N-acetylcysteine, Alpha-Lipoic Acid, L-Glutamine, and L-Carnitine - Nutrients and HIV, part 3

Alternative Medicine Review, August, 2000 by Lyn Patrick

Variable   Time points   NO.   Mean    St. Dev.

CD4             T0       11    305.2     139.4
                T1       11    317.7     136.3
                T2       11    322.0     142.3
                T3       11    377.5     154.5
                T4       11    406.3     167.9
CD8             TO       11    860.7     353.7
                T1       11    926.3     392.9
                T2       11    920.3     425.7
                T3       11    947.5     405.4
                T4       11    1,025.1   700.0
HIV RNA         TO       11    3.67       0.64
(log 10)        T1       NA
                T2       10    3.82       0.72
                T3       NA
                T4       11    3.89       0.54

Variable    Min   Median    Max

CD4          61    331       558
             62    311       504
            100    337       522
            100    390       580
            101    476       670
CD8         352    844     1,460
            419    918     1,745
            525    737     1,865
            401    922     1,577
            395    947     2,887
HIV RNA     2.60   3.84     4.52
(log 10)
            2.65   4.13     4.52

            2.90   4.07     4.51

T0, baseline; T1 =day 15; T2=day 30; T3=day 90; T4=day 150. Abbreviations: NA=not available; St. Dev.=standard deviation. Taken from Moretti S, et al. Blood 1998; 91:3817-3824.[89] [C], 1998. Blood. All rights reserved.

A follow-up trial by the same group[90] with 11 HIV-positive asymptomatic individuals evaluated three grams of oral acetyl-L-carnitine daily for five months. Again, significant reductions were seen in CD4 apoptosis and ceramide levels. No significant changes, however, were seen in absolute CD4 or CD8 cell counts or levels of viremia. The treatment did increase serum IGF-1 levels and had no impact on serum growth hormone levels. It is interesting to note that the baseline IGF-1 and growth hormone levels in the HIV-positive individuals were not lower than healthy age-matched normals. There were no side-effects or toxicity reported in this trial, and the authors noted that all subjects reported an improved sense of well-being by the second or third week of therapy.

A randomized trial[91] of six grams oral L-carnitine daily in 20 male AIDS patients on AZT for 14 days resulted in significant decreases in TNF-[Alpha] and in serum triglycerides. Hypertriglyceridemia occurs in HIV as a result of increased cytokine production and is also a recognized side-effect of protease-inhibitor therapy. Whether L-carnitine will reduce the hypertriglyceridemia and hypercholesterolemia secondary to protease-inhibitor therapy remains to be seen.

L-Carnitine, Mitochondrial Myopathy, and Neuropathy

L-carnitine is a recognized treatment for mitochondrial myopathy and encephalomyopathy, a group of neurological disorders characterized by progressive neurological and muscular weakness and degeneration.[92] AZT and other reverse transcriptase inhibitors have been associated with mitochondrial toxicity. This is most evident in the research exploring mitochondrial myopathy after long-term therapy with AZT as a single antiviral agent.[93] AZT affects muscle mitochondria by inhibiting the [Gamma]-DNA polymerase enzyme, resulting in depletion of muscle mitochondrial DNA, and creating defects in the cytochrome system of the respiratory chain.[94] This results in a functional "uncoupling" of the oxidation and phosphorylation of mitochondrial energy production, and an inability of the mitochondria to use fatty acids as energy, instead being stored as lipid in the muscle tissue. Low levels of carnitine are also found in the muscle tissue of AZT patients, not correlative of the duration of treatment or cumulative dosage of the drug.[93] A small trial of six patients on AZT and lamivudine found that carnitine depletion was occurring through increased renal excretion. Supplementation with 800 mg oral L-carnitine, 3000 mg magnesium chloride, 800 mg L-arginine, and 240 mg glycine daily was able to increase carnitine levels. No symptom-related data was available.[95]