GSH Support Strategies: How Can We Improve GSH Status?
GSH Support Strategies: How Can We Improve GSH Status?
GSH is synthesized from amino acid precursors, glutamate, cysteine and glycine. A considerable number of trials have used N-acetylcysteine (NAC) as a cysteine precursor, expecting it to provide a means to increase GSH synthesis. The logic for using NAC is complicated but generally assumes that cysteine is limiting for GSH synthesis. However, the American diet typically has an excess of sulfur amino acids. According to NHANES III, 99% of adult American males and females consume greater than the RDA, 50% consume more than twice the RDA and 1% of people consume more than 4 times the RDA for sulfur amino acids. Consequently, while NAC is likely to benefit individuals with insufficient sulfur amino acid intake, additional approaches are needed to address a functional need for GSH in most Americans. Supplementation with glutamate, cysteine, and glycine provides one alternative, and others include related sources of these amino acids (eg, whey), supplements to enhance synthesis (eg, silymarin), as well as the naturally occurring compound itself, GSH.
A common assumption is that dietary or supplemental GSH is not available for use by the human body because the intestines contain an enzyme (ie, γ-glutamyl transpeptidase; GGT) that degrades GSH. However, a substantial amount of scientific evidence shows that supplemental GSH is bioavailable. As indicated above, added GSH supports detoxification in body fluids such as the lining fluid of the lung and intestines, enhances macrophage function, and decreases influenza virus production. Thus, even for cells that do not absorb GSH, protection can be provided by supplemental GSH.
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Different research groups have also shown that GSH is transported across intestinal membranes, across the intestinal epithelium, into human intestinal cells, and from the intestinal lumen into the vascular circulation. Orally administered GSH increases GSH in mouse, rat, and human plasma, and the extent of increase is increased by a stress response. While studies are not universally consistent, and most organs do not take up GSH, experiments with isotopic tracers, inhibitors of GSH synthesis, inhibitors of GSH transport, and inhibitors of GSH degradation provide detailed evidence for GSH transport in intestines, lung, and kidneys. This subject has been recently reviewed by Lawrence Lash, and this should be consulted for additional details. Animal and human studies further show direct benefit of oral GSH in protection against age-related decline in immune function; enhancement of lymphocyte function; and protection against oxidative injury in newborn lung, influenza viral infection, chemically induced oral cancer, and uptake of peroxidized lipids and other toxic chemicals.