S-Lipoic Acid

S-lipoic acid is a by-product from the conventional (non-enantioselective) chemical synthesis of alpha lipoic acid, yielding a 50/50 (racemic) mixture of R-alpha-lipoic acid and S-alpha-lipoic acid

Unlike R-lipoic acid, S-lipoic acid is not found in nature and never existed or was utilized by a living system prior to its chemical synthesis in 1952. Until recently it was believed that S-Lipoic acid was physiologically inactive. Now there are a few reports from the patent literature suggesting this is not the case. S-lipoic acid may inhibit some of the most essential properties of the R form, including interactions with proteins, enzymes and genes.

Since the inhibitory effect of S-lipoic acid on PDH activity was negligible at physiological levels this indicates the possibility of competition for R-Lipoic Acid uptake or transport which may occur outside the mitochondria.

There are also reports of the superiority of racemic alpha lipoic acid over R-lipoic acid in terms of a non-enantioselective reduction to S-DHLA.

To date, there have been no human clinical trials that directly compare R-lipoic acid (RLA) S-lipoic acid (SLA) and racemic Alpha lipoic acid, although this is presently underway. In the meantime, we believe that there is enough evidence reported from in vitro and animal studies to warrant the use of the naturally occurring R-Lipoic Acid over racemic ALA when there is a choice.

  • S-lipoic acid produces different biological actions than R-lipoic acid that may be undesirable.1-7
  • S-lipoic acid is metabolized in the outer cell membrane or cytoplasm. This may interfere with R-lipoic acid's ability to penetrate the inner mitochondrial membrane, thus limiting energy production.
  • At high concentrations, S-Lipoic acid inhibits mitochondria metabolism.8
  • S-lipoic acid cannot bind with critical mitochondrial enzymes and inhibits ATP production.9
  • S-lipoic acid increases HbA1c.10
  • S-lipoic acid increases mortality in rats.11

References

  1. Cytokine-induced glucose uptake in skeletal muscle: redox regulation and the role of alpha-lipoic acid. Khanna S, Packer L, et al. Am J Physiol. 1999 May;276(5 Pt 2):R1327-33.
  2. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation. Lykkesfeldt J, Ames BN et al. FASEB J 1998 Sep; 12(12): 1183-9.
  3. Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson's disease therapy. Bharat S, Cochran BC, et al. Neurotoxicology. 2002 Oct;23(4-5):479-86.
  4. Stereospecific effects of lipoic acids on mammalian pyruvate dehydrogenase complex. Hong YS, Jacobia SJ, et al. Free Radic Biol Med. 1999 Mar;26(5-6):685-94.
  5. Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Streeper RS, Henriksen EJ, Tritschler HJ, et al. Am J Physiol 1997 Jul; 273(1 Pt 1): E185-91.
  6. Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of alpha-lipoic acid. Haramaki N, Han D, et al. Free Radic Biol Med 1997; 22(3): 535-42.
  7. Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats. Maitra I, Serbinova E, et al. Biochem Biophys Res commun 1996; 221:422-429.
  8. Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice. Freisleben HJ, Neeb A, et al. Arzneimittelforschung 1997 Jun; 47(6): 776-80.
  9. Cytokine-induced glucose uptake in skeletal muscle: redox regulation and the role of alpha-lipoic acid. Khanna S, Packer L, et al. Am J Physiol. 1999 May;276(5 Pt 2):R1327-33.
  10. US PATENT 5,693,664.
  11. US PATENT 5,693,664.
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