Effect of antioxidants on mitochondrial function in HIV-1-related lipoatrophy: a pilot study.
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.
Milazzo
Laura
L
Università degli Studi di Milano, Department of Clinical Sciences, L. Sacco Hospital, Section of Infectious Diseases and Immunopathology, Milan, Italy. laura.milazzo@unimi.it
Menzaghi
Barbara
B
Caramma
Ilaria
I
Nasi
Milena
M
Sangaletti
Ornella
O
Cesari
Miriam
M
Zanone Poma
Barbara
B
Cossarizza
Andrea
A
Antinori
Spinello
S
Galli
Massimo
M
D015502:Absorptiometry, Photon; D000108:Acetylcarnitine / Q000008:administration & dosage; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D001823:Body Composition; D001944:Breath Tests; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002247:Carbon Isotopes / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010865:Pilot Projects; D008063:Thioctic Acid / Q000008:administration & dosage
D000975:Antioxidants; D002247:Carbon Isotopes; D000108:Acetylcarnitine; D008063:Thioctic Acid; D008715:Methionine; D005947:Glucose