46 replies to this topic

[glexia]

Hi,


I´m going to buy Lipoic Acid , but there are a lot of brands and forms of this supplement. I know R-ALA is the most bioavailable, but i don,t know the differences between Brands.

-Which is best? (Brand and form)
-Why?
-Mg/day??

I found a lot of information but i can´t decide on any.





Thanks! [thumb]

Glexia 25 Spanish girl.

[FunkOdyssey]

This is AOR's stance on R-DHLA, which I happen to agree with:

After a careful review of the evidence, the team at AOR has concluded that these arguments do not hold up to scientific scrutiny. R-lipoic acid is by far the more evidence-backed supplement, and many of its key benefits – on cellular homeostasis, mitochondrial function, and perhaps aging itself – cannot be gained from substituting preformed R-dihydrolipoic acid in its place.

This argument is presented in much greater detail here:

http://aor.ca/magazi...lipoic_Acid.pdf

Geronova has yet to counter AOR's blasting of R-DHLA, and I'm starting to wonder if they ever will. That leaves a sustained-release, RLA only product as our best bet. The two options there are AOR's R,SR, or Geronova's RLA-MCT25. The former is relatively expensive but is conveniently encapsulated. The latter is available in an economical bulk powder form.

With regard to dosage:

MR:

Based on the Hagen/Ames studies, an appropriate dose after adjusting for allometric metabolic scaling would be 1.29 to 4.3 g of ALCAR and 612.6 - 1225.2 mg R-Lipoic. Happily, these dosages span the ranges used in human clinical trials for neurodegenerative disease, so we can have some confidence that these are appropriate dosages in terms of safety and efficacy in humans.

Edited by FunkOdyssey, 01 June 2006 - 03:24 PM.

[zoolander]

I have done some calculations myself from other studies with R-lipoic acid and they all seem to come out close to the 1000 mg mark. Most companies sell R-lipoic acid is 100mg caps and taking 6-12 caps a day seems alot. It also works out (at cheapest) to be around $1-2 dollars a day.

Some could probably benefit from ditching some of their snake oil supplements and invest in something with a little research behind it though

[FunkOdyssey]

I have done some calculations myself from other studies with R-lipoic acid and they all seem to come out close to the 1000 mg mark.

I'm using 900mg a day myself. Strangely, no symptoms of low blood sugar like I experienced at only 600mg last year. I think adrenal fatigue left me particularly susceptible to that side effect.

[FunkOdyssey]

Bruce Ames:

Lipoic acid sold in a health food store is a synthetic mixture, a racemic mixture. And R is the natural form and S is some unnatural one. R is reduced in mitochondria, S is reduced in the cytoplasm. And in our hands R works and S doesn't.

You can draw your own conclusions, but bear in mind that Bruce Ames is the world's leading lipoic acid researcher.

That quote is from the original SENS conference. The full transcript is available here:

http://www.som.ucla..../transframe.htm

[unbreakable]

I read on sci.life-extension that immediate release ®-ALA might be more effective than the sustained release versions. Here is the explanation:

Here is what we know about absorption of alpha-lipoic acid. It is
quickly absorbed with dosage proportionality – meaning that roughly
the same percentage is absorbed whether the dosage is 50 or 600 mg.
The absolute bioavailability of alpha-lipoic acid based on
radioactive studies indicate it amounts to roughly 93% of the
administered dose. 1,2


So, we know that alpha-lipoic acid is quickly absorbed and there is
dosage proportionality. Those facts alone indicate that it is a poor
candidate for a timed-released preparation, but there is more. As
drugs and nutrients are absorbed in the gastrointestinal tract they
pass through the liver. Considerable research data indicates that
alpha-lipoic acid is extensively metabolized in the liver. In the
pharmaceutical world, it would be stated that alpha-lipoic acid has a
high first pass effect. What this means is that the amount of drug
that actually enters the systemic circulation is considerably less
than the amount absorbed because the first pass through the liver is
so effective at converting or breaking down the substance. That is
exactly the case with alpha-lipoic acid. While 93% may be absorbed,
only about 30% actually gets into the bloodstream before it is broken
down. Taking a timed-release preparation only enhances the first pass
effect and produces significantly lower peak and overall blood values
than an immediate release preparation.


While we know a great deal about how immediate release alpha-lipoic
acid is handled by the body, there has been only one study with a
timed released preparation. 3  It was not a double-blind study and
the clinical results were not all that significant. For example,
there was no improvement in fasting blood sugar levels and the degree
of glycosylation was improved by less than 10% in 15 subjects taking
1,200 mg of a timed released alpha-lipoic acid supplement for 12
weeks. That is quite a hefty dosage to show such limited benefit.


While the timed-release product was absorbed more slowly over time and
appears to persist in the plasma longer, it did not produce as high of
peak value as the immediate release nor was the area under the curve
(AUC) as high as the immediate release. The AUC is often used to show
the total absorption of compound over time. The AUC for the immediate
release alpha-lipoic acid was 4,466 ng/ml compared to 2,621 ng/ml.
Even the author of the study concluded that the timed-released
formula was associated with an approximately 40% reduction in overall
bioavailability compared to the immediate release product. What this
data seems to signify is that because a timed-release product will be
absorbed slowly over time, the liver is much better able to grab hold
of and breakdown the alpha-lipoic acid into inactive forms.


It also appears to gain the greatest clinical benefits with oral
alpha-lipoic acid what is required is to flood or overwhelm the
liver’s ability to grab hold of the alpha-lipoic acid and thereby
allow it into the general circulation leading to rapid elevations in
blood levels and delivery to other vital tissues. This goal appears
best achieved with immediate release products. Most double-blind
studies have shown benefits with 300 to 600 mg daily of immediate
release alpha lipoic acid in improving diabetic neuropathy and
insulin sensitivity.


The existing evidence does not seem to support an advantage to taking
a timed-release product. In fact, it looks like immediate release
formulations are better utilized.


References:


Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in
the prevention of diabetes complications. Nutrition
2001;17(10):888-95.


Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss R. Investigations
on the pharmacokinetics of alpha-lipoic acid in healthy volunteers.
Int J Clin Pharmacol Ther 1998;36(12):625-8


Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics,
tolerability, and fructosamine-lowering effect of a novel,
controlled-release formulation of alpha-lipoic acid. Endocr Pract
2002;8(1):29-35

What do you think?

[zoolander]

Cell Biochem Funct. 2006 Jan-Feb;24(1):79-85. 
   
    Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing rat.

    Kayali R, Cakatay U, Akcay T, Altug T.

    Istanbul University, Cerrahpasa Faculty of Medicine, Department of Biochemistry, Kocamustafapasa, 34303, Istanbul, Turkey.

    In the present study, we investigated whether DL-alpha-lipoic acid (LA) supplementation could have prooxidant or antioxidant effects on oxidative protein damage parameters such as protein carbonyl (PCO), nitrotyrosine (NT), advanced oxidation protein products (AOPP), and protein thiol (P-SH), as well as oxidative stress parameters such as total thiol (T-SH), non-protein thiol (Np-SH), and lipid hydroperoxide (LHP) in the brain and the skeletal muscle tissue of aged rats. PCO, and NT levels were increased, AOPP and P-SH levels were not changed in the brain tissue of aged rats given LA supplementation. On the other hand, TSH, Np-SH, and LHP levels were decreased in the brain tissue of aged rats given LA supplementation. The levels of the same parameters were not significantly different in the skeletal muscle tissue of aged rats given LA supplementation. The increased levels of protein oxidation markers such as PCO, and NT in the brain tissue of LA-supplemented aged rats compared with non-supplemented aged rats may suggest that oxidative protein damage is increased in LA-supplemented aged rats. We assume that an explanation for our findings regarding LA supplementation on protein oxidation markers in the brain tissue of aged rats may be due to the prooxidant effects of LA. Depending on post-mitotic tissue type and dosage of LA, the prooxidant effects of LA supplementation, should be considered in future studies. Copyright 2004 John Wiley & Sons, Ltd.

    PMID: 15532093 [PubMed - indexed for MEDLINE]

This is an in vivo study. A few that were mentioned in the bulk of the paper do not appear in the abstract. It was mentioned that the proxidant effect of DHLA was inhibited by LA (1) and that the above results regarding protein oxidation may be attributed to the prooxidant property of DHLA.

[spins]

I read on sci.life-extension that immediate release ®-ALA might be more effective than the sustained release versions. Here is the explanation:

What do you think?

I'm currently taking R(+) SR by AOR, as you all know this is sustained release. Would I be better of switching, it would certainly be much cheaper and judging by the post by unbreakable I'd be getting more benefit? [huh]

[FunkOdyssey]

It also appears to gain the greatest clinical benefits with oral
alpha-lipoic acid what is required is to flood or overwhelm the
liver’s ability to grab hold of the alpha-lipoic acid and thereby
allow it into the general circulation leading to rapid elevations in
blood levels

That might be the best approach if you're trying to lower blood sugar dramatically in diabetic patients. We aren't trying to treat diabetes here -- ideally, we would like our r-lipoic acid to reduce mitochondrial ROS production around the clock. I'm not an expert, but with a half-life of 22 minutes, it doesn't seem like immediate release RLA can serve this purpose.

[opales]

It also appears to gain the greatest clinical benefits with oral
alpha-lipoic acid what is required is to flood or overwhelm the
liver’s ability to grab hold of the alpha-lipoic acid and thereby
allow it into the general circulation leading to rapid elevations in
blood levels

That might be the best approach if you're trying to lower blood sugar dramatically in diabetic patients. We aren't trying to treat diabetes here -- ideally, we would like our r-lipoic acid to reduce mitochondrial ROS production around the clock. I'm not an expert, but with a half-life of 22 minutes, it doesn't seem like immediate release RLA can serve this purpose.

The problem with this is that while the immidiate release R-ALA has a plasma half-life of 22min, does not mean that it still can't exert it's benefits *IN* the cell (or was it mitochondria) for a longer time, where I believe it accumulates and can be detected even after 22min. I believe this was mentioned by a one particular science savvy CR society member in the CR society list, ut I can't find it.

[FunkOdyssey]

AOR:

Sustained release ALA formulations allow for constant improvements in insulin sensitivity and the results obtained in human trials done with sustained release R(+)-lipoic acid are impressive. Supplementation resulted in sustained decreases in blood glucose that averaged 184mg/dl or just over a 46% decrease.

Let me know if anyone finds the reference(s) for this statement.

[doug123]

What that might mean is that the MCT might make the R-LA be able to reach farther than the stomach, so more should get absorbed; possibly at different stages of digestion; and that might simulate the "time release" effect. I guess that is the hypothesis GeroNova is using to support the time release claim.

If one wants to take the therapeutically relevant "anti aging/cognitive enhancement" dose of R-alpha-lipoic acid, you would need to take at least 400mg - 600mg/day actual R-alpha lipoic acid. 800mg RLA-MCT25 has 200mg elemental R-LA.

RLA-MCT25 is essentially 25% R-alpha-lipoic acid in medium chain triglycerides (MCT). The integration of medium chain triglycerides into this GeroNova R-lipoic acid product may make the MCT perform as a self-emulsifying drug delivery system (SEDDS). According to this study, MCT: "enhances the oral bio availability by raising the solubility of poorly water soluble compounds."

This paper seems to suggest something similar -- that a combination of a medium-chain triglyceride (Neobee M5) and Peanut Oil) increased bio availability. I could be wrong, and I have not dug through all of the research on MCT -- but it apparently is used in some forms of advanced drug delivery systems...to positively affect bio-availability.

Edited by nootropikamil, 02 July 2006 - 08:35 AM.

[glexia]

Thanks everybody for the info! [thumb]

Now i doubt in my decision of buy R(+) SR by AOR ...

i´m with Spins : immediate release ®-ALA or sustained release versions?? [huh]

I think the first option is best :

because a timed-release product will be
absorbed slowly over time, the liver is much better able to grab hold
of and breakdown the alpha-lipoic acid into inactive forms.

and:

While we know a great deal about how immediate release alpha-lipoic
acid is handled by the body, there has been only one study with a
timed released preparation. It was not a double-blind study and
the clinical results were not all that significant.

So that, which brand is a better option for immediate release ®-ALA ??

Anyone can give me more information about this?

[glexia]

Sorry nootropikamil i haven´t seen yor post.

Maybe what says Geronova about MCT could be the "key" of R-ALA time -release bio availability....

I will search for more information.. [sfty]

[xanadu]

I tend to agree with da sense in that ordinary ala gives a good value and has been shown to be effective. Why would 1gm a day be the target amount to take? Just because lab studies used this amount does not make it the optimal amount. Just from my layman's perspective, many studies are done with very large amounts of the drug in question. Later, it's often found that smaller amounts work just as well or better than the large amounts. I tend to avoid anything approaching megadoses myself. Megadoses may be good to treat an acute condition but not in every case.

[unbreakable]

Here is the study that compares immediate release ALA with a time released version: Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid.

The total absorbed amount of the immediate release ALA (measured as the AUC) is nearly twice that of the controlled release version in this study. Maybe it's the best idea to take immediate release R-ALA in divided doses?

[FunkOdyssey]

We know that immediate release R-LA will result in a higher peak plasma concentration than the same dose of sustained release R-LA. The assumption, however, that this translates to superior efficacy seems like quite a leap when there are no studies comparing their effects against one another.

Maybe it's the best idea to take immediate release R-ALA in divided doses?

In that case, you would be acknowledging the value of maintaining relatively high/stable plasma levels of R-LA over time. You would then have to consider whether taking immediate release R-LA every 30 minutes really makes more sense than taking perhaps a slightly larger dose of a sustained release product far less often.

[unbreakable]

We know that immediate release R-LA will result in a higher peak plasma concentration than the same dose of sustained release R-LA.

It's not so much about the peak plasma concentration but more about the total amount absorbed (AUC).

[FunkOdyssey]

Here is the study that compares immediate release ALA with a time released version: Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid.

From that paper:

The therapeutic implication of maintaining LA in plasma for a longer duration than can be achieved with the typical oral QRLA formulation is suggested by the clinical benefit of LA on whole-body insulin sensitivity when administered by intravenous infusion (9-11).

The references:

9. Jacob S, Henriksen EJ, Schiemann AL, et al.
Enhancement of glucose disposal in patients with type 2
diabetes by alpha-lipoic acid. Arzneimittelforschung.
1995;45:872-874.

10. Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ,
Dietze GJ. Improvement of insulin-stimulated glucosedisposal
in type 2 diabetes after repeated parenteral administration
of thioctic acid. Exp Clin Endocrinol Diabetes.
1996;104:284-288.

11. Evans JL, Goldfine ID. α-Lipoic acid: a multi-functional
antioxidant that improves insulin sensitivity in patients
with type 2 diabetes. Diabetes Tech Ther. 2000;2:401-413.

[glexia]

NEW PRODUCT : GERONOVA R-PLUS WITH ASTAXANTHIN

From Pete´s Place:

Thursday, June 01, 2006
New From GeroNova Research- R-Plus with Astaxanthin
Wow! I am loving this. Two awesome antioxidants and anti-inflammatories in one supplement. New R-Plus with Astaxanthin is 150 mg of R-Lipoic Acid (75mg R-Lipoic/75mg of R-Dihydrolipoic Acid) with 2mg per capsule of pharma quality AstaREAL Astaxanthin from Fuji Health Science.

What do you think of the add of astaxanthin to R-ALA ?? [huh]

After the info we have read about "time release" products...
which brand do you recommend to me?

-Aor R(+) SR (transamine salt)
-Geronova RLA-MCT25 (25% R-alpha-lipoic acid in medium chain triglycerides (MCT)
-Other suggestions..

-Astaxanthin ??? Why ?? mg/day? (geronova´s R-Plus with Astaxanthin have 2mg)


This of choosing the best supplement is more complicated than what I never thought! [tung]

[unbreakable]

In that case, you would be acknowledging the value of maintaining relatively high/stable plasma levels of R-LA over time.

Is there any evidence that maintaining relatively high/stable plasma levels of ®-LA over time is more effective at reducing mitochondrial ROS production than just taking the same dose of a quick release ®-ALA preparation (which is much cheaper and probably more bioavailable)?

The problem with this is that while the immidiate release R-ALA has a plasma half-life of 22min, does not mean that it still can't exert it's benefits *IN* the cell (or was it mitochondria) for a longer time, where I believe it accumulates...

Edited by unbreakable, 02 June 2006 - 02:24 PM.

[FunkOdyssey]

Is there any evidence that maintaining relatively high/stable plasma levels of ®-LA over time is more effective at reducing mitochondrial ROS production than just taking the same dose of a quick release ®-ALA preparation (which is much cheaper and probably more bioavailable)?

I haven't found any studies comparing the two. As it stands, I think sustained release forms are preferred and assumed to be more effective on an intuitive basis. If anyone has access to those references regarding administration by intravenous infusion, that might shed some more light on this -- apparently those studies produced superior results to traditional oral administration and spurred the development of a sustained release oral product.

[doug123]

Here is the study that compares immediate release ALA with a time released version:
Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid.

The total absorbed amount of the immediate release ALA (measured as the AUC) is nearly twice that of the controlled release version in this study. Maybe it's the best idea to take immediate release R-ALA in divided doses?

That is an interesting study...however, I did not see them state how the "time release" effect is implemented...It does not say..."MCT transport" or anything...

Edited by nootropikamil, 02 July 2006 - 08:35 AM.

[unbreakable]

Development of a sustained release dosage form for alpha-lipoic acid. I. Design and in vitro evaluation.

The purpose of this study was the design and evaluation of a sustained release dosage form for the oral administration of alpha-lipoic acid. The cationic polymer chitosan was used in order to provide a controlled drug release based on ionic interactions with the anionic drug. The effect of such ionic interactions on the release of alpha-lipoic acid could be verified by diffusion studies. In vitro release studies with tablets (diameter: 10.0 mm; thickness: approximately 4 mm) containing 80% alpha-lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release. In addition, permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs demonstrated no significant (p < 0.05) influence of the degree of drug ionization on its absorption behavior. The apparent permeability coefficient (Papp) for alpha-lipoic acid was determined to be 1.39 +/- 0.28 x 10(-5) cm/sec at pH 6.4 (means +/- SD). The use of a sustained delivery system for alpha-lipoic acid, which is based on ionic interactions, should therefore have no influence on the absorption behavior of the drug. The sustained release dosage forms described here might provide a constant plasma level of the drug being highly beneficial for various therapeutic reasons.



Development of a sustained release dosage form for alpha-lipoic acid. II. Evaluation in human volunteers.

Within this study an oral sustained release dosage form of alpha-lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% alpha-lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. alpha-Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed-phase high-performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC(0-12) was determined to be 183.8 +/- 101.4 microg x min/mL (mean +/- SD; n = 8). Because of the pulsed sustained release of alpha-lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.

Edited by unbreakable, 02 June 2006 - 08:36 PM.

[doug123]

So the bottom line is that neither GeroNova nor AOR uses a clinically proven time release methodology?

[doug123]

Are any of the "time release" r-alpha-lipoic acid products on the market using 20% chitosan acetate to mediate the effect? 24 hour release?! That's what I want...

In vitro release studies with tablets (diameter: 10.0 mm; thickness: approximately 4 mm) containing 80% alpha-lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release.

edit: I didn't see those were in vitro results...and that research is with racemate Alpha Lipoic acid and not R-ALAwhich might make the release effect differently.

Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached.  The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon.

I can easily argue that the MCT delivery system should increase bio availability...but 12 hour time release? Theoretically, the R-lipoic acid integrated into the MCT should be able to reach farther than the stomach...but can the R-lipoic acid itself reach as far as the colon without polymerizing or otherwise?

[glasses]

Edited by nootropikamil, 04 June 2006 - 04:08 AM.

[syr_]

24 hour release?!  That's what I want...

I would be happy with 12-16h

[unbreakable]

I would be happy with 12-16h

I'd prefer 60-80 years, must be a huge pill tough, pretty hard to swallow.

[glexia]

unbreakable:

I'd prefer 60-80 years, must be a huge pill tough, pretty hard to swallow.

[lol] [lol] [lol] [thumb]