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
<b>Background:</b> 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...
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MDPI AG
2020-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/10/390 |
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| author | Premranjan Kumar Chun Liu James W. Suliburk Charles G. Minard Raja Muthupillai Shaji Chacko Jean W. Hsu Farook Jahoor Rajagopal V. Sekhar |
| author_facet | Premranjan Kumar Chun Liu James W. Suliburk Charles G. Minard Raja Muthupillai Shaji Chacko Jean W. Hsu Farook Jahoor Rajagopal V. Sekhar |
| author_sort | Premranjan Kumar |
| collection | DOAJ |
| description | <b>Background:</b> 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). <b>Methods:</b> 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. <b>Results:</b> PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. <b>Conclusions:</b> 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. |
| first_indexed | 2024-03-10T15:55:38Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T15:55:38Z |
| publishDate | 2020-09-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-27516905e0c64d6fb9a2f67c97be84192023-11-20T15:38:22ZengMDPI AGBiomedicines2227-90592020-09-0181039010.3390/biomedicines8100390Supplementing 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 TrialPremranjan Kumar0Chun Liu1James W. Suliburk2Charles G. Minard3Raja Muthupillai4Shaji Chacko5Jean W. Hsu6Farook Jahoor7Rajagopal V. Sekhar8Translational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USATranslational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USADepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAInstitute of Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USABaylor-St. Luke’s Medical Center, Houston, TX 77030, USAUSDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USAUSDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USAUSDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USATranslational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA<b>Background:</b> 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). <b>Methods:</b> 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. <b>Results:</b> PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. <b>Conclusions:</b> 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.https://www.mdpi.com/2227-9059/8/10/390premature agingHIVmitochondrial functionoxidative stressGlyNACGlutathione |
| spellingShingle | Premranjan Kumar Chun Liu James W. Suliburk Charles G. Minard Raja Muthupillai Shaji Chacko Jean W. Hsu Farook Jahoor Rajagopal V. Sekhar 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 premature aging HIV mitochondrial function oxidative stress GlyNAC Glutathione |
| 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 | premature aging HIV mitochondrial function oxidative stress GlyNAC Glutathione |
| url | https://www.mdpi.com/2227-9059/8/10/390 |
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