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

Alternative Medicine Review, August, 2000 by Lyn Patrick

Antioxidant Effects of Alpha-Lipoic Acid

Alpha-lipoic acid is a dithiol antioxidant found primarily in the mitochondria where it acts as a coenzyme in the [Alpha]-keto-acid dehydrogenase complex.[65] Because it is a low weight molecular substance and is bioavailable from the diet, lipoic acid is absorbed from the gut and readily passes through the blood-brain barrier.[66] Active as an antioxidant in both lipid and non-lipid components, it can act in membranes of the brain and nervous tissue, lymphoid tissue, and in most other cell types.[67] Both as alpha-lipoic acid and in its reduced form dihydrolipoate, it is a potent antioxidant that can scavenge a wide variety of reactive oxygen species, including superoxide and peroxyl radicals formed during lipid peroxidation.[66] Lipoic acid is able to regenerate ascorbate and tocopherol and to raise glutathione levels (Figure 4).[67]

[Figure 4 ILLUSTRATION OMITTED]

Lipoic acid has recently been the subject of research in HIV as a result of its ability to raise glutathione levels significantly (30-70%) both in vivo and in vitro.[68] Alpha-lipoic acid also interrupts HIV replication by completely blocking the activation of NF-kB in cell cultures at a concentration of 2 mM.[69] Lipoic acid has direct action as an HIV-1 replication inhibitor at concentrations of 70 mg/L and has a synergistic antiviral effect when combined with zidovudine (AZT) at a concentration of 7 mg/mL.[70] The authors of this study conclude that since a 7 mg/mL concentration is reachable with oral therapy and since alpha-lipoic acid works to reduce levels of reverse transcriptase in a manner that is synergistic with AZT, it should be the subject of further research in HIV treatment.

A clinical trial in 11 AIDS-diagnosed patients taking 450 mg lipoic acid daily for 14 days resulted in increases in plasma ascorbate, total glutathione, total plasma thiols, CD4 and CD4/CD8 ratios, and decreases in lipid peroxide levels. The increases in CD4 cells in those patients who responded to the lipoic acid (6 out of 10) were significant: an average increase of 141 [ or -] 121 CD4 cells.[71]

Alpha-lipoic Acid and HIV Therapeutics

Lipoic acid has been used in multiple trials to successfully treat diabetic neuropathy[66] and has been shown to limit excessive free radical-induced damage in the central nervous system. Although no studies have been published to date on the effect of alpha-lipoic acid in HIV-related peripheral neuropathy, a small placebo-controlled trial comparing alpha-lipoic acid to deprenyl was conducted to assess its effect in HIV dementia.[72] The study involved 36 patients with diagnosed HIV-related cognitive damage taking either lipoic acid, deprenyl, the combination, or placebo, and was designed as a tolerability trial, not an efficacy trial. Patients were given 600 mg alpha-lipoic acid twice daily, deprenyl 2.5 mg three times weekly, or both in combination for ten weeks. The alpha-lipoic acid was well tolerated with no apparent side-effects. Although the study did not show any beneficial effect in cognitive function or daily functioning, the authors commented the trial may have been too short. The subjects were all intravenous drug users and were using injectable drugs during the study. Alpha-lipoic acid may also have usefulness in decreasing risk of kidney stones, a side-effect of the protease-inhibitor, antiviral drug indinavir (Crixivan).[73]