What The Experts Are Saying About R-Lipoic Acid

R- and S- enantiomers of the physiological compound alpha-Lipoic Acid have been synthesized. The S-enantiomer is not a naturally occurring compound. This part of the racemate, which is present as about a 50% impurity, needs to be eliminated.

Zimmer, G, ATP Synthesis and ATPase activities in Heart Mitoplasts Under Influence of R- and S- Enantiomers of Lipoic Acid. Methods in Enzymology vol.251 p.332-340. 1995.

“In the case of the purely optical isomers of alpha-Lipoic Acid (R- and S- form, i.e. R-alpha-Lipoic Acid and S-alpha-Lipoic Acid), unlike the racemate, the R-enantiomer mainly has an anti-inflammatory activity…, being stronger by a factor of 10 than that of the racemate. The enantiomers therefore constitute very much more specific and stronger acting active substances than the racemate.”

Ulrich H, Weischer CH, et al. Pharmaceutical composition containing R-alpha-Lipoic Acid or S-alpha-Lipoic Acid as active ingredient. US Patent 5,728,735,1998.

“… R-Lipoic Acid, a mitochondrial coenzyme, but not S-Lipoic Acid, an unnatural isomer which is reduced in the cytoplasm, reverses the sensitivity of hepatocytes from old rats to an oxidative mutagen.”

Progress Report: Mutagenesis and Carcinogenesis Core National Institute of Environmental Health Sciences Center. Univ of Cal at Berkeley. Allan H. Smith, Core Director, Bruce Ames, et al. 2001.

“(R)-form of lipoic…is the naturally occurring enantiomer in mammalian cells. Only the (R)-form is used by mitochondrial – keto acid dehydrogenases and specifically reduced to dihydroLipoic Acid, a powerful antioxidant… (R)-Lipoic Acid supplementation may be more potent than either the racemic mixture (the form sold commercially as – Lipoic Acid) or (S)- enantiomer… (R)-Lipoic Acid increases ATP synthesis and aortic blood flow during reoxygenation after hypoxia… The (S)-enantiomer had no effect on ATP synthesis and improved blood flow at only 10-fold the effective dose of (R)-Lipoic Acid…. (R)-Lipoic Acid supplementation may be a safe and effective means to improve general metabolic activity and increase antioxidant status, affording increased protection against external oxidative and xenobiotic insults with age.”

Tory Hagen, Russell Ingersoll, et al. (R)–Lipoic Acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB 13:411-418, 1999.

“…R-(+) alpha Lipoic Acid is suitable for the treatment of diabetes and insulin resistance… the S-(-) alpha Lipoic Acid practically is not usable for this… Our own investigations have shown … the key enzyme, pyruvate dehydrogenase, surprisingly was inhibited by the S-(-) alpha Lipoic Acid… preferably R-(+)-.alpha.-Lipoic Acid proves to be suitable for the treatment of diabetes mellitus types I and II and its sequelae and late complications and for the treatment of sub clinically and clinically manifest insulin resistance and its sequelae.”

Use of R-(+)-alpha.-Lipoic Acid, R-(-)-dihydroLipoic Acid and metabolites in the form of the free acid or as salts or esters or amides for the preparation of drugs for the treatment of diabetes mellitus as well as its sequelae. United States Patent 6,117, 889. September 2000. Klaus Wessel, Harald Borde, et al.

“The racemate of Lipoic Acid at high dosage (350 mg/kg body weight) reduced the life span significantly. The S (-)-enantiomer of Lipoic Acid (75 mg/kg body weight) increased the 50% survival rate, whereas the physiologic R (+)-enantiomer (9 mg/kg body weight) expanded the total life span of its group.”

Freisleben HJ, Neeb A, et al. Influence of selegiline and Lipoic Acid on the life expectancy of immunosuppressed mice. Arzneimittelforschung. Jun; 47 (6):776-80. 1997.

“Cells from old animals were incubated with either (R) – or (S)-Lipoic Acid… The physiologically relevant (R)-form, a coenzyme in mitochondria, as opposed to the (S)-form significantly protected hepatocytes against t-BuOOH toxicity. Dietary supplementation of (R)-Lipoic Acid [0.5% (wt/wt)] for 2 weeks also completely reversed the age-related decline in hepatocellular GSH levels and the increased vulnerability to t-BuOOH as well… cells from old animals are more susceptible to oxidant insult and (R)-Lipoic Acid, after reduction to an antioxidant in the mitochondria, effectively reverses this age-related increase in oxidant vulnerability.”

Bruce Ames, et al. Delaying Aging with Mitochondrial Micronutrients and Antioxidants. Miami Nature Biotechnology Short Reports. The Scientific World, 2001.

“…(R)-Lipoic Acid may be a more potent supplement than the racemic mixture (which contains both (R) and (S) forms) sold commercially as alpha-Lipoic Acid… (R)-Lipoic Acid increased glucose uptake and the number of glucose transporters in muscle tissue much more effectively than (S)-Lipoic Acid and that the (R)-form more effectively chelated copper and prevented copper-induced lipid peroxidation… (R)-Lipoic Acid increased ATP synthesis and aortic blood flow during reoxygenation after hypoxia in a working heart model, but (S)-Lipoic Acid had no effect on ATP synthesis and only improved blood flow at ten times the effective concentration of (R)-Lipoic Acid.”

The Durk Pearson & Sandy Shaw® Life Extension News. Volume II, Issue #3, April 1999.

“R-alpha-Lipoic Acid is found naturally occurring as a prosthetic group in alpha-keto acid dehydrogenase complexes of the mitochondria, and as such plays a fundamental role in metabolism… it has the ability to alter the redox status of cells and interact with thiols and other antioxidants… that this compound has important therapeutic potential in conditions where oxidative stress is involved.”

Bustamante J, Lodge JK, et al. Alpha-Lipoic Acid in liver metabolism and disease. Free Radic Biol Med. Apr 24 (6): 1023-39, 1998.

“…R-(+)- ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-) – ALA had no significant effect. Although chronic R-(+)- ALA treatment significantly reduced plasma insulin (17%) and free fatty acids ( FFA ; 35%) relative to vehicle-treated obese animals, S-(-)- ALA treatment further increased insulin (15%) and had no effect on FFA.”

Streeper RS, Henriksen EJ, et al. Differential effects of Lipoic Acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol 1997 Jul: 273(1)1,1997.

“An intact organ, the isolated perfused rat heart, reduced R-Lipoate six to eight times more rapidly than S-lipoate, consistent with high mitochondrial dihydrolipoamide dehydrogenase activity and results with isolated cardiac mitochondria.”

Haramaki N, Han D, et al. Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of alpha-Lipoic Acid. Free Radic Biol Med. 7;22(3):535-42, 1997.

“Addition of 1 mM racemic Lipoic Acid reduces these damaging effects to the lens by one-half, while S-Lipoic Acid potentiated LDH leakage. Therefore, stereospecific protection against this opacity is consistent with specific reduction of R-Lipoic Acid in mitochondria of the vulnerable cells at the lens equator…”

Kilic F, Handelman GJ, et al. Modeling cortical cataractogenesis 17: in vitro effect of a-Lipoic Acid on glucose-induced lens membrane damage, a model of diabetic cataractogenesis. Biochem Mol Biol Int. 37(2): 361-70,1995.

“Overall, the results indicate a greater effect of R-thioctic compared to the S isomer. This finding is consistent with the results of previous studies on the ability of the isomers of thioctic acid to alter glucose uptake in both in vitro and ex vivo paradigms. Thus, in vivo administration of R-thioctic acid stimulates the subsequent in vitro transport of glucose into skeletal muscle to a greater extent than the S isomer. Similarly, in vitro R-thioctic acid stimulates glucose transport into isolated muscle cells to a greater extent than the S isomer. The R isomer has an additive effect on insulin stimulated glucose transport, but S thioctic acid inhibits insulin’s action. In addition, R-thioctic acid promoted the translocation of GLUT-1 and GLUT-4 to the plasma membrane, where the S isomer does not.”

Peter Jenne, T.A. Seaton, and C.D. Marsden. Chapter 16 in Lipoic Acid in Health and Disease; Altered C-Deoxyglucose Incorporation in Rat Brain Follwing Treatment with Alpha-Lipoic Acid; ed. Fuchs J, Packer L, Zimmer G Marcel Dekker, Inc New York, Basel, Hong Kong (1997) pp259-268.

“At a concentration of 0.05-0.1 mumol of the R-enantiomer, aortic flow rises precipitously during reoxygenation, reaching over 70% of normoxic values compared to 50% of the controls. By contrast, with the S-enantiomer a value of about 60% is attained at 1 mumol, only. Accordingly, ATPase activity in mitochondria isolated from rat hearts previously treated with 0.05-0.1 mumol of the R- or S-enantiomer was significantly decreased or increased respectively. Consequently, whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity, measured with diphenylhexatriene, revealed a trend towards increase with the R- and decrease with the S-enantiomer.”

Zimmer G, Beikler TK, Schneider M, Ibel J, Tritschler H, Ulrich H. Dose/response curves of Lipoic Acid R- and S- forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow. J Mol Cell Cardiol. 1995 Sep;27(9):1895-903.