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Thursday, December 03, 2020 1:08:11 PM
This is 100% true.
This is why NAC works:
2.3. Cysteine Pro-Drugs
L-cysteine is the rate limiting amino acid in de novo synthesis of GSH [2], so naturally, cysteine supplementation should be investigated as a possible approach to improve GSH status and counter disease-associated oxidative stress. Yet according to studies on this topic, direct administration of cysteine is limited by spontaneous oxidation to its corresponding disulfide cystine [56], significant toxicity [57,58,59,60,61,62], and mutagenicity risks [63,64]. Because of these issues, focus has shifted from cysteine to its precursors, which may provide an alternate avenue to raising GSH concentrations by increasing the available cysteine pool.
The efficacy of cysteine precursors N-acetylcysteine (NAC), S-Adenosyl-L-methionine (AdoMet), and L-2-oxothiazolidine-4-carboxylate (OTC) supplementation on GSH levels are evaluated in the next sections. Methionine is also a cysteine prodrug that increases RBC GSH levels when supplemented orally [65], but supplementing with methionine is not recommended due to the increased risk of raising homocysteine levels [66,67], so it will not be discussed in this review.
2.3.1. N-Acetylcysteine (NAC)
NAC is a cysteine precursor that, when administered orally, increases GSH concentrations in individuals with GSH deficiency caused by infections, genetic defects, or metabolic disorders [68]. Orally administered NAC is readily absorbed in the stomach and gut [69] and then converted to cysteine in the liver [70], where it is used locally for GSH synthesis or transported throughout the body to individual tissues [71]. Pharmokinetics studies have revealed that NAC is almost entirely metabolized by the liver and kidneys [70], and as a result, NAC is nearly undetectable in plasma [72]. Therefore, measuring NAC in plasma is not representative of NAC status [72].
In a study by De Rosa et al., HIV-infected individuals were orally supplemented with 8000 mg NAC daily for 8 months, and whole blood GSH levels significantly increased with no major adverse effects [73]. An additional study found that when 12 HIV+ patients were orally supplemented with NAC (1 g/day), plasma GSH, cysteine, homocysteine, taurine, methionine, and glutamine concentrations increased significantly [38]. In a separate treatment group, glutamine was supplemented (20 g/day) daily, and results were contrasted against those of NAC. The effects of NAC were greatest, achieving an almost two-fold increase in plasma GSH levels [38]. In addition, NAC supplementation was found to benefit individuals with low resting GSH levels [74], and may be even more effective when supplemented with glycine [75].
Overall, orally administered NAC is an effective way to replenish GSH in HIV-infected patients, but more research is needed to better understand the effect of NAC supplementation on GSH levels in healthy individuals. Despite its potential benefits, NAC is limited by potentially harmful side effects, such as nausea or gastric distress, but investigators hypothesize that the intestinal side effects found in the trial may have been due to the ingestion of the excipient, which contained lactose [68].
https://www.mdpi.com/2072-6643/11/5/1056/htm
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