Glutathione is known to be a critical component of both the antioxidant and detoxification systems.
Glutathione is a tripeptide, a naturally occurring protein that is composed of three amino acids: glycine, glutamine and cysteine. It is made by every cell in the human body and it plays a part in the function of every cell in the body. Glutathione also contains a sulfur molecule. Sulfur plays a major role in glutathione’s antioxidant and detoxification functions, and it also gives glutathione its distinctive sulfurous aroma.
Powerful Antioxidant
While vitamin C and vitamin E are better known, the ability of glutathione to work with enzymes makes it the more reliable antioxidant workhorse for the human antioxidant system. When nutrients are discussed, the topic of oxidative stress frequently comes up. Oxidative stress refers to the changes that occur in the biochemistry of molecules in the body when they interact with oxygen. In the outside world oxidative stress shows up as rust. Inside the body, oxidative stress is harder to visualize, but it causes damage to cells and the membranes of cells.
Without adequate glutathione function, oxygen metabolism in the energy producing sites in the cell called mitochondria can form an increased number of free radicals. Free radicals are electron “hungry” and will pull electrons from surrounding structures such as proteins or membranes, causing them to stop functioning normally. When this happens it is called “free radical damage,” which will cause a decrease in the function of the cell. Free radicals must be neutralized or this “rust” will cause cells to perform poorly or die. Accumulation of damage to cells leads to problems in entire organs and eventually disease. Illnesses such as the Chronic Fatigue Syndrome may be related to decreased energy production from individual cells.11
Glutathione is one of the major defenders against oxidative stress. In its “reduced” (active) form it can donate an electron and behave as an antioxidant. After losing an electron, it becomes non-functional, or “oxidized.” The ratio of reduced to oxidized glutathione in cells is a measure of oxidative stress. Studies have shown that oxidative stress increases with aging and it is no wonder that over time free radicals can lead to degenerative diseases: heart disease, memory problems, cancer, diabetes, arthritis.
The discovery and path of understanding of glutathione began in 1888, culminating in 1926 when its structure was finally determined.1-2 Glutathione is so important to the utilization of oxygen in our bodies that is difficult to write about oxidative stress without mentioning it, so glutathione shows up often in the scientific literature. In 1999 a single-word search on glutathione pointed out that 40,000 articles were found in the government library under the search term “glutathione.”3 In the past ten years, this number has more than doubled and is now over 87,000 references. The numbers of research articles show that research into the role that glutathione plays in maintaining cell function is ongoing and important.
In certain disease conditions, glutathione does not get manufactured as efficiently as needed. The lack of glutathione can result in disease conditions from a systemic decrease as we see in atherosclerosis. Glutathione can also be deficient in local tissues as has been shown with asthma.4 In situations where there is a lot of oxidative stress, as occurs in diabetes that is not well controlled, glutathione is not formed and becomes deficient even when the building block amino acids such as cysteine are abundantly available.5
The Great Detoxifier
Glutathione is also known as a detoxifying agent. Most toxins are able to pass through fatty membranes, so they tend to accumulate inside of cells. Binding toxins with glutathione makes the combination water soluble and allows its removal.
The liver harbors the most concentrated source of glutathione because it is the organ of detoxification. Your body uses glutathione to protect you from pollution, radiation, drugs, carcinogenic chemicals and heavy metals. Modern living even exposes us to toxins in our water and food. Dealing with this onslaught is especially difficult for people with certain neurological conditions such as autism, because they have difficulty ridding their bodies of toxins.
Glutathione has the ability to bind with toxins directly, especially if the correct type of matchmaker enzyme is present. About 10-30 percent of the population will not have this enzyme that enhances glutathione function,7 and in these cases increasing the presence of glutathione may help increase the chance of a GSH molecule matching up with a toxin.
Toxins such as mercury are removed from the body by direct conjugation with glutathione.8
Glutathione can attach to metals and other toxins directly and there is an extensive list of biochemicals that can be bound to glutathione.9 Once bound to glutathione, toxins become water soluble and can be transported out of the cell and out through the liver for excretion. Maintaining normal bowel flora and a high-fiber diet is important during detoxification to prevent the reabsorption of toxins like methyl mercury from the bowel.10 Other toxins, such as those produced from molds or fungus called mycotoxins have also been shown to cause an increase in oxidative stress and will also deplete glutathione. With all the roles that glutathione plays, it is easy to see why there are so many articles written about glutathione in the medical science literature.
Glutathione and Disease
We have already mentioned several health conditions in which glutathione plays a role. In addition, studies have shown that alcoholics have low glutathione and so do people with Alzheimer’s disease. Cigarette smoking depletes glutathione, and children with autism are predisposed to low glutathione so they cannot detoxify normally. Glutathione is suggested as a promising treatment to combat the oxidative stress found in HIV-infected people. Long-lived women have high levels of glutathione, and people with Parkinson’s disease often benefit from treatment with glutathione. It also is posited that the oxidative stress that depletes cells of glutathione increases vulnerability to influenza.
Because heart muscle requires a lot of energy for its continual function, it has the largest number of mitochondria per cell of any tissue in the body. It would be logical to expect that glutathione is also needed in the heart muscle cells to maintain function. It turns out that studies have shown that a deficiency of glutathione is correlated with the recurrence of heart problems after heart attacks.12 It has also been shown that low glutathione is associated with the progression of coronary artery disease even in healthy adults.13
Liposomal Glutathione
Recent developments with a liposomal form of glutathione suggest that wrapping glutathione in a tiny lipid bubble called a liposome is an excellent way to keep glutathione stable and make it available for use in cells.6 A liposome is an extremely small (1/2 the width of a human hair) bubble, which is also called a vesicle. Liposomes have a fat-soluble exterior and an interior that is watery. This watery interior can combine with water soluble materials such as glutathione.
Liposomes are made from the same type of material as our cell membranes, phospholipids. Because they are made of the same type of material as our cell membranes, liposomes penetrate mucosal tissues allowing for rapid release into the blood stream. Nutrients that are not in liposomes have to pass through the stomach to reach the liver where they are metabolized and released into the bloodstream. Some nutrients are destroyed or compromised by stomach acids. Liposomes avoid the digestive system by penetrating the mucosal tissue.
Laboratory testing shows that the liposome can maintain glutathione in the biochemical “reduced” state, the state that means it is active and can donate an electron as an antioxidant. In an animal study, Liposomal Glutathione was able to maintain the function of glutathione allowing the scavenger cells to metabolize cholesterol and slow the deposition and progression of plaque in the arteries.14 Further studies will be needed before a definitive statement about the role that glutathione plays in maintaining normal function in the cells lining arteries can be made.
LipoCeutical™ Glutathione, now available here as a dietary supplement, is a promising way to obtain a crucial antioxidant that has a wide role to play in health.
References
1. Simoni RD, Hill RL, Vaughan M. On glutathione. II. A thermostable oxidation-reduction system (Hopkins, F. G., and Dixon, M. (1922) J. Biol. Chem. 54, 527-563). The Journal of biological chemistry. 2002;277(24):e13.
2. Meister A. On the discovery of glutathione. Trends in biochemical sciences. 1988;13(5):185-8.
3. Sies H. Glutathione and its role in cellular functions. Free radical biology & medicine. 1999;27(9-10):916-21.
4. Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA. Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. The Journal of allergy and clinical immunology. 2009;123(1):146-52 e8.
5. Darmaun D, Smith SD, Sweeten S, Hartman BK, Welch S, Mauras N. Poorly controlled type 1 diabetes is associated with altered glutathione homeostasis in adolescents: apparent resistance to N-acetylcysteine supplementation. Pediatric diabetes. 2008;9(6):577-82.
6. Zeevalk G, Guilford F, Bernard L. Liposomal glutathione for replenishment and maintenance of intracellular glutathione in mesencephalic cultures. Abstract Neuroscience 2009: Soc. for Neuroscience 2009.
7. Kempkes M, Golka K, Reich S, Reckwitz T, Bolt HM. Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder. Archives of toxicology. 1996;71(1-2):123-6.
8. Clarkson TW, Vyas JB, Ballatori N. Mechanisms of mercury disposition in the body. Am J Ind Med. 2007;50(10):757-64.
9. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biological chemistry. 2009.
10. Rowland IR, Mallett AK, Flynn J, Hargreaves RJ. The effect of various dietary fibres on tissue concentration and chemical form of mercury after methylmercury exposure in mice. Archives of toxicology. 1986;59(2):94-8.
11. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. International journal of clinical and experimental medicine. 2009;2(1):1-16.
12. De Chiara B, Mafrici A, Campolo J, Famoso G, Sedda V, Parolini M, et al. Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events. Coron Artery Dis. 2007;18(2):77-82.
13. Ashfaq S, Abramson JL, Jones DP, Rhodes SD, Weintraub WS, Hooper WC, et al. The relationship between plasma levels of oxidized and reduced thiols and early atherosclerosis in healthy adults. Journal of the American College of Cardiology. 2006;47(5):1005-11.
14. Rosenblat M, Volkova N, Coleman R, Aviram M. Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice. Atherosclerosis. 2007;195(2):e61-8.