Glycine/N-Acetylcysteine Supplementation May Slow HIV-Related Premature Aging

By Will Boggs MD

October 23, 2020

NEW YORK (Reuters Health) - Supplementation with glycine and N-acetylcysteine (GlyNAC) appears to slow premature aging in people living with HIV (PWH), according to results from a pilot open-label clinical trial.

"Supplementing GlyNAC is a highly practical and efficient approach to promote healthy aging and improve the health of older humans by correcting deficiencies in and boosting levels of glycine, cysteine, and glutathione," Dr. Rajagopal V. Sekhar of Baylor College of Medicine, in Houston, Texas, told Reuters Health by email.

PWH have elevated oxidative stress and impaired mitochondrial fuel oxidation, key factors responsible for geriatric aging. But it remains unclear whether correcting these defects could improve or reverse premature aging.

Dr. Sekhar and colleagues investigated the effects of GlyNAC supplementation in eight PWH on various measures of aging. PWH were studied at baseline, 12 weeks after receiving GlyNAC, and eight weeks after stopping GlyNAC. Eight matched, uninfected controls were studied at baseline and did not receive supplementation.

At baseline, PWH had glutathione deficiency in muscle and red blood cells and significantly higher plasma oxidative stress, both of which improved significantly after GlyNAC supplementation and returned towards baseline after stopping GlyNAC.

Compared with controls, PWH had significantly lower mitochondrial fuel oxidation and higher mitochondrial glucose oxidation. GlyNAC supplementation led to significant increases in mitochondrial fatty-acid oxidation and decreases in mitochondrial glucose oxidation that were lost after withdrawal of GlyNAC, the researchers report in Biomedicines.

GlyNAC supplementation was also followed by decreases in elevated proinflammatory biomarkers, improvements in endothelial dysfunction, and reductions in genomic damage. These improvements receded but did not disappear completely after withdrawal of GlyNAC.

Impaired physical function and cognition in PWH (compared with controls) improved after GlyNAC supplementation but declined following withdrawal of GlyNAC.

PWH had significantly lower protein expression of regulators of mitochondrial energy metabolism, autophagy, and mitophagy, all of which improved significantly after GlyNAC. These measures were not repeated after GlyNAC withdrawal.

"GlyNAC offers powerful cellular protection and corrects defects in mitochondrial energy metabolism," Dr. Sekhar said. "At the clinical level, GlyNAC improves muscle strength, exercise capacity, cognition, and abdominal obesity, and at the cellular level, GlyNAC lowers oxidative stress, inflammation, endothelial dysfunction, and insulin resistance."

"The overall effect is that GlyNAC is a simple and safe nutritional approach which could improve health and promote healthy aging," he said.

"We have also completed two other trials in aging, where we studied the effect of supplementing GlyNAC in older adults, and these exciting results in aging will be forthcoming shortly," Dr. Sekhar said. "I am also leading two ongoing randomized clinical trials evaluating the effect of GlyNAC in mild cognitive impairment (ongoing) and Alzheimer disease (just funded, and due to begin)."

The study had no commercial funding, and the researchers report no conflicts of interest.

SOURCE: Biomedicines, online September 30, 2020.