Effect of Antioxidants on Mitochondrial Function in HIV-1–Related Lipoatrophy: A Pilot Study

Abstract

We investigated the effect of antioxidant supplementation on mitochondrial function, fat distribution, and lipid and glucose metabolism in HIV-1-infected patients with antiretroviral therapy (ART)-related lipoatrophy. 61 ART-treated HIV-1-infected patients with lipoatrophy were randomized to receive either n-acetyl-L-carnitine (n = 21), lipoic acid + n-acetylcisteine (LA/NAC) (n = 20), or no supplementation (n = 20) for 48 weeks. At baseline and at the end of treatment, mitochondrial function was studied by (13)C-methionine breath test and by mitochondrial (mt)-DNA quantification on circulating T-cells and subcutaneous adipose tissue. Body composition was assessed by dual-energy X-ray absorpiometry (DEXA). (13)CO(2)-exhalation increased between baseline and week 48 in both supplementation arms as evidenced by a higher delta over baseline excretion at 45 min (from mean ± SEM of 7.8 ± 1.08 to 9.9 ± 0.6, p = 0.04 in the n-acetyl-carnitine arm, and from 7.4 ± 0.8 to 11.5 ± 1.6, p = 0.01 in LA/NAC arm). Cumulative (13)CO2 excretion increased from median (interquartile range; IQR) of 3.25 (2.55-4.2) to 4.51 (4.12-5.2) in the carnitine arm; from 3.79 (2.67-4.37) to 4.83 (4.25-5.56) in the LA/NAC arm; p = 0.004, 0.02, respectively. mtDNA content increased in CD4+ T-cells from patients who received n-acetyl-carnitine (+30 copies/cell; p = 0.03), without significant difference by the overall comparison of the study groups. Fat body mass and lipid profile did not change significantly in any of the arms. Our study showed that antioxidant supplementation may have a protective role on mitochondrial function, with limited effects on the reversal of clinical lipodystrophic abnormalities in HIV-1-infected patients.

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

“…Some studies and clinical research found that some ART toxic effect could partially be reversed by previous and concomitant antioxidant treatment [74,75].…”

Oxidative Stress Associated to Disease Progression and Toxicity during Antiretroviral Therapy in Human Immunodeficiency Virus Infection

“…Mallon (2007), Miro et al (2005), Milazzo et al (2010) and Vassimont et al (2010) mentioned that the body shape abnormalities in HIV evolution include subcutaneous fat atrophy and visceral or central fat accumulation. The metabolic abnormalities include elevations in serum triglycerides and total cholesterol, suppression of serum high-density lipoprotein cholesterol levels, and hyperinsulinemia in normoglycemic individuals.…”

“…Meanwhile Masiá et al (2007) found increased plasma peroxide associated with established cardiovascular risk factors in the study context. McComsey et al (2005) describe some clinical and metabolic benefits during replacement of antiviral treatment while others by Milazzo et al (2010), Yousefi et al (2011), Hurwitz et al (2007 and Gil et al (2005a) found clinical and metabolic benefits during dietary micronutrient intake improvement in treatment or naive patients. For several years, the attention of different research groups as Aukrust et al (2003), Hulgan et al (2006) and Hurwitz et al (2007) has been largely focused on damages induced by ART on mtDNA and on the consequence of its depletion.…”

“…Researches by Gil et al (2005), Milazzo et al (2010), Mandas et al (2009) and Sundaram et al (2008) showed that highly oxidative state during the progress of HIV infection can be promoted by the host. Thus, treating the patients with antioxidants since early stages of the disease is believed to be beneficial argued by Tang et al (2005), Gil et al (2005a) and Hurwitz et al (2007).…”

“…Under such circumstances, assuming that an administered antioxidant Journal of Virology & Microbiology 10 could reach the site of increased ROS formation, it would at best marginally affect secondary tissue damage and could even be deleterious. Sometimes pro-oxidants might be more beneficial as suggested Ma (2010) and Milazzo et al (2010). Indeed, flavonoids may act just as much as pro-oxidants in the gastrointestinal tract and in cell culture systems as they do as antioxidants.…”