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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

1
Translational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
2
Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
3
Institute of Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
4
Baylor-St. Luke’s Medical Center, Houston, TX 77030, USA
5
USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
6
Thomas Street HIV-Health Center, Harris Health, Houston, TX 77009, USA
*
Author to whom correspondence should be addressed.
Authors contributed equally.
Biomedicines 2020, 8(10), 390; https://doi.org/10.3390/biomedicines8100390
Received: 8 September 2020 / Revised: 27 September 2020 / Accepted: 27 September 2020 / Published: 30 September 2020
(This article belongs to the Section Molecular and Translational Medicine)
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. View Full-Text
Keywords: premature aging; HIV; mitochondrial function; oxidative stress; GlyNAC; Glutathione; cognition; physical function premature aging; HIV; mitochondrial function; oxidative stress; GlyNAC; Glutathione; cognition; physical function
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Kumar, P.; Liu, C.; Suliburk, J.W.; Minard, C.G.; Muthupillai, R.; Chacko, S.; Hsu, J.W.; Jahoor, F.; Sekhar, R.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. Biomedicines 2020, 8, 390.

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