Effect of antioxidant supplementation on immune reconstitution and mitochondrial damage
M. Baum1, R. Marlink2, D. Jayaweera3, S. Sales1, D.-H. Shin1, T. Stewart1, D. Roy1, S. Barr1, A. Campa1
1Florida International University, R Stempel College of Public Health and Social Work, Miami, United States, 2Harvard University, Harvard School of Public Health, Boston, United States, 3University of Miami, Miller School of Medicine, Miami, United States
Background: HIV infection and the long-term use of antiretrovirals are associated with increased mitochondrial damage and oxidative stress. In addition, several clinical trials suggest that antioxidant and micronutrient supplementation improves immunologic and virologic clinical outcomes in HIV-infection. The objective of this study was to determine whether antioxidant supplementation has a beneficial effect on immune reconstitution, and on reducing mitochondrial damage using OXPHOS Comlex I (CI) and Complex IV (CIV) as biochemical surrogate markers of mitochondrial toxicity.
Methods: After consenting, 25 HIV+ adults on stable ART (viral load < 50 copies/mL) were randomized into antioxidant supplementation (B-complex, Vitamins C and E, Selenium, Zinc, N-acetyl cysteine, and α-lipoic acid), N=13, or placebo, N=12, and followed for 8 weeks. At baseline and at 8 weeks, fasting blood was drawn for markers of HIV disease progression (CD4 cell count and viral load), mitochondrial oxidative damage (OXPHOS Complex I and Complex IV enzyme activity), insulin resistance (fasting plasma glucose and insulin for HOMA), and anthropometries were measured. Homa was calculated using the formula HOMA-IR = Fasting insulin (µU/ml) × Fasting glucose (mg/dl)/405.
Results: Mean age was 48.88±SD5.20 years, 56% were men, and mean CD4 cell count was 506.2±SD 155.3 cells/mm3. In a Mixed Models analysis over time, supplementation with antioxidants increased CD4% (β=8.61, p=0.06), and CD4/CD8 ratio (β=0.277, p=0.09), and increased Complex IV (β=16.53, p=0.0163), which remained significant after controlling for baseline Complex IV (p=0.046), and reduced HOMA (β=-1.7, p=0.09) after controlling for BMI.
Conclusions: Supplementation with the antioxidant formula improved immune reconstitution, significantly reduced mitochondrial damage and was safe. Longitudinal studies with adequate sample size are needed to evaluate whether antioxidants given as adjuvant therapy with ART improve immune reconstitution and reduce mitochondrial toxicity and oxidative stress in HIV+ patients on ART.
Funded by NIDA
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