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-alphalipoic acid and S-alpha-lipoic
acid), unlike the racemate, the R-enantiomer mainly has an antiinflammatory
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
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 studies
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 lifeexpectancy 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 other antioxidants. ...that this compound
has important therapeutic potential in conditions where oxidative stress is
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):53542, 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 Jenner, T.A. Seaton, and C.D. Marsden. Chapter 16 in Lipoic Acid in Health and Disease; Altered CDeoxyglucose 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 Renantiomer 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.
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