α-lipoic acid

α-lipoic acid is an organosulfur compound with various antioxidant properties. It acts as a catalyst for mitochondrial dehydrogenase reactions. α-lipoic acid reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, and peroxyl radicals, and neutralizes them.1,2α-lipoic acid can protect tissue membranes by interacting with vitamin C and glutathione, which is important for the recycling of vitamin E. α-lipoic acid has been shown to be effective in reducing oxidative stress in models of reperfusion injury, diabetes, and neurodegeneration.2

Pharmacology of α-lipoic acid

α-lipoic acid is an organosulfur compound with various antioxidant properties. It acts as a catalyst for mitochondrial dehydrogenase reactions. α-lipoic acid reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, and peroxyl radicals, and neutralizes them.2α-lipoic acid can protect tissue membranes by interacting with vitamin C and glutathione, which is important for the recycling of vitamin E. Furthermore, α-lipoic acid has been known to facilitate glucose transport in the body.

alpha_lipoic_acid_structure

Biochemical structure of α-lipoic acid.

α-lipoic acid is involved in metabolism and energy production. For example, α-lipoic acid catalyzes the pyruvate dehydrogenase3and alpha-ketoglutarate dehydrogenase4enzymes in the citric acid cycle, which plays an important role in ATP synthesis from glucose. In addition, α-lipoic acid is a component of the branched-chain keto-acid dehydrogenase complex, which is involved in the synthesis of ATP from from branched chain amino acids.5

tca_cycle

α-lipoic acid plays a key role in catalyzing several parts of the citric acid cycle, as pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.

Standard Dosage

Standard dosages of α-lipoic acid range from 300-600 mg per day.

α-lipoic acid and Cognition

α-lipoic acid has been found to have effects on cognitive function with respect to memory.

Memory

In a study in mice, it was found that administration of alpha-lipoic acid for a two-week period was found to improve memory in mice. The Barnes maze test was used to assess performance.6

While there is a limited amount of research on healthy humans with respect to the effects of α-lipoic acid, it has been studied in the context of intervention for Alzheimer's disease patients. One study on 43 patients found that daily administration of 600 mg lipoic acid led to a slower progression of disease.7Specifically, in patients in the study there was a steady decrease in cognitive performance (2 points/year decrease in the Mini-Mental Status Examination (MMSE) and a 4 point/year increase in the Alzheimer's Disease assessment scale (ADAScog)). However, once these patients were initiated treatment of lipoic acid for a period of 48 months, they exhibited a stabilization of cognitive function.8At the end of the 48 month treatment period, it was found that patients with mild dementia ended up exhibited dramatically slowed progression of the disease, showing a decline in MMSE scores of only 0.6 points/year and increase in ADAScog of only 1.2 points/year.9

Editorial Opinion

α-lipoic acid has a strong safety profile and is an FDA-classified Generally Regarded as Safe (GRAS) compound. α-lipoic acid acts as a strong antioxidant that benefits many tissues throughout the body. Multiple studies have found beneficial effects on metabolic processes. While the research on cognition is limited, there are promising results from animal studies. Supplementation of α-lipoic acid in quantities of 300-600 mg per day could be beneficial for healthy humans.

  1. Shay, K. P., Moreau, R. F., Smith, E. J., Smith, A. R., & Hagen, T. M. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta (BBA)-General Subjects, 1790(10), 1149-1160.

  2. Packer, L., Witt, E. H., & Tritschler, H. J. (1995). Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine, 19(2), 227-250.

  3. Williamson, J. R., & Cooper, R. H. (1980). Regulation of the citric acid cycle in mammalian systems. FEBS letters, 117(S1), K73-K85.

  4. Tretter, L., & Adam-Vizi, V. (2005). Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 360(1464), 2335-2345.

  5. Broquist, H. P. (1976). Amino acid metabolism. Nutrition reviews, 34(10), 289-293.

  6. Farr, S. A., Price, T. O., Banks, W. A., Ercal, N., & Morley, J. E. (2012). Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. Journal of Alzheimer's Disease, 32(2), 447-455.

  7. Maczurek, A., Hager, K., Kenklies, M., Sharman, M., Martins, R., Engel, J., ... & Münch, G. (2008). Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease. Advanced drug delivery reviews, 60(13), 1463-1470.

  8. Hager, K., Marahrens, A., Kenklies, M., Riederer, P., & Münch, G. (2001). Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Archives of gerontology and geriatrics, 32(3), 275-282.

  9. Hager, K., Kenklies, M., McAfoose, J., Engel, J., & Münch, G. (2007). α-Lipoic acid as a new treatment option for Alzheimer’s disease—a 48 months follow-up analysis (pp. 189-193). Springer Vienna.

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