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Skin Health, Detoxification, and Liposomal Antioxidant Delivery

You’ve realized the vast benefits that a liposomal delivery format brings to your oral supplements, but did you know that many of these products also can be helpful if applied to the skin? If not, read on to learn about some of the potential topical applications of your liposomal products

If you are not a dermatologist or follower of skin care trends, it’s likely that you haven’t put thought into how innovations such as liposomal delivery systems are being incorporated into topical delivery of nutrients and drugs for that matter.  Aware or not, this is a very active topic of research for the transdermal, or skin, delivery of substances.[1]

Fats and skin healthPicture1

Lipids, also known as oils or fats, are very nourishing and important for the health of the skin. The natural oils of the skin are protective to it – supporting hydration and protecting it from damage. Many people utilize natural fatty substances such as coconut or olive oil and avocado for the purpose of nourishing the skin, as they support the skin health providing antioxidants (avocado) or antimicrobials (coconut and olive oil) along with fats.[2],[3] Liposomal delivery systems inherently deliver lipids, in the form of phosphatidyl choline, which nourish the cells of the skin, particularly at the deeper layers of the skin where cells are still alive. The phosphatidyl choline which forms the outer shell of the liposome fuses with cellular membranes which are also comprised of phospholipids, the main one being phosphatidyl choline. As the phospholipid liposomes fuse with the cells of the skin, their contents are directly delivered intracellularly, while the phospholipids provided nourish and repair cellular membranes.

Transdermal delivery of nutrients

Fat-soluble compounds are able to enter the body through the skin, which we see in the topical delivery of medications such as hormones.[4] Small liposomes have been shown to penetrate the layer of the skin known as the stratum corneum, which blocks liposomes of larger sizes (>105 – 120 nm) from delivering their contents into the deeper layers of the skin.[5],[6] Smaller liposomes of roughly 30 – 40 nm in diameter have been shown to rapidly pass through the stratum corneum, without breaking, and deliver their contents to the deeper layers of the skin. The penetration of liposomes 31 nm in size through the stratum corneum was shown to be 590% greater than liposomes larger than 105 nm.6 Enhanced skin penetration also occurs through other features of the skin like hair follicles and pores.[7] When the healthy skin barrier is disrupted by skin conditions such as eczema, psoriasis, or even a surface wound, topical compounds are able to transfer through it more readily.

The skin as an organ of detoxification

The skin serves as an organ of detoxification, and a substantial amount of toxins are excreted in our sweat and the oily/waxy matrix that from the sebaceous glands. In fact, the dermal excretion of some toxic metals has been shown to exceed urinary elimination.[8] A variety of other toxic substances including bisphenol A and organochlorinated pesticides are also excreted through the skin, again, some at higher levels than in the urine.[9],[10] And perhaps not surprisingly, these toxins can also cause damage and irritation to the skin.[11] Although topical use of products does not directly enhance the dermal elimination of toxins, other activities that promote sweating such as exercise and therapeutic saunas do.

 Topical applications of liposomal-delivered nutrients and compounds

One setting in which liposomal delivery systems are an active topic of research is for skin aging. Some things which “age” the skin progressively are oxidative damage, which can be due to sun and other environmental exposures,[12] and the reduced formation and gradual degradation of the collagen and elastin[13] which give the skin the quality of turgor – the structural integrity that prevents issues such as wrinkles. Oxidative stress damages cellular membranes (lipids), proteins, and DNA, and contributes to dermatological diseases and some forms of skin cancer.[14],[15] Knowledge of these factors sheds light on the importance of antioxidants for the skin, and why the liposomal delivery of antioxidants may be beneficial.[16]

In addition to being an antioxidant, vitamin C is critical for the health of many tissues in the body including the skin, as it plays a role in collagen formation. Vitamin C has been shown to stimulate collagen synthesis, particularly that of Type I and Type III collagen.[17],[18] Phosphatidyl choline liposomes delivering ascorbic acid have been shown to deliver ascorbate to the dermis, the deeper layer of the skin, and to prevent oxidative damage and inflammation associated with exposure to UVA and UVB light.[19] Coenzyme Q10 (CoQ10) is necessary for the function of mitochondria within the cells of the skin, and as an antioxidant also prevents sun damage.[20] Because of this, CoQ10 also has been studied as a skin anti-aging and wrinkle-preventing substance.[21] Again, liposomal delivery systems have been shown improve delivery of CoQ10 to the skin.[22] These studies and others continue to spur ongoing research in additional applications for the cutting-edge technology of liposomal delivery systems.[23] We can only anticipate more promising findings and advancement in skin-care related products with nanoscale liposomal technologies.

Dr. Carrie Decker is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Dr. Decker also has graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectfully. Dr. Decker sees patients at her office in Portland, OR, as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, chronic fatigue, and skin conditions. Dr. Decker also supports integrative medicine education as a writer and contributor to various resources. 



[1] Kakadia PG, Conway BR. Lipid nanoparticles for dermal drug delivery. Curr Pharm Des. 2015;21(20):2823-9. View Abstract

[2] Wang W, Bostic TR, Gu L. Antioxidant capacities, procyanidins and pigments in avocados of different strains and cultivars. Food Chemistry. 2010 Oct 15;122(4):1193-8. View Abstract

[3] Verallo-Rowell VM, et al. Novel antibacterial and emollient effects of coconut and virgin olive oils in adult atopic dermatitis. Dermatitis. 2008 Nov-Dec;19(6):308-15. View Full Paper

[4] Abadilla KA, Dobs AS. Topical testosterone supplementation for the treatment of male hypogonadism. Drugs. 2012 Aug 20;72(12):1591-603. View Abstract

[5] Verma DD, et al. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm. 2003 Jun 4;258(1-2):141-51. View Full Paper

[6] Hood RR, et al. Microfluidic-enabled liposomes elucidate size-dependent transdermal transport. PLoS One. 2014 Mar 21;9(3):e92978. View Full Paper

[7] Lauer AC, et al. Transfollicular drug delivery. Pharm Res. 1995 Feb;12(2):179-86. View Abstract

[8] Sears ME, Kerr KJ, Bray RI. Arsenic, cadmium, lead, and mercury in sweat: a systematic review. J Environ Public Health. 2012;2012:184745. View Full Paper

[9] Genuis SJ, et al. Human excretion of bisphenol A: blood, urine, and sweat (BUS) study. J Environ Public Health. 2012;2012:185731. View Full Paper

[10] Genuis SJ, Lane K, Birkholz D. Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study. Biomed Res Int. 2016;2016:1624643. View Full Paper

[11] Rosenmai AK, et al. Are structural analogues to bisphenol a safe alternatives? Toxicol Sci. 2014 May;139(1):35-47. View Full Paper

[12] Fisher GJ, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol. 2002 Nov;138(11):1462-70. View Abstract

[13] Uitto J. Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. Dermatol Clin. 1986 Jul;4(3):433-46. View Abstract

[14] Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 2006 Dec;126(12):2565-75. View Full Paper

[15] Valko M, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006 Mar 10;160(1):1-40. View Full Paper

[16] Montenegro L. Lipid-Based Nanoparticles as Carriers for Dermal Delivery of Antioxidants. Curr Drug Metab. 2017 Feb 22. View Abstract

[17] Pinnell SR. Regulation of collagen biosynthesis by ascorbic acid: a review. Yale J Biol Med. 1985 Nov-Dec;58(6):553-9. View Full Paper

[18] Tajima S, Pinnell SR. Ascorbic acid preferentially enhances type I and III collagen gene transcription in human skin fibroblasts. J Dermatol Sci. 1996 Mar;11(3):250-3. View Abstract

[19] Serrano G, et al. Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders. Clin Cosmet Investig Dermatol. 2015 Dec 17;8:591-9. View Full Paper

[20] Inui M, et al. 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

[21] Prahl S, et al. 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] Gokce EH, et al. A comparative evaluation of coenzyme Q10-loaded liposomes and solid lipid nanoparticles as dermal antioxidant carriers. Int J Nanomedicine. 2012;7:5109-17. View Full Paper

[23] Aparajita VA, Ravikumar PA. Liposomes as carriers in skin ageing. Int J Curr Pharm Res. 2014;6(3):1-7. View Full Paper

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Nutritional Outlook Takes Notice of Quicksilver Scientific

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Featured in Nutritional Outlook, Michael Crane discusses with Dr. Shade the science behind Quicksilver Scientific's liposomal technology. Dr. Shade explains what makes the Quicksilver Scientific liposomes superior to competitors and how difficult it can be to create liposomes with multiple nutrients.

"Liposomal delivery technology from a company called Quicksilver Scientific (Lafayette, CO) is front and center in several new 2017 product launches, including an “ultra-strength multivitamin,” an energy supplement, and a hemp cannabidiol (CBD) serum. And while the ingredients in these products may be very different, the liposomal delivery system they all use serves a similar function in each—enhancing bioavailability and supporting cellular membrane function, says Quicksilver."

Read the full story here!

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Bitters: Balancing Agents for the Gut, and Support for Liver/Kidney Detoxification

Bitters: Balancing Agents for the Gut, and Support for Liver/Kidney Detoxification

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.


Bitter herbs broadly encompass many botanicals, and are most often thought of as herbs with effects on the digestive system. Herbal bitters have a long history of use, and are commonly served in cocktails known as aperitifs and digestifs before or after meals to stimulate appetite and digestion. Strong bitter herbs like gentian stimulate stomach acid and other accompanying digestive secretions, while slightly milder bitters such as sweet orange essential oil also calms digestive upset and balances the central nervous system. Bitter herbs act far beyond the digestive system however, and broadly impact the liver, kidneys, skin, immune system, and detoxification pathways.[1] Bitter taste receptors exist not only on the back of the tongue but also throughout the digestive system and beyond.[2] They have been shown to trigger a wide variety of biological processes including regulation of blood sugar and activation of the immune system in response to infections.[3],[4],[5]

 

The impact of liver, kidney, and gastrointestinal function on detoxification

Although the process of detoxification occurs in every cell of the body, organs in which detoxification occurs at a higher level are the liver and kidneys. It is well known that in individuals with compromised liver or kidney function, dosages of many medications must be altered. The small intestine mucosa also plays an important role in detoxification, as proteins important for all phases of detoxification are expressed at a high level here.[6],[7] When any of these organs (liver, kidneys, intestines) experience less than optimal function, a backup in processing of toxins will occur.  With understanding of this, it is easy to see the importance of an integrated process where the intestines, liver, and kidneys are all functioning in an optimal fashion simultaneously.

Gastrointestinal inflammation also effects detoxification, increasing susceptibility of the organism to toxicity from external and internal agents.[8] Leaky gut and damage to the gastrointestinal barrier allows endotoxin, also known as lipopolysaccharide (LPS), to be released into circulation. Exposure to endotoxin effects the other stages of detoxification, downregulating expression of some of the drug and toxin-metabolizing enzymes and Phase III transporters.[9],[10]

The broad impact of the bitter herbs in Dr. Shade’s Bitters No. 9

The proprietary bitters combination of Dr. Shade’s Bitters No. 9 includes dandelion, milk thistle, solidago (goldenrod), gentian, burdock, and essential oils of sweet orange, myrrh, juniper, and clove, which are delivered along with phospholipids that comprise the liposomes in which these herbs are carried. The combination of these herbs is thoughtfully selected to support the gastrointestinal tract, liver, and kidneys in their necessary functions for health and detoxification. Just a small snippet of the vast amounts of research
on these herbs is highlighted below.

Dandelion 

Dandelion is known for its action on the liver and gallbladder, but also acts as an antioxidant and anti-inflammatory, and may have cholesterol lowering effects.[11],[12],[13] In animal models, supplementation with dandelion leaf extract has been shown to alleviate hepatic inflammation associated with a high-fat diet, and protect the liver from alcohol-induced oxidative stress.[14],[15] In the setting of alcohol injury, supplementation with dandelion root extract was observed to increase hepatic antioxidant activity, including glutathione (GSH), GSH-S-transferase, GSH reductase, and GSH peroxidase.  

 

Milk thistle 

Milk thistle has been vastly studied for its antioxidative, anti-inflammatory, and hepatoprotective effects in settings including acetaminophen, radiation, iron overload, alcohol and Amanita phalloides (also known as “death cap” mushroom) induced liver damage.[16] Silymarin is the active complex extracted from the seeds of the plant, with the flavonolignan silybin being the most biologically active moiety comprising 50% to 70% of silymarin. Silybin has been observed to inhibit human intestinal β-glucuronidase, blocking the release and reabsorption of free xenobiotics and their metabolites from their glucuronide conjugates.[17] Silymarin acts as an antioxidant, enhancing hepatic and intestinal GSH levels, and stabilizing membranes by inhibiting membrane peroxidation.[18],[19]

Solidago Solidago, commonly known as goldenrod, is known for its action on the urinary tract, and is classically used for infections, inflammation, and prevention of kidney stones.[20] Solidago is rich in compounds including flavonoids, phenolic acids, sesquiterpenes, diterpenes, saponins, and several caffeoylquinic acids.[21],[22] Solidago acts as an anti-inflammatory, antimicrobial, diuretic, antispasmodic, and analgesic due to these many compounds found within it.[23] Research has also shown that the flavonoids from solidago have an activating effect on GSH-S-transferases, a critical enzyme in phase II detoxification, in a dose-dependent fashion.[24]

Gentian Gentian is one of the strongest herbal bitters most often utilized in digestive bitter formulations. Gentian is a digestive toner and modulator of stomach acid secretion, improving function in a state of deficiency but also having a protective effect on conditions such as gastritis or gastric ulcers possibly through prostaglandin pathways.[25] Gentian also acts beyond the digestive system, as the compounds in it exhibit hypoglycemic, hepatoprotective, anti-inflammatory, antioxidant, antimicrobial, immunomodulatory, and adaptogenic properties.[26],[27] As a liver protective agent, gentian has been observed to increase levels of reduced GSH, catalase, superoxide dismutase and GSH peroxidase in various settings of toxin-induced oxidative damage.[28],[29],[30]
 

Burdock

Burdock root is commonly utilized in digestive and metabolic balancing formulas, with hypoglycemic, antioxidant, anti-inflammatory, hepatoprotective, and antimicrobial actions.[31] Burdock root has been observed to reverse decreases in GSH and increases in malondialdehyde (a marker of oxidative stress) induced by toxin exposure.[32] Caffeoylquinic acid derivatives from burdock root have been observed to have a strong antioxidant effect, greater than that of α-tocopherol.[33] Burdock extract has been shown to inhibit lipoprotein oxidation while increasing GSH, GSH reductase, GSH peroxidase, GSH-S-transferase and catalase levels.[34]


Essential oils of sweet orange, myrrh, juniper, and clove

Each of these oils contains many active compounds, a sense of which we only begin to have from the aromatic expression of its essence. Sweet orange essential oil is derived from the outer peel of the orange, which anyone who has tasted is familiar with its bitter nature. Sweet orange essential oil has been observed to have antibacterial, antifungal, and antioxidant effects.[35],[36] Myrrh has a long history of medicinal use, and is perhaps most recognized for its antimicrobial effects.[37],[38] Additionally, myrrh has been used as an anesthetic, anti-inflammatory, antioxidant, and cholesterol lowering agent.[39]



Juniper essential oil also has been shown to have broad antimicrobial action, with traditional use as an antiseptic, antidiarrheal, anti-inflammatory, and astringent, with an affinity for the urinary tract. [40],[41] Juniper also acts as an antioxidant, with metal chelating, free radical, superoxide anion radical, and hydrogen peroxide scavenging activities.[42],[43] Finally, clove essential oil also has antimicrobial, antiviral, antiulcer, anti-inflammatory and antioxidant properties.[44],[45] As an antioxidant it has a
 significant inhibitory effect against hydroxyl radicals and forms complexes with reduced metals.[46],[47],[48]

 

Author, Dr. Carrie Decker

Dr. Decker is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Dr. Decker also has graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectfully. Dr. Decker sees patients at her office in Portland, OR, as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, chronic fatigue, and skin conditions. Dr. Decker also supports integrative medicine education as a writer and a contributor to various resources.


[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] Jaggupilli A, et al. Analysis of the expression of human bitter taste receptors in extraoral tissues. Mol Cell Biochem. 2017 Feb;426(1-2):137-147. View Abstract

[3] Yu Y, et al. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochem Pharmacol. 2015 Sep 15;97(2):173-7. View Abstract

[4] 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

[5] Gaida MM, et al. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog Dis. 2016 Apr;74(3). View Full Paper

[6] 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

[7] 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

[8] 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

[9] Tang W, et al. 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

[10] Kalitsky-Szirtes J, 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 Full Paper

[11] Schütz K, Carle R, Schieber A. Taraxacum--a review on its phytochemical and pharmacological profile. J Ethnopharmacol. 2006 Oct 11;107(3):313-23. View Abstract

[12] González-Castejón M, et al. Diverse biological activities of dandelion. Nutr Rev. 2012 Sep;70(9):534-47. View Abstract

[13] Choi UK, et al. Hypolipidemic and antioxidant effects of dandelion (Taraxacum officinale) root and leaf on cholesterol-fed rabbits. Int J Mol Sci. 2010 Jan 6;11(1):67-78. View Full Paper

[14] Davaatseren M, et al. Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver. Food Chem Toxicol. 2013 Aug;58:30-6. View Abstract

[15] 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

[16] Abenavoli L, et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010 Oct;24(10):1423-32. View Abstract

[17] Kim DH, et al. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull. 1994 Mar;17(3):443-5. View Abstract

[18] Valenzuela A, et al. Selectivity of silymarin on the increase of the GSH content in different tissues of the rat. Planta Med. 1989 Oct;55(5):420-2. View Abstract

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

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

[21] Bradette-Hébert ME, et al. A new labdane diterpene from the flowers of Solidago canadensis. Chem Pharm Bull (Tokyo). 2008 Jan;56(1):82-4. View Full Paper

[22] Bohlmann F, et al. Sesquiterpene and diterpene derivatives from Solidago species. Phytochemistry. 1980 Jan;19(12):2655-61. View Abstract

[23] Yarnell E. Botanical medicines for the urinary tract. World J Urol. 2002 Nov;20(5):285-93. View Full Paper

[24] 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

[25] Niiho Y, et al. 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

[26] Dinda B, et al. Naturally occurring iridoids, secoiridoids and their bioactivity. An updated review, part 3. Chem Pharm Bull (Tokyo). 2009 Aug;57(8):765-96. View Full Paper

[27] Ghisalberti EL. Biological and pharmacological activity of naturally occurring iridoids and secoiridoids. Phytomedicine. 1998 Apr;5(2):147-63. View Abstract

[28] 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

[29] Lian LH, et al. 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

[30] Wang AY, et al. 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

[31] Chan YS, et al. A review of the pharmacological effects of Arctium lappa (burdock). Inflammopharmacology. 2011 Oct;19(5):245-54. View Abstract

[32] Lin SC, et al. Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage. Am J Chin Med. 2000;28(2):163-73. View Abstract

[33] Maruta Y, Kawabata J, Niki R. Antioxidative caffeoylquinic acid derivatives in the roots of burdock (Arctium lappa L.). Journal of Agricultural and Food Chemistry. 1995 Oct;43(10):2592-5. View Abstract

[34] Wang BS, et al. Protective effects of burdock (Arctium lappa Linne) on oxidation of low-density lipoprotein and oxidative stress in RAW 264.7 macrophages. Food Chemistry. 2007 Dec;101(2):729-38. View Abstract

[35] Geraci A, et al. Essential oil components of orange peels and antimicrobial activity. Nat Prod Res. 2016 Aug 18:1-7. View Abstract

[36] Guimarães R, et al. Targeting excessive free radicals with peels and juices of citrus fruits: grapefruit, lemon, lime and orange. Food Chem Toxicol. 2010 Jan;48(1):99-106. View Abstract

[37] Dolara P, et al. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med. 2000 May;66(4):356-8. View Abstract

[38] Sheir Z, et al. A safe, effective, herbal antischistosomal therapy derived from myrrh. Am J Trop Med Hyg. 2001 Dec;65(6):700-4. View Full Paper

[39] Shen T, et al. The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2012 Jul 13;142(2):319-30. View Abstract

[40] Pepeljnjak S, et al. Antimicrobial activity of juniper berry essential oil (Juniperus communis L., Cupressaceae). Acta Pharm. 2005 Dec;55(4):417-22. View Abstract

[41] Bais S, et al. A Phytopharmacological Review on a Medicinal Plant: Juniperus communis. Int Sch Res Notices. 2014 Nov 11;2014:634723. View Full Paper

[42] Miceli N, et al. Comparative analysis of flavonoid profile, antioxidant and antimicrobial activity of the berries of Juniperus communis L. var. communis and Juniperus communis L. var. saxatilis Pall. from Turkey. J Agric Food Chem. 2009 Aug 12;57(15):6570-7. View Abstract

[43] Elmastaş M, et al. A study on the in vitro antioxidant activity of juniper (Juniperus communis L.) fruit extracts. Analytical letters. 2006 Jan;39(1):47-65. View Abstract

[44] Santin JR, et al. Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn Schmiedebergs Arch Pharmacol. 2011 Feb;383(2):149-58. View Abstract

[45] Chaieb K, et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phytother Res. 2007 Jun;21(6):501-6. View Abstract

[46] Misharina TA, et al. [Antiradical properties of essential oils and extracts from clove bud and pimento]. Prikl Biokhim Mikrobiol. 2015 Jan-Feb;51(1):99-104. View Abstract

[47] Jirovetz L, et al. Chemical composition and antioxidant properties of clove leaf essential oil. J Agric Food Chem. 2006 Aug 23;54(17):6303-7. View Abstract

[48] Ito M, et al. Antioxidant action of eugenol compounds: role of metal ion in the inhibition of lipid peroxidation. Food Chem Toxicol. 2005 Mar;43(3):461-6. View Abstract

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Phosphatidyl Choline: A simple yet necessary nutrient

Phosphatidyl Choline: A simple yet necessary nutrient

Phosphatidyl choline is the predominant building block of plant and animal cell membranes. Adequate levels of phosphatidyl choline are necessary for cellular function, communication, and transport. Phosphatidyl choline is also critical for many aspects of physiology from neurotransmitter production to fat and cholesterol metabolism.


Phosphatidyl choline (PC) is the predominant building block of animal and plant cell membranes. It is required for the integrity of the phospholipid bilayers that contain the cell and the organelles within the cell. Although small amounts of choline, the primary and necessary nutrient derived from PC, can be synthesized from methionine or serine, it is considered an essential nutrient and must be obtained from the diet.[1] Although thresholds have been established for adequate intake of choline, studies have shown that this may not be sufficient for prevention of symptoms of choline deficiency such as fatty liver or muscle damage.[2] Higher amounts of PC can be found in foods such as egg yolks, liver, meats, broccoli, brussel sprouts, and milk.[3] Because higher amounts of choline are found in animal products, there is a risk of deficiency in individuals who are vegetarian or vegan. A higher risk of deficiency has also been observed at in men, postmenopausal women, and individuals with genetic polymorphisms related to folate or choline metabolism.2,[4] Supplemental intake of PC is one means of providing sufficient choline for the body’s needs.

Although thresholds have been established for adequate intake of choline, studies have shown that this may not be sufficient for prevention of symptoms of choline deficiency such as fatty liver or muscle damage.


 
Cellular and biochemical function. The phospholipid bilayers that form the external cellular membrane as well as that of the mitochondria, endoplasmic reticulum, Golgi apparatus all depend upon PC for their existence. It is critical for membrane integrity, structure, and function, and depletion has been shown to adversely affect the function of these organelles.[5],[6] Choline supports the body’s antioxidant status, reducing lipid peroxidation.[7] Deficiency of PC has been shown to lead to cellular damage via oxidative mechanisms in the liver, heart, kidneys, and brain. [8]

Sufficient levels of PC are necessary for many biochemical pathways, supporting critical functions and physiology. This includes fat and cholesterol metabolism, homocysteine metabolism, fetal development, neurocognitive health and development, and liver detoxification of chemicals, heavy metals, and xenobiotics. Choline provided by PC is a precursor for the synthesis of acetylcholine, an important neurotransmitter centrally in the brain, and necessary peripherally for muscle control and other aspects of cholinergic signalling.[9] PC is also a major source of methyl groups via its metabolite trimethylglycine (TMG), which is important for Phase II hepatic detoxification.

Clinical research surrounding phosphatidyl choline

Issues associated with metabolic syndrome. PC is a normal constituent of bile and facilitates fat emulsification, absorption, and transport. PC also is an integral part of the structure of circulating lipoproteins. Supplementation with lecithin, providing PC, has been shown to significantly reduce total cholesterol, low-density lipoprotein (LDL), and triglyceride levels while simultaneously increasing high-density lipoprotein (HDL) levels in individuals with hyperlipidemia.[10] In animal models, restoration of PC levels has been shown to be protective against hepatic steatosis and in part by supporting antioxidant status.[11]

Central nervous system effects. Lower plasma levels of PC have been observed in individuals with cognitive impairment, Alzheimer’s disease and other types of dementia.[12] Levels of acetylcholine, a neurotransmitter of significant interest particularly in settings of cognitive function, are supported by sources of choline such as PC. In an animal model, supplementation with PC have been shown to improve memory of mice with dementia as well as increase the brain acetylcholine concentration.[13] In a double-blind test with healthy college students utilizing a low and high dose of PC, higher doses of PC were shown to explicit memory, with greatest increases at 90 minutes after ingestion.[14] In a placebo-controlled double-blind study, supplementation of choline in the form of choline bitartrate improved performance on a speed-based visuomotor test as well as significantly decreased pupil size, a cognition-sensitive biomarker.[15] In a slightly different setting yet still related to the central nervous system, choline bitartrate was found to substantially reduce manic symptoms as well as improve symptoms of mood in patients taking lithium for the treatment of bipolar disorder.[16]

Gastrointestinal disorders. The intestinal mucus contains high amounts of PC, with PC comprising 90% of the phospholipids found in it.[17] PC is protective and supportive to the gastrointestinal mucosal barrier, and has been shown to exert an anti-inflammatory effect in colon cells.[18] An increased intake of foods high in phospholipids has been shown to be protective against gastric and duodenal ulcer formation and to promote ulcer healing.[19] In patients with ulcerative colitis (UC), the protective colonic mucus PC content has been shown to be reduced by 70% from that of a normal population regardless of the state of inflammation.17 The colon mucus barrier is critical to protecting the underlying tissue from irritation as well as infection, and the lower content of PC may be one factor that contributes to inflammation and immune activation in UC. Supplementation of PC to patients with UC has been shown to improve remission and reduce the need for corticosteroid treatment.[20]

Exercise performance and recovery. As intense exercise for an extended duration can lead to depletion of circulatory choline, PC has been studied for the potential impact it may have on sport performance.[21] Choline from PC is involved in the formation of acetylcholine, the neurotransmitter that is necessary for peripheral muscle contractions. Acute supplementation of PC prior to exercise has been shown to improve some aspects of athletic performance and markers of recovery such as decreased lactic acid concentrations and faster return to normal heart rate.

 

Author, Dr. Carrie Decker

Dr. Decker is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Dr. Decker also has graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectfully. Dr. Decker sees patients at her office in Portland, OR, as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, chronic fatigue, and skin conditions. Dr. Decker also supports integrative medicine education as a writer and a contributor to various resources.


[1] Canty DJ, Zeisel SH. Lecithin and choline in human health and disease. Nutr Rev. 1994 Oct;52(10):327-39. View Abstract

[2] Fischer LM, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007 May;85(5):1275-85. View Full Paper

[3] Linus Pauling Institute. Micronutrient Information Center. Choline. Accessed on March 7, 2017. View Website

[4] Zeisel SH. Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline. IUBMB Life. 2007 Jun;59(6):380-7. View Full Paper

[5] Spector AA, Yorek MA. Membrane lipid composition and cellular function. J Lipid Res. 1985 Sep;26(9):1015-35. View Full Paper

[6] Testerink N, et al. Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex. J Lipid Res. 2009 Nov;50(11):2182-92. View Full Paper

[7] Grattagliano I, et al. Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet. J Nutr. 2000 Sep;130(9):2131-6. View Full Paper

[8] Repetto MG, et al. Oxidative damage: the biochemical mechanism of cellular injury and necrosis in choline deficiency. Exp Mol Pathol. 2010 Feb;88(1):143-9. View Abstract

[9] Löffelholz K, Klein J, Köppen A. Choline, a precursor of acetylcholine and phospholipids in the brain. Prog Brain Res. 1993;98:197-200. View Abstract

[10] Wojcicki J, et al. Clinical evaluation of lecithin as a lipid‐lowering agent. Phytother Res. 1995 Dec;9:597-9. View Abstract

[11] Kharbanda KK, et al. Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J Hepatol. 2007 Feb;46(2):314-21. View Abstract

[12] Conquer JA, et al. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids. 2000 Dec;35(12):1305-12. View Abstract

[13] Chung SY, et al. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. J Nutr. 1995 Jun;125(6):1484-9. View Abstract

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

[15] Naber M, Hommel B, Colzato LS. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study. Sci Rep. 2015 Aug 14;5:13188. View Full Paper

[16] Stoll AL, et al. Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry. 1996 Sep 1;40(5):382-8. View Abstract

[17] Stremmel W, et al. Mucosal protection by phosphatidylcholine. Dig Dis. 2012;30 Suppl 3:85-91. View Abstract

[18] Treede I, et al. Anti-inflammatory effects of phosphatidylcholine. J Biol Chem. 2007 Sep 14;282(37):27155-64. View Full Paper

[19] Tovey FI. Role of dietary phospholipids and phytosterols in protection against peptic ulceration as shown by experiments on rats. World J Gastroenterol. 2015 Feb 7;21(5):1377-84. View Full Paper

[20] Stremmel W, et al. Delayed release phosphatidylcholine as new therapeutic drug for ulcerative colitis--a review of three clinical trials. Expert Opin Investig Drugs. 2010 Dec;19(12):1623-30. View Abstract

[21] Jäger R, Purpura M, Kingsley M. Phospholipids and sports performance. J Int Soc Sports Nutr. 2007 Jul 25;4:5. View Full Paper

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A Conversation on Detoxification With Dr. Shade

dr-shade

"Detoxification" may seem like a buzzword tossed around these days, but it's quite a serious process. There's also a lot of misinformation surrounding heavy metals, detoxification, and traditional vs. alternative medicinal options.

Dr. Christopher Shade is a world renown expert on heavy metals detoxification and liposomal delivery of dietary supplements. In this interview with Natural Medicine Journal, he delves into his patented mercury testing and how to remove mercury and other heavy metals from the body.

He also discusses Quicksilver Scientific's industry leading liposomal supplements for detoxification.  

You can read the full article with Natural Medicine Journal here

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