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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