Increasing glutathione concentrations with cysteine and glycine supplementation lowers inflammation in HIV patients

Dietary Sulfur-Containing Amino Acids Are Associated with Higher Prevalence of Overweight/Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

“…In human coronary arterial endothelial cells, cysteine, histidine, and glycine can inhibit nuclear factor-kappa B activation, IκBα degradation, CD62E expression, and IL-6 production, exhibiting anti-inflammatory effects [38]. And in HIV patients, increasing glutathione concentrations with cysteine and glycine supplementation lowers inflammation [39]. However, in excessive methionine intake-induced hyperhomocysteinemia rat model, the level of serum IL-6 was higher [40].…”

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial

“…PPARα is widely implicated in the upregulation of mitochondrial uptake and oxidation of fatty-acids, and downregulation of OxS, inflammation, insulin resistance, metabolic syndrome and fatty liver. Hence decreased expression of PPARα in PWH is relevant, because PWH are reported to have an increased prevalence of impaired MFO, metabolic syndrome, inflammation, insulin resistance, endothelial dysfunction, and cardiovascular disease [ 14 , 15 , 16 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Mitochondrial sirtuins are NAD + dependent enzymes, which are conserved from bacteria to humans.…”

“…Elevated inflammation and endothelial dysfunction occurs in PWH [ 14 , 15 , 16 ], but their mechanistic origins are not well understood. We found that GlyNAC supplementation significantly improved plasma concentrations of key biomarkers of inflammation (IL-6, TNFα, hsCRP) and endothelial dysfunction (sICAM1, sVCAM1and E-selectin), but accrued benefits receded after stopping GlyNAC supplementation.…”

“…For example, a recent study in 336 young PWH (median age 44 years) found that compared to age, sex, and ethnicity-matched uninfected controls, the burden of geriatric conditions was significantly higher in PWH, together with lower quality of life scores, 5-fold higher healthcare utilization, and 4-fold higher mortality [ 6 ]. Other reports have linked early aging in PWH to diverse health conditions ranging from declining gait speed [ 8 ], physical function [ 9 ] and cognition [ 10 , 11 ], mitochondrial aging [ 12 , 13 ], and elevated inflammation [ 14 , 15 , 16 ]. Additional evidence for early aging in PWH comes from studies in corneal epithelial cells, monocyte, and immune dysfunction, and the emergence of frailty at an earlier age [ 6 , 7 , 17 ].…”

“…In translational studies in aged mice, we discovered that inducing GSH deficiency results in impaired mitochondrial fatty-acid oxidation (MFO), and that correcting naturally occurring GSH deficiency improves defective MFO [ 23 ]. In a small pilot study in such ‘older’ PWH with premature aging, we investigated the mechanisms contributing to GSH deficiency and its link with mitochondrial fat and glucose oxidation, and reported that (a) GSH deficiency in PWH occurs due to diminished synthesis caused by deficiency of its precursor amino-acids glycine and cysteine [ 13 ]; (b) supplementing GlyNAC (combination of glycine and N-acetylcysteine, a cysteine donor) for 2 weeks improved red blood cells (RBC)-GSH synthesis, RBC-GSH concentrations, mitochondrial fuel oxidation, and muscle (grip) strength [ 13 ], and lowered inflammation [ 14 ]. Based on these observations, we hypothesized that (a) PWH in the 45–65 year age group will have GSH deficiency and multiple defects associated with premature aging; (b) these defects could be improved/reversed with a longer 12-week duration of oral, nutritional supplementation with GlyNAC to correct GSH deficiency; and (c) any accrued benefits could be lost after withdrawing GlyNAC supplementation.…”