Kevin wrote:
When using alpha lipoic acid remember that the 'R' enatiomer is the one which research suggests is biologically active. Most health food store formulations include both the 'S' and 'R' enationmers in a 50/50 split.. so you are really paying for half of what your body actually uses. It's even been suggested that the "S" enationmer might affect the benefical aspects of the "R". I recommend finding a good source of the "R".shpongled replied:
I disagree... the S isomer is biologically active as well, just not as much so. When you consider the price difference, getting ALA is more than twice as cheap as R-ALA so you still save money that way. The only reason to prefer the R isomer alone I think is if you have diabetes or are at high risk of diabetes, but if using it as an antioxidant I would go with regular ALA. Also pure R-ALA is harder to find and degrades more easily.The S isomer is biologically active in the sense that a xenobiotic drug is biologically active -- ie, it has effects on the organism. However, only the R(+) enantiomer is
physiologically active. It is the orthomolecular form -- the form for which the body's DNA is coded and for which the body is designed to work.
The effects of the different forms of "lipoic acid" have varying antioxidant potency, depending on the exact nature of the free radical challenge (some examples are discussed beginning here:
http://www.r-lipoic....nt_Activity.htm ). But after all, even cyanide has antioxidant activity
. From the perspective of the radical life extensionist, the key issues are mitochondrial function and insulin signaling, both of which are emerging as key factors in the effects of caloric restriction and in genetically-modified model organisms. For these effects, it is clear that the orthomolecular R(+)-form is superior, and that in fact the S(-) enantiomer found in common (racemic) "alpha-lipoic acid" supplements is actively counterproductive. See:
http://www.r-lipoic....tochondrion.htmhttp://www.r-lipoic...._metabolism.htmTherefore, while conventional "alpha lipoic acid" supplements may be satisfactory in persons who already have a shortened life expectancy (for instance, in diabetics, for whom the benefits in symptomatic neuropathy may themselves be preferrable to most of the alternatives), healthy life extensionists wishing to gain maximum benefit should choose R(+)-lipoic acid over the racemic compound.
ex_banana_eater wrote:
Then again there is a study with increased mortality in rats fed only the S Isomer I believe. Whether this is related to the lessened risk of preventing diabetes I do not know, nor do I think all avenues were examined in the literature. You've probably encountered both of those studies preparing for your article.shpongled replied:
I don't recall coming across that, although I did the research quite some time ago. A possible explanation would be, if they gave rats high amounts of S-ALA, maybe it displaced the naturally occuring R isomer leading to some sort of negative effect. I don't know how sound this theory is. Either way I doubt this effect is of any consequence at supplemental doses of racemic ALA.I think that the study to which the
Musa apostate refers is:
Freisleben HJ, Neeb A, Lehr F, Ackermann H. Influence of selegiline or lipoic acid on the life expectancy of immunosuppressed mice. Arzneimittelforschung. 1997 Jun;47(6):776-80
This study is discussed here (note the graph):
http://www.r-lipoic....xir_of_life.htmThe effects of the racemic, R(+), and S(-) forms of lipoic acid on 50% survival were similar. But whereas R(+)-lipoic acid extended maximum lifespan, there was no statistically significant effect of the racemate (common "alpha lipoic acid") or of the S(-)-enantiomer on this parameter. I think that Ex Banana Eater was thinking of the
apparent reduction in maximum lifespan induced by the
racemate. And the dosages were
The problem was not the dosage, as the researchers fed the animals supplements at a concentration which, in a human, would only be about 630 mg - not at all out of line with what human users are taking. However, because this result was observed in a very short-lived strain of mouse, it cannot be considered definitive. More recently, Weindruch et al have reported no effect of racemic lipoic acid on survival in a longevous strain:
Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA. The impact of alpha-lipoic acid, coenzyme Q(10) and caloric restriction on life span and gene expression patterns in mice. Free Radic Biol Med. 2004 Apr 15;36(8):1043-57.
"[Racemic] LA ... had no impact on longevity or tumor patterns compared with control mice fed the same number of calories, whereas CR increased maximum life span by 13% (p <.0001) and reduced tumor incidence. ... [Racemic] LA ... inhibited age-related alterations in the expression of genes involved in the extracellular matrix, cellular structure, and protein turnover. However, unlike CR, [Racemic] LA ... did not prevent age-related transcriptional alterations associated with energy metabolism. [Racemic] LA supplementation lowered the expression of genes encoding major histocompatibility complex components and of genes involved in protein turnover and folding."It is worth noting that all of the exciting studies of Drs Tory Hagen and Bruce Ames, showing mitochondrial rejuvenation and reversal of age-related cognitive and cardiovascular deficits, resulted from the use of R(+)-lipoic acid. For their reasons for preferring R(+)-lipoic acid over the readily-available racemate, see the "Discussion" in their first FASEB Journal report on this subject, available for free in full text here:
http://www.fasebj.or...t/full/13/2/411"The ®-form of lipoic acid used in this study is the naturally occurring enantiomer in mammalian cells (24) . Only the ®-form is used by mitochondrial -keto acid dehydrogenases and specifically reduced to dihydrolipoic acid, a powerful antioxidant, via mitochondrial lipoamide dehydrogenase. There is evidence that ®-lipoic acid supplementation may be more potent than either the racemic mixture (the form sold commercially as alpha-lipoic acid) or (S)-enantiomer, and thus a more relevant supplement for this study. Addition of ®-lipoic acid increases ATP synthesis and aortic blood flow during reoxygenation after hypoxia in a working heart model (25) . The (S)-enantiomer had no effect on ATP synthesis and improved blood flow at only 10-fold the effective dose of ®-lipoic acid. Packer and colleagues (26) also showed that ®-lipoic acid significantly reduced buthionine-S,R-sulfoximine-induced cataract formation, but (S)-lipoic acid had little effect at the same concentration. ®-Lipoic acid increased glucose uptake and the number of glucose transporters in muscle tissue much more effectively than (S)-lipoic acid (27) . The ®-enantiomer more effectively chelated copper and prevented copper-induced lipid peroxidation (28) ."See also some of their later reports:
"Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-alpha-lipoic acid"
http://www.pnas.org/.../full/99/4/2356"Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha-lipoic acid"
http://www.pnas.org/.../full/99/4/1876"Feeding acetyl-L-carnitine and [R-alpha]-lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress."
http://www.pnas.org/.../full/99/4/1870It's unfortunate that many companies use these studies, for which Hagen and Ames very consciously chose the orthomolecular R(+)-enantiomer, to promote the use of racemic "lipoic acid" supplements.
Here are some comments by other prominent lipoic acid research scientists:
"We're finding - and others are, too - that the R(+)-form - the natural form - is much more powerful than the racemic mixture ... Hopefully ... companies are going to be producing on more of a clinical scale the R(+)-form of lipoic acid, because we're finding very significant effects using this, as opposed to the racemic mixture."
Dr. Tory Hagen, in Mitochondrial Decay in Aging.
"We have presented in this study new information indicating that this enhancement of glucose metabolism is sterospecific, with the R(+)-enantiomer being much more effective than the S(-)- enantiomer."
Dr. Ryan Streeper and colleagues, in The American Journal of Physiology.
"Lipoic acid sold in a health food store is a synthetic mixture, a racemic mixture. And R[+]- is the natural form and S[-]- is an unnatural one ... And in our hands R[+]- works and S[-]- doesn't."
Dr. Bruce Ames, in Strategies for Engineered Negligible Senescence.
"R[+]-LA [that is, R(+)-lipoic acid], and not a racemic mixture of R[+]-and S[-]- LA, should be considered a choice for therapeutic applications."
Dr. Lester Packer and colleagues, in Free Radical Biology and Medicine.
"The S[-]-enantiomer … part of the racemate, which is present as about a 50% impurity, needs to be eliminated."
Dr. Guido Zimmer and colleagues, in Methods in Enzymoogy.
AOR was proud to be the first supplement company in the world to make R(+)-lipoic acid available as a pharmaceutical-gradde dietary supplement (as opposed to as a research chemical), for the use of the life extension community.
To your health!
AOR
LongeCity
