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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

Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to mu...

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Autores principales: Kumar, Premranjan, Liu, Chun, Suliburk, James W., Minard, Charles G., Muthupillai, Raja, Chacko, Shaji, Hsu, Jean W., Jahoor, Farook, Sekhar, Rajagopal V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601820/
https://www.ncbi.nlm.nih.gov/pubmed/33007928
http://dx.doi.org/10.3390/biomedicines8100390
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author Kumar, Premranjan
Liu, Chun
Suliburk, James W.
Minard, Charles G.
Muthupillai, Raja
Chacko, Shaji
Hsu, Jean W.
Jahoor, Farook
Sekhar, Rajagopal V.
author_facet Kumar, Premranjan
Liu, Chun
Suliburk, James W.
Minard, Charles G.
Muthupillai, Raja
Chacko, Shaji
Hsu, Jean W.
Jahoor, Farook
Sekhar, Rajagopal V.
author_sort Kumar, Premranjan
collection PubMed
description Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms 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 precursors glycine and N-acetylcysteine (GlyNAC). Methods: 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, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: 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.
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spelling pubmed-76018202020-11-01 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 Kumar, Premranjan Liu, Chun Suliburk, James W. Minard, Charles G. Muthupillai, Raja Chacko, Shaji Hsu, Jean W. Jahoor, Farook Sekhar, Rajagopal V. Biomedicines Article Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms 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 precursors glycine and N-acetylcysteine (GlyNAC). Methods: 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, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: 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. MDPI 2020-09-30 /pmc/articles/PMC7601820/ /pubmed/33007928 http://dx.doi.org/10.3390/biomedicines8100390 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kumar, Premranjan
Liu, Chun
Suliburk, James W.
Minard, Charles G.
Muthupillai, Raja
Chacko, Shaji
Hsu, Jean W.
Jahoor, Farook
Sekhar, Rajagopal V.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601820/
https://www.ncbi.nlm.nih.gov/pubmed/33007928
http://dx.doi.org/10.3390/biomedicines8100390
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