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To begin, glutathione is a powerful antioxidant created in our cells that has been shown to fight cellular inflammation, detoxify cells, improve liver function and support the immune system. Glutathione (GSH) is not an essential nutrient since it is synthesized from three amino acids:
In fact none of the three amino acids are essential nutrients either since all of them can be synthesized from various proteins that we consume. L-cysteine is synthesized from the essential amino acid methionine. L-glutamic acid is synthesized from glutamine (among others) and its salts (electrical neutral compounds) are called glutamates of which our old friend and headache maker, MSG (monosodium glutamate) is one. Glycine is synthesized in the body from the amino acid serine. GSH is synthesized in the cell by way of two adenosine triphosphate (ATP) dependent steps.
Recall that adenosine triphosphate (ATP) is created in the mitochondria of the cell and is used as a source of chemical energy. For this reason, mitochondria are often referred to as the cells power plant. ATP is a cofactor; that is, a chemical compound that is required for the protein's biological activity. These proteins are commonly enzymes and cofactors (or coenzymes) and can be considered "helper molecules and/or ions" that assist in biochemical transformations. Having reviewed ATP, we can now describe steps one and two in the synthesis of glutathione. In step one, two of the three amino acids, L-glutamate and L-cysteine, in conjunction with an enzyme, gamma-glutamylcysteine synthetase (glutamate cysteine ligase, GCL), form the protein gamma-glutamylcysteine. This first step is rate limiting; in other words, it controls how fast glutathione can be synthesized. In step two, the third amino acid, glycine, is added to gamma-glutamylcysteine (the product of step one), using another enzyme glutathione synthetase. The product of step two is glutathione. As you might have gathered, any chemical substance that ends in "ase" is most likely an enzyme. Amylase and lipase are two enzymes in saliva that break down protein and fats respectively. A logical question might be, "Why does glutathione have to be synthesized in the cell?" and the answer is that the GSH molecule is too big to be taken into the cell directly; thus the building blocks (the three amino acids) enter the cell where the ATP already resides and then the two-step construction process can proceed. Attempts have been made to create GSH supplements but have not been very successful due to the small molecular size plus the fact that when the preformed GSH hits the digestive tract, the proteins get digested and it is destroyed. So even if it were of a size suitable for absorption, the digestive environment would preclude it from ever having a chance to be absorbed. Our choices then become one of ensuring that we get enough of the three glutathione building blocks in our food or supplement with the three components (or both). There are also several other natural substances that enhance the conversion of proteins to GSH and are necessary for the recycling of glutathione, both of which will be discussed shortly. Looking for something? Use the Google Search Box! Before going on, note the Google Search Box below. It is here to use in locating anything on the Healthy by Nature website. just type in your search term, hit the "Search" button and a list of URLs containing the requested information will appear.
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Food Sources of the Glutathione ComponentsSince GSH synthesis depends on the presence of certain amino acids, it figures that most foods rich in protein would be good sources of the basic building blocks, and they are. L-cysteine is found in most high-protein foods, including pork, sausage meat, chicken, turkey, duck, luncheon meat, eggs, milk, whey protein, ricotta, cottage cheese and yogurt. Vegetable sources include red peppers, garlic, onions, broccoli, Brussels sprouts, oats, granola and wheat germ. Whey protein contains 8 times more of the amino-acid cysteine than casein, a protein that accounts for about 80% of the protein in cow’s milk and cheese. However, it is important that if one is supplementing whey protein for GSH production, it must be bio-active, meaning not denatured and not pasteurized. L-glutamic acid comes from all meats, poultry, fish, eggs and dairy products. An edible kelp known as kombu, or konbu, in Japan is extremely rich in glutamic acid. In addition, some protein-rich plant foods are also good sources, Ninety-five percent of the dietary glutamate is metabolized by intestinal cells. Glycine also comes from high-protein foods, such as fish, meat, beans, milk, and cheese. If the protein building blocks are so plentiful in such common foods, why should we ever have low GSH levels, especially as we age? The answer most likely is in the cooking and preparation. These proteins are delicate and can be injured or destroyed by heat or by rapid agitation such as blending. So we think we are getting a lot of the three amino acids from eggs? Not if they are fried, poached, scrambled, hard boiled or whipped into a froth and baked into grandma’s pies and cakes. For GSH purposes at least, raw is the way to go when it comes to eggs and other amino acid containing foods. So who eats raw eggs, raw meat or raw fish (besides the Japanese)? Not many people in North America. Well, that leaves us with glutathione supporting supplements. Read on. Glutathione Support SupplementationThere are several products on the market that attempt to function as glutathione supplements but three stand out and are discussed below. None of the three involve the direct intake of glutathione for reasons previously given; namely that it doesn't work. Rather all three take the more proven approach of providing nutrients that cells can absorb and use to produce GSH. Furthermore, all three use the network marketing sales model and none of the products are sold in retail establishments. MaxGXL, from Max International in Salt Lake city, Utah, is a product uniquely designed and focused on supporting the cellular production of glutathione. It is arguably the best, most effective product of its type on the market today; in fact, due to the company’s tight patents, it may be the only product of its type on the market.
MaxGXL incorporates the GSH building blocks and supporting nutrients into its menu of ingredients. From the label, MaxGXL has fairly high levels of the GSH building blocks; 750 mg of L-Glutamine per serving which would give us 1500 mg if taking the recommended two servings per day and 375 mg of N-acetyl-cysteine (NAC) for 750 mg per day. The GSH recycling and absorption blend consisting of 488 mg (976 mg/day) of cordyceps, N-acetyl-D-glucosamine, quercetin, and milk thistle extract is a super supporting cast for the GSH toolkit. And the daily 150 mg of alpha lipoic acid (ALA) and 500 mg/day of vitamin C round out a great list of ingredients. ALA is so important to glutathione support that it will be discussed separately later in the article. MaxGXL™ is described as a compositionally patented nutritional product developed by the immunologist, Dr. Robert Keller. After ten years or so of research and development, Dr. Keller succeeded in creating a product that provides the necessary components of GSH that are not destroyed in the GI tract and that are absorbed readily through the cell membrane. The end result is the stimulation of the body’s own production of glutathione that is used by every cell in the body, all 60 trillion of them, give or take a few trillion.
Sadly, Dr. Robert H. Keller, MD, MS, FACP, the creator of the MaxGXL formula passed away on June 5, 2009 from Amyloidosis, a very rare abnormal deposition of protein mass in various organs and tissues, resulting in total organ shutdown. According to the Mayo Clinic, there is no known cause or cure. As an aside, several amyloid proteins are associated with catastrophic human diseases; for example, beta amyloid is associated with Alzheimer's disease.
Of late, Max International has been on an expansion path, having acquired the Glutathione technology company, Cellgevity, as announced by the company on June 27, 2009. MAX International is a young company, having been founded in February 2007 and if all goes as planned, should become a household name in the health and wellness industry. So far it is a privately held company. As a proud independant associate of Max International, I invite you to visit https://HealthyByNature.max4U.com for more information on Max International and its products and to order or become an associate yourself to take advantage of this ground floor opportunity. You are also free to contact me for further information on MaxGXL and how to obtain it.
The next product to be discussed is Immunocal from Immunotec, Inc. in Quebec, Canada. Immunocal is a public company, listed on the Toronto Stock Exchange under the symbol IMM.
They provide a glutathione support product based on the amino acid building blocks but take a different approach than does Max International. Immunocal gets its building blocks (the GSH precursors) from whey protein. Their product is described as an "all-natural non-prescription health product available worldwide". It is also patented worldwide. Immunocal is the result of years of research by Dr. Gustavo Bounous, MD who is a strong believer that "nature holds many secrets for optimal health. Secrets that are hidden and waiting to be discovered by anyone willing to put in the time and effort necessary to uncover them." Sounds a bit like the quote from Paracelsus who said, "All that man needs for health and healing has been provided by God in nature, the challenge of science is to find it." Therefore the physician must start from nature and proceed with an open mind.
From company literature, it takes about 125 gallons of fresh raw milk to make a pound of Immunocal. The end product is a derivative of whey protein isolate engineered to have the highest amounts of glutathione precursors possible. Before talking about what GSH is, and what it does, let’s look at some of the benefits of taking Immunocal, besides its clinically-proven ability to raise glutathione levels. Whey protein, especially whey protein isolates (over 90% protein); supply most of what we need for muscle mass generation. It is sometimes referred to as the “perfect” protein, because it contains all the essential amino acids required for the body’s protein synthesis. With a biological value (BV) of over 110, it would be challenging to find a whey protein utilized more efficiently than Immunocal. Immunocal's website is http://www.immunocal.com/ or if you want more in-depth reading on Immunocal or whey protein, a couple of recommended websites are: "Glutathione: New Supplement on the Block" at MedicineNet.com is an article from WebMD that talks a bit about Dr. Bounous and Immunocal. Click on "Cure-all or Snake Oil" by Alison Palkhivala to read it. For information on whey protein, click on A Former Fat Guy's website, which would be Will Brink, a fitness columnist and writer for various fitness, medical and body building publications who has written an article covering everything you want to know about whey protein and its processing.
Mannatech is a supplement producer based in the Dallas, Texas suburb of Coppell, offering a stable of 30 or more products focused on the whole body approach to health and wellness. Most of their products are based on the science of glycobiology and its flagship product, Ambrotose. Ambrotose is a blend of bioactive sugars referred to as glyconutrients and work to enhance cell-to-cell communications and stems from early research on the healing properties of Aloe Vera.
Mannatech has no glutathione product per se but six of their product family members collectively contain all the ingredients necessary for the cellular production and support of GSH, taking the same approach as MaxGXL. Another of Mannatech's products focused on weight loss is based on whey protein as in the approach taken by Immunocal.
Mannatech's products are designed to address the basic areas of health and wellness: intercellular communication; regulation of the endocrine system and hormone balance; nutrition; and anti-oxidant protection from free-radicals, toxins, stress and other harmful effects of daily living. Mannatech's PLUS product is an herbal-amino acid caplet containing (per serving):
Their Phytomatrix vitamin, mineral and phytochemical product contains 100% of the daily requirement for:
The antioxidant product Ambrotose AO provides antioxidant cell protection and immune support with:
The phyto formula is interesting and relevant to glutathione support in that it contains a wide spectrum of cruciferous vegetable extracts including broccoli, Brussels sprouts, cabbage leaf, carrot, cauliflower, garlic, kale, onion, tomato, turnip, papaya and pineapple juice powder. A heart health formula called CardioBalance contains the third GSH building block, N-acetylcysteine. Mannatech's OsoLean is a targeted weight loss product that contains partially hydrolyzed whey protein isolate. The objective of OsoLean is not glutathione production but the whey protein would be expected to have much the same effect on glutathione levels as Immunocal. It seems odd that Mannatech would not have come out with a dedicated glutathione product by now especially since they have all the required ingredients in the various products named above. It shouldn't be all that difficult to structure a GSH formula that would not infringe on existing patents of the competing companies. Mannatech's website is http://www.mannatech.com or contact me for more information on these products and how to get them or visit the supplement section of the website's mall.
Supplementation of GlutathioneAs we alluded to earlier, supplementing GSH directly has been difficult. Research suggests that it is not well absorbed in the Gastrointestinal tract due to its molecular size and acidic environment of the digestive tract. In a study of oral administration of a very large dose (3 grams) of GSH, it was found that 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. The following is a U-tube video by Dr. Mark Hyman, M.D. and co-author of the "UltraPrevention" books that have been highly recommended throughout this "Healthy by Nature" website. It would be productive and highly informative to take time now to watch this nine minute video and then read on for additional discussion of Dr. Hyman's comments on GSH supplementation. To my knowledge, Dr. Hyman is not selling any products and his tutorial should be totally unbiased by commercial considerations.
The Genetic ConnectionAs Dr. Hyman alluded to in the video, there is a genetic connection to low GSH levels. A gene designated GSTM1 (glutathione S-transferase Mu 1) is a human glutathione S-transferase (GST) enzyme thought to play a role in the biotransformation of pollutants, drugs, toxins, all generally known as xenobiotics. GSTM1 is one of the family of glutathione S-transferases, which allow GSH to interact with harmful organic hydroperoxides to neutralize and excrete them from the body. There is strong evidence linking chronic fatigue syndrome and GSTM1 dysfunction. It is possible that the effectiveness of GSH supplementation in those with chronic fatigue syndrome may be in part dependent upon their genetic status with reference to the GSTM1 gene. It is also possible to possess a mutant genetic makeup (GSTM1-0/0) that does not allow for the production of GSH. It has been estimated that 40-60% of the population may have two copies (one from each parent) of the same mutant form of the GSTM1 gene, lacking that gene's normal function. The health outlook for chronic fatigue patients with GSTM1-0/0 is worse than for those who do not possess that genetic make-up. If someone is in that population without an active GSTM1 gene, they may need to compensate by eating more broccoli or by eating “super broccoli” that has higher levels of the active plant chemical sulforaphane. Consuming larger portions of broccoli or super broccoli makes it possible to retain greater amounts of sulforaphane not to mention other vitamins and minerals. Considering that most of us have no idea what type of GSTM1 gene we carry nor do we know how much broccoli is enough, eating broccoli and other cruciferous vegetables as part of a healthy lifestyle is highly recommended. If someone can't handle all that broccoli, then consider broccoli sprouts in salads or on sandwiches. They are higher in sufloraphane anyway. Genetics aside, as Dr. Hyman stated, as we age our levels of glutathione steadily decline.
This correlates with his observations that the lowest GSH levels are seen in the oldest, sickest, hospitalized patients and the highest levels in the younger, healthier individuals. The chart illustrates this quite well.
The good news is that with supplementation by a product such as MaxGXL, glutathione levels are restored across all groups, both healthy and catastrophically ill. ![]() The chart above illustrates the remarkable increase in GSH after even short periods of supplementation.
Methylation refers to the attachment or substitution of a methyl hydrocarbon group on various molecules through the interaction of appropriate enzymes. It's called methylation because the hydrocarbon in question is methane and in human biochemistry, a hydrogen atom gets replaced with the methyl group. Dr. Van Konynenburg, PhD., an independent researcher in glutathione and the methylation cycle for many years, believes that the fundamental biochemical issue in a large subset of chronic fatigue syndrome (CFS) patients is that the methylation cycle is blocked. The main goal of this treatment approach is to remove this block and restore the methylation cycle. He also believes that glutathione depletion is directly responsible for many of the features of CFS, but that it is usually not possible to normalize the GSH levels on a permanent basis by direct supplementation of glutathione building blocks. Rather, the methylation cycle block must be corrected first to break the cycle that is holding down the glutathione levels. In addition to this, about one-third of CFS patients, because of particular genetic mutations described in the previous paragraph, cannot tolerate supplementation with GSH or other substances intended to help them directly build glutathione. In biological systems, methylation is enabled by enzymes and is extremely important in several areas. Methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA metabolism. Methylation of heavy metals can also occur outside of biological systems. Thus, if the process is blocked and unable to occur, we will have problems in a lot more areas than chronic fatigue. For a very comprehensive article on the methylation cycle including a list of supplements to take to get the cycle kick-started once it has stalled, go to Dr. Myhill's site, "CFS-The Methylation Cycle-Updated May 2009".
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How about a cosmetic application for the Mother of all Antioxidants.
Skin WhiteningWho would ever believe an antioxidant could be used to lighten dark skin? Nevertheless, GSH has recently been used by the cosmetics industry to inhibit melanin. Melanin is the substance that gives skin its color and is formed as part of the process of metabolizing the amino acid tyrosine.
It's not so hard to believe knowing that GSH is the product of enzyme reactions on several amino acids driven by cellular adenosine triphosphate. Melanin production is dependent on reactions involving the amino acid enzyme tyrosinase and the dopamine precursor L-Dopa.
GSH has been shown in studies to inhibit melanin synthesis in the reaction of tyrosinase and L-DOPA.
When melanin synthesis was inhibited, it was restored by increasing the concentration of L-DOPA, but not by increasing tyrosinase indicating that GSH inhibited the binding between tyrosinase and L-DOPA. Although the synthesized melanin was concentrated within an hour, the aggregation or concentration was inhibited by the addition of glutathione.
These results indicate that glutathione inhibits the creation and joining of melanin molecules by interrupting the function of L-DOPA. The end result of the inhibition is a reduction of melanin in the skin and thus a lighter skin color.
So because of the relationship between GSH, L-dopa and tyrosinease, we have a whole host of cosmetic products designed to make dark skin lighter. In several countries, glutathione products (or counterfeit GSH) are sold as whitening soaps, creams or lotions.
GSH and Acetaminophen
Acetaminophen, the active ingredient in Tylenol, has been in the news lately for its implication in liver failure.
The FDA will likely put new restrictions on acetaminophen per an advisory committee recommendation, saying "the move would protect people from the potential toxicity that can cause liver failure and even death".
The implications for glutathione and treatment of acetaminophen toxicity are impressive.
Baby mice have a story to tell. While every cell in the human body is capable of synthesizing GSH, liver synthesis of glutathione has been shown to be essential.
If fetal mice are genetically modified to block the synthesis of GSH only in their liver, they will die within 1 month of birth. So the ability of the liver to correctly construct glutathione would seem to be a life or death proposition.
Thus it follows that if acetaminophen toxifies a liver to the point of failure and knowing that GSH is the best antioxidant and detoxifying agent known and if GSH levels in the body and liver in particular are low, the patient’s fate is sealed.
The very scientific description of the acetaminophen and glutathione reactions as given in Wikipedia is,
However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of N-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by acetaminophen that becomes toxic when GSH is depleted by an overdose of acetaminophen".
and furthermore...
"Glutathione conjugates to NAPQI and helps to detoxify it, in this capacity protects cellular protein thiol groups, which would otherwise become covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process.
The preferred treatment for an overdose of this painkiller is the administration of N-acetyl-L-cysteine, which is processed by cells to L-cysteine and used in the de novo synthesis of GSH."
What all this means in plain English is that if we take large doses of Tylenol (or any acetaminophen compound) we should keep our GSH levels as high as possible because it protects and detoxifies the liver. Now wasn't that easy?
In leaving "Glutathione", the message should be clear that everyone needs to maintain their intracellular levels of GSH as high as possible and the only way to do that these days is through supplementation.
Contact Me for more information on products containing the glutathione building blocks, whey protein and GSH support nutrients. It is never too late to start; well it might be too late when they start to shovel the dirt onto our casket.
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