavish red, purple and black berries and grapes rich in antioxidants like anthocyanins and resveratrol.[1]

What we may not know is that the very same nutrients, vitamins and minerals that are good for the heart are also great for the brain. If we want to keep our memory sharp, improve our ability to focus, banish brain fog, and increase mental acuity, we must consider the critical role of phytonutrients, vitamins and minerals.[2]

"Research over the past 5 years has provided exciting evidence for the influence of dietary factors on specific molecular systems and mechanisms that maintain mental function," writes integrative biologist, Fernando Gomez-Pinilla, a UCLA professor of neurosurgery. Gomez-Pinilla analyzed over 160 studies on how food affects the brain.[3] In fact, Gomez-Pinilla believes that "dietary management may become a natural, non-invasive, and cost-effective therapeutic solution to maintaining a healthy brain and a strong defense system against some of the most common disorders in the world. In addition… it is likely that the effects of lifestyle on the brain have the capacity to influence neurological health of future generations."

And yet, according to the latest research, Americans are eating nowhere near the amount of healthy fruits and vegetables they need to optimize health. The 2010 Dietary Guidelines for Americans recommend that most people eat at least 9 servings of fruits and vegetables per day, 4 servings of fruits and 5 servings of vegetables.[4] Yet a study found that the average consumption of fruits and vegetables in the United States is only 3.6 servings of fruits and vegetables (1.4 servings of fruits and 2.2 servings of vegetables) per person per day.[5]


Highlights of The Latest Research on Diet and Brain Health

Here are some highlights of the latest research on phytonutrients, vitamins and minerals and brain function.

  • Scientists recently discovered that the DASH diet (Dietary Approaches to Stop Hypertension) is not only good for the heart, it can reduce depression. The diet, based on research sponsored by the National Institutes of Health, emphasizes fruits, vegetables, low fat or nonfat dairy, whole grains, lean meats, fish, poultry, nuts and beans.

  • Berries, so richly colored, contain phytonutrients that can slow cognitive decline. One recent study, from Brigham and Women's Hospital and Harvard Medical School, followed 16,000 older women over 15 years, and found that those who ate at least a half cup of blueberries or a full cup of strawberries once a week delayed memory decline by 2.5 years.[6] In particular, antioxidants in blueberries such as the anthocyanins cross the blood-brain barrier, and increase levels of brain-derived neurotrophic factor (BDNF), which helps promote new nerve connections correlated with healthy cognitive function.[7] BDNF levels decline with age

  • Both nuts and berries can forestall cognitive decline. The synergy of the nutrients and in nuts and berries can "alter cognitive performance in humans, perhaps forestalling or reversing the effects of neurodegeneration in aging."[8]

  • Omega 3's, found in fish, can keep mental focus sharp. Consuming omega-3 rich fish just once a week is linked to a 10% per year slower rate of cognitive decline among older adults. And individuals who consume fish at least once per week have a 60% lower risk of Alzheimer's disease. Oily fish such as salmon, herring and sardines are rich in Omega 3 fatty acids but lower in mercury and PCB's.[9]

  • A cornucopia of leafy greens can keep your brain humming along in tip-top shape. Researchers at the Rush Institute for Healthy Aging and the MIND Center for Brain Health looked at nearly a thousand healthy adults and discovered that those who ate merely a single serving of leafy greens per day appeared 11 years younger in terms of their cognitive health compared with those who rarely consumed leafy green veggies.[10]

Beyond Diet: Supplements for Energy and Focus

As important as a healthy diet is to longevity, cardiovascular health and cognitive function, many people want an extra edge beyond what diet might provide. What specialized nutrients are associated with enhanced memory, mood, creativity, and ability to pay attention? Are there specific vitamins for memory, or brain health supplements for mental focus?

First and foremost, a complete vitamin, mineral and phytonutrient supplement can offer broad spectrum support, ensuring that even if there are gaps in the diet, or in digestive capacity, nutrient intake will be more than adequate. From infants to teens to the elderly, nutrient and micronutrient deficiencies are not uncommon.[11],[12] Finding one supplement that blends state-of-the-art nutraceuticals and super-nutrients, along with adaptogenic herbs and molecules that support mitochondrial function, can help protect cognitive health and function, as well as boost the energy required for sustained concentration. Certain adaptogenic herbs are known for their ability to protect and enhance cognition; these include ginseng, which has has shown remarkable benefits for cognition and alertness.[13]

A generous supply of phospholipids is also important. Lipids might be called the liquid gold of your brain: about 60% of your entire brain is composed of fats that keep cell membranes flexible and structurally sound. Brain cells are especially rich in a lipid called phosphatidylcholine (PC). A pure source of PC can be beneficial for cognition.[14]

Neuroprotective antioxidants can boost cognitive function and support neuronal function. These include Coenzyme Q10 (CoQ10), which not only supports the cardiovascular system, but the brain and nervous system.[15] Melatonin is another neuroprotective antioxidant that restores healthy sleep cycles and supports healthy mood and cognitive function. Molecular hydrogen is a universal and well-tolerated antioxidant. Hydrogen is one of nature's purest and simplest antioxidants, created by the natural reaction of magnesium with water. Molecular hydrogen is easily able to pass through cellular membranes and the blood brain barrier.[16]

Trace mineral deficiencies are common, even in well-nourished individuals.[17] Adding a good source of trace minerals, such as that provided by seawater harvested from protected plankton blooms, can offer biologically important support to the immune system, nervous system, and neurotransmitters.


You may also be interested in:
https://www.quicksilverscientific.com/resource-center/the-blog/stress-support-101-gaba-and-l-theanine-the-fast-acting-stress-and-anxiety-antidote


[1] Nichols PD, McManus A, Krail Ket al. Recent advances in omega-3: Health Benefits, Sources, Products and Bioavailability. Nutrients. 2014 Sep 16;6(9): 3727-33. View Full Paper

[2] Liu RH. Health benefits of fruits and vegetables are from additive and synergistic combination of phytochemicals. Am J Clin Nutr.2003;78:517S–20S View Abstract

[3] Gomez-Pinilla F. Diet and cognition: interplay between cell metabolism and neuronal plasticity. Curr Opin Clin Nutr Metab Care. 2014 Nov 1. View Full Paper

Published in final edited form as: Curr Opin Clin Nutr Metab Care. 2013 Nov; 16(6): 726–733

[4] USDA. Dietary Guidelines for Americans 2010. USDA Human Nutrition Information Service, Hyattsville, MD. 2010.

[5] PBH, Produce for Better Health Foundation. State of the plate: 2010 Study on American consumption of fruits and vegetables. 2010.

[6] Devore E, Kang JH, Breteler MB Dietary Intakes of Berries and Flavonoids in Relation to Cognitive Decline. Ann Neur 2012 Vol 72(1) pp.135-144 View Full Paper

[7] Williams CM, El Mohsen MA, Vauzour D Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med. 2008 Aug 1;45(3):295-305. View Abstract

[8] Pribis P, Shukitt-Hale B. Cognition: the new frontier for nuts and berries. Am J Clin Nutr. 2014 Jul;100 Suppl 1:347S-52S View Abstract

[9] Okyere H, Voegborlo RB, Agorku SE. Human exposure to mercury, lead and cadmium through consumption of canned mackerel, tuna, pilchard and sardine. Food Chem. 2015 Jul 15;179:331-5 View Abstract

[10] Morris MC, Wang Y, Barnes LL. Nutrients and bioactives in green leafy vegetables and cognitive decline. Neurology Jan 2018. 90 (3) e214-e222 View Abstract

[11] Weeden A, Remig V, Holcomb CA Vitamin and mineral supplements have a nutritionally significant impact on micronutrient intakes of older adults attending senior centers. J Nutr Elder. 2010 Apr;29(2):241-54

[12] Stang J, Story MT, Harnack L, Relationships between vitamin and mineral supplement use, dietary intake, and dietary adequacy among adolescents. J Amer Diet Assoc. 2000 Aug;100(8):905-10. View Abstract

[13]Smith I, Williamson EM, Putnam S et al. Effects and mechanisms of ginseng and ginsenosides on cognition. Nutr Rev. 2014 May;72(5):319-33 View Abstract

[14] Rondanelli M, Opizzi A, Faliva Met al. Effects of a diet integration with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan in elderly patients suffering from mild cognitive impairment. Nutr Neurosci. 2012 Mar;15(2):46-54 View Abstract

[15] Sandhir R, Sethi N, Aggarwal A, Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause. Neurochem Int. 2014 Jul;74:16-2 View Abstract

[16] Ostojic SM. Molecular hydrogen: An inert gas turns clinically effective. Ann Med. 2015 Jun;47(4):301-4 View Abstract

[17] Dreosti IE. Trace Elements in Nutrition. Med J Aust. 1980 Aug 9;2(3):117-23. View Abstract 

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Why Liposomal Supplements Are the Next Wave of Good Nutrition:

Breakthrough Liposomal Technology Uses NanoScale Science to Nourish Cells

We live in a time of extraordinary food abundance—just walk into any supermarket and you'll find a veritable Garden of Eden, with fresh fruits, greens and vegetables from around the globe, as well as freshly baked whole grain breads, wild-caught fish, and a panoply of yogurts crafted from dairy or nut milks. We also luxuriate in the cheapest food available in history--in the 1930s, Americans spent a quarter of our disposable income on food while today we spend under a tenth. And our choice of healthy foods has expanded—there has been a 27% increase in consumption of fresh fruit and a 21% increase in consumption fresh vegetables from 1970 to 2010. We're eating more broccoli, cauliflower, tomatoes, onions, apples, bananas, and grapes.[1]

Yet in spite of all this bounty, we are often nutrient-deficient-- over 40 percent of adults have dietary intakes of vitamin A, C, D and E, calcium and magnesium below the average requirement for their age and gender. And these statistics do not even take into account the important antioxidants that keep us healthy, such as glutathione, Coenzyme Q10, and resveratrol.

Are standard, oral multivitamin supplements the answer? Nearly two out of three adults in America think so, since they take vitamin, mineral or herbal supplements. But the typical oral supplement may not deliver its full therapeutic potential. Enzymes in the stomach and gastrointestinal tract can degrade oral supplements. On their own, potent antioxidants may not be able to efficiently cross cell membranes. For instance, numerous flavonoids that show potent antioxidant activity in vitro in the laboratory, achieve only very low concentrations in the blood after oral consumption.[2] One of the most storied antioxidants, resveratrol, associated with longer lifespan, lower risk of heart disease, and lower levels of inflammation, is poorly absorbed in oral supplement form.[3] CoQ10 supplementation can be challenging: as a lipid-loving (lipophilic) molecule, CoQ10 is best digested with fats and suffers poor absorption in water. According to William Judy, founder of SIBR Research, less than 1 percent of simple CoQ10 powder is absorbed. Similarly, typical oral delivery of glutathione, the most potent intracellular antioxidant our bodies make, is greatly inhibited by its breakdown in the stomach. In one study of 40 healthy adults, supplementation with oral glutathione had no effect on blood levels of the antioxidant, and no significant changes were observed in biomarkers of oxidative stress.[4]

In order to offer health benefits, vitamins and minerals need to reach the target tissue of action. Bioavailability is key for supplements and functional foods and related health claims.[5] Many factors affect bioavailability—including digestive problems, low stomach acid, low uptake of a nutrient. In addition, supplements themselves vary in the amounts of vitamins, minerals and antioxidants they offer—some offer more than the recommended daily amount, some less. Products are sold in many different forms (powders, liquids, tablets, capsules, chewables, and gummy candies), all of which result in variable amounts. According to one study:"Many ingredients in adult MVMs had mean percentage differences that were above label claims and were highly variable between individual products in a representative sampling of the US market."[6]

Enter Liposomal Delivery Systems: Taking a Cue From Nature

The starburst of complex life we see all around us every day began with single cells 3.8 billion years ago—simple, free floating bacteria that were one of life's earliest and most ingenious inventions.

Those simple cells, just like our cells today, possessed a membrane composed of a lipid bilayer. The membrane performed all kinds of extraordinary feats: not only did it protect the inside of the cell, it allowed nutrients to pass through and wastes and toxins to be expelled. And it evolved the capacity to carry electricity, and to store energy as ATP molecules. Mostly composed of phospholipids, the cell membrane was not only protective, it was highly active.

Fast forward to the 1960's, when smart scientists began to experiment with liposomal delivery of medications.[7] Liposomes are tiny phospholipid bubbles with a bilayer structure very similar to that of our cell membranes. Liposomes turn out to be ideal carriers for therapeutic molecules, highly effective at delivering nutrients directly into the cell. Liposomes are highly biocompatible, and they are capable of holding either water-soluble or fat-soluble molecules. Their size, electrical charge, and surfaces can be tweaked in a lab. Liposomal delivery systems have been used successfully in clinical trials for an astonishing variety of therapeutics—delivering everything from anticancer to antifungal, anti-inflammatory and antibiotic medications as well as sophisticated gene medicines and vaccines.[8]

Liposomal supplements offer a nutritional delivery system with rapid uptake and effective delivery into the cells. Liposomes are highly efficient in terms of facilitating antioxidant delivery, and because they are prepared from natural phospholipids, they are biocompatible and nontoxic. Liposomal delivery systems are becoming increasingly popular for nutraceuticals because they protect these therapeutic molecules from breakdown in the digestive system. In cell culture studies, liposomes can increase intracellular delivery 100-fold over non-liposomal delivery.[9]

Liposomal nutraceuticals and health supplements offer many benefits over typical oral formulations. These include:

  • High bioavailability and absorption
  • Protecting nutrients against the harsh environment of the GI tract
  • Increasing oral uptake in the mouth via the mucosa
  • Increased uptake into cells
  • Liposomes can be formulated to hold both water-soluble and fat
  • The liquid format of liposomes may be more compatible for those who have trouble swallowing large tablets

Size Matters—And Small is Better

Not all liposomes are alike. Smaller liposomes are far likelier to persist and deliver their therapeutic molecules. These smaller liposomes offer the most rapid uptake and are less easily scavenged and cleared by our immune systems. Liposomal delivery systems usually fall into three categories:

  • MLV (Multi-Lamellar Vesicles) are about 500-5000nm (nanomolars) and have more than one bilayer.
  • LUV (Large Unilamellar Vesicles) are ~200-800nm with a single bilayer.
  • SUV (Small Unilamellar Vesicles) range from 20-150nm and have a long circulation half-life and better cellular delivery than larger particles.

The ultra-small, unilamellar liposomes are created with sophisticated high-shear equipment. The result is tightly controlled, tiny vesicles that are actually the size of nanoparticles. The smallest, unilamellar (one layer) liposomes circulate in the blood the longest and are most stable. Cellular uptake is markedly increased—as much as nine times--as liposome size decreases from 236nm down to 97nm. At the smallest size (64 nm), uptake is 34 times higher.[10]

Lipid nanoparticle delivery systems have been shown to dramatically improve absorption of many natural substances such as DIM (Diindolylmethane) and milk thistle, which are known to have poor bioavailability on their own.[11] Nanoparticle liposomes are ideal for the delivery of numerous molecules, especially when longer term effects are desirable.

A Closer Look at Liposomal Supplements

Glutathione benefits dramatically from liposomal formulations. Liposomal glutathione can restore immune system responses.[12] Liposomal technology is also superbly suited to a water-soluble antioxidant like Vitamin C, increasing blood levels over standard oral supplements.[13] Coenzyme Q10, our most potent lipid-soluble antioxidant, also benefits from liposomal formulation. High-quality complex mixtures of pure compounds and botanicals compounded into liposomal formulations offer superb efficacy and ease of use.[14]

Although many liposomal products claim improved bioavailability, few are able to truly deliver the increased absorption these formulations can offer. With sophisticated, well-designed, lipid nanoparticle delivery systems, the bioavailability, absorption and cellular uptake of many natural substances can be dramatically enhanced. And as a side benefit, phosphatidylcholine, which composes the membrane of lipid nanoparticles, also nourishes the lipid membranes of cells, providing phospholipids that can be used for cellular repair.


[1] Sturm R, An R. Obesity and economic environments. CA Cancer J Clin. 2014 Sep-Oct;64(5):337-50. View Full Paper

[2] Suntres, ZE. Liposomal Antioxidants for Protection Against Oxidant-Induced Damage. J Toxicol. 2011; 2011: 152474 View Full Paper

[3] Gambini J, . Inglés M, Olaso G et al. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans Oxid Med Cell Longev. 2015; 2015: 837042

[4]Allen J, Bradley RD. Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers.J Altern Complement Med. 2011 Sep; 17(9): 827–833. View Full Paper

[5] Rein MJ, Renouf M, Cruz-Hernandez C et al. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. Br J Clin Pharmacol. 2013 Mar; 75(3): 588–602. View Full Paper

[6] Andrews KW, Roseland JM, Gusev PA. Analytical ingredient content and variability of adult multivitamin/mineral products: national estimates for the Dietary Supplement Ingredient Database Am J Clin Nutr. 2017 Feb; 105(2): 526–539. View Full Paper

[7] D. Bangham, M.M. Standish, J.C. Watkins, Diffusion of univalent ions across the lamellae of swollen phospholipids, J. Mol. Biol. 13 (1965) 238–252. View Abstract

[8] Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013 Jan;65(1):36-48. View Abstract

[9] Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010 Oct;35(10):1575-87 View Abstract

[10] Hood RR, Andar A, Omiatek DM, Verrland WN, Swaan PW, DeVoe DL. Pharmacy-on-a-Chip: Microfluidic Synthesis of Pegylated and Folate Receptor-targeted Liposomes for Drug Delivery. 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 28 - November 1, 2012, Okinawa, Japan

[11] Yang KY, Hwang du H, Yousaf AM, et al. Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation. Int J Nanomedicine. 2013;8:3333-43

[12] Ly J, Lagman M, Saing T et al. Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals J Interferon Cytokine Res. 2015 Nov 1; 35(11): 875–887. View Full Paper

[13] Davis JL, Paris HL, Beals JW. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia–Reperfusion Injury Nutr Metab Insights. 2016; 9: 25–30. View Full Paper

[14] Shade, CW. Liposomes as Advanced Delivery Systems for Nutraceuticals. Integr Med (Encinitas) 2016 Mar; 15(1): 33–36. View Full Paper 

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Pamper Your Gut and Heal Your Intestines With Beneficial Soluble Fiber

When we think about our immune system, we don't instantly zoom in on the gut. And yet an astonishing eighty percent of the immune system actually lives in our GI tract. For most of those immune cells, it's the intestinal wall that is home sweet home. Many of them spend their entire lives secreting huge quantities of immune antibodies into the gut. Those antibodies help protect us from pathogens and infection.

Our gut is under stress today because of our industrialized food supply, which beckons us daily with seemingly irresistible processed, high-sugar, high-fat, low-fiber foods. None of those 'foods' feed our gut flora the way a diet rich in healthy whole grains, fruits and vegetables can. When our gut flora is balanced, our gut's immune system functions optimally.

Take fiber, for instance. It is essential to gut health and provides food for our friendly gut bacteria. The average adult consumes about 15 grams of fiber per day. Yet optimal amounts for good gut health are two to three times higher—25 grams of fiber per day for women, and 38 grams per day for men, according to the Institute of Medicine. This nourishing fiber is essentially indigestible to us, but is a perfect meal for our friendly microbes.

A Highly Beneficial Soluble Fiber

One versatile and well-tolerated, gentle fiber comes in the form of acacia gum. This natural gum, derived from the sap of the acacia tree, has been used in medicine and as a baking ingredient for many centuries. Acacia gum is packed with soluble fiber—95%--and that fiber offers unique benefits. [1]

Daily consumption of soluble fiber has been shown to increase levels of beneficial gut bacteria, support healthy cholesterol levels, soothe sensitive stomachs, help normalize gut transit time and both ease constipation and yet improve diarrhea, and have a beneficial effect on blood sugar, blood pressure and weight.[2],[3],[4] Many of these benefits are correlated with the ability of the soluble fiber, such as acacia, to attract water and form a soothing gel. (In contrast, insoluble fiber, such as that found in bran or psyllium, provides bulk to the waste in the digestive tract and helps regulate bowel function).

Acacia is also very well tolerated, even by sensitive individuals. In a 2003 study, the gum did not trigger adverse gastrointestinal symptoms such as bloating, gas and diarrhea, even when consumed at high doses of 30 grams a day.[5] Acacia gum is popular among those suffering from irritable bowel syndrome, which leads to bloating, gas, and alternating constipation and diarrhea. When mixed with yogurt and bifidobacteria, acacia gum has a substantial beneficial effect on irritable bowel syndrome.[6]

As far back as 1983, scientists discovered the ability of acacia gum to significantly lower cholesterol.[7] This was confirmed in further research in 1997, and again in 2015.[8],1 And acacia, like other prebiotics, may help regulate blood sugar. By replacing typical sugars in foods, they can lower the glycemic response after eating a meal. In addition, acacia has been shown to reduce inflammatory cytokines.[9]

Prebiotics: Ideal Nourishment for Your Friendly Flora

But perhaps acacia is most valued for its reputation as a well-tolerated prebiotic—ideal food for our beneficial flora, selectively stimulating the growth of gut microbes such as bifidobacteria and lactobacilli.

More than twenty studies have been conducted since the late 1970s to unpack the relationship between gum acacia and our gut flora. Acacia's prebiotic impact on our gut flora is substantial; it not only selectively stimulates our beneficial flora, it can help reduce troublesome strains such as clostridium. It appears to resist digestion and absorption in the stomach and small intestine, and instead is metabolized entirely in the colon by our flora, and cannot be recovered at all from stool.[10] When fermented in the colon by bacteria, it yields two important short-chain fatty acids, butyrate and propionate, both of which are beneficial to the immune and epithelial cells in the gut.[11]

The importance of prebiotics cannot be overstated, for in the colon a true symbiosis between our gut bacteria, and the immune and nervous system exists. Studies show soluble fibers' beneficial impacts in conditions ranging from irritable bowel disease to Type 2 diabetes and obesity.[12]

If you think about the magnificent work your gut carries out every day—breaking down food, absorbing its life-giving nutrients, getting rid of toxins, communicating constantly with the immune and nervous systems—you may conclude it makes sense to pamper it. Gut bacteria thrive or starve, depending on what you feed them. Providing your gut—and thus your whole body health—with a soluble fiber with demonstrated benefits makes sense.

You may also be interested in:

The Healing Potential of a Universal Binder Blend

Bitters: Balancing Agents for the Gut


[1] Mohamed RE, Gadour MO, Adam I. The lowering effect of Gum Arabic on hyperlipidemia in Sudanese patients. Front Physiol. 2015 May 18;6:160. View Abstract

[2] Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol. 2013 May;108(5):718-27. View Abstract.

[3] Silva FM, Kramer CK, de Almeida JCet al. Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. Nutr Rev. 2013 Dec;71(12):790-801. View Abstract

[4] Chutkan R, Fahey G, Wright WL, McRorie J. Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits. J Am Acad Nurse Pract. 2012 Aug;24(8):476-87. View Abstract

[5] Cherbut C, Michel C, Raison V, et al. Accacia gum is a bifidogenic dietary fiber with high digestive tolerance in healthy humans. Microbial Ecol Health Dis2003; 15, 43–50.

[6] Yang Won Min, Sang Un Park, Yeon Sil Jang Effect of composite yogurt enriched with acacia fiber and Bifidobacterium lactis World J Gastroenterol. 2012 Sep 7; 18(33): 4563–4569. View Full Paper

[7] Ross AH, Eastwood MA, Brydon WG A study of the effects of dietary gum arabic in humans.

Am J Clin Nutr. 1983 Mar;37(3):368-75. View Abstract

[8] Mee KA, Gee DL.Apple fiber and gum arabic lowers total and low-density lipoprotein cholesterol levels in men with mild hypercholesterolemia J Am Diet Assoc. 1997 Apr;97(4):422-4. View Abstract

[9] Daguet d, Pinheiro I, VVerhelst A, et al. Acacia gum improves the gut barrier functionality in vitro. Agro FOOD Industry Hi Tech 26(4) 2015;29-33.

[10] Ross AH, Eastwood MA, Brydon WG A study of the effects of dietary gum arabic in humans.

Am J Clin Nutr. 1983 Mar;37(3):368-75. View Abstract

[11] Walter DJ, Eastwood MA, Brydon WG, Elton RA. Fermentation of wheat bran and gum arabic in rats fed on an elemental diet. Br.J.Nutr. 1988;60:225-32.

[12] Roberfroid M, Gibson GR, Hoyles L et al. Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010 Aug;104 Suppl 2:S1-63 View Abstract

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The Ultimate Detoxification Strategy - Push and Catch: How to Detoxify Rapidly With Ease

Toxins in air pollution are widespread and can damage our health—and the health of our children—a sweeping new study warns. The new research maps air pollution for nearly 90,000 schools across America and finds widespread exposure to airborne toxins, including mercury and other metals.[1] These toxins can build up in our bodies and are associated with increased risk of diabetes, cardiovascular disease, Alzheimer's disease, respiratory disease, autoimmune conditions and many other conditions.[2],[3]

We truly do live in toxic times. Almost all of us are walking around with measurable levels of mercury and bisphenol A (BPA) in our urine. Toxins can accumulate within tissues and cells, burden our antioxidant defenses, and lead to chronic inflammation and leaky gut syndrome. An inflamed and leaky gut further allows toxins to slip into the bloodstream and trigger a systemic inflammatory response.[4] It is the classic vicious circle.

Optimal health is built by supporting our body's built-in, profound detoxification abilities on a regular basis. Ideally, this is a lifelong approach, not simply a quick 3- or 7- or 10-day detox diet like those popularized by well-loved sources such as Dr. Oz or Prevention Magazine.

Effective daily detoxification hinges on a simple but profound insight into the way our body cleanses and replenishes itself. Quite simply: we push toxins out of the cells and then catch and bind them before they have a chance to do further damage. Push and catch. Though it might sound like a quirky new sports game, push and catch is actually a deep way of reconceptualizing how our bodies manage toxic exposures. We want toxins to be safely flushed out of cells and circulation through the liver into the large intestine, and out through the kidneys into the bladder.

Your Liquid Gold

Our body has a natural answer for toxins—and that is bile, the liver's liquid gold. Bile is produced by your liver and stored in your gallbladder, and is essential to healthy digestion and effective detoxification.[5] Toxins flow with bile out of the liver and into the gallbladder, and then into the gastrointestinal tract, where they are bound into stool and excreted.[6] Stagnant bile flow impairs that precious process: think of the difference between rushing white-water rapids and a slow-moving, muddy river.

Even those blessed individuals with healthy bile flow can be overwhelmed when exposed to excess pollution, or when they intentionally ramp up their detoxification processes. Detoxification can be stimulated through vigorous exercise, therapeutic sweating in saunas, lymphatic massage, changes in diet, or the judicious use of herbs, chelating substances, and nutraceuticals.

Bitter herbs are classic remedies for stimulating the flow of bile and the mobilization of toxins. The moment bitters touch our tongue they send signals directly to our body and brain. That is because we have a few dozen different receptors that detect bitter molecules—and these receptors are so important they line our tongues, lungs, heart, intestines, even our genitals.

Bitters open the gates of detoxification and let the bile flow. These herbs have a long history as tasty aperitifs and digestifs sipped before or after meals to stimulate digestion. Bitter herbs such as dandelion, gentian, solidago, milk thistle and others, help stimulate production of bile as well as increase bile flow, and support the organs of detoxification—the liver, gallbladder, kidney and urinary tract. Essential oils such as myrrh and clove also stimulate bile flow, and are antimicrobial and anti-inflammatory.

In addition, phosphatidylcholine, the main lipid that forms cell membranes, is an essential component of bile and can improve excretion of bile and toxins.[7]

All these aids may be regarded as the 'push' phase of detoxification. But 'push' alone is not enough. When toxins are rapidly mobilized they can spill back out of the bile into circulation again, only to be stored anew in tissue and fat. Rashes, brain fog, aches and pains, and fatigue may result.

Playing Catch

It benefits us to first push toxins out of our cells, and then efficiently 'catch' them after they've been released. One powerful and yet gentle way to do that is with a coordinated mélange of broad spectrum binders.

There is no universal binder that has an equal affinity for all toxins—the common metals, pollutants, mold and bacterial toxins, plastic residues, flame retardants and more that we encounter daily. A blend of carefully calibrated binders can capture an impressive array of toxins. Binders such as clay and charcoal have been trusted remedies for thousands of years. Newer substances such as chitosan (a highly purified long chain sugar made from the shells of shrimp) or unique proprietary binders can latch onto toxins and prevent them from recirculating. Binders can sometimes contribute to constipation, and it can be useful to offset this with additional health-promoting molecules that bulk up the stool, soothe the intestinal lining and support gut motility.Fibers like acacia gum, and soothing molecules like aloe vera, can be mixed into a universal binder blend for optimal effect.

With a rapid delivery system, such as nanoscale lipid-based liposomal deliveries, it is possible to rapidly stimulate bile flow with bitters (push) and then, shortly after, follow with a universal binder blend (catch).This effective approach can be utilized daily, helping to avoid common 'detox' and 'die-off' symptoms.

Push and catch. These two simple concepts can reinvigorate your daily approach to detoxification.


You may also be interested in:

Mercury: A Potent Toxin with Widespread Health Impacts

Small But Dangerous Air

Sperm Counts Are Plummeting, And Researchers Think They Know Why


[1] Grinseki SE, Collins TW. Geographic and social disparities in exposure to air neurotoxicants at U.S. public schools. Environ Res. 2018 Feb;161:580-587. View Abstract

[2] Bonini MG, Sargis RM. Environmental Toxicant Exposures and Type 2 Diabetes Mellitus: Two Interrelated Public Health Problems on the Rise. Curr Opin Toxicol. 2018 Feb;7:52-59. View Abstract.

[3]Hodjat M, Rahmani S, Khan F et al. Environmental toxicants, incidence of degenerative diseases, and therapies from the epigenetic point of view. Arch Toxicol. 2017 Jul;91(7):2577-2597. View Abstract

[4] Ahmad R, Sorrell MF, Batra SK, et al. Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal Immunol. 2017 Mar;10(2):307-317 View Abstract

[5] Sharma R, Long A, Gilmer JF. Advances in Bile Acid Medicinal Chemistry. Curr Med Chem. 2011;18(26):4029-52 View Abstract

[6] Hellström PM, Nilsson I, Svenberg T. Role of bile in regulation of gut motility. J Intern Med. 1995 Apr;237(4):395-402. View Abstract

[7] Hişmioğullari AA, Bozdayi AM, Rahman K. Biliary lipid secretion. Turk J Gastroenterol. 2007 Jun;18(2):65-70.

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Supporting Detoxification with Sleep

Supporting Detoxification with Sleep

Our bodies are constantly challenged by environmental toxicities and the continual effort of detoxication. Although dietary support for detoxification is one important leg of the supportive "stool," so is healthy sleep. So many individuals are sleep deprived today, whether due to nighttime awakenings to care for children or loved ones, a job that is demanding or requires work at evening hours, or chronic health conditions, including chronic infections or heavy metal toxicity, that contribute to insomnia. Many cytokines, inflammatory markers, and hormones are impacted by sleep and the lack thereof.[1],[2],[3]Studies have shown that both acute total and short-term partial sleep restriction increases many pro-inflammatory signaling molecules in the body. [4],[5] Not only do these inflammatory markers rise acutely, but this effect can persist beyond the days with diminished sleep, despite normal recovery sleep in subsequent nights.

The integrity of the blood-brain barrier is negatively affected by sleep restriction as well.[6] The blood-brain barrier protects the central nervous system from circulatory proteins and toxins that may contribute to neuroinflammation and damage. An altered blood-brain barrier may contribute to numerous neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and more.[7] Stress also increases permeability of the blood-brain barrier.[8] The stress-associated increase in blood-brain barrier permeability may contribute to increased symptoms with stress in neuroinflammatory conditions such as multiple sclerosis.

Cleaning up the diet is one thing that can support healthy sleep. By reducing inflammation and its mediators such as histamine, the blood-brain barrier integrity is improved, and related neuroinflammation and excess agitation is diminished.[9] In addition to addressing diet from a larger standpoint, the foods and beverages consumed directly before bed also can have an impact on sleep. If a snack is consumed before bed, it should be higher in protein and fats as this will help keep the blood sugar levels stable through the night. Alcohol also has a negative impact on sleep quality, in part due to the fact that the blood sugar level will fall during the night.[10] As larger meals before bed can contribute to evening symptoms of gastroesophageal reflux, this should be avoided, particularly in susceptible individuals.[11]

Intense exercise later in the day can have a negative impact on sleep, as it leads to a rise in cortisol and catecholamines, promoting a 'fight or flight' sympathetic state in the nervous system.[12],[13] Activities that are considered to be good "sleep hygiene" include the avoidance of the use of electronics and other intense blue light sources for at least 1 hour before bed. Blue light has a wakeful effect, and suppresses melatonin secretion.[14],[15] Electronics should not be present in the sleep environment due to their potential distracting effects, and sensitive individuals may find benefit from turning off the WiFi signal in the house.[16]

Detoxification and treatment of chronic infections can improve sleep, particularly in the long run, as doing so reduces systemic and central nervous system inflammation which can negatively affect sleep. On an as needed basis, supplemental therapies can be used to support healthy sleep. Trace minerals support neurotransmitter metabolism and the function of all the enzymatic systems of the body, and can help the body and brain to turn down at night. GABA and L-theanine support alpha wave rhythms in the brain, similar to the relaxed state which occurs with meditation.[17],[18] Cannabinoids, which are endogenous in our body but also found in hemp oil, can also impact sleep, calming neuroinflammation and improving the integrity of the blood-brain barrier. [19],[20], [21]

To learn more, read on at:


[1] Kim TW, Jeong JH, Hong SC. The impact of sleep and circadian disturbance on hormones and metabolism. Int J Endocrinol. 2015;2015:591729. View Full Paper

[2] Meier-Ewert HK, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004 Feb 18;43(4):678-83. View Abstract

[3] Vgontzas AN, et al. Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime. Metabolism. 2002 Jul;51(7):887-92. View Abstract

[4] van Leeuwen WM, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS One. 2009;4(2):e4589. View Full Paper

[5] Chennaoui M, et al. Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men. Cytokine. 2011 Nov;56(2):318-24. View Abstract

[6] He J, et al. Sleep restriction impairs blood-brain barrier function. J Neurosci. 2014 Oct 29;34(44):14697-706. View Full Paper

[7] Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008 Jan 24;57(2):178-201. View Abstract

[8] Esposito P, et al. Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther. 2002 Dec;303(3):1061-6. View Full Paper

[9] Abbott NJ. Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol. 2000 Apr;20(2):131-47. View Abstract

[10] Freinkel N, et al. Alcohol hypoglycemia. Iv. Current concepts of its pathogenesis. Diabetes. 1965 Jun;14:350-61. View Abstract

[11] Jarosz M, Taraszewska A. Risk factors for gastroesophageal reflux disease: the role of diet. Prz Gastroenterol. 2014;9(5):297-301. View Full Paper

[12] Hill EE, Zack E, Battaglini C, et al. Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Invest. 2008 Jul;31(7):587-91. View Abstract

[13] Dimsdale JE, Moss J. Plasma catecholamines in stress and exercise. JAMA. 1980 Jan 25;243(4):340-2. View Abstract

[14] Viola AU, James LM, Schlangen LJ, Dijk DJ. Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality. Scand J Work Environ Health. 2008 Aug;34(4):297-306. View Abstract

[15] West KE, Jablonski MR, Warfield B, et al. Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans. J Appl Physiol (1985). 2011 Mar;110(3):619-26. View Full Paper

[16] Warnke U. Electromagnetic Sensitivity of Animals and Humans: Biological. Bioelectrodynamics and Biocommunication. 1994 Oct 17;6:365

[17] Yoto A, Murao S, Motoki M, et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43(3):1331–1337. View Abstract

[18] Kakuda T, Nozawa A, Sugimoto A, et al. Inhibition by Theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002;66(12):2683–2686. View Abstract

[19]Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res. 2009 Aug;60(2):77-84. View Abstract

[20] Walter L, Stella N. Cannabinoids and neuroinflammation. Br J Pharmacol. 2004 Mar;141(5):775-85. View Full Paper

[21] Ramirez SH, et al. Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J Neurosci. 2012 Mar 21;32(12):4004-16. View Full Paper

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Supporting Detoxification with Diet

Supporting Detoxification with Diet

Many individuals who embark upon detoxification protocols seek advice on what dietary strategies may help and improve the process of detoxification. Unfortunately, dietary choices are not “one size fits all.” However, there are some choices worthy of emphasis, particularly where minimizing exposures to potential toxins is concerned. In addition, choosing a diet that can help reduce inflammation is supportive to detoxification, as the body and immune system is challenged by the burden of toxins, which creates oxidative stress.

Supporting Detoxification with Diet JEN CD html 5c1a1a7a

Eating a diet that is well-balanced and organic whenever possible, and shopping the periphery of grocery stores rather than the aisles a great place to start. By doing this, it is easier to avoid the artificial flavorings, dyes, and preservatives which are added to processed foods, which heavily line the shelves and freezer section of the grocery. In addition to this, metal food and drink cans are commonly coated internally with polymeric films that contain bisphenol A (BPA), which has been found to leach into the majority of the foods which they contain.1,2 If there are ingredients on a food label that are difficult to pronounce, and sound more like a chemical than a food substance, or if a pre-made food contains an extremely long list of ingredients relative to its contents, it often is wise to avoid as well. Consumption of sugar should be minimized, as excess sugars and simple carbohydrates can have an inflammatory effect in the body, raising blood sugar, and serving as food for dysbiotic microbes such as yeast.3,4

Avoidance of known food sensitivities or allergies will help to balance the body’s immune response and reduce inflammation. There are a variety of testing options that are used by holistic medical practitioners to evaluate which foods the body may be sensitive to.5,6 Many individuals also find an elimination diet helpful to determine food sensitivities or food intolerances. 

Supporting Detoxification with Diet JEN CD html 8e44bccdWhen following an elimination diet, foods that people are commonly sensitive to (dairy, gluten, soy, eggs, peanuts, shellfish) are eliminated for a period of time (2 – 4 weeks), and then slowly re-introduced. When a food is reintroduced, it should be eaten in significant volume on the day it is consumed to truly challenge the body. These challenges should be spaced out (over days) so that changes in symptoms can be fully noted. Because produce from the nightshade family (tomatoes, peppers, eggplants, potatoes) can trigger an inflammatory response in some individuals, they also may be removed in the process of an elimination diet.7

 Through the elimination process and food re-introduction, it is important to keep a journal of food intake and symptoms in order to understand which foods may be impacting your health. Ideally, this also should be guided by a practitioner who is familiar with the process.

Grass-fed, free-range, antibiotic-free, and rBGH-free (bovine growth hormone) are descriptors to look for when purchasing animal-sourced products. Chicken, particularly that from non-organic sources, contains high levels of arsenic, and for this reason should be avoided or minimized.8 Rice also contains high levels of arsenic even when organic, although white basmati rice from California, India, and Pakistan, and sushi rice from the U.S. have been shown to contain lower amounts.9 Brown rice actually has more arsenic than white rice on average as it accumulates in the outer layers of the grain.10 Rinsing rice well and cooking it with excess water can help to reduce arsenic content.11

Supporting Detoxification with Diet JEN CD html 3679dc21When it comes to seafood and shellfish, one should minimize consumption of larger predatory fish including shark, swordfish, marlin, tuna, and tilefish, as these fish are highly contaminated with mercury.12 Tuna is popular with many due to its high-protein and low-fat content as well as ease of availability, but should not be consumed in excess of 6 oz. per week, or should be avoided altogether, especially by pregnant women and children. Salmon and shrimp offer a higher balance of omega-3 fatty acids to the deleterious mercury, and are better choices, yet even these still should be eaten in moderation.13 The Environmental Working Group recommends 4 to 8 ounces weekly of salmon, or of other affordable seafood such as anchovies, sardines, and mussels.14

Mycotoxins, the toxins associated with molds, are another category of harmful substances which can be found in many foods and beverages. Aflatoxin is a common mold toxin, well-known for being found in tree nuts (particularly peanuts). Aflatoxin also can exist at high levels in beans, corn, rice, wheat, as well as milk, eggs, and meat.15 Ochratoxin A is another common food-related mold toxin that blocks detoxification, inhibiting the body’s Nrf2 pathway via which endogenous antioxidant production occurs.16 It can be found in cereal grains, wine, grape juice, spices, dairy, coffee, and dried vine fruit products.17,18 Supporting Detoxification with Diet JEN CD html 1a85b8a2Aflatoxin’s precursor, the mycotoxin sterigmatocystin, can be found in many grains, corn, spices, coffee beans, soybeans, as well as cheese.19,20 There also is zearalenone, a mycotoxin with estrogenic effects commonly found on stored grains as well as rice and corn, and fumonisin B1, a mycotoxin most often found on corn. 21,22 Although binding agents exist such as bentonite clay and chitosan which can help to remove these toxins from the body, 23,24,25,26 for those who struggle with mold toxicity, avoidance of possibly contaminated substances is also recommended.

 Of course, there are still other categories of foods beyond these that might trigger reactions, especially in a sensitive population. Histamine, found at high levels in aged products such as cheese or meat, fermented foods, many types of alcohol, as well as certain vegetables such as tomatoes, can lead to gastrointestinal symptoms and systemic symptoms similar to an allergy.27 

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This can be an issue not only in individuals who genetically have low levels of activity of the histamine-degrading enzyme diamine oxidase (DAO), which is produced in the cells lining the small intestine, but also for those with conditions that lead to damage and inflammation of the small intestinal mucosa. This includes celiac disease or small intestinal bacterial overgrowth (SIBO). Sulfite sensitivity also can be an issue for some, and symptoms may appear similar to histamine intolerance. Sulfites are found predominantly as a consequence of fermentation, although they also occur naturally in a number of foods and beverages.28 They also may be found as food additives, as they serve to help preserve and prevent microbial growth as well as browning and spoilage.

The many issues with possible contaminants in water have been discussed previously, shedding light on the importance of ensuring a clean and safe water source. A guide to help you select an appropriate water filter for the possible exposures you may have in your region can be found on the Environmental Working Group webpage. Consuming half your body weight in ounces of water is a general daily guideline, however roughly 2 cups more should be included for every cup of coffee, which is a diuretic, and for every 30 minutes of exercise. As bitter substances support digestion, and detoxification pathways as well, digestive bitters can be added to water or sparkling water as an alternative beverage, also giving health a boost. For individuals who do not have adverse reactions to fermented products, there are options such as kombucha which can be a refreshing change, also supporting the health of the gut with the probiotics they contain.

To learn more, read on at:


1 Noonan GO, Ackerman LK, Begley TH. Concentration of bisphenol A in highly consumed canned foods on the U.S. market. J Agric Food Chem. 2011 Jul 13;59(13):7178-85. View Abstract

2 Cao XL, Corriveau J, Popovic S. Bisphenol a in canned food products from Canadian markets. J Food Prot. 2010 Jun;73(6):1085-9. View Abstract

3 Martinez-Medina M, Denizot J, Dreux N, et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 2014 Jan 1;63(1):116-24. View Abstract

4 Weig M, Werner E, Frosch M, Kasper H. Limited effect of refined carbohydrate dietary supplementation on colonization of the gastrointestinal tract of healthy subjects by Candida albicans. Amer J Clin Nutri. 1999 Jun 1;69(6):1170-3. View Abstract

5 Moneret-Vautrin DA, Kanny G, Frémont S. Laboratory tests for diagnosis of food allergy: advantages, disadvantages and future perspectives. Eur Ann Allergy Clin Immunol. 2003 Apr;35(4):113-9. View Abstract

6 Pasula MJ. The ALCAT test: in vitro procedure for determining food sensitivities. Folia Med Cracov. 1993;34(1-4):153-7. View Abstract

7 Childers NF, Margoles MS. An apparent relation of nightshades (Solanaceae) to arthritis. Journal of Neurological and Orthopaedic Medicine and Surgery. 1993 Jan 1;14:227 -231. View Full Paper

8 Nachman KE, Baron PA, Raber G, et al. Roxarsone, inorganic arsenic, and other arsenic species in chicken: a US-based market basket sample. Environ Health Persp. 2013 Jul;121(7):818. View Full Paper

9 Meharg AA, Williams PN, Adomako E, et al. Geographical variation in total and inorganic arsenic content of polished (white) rice. Enviro Sci & Tech. 2009 Jan 21;43(5):1612-7. View Abstract

10 How Much Arsenic Is in Your Rice? Consumer Reports. Accessed November 27, 2017. View Website

11 Gray PJ, Conklin SD, Todorov TI, Kasko SM. Cooking rice in excess water reduces both arsenic and enriched vitamins in the cooked grain. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2016;33(1):78-85. View Abstract

12 Balshaw S, Edwards J, Daughtry B, Ross K. Mercury in seafood: mechanisms of accumulation and consequences for consumer health. Rev Environ Health. 2007 Apr-Jun;22(2):91-113. View Abstract

13 Mania M, Wojciechowska-Mazurek M, Starska K, et al. [Fish and seafood as a source of human exposure to methylmercury]. Rocz Panstw Zakl Hig. 2012;63(3):257-64. View Abstract

14 EWG’s Consumer Guide to Seafood: Executive Summary. Environmental Working Group. Accessed November 27, 2017. View Website

15 Rustom IY. Aflatoxin in food and feed: occurrence, legislation and inactivation by physical methods. Food Chem. 1997 May 1;59(1):57-67. View Abstract

16 Limonciel A, Jennings P. A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity. Toxins (Basel). 2014 Jan 20;6(1):371-9.

17 Duarte SC, Pena A, Lino CM. A review on ochratoxin A occurrence and effects of processing of cereal and cereal derived food products. Food microbiology. 2010 Apr 30;27(2):187-98. View Full Paper

18 Studer-Rohr I, Dietrich DR, Schlatter J, Schlatter C. The occurrence of ochratoxin A in coffee. Food Chem Toxicol. 1995 May 1;33(5):341-55. View Abstract

19 Northolt MD, Van Egmond HP, Soentoro P, Deijll E. Fungal growth and the presence of sterigmatocystin in hard cheese. Assoc Official Analyt Chem. 1980 Jan;63(1):115-9. View Abstract

20 Veršilovskis A, De Saeger S. Sterigmatocystin: occurrence in foodstuffs and analytical methods–an overview. Molec Nutr & Food Res. 2010 Jan 1;54(1):136-47. View Abstract

21 Abbès S, Salah-Abbès JB, Ouanes Z, et al. Preventive role of phyllosilicate clay on the Immunological and Biochemical toxicity of zearalenone in Balb/c mice. Int Immunopharmacol. 2006 Aug;6(8):1251-8. View Abstract

22 Hopmans EC, Murphy PA. Detection of fumonisins B1, B2, and B3 and hydrolyzed fumonisin B1 in corn-containing foods. J Agri Food Chem. 1993 Oct;41(10):1655-8. View Abstract

23 Bornet A, Teissedre PL. Chitosan, chitin-glucan and chitin effects on minerals (iron, lead, cadmium) and organic (ochratoxin A) contaminants in wines. Euro Food Res Tech. 2008 Feb 1;226(4):681-9. View Abstract

24 Tuomi T, Reijula K, Johnsson T, et al. Mycotoxins in crude building materials from water-damaged buildings. Appl Enviro Microbiology. 2000 May 1;66(5):1899-904. View Abstract

25 Abdel-Wahhab MA, Hasan AM, Aly SE, Mahrous KF. Adsorption of sterigmatocystin by montmorillonite and inhibition of its genotoxicity in the Nile tilapia fish (Oreachromis nilaticus). Mutat Res. 2005 Apr 4;582(1-2):20-7. View Abstract

26 Mitchell NJ, Xue KS, Lin S, et al. Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin. J Appl Toxicol. 2014 Jul;34(7):795-804. View Full Paper

27 Maintz L, Novak N. Histamine and histamine intolerance. Amer J Clin Nutri. 2007 May 1;85(5):1185-96. View Abstract

28 Lester MR. Sulfite sensitivity: significance in human health. J Amer Col Nutri. 1995 Jun 1;14(3):229-32. View Abstract

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Reflections on Health and Direction in the New Year

Reflections on Health and Direction in the New Year           

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 As we close out the year, taking a moment to reflect on the past, and our desired direction for the future, can be insightful. Both the accomplishments and challenges of the year(s) past help to shape us – they build character, wisdom, and an ability to experience greater compassion for ourselves, and the challenges of others. By taking a moment to reflect upon the year past, we are better able to shape and direct the activities of tomorrow, whether this be making changes in a job, our relationships, or addressing other aspects of our health and lifestyle.

            If health has been a challenge of the year past, you are not alone. Many people face chronic illness, whether it be diabetes, autoimmune disease, allergies, mental health challenges, or other symptoms for which a diagnosis eludes us. We struggle with the health systems, and lack of improvements when offered standard care. Often, the best standard treatment only stabilizes the disease, with potential side effects that are greatly concerning. The vast population with an autoimmune disease know this far too well, as the risks associated with immunosuppression include not only infection and illness, but increased risks of malignancy as well.[1] If treatment includes a glucocorticoid, the risks also include weight gain, insulin resistance, and osteoporosis.[2] The medications compound, as we are offered an anti-diabetic or bone supportive prescription which also have their own array of potential side effects such as further weight gain or gastrointestinal reflux.

            Although chronic illness manifests outwardly in different types of diseases, environmental toxicities and the health of the gut can contribute to the development of all these conditions.[3],[4],[5],[6],[7] Even though the medical community has a growing understanding of this, treatments directed at these contributing factors will take decades to gain acceptance, and for many of us, that may not be within our lifetime. As such, the burden lies on us to seek out practitioners and solutions that holistically address our health, and consider the many contributing factors if we truly want to heal from or prevent chronic disease.

            Detoxification, although often grossly simplified as a week or month-long change in diet, with the occasional supportive supplement or yoga class, has the potential to play a far more significant role in bringing the body back to health than just this temporary change. Effective detoxification supplements and protocols exist that are capable of removing these toxic substances, restoring a healthy microbial balance in the gut, and replenishing the body’s protective antioxidant systems, while qualified practitioners who use these tools can easily be found. If you are contemplating how you can support your health in the new year, a comprehensive detoxification program just may be the restore, rebalance, and reinvigorate solution that you are seeking.

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 At Quicksilver Scientific, we also embrace our accomplishments of the past, and move forward to our future. We look forward to being a part of your health journey, continuing to provide you with educational resources, the highest quality supplements, and superior detoxification packages and protocols. Happy New Year to all, and with it may you prosper and find restoration!

To learn more, read on at:


[1] Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat. 2004 Sep;15(5):280-94. View Abstract

[2] Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002 Oct;96(1):23-43. View Abstract

[3] Schug TT, et al. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol. 2011 Nov;127(3-5):204-15. View Abstract

[4] Diaz-Sanchez D, et al. Diesel fumes and the rising prevalence of atopy: an urban legend? Curr Allergy Asthma Rep. 2003 Mar;3(2):146-52. View Abstract

[5] Bhatnagar A, et al. Environmental cardiology: studying mechanistic links between pollution and heart disease. Circ Res. 2006 Sep 29;99(7):692-705. View Abstract

[6] Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011 Jan;5(1):82-91. View Abstract

[7] Kalliomäki M, Kirjavainen P, Eerola E, et al. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001 Jan;107(1):129-34. View Abstract

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Holiday Support for Detox and Digestive Function

Holiday Support for Detox and Digestive Function

Just one more bite, you think as you teeter on the brink of being somewhere between very full and feeling almost sick. An after-dinner cocktail warms your belly despite the large cube of ice chilling it in the glass. “I’ll detox/exercise/eat better tomorrow” is a common theme through the holidays as we encounter many gatherings with beverages, multiple course meals, and elaborate dishes to try. Although the “enjoy now, pay later” motto is one strategy, support for the body on the front end also can help to mitigate the damage that inevitably accompanies excessive intake of beverages or food.

One way to support digestive and liver health through the holidays is by using bitters. Herbal bitters have a long history of use, and are commonly used in cocktails known as aperitifs and digestifs which are served before and after meals to stimulate appetite and digestion. However, bitter herbs act far beyond the digestive system, and broadly impact the liver, kidneys, skin, immune system, and detoxification pathways.1 They stimulate the body’s production of digestive secretions, supporting the digestion of food and healthy gastrointestinal function. Bitters substances support healthy bile flow, which is necessary for the normal bowel motility and elimination.2 This bile flow also helps keep the gut flora in balance, a balance which can be tipped in the negative direction with excessive consumption of holiday sweets.3 Bitters can be taken before meals to support digestion, but also can be enjoyed in a cocktail or sparkling water between meals to help alleviate digestive discomfort. Some of the herbs used as bitters such as dandelion, milk thistle, and gentian also deliver hepatoprotective benefits, supporting the antioxidant status and health of the liver, giving even more reason to use them in your cocktail.4,5, 6

Holiday Support for Detox and Digestive Function J html fd72455cAt times, with holiday meals, we may consume foods that we normally try to avoid due to sensitivities. Although that carrot cake with cream cheese frosting may taste good for a moment, cloudy thinking, anxiety, itching, or digestive discomfort may soon follow. One substance which can help restore immune system balance and reduce food reactions, even when taken after the fact, is diindolylmethane, commonly known as DIM. DIM is derived from cruciferous vegetables and is commonly used as support for hormone metabolism, but its potential benefits are much broader than this. DIM has been shown to induce a regulatory T cell response, reducing the T cells associated with allergy and the pro-inflammatory response.7 A bolus of DIM, taken in a rapidly absorbable form such as a nanoemulsion, can help restore the body to balance quickly. DIM also has the effect of “turning on” the Nrf2 pathway, the switch that turns on the body’s expression of many drug metabolizing enzymes, detoxification transporters (necessary to get toxins out of the cell), and other antioxidant enzymes.8,9

Holiday Support for Detox and Digestive Function J html c878cdd2Although the liver technically is a part of the gastrointestinal system, it really serves a much larger job than just digestion. Many are familiar with the burden that alcohol consumption places on the liver, but excessive food is taxing to the liver as well and contributes to a condition known as non-alcoholic fatty liver disease. One of the molecules that is important for supporting the health of the liver is glutathione, the body’s main intracellular antioxidant.10 Consumption of alcohol induces oxidative stress that damages the liver, impairing antioxidant defenses and producing reactive oxygen species, as well as depleting glutathione.11,12 Glutathione is important for cellular health, energy production, and a normal immune system response.13,14

Alcohol, particularly in excess, has an effect of increasing intestinal permeability, leading to what is commonly known as leaky gut. With leaky gut, endotoxin associated with bacteria in the gut is able to enter into circulation, creating a strong inflammatory response, blocking detoxification pathways, and damaging liver and kidney function.15 This is, in part, what leads to symptoms of a hangover -- including difficulty thinking, aches and pains, and digestive symptoms after consuming excess alcohol. One effective tool to reduce these symptoms is the use of a binder such as activated charcoal and chitosan which both bind endotoxin and also help to reduce related inflammation.16,17,18 A comprehensive binder also can help the body to clear other things which it may be reacting to such as pesticides and herbicides, as well as mold toxins found in food, wine, and beer.19,20,21,22

For a comprehensive liver support package, one must also consider phosphatidylcholine. Phosphatidylcholine is the predominant phospholipid building block of cellular membranes, and comprises over 90% of the bile phospholipid content.23 It helps maintain the fluid nature of cellular membranes for transport of nutrients in, and toxins out of the cells. It is of particular importance for the function of hepatocytes in removing toxins from the body, which are transported out complexed with the bile and phosphatidylcholine. Inadequate intake contributes to impaired biliary excretion of bile and toxins, and promotes cholesterol crystallization and gallstone formation.24 Increased intake of phosphatidylcholine has been shown to enhance biliary lipid secretion, preventing cholestasis and subsequent liver damage.25,26

Holiday Support for Detox and Digestive Function J html ff4281d4So, before you head out to your holiday parties, make sure you are prepared with your arsenal of support! Crafty cocktails with charcoal in them are also even a trend, showing up in trendy lounges in major cities and with do-it-yourself guides on the internet. Enjoy your pre-dinner bitter-filled aperitif and make an after-dinner cocktail everyone will be talking about still the next year!

 

To learn more, read on at:


1 Shaik FA, et al. Bitter taste receptors: Extraoral roles in pathophysiology. Int J Biochem Cell Biol. 2016 Aug;77(Pt B):197-204. View Abstract

2 Hellström PM, Nilsson I, Svenberg T. Role of bile in regulation of gut motility. J Intern Med. 1995 Apr;237(4):395-402. View Abstract

3 Islam KB, Fukiya S, Hagio M, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81. View Abstract

4 Mihailović V, et al. Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats. Food Chem Toxicol. 2013 Feb;52:83-90. View Abstract

5 Rui YC. Advances in pharmacological studies of silymarin. Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:79-85. View Full Paper

6 You Y, et al. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food Chem Toxicol. 2010 Jun;48(6):1632-7. View Abstract

7 Huang Z, Jiang Y, Yang Y, et al. 3,3'-Diindolylmethane alleviates oxazolone-induced colitis through Th2/Th17 suppression and Treg induction. Mol Immunol. 2013 Apr;53(4):335-44. View Abstract

8 Ernst IM, Schuemann C, Wagner AE, Rimbach G. 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. Free Radic Res. 2011 Aug;45(8):941-9. View Abstract

9 Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. View Full Paper

10 Yuan L, Kaplowitz N. Glutathione in liver diseases and hepatotoxicity. Mol Aspects Med. 2009 Feb-Apr;30(1-2):29-41. View Abstract

11 Albano E. Alcohol, oxidative stress and free radical damage. Proc Nutr Soc. 2006 Aug;65(3):278-90. View Abstract

12 Hirano T, et al. Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats. Hepatology. 1992 Dec;16(6):1423-7. View Abstract

13 Palamara AT, et al. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res. 1995 Jun;27(3):237-53. View Abstract

14 Cai J, et al. Inhibition of influenza infection by glutathione. Free Radic Biol Med. 2003 Apr 1;34(7):928-36. View Abstract

15 Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009 Jul;124(1):3-20. View Abstract

16 Nolan JP, McDevitt JJ, Goldmann GS, Bishop C. Endotoxin binding by charged and uncharged resins. Proc Soc Exp Biol Med. 1975 Jul;149(3):766-70. View Abstract

17 de Souza JB, et al. Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate. PLoS One. 2010 Apr 15;5(4):e9867. View Full Paper

18 Davydova VN, Yermak IM, Gorbach VI, et al. Interaction of bacterial endotoxins with chitosan. Effect of endotoxin structure, chitosan molecular mass, and ionic strength of the solution on the formation of the complex. Biochemistry (Mosc). 2000 Sep;65(9):1082-90. View Abstract

19 Quintela S, Villarán MC, López De Armentia I, Elejalde E. Ochratoxin A removal from red wine by several oenological fining agents: bentonite, egg albumin, allergen-free adsorbents, chitin and chitosan. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2012;29(7):1168-74. View Abstract

20 Park Y, Sun Z, Ayoko GA, Frost RL. Removal of herbicides from aqueous solutions by modified forms of montmorillonite. J Colloid Interface Sci. 2014 Feb 1;415:127-32. View Abstract

21 Lagaly G. Pesticide–clay interactions and formulations. App Clay Sci. 2001 May 31;18(5):205-9. View Abstract

22 Mateo R, Medina A, Mateo EM, et al. An overview of ochratoxin A in beer and wine. Int J Food Microbiol. 2007 Oct 20;119(1-2):79-83. View Abstract

23 Hişmioğullari AA, Bozdayi AM, Rahman K. Biliary lipid secretion. Turk J Gastroenterol. 2007 Jun;18(2):65-70. View Full Paper

24 Morita SY, Terada T. Molecular mechanisms for biliary phospholipid and drug efflux mediated by ABCB4 and bile salts. Biomed Res Int. 2014;2014:954781. View Full Paper

25 Chanussot F, Benkoël L. Prevention by dietary (n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced by cyclosporine A in animals. Life Sci. 2003 Jun 13;73(4):381-92. View Abstract

26 Karaman A, Demirbilek S, Sezgin N, et al. Protective effect of polyunsaturated phosphatidylcholine on liver damage induced by biliary obstruction in rats. J Pediatr Surg. 2003 Sep;38(9):1341-7. View Abstract

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A Bioavailability Solution for the Traditional Chinese Botanical Artemisia Annua

A Bioavailability Solution for the Traditional Chinese Botanical Artemisia Annua

Artemisia Annua blog JEN CD html 3d410e77 Artemisia annua, also known as sweet wormwood, or Qinghao, has a long history of use in traditional Chinese medicine primarily as a febrifuge, or an agent to reduce fever. As fever is a symptom of the immune response to infection, the mechanism by which this herb improved upon a fever was likely by reducing the level of infectious microbes and balancing the associated immune response. The primary active moiety artemisinin, a sesquiterpene endoperoxide lactone, is known as Qinghaosu in Chinese medical traditions.1 The plants of the Artemisia genus usually are aromatic with a bitter signature, and thus impact the bitter taste receptors and digestion similarly to other digestive bitters like gentiana lutea.2

 

Mechanism of Action. One of the mechanisms by which artemisinin may impact the body is through the production of carbon-centered free radicals via an iron heme-mediated or mitochondrial-activated degradation of endoperoxidase bridges.3,4 Artemisinin is activated in environments with high iron concentration, releasing reactive oxygen species (ROS).5 The generated free radicals have the potential to trigger apoptosis and arrest cell growth, alter enzyme action, and inhibit angiogenesis – actions which may be beneficial in settings of uncontrolled cellular growth and division.

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Sesquiterpene lactones derived from Artemisia annua have been shown to increase prostaglandin levels in the gastric mucosa, and thus it may be protective against gastric ulceration.6 Artemisinin has been shown to inhibit the secretion of tumor necrosis factor (TNF)-α, interleukin- (IL-) 1β, and IL-6 in a dose-dependent manner, as well as LPS-activated production of prostaglandin E2.7, 8 Artemisinin may have an immunomodulatory effect in settings of contact and delayed hypersensitivity, suppressing the hypersensitivity response and inducing T regulatory cells.9,10

Broad Antimicrobial Effects. Artemisia annua has a long history of use in parasitic infections such as Plasmodium falciparum, Leishmania, Babesia, and Schistosoma, as well as against wide range of bacteria, fungi, and viruses which cause infection.11,12,13,14 Extracts from Artemisia annua have been shown to have antibacterial action against Campylobacter jejuni and Clostridium perfringens, two bacterium which are common causes of foodborne enteritis.15,16 Artemisinin also has been shown to have strong activity against Helicobacter pylori.17 Viral action has been demonstrated against cytomegalovirus, herpes simplex virus type 1, Epstein-Barr virus, and hepatitis B and C virus.18

A Bioavailability Dilemma and Solution. Because of the low solubility of artemisinin in both oil and water, the bioavailability of synthetic artemisinin derivatives such as dihydroartemisinin, artemether, arteether, and artesunate or alternate dosing strategies such as liposomes have been investigated.19 First-pass hepatic metabolism of artemisinin and its semisynthetic derivatives artesunate and artemether limit oral bioavailability to 30%. Longer half-lives are achievable with intramuscular and rectal dosing due to the high level of first-pass metabolism with traditional oral dosing.

Screen Shot 2017 12 11 at 1.55.46 PMBecause liposomes are delivered to circulation via the lymphatics, first-pass hepatic metabolism of the substances they contain is avoided.20 As such, liposomal delivery systems are a potential solution for many substances which have limited bioavailability due to a high extent of first-pass liver metabolism. Liposomes also often prolong bioavailability, reducing clearance by the mononuclear phagocytes of the immune system.21,22 For these reasons, they have been investigated for the delivery of artemisinin.

Liposomal artemisinin formulations have been shown to lead to more stable artemisinin plasma concentrations, suggesting they have a continuous release and thereby prolonged systemic effect.23 More immediate effects have also been seen with liposomal dosing than with conventional artemisinin, which took up to 7 days to achieve the desired therapeutic result. In another study, liposomal artemisinin, with a mean diameter of 130 – 140 nm, was shown to stay in circulation significantly longer, with the area under the curve increasing by a factor of six compared with free artemisinin.24 Free artemisinin was hardly detectible after 1 hour of administration, while the liposomal artemisinin was detected for up to 3 hours, and even up to 24 hours when delivered as a pegylated liposome, another technique often used to improve bioavailability.

 


1 Bilia AR, Santomauro F, Sacco C, et al. Essential Oil of Artemisia annua L.: An Extraordinary Component with Numerous Antimicrobial Properties. Evid Based Complement Alternat Med. 2014;2014:159819. View Full Paper

2 Brockhoff A, Behrens M, Massarotti A, Appendino G, Meyerhof W. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J Agric Food Chem. 2007 Jul 25;55(15):6236-43. View Abstract

3 Meshnick SR. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002 Dec 4;32(13):1655-60. View Abstract

4 Sun C, Li J, CaoY Long G, Zhou B. Two distinct and competitive pathways confer the cellcidal actions of artemisinins. Microb Cell. 2015;2:14–25. View Full Paper

5 Lai HC, Singh NP, Sasaki T. Development of artemisinin compounds for cancer treatment. Invest New Drugs. 2012;31:230–246. View Abstract

6 Foglio MA, Dias PC, Antônio MA, et al. Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua. Planta Med. 2002 Jun;68(6):515-8. View Abstract

7 Wang Y, Huang ZQ, Wang CQ, et al. Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages. Clin Exp Pharmacol Physiol. 2011 Jan;38(1):11-8. View Abstract

8 Zhu XX, Yang L, Li YJ, et al. Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis. Pharmacol Rep. 2013;65(2):410-20. View Abstract

9 Li T, Chen H, Wei N, et al. Anti-inflammatory and immunomodulatory mechanisms of artemisinin on contact hypersensitivity. Int Immunopharmacol. 2012 Jan;12(1):144-50. View Abstract

10 Noori S, Naderi GA, Hassan ZM, et al. Immunosuppressive activity of a molecule isolated from Artemisia annua on DTH responses compared with cyclosporin A. Int Immunopharmacol. 2004 Oct;4(10-11):1301-6. View Abstract

11 Klayman DL. Qinghaosu (artemisinin): an antimalarial drug from China. Science. 1985 May 31;228(4703):1049-55. View Abstract

12 Tariq A, et al. Ethnomedicines and anti-parasitic activities of Pakistani medicinal plants against Plasmodia and Leishmania parasites. Ann Clin Microbiol Antimicrob. 2016 Sep 20;15(1):52. View Full Paper

13 Goo YK, et al. Artesunate, a potential drug for treatment of Babesia infection. Parasitol Int. 2010 Sep;59(3):481-6. View Abstract

14 Xiao SH. Development of antischistosomal drugs in China, with particular consideration to praziquantel and the artemisinins. Acta Trop. 2005 Nov-Dec;96(2-3):153-67. View Abstract

15 Militaru D, et al. In vitro evaluation of the potential antibacterial effect of artemisinin on Campylobacter jejuni. Rom Biotech Let. 2015 Mar 1;20(2):10221-7. View Full Paper

16 Engberg RM, et al. The effect of Artemisia annua on broiler performance, on intestinal microbiota and on the course of a Clostridium perfringens infection applying a necrotic enteritis disease model. Avian Pathology. 2012 Aug 1;41(4):369-76. View Abstract

17 Goswami S, Bhakuni RS, Chinniah A, et al. Anti-Helicobacter pylori potential of artemisinin and its derivatives. Antimicrob Agents Chemother. 2012 Sep;56(9):4594-607. View Full Paper

18 Efferth T, et al. The antiviral activities of artemisinin and artesunate. Clin Infect Dis. 2008 Sep 15;47(6):804-11. View Abstract

19 Medhi B, Patyar S, Rao RS, et al. Pharmacokinetic and toxicological profile of artemisinin compounds: an update. Pharmacology. 2009;84(6):323-32. View Full Paper

20 Ahn H, Park JH. Liposomal delivery systems for intestinal lymphatic drug transport. Biomater Res. 2016 Nov 23;20:36. View Full Paper

21 Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci. 2014 Jan;103(1):29-52. View Full Paper

22 Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013 Jan;65(1):36-48. View Abstract

23 Isacchi B, Bergonzi MC, Grazioso M, et al. Artemisinin and artemisinin plus curcumin liposomal formulations: enhanced antimalarial efficacy against Plasmodium berghei-infected mice. Eur J Pharm Biopharm. 2012 Apr;80(3):528-34. View Abstract

24 Isacchi B, Arrigucci S, la Marca G, et al. Conventional and long-circulating liposomes of artemisinin: preparation, characterization, and pharmacokinetic profile in mice. J Liposome Res. 2011 Sep;21(3):237-44. View Abstract

 

 

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Keeping Holiday Stress in Check

Keeping Holiday Stress in Check

 

It’s that time of year when, no matter what we do, we often suffer some aspect of stress. For some, winter weather may tax the spirit and drain our energy. For others, it may be the stress of preparing for, cooking for, and socializing at holiday gatherings. Yet others may be encountering the holidays while struggling with family illness or feuds which stress and burden the heart. One holiday on top of another, there hardly is time (or daylight) to do all that we need to do, and then darkness hits and it feels like it is time for bed. How can we make it through the next month of celebration and another couple months of darkness when the demands on our lives feel so challenging already?

Nutritional Support for Well-Being

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It is important to try to get regular exposure to daylight and exercise as well as adequate rest during the winter months. Just as many animals hibernate, the human internal clock is dialed in to sleep more when there is more darkness.1 This doesn’t change the fact that many of us still have to fit the same amount of things into our day, but it may ease the worry we feel about being more tired in the darker months! Listening to the body’s clock helps to restore our energy for the times we need it. Supplemental support with a quality multivitamin or B complex vitamins can help the body to get through the winter slump. Many of the B vitamins as well as vitamin D and C support a balanced mood, which is challenged by the winter for many.2,3,4 Vitamin C and B complex vitamins support adrenal function and neurotransmitter metabolism,5,6 while vitamin D and vitamin C support healthy immune system function.7,8,9

Support from Adaptogens

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Adaptogens are substances, primarily herbs, which help the body adapt and respond to stress. Many of these herbs are roots, such as the well-known ginseng and licorice. Other adaptogens include rhodiola, maca, ashwagandha, and schisandra berry. Adaptogenic herbs have a history of use in many cultures for thousands of years. Adaptogens have an effect on the body’s hypothalamus-pituitary-adrenal (HPA) axis, and also can impact mood, memory, concentration, sleep, and immune system function.10,11 Many of these herbs also have antioxidant effects.12 Adaptogens, particularly in combination, can have a tonic effect – supporting increased exertion when needed, and helping the body to turn off when the work is done.13 There also are adaptogenic herbs such as shatavari, an Ayurvedic herb, and yohimbe with more specific “female” or “male” effects, supporting normal hormonal balance and reproductive function.14,15,16 Many individuals find increased motivation and energy throughout the day with the use of adaptogenic herbs.

Keeping Things Calm!

Keeping holiday stress in check JEN CD html 6e1d8994Finally, in addition to supporting the energy needed to make it through the holidays (and winter!), many are looking for healthy approaches to help them wind down in the evening and throughout the day. A combination of gamma-amino butyric acid (GABA) with L-theanine is an excellent choice, as the non-sedating yet relaxing effects can provide benefit throughout the day in times of stress or anxiety. Both GABA and L-theanine support increased alpha wave activity in the brain,17,18 and have been shown to reduce the physiological and emotional response to stress.19,20,21 L-theanine also has been observed to increase expression of brain-derived neurotrophic factor (BDNF),22 a protein that increases neural plasticity and promotes neurogenesis,23 possibly helping you to remember the long-winded story from your beloved great aunt or uncle told after a long, belly-filling dinner.

To learn more, read on at:

 


1 Wehr TA. Melatonin and seasonal rhythms. J Biol Rhythms. 1997 Dec;12(6):518-27. View Abstract

2 Amr M. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive

disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar;12(1):1. View Full Paper

3 Frandsen TB, Pareek M, Hansen JP et al. Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial

BMC Res Notes. 2014; 7: 52 View Full Paper

4 Coppen A1, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005 Jan;19(1):59-65. View Abstract

5 Patak P, Willenberg HS, Bornstein SR. Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocr Res. 2004 Nov;30(4):871-5. View Abstract

6 Ralli EP, Dumm ME. Relation of pantothenic acid to adrenal cortical function. Vitam Horm. 1953;11:133-58. View Abstract

7 Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013 Jan 31;1:CD000980. View Abstract

8 Shaik-Dasthagirisaheb YB, et al. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013; 27(2):291-295. View Abstract

9 Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-90. View Full Paper

10 Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219. View Abstract

11 Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel). 2010 Jan 19;3(1):188-224. View Full Paper

12 Davydov M, Krikorian AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. J Ethnopharmacol. 2000 Oct;72(3):345-93. View Abstract

13 Panossian AG. Adaptogens: Tonic herbs for fatigue and stress. Alternative & Complementary Therapies. 2003 Dec 1;9(6):327-31. View Abstract

14 Velavan S, Nagulendran KR, Mahesh R, Begum VH. Phcog Rev.: Plant Review The Chemistry, Pharmacological and Therapeutic Applications of Asparagus racemosus-A Review. Pharmacognosy Reviews. 2007 Jul;1(2):350-60. View Full Paper

15 Riley AJ. Yohimbine in the treatment of erectile disorder. Br J Clin Pract. 1994 May-Jun;48(3):133-6. View Abstract

16 Rowland DL1, Kallan K, Slob AK. Yohimbine, erectile capacity, and sexual response in men. Arch Sex Behav. 1997 Feb;26(1):49-62. View Abstract

17 Yoto A, Murao S, Motoki M, et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43(3):1331–1337. View Abstract

18 Kakuda T, Nozawa A, Sugimoto A, et al. Inhibition by Theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002;66(12):2683–2686.

19 Abdou AM, Higashiguchi S, Horie K, et al. Relaxation and immunity enhancement effects of gammaaminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201–208. View Abstract

20 Lu K, Gray MA, Oliver C, et al. The acute effects of L-Theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol. 2004;19(7):457–465 View Abstract

21 Kimura K, Ozeki M, Juneja LR, et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39–45. View Abstract

22 Wakabayashi C, Numakawa T, Ninomiya M, et al. Behavioral and molecular evidence for psychotropic effects in L-Theanine. Psychopharmacology (Berl). 2012;219(4):1099–1109. View Abstract

23 Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123–131. View Abstract

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Mercury: A Potent Toxin With Widespread Health Impacts

Mercury: A Potent Toxin With Widespread Health Impacts

Mercury is a potent neurotoxin—in its liquid form it has even been called ‘liquid death’. It has been designated by the World Health Organization as one of the ten most dangerous chemicals to public health.1 Exposure to as little as 1.3 grams of dimethylmercury causes irreversible neurological problems and death.2

The toxicity of mercury is unsettling because the metal is all around us. Volcanoes, mines, and oceans release mercury into air, soil, and groundwater; however, nearly 80% of environmental mercury is a consequence of human activity such as fossil fuel combustion, agriculture, and mining.3 Developing countries produce and release as much as 200 metric tons of mercury every year.2 The US is no less culpable—we create about 10% of the world’s mercury pollution each year.2

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Before we can understand mercury’s damaging health effects, we need to know about the different forms. Mercury can exist as elemental (or metallic) mercury, inorganic mercury salts, and organic mercury. Elemental mercury is the silver liquid found in old thermometers and amalgam dental fillings.4 Elemental mercury enters the body primarily through inhalation of mercury vapors. Most of the mercury in water, soil, plants, and animals exists as inorganicmercury salts.5 Organic mercury includes substances such as methylmercury, dimethylmercury, ethylmercury, and phenylmercuric compounds. Organic mercury is freely absorbed in the gut. The main source of organic mercury exposure, in the form of methylmercury, is from contaminated fish. Vaccines that contain the preservative, thimerosal, contain ethylmercury.6 Methylmercury and dimethylmercury are highly toxic.

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Elemental mercury and most forms of organic mercury (such as methylmercury) are lipophilic, or fat-loving. They can readily cross the blood-brain barrier and the placenta. Once these forms of mercury are absorbed into the bloodstream they can damage the brain, heart, kidneys and numerous tissues and organs throughout the body.7,8 Inhaled elemental mercury is acutely toxic to the lungs, mucous membranes of the mouth, the gastrointestinal tract, the eyes, and the skin. Chronic exposure to elemental mercury vapors has a particularly potent and long-lasting effects on the central nervous system.9

Mercury and the Immune System

Mercury creates a highly destructive, pro-oxidant state that damages immune function. Many immune cells are ultimately damaged, including B cells, total white cell counts, neutrophils, and more.10,11,12 One major target is the T lymphocyte, or the T cell. Mercury blocks the T cell's ability to secrete chemicals, called cytokines, that help coordinate an immune response.2 It also shifts the balance between two types of T cells (helper Th1 and suppressor Th2 cells) to create an environment in which autoimmune disease development is more likely. Essentially, the immune system is shifted toward an excessive helper Th1 response, and this, in conjunction with other factors of risk, leads the immune system cells to recognize normal human proteins as foreign invaders and mount an autoimmune response.13 This relationship is hinted at in epidemiological studies which show that people with autoimmune diseases have higher levels of mercury on average than people without autoimmune diseases.14

Mercury and the Body’s Antioxidant Systems

Mercury impairs the function of our most potent endogenous antioxidant, glutathione. Mercury (particularly methylmercury) binds to glutathione, reducing its availability in the body, as well as creating a glutathione-mercury complex that penetrates virtually all membranes in the body and is highly toxic to cells and tissues.15

Mercury also damages the body through its interference with the important trace mineral selenium. Mercury can actually bind to selenium, indirectly causing a selenium-deficiency state in the body.16 This is significant because mercury then displaces selenium from a family of important enzymes called selenoenzymes, which includes glutathione peroxidase.17 These enzymes have powerful antioxidant ability.18

Mercury and the Nervous, Endocrine and Reproductive Systems

The classic symptoms of acute mercury poisoning include tremor, gingivitis, and bizarre behavior (e.g., excessive shyness or aggression). Inhaled mercury vapor is associated with neuropsychological problems such as emotional lability at high exposures or more subtle motor and memory deficits at low exposures.19

Children are particularly vulnerable to mercury. Numerous studies have shown a correlation between mercury exposure and autism.20,21 Childhood obesity has also been linked to thimerosal-containing vaccines.22

Mercury is a potent disruptor of our adrenal, pituitary, thyroid glands.23 These glands tend to preferentially absorb and store mercury.24 Chronic exposure to mercury has been shown to be associated with autoimmune thyroiditis and subsequent hypothyroidism.25 Mercury in the adrenal gland lowers plasma levels of corticosterone, which can lead to adrenal hyperplasia.26 This effect is believed to contribute to the development of Addison's disease.27

In men, mercury exposure can decrease sperm count, and the sperm cells that are produced have structural problems especially in the tails, which decreases sperm motility.28 Women who are exposed to mercury before or during pregnancy may suffer from menstrual cycle disruption and are at increased risk of miscarriage, preterm delivery, or a newborn with low birth weight.29

Mercury and the Pregnant Woman

Mercury Toxicity 11 19 CD html 2a002a73Pregnant women have reason to be concerned about mercury exposure. The fetus, nestled in the protective womb, is vulnerable to the effects of elemental and organic mercury, because they easily cross from the maternal bloodstream through the placenta.30,31 Heavy metal interference with fetal growth and development can cause long-term physical and cognitive problems. For example, toddlers that were exposed to even low levels of methylmercury during gestation have diminished fine motor skills, correlated with the amount of methylmercury found in the umbilical cord blood.32

Children with in utero exposure to mercury have impaired language and communication skills when measured at the age of five. In this study, it was also found that the amount of seafood consumed during pregnancy correlated with language and communication deficits in the children.33 The neurological effects of mercury on fetuses may extend beyond simple cognitive, motor, and communication deficits. Mercury exposure in prenatal and neonatal periods may increase the risk for autism spectrum disorders.34

Protecting Yourself From Mercury Exposure

Mercury Toxicity 11 19 CD html e0316038Even though mercury is nearly universal in our environment, there are measures we can take to reduce exposure and to mitigate its impact. Perhaps the biggest risk to mercury exposure in the general population is the consumption of mercury contaminated-fish. But not all fish are equal. The amount of mercury contained in seafood varies depending on the species and the source. Fish harvested from polluted freshwater including bass, pike, and walleye may contain high levels of methylmercury. Likewise, fish on the higher end of the food chain such as shark, swordfish, and tuna have particularly high levels of methylmercury because they concentrate the compound from the numerous mercury-contaminated fish that they eat themselves.

Regulatory authorities have established maximum safe levels for mercury in fish, suggesting that only a certain number of fish should be consumed in a given month. These recommendations vary depending on the species of fish and the source; however, without testing the fish directly or monitoring one's blood or urine for mercury it is impossible to determine exactly how much mercury one is consuming. A diet rich in fish can convey a number of health benefits; however, this must be balanced with the risk of mercury exposure.

Certain nutrients may be able to further protect against the effects of mercury. We know that mercury irreversibly inhibits selenoenzymes thioredoxin reductase and glutathione peroxidase.35 These enzymes are important for restoring glutathione, as well as vitamin E, to their reduced forms, so they can function as antioxidants.36 Selenium supplementation to support adequate selenium levels may be protective. A good food source of selenium is the brazil nut. Since mercury exposure decreases the body’s level of glutathione, maintaining adequate glutathione levels is of particular importance. Glutathione supplementation can help to restore levels depleted by mercury exposure. Vitamin E supplementation also may further protect against the pro-oxidative state caused by mercury exposure.37 Of particular importance is binding and removing the toxic mercury from the body, which can be safely and effectively done via oral supplementation with a thiol-functionalized silica, which tightly binds the mercury in the gut, removing it from the body.

To learn more, read on at:

 


1 Bjørklund G, Dadar M, Mutter J, et al. The toxicology of mercury: Current research and emerging trends.

Environ Res. 2017 Nov;159:545-554. View Abstract

2 Nierenberg DW, Nordgren RE, Chang MB, et al. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med. Jun 04 1998;338(23):1672-1676. View Full Paper

3 Rani L, Basnet B, Kumar A. Mercury Toxicity. Encyclopedia of Environmental Health. Burlington: Elsevier; 2011:705-712.

4 Clarkson TW. The three modern faces of mercury. Environ Health Perspect. Feb 2002;110 Suppl 1:11-23. View Full Paper

5 Fisher JF. Elemental mercury and inorganic mercury compounds: human health aspects. World Health Organization. 2003:8-9. View Full Paper

6 Dorea JG, Farina M, Rocha JB. Toxicity of ethylmercury (and Thimerosal): a comparison with methylmercury. J Appl Toxicol. Aug 2013;33(8):700-711. View Abstract

7 Genchi G, Sinicropi MS, Carocci A et al. Mercury Exposure and Heart Diseases. Int J Environ Res Public Health. 2017 Jan 12;14(1). View Abstract

8 Maqbool F, Niaz K, Hassan FI , et al. Immunotoxicity of mercury: Pathological and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2017 Jan 2;35(1):29-46. View Abstract

9 Andrade VM, Aschner M, Marreilha Dos Santos AP. Neurotoxicity of Metal Mixtures. Adv Neurobiol. 2017;18:227-265. View Abstract PMID: 28889271

10 Gill R, McCabe MJ Jr, Rosenspire AJ. Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells.Toxicol Appl Pharmacol. 2017 Sep 1;330:22-29. View Abstract

11 Guardiola FA, Chaves-Pozo E, Espinosa C, et al. Mercury Accumulation, Structural Damages, and Antioxidant and Immune Status Changes in the Gilthead Seabream (Sparus aurata L.) Exposed to Methylmercury.Arch Environ Contam Toxicol. 2016 May;70(4):734-46. View Abstract

12 Desforges JP, Sonne C, Levin M, et al. Immunotoxic effects of environmental pollutants in marine mammals. Environ Int. 2016 Jan;86:126-39. View Abstract

13 de Vos G, Abotaga S, Liao Z, et al. Selective effect of mercury on Th2-type cytokine production in humans. Immunopharmacol Immunotoxicol. 2007;29(3-4):537-548. View Abstract

14 Crowe W, Allsopp PJ, Watson GE, et al. Mercury as an environmental stimulus in the development of autoimmunity - A systematic review. Autoimmun Rev. Jan 2017;16(1):72-80 View Abstract

15 Rubino FM. Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms. Toxics. 2015;3(1):20-62. View Full Paper

16 Das K, Dupont A, De Pauw-Gillet MC et al. Absence of selenium protection against methylmercury toxicity in harbour seal leucocytes in vitro. Mar Pollut Bull. 2016 Jul 15;108(1-2):70-6. View Abstract

17 Suzuki KT, Sasakura C, Yoneda S. Binding sites for the (Hg-Se) complex on selenoprotein P. Biochim Biophys Acta. Dec 08 1998;1429(1):102-112. View Abstract

18 Chen C, Yu H, Zhao J, et al. The Roles of Serum Selenium and Selenoproteins on Mercury Toxicity in Environmental and Occupational Exposure. Environ Health Perspect. 2006;114(2):297-301. View Abstract

19 Clarkson TW. The toxicology of mercury. Crit Rev Clin Lab Sci. 1997;34(4):369-403.

20 The Putative Role of Environmental Mercury in the Pathogenesis and Pathophysiology of Autism Spectrum Disorders and Subtypes. Mol Neurobiol. 2017 Jul 22. View Abstract

21 Geier DA, Kern JK, Geier MR Increased risk for an atypical autism diagnosis following Thimerosal-containing vaccine exposure in the United States: A prospective longitudinal case-control study in the Vaccine Safety Datalink. J Trace Elem Med Biol. 2017 Jul;42:18-24. View Abstract

22 Thimerosal-containing Hepatitis B Vaccine Exposure is Highly Associated with Childhood Obesity: A Case-control Study Using the Vaccine Safety Datalink. N Am J Med Sci. 2016 Jul;8(7):297-306. View Abstract

23 Pantaleão TU, Ferreira ACF, Santos MCS et al. Effect of thimerosal on thyroid hormones metabolism in rats. Endocr Connect. 2017 Nov;6(8):741-74 View Full Paper

24 Zhu X, Kusaka Y, Sato K, et al. The endocrine disruptive effects of mercury. Environ Health Prev Med. 2000 Jan;4(4):174-83. View Full Paper

25Kisakol G. Dental amalgam implantation and thyroid autoimmunity Bratisl Lek Listy. 2014;115(1):22-4. View Abstract

26 Iavicoli I, Fontana L, Bergamaschi A. The effects of metals as endocrine disruptors. J Toxicol Environ Health B Crit Rev. Mar 2009;12(3):206-223.

27 Wada H, Cristol DA, McNabb FM, et al. Suppressed adrenocortical responses and thyroid hormone levels in birds near a mercury-contaminated river. Environ Sci Technol. Aug 01 2009;43(15):6031-6038. View Abstract

28 Zeng Q, Feng W, Zhou B Urinary metal concentrations in relation to semen quality: a cross-sectional study in China. Environ Sci Technol. 2015 Apr 21;49(8):5052-9. View Abstract

29 Buck Louis GM, Smarr MM, Sundaram R et al. Low-level environmental metals and metalloids and incident pregnancy loss. Reprod Toxicol. 2017 Apr;69:68-74. View Abstract

30 Gundacker C, Neesen J, Straka E. Genetics of the human placenta: implications for toxicokinetics. Arch Toxicol. 2016 Nov;90(11):2563-2581. View Abstract

31 Gundacker C, Hengstschläger M. The role of the placenta in fetal exposure to heavy metals. Wien Med Wochenschr. 2012 May;162(9-10):201-6. View Abstract

32 Prpic I, Milardovic A, Vlasic-Cicvaric I, et al. Prenatal exposure to low-level methylmercury alters the child's fine motor skills at the age of 18 months. Environ Res. Jan 2017;152:369-374 View Abstract

33 Vejrup K, Brandlistuen RE, Brantsaeter AL, et al. Prenatal mercury exposure, maternal seafood consumption and associations with child language at five years. Environ Int. Jan 2018;110:71-79. View Abstract

34 Yoshimasu K, Kiyohara C, Takemura S, et al. A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology. Sep 2014;44:121-131. View Abstract

35 Branco V, Canario J, Lu J, et al. Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase. Free Radic Biol Med. Feb 15 2012;52(4):781-793. View Abstract

36 Ganther HE. Modification of methylmercury toxicity and metabolism by selenium and vitamin E: possible mechanisms. Environ Health Perspect. 1978 Aug; 25: 71–76. View Full Paper

37 Al-Attar AM. Vitamin E attenuates liver injury induced by exposure to lead, mercury, cadmium and copper in albino mice. Saudi J Biol Sci. Oct 2011;18(4):395-401. View Full Paper

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Vitamin C: Essential Protection for the Winter and Beyond

Vitamin C: Essential Protection for the Winter and Beyond

In an era of astounding scientific breakthroughs—where healthy babies are crafted from the genes of three parents and we use CT scans to analyze 99- million-year-old baby bird hatchlings preserved in amber—we can sometimes forget the simple things. That includes the well-known goodness of vitamin C, famous for preventing the fatal disease scurvy in 18th century sailors and for winning the unbridled enthusiasm of two-time Nobel winner Linus Pauling.

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Vitamin C—also known as ascorbic acid—is one of those essential nutrients that we cannot synthesize ourselves. It is a water soluble molecule and must be obtained from our diet or from supplements. It is absorbed in our small intestine about 2-3 hours after we consume it, and distributed from the blood through the entire extracellular space, though it is most highly concentrated in the liver, brain and skeletal muscle.1 Vitamin C has been shown to be important in immune function, wound healing, mood, allergies, and more.2,3,4

Screen Shot 2017 11 20 at 2.26.24 PMVitamin C works its magic as an “electron donor”—when it donates electrons, it offers energy to fifteen different enzymes that are crucial for many functions in mammals.5 When an oxidized molecule gains an electron, it not only gains energy—it is then stabilized and called “reduced.” By donating electrons to oxidized molecules, vitamin C can function as a powerful antioxidant.6 In fact, vitamin C is one of the most potent water-soluble antioxidants in the body.7 The vitamin not only scavenges free radicals, it also reduces lipid peroxidation of cellular membranes, and supports other important antioxidants, including vitamin E and glutathione.8,9 It is essential for collagen synthesis, as well as the synthesis of carnitine and important neurotransmitters.10

You might think you get enough vitamin C from your diet—after all, it is abundant in foods ranging from strawberries to oranges, grapefruits, papaya, broccoli, kale and more. However, low dietary intake and plasma concentrations of the vitamin are surprisingly common. One survey of over 7,000 Americans found that 8.2% of males and 6% of females had such low concentrations of vitamin C in their blood they could actually experience symptoms of scurvy.11 In addition, the vitamin is depleted by smoking, serious illness, and heart attacks.12,13

Vitamin C CD html dba55986Increasing our vitamin C intake can have many beneficial effects. The vitamin can help prevent, as well as decrease the severity of infections, particularly the common cold. Vitamin C along with zinc has been shown to reduce symptoms of the common cold over a five day period.14 Nearly 150 animal studies have shown that vitamin C may alleviate or prevent infections caused by bacteria, viruses, and protozoa. It has been shown to reduce the number of colds in physically active people by half, and shorten the duration of colds as well; also helping to prevent pneumonia in two studies.15 In addition, case reports suggest it may help ameliorate outbreaks of herpes zoster (commonly called shingles), as well as reduce the painful neuralgia associated with it.16,17

Vitamin C can improve the function of the immune system’s first line of defense, natural killer cells.18 Neutrophils, which when activated produce oxidants such as ozone and hydrogen peroxide that kill pathogenic bacteria, rapidly absorb vitamin C, increasing their concentrations as much as ten times.19

Screen Shot 2017 11 20 at 2.26.31 PMVitamin C may be necessary for a healthy response to stress. It is necessary to help our adrenal glands synthesize several hormones and neurotransmitters. In fact, the adrenals are one of the organs with the highest concentration of vitamin C, and they actually secrete the vitamin in response to the stress hormone, adrenocorticotrophic hormone (ACTH).20

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Stress can impact mood, so it’s not surprising to learn that vitamin C is also important in balancing mood. The vitamin enhances the production of the feel-good, energizing neurotransmitter norepinephrine.21 Deficiency of vitamin C has been linked to lower levels of metabolites of two major mood-enhancing neurotransmitters, dopamine and serotonin.22 Low plasma ascorbic acid levels correlate with major depression.23 Vitamin C also appears to reduce anxiety and depression in double-blind, randomized, placebo-controlled trials.24,25 The vitamin has even been shown to improve mood in hospitalized patients.26

When we take conventional vitamin C by mouth as a supplement, absorption actually decreases with increasing dosage due to gastrointestinal saturation. A liposomal delivery form can circumvent that loss and enable effective high-level dosing without intravenous therapy.27,28 In addition, sodium ascorbate, a mineral salt of ascorbic acid, is buffered and generally better tolerated than regular ascorbic acid supplements by those with gastrointestinal sensitivity.

Vitamin C’s diverse benefits show just how versatile and fundamental this simple, water-soluble molecule really is. As an electron donor, vitamin C is essential to the exchange of energy throughout your body. It is also necessary for recycling and recharging other antioxidants to control free radical damage. No wonder it impacts everything from your immune system to your mood.


 

1 Padayatty SJ, Levine M. Vitamin C physiology: the known and the unknown and Goldilocks.

Oral Dis. 2016 Sep;22(6):463-93. View Full Paper

2 Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, et al. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013; 27(2):291-295. View Abstract

3 Hagel AF, Layritz CM. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013 Sep

1;386(9):789-93. View Abstract

4 May JM, Qu Z, Nazarewicz R, et al. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013 Jan;90:35-42. View Full Paper

5 Stone, I. The Natural History of Ascorbic Acid in the Evolution of the Mammals and Primates and Its Significance for Present Day Man. 1956 [Cited Nov 10, 2017] Available at: https://www.seanet.com/~alexs/.../stone-i-orthomol_psych-1972-v1-n2-3-p82.htm

6 Bendich A, et al. The antioxidant role of vitamin C. Adv Free Radic Biol Med. 1986 Dec;2(2):419-44. View Abstract

7 Druoin G, Godin JR, Pagé B. The Genetics of Vitamin C Loss in Vertebrates. Curr Genomics. 2011 Aug; 12(5): 371–378 View Full Paper

8 Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients.

FASEB J. 1987 Dec;1(6):441-5 View Full Paper

9 Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem. 1994 Apr

1;269(13):9397-400. View Full Paper

10 Padh H. Cellular functions of ascorbic acid. Biochem. Cell Biol. 1990;68:1166–1173 View Abstract

11 Schleicher RL, Carroll MD, Ford ES et al. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr. 2009 Nov;90(5):1252-63. View Abstract

12 Schectman G, Byrd JC, Gruchow HW. The influence of smoking on vitamin C status in adults. Am J Public Health. 1989 Feb;79(2):158-62 View Full Paper

13 Padayatty SJ, Levine M. Vitamin C and myocardial infarction: the heart of the matter.

Am J Clin Nutr. 2000 May;71(5):1027-8 View Full Paper

14 Maggini S, Beveridge S, Suter M. A combination of high-dose vitamin C plus zinc for the common cold.

Int Med Res. 2012;40(1):28-42. View Full Paper

15 Hemilä H. Vitamin C and Infections. Nutrients. 2017 Mar 29;9(4). View Full Paper

16 Orient, J.M. Treating herpes zoster with vitamin C: Two case reports. J. Am. Phys. Surg. 2006, 11, 26–27. View Full Paper

17 Schencking M, Sandholzer H, Frese T. Intravenous administration of vitamin C in the treatment of herpetic neuralgia: two case reports. Med Sci Monit. 2010 May;16(5):CS58-61. View Abstract

18 Huijskens MJ, Walczak M, Sarkar S et al. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy. 2015 May;17(5):613-20 View Abstract

19 Wang Y, Russo TA, Kwon O, et al. Ascorbate recycling in human neutrophils: induction by bacteria. Proc Natl Acad Sci USA 1997; 94:13816–9. View Abstract

20 Padayatty SJ, Doppman JL, Chang R et al. Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. Am J Clin Nutr. 2007 Jul;86(1):145-9. View Full Paper

21 May JM, Qu ZC, Nazarewicz R, et al. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013 Jan;90:35-42. View Full Paper

22 Ward MS, Lamb J, May JM, et al. Behavioral and monoamine changes following severe vitamin C deficiency. J Neurochem. 2013 Feb;124(3):363-75. View Full Paper

23 Khanzode SD, et al. Oxidative damage and major depression: the potential antioxidant action of

selective serotonin re-uptake inhibitors. Redox Rep. 2003;8(6):365-70. View Abstract

24 de Oliveira IJ. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind,

Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015 Jan;18(1):11-8. View Abstract

25 Amr M. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive

disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar;12(1):1. View Full Paper

26 Zhang M, Robitaille L, Eintracht S et al. Vitamin C provision improves mood in acutely hospitalized

patients. Nutrition 2011, 27, 530–533. View Abstract

27 Ahn H, Park JH. Liposomal delivery systems for intestinal lymphatic drug transport. Biomater Res. 2016 Nov 23;20:36. View Abstract

28 Yang Z, Lu A, Wong BC, et al. Effect of liposomes on the absorption of water-soluble active pharmaceutical ingredients via oral administration. Curr Pharm Des. 2013;19(37):6647-54. View Abstract

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CoQ10: The Heart of the Matter

CoQ10: The Heart of the Matter

Coenzyme Q10 (CoQ10), also commonly known by the names of its oxidized and reduced forms ubiquinone and ubiquinol, is one of our body’s most essential bionutrients. It is a potent, lipid-soluble antioxidant found in every one of our fifty trillion cells—and it is the only lipid-soluble antioxidant our bodies actually synthesize. The concentration of CoQ10 is greatest in organs with high rates of metabolism, such as the heart, kidney, adrenals, spleen and liver. Because of its energy-rich, antioxidant-rich ability, it has a significant, broad impact on aging and health. CoQ10 supports the health of the circulatory system, lungs, brain, nervous system, reproductive system, and the eyes and oral tissues.1CoQ10 CD html ef83acee

CoQ10 is a potent antioxidant that can neutralize free radicals and reactive oxygen species, preventing lipid, protein and DNA oxidation. Like all antioxidants, CoQ10 exists in an electron-rich reduced form called CoQH2 or ubiquinol, which donates electrons to highly reactive, unstable molecules called free radicals—and stabilizes them. Once it has donated its electrons, it is oxidized to ubiquinone, and then the body adds electrons back to it, essentially recycling it to once again scavenge free radicals.

CoQ10 is very important for the health of our mitochondria, the energy powerhouses that reside in all of our cells. It is essential to the process of cellular respiration that produces energy (in the form of adenosine triphosphate, or ATP). And thus, it plays a key role in cardiovascular health and healthy aging.2 

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The heart beats 100,000 times each day, and 2.5 billion times by age 70, which requires a huge amount of energy. The heart, comprised of muscle tissue, contains the largest amount of energy-generating mitochondria of any muscle, so it is not surprising that CoQ10 has been shown to be very important for cardiovascular health.3

CoQ10 inhibits the peroxidation of cell membrane lipids, and has been shown to decrease the concentration of lipid hydroperoxides (damaged lipids which generate further oxidative damage) in atherosclerotic lesions, simultaneously minimizing the size of these lesions in the heart’s aorta.4 It also prevents both the initiation and the propagation of lipid peroxidation, while vitamin E, in contrast, only inhibits propagation.5 In animal studies, CoQ10 helped protect against aging-related oxidative stress, and also improved mitochondrial function in the heart.6 A landmark 1985 double-blind, placebo-controlled, cross-over study found significant benefits of CoQ10 in heart failure, including improvements in cardiac function and well-being.7

CoQ10 levels tend to be lower in individuals with high cholesterol compared to healthy individuals of the same age. Worsening the situation, certain cholesterol-lowering drugs called statins inhibit the same enzyme that is necessary to make CoQ10, known as HMG-CoA reductase, and can lead to further decreases.8,9 CoQ10 supplementation may decrease the muscle pain associated with statin treatment.10

CoQ10 CD html 4c5ec084The antioxidant activity of CoQ10 is significant. The inner membrane of each mitochondrion contains CoQ10 as well as vitamin E in the form of α-tocopherol, both of which have antioxidant properties. CoQ10 and α-tocopherol act together to quench free radicals during autoxidation of mitochondrial membranes.11,12 This action is important, because oxidative stress—often triggered by environmental toxins, stress, and chronic inflammation—can impair mitochondrial function and thus contribute to aging and disease. Healthy mitochondria function is not only important for cardiovascular health and muscle function, but also for the function of our brain. Impairments in mitochondrial function have been demonstrated in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, and more.13

CoQ10 is neuroprotective. In studies of Parkinson’s patients, it appeared to protect against the well-known “wearing off” effect that occurs with long-term levodopa use. It also significantly improved symptoms, and was found to be safe and well tolerated.14 In animal studies, it has been shown to actually increase concentration of the nutrient in mitochondria in the brain. As the researchers note: “If defects in energy metabolism and oxidative damage play a role in the pathogenesis of neurodegenerative diseases, then treatment with coenzyme Q10 could exert beneficial therapeutic effects.”15

When we are young and healthy, we synthesize CoQ10 readily on our own. However, this requires a 17-step process dependent on at least seven vitamins (vitamins B2, B3, B5, B6, B12, C, and folic acid) and several trace elements. Renowned chemist Karl Folkers, whose laboratory helped synthesize CoQ10, argued that suboptimal nutrient intake is nearly universal and that this might lead to widespread impairment in CoQ10 biosynthesis.16 Moreover, stress—such as illness or an accident—also depletes this essential molecule. Decreased blood levels of CoQ10 are seen in a broad range of critically ill patients.17

CoQ10 CD html 721e0ab2Though CoQ10 can be found in oily fish (such as salmon and tuna), organ meats (such as liver), and whole grains, it can be hard to get all we need as we get older. A slow continuous decline in our own production of CoQ10 becomes apparent around forty years of age, and by age 80 we will only be making about 35% of your youthful levels.18 “A steady, lifetime decrease in CoQ10 is far more common than we may have assumed,” states biochemist Magnus Bentinger of Stockholm University and the Rolf Luft Center for Diabetes and Endocrinology in Stockholm.19 Declining levels of CoQ10 are associated with heart disease, neurodegenerative diseases, cancer, diabetes, and the loss of stamina and energy that accompanies aging.7 Research suggests that CoQ10 may even help protect female reproductive capacity, which declines dramatically after age forty. Aging of female eggs (oocytes) are accompanied by mitochondrial dysfunction and diminished expression of the enzymes responsible for CoQ10 production.20

CoQ10 might even help retard aging of the skin, since it is necessary for the function of mitochondria within the cells of the skin as well. Because of this, CoQ10 also has been studied as a wrinkle-preventing, anti-aging skin molecule.21 It has been shown to exert protective effects against sun damage through its antioxidant action as well.22

Gastrointestinal absorption of supplemental CoQ10 is limited, but it is dramatically increased in a nanoemulsified liposomal format, which allows for direct uptake into the into circulation, and also promotes delivery into the cell and mitochondria where its benefits are most seen.23

Read more about mitochondria and their importance for health and aging


1 Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: An update. Nutrition. 2010;26(3):250-254. View Abstract

2 Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011;3(3): 466–467. View Abstract

3 Saljoughian M. Coenzyme Q10: A Potential Cardiotonic and Antioxidant US Pharm. 2011;36(2):HS21-HS-26. View Full Paper

4 Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments Mol Biotechnol. 2007; 9;37(1):31-7. View Abstract

5 Sohal RS, Forster MJ. Coenzyme Q, oxidative stress and aging. Mitochondrion. 2007 6;(7): Suppl:S103-11. View Full Paper

6 Ochoa JJ, Quiles JL, Huertas JR et al. Coenzyme Q10 Protects From Aging-Related Oxidative Stress and Improves Mitochondrial Function in Heart of Rats Fed a Polyunsaturated Fatty Acid (PUFA)-Rich Diet, The Journals of Gerontology 2005;60(8):970-975.View Full Paper

7 Langsjoen PH, Vadhanavikit S, Folkers K. Effective treatment with coenzyme Q10 of patients with chronic myocardial disease. Drugs Under Experimental and Clinical Research 1985; 11:(8): 577-579 View Abstract

8 Mortensen SA1, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18 Suppl:S137-44. View Abstract

9 Nawarskas JJ. HMG-CoA reductase inhibitors and coenzyme Q10. Cardiol Rev. 2005 Mar-Apr;13(2):76-9. View Abstract

10 Caso G, Kelly P, McNurlan MA, et al. Effect of coenzyme Q10 on myopathyic symptoms in patients treated with statins. Am J Cardiol. 2007;99(10):1409-1412. View Abstract

11 Kagan V, Serbinova E, Packer L. Antioxidant effects of ubioquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophy Res Commun. 1990:(169):851–857 View Abstract

12 Kamzalov S, Sumien N, Forster MJ et al. Coenzyme Q intake elevates the mitochondrial and tissue levels of coenzyme Q and α-tocopherol in young mice. J Nutr. 2003;(133):3175–3180. View Abstract

13 Kidd PM. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev. 2005 12;10(4):268-93. View Abstract

14 Yoritaka A, Kawajiri S, Yamamoto Y. Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease. Parkinsonism Relat Disord. 2015;8(8):911-6. View Abstract

15 Matthews RT, Yang L, Browne S. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. PNAS 1998;95(15):8892-8897 View Full Paper

16 Shinde S, Patil N, Tendolkar A. Coenzyme Q10: A Review of Essential Functions. The Internet Journal of Nutrition and Wellness. 2004 1:(2) View Full Paper

17 Coppadoro A1, Berra L, Kumar A Critical illness is associated with decreased plasma levels of coenzyme Q10: a cross-sectional study. J Crit Care. 2013;28(5):571-6 View Full Paper

18 Fuke C, Krikorian SA, Couris RR. Coenzyme Q10: a review of essential functions and clinical trials. US Pharmacist, 2000;25(10): 28-41

19 Bentinger M, Brismar K, Dallner G. The antioxidant role of coenzyme Q10. Mitochondrion 2007 6;(7s): 41-50. View Abstract

20 Ben-Meir A, Burstein E, Borrego-Alvarez A Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging Aging Cell. 2015;10;14(5):887-95. View Full Paper

21 Prahl S. Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care. Biofactors. 2008;32(1-4):245-55. View Full Paper

22 Inui M. Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivo. Biofactors. 2008;32(1-4):237-43. View Abstract

23 Beg S, Javed S, Kohli K. Bioavailability enhancement of coenzyme Q10: an extensive review of patents. Recent Pat Drug Deliv Formul. 2010;11(3):245-55. View Abstract

 

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Boost Your Immunity & Banish Winter Blues

Boost Your Immunity & Banish Winter Blues

A Look at the Protective Power of Vitamins D3 and K2

Ah, that summer sun—how we all look forward to it, at the beach, poolside, park, patio, or just walking down the street on a midsummer day. Our mood lifts. Our bodies feel stronger. In essence, we feel more vital. But alas, autumn and winter are not far behind, and bring with them shorter days, longer nights, and for many, a slump in mood that seems abetted by darkness, as well as seasonal colds and flus as we shiver through winter’s wind and snow or rain. Why can’t it be eternal summer? Or if it can’t, are there ways we can mimic summer’s blessings by supporting our body nutritionally?

Supplemental vitamin D is one such tool that helps us to combat winter’s challenges. Most of life on earth is dependent on the sun for energy, warmth and often, vitamin D.1 For humans, vitamin D3 (cholecalciferol) is literally light transformed. During exposure to sunlight, a molecule in our skin called 7-dehydrocholesterol absorbs ultraviolet B radiation, which is the initial reaction in the process of several steps which are necessary for conversion to the active form of vitamin D3. Vitamin D3 is then metabolized in the liver into 25-hydroxyvitamin D (the form we measure) and in the kidneys to 1,25-dihydroxyvitamin D (the biologically active form).

Receptors for vitamin D are widely expressed throughout the body, being found in over 36 different cell types.2 In 2012, a remarkable feat of sequencing revealed that the human genome itself literally has thousands of binding sites for vitamin D, reaffirming how fundamental this vitamin is for the body.3 And yet, there is widespread vitamin D deficiency—as many as a billion people worldwide are deficient in vitamin D, according to a 2017 review.4 Vitamin D deficiency has been linked to numerous health issues: autoimmune disease, allergies, certain cancers, depression, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes, and cardiovascular disease, to name a few.5,6,7,8,9,10,11,12,13 Vitamin D3 is also the precursor to a class of D3-related hormones that have numerous functions in the body beyond balancing levels of calcium.

Vitamin D synthesis is influenced by season, time of day, latitude, altitude, as well as less well known factors of air pollution, skin pigmentation, aging, and whether or not you use sunscreen.14 One of the most dramatic factors is latitude, and in the shorter days of winter, the skin makes very little vitamin D at above 37 degrees north or below 37 degrees south of the equator.15 As the 37th parallel defines the southern borders of Utah, Colorado, and Kansas, and the northern borders of Arizona, New Mexico, and Oklahoma, this represents a large population of the US. Anyone living to the north of this line, including major cities such as San Francisco, Chicago, New York, St. Louis, Denver, Boston, and Seattle, are at an increased risk of winter vitamin D deficiency. Even people living in regions with abundant sunlight year-round often do not get enough sun exposure to ensure vitamin D adequacy, as winter simply adds to the burden of long hours in offices, commutes by train, subway or car, and evenings spent indoors.

Vitamin D supplementation is not only important for reversing or preventing deficiency, but also for healthy immune system function and mood.16,17 Adequate levels of vitamin D are necessary for the innate immune system, our body’s first defenders, to function normally, preventing infection by bacterial, fungal, and viral invaders.18 Lower vitamin D levels are associated with larger tonsil size and recurrent tonsillopharyngitis in children,19 as well as increased incidence of upper respiratory infection (URTI) and community acquired pneumonia in adults.20,21 Vitamin D supplementation also may help prevent URTI in children with asthma.22

Vitamin D deficiency has been found in many studies to be associated with depression, which a recent systematic review and meta-analysis of observational studies and randomized controlled trials also reaffirmed.23 Supplementation of vitamin D was associated with an improvement in vitamin D levels as well as depression scale scores in patients with seasonal affective disorder, while those in the light therapy group only had improvements in their vitamin D levels.24 Although larger meta-analysis have failed to show an impact of vitamin D supplementation on mood in a broad population, improvements have been seen in smaller studies with an overweight or obese population,25 patients with major depressive disorder,26 and women with seasonal depressive symptoms.27

In addition to its importance for mood and immune function, vitamin D is important for maintaining healthy bones. Without it, the body can't absorb the calcium it ingests, and may borrow calcium from bones, increasing the risk of osteoporosis and fractures.28 It is important to note, however, that vitamin D should not be supplemented alone. Scientific studies, especially focusing on bone health and vascular calcification, find that supplementing with vitamin K at the same time is important.29,30,31 Vitamin K is important for arterial health and assists vitamin D in accomplishing many of its activities in the body.32 Vitamin K helps direct calcium deposition to the bone matrix, by activating osteocalcin. Vitamin K deficiency may be associated with soft tissue calcification and lower bone mineral density.33

Certain forms of vitamin K are more active in the body than others. Menaquinone-7, or MK-7, is a highly bioactive form of vitamin K2.34 MK-7 also has been shown to have a longer half-life than vitamin K1, resulting in more stable serum levels. Similarly, for vitamin D, vitamin D3 has been shown to be up to 3 times more effective than vitamin D2 (calciferol) at raising the body’s serum 25-hydroxyvitamin D levels.35 Absorption of both vitamin D and K also can be dramatically improved when they are provided in a nanemulsified format.

 

 


 

1 Holick M. Phylogenetic and evolutionary aspects of vitamin D from phytoplankton to humans. Verebrate Endocrinology: Fundamentals and Biomedical Implications Academic Press, Inc (Harcourt Brace Jovanovich) Orlando, FL 1989;3:7-43.

2 Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008 Aug;88(2):491S-499S. View Full Paper

3 Carlberg C, Seuter S, Heikkinen S. The first genome-wide view of vitamin D receptor locations and their mechanistic implications. Anticancer Res. 2012 Jan;32(1):271-82. View Full Paper

4 Kim M. Pfotenhauer, Jay H. Shubrook. Vitamin D Deficiency, Its Role in Health and Disease, and Current Supplementation Recommendations. J Am Osteopath Assoc. 2017 May 1;117(5):301-305. View Abstract

5 Grant WB. The prevalence of multiple sclerosis in 3 US communities: the role of vitamin D. Prev Chronic Dis. 2010;7:A89-A90. View Full Paper

6 Antico A, Tampoia M, Tozzoli R, et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12:127–36 View Abstract

7 Mohr SB, Garland CF, Gorham ED, et al. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. 2008;51:1391–8. doi: 10.1007/s00125-008-1061-5. View Abstract

8 Schultz M, Butt AG. Is the north to south gradient in inflammatory bowel disease a global phenomenon? Expert Rev Gastroenterol Hepatol. 2012;6:445–7. View Abstract

9 ieira VM, Hart JE, Webster TF, Weinberg J, Puett R, Laden F, et al. Association between residences in U.S. northern latitudes and rheumatoid arthritis: A spatial analysis of the Nurses’ Health Study. Environ Health Perspect. 2010;118:957–61. View Abstract

10 Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76. doi: 10.1210/er.2008-0004. View Abstract

11 Iho S, Takahashi T, Kura F, et al. The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells. J Immunol. 1986;136:4427–31. View Abstract

12 Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl) 2010;88:441–50. View Abstract

13 Gowda U, Mutowo MP, Smith BJ, et al. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. 2015 Mar;31(3):421-9 View Abstract

14 Wacker M, Holick M. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108. View Full Paper

15 Harvard Women’s Health Watch. Time for more vitamin D. Sept 2008. [Cited October 18, 2017] Available at: https://www.health.harvard.edu/staying-healthy/time-for-more-vitamin-d

16 Peterson AL, Murchison C, Zabetian C et al. Memory, mood, and vitamin D in persons with Parkinson's disease. J Parkinsons Dis. 2013;3(4):547-55 View Full Text

17 Frandsen TB, Pareek M, Hansen JP et al. Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial

BMC Res Notes. 2014; 7: 52 View Full Paper

18 White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun. 2008 Sep;76(9):3837-43. View Full Paper

19 Yildiz I, Unuvar E, Zeybek U, et al. The role of vitamin D in children with recurrent tonsillopharyngitis. Ital J Pediatr. 2012 Jun 8;38:25. View Full Paper

20 Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-90. View Full Paper

21 Quraishi SA, Bittner EA, Christopher KB, Camargo CA Jr. Vitamin D status and community-acquired pneumonia: results from the third National Health and Nutrition Examination Survey. PLoS One. 2013 Nov 15;8(11):e81120. View Full Paper

22 Xiao L, et al. Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials. Br J Nutr. 2015 Aug 27:1-9. View Abstract

23 Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100-7. View Full Paper

24 Gloth FM 3rd, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5-7. View Abstract

25 Jorde R, Sneve M, Figenschau Y, et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008 Dec;264(6):599-609. View Abstract

26 Sepehrmanesh Z, Kolahdooz F, Abedi F, et al. Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial. J Nutr. 2016 Feb;146(2):243-8. View Abstract

27 Shipowick CD, Moore CB, Corbett C, Bindler R. Vitamin D and depressive symptoms in women during the winter: a pilot study. Appl Nurs Res. 2009 Aug;22(3):221-5. View Abstract

28Raef H, Al-Bugami M, Balharith S. Updated Recommendations for the Diagnosis and Management of Osteoporosis: A Local Perspective Ann Saudi Med. 2011 Mar-Apr; 31(2): 111–128. View Full Paper

29 Iwamoto J, Takeda T, Ichimura S. Treatment with vitamin D3 and/or vitamin K2 for postmenopausal osteoporosis. Keio J Med. 2003 Sep;52(3):147-50. View Abstract

30 Iwamoto J, Takeda T, Ichimura S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci. 2000;5(6):546-51 View Full Paper

31 El Asmar MS, Naoum JJ, Arbid EJ. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Med J. 2014 May;29(3):172-7. View Full Paper

32 Bügel S. Vitamin K and bone health in adult humans. Vitam Horm. 2008;78:393-416 View Abstract

33 Inaba N, et al. Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials. J Nutr Sci Vitaminol (Tokyo). 2015;61(6):471-80. View Abstract

34 Schurgers LJ, et al. itamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279-83. View Full Paper

35 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694-7. View Full Paper

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EDTA and Metal Chelation: Can a Liposomal Format Really Deliver?

EDTA and Metal Chelation: Can a Liposomal Format Really Deliver?

Chelation therapy, that is, the removal of toxic metals from the body with an agent known as a chelator, is an important mainstay in toxicology and environmental medicine, both fields which deal with the impact of toxic heavy metals on the human body. Chelating agents are compounds, both organic and inorganic, which strongly bind to metal ions, and remove the metal from the body where it is causing damage. Chelating substances are not only used in medicine, but widely used in water treatment and agriculture as well.

The word chelate is derived from the Greek word chele, which refers to the claws of a crab. Ideally, the affinity of the chelator for the substance it is intended to capture is very high, and it will not form bonds with other biological cations such as calcium, which are readily available in the body fluids. The ability of the chelator to achieve the desired outcome is affected by both pH and its ability to transport into cells or tissues where the toxic metal predominantly resides. Additionally, the compound formed by the chelator and the toxic metal should be stable, and less toxic than the heavy metal, so that additional damage is not incurred as it exits from the body.1

Ethylenediamine-tetraacetic acid (EDTA) was introduced to medicine after World War II, when lead poisoning was observed in many navy personnel who had been exposed when painting ships with lead-based paints. Historically, EDTA has been used for the treatment of childhood lead poisoning as well as cardiovascular disease, and more recently it has been the topic of increasing investigation for neurodegenerative disease.2,3 EDTA has the highest stability constant when complexed with nickel, lead, cadmium, zinc, and cobalt, followed closely by iron and manganese, and a progressively declining stability with calcium, magnesium, and other metals. EDTA also has evidence of forming chelation complexes with aluminum and arsenic.4,5,6,7

Stability is not the only factor which influences the substances which leave the body bound to EDTA. As metals like calcium and zinc are abundant in biological fluids and tissues, they may be bound and removed by EDTA, unless a metal with a higher stability constant is encountered. Thus, supplemental intake of minerals, particularly zinc, is important during therapy. Supplemental intake of the trace elements copper and manganese also is important as these metals can additionally be depleted.8 In addition to maintaining tissue zinc levels, simultaneous zinc administration during EDTA chelation therapy also has been observed to increase urinary lead excretion.9

Traditional (non-liposomal) oral EDTA preparations have low bioavailability, with approximately 5% absorbed in the gastrointestinal tract. It is minimally delivered intracellularly, even with intravenous delivery, and rapidly excreted from the kidneys, having a half-life of 1.4 to 3 hours.10 Although many still use EDTA as a challenge agent to assess the body burden of lead, this diagnostic use is potentially harmful as high challenge dosages can lead to the body redistribution of lead to the brain.11 Dose-dependent reversible damage to the renal proximal tubules has also been observed with EDTA. However, at typical treatment dosages, repeated for a period of time, EDTA has been shown to reduce lead content of the kidneys and blood, and in some studies the brain.12,13Additionally, chelation therapy for the removal of lead has been shown to attenuate the progression of chronic, progressive, renal insufficiency.14

Without the ability to transport into the tissues and cells where biological processes take place and compounds such as EDTA interact with metals, therapies are ineffective. Because liposomal delivery systems have a high oral bioavailability, prolonged systemic circulation, and allow for intracellular delivery, they are ideal for the delivery of EDTA. And, studies have demonstrated just that, showing greater tissue uptake and retention of liposomal EDTA as compared to the non-liposomal form.15 Additionally, the gradual release of EDTA from the liposomes lowers toxicity and enables increased effectiveness of toxic metal removal.16 Liposomal size is of importance however, as only very small liposomes have high levels of absorption intraorally.17 Smaller liposomes are also far more efficient at intracellular delivery.

Lipoic Acid: EDTA’s Noteworthy Sidekick

Lipoic acid is an antioxidant with broad action in the human body, and is the topic of study for many neurodegenerative conditions or other pathologies associated with chronic oxidative stress. This includes peripheral neuropathy, diabetes, hepatitis, obesity, heavy metal toxicity, Alzheimer’s and Parkinson’s disease, migraines, multiple sclerosis, and more.18,19 Lipoic acid is converted to its reduced form, dihydrolipoic acid (DHLA), by enzymes within the mitochondria and cytosol. As an oxidant couple, lipoic acid and DHLA have both lipophilic and hydrophilic properties.20 Both the reduced and oxidized forms have the capability of acting as an antioxidant, and together are able to reduce a multitude of free radical species.21 Collectively this duo is able to scavenge reactive oxygen species, regenerate endogenous antioxidants, and repair oxidative damage.22

The lipoic acid-DHLA duo has been studied and shown to have action as a chelator of metals in vitro and in vivo,forming complexes with metals including copper, cadmium, lead, and mercury.23 Because lipoic acid is able to cross the blood brain barrier, its action as a chelator may benefit conditions affecting the central nervous system as well.24 Not only does lipoic acid support the removal of toxic heavy metals, because it simultaneously supports antioxidant levels, it helps to mitigate the cellular damage these metals may cause.25 Other stronger chelators such as EDTA are thus well supported by the addition of lipoic acid for reducing metal burden while maintaining antioxidant balance during chelation therapy.

 


1 Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Jul;7(7):2745-88. View Full Paper

2 Ibad A, Khalid R, Thompson PD. Chelation therapy in the treatment of cardiovascular diseases. J Clin Lipidol. 2016 Jan-Feb;10(1):58-62.View Abstract

3 Bolognin S, Drago D, Messori L, Zatta P. Chelation therapy for neurodegenerative diseases. Med Res Rev. 2009 Jul;29(4):547-70. View Abstract

4 Bartlett RJ, Riego DC. Effect of chelation on the toxicity of aluminum. Plant and Soil. 1972 Oct 28;37(2):419-23. View Abstract

5 Chappell LT. Applications of EDTA chelation therapy. Alt Med Rev. 1997;2(6):426-432. View Full Paper

6 Kartal SN. Removal of copper, chromium, and arsenic from CCA-C treated wood by EDTA extraction. Waste Management. 2003 Dec 31;23(6):537-46. View Abstract

7 De Gregori I, Fuentes E, Olivares D, Pinochet H. Extractable copper, arsenic and antimony by EDTA solution from agricultural Chilean soils and its transfer to alfalfa plants (Medicago sativa L.). J Enviro Monitor 2004;6(1):38-47. View Full Paper

8 Ibim SE, Trotman J, Musey PI, Semafuko WE. Depletion of essential elements by calcium disodium EDTA treatment in the dog. Toxicology. 1992 Jan 1;73(2):229-37. View Abstract

9 Flora SJ, Tandon SK. Beneficial effects of zinc supplementation during chelation treatment of lead intoxication in rats. Toxicology. 1990 Nov;64(2):129-39. View Abstract

10 Andersen O. Principles and recent developments in chelation treatment of metal intoxication. Chem Rev. 1999 Sep 8;99(9):2683-710. View Full Paper

11 Cory-Slechta DA, Weiss B, Cox C. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy. J Pharmacol Exp Ther. 1987 Dec;243(3):804-13. View Abstract

12 Seaton CL, Lasman J, Smith DR. The effects of CaNa(2)EDTA on brain lead mobilization in rodents determined using a stable lead isotope tracer. Toxicol Appl Pharmacol. 1999 Sep 15;159(3):153-60. View Abstract

13 Sánchez-Fructuoso AI, Cano M, Arroyo M, et al. Lead mobilization during calcium disodium ethylenediaminetetraacetate chelation therapy in treatment of chronic lead poisoning. Am J Kidney Dis. 2002 Jul;40(1):51-8. View Abstract

14 Lin JL, Ho HH, Yu CC. Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. A randomized, controlled trial. Ann Intern Med. 1999 Jan 5;130(1):7-13. View Abstract

15 Jonah MM, Cerny EA, Rahman YE. Tissue distribution of EDTA encapsulated within liposomes of varying surface properties. Biochim Biophys Acta. 1975 Sep 2;401(3):336-48. View Abstract

16 Rahman YE, Rosenthal MW, Cerny EA, Moretti ES. Preparation and prolonged tissue retention of liposome-encapsulated chelating agents. J Lab Clin Med. 1974 Apr;83(4):640-7. View Abstract

17Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci. 2014 Jan;103(1):29-52. View Full Paper

18 Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50. View Abstract

19 Bustamante J, Lodge JK, Marcocci L, et al. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med. 1998 Apr;24(6):1023-39. View Abstract

20 Moini H, et al. Antioxidant and prooxidant activities of α-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharm 2002;182:84-90. View Abstract

21 Packer L, et al. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17:888-895.View Abstract

22 Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31. View Abstract

23 Shay KP, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. View Full Paper

24 Bush AI. Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. 2002 Nov-Dec;23(6):1031-8. View Abstract

25 Gurer H, et al. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med. 1999 Jul;27(1-2):75-81. View Abstract

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Gut Health: A Critical Facet for Effective Detoxification

As many holistic practitioners who work with chronic disease will tell you, if you don’t consider and address gut function, the body will struggle to get well. This concept has long been emphasized regarding conditions as diverse as chronic infections, autoimmune disease, skin conditions, allergies, mental health, neurodegenerative conditions, autism, metabolic syndrome, and so much more. And now, with the onslaught of research on the health and microbiota of the gut, we have many new insights into the gut’s connection to these medical conditions.1,2,3 Probiotics, micro-organisms that have been shown to exert a beneficial impact on health, are big business, for food and supplement companies alike.

 

But gut health goes beyond a balanced flora, and most people with even a passing interest in holistic health are familiar with the phrase “leaky gut.” Leaky gut, which in medical research settings is called “increased intestinal permeability,” also is making its mark in medical publications and supplement development. Just as gut dysbiosis affects health, so does increased intestinal permeability, which has shown associations with autism, mood, immune system activation, cognitive health, and many more conditions.4,5,6,7 Increased gut permeability usually comes hand-in-hand with intestinal inflammation, and can be caused by infection, food sensitivities or allergies, alcohol intake, heavy metal or toxin exposure, intense exercise, and even stress. 8,9,10,11 With increased gut permeability, bacterial components from the gut lumen, including the immune response-triggering portion known as endotoxin, or lipopolysaccharide (LPS), are able to enter into systemic circulation. Because of this, inflammation does not just stop at the gut, and affects the body systemically.

 

Endotoxin-associated inflammation has a negative effect on detoxification by multiple mechanisms. Exposure to endotoxin, and related inflammatory cytokines, downregulates expression of some of the important components of detoxification known as Phase I cytochrome P450 enzymes and Phase III transporters.12,13 Endotoxin also inhibits the kidney elimination of mercury, and further contributes to renal damage.14 Last, but not least, endotoxin has a dramatic negative effect on bile flow.15 Because many of the toxins, particularly heavy metal-glutathione conjugates, are removed from circulation via the bile,16 when bile flow is impeded, elimination is impaired at the level of the kidneys as well. The body then has difficulty overcoming the situation. The toxic metals become stuck in circulation, and seep back into tissues, including the brain, where they cause inflammation and damage.17

 

Gut health is important for detoxification from heavy metals, as high levels of the proteins necessary for all phases of detoxification are expressed here.18,19 Unfortunately, with exposure to heavy metals such as mercury, gut mucosa inflammation and increased intestinal permeability occur, associated with oxidative stress and glutathione depletion.20 Although a probiotic can help mitigate these issues, it often is not enough, and a more strategic approach to treatment is necessary. In addition to bitter compounds which promote the movement of bile out through the liver and gallbladder, as well as a healthy gut flora balance, support for intestinal mucosa health and function in detoxification also is important.

 

Clearing the Way for Effective Detoxification

One thing which has a negative impact on detoxification is biofilm. Biofilms can occur with colonization of dysbiotic or pathogenic gastrointestinal flora.21 A biofilm is a matrix of extracellular polymeric substances (also known as exopolysaccharides) that vary greatly depending on the organism by which they were created, and the environment in which they develop.22 In addition to facilitating a communication network and serving as protection for the community which created them, biofilms can further contribute to heavy metal accumulation and retention, as heavy metals are also trapped here.23,24 Nattokinase, a fibrinolytic enzyme, has been shown to disrupt biofilms.25

 

The interactions of selenium with mercury in the body have long been recognized. Mercury binds to selenium with a very high affinity, and it has a specific and irreversible effect of inhibiting selenium-dependent enzymes.26, 27 Selenium-dependent enzymes, also known as selenoproteins, act to repair oxidative damage in the body, particularly in the brain, and include glutathione peroxidase.28 Because of the strong interactions with mercury, selenium is sequestered and depleted with mercury exposure. Studies in fish, our main source of dietary mercury, have shown that selenium interacts with methylmercury in the gut, reducing methylmercury accumulation.29 Selenium also induces the Nrf2 pathways, which promotes cellular products of antioxidants and antioxidant enzymes.30 The protective role of selenium has not only been shown with mercury, but other damaging metals such as cadmium and aluminum.31,32

Terminalia chebula, also known as Haritaki, is widely used in Ayurvedic medicine and is part of the famous blend of three herbs known as Triphala, having a long history of use for a variety of digestive complaints.33 Haritaki, as a part of this combination, has been shown to play a role in healing the brush border membrane of intestine, as well as restoring phospholipid and glutathione content after damage.34 Haritaki also has been shown to have a protective effect on the gastrointestinal mucosa, reducing the formation of gastric ulcers in addition to demonstrating potent systemic inflammatory activity.35,36 It supports the reduction of constipation, and the movement of digestive waste and toxins from the gastrointestinal tract as well.37

Although liposomal formats are ideal for nutritional supplements which are directed at supporting the body systemically, non-liposomal formats are appropriate for delivering nutrients intended for local action in the gut. Because each of the phases of detoxification occur at high levels locally in the gut, supporting the antioxidant systems of the cells of the small intestinal mucosa also is important. Polyphenolic antioxidants such as epicatechin (found in pine bark extract) and lipoic acid have demonstrated tremendous efficacy in doing this by "turning on" Nrf2, the master intracellular antioxidant switch that promotes transcription of antioxidants and enzymes necessary for detoxification. 38,39,40 Pomegranate, well known for its antioxidant effects, not only supports glutathione and glutathione peroxidase levels in the cells lining the gastrointestinal tract, but by doing so also has been shown to protect the gastrointestinal mucosa from aspirin and alcohol-induced inflammation and injury. 41

 

 


1 Sherwin E, Dinan TG, Cryan JF. Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann N Y Acad Sci. 2017 Aug 2. View Abstract

2 Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31;120(7):1183-1196. View Abstract

3 Felix KM, Tahsin S, Wu HJ. Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2017 Oct 6. View Abstract

4 Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005 Mar 25;307(5717):1920-5. View Abstract

5 Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24. View Abstract

6 Daulatzai MA. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia. Neurochem Res. 2014 Apr;39(4):624-44. View Abstract

7 Heberling CA, Dhurjati PS, Sasser M. Hypothesis for a systems connectivity model of Autism Spectrum Disorder pathogenesis: links to gut bacteria, oxidative stress, and intestinal permeability. Med Hypotheses. 2013 Mar;80(3):264-70. View Abstract

8 Lindén SK, et al. Mucin dynamics in intestinal bacterial infection. PLoS One. 2008;3(12):e3952.

9 Purohit V, Bode JC, Bode C, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008 Aug;42(5):349-61. View Abstract

10 Pals KL, Chang RT, Ryan AJ, Gisolfi CV. Effect of running intensity on intestinal permeability. J Appl Physiol (1985). 1997 Feb;82(2):571-6. View Abstract

11 Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011 Dec;62(6):591-9. View Abstract

12 Tang W, Yi C, Kalitsky J, Piquette-Miller M. Endotoxin downregulates hepatic expression of P-glycoprotein and MRP2 in 2-acetylaminofluorene-treated rats. Mol Cell Biol Res Commun. 2000 Aug;4(2):90-7. View Abstract

13 Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, Piquette-Miller M. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004 Jan;32(1):20-7. View Abstract

14 Rumbeiha WK, et al. Augmentation of mercury-induced nephrotoxicity by endotoxin in the mouse. Toxicology. 2000 Oct 26;151(1-3):103-16. View Abstract

15 Kosters A, Karpen SJ. The role of inflammation in cholestasis: clinical and basic aspects. Semin Liver Dis. 2010 May;30(2):186-94. View Abstract

16 Ballatori N, Clarkson TW. Biliary secretion of glutathione and of glutathione-metal complexes. Fundam Appl Toxicol. 1985 Oct;5(5):816-31. View Abstract

17 Monnet-Tschudi F, Zurich MG, Boschat C, et al. Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases. Rev Environ Health. 2006 Apr-Jun;21(2):105-17. View Abstract

18 Doherty MM, Charman WN. The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet. 2002;41(4):235-53. View Abstract

19 Berggren S, et al. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol Pharm. 2007 Mar-Apr;4(2):252-7. View Abstract

20 Vázquez M, et al. In vitro evaluation of inorganic mercury and methylmercury effects on the intestinal epithelium permeability. Food Chem Toxicol. 2014 Dec;74:349-59. View Abstract

21 Macfarlane S, Dillon JF. Microbial biofilms in the human gastrointestinal tract. J Appl Microbiol. 2007 May;102(5):1187-96. View Abstract

22 Sutherland I. Biofilm exopolysaccharides: a strong and sticky framework. Microbiology. 2001 Jan;147(Pt 1):3-9. View Abstract

23 Dominique Y, Maury-Brachet R, Muresan B, et al. Biofilm and mercury availability as key factors for mercury accumulation in fish (Curimata cyprinoides) from a disturbed Amazonian freshwater system. Environ Toxicol Chem. 2007 Jan;26(1):45-52. View Abstract

24 Teitzel GM, Parsek MR. Heavy metal resistance of biofilm and planktonic Pseudomonas aeruginosa. Appl Environ Microbiol. 2003 Apr;69(4):2313-20. View Abstract

25 Zapotoczna M, et al. An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections. J Infect Dis. 2015;212(12):1883–93. View Abstract

26 Berry MJ, Ralston NV. Mercury toxicity and the mitigating role of selenium. Ecohealth. 2008 Dec;5(4):456-9. View Abstract

27 Ralston NV, Raymond LJ. Dietary selenium's protective effects against methylmercury toxicity. Toxicology. 2010 Nov 28;278(1):112-23. View Abstract

28 Chen J, Berry MJ. Selenium and selenoproteins in the brain and brain diseases. J Neurochem. 2003 Jul;86(1):1-12. View Abstract

29 Wang X, Wang WX. Selenium induces the demethylation of mercury in marine fish. Environ Pollut. 2017 Sep 16. View Abstract

30 Zhang C, Lin J, Ge J, et al. Selenium triggers Nrf2-mediated protection against cadmium-induced chicken hepatocyte autophagy and apoptosis. Toxicol In Vitro. 2017 Oct;44:349-356. View Abstract

31 Liu L, Yang B, Cheng Y, Lin H. Ameliorative Effects of Selenium on Cadmium-Induced Oxidative Stress and Endoplasmic Reticulum Stress in the Chicken Kidney. Biol Trace Elem Res. 2015 Oct;167(2):308-19. View Abstract

32 Viezeliene D, Jansen E, Rodovicius H, et al. Protective effect of selenium on aluminium-induced oxidative stress in mouse liver in vivo. Environ Toxicol Pharmacol. 2011 Mar;31(2):302-6. View Abstract

33 Baliga MS, Meera S, Mathai B, et al. Scientific validation of the ethnomedicinal properties of the Ayurvedic drug Triphala: a review. Chin J Integr Med. 2012 Dec;18(12):946-54. View Abstract

34 Nariya M, et al. Comparison of enteroprotective efficacy of triphala formulations (Indian Herbal Drug) on methotrexate-induced small intestinal damage in rats. Phytother Res. 2009 Aug;23(8):1092-8. View Abstract

35 Sharma P, et al. Antiulcerogenic activity of Terminalia chebula fruit in experimentally induced ulcer in rats. Pharm Biol. 2011 Mar;49(3):262-8. View Abstract

36 Pampattiwar SP, Adwani NV, Sitaram B, Rao PM. Pharmacological study of anti-inflammatory action of haritaki preparations on wistar rats in hemorrhoids (piles). Global J Res Med Plants Indig Med. 2013 Mar 1;2(3):178. View Abstract

37 Bag A, Bhattacharyya SK, Chattopadhyay RR. The development of Terminalia chebula Retz. (Combretaceae) in clinical research. Asian Pac J Trop Biomed. 2013 Mar;3(3):244-52. View Full Paper

38 Rohdewald P, et al. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68. View Abstract

39 Na HK, Surh YJ. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem Toxicol. 2008 Apr;46(4):1271-8. View Abstract

40 Suh JH, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3381-6. View Abstract

41 Ajaikumar KB, Asheef M, Babu BH, Padikkala J. The inhibition of gastric mucosal injury by Punicagranatum L. (pomegranate) methanolic extract. J Ethnopharmacol. 2005 Jan 4;96(1-2):171-6. View Abstract

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BitterX Bigger Better

Detoxification: The Importance of Moving Bile with a Bigger Bitter

Bile. It doesn’t have the best reputation. You know it as that bitter fluid you burp up on occasion. It’s also a synonym for spite and malice. As an adjective—bilious—it means spiteful and ill-tempered.

So, you might be surprised to know that bile is, metabolically, like precious gold. The smooth flow of that dark green to yellowish brown liquid produced by your liver and stored in your gallbladder is a key player in detoxification, proper digestion, an intact gut lining, healthy small intestine flora, normal cholesterol and blood sugar levels, and perhaps even the proper function of neurons in the brain.1,2,3,4 Bile salts can modify lipids, destroy bacterial endotoxins, and function as an antimicrobial.5,6

In many people, however, bile flow is impaired, leading to stagnation.7 That stagnation can have profound health consequences. Stagnant bile flow impairs the movement of toxins, which flow with the bile out of the liver into the gallbladder, and then into the digestive tract for excretion.8 The lack of bile flow can also contribute to gastrointestinal dysbiosis and small intestinal bacteria overgrowth (SIBO). 9,10 Endotoxin, associated with dysbiosis and gram-negative flora, irritates the mucosal lining of the gastrointestinal tract and increases inflammation.11 An inflamed and “leaky” gut then lets bacterial and other toxins slip into the bloodstream, triggering a systemic inflammatory response.12 That inflammatory response can further impair liver and gallbladder function and inhibit bile flow, contributing to what is known as cholestasis.13

As if that’s not enough, endotoxins downregulate critical pumps (called Phase III transporters) that transport toxins out of our cells.14 This stepwise buildup of toxins depletes our most potent antioxidant, glutathione--further stressing the liver, which relies heavily on glutathione in detoxification reactions.15,16 In addition, a gut inflamed by endotoxin renders the liver more susceptible to damage by xenobiotics, chemicals foreign to our body, found in our environment.17

Let it flow, then. Bile flow is supremely important to overall health. And if there is one simple and powerful way to assist the healthy flow of bile, it is the classic bitter herbs that have been part of our medicine chest for centuries. These herbs long ago migrated from the apothecary to the cocktail bar, transforming into cherished aperitifs and digestifs that are taken before or after meals to stimulate appetite and digestion. These bitter substances offer the body not only support for digestion, but have an impact on the function of many other systems. Receptors for bitter cover not only the back of the tongue, but are also found in the lungs, ovaries, pancreas and other tissues. They can trigger numerous biological processes including regulation of blood sugar and activation of the immune system in response to infections.18,19,20,21

Bitters inherently turn on the digestive processes, but there are some bitter herbs that are more targeted for supporting the movement of bile, and toxins, from the liver and out through the gallbladder. Here are four such bitters:


*Dandelion (Taraxacum officinale). Dandelions produce bright yellow flower that turn to wispy puffs. The leaves are grooved and the brown roots fleshy, filled with a bitter, milky material. The pleasant (to some!) bitter taste in the leaves and root are due to molecules called sesquiterpene lactones that increase bile production and stimulate digestion.22,23 Dandelion stimulates the flow of bile into the duodenum (cholagogue) and simultaneously stimulates the production of bile by the liver (choleretic). It increases the activity of glutathione (GSH) and GSH-related enzymes in the liver.24 It is a diuretic and supports elimination of toxins through the urine.25 The long-chain saccharides in dandelion also have anti-inflammatory effects, possibly due to its inhibition of nitric oxide production and COX-2 expression (cyclooxygenase, or COX, an enzyme that produces prostaglandins that promote inflammation, pain, and fever).26,27

*Gentian (Gentianinae, family of 400 species). Well known as one of the strongest bitter herbs—or the most bitter bitter—gentian stimulates digestive secretions of all kinds, including saliva and bile flow.28 It modulates stomach acid secretion, increasing it in a state of deficiency, yet protecting stomach tissues against gastritis or gastric ulcers, possibly by regulating inflammatory prostaglandin pathways.29 Gentian is hepatoprotective, and as a liver protective agent has been observed to increase levels of catalase, superoxide dismutase and reduced GSH.30 Gentian has been observed in animal studies to increase GSH, GSH peroxidase, and superoxide dismutase levels in the setting of alcohol or acetaminophen-induced oxidative damage—and in this way, supporting and protecting the liver.31,32

*Goldenrod (Solidago canadensis) is a classic herb that supports the urinary system, promotes urination and thus the elimination of toxins.33 This helps support the liver, as some toxins, once conjugated, may be more efficiently drained through the kidneys. At the same time, flavonoids from solidago help activate GSH-S-transferase, a critical enzyme in phase II detoxification, which also brings relief to the liver.34

*Myrrh (Commiphora myrrha). Myrrh is a resinous exudate from trees of Commiphora species. It contains many highly bioactive molecules such as terpenoids and sesquiterpenoids as well as furanosesquiterpenoids, which have antifungal, antibacterial, anti-inflammatory, and smooth-muscle relaxing action.35

Myrrh strongly promotes healthy bile flow, and it has microbial-balancing qualities as well.36,37 Myrrh is popular in both Ayurvedic and Chinese medicine, and is considered a primary detoxifier that is both tonifying and strengthening. Its reputation for moving stagnant blood, including menstrual blood, leads to its popular use as a female remedy.38 Myrrh, like its popular Ayurvedic herbal cousin guggul, contains molecules called sterones that have impressively diverse biological activity. They can increase iodine uptake in the thyroid, and inhibit the inflammation triggered by endotoxin-induced nitric oxide production, having even more potent activity than curcumin.39

Just as significant, these sterones help turn on the bile salt export pump (Bsep).40 Bsep is located on the cell surfaces which connect the hepatocytes (liver cells) to the bile canaliculus, which drains bile from the liver to the gallbladder. This is one of the mechanisms by which guggul may have cholesterol-lowering effects, as the conversion of cholesterol to bile acids in the liver helps eliminate excess cholesterol, but also supports the movement of bile out of the liver, reducing cholestasis.

This blend of bitter herbs (dandelion, goldenrod, gentian, and myrrh) brings together the traditional use of bitters from multiple medicine systems, supported by research, to support gastrointestinal function and the processes of detoxification, more strongly than any other bitter combination. It’s bigger. It’s better. It’s badder. It’s bitter!

 


1 Lefebvre P, Cariou B, Lien F et al. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009 Jan;89(1):147-91 View Abstract

2 Gadaleta RM, Oldenburg B, Willemsen EC et al. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim Biophys Acta. 2011 Aug;1812(8):851-8 View Abstract

3 Sharma R, Long A, Gilmer JF. Advances in Bile Acid Medicinal Chemistry. Curr Med Chem. 2011;18(26):4029-52 View Abstract

4Islam KB, Fukiya S, Hagio M Bile acid is a host factor that regulates the composition of the cecal microbiota in rats.Gastroenterology. 2011 Nov;141(5):1773-81. View Abstract

5 Fernandesa CF, Shahani KM, Amer MA. Effect of Nutrient Media and Bile Salts on Growth and Antimicrobial Activity of Lactobacillus acidophilus. Journal of Dairy Science Volume 71, Issue 12, December 1988, Pages 3222-32299. View Abstract

6 D'Aldebert E, Biyeyeme Bi Mve MJ, Mergey M et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology. 2009 Apr;136(4):1435-43. View Abstract

7 Dietrich CG, Geier A, Wasmuth HE Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen. Gut. 2004 Dec;53(12):1850-5. View Full Paper

8 Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation.

Physiol Rev. 2003 Apr;83(2):633-71. View Full Paper

9 Islam KB, Fukiya S, Hagio M, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81.

10 Hellström PM, Nilsson I, Svenberg T. Role of bile in regulation of gut motility. J Intern Med. 1995 Apr;237(4):395-402.

11 Awad WA, Hess C, Hess M. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens. Toxins (Basel). 2017 Feb 10;9(2). View Abstract

12 Ahmad R, Sorrell MF, Batra SK, et al. Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal Immunol. 2017 Mar;10(2):307-317 View Abstract

13 Whiting JF, Green RM, Rosenbluth AB et al. Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology. 1995 Oct;22(4 Pt 1):1273-8. View Abstract

14 Kalitsky-Szirtes J, Shayeganpour A, Brocks DR et al. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004 Jan;32(1):20-7. View Abstract

15 Kaplowitz N. The importance and regulation of hepatic glutathione. Yale J Biol Med. 1981 Nov-Dec; 54(6): 497–502. View Full Paper

16 Carbonell LF, Nadal JA, Llanos MC, et al. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Critical care medicine. 2000 Jun 1;28(6):2002-6. View Abstract

17 Ganey PE, Roth RA. Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents. Toxicology. 2001 Dec 28;169(3):195-208. View Abstract

18 Yu Y, Hao G, Zhang Q, Hua W, Wang M, Zhou W, Zong S, Huang M, Wen X. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochem Pharmacol. 2015 Sep 15;97(2):173-7. View Abstract

19Shaik FA, Singh N, Arakawa M, Duan K, Bhullar RP, Chelikani P. Bitter taste receptors: Extraoral roles in pathophysiology. Int J Biochem Cell Biol. 2016 Aug;77(Pt B):197-204. View Abstract

20 Lee RJ, Cohen NA. The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Am J Rhinol Allergy. 2013 Jul-Aug;27(4):283-6. View Abstract

21 Gaida MM, Dapunt U, Hänsch GM. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog Dis. 2016 Apr;74(3). View Full Paper

22 You Y, Yoo S, Yoon HG et al. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress.Food Chem Toxicol. 2010 Jun;48(6):1632-7. View Abstract

23 Park CM, Cha YS, Youn HJ Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in Sprague-Dawley rats. Phytother Res. 2010 Sep;24(9):1347-53 View Abstract

24 Ung-Kyu C, Ok-Hwan L, Joo Hyuk Y et al. Hypolipidemic and Antioxidant Effects of Dandelion (Taraxacum officinale) Root and Leaf on Cholesterol-Fed Rabbits Int J Mol Sci. 2010 Jan; 11(1): 67–78. View Full Paper

25 Clare BA, Conroy RS, Spelman K. The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over a Single Day J Altern Complement Med. 2009 Aug; 15(8): 929–934. View Full Paper

26 Park CM, Cho CW, Song YS. TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells. Food Chem Toxicol. 2014 Apr;66:56-64. View Abstract

27 Jeon HJ, Kang HJ, Jung HJ et al. Anti-inflammatory activity of Taraxacum officinale. J Ethnopharmacol. 2008 Jan 4;115(1):82-8. View Abstract

28 P Oztürk N, Herekman-Demir T, Oztürk Y et al. . Choleretic activity of Gentiana lutea ssp. symphyandra in rats.Phytomedicine. 1998 Aug;5(4):283-8 View Abstract

29 Niiho Y, Yamazaki T, Nakajima Y, Yamamoto T, Ando H, Hirai Y, Toriizuka K, Ida Y. Gastroprotective effects of bitter principles isolated from Gentian root and Swertia herb on experimentally-induced gastric lesions in rats. Journal of natural medicines. 2006 Jan;60(1):82-8. View Abstract

30 Mihailović V, Mihailović M, Uskoković A et al. Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats. Food Chem Toxicol. 2013 Feb;52:83-90. View Abstract

31 Lian LH, Wu YL, Song SZ, Wan Y, Xie WX, Li X, Bai T, Ouyang BQ, Nan JX. Gentiana manshurica Kitagawa reverses acute alcohol-induced liver steatosis through blocking sterol regulatory element-binding protein-1 maturation. J Agric Food Chem. 2010 Dec 22;58(24):13013-9. View Abstract

32 Wang AY, Lian LH, Jiang YZ, Wu YL, Nan JX. Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway. World J Gastroenterol. 2010 Jan 21;16(3):384-91. View Abstract

33 Melzig MF. [Goldenrod--a classical exponent in the urological phytotherapy]. Wien Med Wochenschr. 2004 Nov;154(21-22):523-7. View Abstract

34 Apáti P, et al. In-vitro effect of flavonoids from Solidago canadensis extract on GSH S-transferase. J Pharm Pharmacol. 2006 Feb;58(2):251-6. View Abstract

35 Shen T, Lou, HX. Bioactive Constituents of Myrrh and Frankincense, Two Simultaneously

Prescribed Gum Resins in Chinese Traditional Medicine. Chemistry & Biodiversity. 2008; 5: 541-543

36 Dolara P, Corte B, Ghelardini C, Pugliese AM, Cerbai E, Menichetti S, Lo Nostro A. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med. 2000 May;66(4):356-8. View Abstract

37 Sheir Z, Nasr AA, Massoud A, Salama O, Badra GA, El-Shennawy H, Hassan N, Hammad SM. A safe, effective, herbal antischistosomal therapy derived from myrrh. Am J Trop Med Hyg. 2001 Dec;65(6):700-4. View Full Paper

38 Engels G, Brinckmann J. Myrrh. American Botanical Council. 2012. [Cited October 9, 2017] Available at: cms.herbalgram.org/herbalgram/issue93/HERBPRO_myrrh.html

39 Frawley D, Lad V. The Yoga of Herbs: An Ayurvedic Guide to Herbal Medicine. Lotus Press, 1986.

40 Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem. 2003 Mar 21;278(12):10214-20. View Abstract

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Thrivagen, the Herbal Elixir for Total Woman’s Well Being

A Liposomal Adaptogenic Blend Directed at Female Physiology

“'The great question that has never been answered,” confessed famous psychoanalyst Sigmund Freud, “and which I have not yet been able to answer, despite my thirty years of research into the feminine soul, is "What does a woman want?”1

               There’s at least one seemingly straightforward answer to that. A woman wants balanced hormones. She doesn’t want to suffer from premenstrual headache, bloating, weight gain, sore breasts, irritability, depression, and moodiness every month. Nor does she want to endure the soaking sweats, hot flushes, insomnia and flagging energy of perimenopause. She doesn’t want the vaginal dryness that may come with waning hormones as she ages or the fibroids that may bloom in the presence of too much estrogen. She even may want a libido and sex drive to rival that of men’s, one that does not take a dive immediately after it peaks before menopause. In essence, she wants her hormonal cycle—a delicate and complex choreography compared to men’s—to be a source of joy, energy, and feminine power.

But it isn’t always easy to achieve. Herbalist Daniel Moriarty, founder of Sun Horse Energy and creator of the Thrivagen Formula, knows that firsthand. “My mom was an herbalist, and women used to come over to our house endlessly for help with hormonal issues. Then I met my current partner, Mona. The first time I saw her suffer through her menstrual period, I was ready to call 911. She was sweating and shivering and in such incredible cramping pain. When I realized she went through this every month I knew I had to do something to help her.”

Moriarty spent two years tweaking a uniquely female formula with herbs suited to women’s health. He chose adaptogens, nontoxic and potent herbs that stabilize and restore normal physiological functioning, increase resistance to long-term stress and are often immune-modulating.2,3 To qualify as an adaptogen, an herb must have a balancing effect on the mental and physical response to stress. Adaptogens are bi-directional, meaning they can either calm the activity of hyperactive systems, or boost and stimulate activity of weak systems in the body--particularly the endocrine, nervous and immune systems.

Every small incremental change in ratios of the herbs Moriarty blended had a huge effect on Mona. “God blessed the bumpy road that led her to me,” he says, “because she was so sensitive and yet so willing to experiment.”

Today, Mona has completely normal menstrual cycles, and the blend of herbs she inspired is the company’s top selling formulation. Moriarty views the formula as having two aspects. First, are the synergistic general adaptogens also found in the popular combination, Nano Mojo, formulated in different ratios geared to female physiology and sensitivity. Moriarty says these adaptogens activate all cells in the body and bring their charge and function up. Second are the women’s adaptogens, also included in very specific ratios to support their function, of which he says, “they are like the conductors of a symphony.” These botanicals are:

  • Shatavari (Asparagus racemosus): This herb is a favorite Ayurvedic tonic for females, and common throughout Nepal, Sri Lanka, India and the Himalayas. The translation of its name says it all: “The one who possesses a hundred husbands”—implying a woman of potent seductive ability and fertility, as well as the stamina and patience to handle multiple men. Structurally, the active constituents of this herb are similar to estrogen produced within the body, yet these plant-derived estrogens, known as phytoestrogens, have a more gentle, and balancing effect.4 It is reputed to be beneficial in female infertility, to moisten dry vaginal tissues, enhance ovulation, and act as post-partum tonic by increasing lactation.5,6,7 It also can reduce painful periods (dysmenorrhea) and premenstrual syndrome.8,9,10
  • Ashwagandha (Withania somnifera): Ashwagandha is another revered Ayurvedic herb, with a 6000-year-old reputation for protecting against the effects of acute and chronic stress.11,12,13 It is often referred to as the Indian ginseng, because it compares well with Siberian Ginseng (Eleutherococcus senticosus) and Chinese Ginseng (Panax ginseng). It has been shown to increase physical endurance and may increase testosterone levels. 14,15 Testosterone is an essential hormone for women as well as men, and low testosterone is associated with low libido.16 In animal studies, the herb’s calming effect was pronounced, as was its antidepressant effect.17
  • Angelica (Angelica archangelica). Angelica belongs to the parsley family, and the dried root is used medicinally in both western and Asian traditional medicine. This particular herb is a cousin of the well-known Chinese herb, dong quai (Angelica sinensis), which has long been regarded as a potent female tonic. The roots and leaves of both Angelica spp. are warming, strengthening, and energizing to the reproductive organs and endocrine systems. Angelica is regarded as a woman’s herb in part because it increases blood flow and circulation, and can relieve menstrual cramps by warming, decongesting, and stimulating menstrual flow.18 Traditionally, Angelica species have been used to regulate menstruation, relieve menstrual cramping, balance hormones, and smooth the challenging experiences of both childbearing and menopause. Angelica contains generous amounts of hormonal precursors—phytosterols such as glycocides, saponins, and flavonoids.19

Angelica has an almost mystical quality. A 2011 review article on this herb calls it an “angel on earth,” and recounts how its name was “derived from a monk’s dream in which St. Michael, the Archangel, appeared telling the monk what herb to use to help victims of the bubonic plague that was decimating Europe in 1665.20 Renowned herbalist Stephen Harrod Buhner describes how angelica helped a young woman recover from heavy, irregular, cramping periods. “I told her there was a plant I thought she should meet. We went for a walk through a pine forest, and when she saw the plant at the edge of a stream, a kind of force drew the woman and the plant together. The plant was Angelica, which has been used for thousands of years to help treat menstrual cramping. She spent a long time with it, then said a prayer and asked for help, and then we went to look for just the right Angelica. When we found it, she dug up the root, which has a beautiful smell. On the walk back she held it close to her. She was already carrying herself differently. The healing had started. She took a tincture made from the root, and within a month her period had normalized.”21

  • Chaste tree berry (Vitex agnus-castus): Chaste tree berry has active molecules that mimic the female hormone progesterone. A review of twelve randomized, controlled trials found that the herb was effective in ameliorating premenstrual syndrome and premenstrual dysphoric disorder (moodiness and depression).22 Premenstrual breast pain also improved with chaste tree berry.23,24

Although some practitioners use these herbs as monotherapies, the combination may have a synergistic effect, balancing both the hypothalamic-pituitary-ovary and the slightly more well-known hypothalamic-pituitary-adrenal (HPA) axis. The liposomal blend of these herbs is especially potent, allowing for rapid intraoral absorption and enhanced cellular delivery. Liposomal formulations have demonstrated abilities to deliver nutrients throughout the tissues in the body, and have sustained delivery. This enables once or twice daily dosing to have a prolonged systemic effect, supporting energy and balanced function throughout the day.

Related blogs:

1. NanoMojo: A Liposomal Adaptogenic Tonic Forged From A Global Selection of Medicinal-Grade, Potent Herbs

2. Sperm Counts Are Plummeting, and Researchers Think They Know Why

3. Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule Called DIM

 


1 Jones, E. Sigmund Freud: Life and Work (Hogarth Press, 1953) Vol. 2, Pt. 3, p. 421.

2 Levin O. Phyto-adaptogens--protection against stress? Harefuah. 2015 Mar;154(3):183-6, 211 View Abstract

3 Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. View Abstract

4 Alok S, Jain SK, Verma A et al. Plant profile, phytochemistry and pharmacology of Asparagus racemosus (Shatavari): A review. Asian Pac J Trop Dis. 2013 Jun; 3(3): 242–251. View Full Paper

5 Sharma K, Bhatnagar M. Asparagus racemosus (Shatavari): A Versatile Female Tonic. Intl Jnl of Pharmaceutical & Biological Archives 201; 2(3):855-863. View Full Paper

6 Vihan VS, Panwar HS. A note on galactagogue activity of Asparagus racemosus in lactating goats. Indian Journal of Animal Health 1988; 27: 177-178

7 Tewari PV, Mata HC, Chaturvedi C. Experimental study on estrogenic activity of certain indigenous drugs. J.Res.Ind.Med.Yoga and Homeo 1968;11: 4-12.

8 Jetmalani MH, Sabins PB, Gaitonde BB. A study on the pharmacology of various extracts of Shatavari- Asparagus racemosus (Willd). J Res Ind Med 1967; 2:1-10

9 Mitra SK, Sunitha A, Kumar VV, Pooranesan R, Vijaylakshmi M. U-3107 (EveCare) as a uterine tonic – Pilot Study. The Ind. Pract. 1998; 51: 4, 269-274.

10 Dhaliwal KS. Method and composition for treatment of premenstrual US Patent number 698662. 2003.

11 Singh N, Bhalla M, de Jager P An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13. View Full Paper

12 Singh N, Singh SP, Sinha JN, Shanker K, Kohli RP. Withania somnifera (Ashwagandha) A rejuvenator herbal drug which enhances survival during stress (An adaptogen) Int J Crude Drug Res. 1982;3:29–35.

13 Singh N. A pharmaco-clinical evaluation of some Ayurvedic crude plant drugs as anti-stress agents and their usefulness in some stress diseases of man. Ann Nat Acad Ind Med. 1986;2(1):14–26.

14 Singh N. A new concept on the possible therapy of stress disease with ‘Adaptogens’ (Anti-stress drugs) of indigenous plant origin. Curr Med Prac. 1981;25:50–55.

15 Ilayperuma I, Ratnasooriya WD, Weerasooriya TR. Effect of Withania somnifera root extract on the sexual behaviour of male rats. Asian J Androl. 2002 Dec;4(4):295-8. View Abstract

16 Davis SR, Wahlin-Jacobsen S. Testosterone in women--the clinical significance. Lancet Diabetes Endocrinol. 2015 Dec;3(12):980-92 View Abstract

17 Bhattacharya SK, Bhattacharya A, Sairam K, et al. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000 Dec;7(6):463-9. View Abstract

18 California School of Herbal Studies, Angelica: Garden Angelica. [Cited September 29, 2017] Available at: http://www.cshs.com/herbsOfMonth/angelica.html

19 Herbal Resource, Angelica Uses, Benefits and Side Effects. [Cited September 29, 2017] Available at: https://www.herbal-supplement-resource.com/angelica-benefits.html

20 Bhat ZA, Kumar D, Shah MY. Angelica archangelica Linn. is an angel on earth for the treatment of diseases. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2011 Jan;1(1): 36-50 View Full Paper

21 Ahuja, A. Living Medicine: Stephen Harrod Buhner On Plant Intelligence, Natural Healing, And The Trouble With Pharmaceuticals. Dec 2014 [Cited September 29, 2017] Available at: https://www.thesunmagazine.org/issues/468/living-medicine

22 van Die MD, Burger HG, Teede HJ, et al. Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials. Planta Med. 2013 May;79(7):562-75 View Abstract

23 Wuttke W, Jarry H, Christoffel V, et al. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Phytomedicine. 2003 May;10(4):348-57.

24 Roemheld-Hamm B. Chasteberry. Am Fam Physician. 2005 Sep 1;72(5):821-4. View Full Paper

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Post-Concussion Syndrome: The Risks and Potential Longer-Term Impacts of a Knock on the Head

With football and soccer season in full swing, and the risk of falls due to icy winter weather ahead, there is no time like the present to discuss the potential implications of head injuries, and effective approaches that may help mitigate injury-related consequences.

As many parents and sport-enthusiasts line the fields to cheer for their kids and favorite sport teams, we not only bring with us the excitement for the sport, but a continuously increasing awareness of the potential short and long-term impacts of head injuries. When we watch a player go down, or see an impact that is even more dramatic, we can’t help but gasp at times, knowing that there is no avoiding an injury with these high momentum collisions. Hands clenched, and breath held, we hope the player will get up, upon which we all cheer and breathe a sigh of relief. But even if he or she does get up, an injury may have occurred to the brain that is not immediately obvious, and that may have long-term consequences

Awareness in the medical community of post-concussion syndrome and chronic traumatic encephalopathy--the brain-related changes associated with chronic trauma to the head – has skyrocketed in recent years, with PubMed indexed publications on these topics increasing between 3 to 10-fold since 2010. A very recent study, highlighted in Scientific American, brought even further interest to the topic, as it was shown that the impact of head injuries on females is even greater than the impacts on men. This study looked at the medical records of 110 male and 102 female athletes who had a sport-related concussion injury, and found that the median recovery time for female athletes was 28 days – more than double the 11 days necessary for the males to recover.1

Males experienced a higher incidence of loss of consciousness and anterograde amnesia (defined as the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past), symptoms which many would associate with a more significant injury. Yet, surprisingly, this had no impact on the time to recovery from post-concussion symptoms. Other studies also have not shown a loss of consciousness and amnesia at the time of injury to be associated with symptom duration.2 Prior to concussion, females had a significantly higher history of migraines than males, a symptom which has previously been associated with an increase in time to recovery from concussion. However, there was no significant difference in recovery time between females with or without a pre-concussion history of migraines.3

Mechanisms and Symptoms of Concussion-Related Damage

Various potential explanations have been offered for the differences between males and females, including hormones, musculoskeletal variations, glucose metabolism, and gender differences in reporting physical symptoms.4,5,6 In females, symptoms of anxiety and depression and higher stress levels are also more frequent, and also may be a contributing factor.7 Overall, the pathophysiology of concussion is complex, and factors such as disruption of neurons known as axons, alterations in neurotransmitter release (due to impact-related effects, such as depolarization), neuroinflammation, and related excitotoxicity have been shown to play a role.8 Concussions also impact the integrity of the blood-brain barrier, which may additionally contribute to neuroinflammation and related oxidative stress as bloodborne neurotransmitters and mediators of inflammation also can then pass into the central nervous system.9 Elevated plasma levels of C-reactive protein (CRP), a marker of inflammation, have also been shown to be related to an increased incidence of post-concussion syndrome.10

In recognizing post-concussion syndrome, it is important to be aware that loss of consciousness does not indicate the severity of impact, and a broad range of physical, cognitive, and emotional symptoms may manifest. This can include headache, dizziness, hypersomnia or insomnia, difficulty with concentration and/or memory, depression, anxiety, and mood liability. Thus, anyone experiencing these types of symptoms with a recent head injury should question the potential of post-concussion syndrome, and should seek medical evaluation.

Support for Recovery from Post-Concussion Syndrome

The primary interventions which are important for post-concussion syndrome are rest, and abstinence from activities which put one at a high risk for a subsequent injury. However, in addition, neurocognitive, or brain, rest is also important. Any activities including physical activity or cognitive effort which worsen symptoms should be avoided.11 This even includes seemingly restful activities such as reading a book or watching television, as these actually require cognitive effort. Cognitive activities increase metabolic processes, and thus alter neurotransmitter levels and other aspects of central nervous system balance.

Nutraceutical support also has some evidence for reducing the potential impact of post-concussion issues. Melatonin has been recommended to support sleep for post-concussion sleep difficulties,12 and as an antioxidant may be a potential agent that helps the central nervous system to recover from the injury.13,14 Lipoic acid also is a neuroprotective antioxidant, and has been shown to reduce cellular death and scarring while promoting cell proliferation and new blood vessel formation after traumatic brain injury.15 CoQ10, another antioxidant with neuroprotective effects, has been studied in other conditions associated with neuroinflammation such as Alzheimer’s and Parkinson’s disease, and may support the restoration of antioxidant balance after head injuries.16

Essential fatty acids including omega-3’s as well as phosphatidylcholine also support recovery after traumatic brain injury. Omega-3 fatty acids reduce oxidative damage and help to normalize brain derived neurotrophic factor (BDNF), a signaling factor that facilitates synaptic transmission and learning ability, restoring homeostasis at cellular and molecular levels.17,18 Phosphatidylcholine, the predominant phospholipid that forms animal and plant cell membranes, promotes cellular repair and is a precursor for the synthesis of acetylcholine, a neurotransmitter important for cognitive function.19

Restoring the balance of inhibitory and excitatory neurotransmitters is also of importance. Glutamate is released in abundance with traumatic head injuries, and is a primary excitatory neurotransmitter.20 Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter that serves to balance glutamate, and shifts out of balance with glutamate subsequent to head injuries, in part due to the loss of GABA producing cells.21 Support for GABA thus also may help restore balance and homeostasis more rapidly. L-theanine, an amino acid derived from green tea, has a protective effect on the brain and supports BDNF levels, and functions complementary to GABA.22 Cannabidiol (CBD), the non-psychoactive constituent of marijuana, also has neuroprotective effects, and has been shown to be a superior antioxidant in preventing glutamate toxicity.23

 

In summary, although protective measures such as helmets and appropriate training may help to prevent head injuries, it is important to understand the symptoms which occur post-concussion, and to take protective measures to minimize adverse outcomes. Keeping a selection of supportive supplements around the home or in the gym bag to use when needed, or even taking them in an ongoing manner for protection, may be worth consideration, depending on the sports which you or your loved ones choose to participate in.

  

See videos on Phosphatidyl Choline (PC), GABA (gamma-aminobutyric acid) to learn more!


1 Niedecker JM, Gealt DB, Luksch JR, Weaver MD. First-Time Sports-Related Concussion Recovery: The Role of Sex, Age, and Sport. J Amer Osteo Assoc. 2017 Oct 2;117:635-642. View Full Paper

2 Meehan WP 3rd, Mannix RC, Stracciolini A, et al. Symptom severity predicts prolonged recovery after sport-related concussion, but age and amnesia do not. J Pediatr. 2013 Sep;163(3):721-5. View Full Paper

3 Scopaz KA, Hatzenbuehler JR. Risk modifiers for concussion and prolonged recovery. Sports Health. 2013 Nov;5(6):537-41. View Full Paper

4 Covassin T, Elbin RJ. The female athlete: the role of gender in the assessment and management of sport-related concussion. Clin Sports Med. 2011 Jan;30(1):125-31. View Abstract

5 Tierney RT, Sitler MR, Swanik CB, et al. Gender differences in head-neck segment dynamic stabilization during head acceleration. Med Sci Sports Exerc. 2005 Feb;37(2):272-9.

6 Andreason PJ, Zametkin AJ, Guo AC, et al. Gender-related differences in regional cerebral glucose metabolism in normal volunteers. Psychiatry Res. 1994 Feb;51(2):175-83. View Abstract

7 Hankin BL. Development of sex differences in depressive and co-occurring anxious symptoms during adolescence: descriptive trajectories and potential explanations in a multiwave prospective study. J Clin Child Adolesc Psychol. 2009 Jul;38(4):460-72. View Full Paper

8 Steenerson K, Starling AJ. Pathophysiology of Sports-Related Concussion. Neurol Clin. 2017 Aug;35(3):403-408. View Abstract

9 Sahyouni R, Gutierrez P, Gold E, et al. Effects of concussion on the blood–brain barrier in humans and rodents. J Concussion. 2017 Jan;1:2059700216684518. View Full Paper

10 Su SH, Xu W, Li M, et al. Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: a preliminary study. Brain Behav Immun. 2014 May;38:111-7. View Abstract

11 Sady MD, Vaughan CG, Gioia GA. School and the concussed youth: recommendations for concussion education and management. Phys Med Rehabil Clin N Am. 2011 Nov;22(4):701-19. View Full Paper

12 Meehan WP 3rd. Medical therapies for concussion. Clin Sports Med. 2011 Jan;30(1):115-24. View Full Paper

13 Samantaray S, Das A, Thakore NP, et al. Therapeutic potential of melatonin in traumatic central nervous system injury. J Pineal Res. 2009 Sep;47(2):134-42. View Abstract

14 Barlow KM, Brooks BL, MacMaster FP, et al. A double-blind, placebo-controlled intervention trial of 3 and 10 mg sublingual melatonin for post-concussion syndrome in youths (PLAYGAME): study protocol for a randomized controlled trial. Trials. 2014 Jul 7;15(1):271. View Abstract

15 Rocamonde B, Paradells S, Barcia JM, et al. Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury. Neuroscience. 2012 Nov 8;224:102-15. View Abstract

16 Beal MF. Mitochondrial dysfunction and oxidative damage in Alzheimer's and Parkinson's diseases and coenzyme Q 10 as a potential treatment. Journal of bioenergetics and biomembranes. 2004 Aug 1;36(4):381-6. View Abstract

17 Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004 Oct;21(10):1457-67. View Abstract

18 Wu A, Ying Z, Gomez-Pinilla F. Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury. J Neurotrauma. 2007 Oct;24(10):1587-95. View Abstract

19 Ladd SL, et al. Effect of phosphatidylcholine on explicit memory. Clin Neuropharmacol. 1993 Dec;16(6):540-9. View Abstract

20 Katayama Y, et al. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990 Dec;73(6):889-900. View Abstract

21 Guerriero RM, Giza CC, Rotenberg A. Glutamate and GABA imbalance following traumatic brain injury. Curr Neurol Neurosci Rep. 2015 May;15(5):27. View Full Paper

22 Cho HS, Kim S, Lee SY, et al. Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology. 2008 Jul;29(4):656-62. View Abstract

23 Hampson AJ, Grimaldi M, Lolic M, et al. Neuroprotective antioxidants from marijuana. Ann N Y Acad Sci. 2000;899:274-82. View Abstract

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Water, Water Everywhere, and Not a Drop to Drink?

 

The Many Pollutants that Imperil Our Drinking Water Today

Did you ever wonder why scientists get so excited over the possibility of water on other planets? Why should the presence of ordinary H2O—one oxygen and two hydrogen atoms—be so momentous? Because, as the popular magazine Scientific American puts it, water is “the unique molecule that cradles and nurtures life.” If other planets carry water, they just might harbor life.

But these days, water isn’t just water. Our water is often tainted, and the chemicals it contains may be hazardous to our health. Heavy metals, pesticides, drug and antibiotic residues, harmful bacteria and waste—all contaminate our water. “Water is essential for life,” wrote scientists from around the world in a 2014 review article, “and exposures to chemicals in drinking water, even at low concentrations, may have important consequences across the entire population.”1

We know of the tragedy in Flint, Michigan, where lead in drinking water made many residents ill—and according to a new 2017 study, not only did the fertility rate drop precipitously but fetal death rates soared a shocking 58 percent.2 But lead in water is just the one tiny aspect of our national water problem. Many communities still lack proper wastewater treatment facilities, infrastructure to retain and control polluted storm water runoff, and are in need of repairs to outdated sewage systems.3 Pesticide runoff from agriculture, as well as covert industrial dumping into lakes, rivers and the ocean, are also issues.4 According to Environment America, 206 million pounds of toxic chemicals were dumped into America’s waterways in 2012.5 We are all increasingly exposed to a slew of toxins in water. Here is a list of just a few:

* Perfluorinated chemicals (PFCs), which include perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), were recently found in 162 water systems in the US, exposing at least 15 million Americans in 27 states, according to the Environmental Working Group (EWG) and Northeastern University in Boston.6 PFCs not only persist in the environment, they accumulate in our bodies, and animal studies have shown they harm reproduction, development and immune function.7

*Halogens, especially fluorine, chlorine and bromine. Halogens are a group of five non-metallic elements and include fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and astatine (At). Unfortunately, we all too often find toxic fluorine, chlorine and bromine in our water.

Back in the 1940’s, we began adding fluoride to drinking water to help prevent tooth decay.8 Fluoride is a neurotoxin and an endocrine disruptor.9,10 Fluoride consumption has been linked to cancer.11 Chlorine, in turn, is added to water to disinfect it—whether drinking water, swimming pools, sewage or industrial waste. Chlorine exposure can cause respiratory problems, increase allergic inflammation and activate inflammatory pathways in the body.12 Chronic ingestion in chlorinated water may be associated with bladder cancer.13 And bromine—widespread in the environment, including our drinking water—comes to us by virtue of the brominated flame retardants in everything from our computers to our carpet.14,15 Brominated flame retardants are potent endocrine disrupters, and may be implicated in diabetes, neurobehavioral and developmental disorders, cancer, reproductive problems, and alteration in thyroid function.16

Perhaps most significantly, all three of these common halogens (fluorine, chlorine and bromine) are able to displace iodine17,18, an essential trace mineral necessary for the thyroid to manufacture the thyroid hormones, T3 and T4. An iodine deficiency can lead to impaired thyroid function, and thus slowed metabolism, weight gain, fatigue, neurological, musculoskeletal, and gastrointestinal symptoms.19

*Heavy metals, including lead, arsenic, mercury and aluminum. Though Flint, Michigan, is an isolated city with national fame, lead in drinking water is a nationwide problem. Lead was allowed in paint until 1978, and approximately 24 million housing units still contain deteriorating lead paint that contaminates household dust.20 In addition, the metal is present in old lead pipes, some vinyl-based products like shower curtains and raincoats and even children’s antique or imported toys.21 Lead can lead to cognitive dysfunction in adults,22 and can lower IQ in children, because the developing brain is vulnerable.23 Lead is also a neurotoxin, and lead-induced damage can be associated with mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinson’s disease, and schizophrenia.24

Arsenic can often be found in water from private wells.25 The Natural Resources Defense Council estimates that over 55 million Americans are drinking water with dangerous levels of arsenic. The USGS website offers maps showing where arsenic occurs in ground water. .According to the Center for Public Integrity: “The EPA has been prepared to say since 2008, based on its review of independent science, that arsenic is 17 times more potent as a carcinogen than the agency now reports. Women are especially vulnerable. Agency scientists calculated that if 100,000 women consumed the legal limit of arsenic every day, 730 of them would eventually get bladder or lung cancer from it.” Unfortunately, the EPA was prevented from lowering safe limits by Congress.26

Mercury is a global and potent neurotoxin, and can be carried on the jetstream and brought down in storms. Certain bacteria present in water and swampy areas can then transform it into methylmercury, which is particularly harmful.27 Mercury accumulates in larger, predatory fish, to which the majority of us are also exposed when we eat them.28

*Drug residues, including antibiotics, painkillers and antidepressants. Researchers have identified traces of pharmaceutical drugs in the drinking water of at least 40 million Americans, along with residues from personal care products.29,30,31

 

This is only a short list of contaminants in water. With all the pollutants in your regular drinking water, it is easy to feel discouraged. But there are simple actions we can take to protect ourselves. First and foremost: filter your drinking water. Even easily available countertop filters, or those that attach to the tap, such as Brita and Pur, do a good job of filtering out contaminants like chlorine and lead. They do this through an activated charcoal medium. However, to filter out fluoride and other chemicals, a filter needs to use reverse osmosis, deionizers (which use ion-exchange resins), and/or activated alumina. To read more about different water filters, go to Fluoride Alert. When purchasing a filter or other equipment which is used for water filtration, be sure to investigate the manufacturers specifications, as these will indicate how tightly they are able to control for various substances. This will help to best select a filter to remove substances which you are at risk of exposure to.


1 Villaneuva CM, Kogevinas M, Cordier S et al. Assessing Exposure and Health Consequences of Chemicals in Drinking Water: Current State of Knowledge and Research Needs Environ Health Perspect. 2014 Mar; 122(3): 213–221 View Full Paper

2 Grossman D, Slusky D. The effect of an increase in lead in the water system on fertility and birth outcomes: the case of Flint, Michigan. Working Papers Series in Theoretical and Applied Economics, No 201703. 2017. View Full Paper

3 Wu, M. Robbing Peter to pay Paul won't stop future drinking water disasters. Feb 2016 [cited September 20, 2017] Available at: https://www.nrdc.org/experts/mae-wu/robbing-peter-pay-paul-wont-stop-future-drinking-water-disasters

4 United States Environmental Protection Agency. Lear about ocean dumping. [cied September 21, 2017] Available at: https://www.epa.gov/ocean-dumping/learn-about-ocean-dumping

5 Rumpler, J. 206 Million pounds of toxic chemicals dumped into America’s waterways June 2014 [Cited September 21, 2017] Available at: http://www.environmentamerica.org/news/ame/206-million-pounds-toxic-chemicals-dumped-america%E2%80%99s-waterways

6 Trager, R. Perfluorinated chemicals in drinking water of 15 million Americans June 2017. [cited September 20, 2017]. Available at: https://www.chemistryworld.com/news/perfluorinated-chemicals-in-drinking-water-of-15-million-americans/3007589.article

7 Corsini E, Luebke RW, Germolec DR et al. Perfluorinated compounds: emerging POPs with potential immunotoxicity.Toxicol Lett. 2014 Oct 15;230(2):263-70. View Full Paper

8 National Cancer Institute, Fluoridated Water. May 2017. [cited September 20, 2017] Available at: https://www.cancer.gov/about-cancer/causes-prevention/risk/myths/fluoridated-water-fact-sheet

9 Jianjie C, Wenjuan X, Jinling C et al. Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio).Aquat Toxicol. 2016 Feb;171:48-58 View Abstract

10 Choi AL, Sun G, Zhang Y et al. Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect. 2012 Oct;120(10):1362-8 View Full Paper

11 National Research Council, Subcommittee on Health Effects of Ingested Fluoride. Carcinogenicity of fluoride. In: Health Effects of Ingested Fluoride. Washington, DC: National Academy Press, 1993.

12 Sae-Hoon Kim, Da-Eun Park, Hyun-Seung Lee et al. Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

PLoS One. 2014; 9(9): e106861. View Full Paper

13 Hrudey SE, Backer LC, Humpage AR et al. Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products. J Toxicol Environ Health B Crit Rev. 2015 Jul 4; 18(5): 213–241 View Full Paper

14 Vorkamp K, Bossi R, Bester K, et al. New priority substances of the European Water Framework Directive: biocides, pesticides and brominated flame retardants in the aquatic environment of Denmark. Sci Total Environ. 2014 Feb 1;470-471 View Abstract

15 Cristale J, Quintana J, Chaler R et al. Gas chromatography/mass spectrometry comprehensive analysis of organophosphorus, brominated flame retardants, by-products and formulation intermediates in water. J Chromatogr A. 2012 Jun 8;1241:1-12. View Abstract

16 Kim YR, Harden FA, Toms LM et al. Health consequences of exposure to brominated flame retardants: a systematic review. Chemosphere. 2014 Jul;106:1-19. View Abstract

17 Butt CM, Wang D, Stapleton HM. Halogenated phenolic contaminants inhibit the in vitro activity of the thyroid-regulating deiodinases in human liver. Toxicol Sci. 2011 Dec;124(2):339-47. View Abstract

18 Susheela AK, et al. Excess fluoride ingestion and thyroid hormone derangements in children living in Delhi, India. Fluoride. 2005;38(2):98-108

19 Diaz A, Lipman DE. Hypothyroidism. Pediatr Rev. 2014 Aug;35(8):336-47. View Abstract

20 Centers for Disease Control, Lead prevention tips. June 2014 [Cited September 21, 2017] Available at: https://www.cdc.gov/nceh/lead/tips.htm

21 Centers for Disease Control, Lead prevention tips. Oct 2013 [Cited September 21, 2017] https://www.cdc.gov/nceh/lead/tips/toys.htm

22 Seo J, Lee BK, Jin SU et al. Altered executive function in the lead-exposed brain: A functional magnetic resonance imaging study. Neurotoxicology. 2015 Sep;50:1-9 View Abstract

23 Schneider JS, Talsania K, Mettil W et al. Genetic diversity influences the response of the brain to developmental lead exposure. Toxicol Sci. 2014 Sep;141(1):29-43 View Full Paper

24 Liu KS, Hao JH, Zeng Y et al. Neurotoxicity and biomarkers of lead exposure: a review. Chin Med Sci J. 2013 Sep;28(3):178-88. Review. View Abstract

25 Sorg TJ, Chen AS, Wang L. Arsenic species in drinking water wells in the USA with high arsenic concentrations. Water Res. 2014 Jan 1;48:156-69 View Abstract

26 Heath, D. How politics derailed EPA science on arsenic, endangering public health. June 2014 [Cited September 21, 2017] Available at: https://www.publicintegrity.org/2014/06/28/15000/how-politics-derailed-epa-science-arsenic-endangering-public-health

27 Grandjean P, Weihe P, Debes F et al. Neurotoxicity from prenatal and postnatal exposure to methylmercury. Neurotoxicol Teratol. 2014 May-Jun;43:39-44. View Abstract

28 Mercury Levels in Commercial Fish and Shellfish (1990-2012). U.S. Food and Drug Administration. Accessed February 8, 2017. View Table

29 Guerrero-Preston R, Brandt-Rauff P. Pharmaceutical residues in the drinking water supply: modeling residue concentrations in surface waters of drugs prescribed in the United States. P R Health Sci J. 2008 Sep;27(3):236-40. View Abstract

30 Derksen JG, Rijs GB, Jongbloed RH. Diffuse pollution of surface water by pharmaceutical products.

Water Sci Technol. 2004;49(3):213-21. View Abstract

31 Li Z, Xiang X, Li M et al. Occurrence and risk assessment of pharmaceuticals and personal care products and endocrine disrupting chemicals in reclaimed water and receiving groundwater in China. Ecotoxicol Environ Saf. 2015 Sep;119:74-80 View Abstract

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Small But Dangerous Air

 

The air we breathe might be more dangerous than we think...

 

2017 has been a year of hurricanes, floods and fires—Harvey, Irma, Jose, and rampant wildfires raging across the west and Canada, including Montana, Idaho, Oregon, California and Vancouver. We don’t think much about the air we breathe every moment of our waking and sleeping lives—until it morphs into 125 mph winds, or brings a haze of acrid smoke whose finest particles — particulate matter that's 2.5 microns or less in diameter — are not even visible to the naked eye. It is, however, those fine particles that are most dangerous, and can penetrate the lungs and enter the bloodstream, with harmful health effects.1,2,3smoke causing damage to lungs

It is often what we cannot see in air that causes us trouble. All particulate matter can be detrimental to health—and it is all on the increase, with urban development and industrialization. The smaller the particulate matter (PM) in air, the more harmful it can be. The two size thresholds most commonly studied are 10 micrometers or less (referred to as PM10) and 2.5 micrometers or less (referred to as PM2.5). There is an even finer threshold of PM, known as ultrafine particulates, that is about 100 nanometers, or PM0.1. Regulations do not even exist for PM0.1, which are far smaller than the regulated PM10 and PM2.5 particle classes.4

Air pollution and smog are composed of high concentrations of PM2.5—which can carry toxins right past the nose hairs, accumulating by diffusion in the lungs, where they irritate and inflame the tissue and impair lung function.5 These fine particles are linked to mortality—a 1996 study found that PM2.5 is one of the leading causes of human non-accidental death.6 About 3.3 million premature deaths per year occur globally due to outdoor air pollution, linked mainly to PM2.5 exposure.7

The tiny size of PM allows them to penetrate vulnerable tissues: in fact, by moving from lung tissue into circulation, they can affect the ability of the blood to flow freely, the functioning of the autonomic nervous system, and even the health of cells themselves.8 They can cause oxidative stress and inflammation.9 Ultrafine PM0.1 particles can even penetrate and damage the mitochondria, the energy powerhouses within every cell, and also cause damage via oxidative stress to our DNA.10 They can damage the delicate membranes of the mitochondria, and deplete intracellular levels of our most important antioxidant, glutathione.11 A 2014 study found harmful ultrafine particles from takeoffs and landings at Los Angeles International Airport to be of much greater magnitude than previously believed—and possibly harming communities as far as ten miles away.12small particulate matter is dangerous

PM sources are many. We are exposed to harmful particulates in everything from ocean spray and volcanic eruptions to wildfire smoke, combustion, automobile and airplane exhaust, photocopiers, tobacco smoke, vacuum cleaners, coal and biomass plant emissions, ozone, fresh paint, and airborne heavy metals brought down from the jet stream in storms, to name just a few. Aside from PM, there also is the fact that climate change and a warming planet are increasing the risks of airborne pathogens and toxins such as the fungus that causes Valley Fever13, the cyanotoxins from algae blooms,14,15 and molds arising from water-damaged buildings as flood events become more common.16 Pesticide exposure and drift is also an issue, both from agriculture and aerial spraying to combat pests such as mosquitoes.

Air pollutionAvoiding air pollution can be tough. One way to address the issue is to minimize exposure. Hepa air filters and whole house filtering systems can help filter out some of these particles. Air quality can vary widely by city, state, region, and season. Most states offer air monitoring data available on websites. Weather apps will also include air quality alerts. Outdoor activities can, and for many should, be minimized during times when there are higher levels of air pollution. Exercise actually has been shown to increase the pro-thrombotic effect of air pollutant exposure.17

Forest bathing—a term coined by the Japanese in the 1990’s—is an increasingly popular way to find fresher air and improve immune function. A 2011 study found that forest walks, as opposed to city walks, led to more significant reductions in blood pressure and stress hormones after just four hours.18 Trees remove air pollution by intercepting PM on the surface of their leaves. The leaves also help absorb gaseous pollutants.19

combat the oxidative stress associated with air pollution

In this increasingly polluted world, lifestyle changes and avoidance of high exposure often is not enough, or simply not possible. In this setting, antioxidants or antioxidant-promoting strategies become necessary to help our bodies offset the negative health impacts of air pollution. Supplemental antioxidants such as glutathione and vitamin C help our body to combat the oxidative stress associated with air pollution,20 while additional support for our body’s endogenous production of glutathione with supplements like lipoic acid and diindolylmethane also are key.21,22

 

 

  


1 Haikerwal A, Reisen F, Sim MR et al. Impact of smoke from prescribed burning: Is it a public health concern? J Air Waste Manag Assoc. 2015 May;65(5):592-8 View Abstract

2 Dennekamp M, Straney LD, Erbas B et al. Forest Fire Smoke Exposures and Out-of-Hospital Cardiac Arrests in Melbourne, Australia: A Case-Crossover Study. Environ Health Perspect. 2015 Oct;123(10):959-64. View Full Paper

3 Haikerwal A, Akram M, Del Monaco A. Impact of Fine Particulate Matter (PM2.5) Exposure During Wildfires on Cardiovascular Health Outcomes. J Am Heart Assoc. 2015 Jul 15;4(7). View Full Paper

4 Howard V. Statement of Evidence: Particulate Emissions and Health (An Bord Plenala, on Proposed Ringaskiddy Waste-to-Energy FacilityDurham Environment Watch. 2009 Jun:1-38 View Full Paper

5 Xing YF, Xu YH, Shi MH et al. The impact of PM2.5 on the human respiratory system.J Thorac Dis. 2016 Jan;8(1):E69-74. View Full Paper

6 Schwartz J, Dockery DW, Neas LM. Is daily mortality associated specifically with fine particles? J Air Waste Manag Assoc 1996;46:927-39 View Abstract

7 Lelieveld J, et al. The contribution of outdoor air pollution sources to premature mortality on a global scale. Nature. 2015 Sep 17;525(7569):367-71 View Abstract

8 Terzano C, et al. Air pollution ultrafine particles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci. 2010 Oct;14(10):809-21 View Abstract

9 Mazzoli-Rocha F, et al. Roles of oxidative stress in signaling and inflammation induced by particulate matter. Cell Biol Toxicol. 2010 Oct;26(5):481-98 View Abstract

10 Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. View Abstract

11 Li N, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect. 2003 Apr;111(4):455-60 View Full Paper

12 Hudda N, Gould T, Hartin K. Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind. Environ Sci Technol. 2014 Jun 17;48(12):6628-35. View Full Paper

13 Johnson L, Gaab EM, Sanchez J et al. Valley fever: danger lurking in a dust cloud.Microbes Infect. 2014 Aug;16(8):591-600. View Full Paper

14Banack SA, Caller T, Henegan P et al. Detection of Cyanotoxins, β-N-methylamino-l-alanine and Microcystins, from a Lake Surrounded by Cases of Amyotrophic Lateral Sclerosis Toxins (Basel) 2015 Feb; 7(2): 322–336 View Full Paper

15 Cheng YS, Zhou Y, Irvin CM et al. Characterization of Aerosols Containing Microcystin Mar Drugs. 2007 Dec; 5(4): 136–150 View Full Paper

16 Andersen B, Frisvad JC, Søndergaard Ib et al. Associations between Fungal Species and Water-Damaged Building Materials Appl Environ Microbiol. 2011 Jun; 77(12): 4180–418 View Full Paper

17 Wauters A, et al. Pro-thrombotic effect of exercise in a polluted environment: a P-selectin- and CD63-related platelet activation effect. Thromb Haemost. 2015 Jan;113(1):118-24. View Abstract

18 Li Q, Otsuka T, Kobayashi M. Acute effects of walking in forest environments on cardiovascular and metabolic parameters. Eur J Appl Physiol. 2011 Nov;111(11):2845-53. View Abstract

19 Nowak DJ, et al. Tree and forest effects on air quality and human health in the United States. Environ Pollut. 2014 Oct;193:119-29. View Full Paper

20Kelly FJ. Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med. 2003 Aug;60(8):612-6. View Full Paper

21 Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3381-6. View Full Paper

22 Ernst IM, Schuemann C, Wagner AE, Rimbach G. 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. Free Radic Res. 2011 Aug;45(8):941-9. View Abstract

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Can Food Really Be Our Medicine?

How Toxins Are Pervading our Food Supply and Harming Our Health

Brilliant Blue. Allura red. Sunset Yellow. The colors sound so delicious — surely they describe some dazzling new interior design, an innovative line of eyeshadows or next season’s shiny sportscars? Or perhaps they are new brilliant hues to fill the artist’s pallet, or trending interior accent colors? 

         None of the above. In fact, they are the names of FDA-approved artificial food colorings and dyes, and they can be hidden in everything from your heart-healthy salsa to your whole grain breakfast cereal and blueberry yogurt.1Food dye consumption per person has increased fivefold in the United States since 1955, with three dyes—Red 40, Yellow 5, and Yellow 6—accounting for 90% of the dyes used in foods. Artificial dyes, some derived from petroleum, are found in thousands of foods, and may be carcinogenic, as well as cause hypersensitivity reactions.2They present what the Center for Science in the Public Interest (CSPI) in Washington, DC, literally calls a “rainbow of risk.” In 2016, when Prevention Magazine took a close look at surprising foods with dyes, they found that 90% of foods marketed to children contain dyes, and that everything from flavored applesauce to smoked salmon, hot sauce, and salad dressing contain dyes.3

          Many foods, unfortunately, harbor more than potentially toxic dyes—they also contain additives and preservatives that may be carcinogenic. Take, for example, BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene), two preservatives that prevent oils in foods from oxidizing and becoming rancid. According to the Berkeley Wellness Letter, “The National Toxicology Program has concluded that BHA ‘is reasonably anticipated to be a human carcinogen,’ while BHT has been linked to an increased—or sometimes decreased—risk of cancer in animals. The consumer group the Center for Science in the Public Interest thus cites BHA as an additive to “avoid” and puts BHT in its “caution” column.”4

          Next up: processed meats—such as hotdogs, salami, ham, bologna, bacon, sausages and more. They contain a chemical called sodium nitrite, which during cooking can form carcinogenic compounds.5A study by the Cancer Research Center of Hawaii and the University of Southern California found a correlation between eating processed meats and cancer risk. The study followed 190,000 people, ages 45-75, for seven years. Those who ate the most processed meats had a 67% higher risk of pancreatic cancer than those who ate the least amount.6

          Then there are the toxins that migrate into food from the wrappings and containers they are packaged in—everything from films to pouches, bottles, trays and lids.7For instance, many fast-food wrappers and boxes contain chemicals that can leach into food, and one out of five paperboard food boxes in a 2017 study contained detectable levels of fluorine.8Fluorinated chemicals, suspected carcinogens9, also are allowed in compostable food packaging.Plasticizers have a low molecular weight and can migrate from packaging materials into the food wrapped within, thus becoming indirect food additives.10And migration of plasticizers from PVC gaskets in the closures of glass jars has been reported for contact with oily foods.11

          Along with additives, preservatives and migrating molecules, heavy metals can be present in many foods. The presence of mercury in large fish is well known. When the Environmental Working Group looked at pregnant women who eat fish, they found that about 30% had mercury levels over the safe limit set by the EPA and 60% had excessive mercury levels in their hair. Frequent fish eaters had 11 times more mercury than a group who rarely ate fish.12And bone broth—in many ways a very healthy, nutritious food—can have excess lead levels. A 2013 study measured the levels of lead in broth made from the bones of organic chickens. The broth was found to have “markedly high lead concentrations” compared to water cooked in the same cookware.13Similarly, rice is well known to sequester arsenic, absorbing it from irrigation water, soil, and even cooking water. Arsenic exposure is linked to heart disease, kidney disease, brain disease, and diabetes.14

          Pesticide residues present another threat to our health from the food supply.15,16,17Pesticide exposure is linked to cancer risk, birth defects, obesity, and other maladies.18More than 1 billion pounds of pesticides are used annually nationwide, according to the Pesticide Action Network North America, an environmental group in Oakland.19,20

           Given all the potential toxins in foods, one might wonder how to eat a truly healthy diet. One option is to source organic and fresh produce whenever possible, to avoid packaged and prepared foods and large fish that often contain high amounts of mercury. In addition, varying your diet rather than focusing on a few foods, spreads the risk of accumulation of a particular toxin that food might carry. Many people who eat excess of one food such as tuna or brown rice, thinking it to be healthy, are actually at risk of accumulating high levels of mercury or arsenic in the blood because intake exceeds the body’s ability to eliminate it.

          Because of our inherent exposure to these toxic substances and many others, it is important to support the body in elimination. By utilizing specific combinations of nutraceutical supplements, the body’s natural detoxification abilities can be upregulated. This helps the body to process and eliminate these potentially damaging substances which often are stored in the tissues of the body. Because many of these substances are stored in the body, even if you make a dramatic change to your diet today in attempts to avoid exposure, the things you were exposed to weeks and months ago remain stuck in the body, and may be causing damage. Toxic substances not only damage our cells and at larger levels impact organ function, but also can have an epigenetic impact which may affect you and your offspring generations to come.21


1  Potera, C. Diet and Nutrition The artificial food dye blues. Environ Health Perspect. 2010 Oct; 118(10): A428.View Full Paper

2  CSPI. Food Dyes: A Rainbow of Risks. Washington, DC: Center for Science in the Public Interest; 2010. [accessed 15 Sep 2010]. Available at http://tinyurl.com/2dsxlvd

3  Parderio, C. 7 Surprising foods that contain artificial dyes. April 2016. [Accessed August 24, 2017]. Available at: https://www.prevention.com/food/surprising-foods-with-food-dyes

4  Berkeley Wellness. Two Preservatives to Avoid? February 2011. [Accessed August 24, 2017]. Available at: http://www.berkeleywellness.com/healthy-eating/food-safety/article/two-preservatives-avoid

6  Nöthlings U, Wilkens LR, Murphy SP, et al. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study.

J Natl Cancer Inst. 2005 Oct 5;97(19):1458-65.View Full Paper

7  Bhunia K, Sablani S, Tang J, et al. Migration of Chemical Compounds from Packaging Polymers during Microwave, Conventional Heat Treatment, and Storage. Comprehensive Reviews in Food Science and Food Safety, 2013. 12: 523–545. (12) 5.View Full Paper

8Schaider, LA, Balan SA, Blum A. Fluorinated Compounds in U.S. Fast Food Packaging Environ. Sci. Technol. Lett., 2017, 4 (3), pp 105–111.View Full Paper

9  Zhang XJ, Lai TB, Kong RY. Biology of fluoro-organic compounds. Top Curr Chem. 2012;308:365-404. doi: 10.1007/128_2011_270. Review.View Abstract

10  Goulas AE, Riganakos KA, Ehlermann DAE, et al. Effect of high dose electron beam irradiation on the migration of DOA and ATBC plasticizers from food-grade PVC and PVDC/PVC films, respectively, into olive oil. J Food Prot 1998. 61:720-4.

11  Fankhauser-Noti A, Grob K. Migration of plasticizers from PVC gaskets of lids for glass jars into oily foods: amount of gasket material in food contact, proportion of plasticizer migratin into food and compliance testing by simulation. Trends Food Sci Tehcnol.. 2006; 17: 105-12

12  EWG, Mercury in seafood: executive summary. March, 2016 [Accessed August 25, 2017]. Available at: http://www.ewg.org/research/us-fish-advice-may-expose-babies-too-much-mercury/executive-summary

13  Monro JA, Leon R, Puri BK. The risk of lead contamination in bone broth diets. Med Hypotheses. 2013 Apr;80(4):389-90.View Abstract

14  WHO, Arsenic Fact Sheet, June 2016. [Accessed August 25, 2017] Available at: http://www.who.int/mediacentre/factsheets/fs372/en/

15  Thapa K, Pant BR. Pesticides in vegetable and food commodities: environment and public health concern.J Nepal Health Res Counc. 2014 Sep-Oct;12(28):208-10.View Abstract

16  Verger PJ, Boobis AR. Reevaluate pesticides for food security and safety. Global food supply. Science. 2013 Aug 16;341(6147):717-8

17  Mol HG, Reynolds SL, Fussell RJ, et al. Guidelines for the validation of qualitative multi-residue methods used to detect pesticides in food.

Drug Test Anal. 2012 Aug;4 Suppl 1:10-6.View Abstract

18  Parrón T, Requena M, Hernández AF.Environmental exposure to pesticides and cancer risk in multiple human organ systems.Toxicol Lett. 2014 Oct 15;230(2):157-65. View Abstract

19  PAN, Pesticides: myths and facts. [Accessed August 25, 2017]Available at: http://www.panna.org/pesticides-big-picture/myths-facts

20  PAN, Protecting farmworkers, protecting crops. [Accessed August 25, 2017] Available at http://www.panna.org/blog/protecting-farmworkers-protecting-crops

21  Skinner MK, et al. Epigenetic transgenerational actions of environmental factors in disease etiology. Trends Endocrinol Metab. 2010 Apr;21(4):214-22.View Full Paper

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Mitochondria: The Key to Reversing Disease and Aging?

If you were to discover the key to reversing or preventing disease processes, slowing or even stopping cellular changes associated with aging, as well as optimizing metabolism and energy production what would you do? Would you hold this treasure for your own, possibly sharing this gift of knowledge only with a few closest to you? Would you make it open public knowledge, free for all who seek to achieve immortality? Or would you establish an enterprise to produce and distribute this priceless commodity to the few which could afford it? Needless to say, you would fast become a highly regarded as well as very wealthy individual if this was your desire.

Such queries of goal or purpose if given the key to eternal youth are, of course, only intended to provoke thought. Yet for many who seek to cure disease and optimize our time in our earthly bodies, this quest is the drive for continued research for the turnkey to solving an abundance of problems with a singly perfect solution.

 

Mitochondria, the Energy Powerhouse of the Cell

Mitochondria, in the simplest of analogies, are the energy-generating powerhouses found in each of our cells. More mitochondria, not surprisingly, are found in muscular tissue – skeletal and cardiac muscle being the highest – because in these locations we need continuous energy production as well as surges of energy on demand. The energy units they generate are known as ATP, short for adenosine triphosphate, which is essential to power the other processes and reactions in the cell. It “costs” ATP to make glucose, to move things in and out of the cell, to perform metabolic reactions, to maintain cellular structures, and for cellular movement. Our body adapts to higher energy, or ATP, demand from activities like exercise by producing more mitochondria in the cell, further enhancing capacity for when it is needed.1,2 A more in-depth, yet easily digestible, discussion of the mitochondria and their function can be found at the Nature Education website.

Dysfunction or damage to these mitochondrial units has been associated with a variety of disease processes: Alzheimer’s and Parkinson’s disease,3 amyotrophic lateral sclerosis (ALS),4 diabetes,5 cardiovascular disease,6 liver disease,7 and autism8 to name a few. Defective mitochondria even appear to be passed, generationally, from parents with type 2 diabetes to their offspring.9 Dysfunction may contribute to the etiology of the disease or may be secondary, but once a dysfunctional state exists it continues to promote further damage on a cellular and even systemic level.

But how do some people’s mitochondria get “broken,” while those of others, particularly top-notch athletes seemingly stay on track?

 

Oxidative Stress = Mitochondrial Damage

Oxidative stress is a primary factor which contributes to mitochondrial damage and dysfunction. When the delicate mitochondria are damaged, they are not able to maintain necessary electrical and chemical gradients which are necessary for the production of ATP. Free radicals, also known as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are inherently present in our body, but when they exceed the ability of our body to neutralize them, the create damage. Similar to our mitochondrial powerhouse analogy, ROS and RNS look like little fireballs that bounce around creating damage and more ROS until they are neutralized by the transfer of an electron. The mitochondria also produce ROS and RNS in the process of doing their cellular jobs as well.10,11

Although a certain amount of oxidative stress is necessary for biological processes and cellular signaling, when excessive amounts of oxidative stress occurs it causes damage.12 Contributors to increased oxidative stress in the body include heavy metals, pesticides and herbicides, air pollution, mold toxins, chronic infections, and even stress and insomnia.13,14 With chronic oxidative stress in excess of what our body has the means to neutralize, our main intracellular antioxidant glutathione, as well as many others, become depleted.15,16 Genetically, some individuals may be more susceptible to disease associated when they experience these additional stressors, however they are something we all have to deal with.

The loss of mitochondrial function comes back to another topic also mentioned in passing – it is a major contributor to the changes we associate with aging.17

 

Mitochondrial Repair and Optimization

Even within our mitochondria there are systems to deal with the oxidative species which are a byproduct of their function. Vitamin E and coenzyme Q10 (CoQ10) are two antioxidants which are important for mitochondrial function, repair, and biogenesis. Vitamin E is found in the mitochondrial membranes, and serves to protect them from lipid peroxidation.18 CoQ10 is crucial for the process of ATP generation in the mitochondria, as well as quenching the oxidative species. CoQ10 is synthesized in our body, however levels of this protective and energy-supportive antioxidant have been shown to decrease with age.19,20,21 Statin medications also have the effect of inhibiting our body’s synthesis of CoQ10.22 Dietary supplementation of vitamin E and CoQ10 has been shown to improve tissue and mitochondrial levels, while supplementation of CoQ10 also has the effect of sparing or partially restoring levels of vitamin E.23 CoQ10 has been shown to preserve mitochondrial function and ATP generation, even increasing their number, when subject to excessive oxidative stress.24

Resveratrol, one of the most well-known polyphenols which we find in red wine, comes from the skins of grapes as well as blueberries and raspberries. It has been studied for its potential health benefits as an antioxidant as well as for anti-aging effects.25,26 One of the mechanisms by which resveratrol may have positive impacts on health is by supporting mitochondrial function. Resveratrol has been shown to improve the mitochondrial function in liver and skeletal muscle cells, as well as to induce the formation of new mitochondria in endothelial cells (specifically the aorta of mice with type 2 diabetes).27 In mice treated with resveratrol, their aerobic capacity was increased, and they were protected against diet-induced obesity and insulin resistance.28 Treatment with resveratrol had an effect similar to exercise on the formation of new mitochondria, although they had a synergistic effect when combined.29 Resveratrol also has been shown to have effects similar to calorie restriction, retarding some of the effects of aging.30 No wonder we get so excited about this wine-associated polyphenol, although the concentration in wine is far too low to achieve such benefits!

Pyrroloquinoline quinone (PQQ) is last but definitely not least on this list of mitochondrial boosting agents. PQQ has been shown to support antioxidant status by inducing Nrf2, the “switch” which turns on our endogenous antioxidant and antioxidant-supporting enzyme production (see DIM and Detoxification blog for more about Nrf2).31 PQQ functions as a cellular nutrient, supporting growth as well as protecting cells in conditions of stress.32 PQQ protects the mitochondria and preserves their function in settings of acute oxidative stress, reducing cellular death.33 It stimulates the production of new mitochondria, similar to resveratrol and CoQ10.34 In humans, consumption of PQQ was shown to enhance mitochondrial function, reducing inflammation as well.35

 

Advanced Delivery Formats Overcome Bioavailability Limitations

Advanced liposomal and nanoemulsified delivery systems offer unmatched bioavailability for both fat- and water-soluble ingredients. The tiny, nano-size particles are not broken down by the harsh acids of the digestive system as they enter circulation with rapid absorption immediately in the mouth. This enables direct delivery of bioavailable nutrients to the bloodstream and cells of the body. Liposomal and nanoemulsified delivery systems dramatically improve bioavailability of substances such as resveratrol and CoQ10 which otherwise have limited bioavailability.36,37 Phospholipids, specifically phosphatidylcholine, form the external sphere of the liposomal and nanoemulsified particles. These phospholipids are additionally utilized by the cell, and are important for mitochondrial membrane health and repair.38

The possibility of enhancing energy production, and reducing damage and cellular changes associated with aging continues to fuel research investigating the impact that improved mitochondrial function may have on our health overall. The disease implications are significant as well, particularly for neurodegenerative disease. Nutritional support with substances such as these, particularly CoQ10, has been a topic of considerable clinical research for this reason. The potential to more dramatically impact many disease conditions with advanced delivery of nutritional substances is equally exciting for medical practitioners and those who struggle with chronic health conditions. Quicksilver Scientific is an ally in your quest for improved health and longevity, supporting you to achieve your optimal genetic potential.


1 Gollnick PD, King DW. Effect of exercise and training on mitochondria of rat skeletal muscle. Am J Physiol. 1969 Jun;216(6):1502-9. View Full Paper

2 Hood DA, Saleem A. Exercise-induced mitochondrial biogenesis in skeletal muscle. Nutr Metab Cardiovasc Dis. 2007 Jun;17(5):332-7. View Full Paper

3 Yan MH, Wang X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med. 2013 Sep;62:90-101. View Full Paper

4 Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2017 Jun 30. View Abstract

5 Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384-7. View Abstract

6 Marzetti E, Csiszar A, Dutta D, et al. Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics. Am J Physiol Heart Circ Physiol. 2013 Aug 15;305(4):H459-76. View Full Paper

7 Mantena SK, King AL, Andringa KK, et al. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic Biol Med. 2008 Apr 1;44(7):1259-72. View Full Paper

8 Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012 Mar;17(3):290-314. View Full Paper

9 Petersen KF, Dufour S, Befroy D, et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med. 2004 Feb 12;350(7):664-71. View Full Paper

10 Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003 Oct 15;552(Pt 2):335-44. View Full Paper

11 Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009 Jan 1;417(1):1-13. View Full Paper

12 Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002 Jan;82(1):47-95. View Full Paper

13 Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011 May 10;283(2-3):65-87. View Abstract

14 Gulec M, Ozkol H, Selvi Y, et al. Oxidative stress in patients with primary insomnia. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jun 1;37(2):247-51. View Abstract

15 Perricone C, et al. Glutathione: a key player in autoimmunity. Autoimmun Rev. 2009 Jul;8(8):697-701. View Abstract

16 Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. View Full Paper

17 Salvioli S, Bonafè M, Capri M, et al. Mitochondria, aging and longevity--a new perspective. FEBS Lett. 2001 Mar 9;492(1-2):9-13. View Full Paper

18 Ham AJ, Liebler DC. Vitamin E oxidation in rat liver mitochondria. Biochemistry. 1995 May 2;34(17):5754-61. View Abstract

19 Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001 Dec;20(6):591-8. View Abstract

20 Lass A, Kwong L, Sohal RS. Mitochondrial coenzyme Q content and aging. Biofactors. 1999;9(2-4):199-205. View Abstract

21 Niklowitz P1, Onur S2, Fischer A, et al. Coenzyme Q10 serum concentration and redox status in European adults: influence of age, sex, and lipoprotein concentration. J Clin Biochem Nutr. 2016 May;58(3):240-5. View Full Paper

22 Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18 Suppl:S137-44. View Abstract

23 Ibrahim WH, Bhagavan HN, Chopra RK, Chow CK. Dietary coenzyme Q10 and vitamin E alter the status of these compounds in rat tissues and mitochondria. J Nutr. 2000 Sep;130(9):2343-8. View Full Paper

24 Noh YH, Kim KY, Shim MS, Choi SH, et al. Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes. Cell Death Dis. 2013 Oct 3;4:e820. View Full Paper

25 Gülçin İ. Antioxidant properties of resveratrol: a structure–activity insight. Innov Food Sci & Emer Tech. 2010 Jan 31;11(1):210-8. View Abstract

26 de la Lastra CA, Villegas I. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res. 2005 May;49(5):405-30. View Abstract

27 Csiszar A, Labinskyy N, Pinto JT, et al. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H13-20. View Full Paper

28[1][1] Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109–1122, 2006. View Abstract

29 Menzies KJ, Singh K, Saleem A, Hood DA. Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis. J Biol Chem. 2013 Mar 8;288(10):6968-79. View Full Paper

30 Barger JL, Kayo T, Vann JM, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One. 2008 Jun 4;3(6):e2264. View Full Paper

31 Zhang Q, Ding M, Gao XR, Ding F. Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes. Genet Mol Res. 2012 Aug 16;11(3):2652-64. View Abstract

32 Misra HS, Rajpurohit YS, Khairnar NP. Pyrroloquinoline-quinone and its versatile roles in biological processes. J Biosci. 2012 Jun;37(2):313-25. View Abstract

33 Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62. View Full Paper

34 Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52. View Full Paper

35 Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84. View Abstract

36 Beg S, Javed S, Kohli K. Bioavailability enhancement of coenzyme Q10: an extensive review of patents. Recent Pat Drug Deliv Formul. 2010 Nov;4(3):245-55. View Abstract

37 Walle T, Hsieh F, DeLegge MH, et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004 Dec;32(12):1377-82. View Full Paper

38 Spector AA, Yorek MA. Membrane lipid composition and cellular function. J Lipid Res. 1985 Sep;26(9):1015-35. View Full Paper

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What is YOUR Multivitamin Really Delivering?

Multivitamin users have been chastened for their health choices in recent years by the media for trying to support their health by taking a daily multivitamin. Multiple literature reviews have pointed at the lack of beneficial outcomes with multivitamin/mineral (MVM) use, which one summary study from the January 2017 issue of Nutrition concludes by stating “In particular, there were no significant differences between treatment and placebo groups.”1Another concludes “Evidence is insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements to prevent cancer and chronic disease.”2Popular media of course takes these conclusions and runs with them, telling everyone are foolish to waste their money in this manner. Not surprisingly, MVM use has declined between 2000 to 2012 from 37% to 31% of those surveyed.3However, what is neglected with this simple summary and broadly broadcasted message are further details about what the supplements are that are being taken.

Over-the-counter supplements: plagued by poor bioavailability and poor-quality ingredients

Part of the problem with MVM supplementation is that even though a label may state that a supplement contains 100% of the recommended daily intake (RDA), our absorption of these substances can be dramatically less than this. Many individuals experience hypochlorhydria and insufficiency of other digestive secretions which are necessary to break down tablets due to fillers and other agents which enable processing and tabletization.4,5,6These necessary digestive secretions generally diminish with age, however factors such as chronic disease (particularly gastrointestinal conditions), alcohol and nicotine use also have an impact.7,8,9

The quality of supplement ingredients also is an issue when cheaper drug-store type supplements are sought.Numerous lower-cost nutritional supplements use ingredients sourced from Asia which may have contaminants or use toxic substances in their processing.10,11,12Many supplement ingredients manufactured in China have been found to contain higher amounts of lead, mercury and aluminium, as well as a wide variety of other undesirable substances.A recent Australian study from the University of Adelaide found that 92% of traditional Chinese medicinal combinations purchased over the counter at random contained undeclared substances or some form of contamination.13This included detection of pharmaceutical agents such as warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol; heavy metals including arsenic (up to 10 times the acceptable limit), lead, and cadmium; and DNA of undeclared plant or animal taxa in 50% of the samples.

The format of nutrients also is an issue. Low-cost supplements most often contain cyanocobalamin for vitamin B12 and folic acid because these ingredients are cheaper than the more bioavailable active form of these nutrients. For some individuals with genetic variants which impact B12 and folate metabolism, it is very important to have these nutrients in active forms (such as methylcobalamin and folinic acid) which the body needs.14,15

 

Dietary deficiencies abound

Despite our knowledge about nutrition, our diets have considerable deficiencies. The estimated average requirement (EAR) for nutrients is often not met in our diets even with the use of MVM supplements as a 2010 National Health and Nutrition Examination Survey (NHANES) showed.16Dietary inadequacies (despite supplemental MVM use in 51% of the population) were observed to exist for vitamin D (74% of population), vitamin E (67%), magnesium (46%), calcium (39%), vitamin A (35%), and vitamin C (31%). Smaller proportions of the population had intakes below the EAR for (in decreasing prevalence) zinc, folic acid, vitamin B6, iron, copper, thiamin, vitamin B12, vitamin B2, phosphorus, niacin, and selenium. Other studies support these findings, and have shown that deficiencies also are common in vitamins B12, B6, and folate, particularly with increasing age.17,18,19

This micronutrient gap is not always one which will outwardly manifest in disease as more severe shortages are usually necessary for symptoms of deficiency disease. However, this micronutrient gap does impact the ability of our body to function optimally, and subtle shifts in performance and metabolism do exist – they just won’t be something showing up on a standard lab test. We need these essential vitamins and minerals – which is why they have been deemed essential in the first place. But we need a format that our body can absorb and utilize, and they won’t just be flushed down the toilet.Making sure supplements are of a high quality is imperative for the many reasons discussed, even more so when supporting detoxification.

Advanced supplement delivery formats

Advanced liposomal and nanoemulsifieddelivery systems offer unmatched bioavailability for both fat- and water-soluble ingredients. Thetiny, nano-size particles are not broken down by the harsh acids of the digestive system as they enter circulation with rapid absorption immediately in the mouth. This enables direct delivery of bioavailable nutrients to the bloodstream and cells of the body. Phospholipids, specifically phosphatidylcholine, form the external sphere of the liposomal and nanoemulsified particles.These phospholipids are additionally utilized by the body, and are important for cellular membrane health and function.20Dietary deficiencies of choline, which phosphatidylcholine provides, also are common, and the inclusion of it in a supplement further enhances health at a cellular level for this reason.

 

Perhaps not surprisingly, individuals who use dietary supplements are already more health conscious, a choice which is reflected by their diet, tendency for a lower body mass index, and higher physical activity level.21We are a population that cares about our health, and are making proactive choices in many ways. Electing to use a higher quality multivitamin and other supplements also is a choice – but one from which you actually reap benefits rather than the low-cost minimally absorbed counterparts that are easily found on shelves of health food and drug stores.

 

 

 

 

 


1Biesalski HK, Tinz J. Multivitamin/mineral supplements: Rationale and safety - A systematic review. Nutrition. 2017 Jan;33:76-82.View Full Paper

2Huang HY, Caballero B, Chang S, et al. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med. 2006 Sep 5;145(5):372-85.View Abstract

3Kantor ED, Rehm CD, Du M, et al. Trends in Dietary Supplement Use Among US Adults From 1999-2012. JAMA. 2016 Oct 11;316(14):1464-1474.View Abstract

4Green R, Allen LH2, Bjørke-Monsen AL Vitamin B12 deficiency. Nat Rev Dis Primers. 2017 Jun 29;3:17040.View Abstract

5Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Drugs Aging. 1998 Apr;12(4):277-92.View Abstract.

6Rothenbacher D, et al. Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study. Scand J Gastroenterol. 2005 Jun;40(6):697-704.View Abstract

7Linnell JC. Effects of Smoking on Metabolism and Excretion of Vitamin B12 J. Br Med J. 1968 Apr 27;2(5599):215-6.View Full Paper

8Pott JW. Detection of vitamin B12 deficiency in alcohol abuse. Acta Ophthalmol. 2014 Feb;92(1):e76-7.View Full Paper

9Pan Y et al. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients. 2017 Apr 13;9(4).View Full Paper

10Genuis SJ, Schwalfenberg G, Siy AK, Rodushkin I. Toxic element contamination of natural health products and pharmaceutical preparations. PLoS One. 2012;7(11):e49676.View Full Paper

11Budnik LT, Baur X, Harth V, Hahn A. Alternative drugs go global: possible lead and/ or mercury intoxication from imported natural health products and a need for scientifically evaluated poisoning monitoring from environmental exposures. J Occup Med Toxicol. 2016 Nov 8;11:49.View Full Paper

12Cohen PA. American roulette--contaminated dietary supplements. N Engl J Med. 2009 Oct 15;361(16):1523-5.View Full Paper

13Coghlan ML, et al. Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM). Sci Rep. 2015 Dec 10;5:17475.

14Watkins D, Rosenblatt DS. Update and new concepts in vitamin responsive disorders of folate transport and metabolism. J Inherit Metab Dis. 2012 Jul;35(4):665-70.View Abstract

15Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017 Feb;16(1):42-49. Review.View Abstract

16Wallace TC, McBurney M, Fulgoni VL 3rd. Multivitamin/mineral supplement contribution to micronutrient intakes in the United States, 2007-2010. J Am Coll Nutr. 2014;33(2):94-102.View Abstract

17Tucker KL, Rich S, Rosenberg I et al. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22.View Abstract

18Kjeldby IK, Fosnes GS, Ligaarden SC, Farup PG. Vitamin B6 deficiency and diseases in elderly people--a study in nursing homes. BMC Geriatr. 2013 Feb 8;13:13.View Full Paper

19Clarke R, Grimley Evans J, Schneede J, et al. Vitamin B12 and folate deficiency in later life. Age Ageing. 2004 Jan;33(1):34-41.View Abstract

20Spector AA, Yorek MA. Membrane lipid composition and cellular function. J Lipid Res. 1985 Sep;26(9):1015-35.View Full Paper

21Rock CL. Multivitamin-multimineral supplements: who uses them? Am J Clin Nutr. 2007 Jan;85(1):277S-279S.View Full Paper

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Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule Called DIM

Wherever you are on your health crusade, you will want to know about a potent, health-promoting compound called diindolylmethane, commonly known as DIM. You are undoubtedly familiar with the vegetable family known as the cruciferous, and its many satisfying, crunchy, often green constituents – kale, collard greens, cabbage, broccoli, and brussels sprouts – to name a few. Cruciferous vegetables seem to be on every menu now – whether it is the taqueria down the street or the invitation-only new trending restaurant in your city. And with good reason! In addition to the flavors and textures they bring to a meal, crucifers have many health benefits.

 

Unique Health Benefits of Cruciferous

Dietary consumption of cruciferous vegetables has been observed to benefit health and overall longevity in many ways. Higher intakes of cruciferous have been associated with a reduction of inflammation, particularly in women,1,2 decreased risk of heart attack and cardiovascular disease-related mortality,3,4 as well as a lower risk of certain types of cancer.5,6,7 DIM is derived from the cruciferous and may be one of the primary contributors to these benefits. DIM is readily formed during the digestive process when indole-3-carbinol (I3C), a somewhat unstable compound directly derived from cruciferous, is exposed to stomach acid.8 It is also increased in crucifers by cooking, which activates an enzyme (myrosinase) responsible for its conversion.9

One of the mechanisms by which this vegetable family may have a positive impact on health is by supporting the body in detoxification.10 There are different estrogen metabolites in the body, some of which are more estrogenic and potentially harmful, while others are more protective.11 Increased intake of the cruciferous vegetables has been observed to shift estrogen metabolism, increasing the balance of the forms of estrogen which may be more protective and reduce risk of hormonal cancers such as breast cancer.5

What is Detoxification?

Unfortunately, the concept of detoxification has been oversimplified in many health-related circles, where fasting, juicing and yoga retreats are often emphasized. Although these approaches may have benefits, they don’t fully encompass the complexities of the larger process and the necessary steps by which detoxification occurs in the body. Thus, to enter in to a discussion of detoxification, some basic higher-level concepts of physiology and biochemistry are necessary to introduce.

Perhaps the most important molecule in detoxification is glutathione. Glutathione is the body’s main antioxidant and is necessary for cellular detoxification throughout your body.12 Glutathione is necessary to protect the cell’s delicate machinery and to transport toxins out of the cell. One of the steps of detoxification involves the binding of toxins to glutathione, creating larger, inactive, water soluble molecules. These water-soluble molecules can easily be transported out of the cell, into the bile, and out of the body via stool.13 Because glutathione is utilized in the process of removing mercury and many other toxins from the cell, it also can become depleted in settings of increased toxicity.14

Arguably as important as glutathione for the process of detoxification is a protein known as Nrf2 (short for nuclear factor E2-related factor). Nrf2 is a cellular switch that orchestrates antioxidant, de­toxification, and cellular defenses. When activated, Nrf2 can switch on over 200 genes that help the cell generate its own highly pro­tective molecules.15,16

Along with Nrf2 is its cellular helper and teammate, known as the antioxidant response element (ARE). Nrf2 is present in the cytosol of the cell, and responds to oxidative stress by translocating to the nucleus and binding to ARE, the promoter region of genes that encode the transcription of critical components of detoxification: antioxidant elements, detoxification enzymes, and proteins required for glutathione synthesis and recycling.17 This includes the phase II detoxification enzymes glutathione S-transferase (GST), glutathione reductase (GSR), and glutathione peroxidase (GPX).18,19,20 The Nrf2/ARE pathway serves a protective role in the body, and is activated by elevated levels of reactive oxygen species (ROS) as well as exposures to air pollution and heavy metals.21,22

Studies have also shown that the ability to upregulate Nrf2 and its antioxidant supporting action declines with age, which may be one reason the elderly are more susceptible to damage from environmental pollutants.23 Additionally, some of the toxic substances which we are exposed to such as ochratoxin A, one of the most common mold toxins found in foods and water-damaged houses, and indoxyl sulfate, a uremic toxin that is increased with exposure to some toxic heavy metals, act as Nrf2 inhibitors, further contributing to toxicity and impaired detoxification.24,25,26,27

Fortunately, there are natural substances that appear to induce Nrf2 and effectively switch on our detoxification pathways and antioxidant defenses. This includes DIM and other favorites such as lycopene (found in tomatoes) and epigallocatechin gallate, or EGCG (found in green tea).28,29 Increasing intake of these substances in the diet definitely can be helpful, but for many who struggle with things such as hormonal imbalance, mold exposure, and other environmental toxicities, dietary intake is usually not enough.

DIM and Hormones

Many integrative healthcare providers utilize DIM to support the body in the metabolism of hormones. The improved metabolism and elimination of the more dangerous forms of estrogen is proposed to be one of the reasons that DIM and cruciferous consumption may be protective against hormone-dependent cancers.30 DIM induces the expression of cytochrome P450 enzymes that are responsible for metabolizing estrogen.31 By inducing these enzymes, DIM helps modify estrogen balance, increasing levels of 2-hydroxy-estrone, a metabolite of estrogen which has been suggested to be protective against breast cancer.32

DIM and Nrf2

Because mold toxins (mycotoxins) can inhibit Nrf2 and our body’s detoxification pathways, we need a strong Nrf2 inducing agent to restore the protective glutathione system, and the associated enzymes necessary for it to do its job as well as recycle it. DIM has a strong Nrf2 activating effect which is not seen with DIM’s precursor I3C.33 By “turning on” the Nrf2 switch, DIM increases the body’s expression of many drug metabolizing enzymes, detoxification-dependent transporters (necessary to get toxins out of the cell), and other antioxidant enzymes.34

The benefits of Nrf2 activation go beyond recovering from mycotoxin exposure and hormone balance. For instance, our skin cells produce Nrf2 to protect themselves from many conditions which increase oxidative stress, such as UVB exposure.35 Improving Nrf2 activation in the skin may be a means to combat sun-related damage,36 as well as immune-mediated conditions of the skin such as dermatitis and vitiligo.37,38

With oral intake, the highest amounts of DIM are found in the liver, followed by the lungs and kidneys.39 The liver and kidneys are the organs in the body most burdened by detoxification, however with exposure to air pollutants, the protective effect of Nrf2 induction by DIM is also important in our lungs.40 Because the body is less effective at inducing Nrf2 with age, substances that promote Nrf2 are not only important to support the body in detoxification, but also may be a means by which to combat the effects that aging has on our body.41

A Bioavailability Problem and Solution

Although DIM may offer a variety of health benefits, when taken in traditional oral formulations such as tablets and capsules it has poor absorption and relatively rapid clearance.42 Lipid-based formulations such as liposomes and nanoemulsions have been shown to dramatically improve bioavailability of DIM as well as a variety of substances.43,44 Absorption of nanoemulsified DIM begins immediately in the oral cavity, as the tiny, nano-sized particles enter circulation, evading breakdown by digestive secretions. Studies have also show that nanoemulsified delivery formats also prolong the time a therapeutic agent is in circulation, leading to reduced need for dosing.45

 


1 Navarro SL, Schwarz Y, Song X, et al. Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial in healthy young adults. J Nutr. 2014 Nov;144(11):1850-7. View Full Paper

2 Jiang Y, Wu SH, Shu XO, et al. Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women. J Acad Nutr Diet. 2014 May;114(5):700-8.e2. View Full Paper

3 Lockheart MS, Steffen LM, Rebnord HM, et al. Dietary patterns, food groups and myocardial infarction: a case-control study. Br J Nutr. 2007 Aug;98(2):380-7. View Abstract

4 Zhang X, Shu XO, Xiang YB, et al. Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. Am J Clin Nutr. 2011 Jul;94(1):240-6. View Full Paper

5 Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36. View Full Paper

6 Tse G, Eslick GD. Cruciferous vegetables and risk of colorectal neoplasms: a systematic review and meta-analysis. Nutr Cancer. 2014;66(1):128-39. View Abstract

7 Lam TK, Gallicchio L, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):184-95. View Full Paper

8 Bradlow HL, Zeligs MA. Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (I3C) during cell culture experiments. In Vivo. 2010 Jul-Aug;24(4):387-91. View Full Paper

9 Ciska E, Verkerk R, Honke J. Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. J Agric Food Chem. 2009 Mar 25;57(6):2334-8. View Abstract

10 Nho CW, Jeffery E. The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables. Toxicol Appl Pharmacol. 2001 Jul 15;174(2):146-52. View Abstract

11 Telang NT, Suto A, Wong GY, et al. Induction by estrogen metabolite 16 alpha-hydroxyestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst. 1992 Apr 15;84(8):634-8. View Abstract

12 Devasagayam TP, et al. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2004 Oct;52:794-804. View Abstract

13 Zamek-Gliszczynski MJ, et al. Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and GSH metabolites. Eur J Pharm Sci. 2006 Apr;27(5):447-86. View Abstract

14 Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. View Full Paper

15 Bruni F, Polosa PL, Galadeta MN. Nuclear Respiratory Factor 2 Induces the Expression of Many but Not All Human Proteins Acting in Mitochondrial DNA Transcription and Replication J Biol Chem. 2010 February 5; 285(6): 3939–3948. View Full Paper

16 Petri S, Körner S, Kiaei M. Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS. Neurol Res Int. 2012;2012:878030. View Full Paper

17 Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009 May 15;284(20):13291-5. View Full Paper

18 Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22. View Abstract

19 Harvey CJ, Thimmulappa RK, Singh A, et al. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009 Feb 15;46(4):443-53. View Full Paper

20 Singh A, Rangasamy T, Thimmulappa RK, et al. Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2. Am J Respir Cell Mol Biol. 2006 Dec;35(6):639-50. View Full Paper

21 Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. View Abstract

22 Simmons SO, Fan CY, Yeoman K, et al. NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent. Curr Chem Genomics. 2011;5:1-12. View Full Paper

23 Zhang H, et al. Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med. 2012 May 1;52(9):2038-46. View Abstract

24 Limonciel A, Jennings P. A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity. Toxins (Basel). 2014 Jan 20;6(1):371-9. View Full Paper

25 Hung SC, et al. Indoxyl Sulfate: A Novel Cardiovascular Risk Factor in Chronic Kidney Disease. J Am Heart Assoc. 2017 Feb 7;6(2). View Full Paper

26 Lan Z, Bi KS, Chen XH. Ligustrazine attenuates elevated levels of indoxyl sulfate, kidney injury molecule-1 and clusterin in rats exposed to cadmium. Food Chem Toxicol. 2014 Jan;63:62-8. View Abstract

27 Bolati D, et al. Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-κB. BMC Nephrol. 2013 Mar 4;14:56. View Full Paper

28 Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signalling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008 Oct;74(13):1526-39. View Full Paper

29 Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. View Full Paper

30 Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016 Jul;74(7):432-43. View Full Paper

31 Szaefer H, Licznerska B, Krajka-Kuźniak V, et al. Modulation of CYP1A1, CYP1A2 and CYP1B1 expression by cabbage juices and indoles in human breast cell lines. Nutr Cancer. 2012 Aug;64(6):879-88. View Abstract

32 Dalessandri KM, et al. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7. View Abstract

33 Ernst IM, Schuemann C, Wagner AE, Rimbach G. 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. Free Radic Res. 2011 Aug;45(8):941-9. View Abstract

34 Saw CL, Cintrón M, Wu TY, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. 2011 Jul;32(5):289-300. View Full Paper

35 Gęgotek A, Skrzydlewska E. The role of transcription factor Nrf2 in skin cells metabolism. Arch Dermatol Res. 2015 Jul;307(5):385-96. View Full Paper

36 Kokot A, Metze D, Mouchet N, et al. Alpha-melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology. 2009 Jul;150(7):3197-206. View Full Paper

37 Tsuji G, Takahara M, Uchi H, et al. Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect. J Invest Dermatol. 2012 Jan;132(1):59-68. View Abstract

38 Guan CP, Zhou MN, Xu AE, et al. The susceptibility to vitiligo is associated with NF-E2-related factor2 (Nrf2) gene polymorphisms: a study on Chinese Han population. Exp Dermatol. 2008 Dec;17(12):1059-62. View Abstract

39 Anderton MJ, Manson MM, Verschoyle R, et al. Physiological modeling of formulated and crystalline 3,3'-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos. 2004 Jun;32(6):632-8. View Full Paper

40 Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. View Abstract

41 Zhang H, Davies KJA, Forman HJ. Oxidative stress response and Nrf2 signaling in aging. Free Radic Biol Med. 2015 Nov;88(Pt B):314-336. View Full Paper

42 Wu TY, Huang Y, Zhang C, et al. Pharmacokinetics and pharmacodynamics of 3,3'-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes. J Pharmacokinet Pharmacodyn. 2015 Aug;42(4):401-8. View Abstract

43 Paltsev M, Kiselev V, Muyzhnek E, et al. Comparative preclinical pharmacokinetics study of 3,3'-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon? EPMA J. 2013 Dec 10;4(1):25. View Full Paper

44 Yang Z, Lu A, Wong BC, et al. Effect of liposomes on the absorption of water-soluble active pharmaceutical ingredients via oral administration. Curr Pharm Des. 2013;19(37):6647-54. View Abstract

45 Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015 Apr;5(2):123-127. View Full Paper

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Stress Support 103: Seawater Minerals Support Parasympathetic Response and Cellular Balance

In this 3-part blog series (Stress Support 101, 102, and 103), the Quicksilver Staff addresses a multipronged approach to supporting the body under stress. Learn more by reading each essential tidbit!

Replenish Your Cells

Even with a good night’s sleep, and with low levels of inflammation, stress will still rear its ugly head, and our nutrients will be depleted. This is why in order to handle stress, we must also replenish and restore our nutrient status.

Though we live on land, we hearken back to the sea. In fact, scientists believe life may have emerged billions of years ago from the ocean’s deep-sea vents, where porous and mineral-rich rock, water and sulfur-rich steam all blended in the perfect recipe for the first living organisms.1 The saline sea is rich in a blend of minerals that support innumerable forms of life, including those which are crucially important for our health and vitality as well.

The French biologist Rene Quinton, who was born in 1866, realized that sea water bears a striking resemblance to the extracellular fluid bathing every cell in our body. He believed that the cellular environment mimics the marine environment in which life first originated. Quinton is remembered today for treating malnourished children with isotonic sea water, administered intravenously, and bringing them back to a healthy, thriving state.2

Seawater contains over 80 bioavailable ionic minerals. Quinton Isotonic™ water has the same concentration of dissolved particles as do our own cells. By supplying the cells with the same isotonic, mineral-rich bath that first nourished long-ago life, these seawater minerals offer cells a gentle, subtle and profound nourishment. Taking isotonic seawater minerals at night supports the body and brain as they detoxify, repair and replenish. These minerals offer natural rehydration, supply necessary iono-minerals to the extracellular fluid bathing the body’s cells, and support normal cellular osmosis and flow of nutrients. Isotonic seawater minerals also support the parasympathetic balance as GABA does, but in a uniquely different mechanism via which all cells are affected and rebalanced, not just those in the brain.3

            The pure Quinton seawater minerals are harvested from protected plankton blooms by Laboratories Quinton, in an area where there is continual upwelling of nutrients and rare minerals from the bottom of the ocean. Harvesting follows strict protocols established by Rene Quinton, including cold filtering the water through 0.22 micrometer dual filters to leave only organic complexes and rare essential minerals. These protocols ensure that the product is of the highest quality and purity. The Quinton Isotonic™ seawater minerals are diluted to an isotonic concentration to conform to the human extracellular matrix (bio-terrain), making it excellent for long-term use and is easily absorbed into the body when taken orally. Collectively, the Quinton Isotonic™ seawater minerals, cannabidiols, and GABA with L-theanine support balance in our body under stress, which can further be enhanced with the support of adaptogenic botanicals and nutrient support. 

 



1 Sojo V, Herschy B, Whicher A et al. The Origin of Life in Alkaline Hydrothermal Vents. Astrobiology. 2016 Feb;16(2):181-97 View Abstract

2 Lane, N. & Martin, WF The origin of membrane bioenergetics. Cell 151, 1406–1416 (2012) View Abstract

3 Alberola J, Coll F. Marine Therapy and Its Healing Properties. Curr Aging Science 2013 Feb;6(1):63-75. Review. View Abstract

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Stress Support 102: Cannabinoids and the Inflammatory Aspect of Stress

Stress Support 102: Cannabinoids and the Inflammatory Aspect of Stress

In this 3-part blog series (Stress Support 101, 102, and 103), the Quicksilver Staff addresses a multipronged approach to supporting the body under stress. Stay tuned for each essential tidbit!

Reduce Inflammation & Restore Resilience

Constant psychological, emotional or physical stress raises the level of cortisol, creating inflammation. In fact, chronic psychological stress is correlated with the body losing its ability to regulate the inflammatory response, according to scientist Sheldon Cohen of Carnegie Mellon University, who was the first to prove that people under lots of stress are more susceptible to the common cold.1 Cohen and his team also found that prolonged stress decreases tissue sensitivity to cortisol, which becomes chronically elevated, much like the body develops a resistance to chronically elevated glucose in type-2 diabetes. When immune cells become insensitive to cortisol's regulatory effect, runaway inflammation is thought to promote the development of numerous chronic diseases.2

Thus, in order to reduce the potentially harmful impact of stress, we need to reduce inflammation. One substance that has a gentle and potent impact on inflammation is cannabidiol, or CBD oil. CBD oil is non-psychoactive and is extracted from hemp—part of the cannabis family. Cannabis contains an array of 400 unique chemicals, with approximately 70 non-psychogenic but potent bioactive cannabinoids that are currently known.3,4 We actually synthesize our own cannabinoids and have a built in endocannabinoid system, discovered in 1992, which is critical for bioregulation and homeostasis in the body.5 For that reason, it shouldn’t be surprising that the bioactive gifts in cannabis also are balancing agents.

Cannabinoids have been shown to help regulate inflammation, appetite, sleep, mood, pain, insulin sensitivity, fat and energy metabolism, and even affect neurologic and immune conditions.6 The cellular receptors to which cannabinoids bind are found in many types of cells throughout the body, and are expressed at high levels in the nervous and immune systems.7 Cannabinoids influence the activity of over a thousand different genes. They may help upregulate our cellular antioxidant defenses and at the same time, may help downregulate many pro-inflammatory mediators.8

CBD oil is a potent anti-inflammatory and antioxidant, and increases levels of the neurotransmitter serotonin as well as that of one of the endocannabinoids we secrete in our body, anandamide.9,10 Anandamide has its origins in the Sanskrit word ananda, meaning joy or bliss, and has been shown to play a role in the experience of pain and anxiety.11 CBD oil stimulates the growth of new neurons in the brain, and by doing such may support the reduction of depression.12 Cannabinoids also modulate the activity of receptors which are associated with symptoms of anxiety.13 Cannabinoids stabilize the NDMA receptor, which is sensitive to glutamate, a powerful excitatory, stimulating neurotransmitter that at excessive amounts can contribute to neurodegenerative conditions such as Alzheimer’s dementia and multiple sclerosis.14 Cannabinoids seem to function as an overall tonic for the brain, protecting against chronic stress, which can decrease the growth and density of new neurons in parts of the brain. They also influence mechanisms that govern the life and death of neurons, suggesting they may be helpful for neurodegenerative conditions.15,16

Overall, CBD oil calms the body and brain, helping quiet inflammation and serving as a powerful foundation which other natural tools such as GABA and L-theanine also enhance (see Stress Support 101: GABA and L-Theanine: The Fast Acting Stress and Anxiety Antidote for further reading).


 

1 Cohen S, Tyrrell DA, Smith AP Psychological stress and susceptibility to the common cold: N Engl J Med. 1991 Aug 29;325(9):606-12. View Abstract

2 Cohen S, Janicki-Deverts D, Doyle WJ et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk.Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):5995-9. View Abstract

3 Elsohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 2005;78:539– 548 View Abstract

4 Mechoulam R, Peters M, Murillo-Rodriguez E, et al. Cannabidiol—recent advances. Chem Biodivers 2007;4:1678–1692 View Abstract

5 Griffing GT. Endocannabinoids. Feb 2015. [cited July 21, 2017] Available at: http://emedicine.medscape.com/article/1361971-overview

6 Witkamp R, Meijerink J. The endocannabinoid system: an emerging key player in inflammation. Curr Opin Clin Nutr Metab Care. 2014 Mar;17(2) View Abstract

7 Pertwee RG, Howlett AC, Abood ME et al. Cannabinoid receptors and their ligands: beyond CB and CB.Pharmacol Rev. 2010 Dec;62(4):588-631 View Full Paper

8 Juknat A, Pietr M, Kozela E. et al. Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells. Br J Pharmacol. 2012 Apr;165(8):2512-28. View Full Paper

9 Grotenhermen F, Müller-Vahl K. The Therapeutic Potential of Cannabis and Cannabinoids Dtsch Arztebl Int. 2012 Jul; 109(29-30): 495–501 View Abstract

10 Leweke FM, Piomelli D, Pahlisch F et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry (2012) 2. View Full Paper

11 McPartland JM, Guy GW, Di Marzo V Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

PLoS One. 2014 Mar 12;9(3):e89566. View Full Paper

12 Guimarães FS, Fogaça MV, Silveria F et al. Cannabinoids, Neurogenesis and Antidepressant Drugs: Is there a Link? Curr Neuropharmacol. 2013 May; 11(3): 263–275. View Full Paper

13 Rey AA, Purrio M, Viveros MP, et al. Biphasic Effects of Cannabinoids in Anxiety Responses: CB1 and GABAB Receptors in the Balance of GABAergic and Glutamatergic Neurotransmission. Neuropsychopharmacology. 2012 Nov; 37(12): 2624–2634 View Abstract

14 Hallak JE, Dursun SM, Bosi DC et al. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jan 15;35(1):198-202. View Abstract

15 More, SV, Choi DK. Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection. Mol Neurodegener. 2015. 10: 17. View Abstract

16 Campbell VA, Gowran A. Alzheimer's disease; taking the edge off with cannabinoids? Br J Pharmacol. 2007 Nov; 152(5): 655–66 View Abstract

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Stress Support 101: GABA and L-Theanine: The Fast Acting Stress and Anxiety Antidote

In this 3-part blog series (Stress Support 101, 102, and 103), the Quicksilver Staff addresses a multipronged approach to supporting the body under stress. Stay tuned for each essential tidbit!

These days, we often view stress as a badge of honor—proof that our hectic lives are packed to the brim with work, play, friends, family, exercise, shopping, cooking, and limitless other tasks from laundry to surfing social media and tuning in to 24-hour weather and news.

We’re drinking every last drop of life. We’re making our mark. We’re also sleep deprived and chronically tense. Since 2007, the American Psychological Association has conducted an annual nationwide survey to assess how stressed Americans are. Between August 2016 and January 2017, the overall average reported stress level of Americans rose from 4.8 to 5.1, on a scale where 1 means little or no stress and 10 means a great deal of stress, according to the APA survey.1

We tend to forget that chronic stress isn’t just an irritant, but can pave the way for ill health by altering the responses of the sympathetic nervous system and the adrenal axis, increasing the flow of stress hormones, and upregulating inflammation and free radical damage.2 Yet it’s hard to jump off the merry-go-round of stressors that confront us at every turn.

If we understand the biology of stress—just how it acts on the body—then we can make choices that help us to relax and restore ourselves, including the support of natural aids that gently soothe and replenish our cells, tissues and organs.

The hypothalamic-pituitary-adrenal (HPA) axis is the primary axis of endocrine organs in the body that adapts in response to stress. This system impacts the function of many other biological systems and processes through the hormone cortisol. Chronic stress is linked to chronically elevated levels of salivary cortisol in both children and adults.3 These high levels are associated with reduced immune response, affecting healing and thus prolonging recovery time; delayed growth in children; and increased blood pressure and heart rate in both children and adults.

Sleep difficulties are common with anxiety disorders and are often associated with mental activity or worrying. They lead to a lower cortisol awakening response (CAR) which is a burst of cortisol secretion that occurs about 20-30 minutes after awakening in the morning, and prepares the body for greeting the demands of the day.4

Sleep is a necessity for creatures ranging from fruit flies to humans. It is actually a cleansing process, wherein your brain flushes itself clean, sending waste and toxins out of the cells and bringing in fresh nutrients, which then diffuse back into cells, refreshing and replenishing them.5 While you sleep, your brain detoxifies itself up to ten times faster than when you are awake.6 No wonder good sleep is the foundation of health, while poor sleep raises our risk of stroke, heart attack and even weight gain and weak bones.7

  

Rest & Relax with GABA and L-Theanine

To restore deep and restful sleep, you might turn to a calming amino acid like gamma-amino butyric acid (GABA), which is known as the premier “calm and connect” molecule. Our brain naturally produces it, and it is capable of inhibiting or slowing down nerve impulses, and balancing out our response to stress. Lower GABA concentrations in individuals suffering from post-traumatic stress disorder (PTSD) have been linked to poor sleep quality.8 GABA supplementation has been found to significantly increase calming alpha-wave patterns during stress, and to reduce anxiety levels in humans.9,10 GABA may fine tune our entire neuroendocrine response.11

GABA is found in teas such as pu-erh and foods such as kimchi (where it is a fermentation byproduct).12 For the pure amino acid, liposomal delivery systems have been shown to facilitate transport across the blood brain barrier (BBB) and increase availability of therapeutic agents in the central nervous system.13 It has also been proposed that supplemental GABA may activate receptors in the enteric nervous system (that of the gut), which may be modulated by and signal to the vagus nerve.14 The vagus nerve is the longest cranial nerve in the body. It contains motor and sensory fibers and, because it passes through the neck and thorax to the abdomen, has the widest distribution in the body.

Another calming amino acid, one that enhances GABA’s effect, is L-theanine. It is found naturally in tea.15 After supplementing with L-theanine, brain wave patterns smooth out, much like they do with meditation.16 L-theanine calms without impairing cognitive ability, reduces stress and levels of cortisol (the stress hormone) in saliva, and also lowers blood pressure.17,18 L-theanine has been observed to promote relaxation and reduce stress, possibly by increasing alpha wave activity and by blocking the binding of L-glutamic acid to excitatory glutamate receptors in the central nervous system.19,20

Continuous administration of L-theanine has been shown to increase expression of brain-derived neurotrophic factor (BDNF)21, a protein that increases neural plasticity and promotes neurogenesis, including that of dopaminergic and serotonergic neurons.22 Increased BDNF levels are thought to be a mechanism by which some anti-depressants, supplements, and exercise have a positive impact on anxiety and depression.23,24,25

Supplementation with L-theanine has been shown to have a relaxing effect, reducing heart rate and salivary immunoglobulin A (sIgA) secretion in settings of acute stress.26,27 It also has been shown to reduce anxiety and attenuate blood pressure during a challenging mental task28 and reduce salivary α-amylase activity and subjective experience of stress during mental challenges.29 L-theanine has been shown to improve aspects of sleep quality in boys with attention-deficit/hyperactivity disorder30, and reverse caffeine-induced decreases in slow-wave sleep in animals.31

GABA in combination with L-theanine truly is a ‘busyness’ antidote and produces a very quick and powerful effect. GABA and L-theanine help balance our nervous system, enabling a good night’s deep sleep, and thus supporting optimal health. On their own, oral GABA supplements like capsules or tablets do not easily cross the blood-brain barrier. 32 Hence, a liposomal delivery system for this nutrient combination is key, as it has demonstrated abilities to deliver nutrients through this barrier and into the brain where they are needed.

 


1 Bethune S, Lewin E. Many Americans Stressed about Future of Our Nation, New APA Stress in America™ Survey Reveals. Feb 2017. [cited July 21, 2017] Available at: http://www.apa.org/news/press/releases/2017/02/stressed-nation.aspx

2 Understanding the Stress Response. Updated Feb 2016. [cited July 21, 2017] Available at: http://www.health.harvard.edu/staying-healthy/understanding-the-stress-response

3 Aguilar Cordero MJ, Sánchez López AM, et al. Salivary cortisol as an indicator of physiological stress in children and adults; a systematic review. Nutr Hosp. 2014 May 1;29(5):960-8. View Abstract

4 Hek K, Direk N, Newson RS, et al. Anxiety disorders and salivary cortisol levels in older adults: a population-based study. Psychoneuroendocrinology. 2013;38(2):300–305

5 Iliff JJ, Wang M, Liao Y et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012 Aug 15;4(147):147ra111. View Abstract

6 Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013 Oct 18;342(6156):373-7. View Full Paper

7 He Q, Zhang P, Li G et al. The association between insomnia symptoms and risk of cardio-cerebral vascular events: A meta-analysis of prospective cohort studies. Eur J Prev Cardiol. 2017 Jan 1:2047487317702043. View Full Paper

8 Meyerhoff DJ, Mon A, Metzler T, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep. 2014;37(5):893–900. View Abstract

9 Yoto A, Murao S, Motoki M, et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43(3):1331–1337. View Abstract

10 Abdou AM, Higashiguchi S, Horie K, et al. Relaxation and immunity enhancement effects of gammaaminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201–208. View Abstract

11 Inoue W, Bains JS. Beyond inhibition: GABA synapses tune the neuroendocrine stress axis.Bioessays. 2014 Jun;36(6):561-9 View Abstract

12 Dhakal R, Bajpai VK, Baek KH. Production of gaba (γ – Aminobutyric acid) by microorganisms: a review. Braz J Microbiol. 2012;43(4):1230–1241. View Full Paper

13 Alyautdin R, Khalin I, Nafeeza MI, et al. Nanoscale drug delivery systems and the blood-brain barrier. Int J Nanomedicine. 2014;9:795–811 View Full Paper

14 Boonstra E, de Kleijn R, Colzato LS, et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520. View Full Paper

15 Nobre AC, Rao A, Owen GN. L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167–168. View Abstract

16 Kakuda T, Nozawa A, Unno T, et al Inhibiting effects of Theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93. View Abstract

17 Rogers, PJ, Smith, JE, Heatherley, SV, et al. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and Theanine administered alone and together. Psychopharmacology (Berl) 2008;195(4):569-577. View Abstract

18 White DJ, de Klerk S, Woods W et al. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients. 2016 Jan 19;8(1) View Abstract

19 Kakuda T, Nozawa A, Sugimoto A, et al. Inhibition by Theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002;66(12):2683–2686.

20 Nathan PJ, Lu K, Gray M, et al. The neuropharmacology of L-Theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21–30. View Abstract

21 Wakabayashi C, Numakawa T, Ninomiya M, et al. Behavioral and molecular evidence for psychotropic effects in L-Theanine. Psychopharmacology (Berl). 2012;219(4):1099–1109. View Abstract

22 Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123–131. View Abstract

23 Björkholm C, Monteggia LM. BDNF – a key transducer of antidepressant effects. Neuropharmacology. 2016;102:72–79. View Full Paper

24 Hurley LL, Akin F, Fresoye L, et al. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav Brain Res. 2013;239:27–30. View Abstract

25 Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295–301. View Abstract

26 Lu K, Gray MA, Oliver C, et al. The acute effects of L-Theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol. 2004;19(7):457–465 View Abstract

27 Kimura K, Ozeki M, Juneja LR, et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39–45. View Abstract

28 Yoto A, Motoki M, Murao S, et al. Effects of L-Theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31:28. View Abstract

29 Unno K, Tanida N, Ishii N, et al. Anti-stress effect of Theanine on students during pharmacy practice: Positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. 2013;111:128–135 View Abstract

30 Lyon MR, Kapoor MP, Juneja LR. The effects of L-Theanine (SunTheanine®) on objective sleep quality in boys with attention defcit hyperactivity disorder (ADHD): a randomized, double-blind, placebo controlled clinical trial. Altern Med Rev. 2011;16(4):348–354. View Full Paper

31 Jang HS, Jung JY, Jang IS, et al. L-Theanine partially counteracts caffeine-induced sleep disturbances in rats. Pharmacol Biochem Behav. 2012;101(2):217–221. View Abstract

32 Kakee A, Takanaga H, Terasaki T, et al. Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier. J Neurochem. 2001;79(1):110-8.

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Sperm Counts Are Plummeting, and Researchers Think They Know Why

              A new study suggests that sperm counts are falling rapidly in developed countries such as North America, Europe, Australia, and New Zealand, and that the steep decline shows no signs of slowing.1 The new research—a meta-analysis that crunched data from over 180 different studies on sperm counts in men from 1973 to 2011—points to a worrying decline in male fertility that may be a warning for all of us.

“Declines in sperm count have implications beyond fertility and reproduction,” the researchers conclude. “Recent studies have shown that poor sperm count is associated with overall morbidity and mortality.”2 This new data, they say, “might be considered as a ‘canary in the coal mine’ for male health across the lifespan” and may be due to influences such as endocrine disruption from chemical exposures. In fact, the study’s lead researcher, epidemiologist Hagai Levine of the Hebrew University of Jerusalem, told BBC News that: “If we will not change the ways that we are living and the environment and the chemicals that we are exposed to…eventually…it may..[lead to] the extinction of the human species.”3

             Though that may sound a bit alarmist, there’s no doubt we are exposed to an unprecedented onslaught of chemicals in modern life--more than 80,000 chemicals have been registered for use in the United States, and an estimated 2,000 new ones are introduced annually. These include chemicals in foods and food wrapping, personal care products, prescription drugs, household cleaners, furniture, bedding, clothing, lawn care products and more. Many of these chemicals haven’t been tested for safety by our government.4

An alarming number of these new chemicals can function as endocrine disrupters—disrupting the body’s hormonal balance and harming the developmental, reproductive, neurological, and immune systems in humans and wildlife.5

            Neurobiologist Frederick Vom Saal, of the University of Missouri-Columbia, has been studying the harmful effects of endocrine disrupters since the 1970s. He has discovered that the familiar standards of toxicology don’t necessarily apply to endocrine disrupters. In fact, as Vom Saal told one of the world’s premier scientific journals, Nature: “Low doses of endocrine disrupters act in ways that are totally unpredicted by the traditional approaches of toxicology.” First of all, endocrine disrupters may exert their effects at astonishingly low exposure levels. Secondly, as Vom Saal explains, whereas classical toxicology looks at a kind of ascending “ski slope” graph of dose and response, endocrine disrupters often form “U” shaped graphs, where low doses are as powerful as high doses. And sometimes, their graphs undulate like successive waves.6

           Secondly, says Vom Saal, our entire biology is responsive to “phenomenally small amounts of hormones in terms of our behavior, our core physiology, our neuroendocrine system, and our ability to metabolize drugs.”7 We are exquisitely sensitive to estrogens, and today our environment is full of chemicals that can stimulate our estrogen receptors. Vom Saal studied extraordinarily low doses of the notorious bisphenol A-- an industrial chemical that has been used to make certain plastics and resins since the 1960s. The doses he studied were 2,500 times lower than other doses previously studied--between 2 and 20 micrograms per kilogram of body weight. He found these low doses still scrambled the male reproductive system in mice.8 That’s concerning, because in 2004 the U.S. Centers for Disease Control (CDC) found traces of BPA in nearly all of the urine samples it collected.9 Similarly, a 2010 Canadian study found BPA in the urine of 91% of the population.10

           BPA and its new relative, BPS, along with other endocrine disrupters such as phthalates used to soften plastics, perfluorooctanoic acid (PFOA) used in Teflon and brominated flame retardants, leach into food and water from containers and cookware, or soak through our skin from store receipts and furniture or enter our lungs in household dust.11,12,13 Correlations exist between the concentrations of perfluorinated carbons in household dust and the percentage of carpeting in the house.14 And most Americans spend more than 90 percent of their time indoors—at home, school, work, and in cars, exposed to dust full of shed chemicals.15

These chemicals are not only widespread in the environment, they persist, and are not easily removed or decomposed, leading to the common references of persistent organic pollutants (POPs). PFOA, for instance, does not easily break down in the environment; the human half-life is estimated at about 3 years.16 PFOA has specifically been found to harm the testicles in animal studies.17

Heavy metals can also be endocrine disruptors. Twenty different metals in the environment, including lead, cadmium, mercury, and arsenic are thought to affect male reproductive health.18,19,20 Arsenic, which is found in everything from chickens to rice to drinking water,21 is a well-known endocrine disruptor.22 One animal study tested the effects on male rabbits of exposure to drinking water containing arsenic, chromium, lead, benzene, chloroform, phenol and trichloroethylene. Everything from mating desire and ability to sperm quality and testosterone secretion were affected.23

Lead is a reproductive toxicant, and exposure to inorganic lead is detrimental to human semen quality.24 Male lead concentration significantly reduces the odds of conception in couples.25 Lead moves throughout ecosystems, with atmospheric lead being deposited in vegetation, and in the ground and water.26 According to the CDC, lead exposure can affect nearly every system in the body, and yet it often occurs with no obvious symptoms and goes unrecognized.27 Lead present in household dust can come from old paint or surrounding soil.28 Mercury, too, is a widespread contaminant in the environment. Atmospheric deposition is the primary source of mercury globally, and once in the atmosphere, mercury can circulate for years.29 Seafood and dental amalgams are other primary sources of mercury that many are exposed to.

           In general, levels of contaminants and potential toxins allowed in the USA are higher than in Europe, Australia and Canada. Fracking is increasingly common in the USA, and chemicals found in water near fracked gas sites may affect reproductive health. More than 15 million Americans live within one mile of hydraulic fracturing sites, and a review of over a hundred studies concluded these activities have potential for environmental release of a complex mixture of endocrine disrupting chemicals.30

Many of the endocrine disruptors that affect male fertility are actual estrogen mimics. There is a saying in estrogen biology, according to Dr. Vom Saal, which is this: “The estrogen receptor never met a phenol that it did not like.”7 Phenols are aromatic organic compounds that are joined in chains to synthesize polycarbonates, nylon, detergents, herbicides and numerous pharmaceutical medicines. The estrogen receptor has an affinity for a component of phenols. According to University of Missouri cell biologist and endocrinologist Wade Welshons, “99.9 percent of what turn out to be chemical estrogens have a phenolic hydroxyl group on the molecule, and any of those can bind to the estrogen receptor.”31 Welshons adds that: “Almost everything that binds to the estrogen receptor turns it on in some way.”

With all this potential for toxic exposure around us, what are we to do? One of the things we are beginning to recognize, at least where conception is concerned, is that having a healthy lifestyle, minimizing toxin exposures, and supporting the body to detoxify from these exposures is necessary far prior to the actual fusing of a sperm and an egg. Many people may not realize that it takes sperm about 2-3 months to develop and mature – if the toxicities are not removed or minimized prior to this, each of these sperm will be nesting and developing in a toxic bath with high levels of oxidative stress leading to DNA damage and impaired spermatogenesis.32 Although antioxidants are one means to improve male fertility,33,34 they are not adequate to overcome the potential damage that chemicals and heavy metals can wreak on the whole body including the reproductive system, and a comprehensive detoxification system is necessary.

 


1 Levine H, Jørgensen N, Martin0-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update, 2017 July; 1-14. View Full Paper

2 Jensen TK, Jacobsen R, Christensen K, et al. Good semen quality and life expectancy: a cohort study of 43,277 men. Am J Epidemiol 2009;170: 559–565. See Abstract

3 Ghosh P, Spermcount drop ‘could make humans extinct’. BBC News Health. July 25 2017 [cited July 29, 2017] Available at: http://www.bbc.com/news/health-40719743

4 National Toxicology Program, US Department of Health & Human Services. February 1 2017 [cited July 29, 2017] Available at: https://ntp.niehs.nih.gov/about/index.html

5 National Institute of Environmental Health Sciences, Endocrine Disruptors. [Cited July 29, 2017] Available at: https://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm

6 Fagin, D. Toxicology: the learning curve. Nature (2012) Oct 25;490(7421):462-5 See Full Paper

7 Personal communication, November 2, 2007.

8 Angle BM, Do RP, Ponzi D et al. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod Toxicol. 2013 Dec;42:256-68 View Full Paper

9 Centers for Disease Control and Information. Fact Sheet. Dec 23 2016 [cited July 29 2017] Available at: https://www.cdc.gov/biomonitoring/bisphenola_factsheet.html

10 Bushnik T, Haines D, Lavallois P et al. Lead and bisphenol A concentrations in the Canadian population. Health Rep 2010 Sep;21(3): 7-18 View Full Paper

11 Begley TH, et al. Perfluorochemicals: potential sources of and migration from food packaging. Food Addit Contam. 2005 Oct;22(10):1023-31 View Abstract

12 Franko J, et al. Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin. J Toxicol Environ Health A. 2012;75(1):50-62. View Abstract

13 D'Hollander W, et al. Perfluorinated substances in human food and other sources of human exposure. Rev Environ Contam Toxicol. 2010;208:179-215 View Abstract

14 Kubwabo C, et al. Occurrence of perfluorosulfonates and other perfluorochemicals in dust from selected homes in the city of Ottawa, Canada. J Environ Monit. 2005 Nov;7(11):1074-8. View Abstract

15 Klepeis NE1, Nelson WC, Ott WR et al. The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants. J Expo Anal Environ Epidemiol. 2001 May-Jun;11(3):231-52. View Abstract

16 Zhang T, et al. Perfluorinated compounds in human blood, water, edible freshwater fish, and seafood in China: daily intake and regional differences in human exposures. J Agric Food Chem. 2011 Oct 26;59(20):11168-76 View Abstract

17 Liu W, et al. Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice. Biol Reprod. 2015 Aug;93(2):41 View Abstract

18 Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions x Drug Chem Toxicol. 2013 Jul;36(3):353-68 View Abstract

19 Alcser KH, Brix KA, Fine LJ et al. Occupational mercury exposure and male reproductive health.Am J Ind Med. 1989;15(5):517-29. View Abstract

20 Hanf V, Forstmann A, Costea JE et al. Mercury in urine and ejaculate in husbands of barren couples.

Toxicol Lett. 1996 Nov;88(1-3):227-31. View Abstract

21 Chung JY, Yu SD, Hong YS. Environmental Source of Arsenic Exposure J Prev Med Public Health. 2014 Sep; 47(5): 253–257. View Full Paper

22 Davey JC, Nomikos AP, Wungjiranirun M et al. Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor-and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metamorphosis. Environ Health Perspect. 2008 Feb;116(2):165-72. View Abstract

23 Veeramachaneni DN, Palmer JS, Amann RP. Long-term effects on male reproduction of early exposure to common chemical contaminants in drinking water. Hum Reprod. 2001 May;16(5):979-87. View Abstract

24 Sallmén M. Exposure to lead and male fertility. Int J Occup Med Environ Health. 2001;14(3):219-22. View Abstract

25 Buck Louis GM, Sundaram R, Schisterman EF et al. Heavy metals and couple fecundity, the LIFE Study.Chemosphere. 2012 Jun;87(11):1201-7. View Full Paper

26 Greene D. Effects of Lead in the environment. LEAD Action News 1993 (1):2 View Full Paper

27 Centers for Disease Control. February 9, 2017 [Cited July 29, 2017] Available at: https://www.cdc.gov/nceh/lead/

28 Laidlaw MA, Zahran S, Pingitore N et al. Identification of lead sources in residential environments: Sydney Australia.Environ Pollut. 2014 Jan;184:238-46 View Abstract

29 Mercury in the Environment. Fact Sheet 146-00. October 2000. [Accessed July 29, 2017] Available at: http://www.usgs.gov/themes/factsheet/146-00/index.html

30 Kassotis CD, Tillitt DE, Lin CH et al. Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures. Environmental Health Perspectives, 2015

31 Neimark J. The Dirty Truth About Plastic. Discover Magazine (2008) April 18. View Full Paper

32 Heller CG, Clermont Y. Spermatogenesis in man: an estimate of its duration. Science. 1963 Apr 12;140(3563):184-6. View Abstract

33 Yang HS, et al. Effects of alpha-tocopherol on cadmium-induced toxicity in rat testis and spermatogenesis. J Korean Med Sci. 2006 Jun;21(3):445-51. View Full Paper

34 Sheweita SA, et al. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab. 2005 Oct;6(5):495-501. View Abstract

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Methyl B12—A Generous Donor Essential to Health

         Vitamin B12 is a highly versatile, water-soluble nutrient that plays a critical role in mood, energy, memory, cognition, cardiovascular function, neurological function, digestion, and hormonal balance. It is vital to a well-functioning and healthy body, and is necessary for DNA synthesis and red blood cell production.1 B12 is so precious to the body that, according to Northeastern University professor of pharmacology Richard Deth, “If you eat a piece of rib eye steak, the B12 released from the proteins is instantly bound right there in the GI tract and chaperoned as if in a football handoff to be carried to cells, transported inside and then processed into the two active forms of the vitamin.”

         And yet vitamin B12 deficiency is a global problem.3 The National Institute of Health’s (NIH) Dietary Office estimates that up to 15 percent of people in the U.S. are deficient in vitamin B12.4 Other studies put the number even higher—suggesting that as much as 39 percent of the population may suffer from a vitamin B12 deficiency.5 In addition, some researchers contend that the current norms for vitamin B12 levels are too low.6

             Vegans and vegetarians are at risk of vitamin B12 deficiency because animal protein, including dairy products, eggs, meat, fish, poultry and organ meats, offers the most absorbable form of vitamin B12. Plant foods do not naturally contain vitamin B12 unless they are synthetically fortified. The elderly are also at risk, because as we age we often have more difficulty absorbing B12 and other nutrients from food due to hypochlorhydria and diminished pancreatic enzyme secretion.7,8,9 Smokers are at risk (since nicotine can block absorption), as are alcoholics, and individuals with digestive disorders like celiac or Crohn’s disease.10,11,12 In addition, those of us with genetic variations that inhibit our ability to transform vitamin B12 into its highly active form, methylcobalamin, can be functionally deficient.13

It is that active form, methylcobalamin (or methyl B12), that supports one of the most fundamental biological processes in our body-- methylation. Methylation seems incredibly simple—in essence, it means that a ‘methyl group’, formed by a single carbon with three hydrogen atoms, has been added to a substance. Methyl B12 is one substance which is able to provide these crucial methyl groups. But in the simplicity of methylation lies its profundity, for nature talks to itself through methylation, and many biochemical pathways are critically dependent on recycling and activating substances via the process of methylation. The simple act of methylation regulates gene expression,14 protein function, and even RNA metabolism.15 It is important for the processes of detoxification, as the methylation of a fat-soluble toxin helps change it to a water-soluble form that can be more easily processed and excreted.16

There are 150-200 enzymes involved in the processes of methylation in the body, and each enzyme can methylate multiple targets. 17 You might picture methylation as an intricate spider web within each cell, a web that has many critical joints and attachments giving it structural integrity, with connections in every direction. The process of methylation is like this – critical for the function of our cellular biochemistry at many points along the pathway, each somehow connected. If a path or a joint is disrupted, there often are alternate routes, but they are less efficient in getting things done.

Methyl B12 in part works its magic by donating an all-important methyl group to a molecule called homocysteine, which then turns into methionine, an essential amino acid. When your levels of methyl B12 are too low, homocysteine can build up. High homocysteine levels have been linked to an increased risk of cardiovascular disease, as well as Alzheimer’s disease. And low levels of methyl B12 have been linked to everything from peripheral neuropathy to autism and mercury toxicity.18,19,20

Enhancing the body’s level of B12 can be achieved by a liposomal delivery system, which improves the bioavailability of vitamin B12, provided as methylcobalamin. Small liposomal vesicles are absorbed intraorally, circumventing issues with gastrointestinal absorption that may exist for other oral, including sublingual, B12 supplements. Studies have shown no significant difference between absorption of oral or sublingual B12, however the absorption of liposomal B12 has been demonstrated to have faster absorption and lead to higher plasma levels (see figure).21 The phospholipids that form the liposomes delivering methyl B12 nourish the membranes of the cells, ensuring proper function for the absorption of nutrients, the excretion of cellular waste products and toxins, and cellular communication.

 


1 Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017 May 11;129(19):2603-2611. View Abstract.

2 Personal interview, August, 2011.

3 Stabler SP, Allen RH Vitamin B12 deficiency as a worldwide problem. Rev Nutr. 2004;24:299-326. View Abstract

4Vitamin B12 Fact Sheet for Consumers. June 24 2011 (cited 17 July 2017). Available from: https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/

5 Tucker KL, Rich S, Rosenberg I et al. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22. View Abstract

6 Goodman M, Chen XH, Darwish D. Are U.S. lower normal B 12 limits too low? J Am Geriatr Soc. 1996 Oct;44(10):1274-5. PMID: 8856015

7 Green R, Allen LH2, Bjørke-Monsen AL Vitamin B12 deficiency. Nat Rev Dis Primers. 2017 Jun 29;3:17040. View Abstract

8 Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Drugs Aging. 1998 Apr;12(4):277-92. View Abstract.

9 Rothenbacher D, et al. Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study. Scand J Gastroenterol. 2005 Jun;40(6):697-704. View Abstract

10 Linnell JC. Effects of Smoking on Metabolism and Excretion of Vitamin B12 J. Br Med J. 1968 Apr 27;2(5599):215-6. View Full Paper

11 Pott JW. Detection of vitamin B12 deficiency in alcohol abuse. Acta Ophthalmol. 2014 Feb;92(1):e76-7. View Full Paper

12 Pan Y et al. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients. 2017 Apr 13;9(4). View Full Paper

13 Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017 Feb;16(1):42-49. Review. View Abstract

14 Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003 Mar;33 Suppl:245-54. View Full Paper

15 Riddihough G. RNA Methylation and Metabolism Science 2013 Feb; 339: 490-491. View Abstract

16 Wilson, L Methylation. The Center for Development. July 2016. (cited July 17, 2017). Available from: drlwilson.com/ARTICLES/METHYLATION.htm

17 Katz, JE, Dlakic M, Clarke S 2003 July. Automated identification of putative methyltransferases from genomic open reading frames. Molecular & Cellular Proteomics. 2: 525–40 View Abstract

18 Li S, Chen X, Li Q, Du J et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial.J Diabetes Investig. 2016 Sep;7(5):777-85. View Full Paper

19 Zhang Y, Hodgson NW, Trivedi MS et al. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PLoS One. 2016 Jan 22;11(1):e0146797. View Full Paper

20 T Kasuya M. The effect of methylcobalamin on the toxicity of methylmercury and mercuric chloride on nervous tissue in culture. Toxicol Lett. 1980 Nov;7(1):87-93. View Abstract

21 Sharabi A, Cohen E, Sulkes J. Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol. 2003 Dec;56(6):635-8. View Full Paper

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NanoMojo: A Liposomal Adaptogenic Tonic Forged From A Global Selection of Medicinal-Grade, Potent Herbs

An Interview with inventor and herbalist Daniel Moriarty, founder of Sun Horse Energy and creator of the Mojo Formula

Forty years ago, when a young Dan Moriarty was asleep at a campsite in Jalisco, Mexico, he had a classic ‘initiation’ experience into the wonders of herbalism. In the middle of the night he was bitten by a venomous scorpion, and instantly woke in extraordinary pain and barely able to draw a breath. He believes his life was saved by a local Huichol Indian who offered him hot tea made from a jungle root called Guaco. Guaco can be a powerful bronchodilator. “Within a minute I could breathe again, and I began to cry with relief,” recalls Moriarty. Later, Moriarty recalls, he visited the man in his hut and “he grabbed me by both wrists and looked deep into my eyes with his own coal black eyes, as if he was imparting something to me.”

            Dan’s Hungarian herbalist mother, who specialized in women’s health, lived  further down the coast in Colima, Mexico, and when he visited her she explained that every genuine healer, every medicine man or woman, has first undergone an experience where they nearly died. She offered to train him how to choose and internalize herbs, teachings given to her by her own immigrant mother, who grew her own herbs in the garden. She also told him to pick a class of herbs, and he chose adaptogens—those marvelous tonics found in every herbal medicine cabinet, that nudge us toward balance and harmony, and help our bodies respond to stress with resilience and vigor, not with fight, flight, or exhaustion.

            

Four decades later, we have NanoMojo, a liposomal formulation of Dan’s adaptogen blend, formulated by Dan, and enhanced by the advanced delivery systems developed by Chris Shade, PhD, founder of Quicksilver Scientific. According to Dr.  Shade, “Dan has been working with herbs almost as long as I’ve been on this earth…. It was an extraordinary challenge to encapsulate these complex herbals in a formula with so many necessary moving parts, for liposomal delivery—especially a tiny, highly absorbable, unilamellar liposome.” But they did it, and the result is a liposomal adaptogenic tonic where a dose 1/8th the amount of a traditional formula actually packs more power and harmonics than any standard herbal formulation. Learn more about Dan’s amazing story in our recent interview with him.

           

Quicksilver Scientific: Tell us why you chose adaptogenic herbs as your specialty.

Moriarty: They possess a broad spectrum of healing properties while being non-toxic to the organs. They essentially support normal functioning, particularly by increasing non-specific resistance to stress. They balance physiology at a cellular level for stress accommodation, and help the body achieve homeostasis. Think of a violin. If tuned too tightly the stress will break the strings. If tuned too loosely, the strings will be floppy. Either way, you won’t have music. Adaptogens tune your body to the right pitch and tension.

 

QS: After your scorpion bite, when your mom, an experienced herbalist, offered to train you, what techniques and insights did she pass on?

Moriarty: One of her great gifts was teaching me how to truly and intimately know an herb. She told me of five aspects of physiology that ultimately blend to help your body stay in balance. Those five aspects are trade and family secrets so I won’t divulge them here, but she instructed me to take a given herb in the morning on an empty stomach, and in the evening before bed, and keep a record of my response for all five aspects during an entire month’s cycle. That would pertain to the cycles of the moon, and how they affect your body. Secondly, she told me to keep the same record for an entire year, through all four solstice seasons. And it blew my mind. I started with ginseng and I discovered that herbs acted differently on me according to the season, as well as over the course of a single month. For instance, an herb will affect you differently if your body is in a hibernation mode as opposed to an energizing mode. That’s when I thought, “My mom really does know what she’s talking about, and she really is a master herbalist.”

So my task, then, was to intimately know each adaptogenic herb by taking it and making notes and observing its effects, and then create a formula that would protect us through all the seasons. And of course, the plants themselves respond to their environment, to altitude, humidity, stress, temperature, local soil, and the seasons. So where they are grown and how they are harvested also matters immensely. All these environmental factors influence the activity and expression of the genes, and the amount of specific phytochemicals they produce. When we consume those plants, they are like messengers, telling us what kind of environment produced them and offering us their plant gifts for handling that environment well. In fact, I think we can even zoom out to think about the entire earth, and the gravitational field around it. There are fluctuations of gravitational strength, gradient and curvature depending on where you are on Earth. I’m convinced adaptogens respond to that and so do we.

 

QS: So how do you bring all that insight into your formula?

Moriarty: By creating a global resonance formula that anybody anywhere on the planet can benefit from. You don’t need large amounts of any particular ingredient, because the beauty here is that small amounts of each herb move you forward, so that the overarching effect on your body is both nonspecific and effective. The ingredients come from all the major geographic areas—Russia, America, South America, Asia, the Indian subcontinent. Some are well known and some a bit surprising. Ancient systems of herbal wisdom inform the choices, from Ayurvedic to Chinese medicine to European herbalism. And that’s verified by the biochemistry of today, which explores mechanisms of action.

 

QS: Let’s go over some of the special qualities of these nineteen choice herbs, why you chose them, what they do, and how you source them. Shall we start with the three varieties of ginseng that you include, and why?

Moriarty: The first is Gynostemma, one of the most popular herbs in all of Asia, and also known as ‘southern ginseng’ because it is a traditional adaptogen and longevity herb. It turns out to contain some ginsenosides that were once thought to be wholly unique to Panax Ginseng. But the bulk of the active constituents are known as gypenosides, and there are over eighty of them, many yet to be fully studied and characterized. This herb is traditionally used to help support and maintain normal healthy respiratory, cardiovascular, digestive and liver functions, as well as help lower blood sugar. Gynostemma has the ability to modulate some of the other herbs in the formula, and that’s why it has such a prominent position.

            The formula also contains Siberian Ginseng root (Eleutherococcus senticosus) and American Ginseng root (Panax quinquefolius). Siberian ginseng’s active components are called eleutherosides, and it is widely used in Russia to increase

energy, longevity, and vitality. American ginseng is a true tonic, which the Asians figured out long ago, and they try to buy the whole crop every year. We work very hard to stabilize our supply of American ginseng.

 

QS: How about Maca?

Moriarty: Maca is fascinating. Maca is a cruciferous vegetable in the mustard family, related to radishes and turnips. It is used as food and medicine in the Andes mountains of Peru. It is also a completely different plant when it grows at 8000 feet altitude as opposed to 5000 feet or below. That’s because of the very different stresses it’s under at high altitude with thin soils and much more UV light. It develops many more protective effects at high altitude. The Lapidium peruvianum strain grown at high altitude is very hard to get, and over the years we have developed a very good source for that part of our formula.  

 

QS: Next up, berries.

Moriarty: We use goji berry, or the “wolfberry fruit”, formally known as Lycium. Long ago in Rome, people noticed that wolves ate these berries, and since wolves were powerful predators, humans began to eat them, too. And as time went on we discovered this berry grows in many places: from the highest elevations of the Himalayas, all the way down into the forests of India, and clear into Europe and lo and behold, all over Mongolia. It is one of the most power-packed little packets of food you could ever put in your body. It benefits your health, energy, eyesight and microbiome. And though it grows in many places we like to get the premium, medicinal grade, high altitude variety. The Lycium we use is simply fantastic.

 

QS: Though there are many other herbs in your formula we could discuss, one of the most interesting may be Chinese licorice root. Tell us a little about that.

Moriarty: Chinese licorice root is a choice that shows exactly what we strive to do here that is special. Almost every Chinese herbal formula uses Asian licorice (Glycyrrhiza glabra) because it is demulcent and modulating and allows the whole formula to be accepted by the body. And unlike the Glycyrrhiza glabra most of us know very well, Chinese licorice does not raise blood pressure or affect the heart. So we don’t use the variety that potentially has deleterious effects on the body.

The formula also uses Schisandra berry, also known as the five-flavor berry. It is purely a medicinal berry, and called five flavor because it’s sweet, sour, salty, bitter and pungent all at once. It is considered an immortality herb, and is used throughout Asia.

If you wish, you can make a beautiful tea from the raw Chinese licorice root, Schisandra berry and Lycium (goji) berry. Drink it at night and you will sleep like a baby and wake like a different person. It’s particularly helpful in winter.

 

QS: Any final thoughts?

Moriarty: Honestly? I think the liposomal formulation here is a true masterpiece. The Mojo formula and the nano-liposomes go together like peanut butter and chocolate. And who doesn’t like peanut butter and chocolate? But on a more serious note, when applied correctly, adaptogens can make a bigger difference in one’s health than any other system out there.


 

Further reading:

Panossian A, Hambardzumyan M, Hovhanissyan A, et al. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug Target Insights. 2007;2:39-54. View Abstract.

 

Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219. View Abstract

 

Wiegant FA, Surinova S, Ytsma E, et al. Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology. 2009 Feb;10(1):27-42. View Abstract

 

Chen Y, Müller F, Rieu I, et al. Epigenetic events in plant male germ cell heat stress. Plant Reprod. 2016 Jun;29(1-2):21-9. View Abstract

 

Seo JY, Kim SK, Nguyen PH, et al. Chemical constituents from a Gyno