[quote]
I decided to research the RLA stability issue for myself. If AOR has so much “integrity” why do they continue to sell unstable and non-bioavailable RLA capsules?[/quote]
The issue of R-LA's tendency to polymerize (which I take to be that to which you refer in saying that RLA is "unstable") has to be taken seriously, but should not be exaggerated. If one starts with quality materials and does one's due dilligence in manufacturing and storage, there is no reason to be concerned about its stability. AOR has 1 and 2 year results for AOR R(+)-LA capsules and OrthoMind (which is a mixed product and thus more likely to run into problems, especially because of the ALCAR salt used, which is hygroscopic (a problem shortly to be remedied)) stored at
controlled room temperature (<21°C) which show negligible polymerization. If the capsules are refrigerated, as we encourage, the issue is even less significant.
[quote]
The posted C of A is meaningless since the polymer content varies depending on the way the sample is isolated for analysis. In other words you can easily de-polymerize the contents of the capsules so that the number doesn’t accurately reflect the amount of polymer in them.[/quote]
It is rather difficult to lowball the polymer content of RLA if one is looking for it. RLA polymer is readily identified precisely because it is so recalcitrant: the material is extremely insoluble, and does not dissolve in acid, alcohol, or acetone.
[quote]
Additionally, you can take pure RLA in powder or a capsule and drop it into any liquid (water, stomach acid etc) and it will instantly polymerize, so even if the caps survive manufacturing they will not survive your GI tract. [/quote]
It
appears that you are assuming that the simple gooey mess made when R-LA is put into water is the RLA polymer. This is not correct. The polymer's chemical and physical features are explored in several papers, including
this one on Geronova's site.
[quote]
More importantly, the testing lab claims they got their standard from Sigma-Aldrich. I called Sigma-Aldrich so I could buy a set of standards, and I was told they do not and have not ever had an RLA or SLA standard! [/quote]
Integrated Biomolecule (IBC Labs) is an extremely reputable independent testing laboratory. If it is true that Sigma does not currently offer these standards, then it may be that they did so in the past, or that IBC misdocumented the source of the standard. I cannot confirm thisdetail at the moment as IBC are closed for the holidays. However, I am extremely confident in their ability to source and utilize their reference standards.
[quote]
AOR lost all their credibility and never had any integrity. They’ve been misleading and deceiving everyone from the beginning about being the “first in the world”. Did they have RLA before DeGussa and Asta Medica in 1987? Lalilabs was selling LaboChim’s RLA in 1999 for $1100/kg and a 25 kg minimum. AOR is a formulating company and re-packager, not a manufacturer and therefore could not be “1st” . They do not make RLA or any of their supplements![/quote]
AOR was the first to make RLA available
as a supplement. I don't think that anyone at AOR has ever implied that we
synthesize RLA
raw material, and clearly the
material pre-existed AOR's release of the supplement since there are published scientific papers using RLA going back decades before our release of it in supplemental form. Indeed, it is exactly on the basis of the impressive body of pre-existing research that AOR first began hunting for a source that could be contracted to supply us with pharmaceutical-grade RLA at a price that life extensionists could afford. This project took some two years, and we were -- and are -- proud of the efforts that we took and in our resulting ability to put RLA where it belongs: in the hands of the life extension community. Other supplement companies have followed down the path that we blazed, and this has in turn brought the price down and made RLA more widely available -- which is also to the best.
[quote]
AOR has done as much to hurt the cause of RLA as help it by overly demonizing SLA and ALA. While a substantial argument can be made for use of the natural form, ALA and SLA are not “thalidomides” or ticking “time bombs” as AOR would have you believe. That is marketing hype, masquerading as science.[/quote]
Again, this is a caricature. AOR has never suggested that SLA is another thalidomide (a poor comparison in any case, as thalidomide is actually quite safe as drugs go, except for women during a narrow window of their pregnancies -- let's say, another Rezulin). Clearly, for at least some people (sufferers of diabetic neuropathy, for instance) the use of the racemate is an entirely sound decision
when nothing else is available. Life extensionists, however, must be exceptionally cautious about what they are putting into their bodies. A metaphor which I have quite often used is that of salted tomato sauce. Tomato sauce (RLA) is good for you; the added salt (SLA), while it has
some benefits (and here of course the metaphor breaks down somewhat, as sodium is an essential nutrient), is for almost everyone detrimental. If you are at high risk of prostate cancer, it is entirely sensible to pound back salted tomato sauce (the racemate) if that's all that's available, because of relative risk. However, once pure tomato sauce becomes available, it is clearly the best choice to make the switch.
I think in any case that we agree that RLA is to be chosen, particularly by healthy people, as the form of choice, and from a pragmatic point of view that is the bottom line, however detrimental one considers SLA to be.
[quote]
There is a big piece of info AOR has neglected to tell us about RLA. All of the animal studies using RLA, reported by Asta Medica, Ames, and Packer used a oral solution of the sodium salt or it was given by injection. Otherwise, it is impossible to get therapeutic levels of RLA from powder, tablets or capsules.[/quote]
This is not the case, as a perusal of any one of
several full-text papers available online for free demonstrates. In each case they state that they are using R-lipoic
acid, not a salt form. They are clearly being careful here, mentioning eg. their use of "ALCAR (hydrochloride salt)". Moreover, the RLA was not provided in "oral solution of the sodium salt or ... by injection": for instance, in the first linked paper above, "R-alpha-lipoic
acid (LA) [0.2% or 0.1% (wt/wt)
in diet]" (all emphasis mine).
[quote]
Where are the dissolution results and plasma pharmacokinetics for their allegedly polymer free caps? You will see that the capsules do not dissolve, and the amount that does dissolve in gastric juice is ~ 9mg and of this only about 30% is bioavailable.[/quote]
I can only assume that you are jumping to this conclusion from data derived from R-LA
tablets (as eg in
this US Patent (emphasis added):
[quote]
When producing dosage forms from R-thioctic acid, due to the active ingredient's low melting point of 50.6-50.70.degree. C., the active ingredient is readily sintered both during
production of the mouldings and during further processing, for example
when applying a taste-masking coating. Sintering of the active ingredient, for example when using slightly elevated temperatures, as are necessary for
drying and solidifying the coating, leads to a reduction in porosity, in extreme cases even to complete sintering
of the moulding.
As a consequence, the moulding (tablet, pellet, granule) dissolves only extremely slowly in the gastro-intestinal tract. This also results in poor bioavailability of the active ingredient.[/quote]
This problem is serious, but it can be avoided by first choosing
encapsulation instead of tabletting, and by then using the right procedures to both avoid elevated temperatures and to take other steps to minimize polymerization. When the final capsule does not have the sinterized material (the result of gumming and polymerization of RLA), none of the above applies. AOR took some time, and threw out several pilot batches, to first produce and then scale up, procedures to soundly encapsulate (not tablet) RLA.
As the op cit Hagen and Ames studies show, even a relatively crude mixture of RLA into rodent chow allows for absorption of RLA and consequent "rejuvenation" of old organisms.
[quote]
Why do you think Juvenon doesn’t even use RLA? Their scientists did the original studies on the benefits of RLA and they don’t use it because of the instability and the essentially non existent bioavailability![/quote]
That isn't
quite correct. First, as stated, it again exaggerates the intractability of the problem. As Ames'
patent states,
[quote]
LA suffers from certain disadvantages, however. In particular, the natural form R-LA is unstable
above 40° C, so it can degrade under
some warehousing conditions. Also
LA is hygroscopic. What is needed is stabilization of this natural form of LA with a natural salt. [/quote]
The temperature issue is readily addressed. It is harder, but not impossible, to overcome the hygroscopicity problem as well. These are particularly difficult issues for the Juvenon product (marketed under agreement with Dr. Ames), for two reasons. First is the fact that they
tablet the stuff, which leads to polymerization during the manufacturing process itself due to high heat (as documented above). Second is the high ratio of RLA to ALCAR hydrochloride (which is highly hygroscopic itself) in their product. To be clear, this ratio is ideal from a dosing perspective, but to combine this much RLA with ALCAR and nothing else in one tablet draws in a lot of moisture, greatly increasing polymerization.
In their animal studies, Hagen and Ames solved this problem by administering RLA and ALCAR
separately despite the inconvenience: for instance, the "Methods" section of
this full-text paper states that (emphasis mine):
[quote]
The rats in the experimental groups were fed either 0.5% or 0.2% (wt/vol) ALCAR
in MilliQ water (pH was adjusted to 5.2 with 1 N NaOH), 0.2% or 0.1% (wt/wt) LA
in AIN93M diet, or a combination ... The food consumption was determined by weighing the diet and measuring the volume of water weekly; the average daily consumption was then calculated.[/quote]
AOR has avoided this by not producing such a product -- yet. It is for this reason that AOR encourages the use of a
separate ALCAR supplement to complement our RLA-only product, and a
separate "top-up" RLA supplement for OrthoMind, whose RLA content is otherwise suboptimal. However, as
previously disclosed,
[quote]
(if the results of some formulation work which we have contracted turns out as we anticipate) we will shortly begin using what we anticipate to be an even more stable, versatile salt[/quote]
... and this should, among other things, allow us to produce a variety of RLA-containing supplements which are currently not viable because of hygroscopicity issues.
[quote]
I subjected AOR’s capsules and contents to standard dissolution protocols, available in any testing label, to see if my results would match those reported. The contents do not disperse or disintegrate. They lump up.[/quote]
Did you use apparatus which sequentially simulate both GI environments -- stomach and jejunum? Standard dissolution protocols should have shown bioavailability in line with published results for RLA. This is of course relatively low -- but the point is that the clinical and experimental studies with RLA are based on exactly this same relatively low bioavailability.
[quote]
I’ve called and emailed AOR several times and asked them to respond. They are apparently not interested in their customer service and no one from AOR ever returned my calls or emails. That’s why I finally decided to post this, since I gave them a chance to respond and explain, and they chose not to. I couldn’t stand the BS, arrogance and deception, posing as science any longer. [/quote]
I can't imagine how this would have happened. We are very diligent about answering technical questions, as AOR posts in this forum should reasonably document. Did you phone 1-403-250-9997? Did you email Tech ATSIGN AOR DOT ca ? Normally, questions which can readily be answered are addressed immediately at the front desk or by our more senior customer service staff; genuinely difficult questions are passed on to myself or one other technical support person, and again we are quite prompt in addressing them. I have often received questions about RLA polymerization and stability both via email and by phone and have always answered them. I am sorry if you genuinely did not receive good service, but I am also baffled how you could have repeatedly called and emailed us and not received a response.
In any case, I hope that I have addressed your concerns adequately here.
Thank you to an Imminst forum participant who PMed me about this thread: I have not been able to spend much time looking on the Forums since just before Christmas, and will not likely be able to do so for several weeks, and would otherwise probably have missed this message.
To your health!
AOR