March 2011 -Glutathione is an endogenously produced compound that protects the body against the bombardment of free radicals. Free radicals attack the polyunsaturated fatty acids (PUFA) in the cell membranes of tissues. PUFA oxidation occurs via a free radical chain mechanism that proceeds through several stages leading to a series of complex chemical changes. PUFAs will lose a hydrogen atom from their backbone and produce “free radicals” which then react with oxygen to form peroxides, which then attack a new lipid molecule. This can lead to tissue damage and is often associated with age-related cellular damage.

 

Glutathione is composed of three amino acids: glutamate, cysteine and glycine; it can be found in all body tissues and fluids but primarily in the detoxifying organs--the liver and kidneys. Research has observed lower levels of glutathione in adults over 45 years old, in comparison to younger people.

Glutathione donates electrons to oxidants to sequester, or squelch, their free radical activity, helping to prevent DNA damage and subsequent chronic disease. Glutathione disulphide, the oxidized form of glutathione that has already reacted with a free radical, is also present in the body. Elevated levels of glutathione disulphide are an indication of a large utilization of glutathione and are often observed in individuals over the age of 45.¹

People that are under oxidative stress, such as smokers, alcoholics and diabetics, have lower levels of glutathione and elevated levels of glutathione disulphide. Elevated levels of glutathione disulfide are associated with increased carotid intima media thickness, a measurement of the thickness of artery walls and an indication of cardiovascular disease risk.¹

Glutathione is present in fresh vegetables and fruits, nuts and non-processed poultry and fish. A diet rich in these foods contains approximately 150mg of glutathione. Processing, such as canning, curing and drying significantly reduce glutathione levels present in food. Additionally, items such as milk, blueberries, bottled apple juice and tea contain glutathione-reactive compounds that reduce the amount of glutathione present in food or lining of the small intestine.¹

The Recommended Dietary Allowance (RDA) for sulphur-containing amino acids (precursors to glutathione) is 1.1 g/day for women and 1.4 g/day for men, which is equivalent to 2.7 and 3.3g of glutathione/day. Some 99% of Americans consume above this recommendation for sulphur-containing amino acids. Therefore, supplementation with amino acids and N-acetylcysteine to increase glutathione in the body will likely only benefit individuals that do not consume enough of these amino acids or who are under oxidative stress. ¹

“Although most Americans consume an adequate supply of dietary precursors for GSH {glutathione} synthesis, there is a gap between the amount synthesized and the amount needed (i.e., a decline in GSH is associated with disease risk)...higher values may be needed to compensate for adverse environmental conditions and disease, but the possible amounts can only be speculated.” ¹

Research has indicated that supplemental glutathione results in increased plasma glutathione levels in humans, despite an expected degradation that may occur in the intestine. Animal research with glutathione supplementation has indicated improvements in immune function,² protection against oxidant injury in newborn lungs,³ reduction in the uptake of oxidized lipids⁴  and protection against other toxic chemicals.⁵ Human research has shown that glutathione from raw fruits and vegetables is associated with a reduced risk of oral cancer⁶ and supplementation with glutathione can prevent nephrotoxicity associated with cancer treatment.⁷ Clinical trials are needed to confirm glutathione supplementation and the proposed associated health benefits seen in animal studies.

Other nutrients can aid in maintaining glutathione status (such as zinc and selenium, which play a role in glutathione synthesis). Antioxidants can also aid in protecting the body against oxidative injury and can help maintain glutathione levels. Other compounds can stimulate liver production of glutathione (such as silymarin, which is present in milk thistle).¹

An optimal diet supplies 150mg of glutathione; however, some researchers suggest we may need more than 300mg/day to combat glutathione reactive substances in our food supply. To maintain overall health, individuals that are susceptible to glutathione deficiency, such as older adults, smokers, individuals with diabetes and those under oxidative stress, should consider adding supplemental glutathione or glutathione synthesis enhancers to their diet.¹  NS

References:

¹Jones DP.  2011. The health dividend of glutathione. Nat Med Journal, February. Retrieved from <http://www.naturalmedicinejournal.com/article_content.asp?article=18>

²Furukawa T, Meydani SN, Blumberg JB. Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech Ageing Dev. 1987;38(2):107-117.

³Brown LA, Bai C, Jones DP. Glutathione protection in alveolar type ii cells from fetal and neonatal rabbits. Am J Physiol. 1992;262(3 Pt 1):L305-312.

⁴Aw TY, Williams MW. Intestinal absorption and lymphatic transport of peroxidized lipids in rats: Effect of exogenous gsh. Am J Physiol. 1992;263(5 Pt 1):G665-672.

 

⁵Matkovics B, Barabas K, Szabo L, Berencsi G. In vivo study of the mechanism of protective effects of ascorbic acid and reduced glutathione in paraquat poisoning. Gen Pharmacol. 1980;11(5):455-461.

⁶Flagg EW, et al. Dietary glutathione intake and the risk of oral and pharyngeal cancer. Am J Epid. 1994;139: 453-465.

⁷Oriana S, Bohm S, Spatti G, Zunino F, & Di Re F. A preliminary clinical experience with reduced glutathione as protector against cisplatin-toxicity. Tumori. 1987;73(4): 337-34

Stephanie Caligiuri is completing a master of science degree in nutrition at the University of Manitoba in Winnipeg, Canada. She is also a research associate with the company NutriTech Consulting.