As the body’s master antioxidant, glutathione is one of the hardest-working, endogenous compounds in the body. In fact, production of glutathione is not limited to mammalian cells, but occurs to some degree in nearly every living thing.1
Based on the amino acid cysteine, glutathione is a tripeptide that also includes glycine and glutamic acid. The critical input is cysteine, however, as it possesses the thiol (-SH) group that confers much of the compound’s functionality and serves as the rate-limiting factor in endogenous production.2
The role of glutathione in the development of life on Earth is so important, some scientists have speculated that life may not have evolved without it.1 Production of glutathione occurs in the cytosol and is then supplied to the mitochondria, where its antioxidant power serves a critical function in reducing methylglyoxal, a toxic oxidative metabolite, into a harmless compound. It also contributes in production of red and white blood cells, supports eye health, and generally benefits overall human health.
Although the protection of mitochondria would likely be enough, by itself, to make glutathione’s effects worth researching, glutathione has become known as the master antioxidant because of the many functions it carries out in the body. “It helps support the immune system and proper functioning in the immune system,” said Danielle Citrolo, PharmD, director of science and regulatory affairs at Kyowa Hakko USA, manufacturer of pharmaceuticals, supplements, and ingredients. “It also helps the liver detoxify some of the harmful substances we are exposed to, whether they are pesticides from food, gas and diesel fumes, or other pollutants in the environment. Drugs, smoking, alcohol—all those things basically provide our bodies with oxidants, chemicals that are harmful to the cells, and then taxing our livers if we ingest any of them. Glutathione is there to rescue our cells and not let them be harmed by these insults, then it helps process those toxins so they can be excreted without creating more harm to the body.”
In this detoxification role, its antioxidant action against endogenous toxins has already been discussed, but it also neutralizes xenobiotic oxidants. It binds to lipophilic toxins and persistent organic pollutants, making them water-soluble so they can harmlessly enter the bloodstream and be flushed out by the kidneys. It acts on heavy metals, conjugating and neutralizing them for excretion. It allows the liver to suspend lipophilic toxins in bile and shed them from the body. In most of these reactions glutathione is assisted by a catalyst, but it is capable of acting directly such as in the case of acetaminophen and some heavy metals.
Dr Citrolo said that glutathione has also been shown to recycle other antioxidants. “The most important one is vitamin C, which people know pretty well,” she said. “When vitamin C acts as an antioxidant, it then becomes oxidized itself. In order to become reduced again, or to continue acting as an antioxidant, glutathione is involved in the pathway that returns vitamin C to its reduced form. Glutathione actually works with other antioxidants, too. By recycling vitamin C it also helps recycle vitamin E; its effects are overwhelming. Unlike other ingredients we work on, which are so simple, this one is diverse in terms of benefits. There is tons of science on glutathione, and I don’t even think we have begun to understand all the things that it does.”
Because it is made in the body, glutathione is a natural part of human physiology. “Our bodies are very good at making it and keep a tight threshold on the glutathione level, because it’s so important,” she said.
“There is research out there showing a link between people who consume higher levels or that have higher blood levels of glutathione and having a lower risk of various diseases. The particular study I am thinking of dealt with cancer. So, an indirect link to disease exists. We understand that glutathione prevents oxidation, damage to our cells and organs, and cell death that when unchecked, lead to the oxidative stress which is indirectly related to various diseases.”
Dr Citrolo cautions that glutathione levels eventually become an issue for everybody. “There was also a study published clearly showing that as we age, levels of glutathione drop significantly in our bodies. It could be that metabolic processes slow down, like with everything else. Glutathione seems, however, to be something that we may need to supplement as we get older. We think we can make enough, but it all depends on our lifestyles and our diets, whether we have enough to fight the various lifestyle choices—even excessive exercise can deplete glutathione.
From the perspective of diet, it is possible to augment glutathione levels with food according to Dr Citrolo. “The problem is that it has a stability issue, so any cooking, any processing, basically denatures it so you don’t get as much. There is data about dietary consumption of glutathione. Beef contains quite a bit—a hamburger has almost 18 milligrams per 100 grams. You don’t want to cook it to death, but even cooked it still has glutathione, and I think we have established the amount present with cooked and raw. Eggs are another good source, and even broccoli and carrots have a good amount. Foods like leafy greens are pretty high. Fruits; apples are pretty good source, but actually the highest levels are in oranges.”
From a direct supplementation standpoint, there is little doubt concerning the body’s ability to take up and use glutathione when delivered in topical, intravenous, intranasal, or nebulized forms. Some debate exists regarding oral supplementation, with evidence pointing both ways in the literature.
“The body can utilize it either as whole glutathione or break it down into its constituent amino acids, said Dr Citrolo. “The body is going to control the levels and I think that’s why some of the previous pharmacokinetic data does not show an immediate jump in the glutathione levels. Our study was published with our oral glutathione product, Setria. I asked our researchers a lot about that phenomenon; the body keeps a tight control over the levels, and so it takes a long time to build up in the body. It took us 6 months to see a significant increase. I obviously wouldn’t recommend taking excessive amounts. But, I think supplementing is an effective way to keep your levels of glutathione to the normal high side, and along with that comes the many benefits we’ve discussed.
From a manufacturing standpoint, Dr Citrolo does not have the exposure to comment on other companies’ production methods, but she can shine a light on how Kyowa Hakko’s Setria Glutathione product is made. “Currently we produce the Setria Glutathione by actually using a direct microbe production,” she said. “We now make all our products that way; we are experts in fermentation. Plant-based glucose is the starting material. Using a microbe to produce the glutathione is the ideal, because you get a more pure product without any potential synthetic contamination. It’s basically a living cell producing it like our bodies would produce it, so that’s the most natural form. It then goes through an ultrapurification process. We do produce glutathione for pharmaceuticals—some other countries consider it that way, but in the United States it is classified as a supplement.”
Research continues to reveal additional applications for glutathione. According to Dr Citrolo, Kyowa Hakko plans to continue adding to the science behind its Setria product, and others are following suit. “Sports is definitely a growing area for glutathione,” she said. “Another area that is already huge in the Asia is the beauty from within category. We’re getting a lot of buzz there. When I went to Japan for the first time, they gave me shots of collagen. Now, you are seeing that here. So, as beauty from within becomes more well-known, it will generate a lot more interest in glutathione. In Asia, it’s been around for a long time. People there have been taking it for system support in terms of beauty because of anti-aging effects and preventing damage to the skin. It helps protect skin from the sun and inhibits related darkening. These uses are just beginning, but I think you are going to see more and more, and we are working on the science there.
To learn more about Setria® Glutatione visit www.setriaglutathione.com
- https://pubchem.ncbi.nlm.nih.gov/compound/124886#section=Metabolite-Description Section 10.5.1 Metabolite Description. Accessed 04/15/2019
- Pizzorno, J. Glutathione! Integrative Medicine: A Clinician’s Journal. 2014;13(1):8-12.