GlyNAC Is Not the Same as NAC-Alone or GSH-Alone
(a) GSH synthesis requires both cysteine (from NAC) and glycine. Supplementing NAC-alone does not provide glycine, and only GlyNAC provides both the glycine and cysteine needed for GSH synthesis. Proof to support this point comes from data in this study which shows that GlyNAC supplementation improves GSH synthesis and GSH concentrations to correct GSH deficiency in multiple vital organs of the body. No study has reported extension of mammalian life with NAC-alone and, on the contrary, supplementing NAC-alone in
C. elegans was found to accelerate aging and shorten lifespan [
61]. However, as reported in this manuscript, GlyNAC supplementation in mice extends life.
(b) As discussed above, cells need to combat OxS and simultaneously avoid reductive stress. As seen in this report, the heart, liver and the kidneys have differing GSH concentrations. Indeed, every organ of the body maintains its own GSH concentrations based on their metabolic activity, generation of ROS and cellular needs. Exogenous compounds with antioxidant potential run into the problem of dosing—too much can induce reductive stress, and too little will not combat OxS. This is further complicated by the fact that every organ maintains a different concentration of GSH, and exogenous antioxidant dosing is unlikely to correct GSH deficiency and OxS, while simultaneously avoiding reductive stress in all organs. GlyNAC does not attempt to override or replace cellular defenses to combat OxS and reductive stress. Instead, by providing precursors to boost GSH synthesis and concentration, GlyNAC works by supporting the ability of cells to autoregulate their own GSH—thus GlyNAC can correct GSH deficiency and OxS in every cell and organ in the body, without inducing reductive stress.
(c) No studies have reported an increase in mammalian lifespan by supplementing exogenous glutathione. On the contrary, supplementation of exogenous GSH was found to accelerate aging and shorten life in
C. elegans [
61]. Because different organs maintain different concentrations of GSH, providing exogenous GSH is associated with the risk of inducing reductive stress. GlyNAC avoids this problem by allowing cells to autoregulate and maintain their required GSH homeostasis, i.e., GlyNAC does not interfere with cellular autoregulation whereby cells make the requisite amount of GSH based on cellular need. This is an important point to understand because the cellular requirement of GSH in each organ is constantly and dynamically changing and is influenced by variations in metabolic activity caused by feeding/fasting, rest/activity and waking/sleep. An additional challenge is that oral GSH is not absorbed well from the gut because it is digested and broken down into its constituent amino-acids, and in this process, cysteine is oxidized by the gut to cystine, which is not a GSH precursor. Even if GSH could be provided in a form which is absorbable, it still runs into dosing issues because cells synthesize their required GSH and do not depend on the plasma to provide GSH. For these reasons, exogenous provision of GSH is impractical and non-physiological, while GlyNAC supplementation corrects GSH deficiency and lowers OxS in vital organs, and extends life.
