What The Scientists 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 NADPHdependent 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 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 Rthioctic 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 Senantiomer.”
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.
