44 replies to this topic

[hamishm00]

Another worrying ALA rat study is set out below. Since Homocysteine = bad; S-adenosylmethionine (SAM) = good, as a result of this paper it might pay dividends for life extensionists to consider whether or not it is worth dropping ALA supplementation levels somewhat and increasing SAM supplementation.

Here is the Extract

Free Radic Biol Med. 2009 Oct 15;47(8):1147-53. Epub 2009 Jul 17.
Alpha-lipoic acid induces elevated S-adenosylhomocysteine and depletes
S-adenosylmethionine.
Stabler SP, Sekhar J, Allen RH, O'Neill HC, White CW.
Department of Medicine and Division of Hematology, University of
Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Sally.Stabler@ucdenver.edu

Lipoic acid is a disulfhydryl-containing compound used in clinical
medicine and in experimental models as an antioxidant. We developed a
stable isotope dilution capillary gas chromatography/mass spectrometry
assay for lipoic acid. We assayed a panel of the metabolites of
transmethylation and transsulfuration 30 min after injecting 100 mg/kg
lipoic acid in a rat model. Lipoic acid values rose 1000-fold in serum
and 10-fold in liver. A methylated metabolite of lipoic acid was also
detected but not quantitated. Lipoic acid injection caused a massive
increase in serum S-adenosylhomocysteine and marked depletion of liver
S-adenosylmethionine. Serum total cysteine was depleted but liver
cysteine and glutathione were maintained. Serum total homocysteine
doubled, with increases also in cystathionine, N,N-dimethylglycine,
and alpha-aminobutyric acid. In contrast, after injection of
2-mercaptoethane sulfonic acid, serum total cysteine and homocysteine
were markedly depleted and there were no effects on serum
S-adenosylmethionine or S-adenosylhomocysteine. We conclude that large
doses of lipoic acid displace sulfhydryls from binding sites,
resulting in depletion of serum cysteine, but also pose a methylation
burden with severe depletion of liver S-adenosylmethionine and massive
release of S-adenosylhomocysteine. These changes may have previously
unrecognized deleterious effects that should be investigated in both
human disease and experimental models.

PMID: 19616616


From the Discussion section of the full paper:

"Commonly used doses of LA in human disease range from 600 to 1800 mg/day [1],
which for a 70-kg person will range from roughly 9 to 26 mg/kg, thus
4- to 10-fold less than in our rat model. However, at the higher doses
it is likely that LA might pose a methylation burden and human subjects
should be tested for changes in transmethylation and transsulfuration
metabolites. A recent report suggests that an improved formulation of
R-(+)-LA has significantly higher bioavailability and, thus, might be
expected to have more effect on methylation status [38]. Placebo-controlled
trials in diabetic neuropathy have shown a clear benefit of LA with
few demonstrated side effects [1]. Fortunately, there is not a dose
response, with lower doses equally effective, which would probably
have less potential to cause hyperhomocysteinemia. In Parkinson
disease treatment with L-dopa, the hyperhomocysteinemia presumptively
attributed to the methylation burden has been correlated with vascular
disease [35]. Therefore some concern may be warranted if large doses
of LA are used in human medicine. An interesting difference in LA dose
toxicity has been described in cats compared to humans and dogs, which
could be investigated for methylation defects [39]. LA is being
investigated in cell models as a cancer chemotherapeutic agent because
high concentrations in the medium (100 umol/L-5 mmol/L) have been
reported to induce apoptosis in a variety of cell lines [40], [41],
[42] and [43]. The impact of probable SAM depletion and SAH-induced
transmethylation inhibition should be investigated in these systems.

"In summary, we have demonstrated that a common experimental dose of
LA causes massive depletion of liver SAM, elevation of serum SAH, and
increased tHcys in rats. Similar depletion of serum cysteine with
MESNA was not accompanied by changes in SAM and SAH, suggesting that
the former effects are due to various aspects of LA metabolism/
catabolism. Further studies in humans may be interesting."

Edited by hamishm00, 06 October 2009 - 07:05 PM.

[Sillewater]

bump,

I am wondering what dose his would be in humans?

[Blue]

No actual harmful effect shown. For all we know this is how ALA achieves its good effect. It is likely a short term stressor that more long-term upregulates various counter-acting systems. Like exercise.

Edited by Blue, 22 October 2009 - 06:51 PM.

[nowayout]

No actual harmful effect shown. For all we know this is how ALA achieves its good effect. It is likely a short term stressor that more long-term upregulates various counter-acting systems.

According to that reasoning, smoking should be good for you.

The evidence is mounting against the use of ALA willy nilly.

[Blue]

No actual harmful effect shown. For all we know this is how ALA achieves its good effect. It is likely a short term stressor that more long-term upregulates various counter-acting systems.

According to that reasoning, smoking should be good for you.

The evidence is mounting against the use of ALA willy nilly.

Smoking is not a short-term stressor. Exercise becomes harmful if you do it enough. Ala disappears very quickly after intake.

What mounting evidence? It has been used for decades in Germany. There are large, multi-years, placebo-controlled studies finding benefits with no evidence of adverse effects. This in addition to numerous animal models show it improves many age-related conditions and damage.

Edited by Blue, 22 October 2009 - 07:54 PM.

[nowayout]

What mounting evidence? It has been used for decades in Germany.

On sick people, not healthy ones. Injecting insulin is also very good for you, if you happen to have diabetes. Otherwise not so much.

When are amateur life extensionists going to realize that everything that is good for a diabetic is not necessarily good for a non-diabetic?

Edited by viveutvivas, 22 October 2009 - 09:09 PM.

[ajnast4r]

On sick people, not healthy ones. Injecting insulin is also very good for you, if you happen to have diabetes. Otherwise not so much.

When are amateur life extensionists going to realize that everything that is good for a diabetic is not necessarily good for a non-diabetic?

pay this man

[Blue]

What mounting evidence? It has been used for decades in Germany.

On sick people, not healthy ones. Injecting insulin is also very good for you, if you happen to have diabetes. Otherwise not so much.

When are amateur life extensionists going to realize that everything that is good for a diabetic is not necessarily good for a non-diabetic?

No one claimed that. But for example vitamin D is good for both diabetics and non-diabetics. Again, in numerous animal models show it improves many age-related conditions and damage. Many of these studies are on the aging brain which is the single organ I most which to preserve as intact as possible. The risk:benefit ratio is excellent in my opinion.

Edited by Blue, 23 October 2009 - 03:29 AM.

[Kutta]

Well, first, the study is pretty much in accordance with what we already knew about ALA. Second, we need typical human dosage trials on humans and not "4 to 10 fold" amounts, and also trials about how ALA affects base homocysteine levels, not only post-LA administration levels. By itself this study has little relevant information to us.

[hamishm00]

IMO there is no way that this study means don't take ALA.

BTW if the standard scaling factor for rats is applicable here (not saying it is) the rat dosages used would then be only 1 to 3 times the commonly used human dosages.

What I think this all means is that if you are taking high dose ALA (say in excess of 600mg a day), it would be wise to supplement SAM.

Edited by hamishm00, 23 October 2009 - 02:44 PM.

[nowayout]

Alpha Lipoic Acid causes massive S-adenosylmethionine (SAM) depletion , Also worrying elevation of homocysteine levels

but then

IMO there is no way that this study means don't take ALA.

It's your funeral, I guess...

[hamishm00]

Yes, but there are ways to lower homocysteine levels and increase SAM levels.

I will continue to take ALA.

[Sillewater]

I'll probably add it too, but I'm going to make sure to get my Hcy levels measured after a couple of months.

[kismet]

On sick people, not healthy ones. Injecting insulin is also very good for you, if you happen to have diabetes. Otherwise not so much.

When are amateur life extensionists going to realize that everything that is good for a diabetic is not necessarily good for a non-diabetic?

pay this man

Actually, this is the time to say: when will people realise that we're not rats and that mechanistic evidence is inferior to outcome studies. Mechanistic evidence in rats is even weaker ("Overdoses of yx increase xy, which may be bad in humans, in rats" So?)
What's a typical LE dose (from those 600 to 1800 mg/d)? What are the strongest RCTs in humans? How much did Hcy increase and is there human data?

I'll probably add it too, but I'm going to make sure to get my Hcy levels measured after a couple of months.

That's probably useless without knowing baseline levels. If lipoic acid caused clinically relevant hyperhomocysteinemia (smth. you could diagnose w/o knowing baseline levels) we'd know it already.

Edited by kismet, 23 October 2009 - 05:21 PM.

[nowayout]

Yes, but there are ways to lower homocysteine levels and increase SAM levels.

But how do you know this is all that ALA does?

Do you know the metabolic pathways causing these deleterious effects, and exactly at what point ALA is disrupting them? If so, please tell the rest of us.

[nowayout]

Actually, this is the time to say: when will people realise that we're not rats ...

You just demolished the entire case in favour of taking ALA in the first place.

[ensun]

100mg/kg is quite a lot. Anybody here taking 7 grams of ALA per day? Didn't think so. Also, did they use the racemic form? That is important to know, you know.

[nowayout]

100mg/kg is quite a lot. Anybody here taking 7 grams of ALA per day? Didn't think so.

That is not how metabolic scaling works. Read Hamish's post above.

[ensun]

Well, divided by 6, it's still quite a lot. But it's very possible that the S isomer is what's causing this damage... we don't know since the scientists were too cheap to use NA-RALA.

[nowayout]

Well, divided by 6, it's still quite a lot. But it's very possible that the S isomer is what's causing this damage... we don't know since the scientists were too cheap to use NA-RALA.

Yes, that is a weakness, but they do speculate that

A recent report suggests that an improved formulation of
R-(+)-LA has significantly higher bioavailability and, thus, might be
expected to have more effect on methylation status [38].

Edited by viveutvivas, 23 October 2009 - 06:07 PM.

[ensun]

Yes, they do speculate that, but that would be an incorrect speculation since the S isomer has been shown to do many things that the R isomer does not.

[somec]

Once SAM-e donates its methyl group to choline, in the formation of creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Under normal circumstances, homocysteine, in the presence of vitamin B6, vitamin B12, and folic acid (SAM-e's main co-factors), will eventually be converted back into methionine, SAM-e, or cysteine, glutathione, and other useful substances. However, if adequate amounts of these vitamins are not present, SAM-e will not break down properly. As a consequence, the full benefits of SAM-e will not be obtained, and homocysteine may increase to unsafe levels.

High levels of homocysteine have been associated with atherosclerosis (hardening and narrowing of the arteries), as well as an increased risk of heart attacks, strokes, liver damage, and possibly Alzheimer's disease. Therefore, Vitamin B supplements are often taken along with SAM-e. These vitamins help metabolize the homocysteine into other useful compounds.

[somec]

I wonder what kind of vitamin B levels the rats in this study had at the time of the experiment. If they were deficient it could explain the significant decrease of SAM. I am also curious if supplementing with the appropriate amount of vitamin B can equalize the apparent depletion of SAM in the rats and hypothetically humans.

[niner]

Yes, they do speculate that, but that would be an incorrect speculation since the S isomer has been shown to do many things that the R isomer does not.

What does the S isomer do that the R isomer does not?

[Blue]

Once SAM-e donates its methyl group to choline, in the formation of creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Under normal circumstances, homocysteine, in the presence of vitamin B6, vitamin B12, and folic acid (SAM-e's main co-factors), will eventually be converted back into methionine, SAM-e, or cysteine, glutathione, and other useful substances. However, if adequate amounts of these vitamins are not present, SAM-e will not break down properly. As a consequence, the full benefits of SAM-e will not be obtained, and homocysteine may increase to unsafe levels.

High levels of homocysteine have been associated with atherosclerosis (hardening and narrowing of the arteries), as well as an increased risk of heart attacks, strokes, liver damage, and possibly Alzheimer's disease. Therefore, Vitamin B supplements are often taken along with SAM-e. These vitamins help metabolize the homocysteine into other useful compounds.

Lots of studies lowering homocysteine with high amounts of B vitamins have found only a very small, if any, effect on clinical outcomes.

[Blue]

Yes, they do speculate that, but that would be an incorrect speculation since the S isomer has been shown to do many things that the R isomer does not.

What does the S isomer do that the R isomer does not?

As far as I know nothing but it does seem to have some weaker activity on its own. Almost all studies have used the mixture. Pure R isomer has a poorer bioavailability than the mixture unless special preparations (Na- or K-RALA) are taken.

Edited by Blue, 24 October 2009 - 01:04 AM.

[Blue]

The discussed study as far as I can see only look at the situation 30 minutes injection of ALA in a rat. Here is another study in humans after a month of daily ala use.

The present study was conducted to see the efficiency of alpha-lipoic acid in the active management of coronary heart disease patients (N=40). Alpha- lipoic acid is a vitamin like powerful antioxidant, which is soluble in both water and fat. At the membrane level we get protection before free radicals enters the cell. Any free radicals that make it past the first line of protection are combated right in the cell. It was seen that alpha-lipoic acid may have beneficial effects in reducing blood lipid profile and fibrinogen significantly (p<0.001) while homocysteine and triglyceride were decreased insignificantly (p>0.05). Observation strongly suggests that alpha lipoic-acid may have beneficial effects in reducing both old and new risk markers in coronary heart disease patients.
http://www.indmedica...;action=article

Regading SAM-e I would consider it much riskier than ALA. There has been lots of discussions regarding the role of folate as promoting/prevention of cancer due to methylation issues. That discussion applies at least as much to SAM-e as a very important methyl donor. Not sure if there has been any studies lasting more than a few months and it is relatively new as a supplement.

Edited by Blue, 24 October 2009 - 01:36 AM.

[ensun]

S-Lipoic acid produces different biological actions than R-Lipoic Acid that may be undesirable. (16-22)

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.   (7) 

S-Lipoic acid cannot bind with critical mitochondrial enzymes and inhibits ATP production. (16)

The studies listed below have shown that:

SLA has effects in the body which are different than RLA.

Although SLA is an excellent antioxidant (but RLA is better) none of the other effects of SLA have been shown to be beneficial.

Since SLA does not naturally occur in the body and consequently the body has not developed mechanisms to deal with it, the effects of non-physiological doses of SLA are more likely to be harmful than are non-physiological doses of RLA which does occur naturally in the body and for which it does have mechanisms to deal with it. Therefore, SLA should not be considered as mere filler in the racemic mixture of enantiomers which is widely available on the supplement market, but should be considered potentially harmful until proven otherwise. This not to say that non-physiological doses of RLA may not also be harmful, only that they are less likely to be so. In particular, RLA is likely to be less harmful and more beneficial than the racemate generally used.

The concluding remarks from the chapter on RLA in The Handbook of Antioxidants, aptly summarize these conclusions:

"Since, the popularity and the interest in LA as an antioxidant are rising, there is, therefore, a need for better understanding of the pharmacology of this compound. Frequently, the two enantiomers of LA the R- and the S- forms do not have the same potency and biological efficacy. Occasionally, the biological effects exerted by one enantiomer were contradicted by the other form. However, so far R-LA, which is the natural ofrm of LA, was superior and with more potent phamacological activity than S-LA in all of in vitro models and clinical experiments. The two enantiomers of LA should be looked on as two different pharmacological agents, antioxidants, or drugs."R

"These findings indicate that (i) the activities of the mammalian pyruvate dehydrogenase complex and its catalytic components are affected by lipoic compounds based on their stereoselectivity; and (ii) the oxidation of pyruvate by intact HepG2 cells is not inhibited by R-LA but is moderately decreased by S-LA. The later finding with the intact cells is in support of therapeutic role of R-LA as an antioxidant" and the reduced value of S-LA.R

"Maximum plasma concentrations (Cmax) of the R-(+)-enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg: 135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA, 978.20 ng/ml S-(-)-TA; geometric means)."R

"The concentrations of glutathione in normal lenses or lenses incubated with R- or racemic alpha-LA were not significantly different, but the concentration of glutathione in lenses incubated with S-alpha-LA was significantly lower than the R-alpha-LA-incubated lenses."R

"Of particular interest is the observation that the lenses are stereospecifically protected by the R-alpha-lipoic acid, but not S-alpha-lipoic acid. A possible mechanism [for this protection from cataract forming processes] is the hypothesis that the stereospecific protection by R enantiomer, but not the S enantiomer, is due to protection of the mitochondria of the newly differentiated lens fiber cells at the equator."R.

The individual effects of the pure R-(+) and S-(-) enantiomers of alpha-lipoic acid to enhance insulin-stimulated glucose metabolism in skeletal muscle was studied in obese Zucker rats: an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia. Generally, RLA had major positive effects on all studied parameters. SLA had either no effect on all parameters except: 1) a negative chronic effect on insulin (15% increase versus 17% decrease for RLA), 2) a lesser positive chronic effect on 2-deoxyglucose uptake (65% increase by RLA versus 29% by SLA), 3) glucose transporter (GLUT-4) protein was unchanged after chronic RLA treatment but was reduced to 81 +/- 6% of obese control with SLA treatment. The study conclusion was: "the R-(+) enantiomer being much more effective than the S-(-) enantiomer."R

In a group of 14 immunosuppressed NMRI-mice (nu/nu) raised and kept under germ-reduced conditions, SLA, even at 75 mg/kg body weight per day, increased the 50% survival rate, but did not expand "the total life span of its group"R.

"An intact organ, the isolated perfused rat heart, reduced R-lipoate six to eight times more rapidly than S-lipoate ... On the other hand, erythrocytes, which lack mitochondria, somewhat more actively reduced S- than R-lipoate ... Thus, mechanisms of reduction of alpha-lipoate are highly tissue-specific and effects of exogenously supplied alpha-lipoate are determined by tissue glutathione reductase and dihydrolipoamide dehydrogenase activity"R.

"In cultured cells from the mesencephalon of C57BL/6 mice, treatment with lipoic acid resulted in partial restoration of 3H-dopamine uptake and dopamine content after exposure of the cells to MPP+ ...; only the naturally occurring R-enantiomer was effective."R

"In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by ®-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin."R

"Rat lens opacity formation and LDH leakage, resulting from incubation in medium containing 55.6 mM glucose to model diabetes, were suppressed by the addition of 1 mM R-lipoic acid. Addition of 1 mM racemic lipoic acid reduced these damaging effects to the lens by only one-half, while S-lipoic acid only potentiated LDH leakage, consistent with the hypothesis that R-lipoic acid is the active form. Although HPLC analysis demonstrated that both stereoisomers of lipoic acid were reduced to dihydrolipoate at comparable rates by the intact lens, the mitochondrial lipoamide dehydrogenase system is highly specific for reduction of exogenous R-lipoic to dihydrolipoic acid. 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 where the first globular degeneration is seen in glucose cataract."R

This study revealed a marked stereospecificity in the prevention of induced cataract, and in the protection of lens antioxidants, in newborn rats by alpha-lipoate, R- and racemic alpha-lipoate Cataract formation was decreased from 100% to 55% by R-alpha-lipoic acid and 40% by rac-alpha-lipoic acid. S-alpha-lipoic acid had no effect on induced cataract formation. The lens antioxidants glutathione, ascorbate, and vitamin E were depleted to 45, 62, and 23% of control levels, respectively, by the cataract inducing treatment, but were maintained at 84-97% of control levels when R-alpha-lipoic acid or rac-alpha-lipoic acid were administered; S-alpha-lipoic acid administration had no protective effect on lens antioxidants. When enantiomers of alpha-lipoic acid were administered to animals, R-alpha-lipoic acid was taken up by lens and reached concentrations 2- to 7-fold greater than those of S-alpha-lipoic acid, with rac-alpha-lipoic acid reaching levels midway between the R-isomer and racemic form. Reduced lipoic acid, dihydrolipoic acid, reached the highest levels in lens of the rac-alpha-lipoic acid-treated animals and the lowest levels in S-alpha-lipoic acid-treated animals. These results indicate that the protective effects of alpha-lipoic acid against induced cataract are probably due to its protective effects on lens antioxidants, and that the stereospecificity exhibited is due to selective uptake and reduction of R-alpha-lipoic acid by lens cellsR.

"Racemic lipoic acid is therapeutically applied in pathologies in which free radicals are involved. The in vivo reduction of lipoic acid may play an essential role in its antioxidant effect. It was found that mitochondrial lipoamide dehydrogenase reduces the R-enantiomer 28 times faster than the S-enantiomer of lipoic acid. S-lipoic acid inhibits the reduction of the R enantiomer only at relatively high concentrations."R

"Whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working rat heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity ... revealed a trend towards increase with the R- and decrease with the S-enantiomer."R

"In feeding experiments, however, R lipoate significantly inhibited glucose oxidase-mediated skin inflammation, while S lipoate was only marginally protective."R

RLA "is the naturally occurring cofactor in alpha-ketoacid dehydrogenases. We show both photometrically by NADH+H+ oxidation and by HPLC product analysis that this enantiomer is rapidly reduced by NADH+H+ catalyzed by porcine heart lipoamide dehydrogenase/diaphorase. The racemate exhibits approximately 40% activity as compared to the form while the S(-) enantiomer photometrically shows little activity and yields no detectable reduced lipoic acid."R

The reduction of exogenous alpha-lipoic acid to dihydrolipoate by mammalian cells and tissues confers additional antioxidant protection to the cell. Both (R+) and (S-) isomers of alpha-lipoic acid were analyzed as substrates with glutathione reductase from several sources and with mammalian lipoamide dehydrogenase. Mammalian glutathione reductase catalyzed faster reduction of (S)-lipoic acid (1.4-2.4-fold greater activity) than of ®-lipoic acid, whereas lipoamide dehydrogenase had a very marked preference for ®-lipoic acid (18-fold greater activity) over (S)-lipoic acid"R.

"The hyperglycemic effects of D-glucose [on erythrocyte membrane fluidity] were corroborated with isolated, reconstituted membrane proteins and erythrocyte glucose carrier, indicating that, in general, the observed divergent biochemical/biophysical changes of the red cell membrane are influenced by the glucose transport protein GluT1. The natural R-form and the S-form of alpha-lipoic acid were compared with racemic R-/S-forms for their efficiencies in alterations of red cell membrane fluidity. Decreased fluidities in presence of 10 mM glucose were found to be influenced in differentiated ways: the S-form was highly active in increasing fluidity at 4 nmol/mg and increasingly less active up to 20 nmol/mg protein. By contrast the R-form of lipoic acid was moderately efficient in increasing fluidity through a larger concentration range between 4 and 80 nmol/mg protein"R.

" 1 SLA has effects in the body which are different than RLA.

" 2 Although SLA is an excellent antioxidant (but RLA is better) none of the other effects of SLA have been shown to be beneficial.

" 3 Since SLA does not naturally occur in the body and consequently the body has not developed mechanisms to deal with it, the effects of non-physiological doses of SLA are more likely to be harmful than are non-physiological doses of RLA which does occur naturally in the body and for which it does have mechanisms to deal with it.

" 4 Therefore, SLA should not be considered as mere filler in the racemic mixture of enantiomers which is widely available on the supplement market, but should be considered potentially harmful until proven otherwise. This not to say that non-physiological doses of RLA may not also be harmful, only that they are less likely to be so. In particular, RLA is likely to be less harmful and more beneficial than the racemate generally used."

Edited by ensun, 24 October 2009 - 01:42 AM.

[Blue]

All the test tube experiments showing different effects may not be that interesting since in the body ALA is rapidly eliminated unlike in test tubes. The good effects may be due to something done during its brief existence before elimination. Furthermore, since we do not know exactly how ALA is causing its effects it may well be that SALA is actually more effective for that effect. Only animal or human studies with the different isomers really count.

[maxwatt]

All the test tube experiments showing different effects may not be that interesting since in the body ALA is rapidly eliminated unlike in test tubes. The good effects may be due to something done during its brief existence before elimination. Furthermore, since we do not know exactly how ALA is causing its effects it may well be that SALA is actually more effective for that effect. Only animal or human studies with the different isomers really count.

It is my understanding that the oxidized S isomer is not cleared from the cell as is the R isomer, and it "clogs" the machinery.

I know lipoic acid has been touted for a decade and a half for health and longevity, but I have still not seen definitive human trials showing a positive effect (or a negative one, for that matter) in healthy, non-diabetic human subjects. I mean definitive, not a single study. It does nothing for my blood sugar, energy levels or anything else I can determine. I find this sadly disappointing.

Edited by maxwatt, 24 October 2009 - 07:59 AM.
typos