A flury of manufacturers and multi-level marketers have jumped on the glutathione bandwagon in the last few years. The objective was to promote a powerful antioxidant to the masses which is integral in ridding the body of harmful substances. The problem is, this non-essential nutrient is absolutely useless as a supplement.
The reason glutathione is not an essential nutrient is that it does not have to be obtained via food since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine.
What is Glutathione?
"Glutathione is a very interesting, very small molecule that's [produced by the body and] found in every cell," says Gustavo Bounous, MD, director of research and development at Immunotec and a retired professor of surgery at McGill University in Montreal, Canada. "It's the [body's] most important antioxidant because it's within the cell."
Glutathione has multiple functions:
- It is the major endogenous antioxidant produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.
- Regulation of the nitric oxide cycle, which is critical for life but can be problematic if unregulated
- Through direct conjugation, it detoxifies many xenobiotics (foreign compounds) and carcinogens, both organic and inorganic. This includes heavy metals such as mercury, lead, and arsenic.
- It is essential for the immune system to exert its full potential, e.g., (1) modulating antigen presentation to lymphocytes, thereby influencing cytokine production and type of response (cellular or humoral) that develops, (2) enhancing proliferation of lymphocytes, thereby increasing magnitude of response, (3) enhancing killing activity of cytotoxic T cells and NK cells, and (4) regulating apoptosis, thereby maintaining control of the immune response.
- It plays a fundamental role in numerous metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs.
So clearly it is one of the most powerful antioxidants in the human body. However, no evidence currently exists in human studies showing any efficacy of glutathione supplements or more specifically, how the supplements can increase the levels of glutathione inside cells. In human studies, oral doses of glutathione had little or no effect in raising blood levels.
Despite the promising evidence about the effects of aerosol, intravenous, and intramuscular glutathione, for people with a wide variety of conditions, there is no direct evidence that taking glutathione supplements provides any benefit at all.
Glutathione supplements appear to be efficiently absorbed in rats. However, the same may not be true for glutathione supplements in humans.
For example, when seven healthy people were given a single application of up to 3,000 mg of glutathione, there was no increase in blood glutathione levels.
The authors of the study concluded "it is not feasible to increase circulating glutathione to a clinically beneficial extent by the oral administrating of a single application of 3,000 mg of glutathione."
Absorption of glutathione may be better in rats because unlike the gastrointestinal tract of rats, the human gastrointestinal tract contains significant amounts of an enzyme (gamma-glutamyltranspeptidase) that breaks down glutathione.
Supplementation with reduced glutathione does not necessarily raise tissue levels of glutathione, and it can be expensive. While the unreduced form is much cheaper, it is not metabolically active. Doctors often report that clinical benefits achieved with intravenous reduced glutathione are not seen when it is taken orally.
Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione."
Dr. Joe McCord, Winner of the Elliot Creson Medal for "co-discovering the study of free radical biology" in living organisms, stated the following regarding taking oral glutathione:
"Taking glutathione doesn't really work. Glutathione doesn't get into the cells. You can take some precursors to glutathione such as cysteine, which is used to make glutathione, but the reason cysteine doesn't get into the cells is the protein XCT, which is the gateway that lets cysteine get into the cell, and so the reason that cell can't make enough glutathione is it doesn't have enough of that XCT protein."
When asked about liposomal glutathione and if it would get into the cell, Dr. McCord stated:
"Probably not. They're still focused on fixing the problem by delivering a little packet of glutathione. Your body has 3 mmols of glutathione if it's healthy, which is a lot of glutathione. That would be taking GRAMS of glutathione to double your body's glutathione, and they don't give that much...they give a token amount. So they don't do the math, and if they did, they would see that it's just not a viable way to approach the problem."
Naturally Increasing Glutathione Production
There are co-factors or substances that can work synergestically for glutathione production. A co-factor is defined as:
1. One of two or more contributing factors.
2. A substance, such as a metallic ion or coenzyme, that must be associated with an enzyme for the enzyme to function.
Selenium, vitamins B1 and B2, Vitamin C, B6, B12, folic acid, vitamin E, and other micronutrients, are included in the substances called co-factors.
Selenium is a component of the enzyme glutathione peroxidase. Selenium functions mainly as an antioxidant, and works synergistically with Vitamin E. It is plentiful in plants and meats and supplementation is not usually necessary, but dosages of between 25-50mcg/day are recommended.
Side effects of over doses occur around 400 mcg/day and include hair loss, numbness or tingling in the fingers or toes, and white spots on fingernails and toenails. Selenium overdose leads to an indirect glutathione side effect.
Both B1 and B2 are essential and maintain GSH at its optimal capacity. Dosages between 50-150mg are suggested, while higher levels appear to show no side effects.
Vitamin C also known as ascorbate and ascorbic acid, has a long list of properties, but is also an antioxidant that works synergistically with E, and the other co-factors to allow GSH to work effectively. Dosages up to 2000 mg can be tolerated, and side effects of over dosages can lead to diarrhea and cramps. An indirect glutathione side effect.
B6, B12, play an indirect, yet important role in glutathione metabolism, while folic acid works with B12 in amino acid metabolism and protein synthesis. Dosages of 10-50mg of B6, 10-50mcg of B12, and 400mcg of folic acid are recommended per day.
Like selenium Vitamin E is an antioxidant, a detoxifier, and helps to keep glutathione in its reduced (non-oxidized) state. Dosages up to 400IU are recommended and excessive intake can be toxic creating gastrointestinal and neurological side-effects.
Milk Thistle is a natural product that has been used by herbalists for centuries. Long before anyone had ever heard about glutathione (GSH) the fruit and seeds of the milk thistle plant were used to treat liver and gall-bladder problems. Herbalists also use it to treat alcoholic cirrhosis, jaundice and hepatitis.
Silymarin, the active extract, derived from the milk thistle plant, is a powerful antioxidant shown to regenerate liver cells. Studies demonstrate that milk thistle (silymarin) protects the liver in cases of acetaminophen overdoses. Even more exciting is the fact that milk thistle (silymarin) has been shown to increase glutathione (GSH) production by as much as 35% so it is potentially useful for raising glutathione (GSH) levels.
There has also been research into the use of milk thistle (silymarin) for the treatment of prostate cancer. This research has demonstrated milk thistle (silymarin) as a potent suppressor of cancer cell growth.
The glutathione (GSH) raising potential of milk thistle (silymarin) is offset by possible side effects including gas, cramps and diarrhea. People with diabetes should use caution with milk thistle (silymarin) as it may lower blood sugar. Milk Thistle (silymarin) may also have an estrogen-like effect so it should be avoided if you have any hormone-sensitive condition such as endometriosis, uterine, breast or ovary cancer.
Glutathione is readily available in fresh fruits, vegetables and meat. You might think that eating foods rich in glutathione would raise the intracellular GSH, but research has found that it has a negligible effect.
A small amount of reduced GSH may reach the blood stream, but most of it is lost in the digestive tract, and is not effective in raising intracellular glutathione level. Increased consumption of foods rich in GSH would result in increased weight, which would be the only glutathione side effect.
It would appear that most of the articles that speak of glutathione’s limited effects are speaking only of the foods rich in glutathione.
It is an essential amino acid and has been identified as readily available in foods, and is a precursor to GSH, but the metabolic transformation into glutathione is very complex. It has side effects at certain doses that lead to toxicity, and is a precursor of homocysteine, which is identified as a high risk factor in atherosclerosis (hardening of the arteries).
Cold ambient and water temperature can have a positive impact on overall health. A study of winter swimmers hints that cold water therapy can stimulate increases in glutathione levels. One study followed ten healthy subjects who swam regularly in cold water, and compared their glutathione levels to non-winter swimmers. They found that immmediately after swimming they had an inflated amount of oxidized glutathione to total glutathione and at baseline, their “reduced glutathione” was greater while their oxidized glutathione was less than non-winter swimmers. Therefore, although immediately after a cold shower your antioxidant glutathione becomes “oxidized”, when you return to baseline the protective form will be more plentiful than it was.
It is a naturally occurring hormone synchronized by the pineal gland, and responsible for the regulation of sleep. It has many functions including acting as an antioxidant, and has been shown to effectively raise glutathione levels in the brain, liver and other tissues. There appears to be no glutathione side effects regarding this hormone, but the long term safety of this hormone has not been established.
Glutamine (GAM) is the most abundant free amino acid in the body. It is important in the maintenance and metabolism of muscle, and is a favorite supplement of athletes when involved in intense sports, because it alleviates muscle wasting.
Glutamine can be taken orally or intravenously and will raise glutathione levels. It is found in many food sources, but is destroyed by cooking. However, GAM is found in raw food including sushi, steak tartar, carpaccio and kibbi.
Healthy people do not need supplemental glutamine, and side effects of over dosing can lead to gastrointestinal upset. Indirect glutathione side effect.
Alpha-lipoic Acid (Lipoic Acid or ALA) has parallel benefits to glutathione. Lipoic acid increases the levels of glutathione.
ALA is an important antioxidant and is particularly important because it helps recycle glutathione (GSH) back into its active, fighting form. ALA’s effectiveness is due to its intimate involved with glutathione (GSH). Therefore, research shows that ALA benefits people with diabetes, HIV/AIDS, liver disease and cataracts. It also increases the endurance of body builders and speeds up muscle recovery time.
Glutathione is called the master antioxidant, because lipoic acid in the absence of GSH promotes oxidation. Glutathione would be greatly reduced in people with AIDs/HIV and Parkinson’s disease.
Recommended dosage of Lipoic acid is 50mg to100mg.Higher dosages can lead to nausea, upset stomach, rash, and even low blood pressure. Again this would be an indirect glutathione side effect.
Whey Proteins are a constituent of milk from all mammals including humans. Milk contains 5-10% protein, where 20% is whey and 80% casein. Denaturation refers to the breakdown in the structure of the protein that will not affect its food value, but will result in less availability (bioactivity) of the active components to the cells of the body.
It is the bioactivity that creates the benefits to the body. Fresh milk is easily denatured, leaving its potent GSH precursors ineffective.
Special processes must be employed to extract the whey from protein and to maintain its bioactivity. Whey products contain anywhere from 20% to 90% whey, some are bioactive and many are not.
Stay away from Multi-level marketers that try and convince you that oral supplement forms of glutathione are effective. Stick to natural co-factors and substances that help to naturally increase your glutathione production. When all else fails, take a cold shower!
Marco Torres is a research specialist, writer and consumer advocate for healthy lifestyles. He holds degrees in Public Health and Environmental Science and is a professional speaker on topics such as disease prevention, environmental toxins and health policy.