Supplementing glycine and n-acetylcysteine (GlyNAC) in aging HIV patients improves oxidative stress, mitochondrial dysfunction, inflammation, endothelial dysfunction, insulin resistance, genotoxicity, strength, and cognition:

Authors: KUMAR, PREMRANJAN - Baylor College Of Medicine; LIU, CHUN - Baylor College Of Medicine; SULIBURK, JAMES - Baylor College Of Medicine; MINARD, CHARLES - Baylor College Of Medicine; MUTHUPILLAI, RAJA - St Luke'S Medical Center; CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC); HSU, JEAN - Children'S Nutrition Research Center (CNRC); JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC); SEKHAR, RAJAGOPAL - Baylor College Of Medicine

Submitted to: Biomedicines
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2020
Publication Date: 9/30/2020
Citation: Kumar, P., Liu, C., Suliburk, J.W., Minard, C.G., Muthupillai, R., Chacko, S., Hsu, J.W., Jahoor, F., Sekhar, R.V. 2020. 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. Biomedicines. 8(10):390. https://doi.org/10.3390/biomedicines8100390.
DOI: https://doi.org/10.3390/biomedicines8100390

Interpretive Summary: Today people with HIV infection (PWH) are living longer because of drugs that are very effective at preventing the virus from multiplying in their bodies. Although they live a relatively healthy life a major problem is premature aging, that is, they grow old faster. For example, a 45-year old PWH may have old age-related diseases like loss of muscle strength and mental sharpness, osteoarthritis, heart disease, cataracts, and high blood pressure that are usually seen in a 70-year old person. What cause PWH to develop these diseases at an earlier age is not known. We believe that it is due to a shortage of a compound called glutathione which is needed to protect and to help all the cells and all the organs of the body to function properly. Glutathione is made by all the cells in our body from three substances called glutamate, glycine and cysteine. People get these three substances from protein in the food they eat. The cells in their body can also make these three substances from other similar compounds. We found that PWH had low levels of glutathione and low levels of two of these substances, glycine and cysteine in their blood. This made us think that the reason PWH had old age-related diseases is because they were not making enough glutathione due to a shortage in the supply of glycine and cysteine in their body. We therefore decided to give a group dietary supplements of glycine and cysteine with their regular food for 12 weeks and we made measurements of cysteine, glycine and glutathione levels in their blood and muscle cells, how well their muscle cells were working, their physical strength and mental sharpness. The measurements were made again after 8 weeks of no supplement. We found that the glycine and cysteine dietary supplements improved all measurements of premature aging in PWH including muscle strength and mental sharpness. However, when the dietary supplements were stopped, these improvements disappeared. These findings are important indicating that nutrition supplemenation can have an impact related to cell function and the prevention of premature aging.

Technical Abstract: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributingmechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursor’s glycine and N-acetylcysteine (GlyNAC). We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscleprotein breakdown rates, body composition, physical function and cognition. PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.