38 replies to this topic

[Chip]

The Ames test has been used for decades now as a screening method to detect possible carcinogens, mutagens and teratogens. He is now researching something else, elevating the ability of mitochondria to function on the cellular level with the supplementation of acetyl-L-carnatine. The general theory is that free radical damage increases with age and most oxidative processes occur at mitochondria so they may show symtoms of age faster than any other component of human cells. The supplementation has been shown with rats to actually add some spunk and increased life spans along with the supplement lipoic acid. Mitochondria besides being the first to suffer from free radicals also are a center of much free radical production. Without the lipoic acid rats became livelier with the acetyl-L-carnatine but also showed more free radical damage consequences from more active and efficient mitochondria. Adding lipoic acid as a nutritional supplement reversed or stopped this side effect and the end result was longer and healthier life spans. Acetyl-L-carnatine is available commercially as a food supplement under the name "Alcar" and lipoic acid is also commonly available. Apparently the dosages for humans to possibly mimic the results with rats is 200 mgs. alpha lipoic acid and 500 mgs. acetyl-L-carnatine twice a day.

[Athanasios]

UPDATE!

I just wanted add this in here as the title was fitting.

Bruce Ames gives an hour talk on LA/ALCAR and supplementation for longer life. It goes over his research on LA/ALCAR, and gives some very nice graphs of "performance" of old and young mice as: controls, LA only, ALCAR only, and LA/ALCAR supplementation.

The second half of the talk is about his effort to boost the health of the poor by supplementation of multi-vitamins/high dose Bs. He says high dose Bs get around all sorts of polymorphisms that shorten lifespan.

His speech:
http://www.ucsd.tv/l...asp?showID=8343

Other talks by SIRA:
http://tinyurl.com/s48tl

For the whole shabang:
click on all health and medicine videos in the tab at the top of the table.


Edit: Sorry if this constitutes as clutter, feel free to move or delete the post if redundant or in wrong forum.

[kottke]

Very very cool

[scottl]

I"m fairly sure he uses R-ala, though it may not always be clear.

[Athanasios]

I"m fairly sure he uses R-ala, though it may not always be clear.

This is what Ames said while talking to a meeting that de grey pulled together:

"Christopher Heward: Can I ask one question? I remember you mentioning at a meeting recently that you were going to be doing the longevity experiments (wiht ALCAR/ALA) at that time or were getting ready to do them. Were there any preliminary experiments that didn't come out?

Bruce Ames: No. We've done dose-response stuff, and we're ready to do it. We've had trouble getting the lipoic acid from this company in Germany, and we had trouble getting the rats from NIA, and there've been various pitfalls, but it's due to start.

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."

edit OOPS: here is link http://research.arc2.../transframe.htm

Also, I see Ames using Rala even before year 2000 in several different studies, so it is pretty safe to say that those graphs were using R-ALA.

Edited by cnorwood19, 14 May 2006 - 03:05 PM.

[Karomesis]

indeed, he was. Which is one of the reasons I only buy gerenova's R-lipoic [thumb]

cnorwood19, are you familiar with his work on N-tert-butyl hydroxylamine? I have been taking it for 4 months now.

[Athanasios]

cnorwood19, are you familiar with his work on N-tert-butyl hydroxylamine? I have been taking it for 4 months now.

No I am not. I haven't done a lot of research on spin traps, cause I cant afford them right now! [lol]

Do you have a good place for me to start a search. I am curious of the workings of it all.

[Karomesis]

sure, here you go [thumb]


http://morelife.org/...hems/NtBHA.html

http://www.jbc.org/c...act/275/10/6741

http://www.blackwell....2002.tb02090.x

[Athanasios]

Have you seen anything comparing the effectiveness of NtBHA to R-ALA. They seem to have similar actions. In fact, I think Ames used PBN before R-ALA in his studies.

[Karomesis]

As I understand it, the effectiveness of NtBHA is based more on pluripotency than R-lipoic.

NtBHA has mechanisms that ames and others have yet to document, it is alleged that there is also a crosslink inhibition factor involved as well as unknown effects.

R- lipoic is far more straightforward in its efficacy and mechanisms. As has been documented in numerous studies.

[opales]

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."

This is quite interesting as the Juvenon (to which Ames is an advisor) claims:
http://www.juvenon.c...oduct/qa.htm#14

14. 

Does Juvenon™ Cellular Health Supplement contain the R+ isomer or enantiomer of lipoic acid, or the racemic mixture?

Stereoisomers or enantiomers are different compounds with the same molecular formula and physical and chemical properties. Lipoic acid has R and S enantiomers, which are mirror images of each other. Consequently, the 3-D structure of the two is different, due to variation in molecular arrangement in space. Because of this variation one form, the R, rotates polarized light to the right, while the S form rotates it to the left.

The alpha lipoic acid present in the Juvenon™ Cellular Health Supplement is called a racemic mixture and contains an equal mixture of R and S. The R form is the one that is synthesized by the body. The R form is the isomer utilized by the enzymes of the mitochondria for the conversion of food metabolites to energy. However, the S form does have antioxidant activity, and does not appear to interfere significantly with the R form, although this is not entirely clear.

Virtually all of the human studies to date (going back some 35 years) have utilized the racemic mixture, which is more stable and considerably less expensive. It is not known whether the R form is in fact more beneficial to humans than the racemic mixture. In spite of claims by some that the S form interferes with the R form, there is no experimental evidence to support this statement. In fact, there is no evidence to date that demonstrates unequivocally that the R form is superior to the R/S mixture in promoting cellular health.

Juvenon scientists continue to evaluate this question. When and if peer-reviewed research establishes that the R form, without the S, is a superior protector of cellular health in humans, Juvenon will offer a product containing only the R form.

[shadowrun]

I think I may start popping one of my old cheap 100 mg ALA with my expensive 100 mg R-ALA when I take 500 mg ALCAR in the morning

[Athanasios]

They both say the same thing, no?

Ames, in his statement, is only concerned with inhibiting free radical production in the mitochondria. Maybe somewhere we can dig up a quote where he references the R/S mixture?

In fact, there is no evidence to date that demonstrates unequivocally that the R form is superior to the R/S mixture in promoting cellular health.

I have not seen any evidence showing that the R/S mixture works as well in conjunction with ALCAR as the R form, whereas there is good evidence that the R form works well. When it comes to this issue, I want to stick with what I have seen to work. That is why I do not use NAC or R/S for this purpose, only RALA, but everyone has their own tolerance when it comes to extrapolation of the evidence.

[maxwatt]

There were several threads in sci.life-extension in 2002 and early 2003 on racemic versus r-lipoic acid. Someone produced studies showing the S antiomer blocked the action of R-lipoic acid in the mitochondrial membrane. Don't recall details, but I never took the racemic mixture again. Also pure r-lipoic acid polymerizes, which may make it useless. Several products combine it in a potassium salt ( eg, K-rla) which stabilizes it.

Curiously, there has been no followup since then. The current hot supplement is resveratrol. I will see if I can come across the study again, but I remember reading theat resveratrol increases the size and number of mitochondria, but IT DOES NOT restore the efficiency of the cardiolipin membrane. R-ALA and acetyl-l-carnitine should do this. The should complement each other very well.


(spelling correction 1/26)

Edited by maxwatt, 26 January 2007 - 12:11 PM.

[lunarsolarpower]

If you have an hour to watch it Ames' talk is pretty educational. The first half of it is about vitamin and mineral supplementation and the last half is about the research into lipoic acid and carnitine he has done.

[xanadu]

Virtually all of the human studies to date (going back some 35 years) have utilized the racemic mixture, which is more stable and considerably less expensive. It is not known whether the R form is in fact more beneficial to humans than the racemic mixture. In spite of claims by some that the S form interferes with the R form, there is no experimental evidence to support this statement. In fact, there is no evidence to date that demonstrates unequivocally that the R form is superior to the R/S mixture in promoting cellular health.

This is what I've been saying for a while. There was no evidence that racemic ala was any sort of a problem but people kept swearing to it based on what they had been told. It's sort of like once a rumor gets to a certain size, people take it as the truth simply because so many people seem to believe it. When you examine the evidence you see that regular ala has some benefits. It doesn't polymerize and the s-ala is an antioxidant. Then when you look at how overpriced r-ala is compared to racemic, the decision is clear.

[eternalone]

I've been taking ALA (200mg)/ALCAR(500mg)/Biotin for a while now. I usually take it before working out, and I can say that it gives me more sustained energy throughout my workout. Kind of like a caffeine buzz without being jittery. When I first heard about the Juvenon product, I explored a bit and found out that Ames' included Biotin in his product. According to Ames', he added biotin in order to offset the competition from alpha-lipoic acid. Look up the the molecular structures of ALA and Biotin (Vitamin B7) and it may be apparent why.
Does anyone know how much Biotin is in the Juvenon product? I've been only adding 300mcg of Biotin to the mix.

[maxwatt]

I found a host of references to alpha-lipoic acid on Paul Wakfer's morelife.org website. He has collected dozens of ALA and R-ALA references at

http://www.morelife....ements/RLA.html

with a brief summary of each. (Information from the papers that is not in its abstract is referenced in his summaries.)

Paul concludes, and I concur:

" 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."

-------------

I found this study among those on Morelife that indicates that, while ALA is beneficial in old rats, it has little effect on young ones. Conclusion: you needn't use this supplement if you are under perhaps 30 or 40, and your need for it will increase with age. You're only wasting your money unless you're an old rat like me. Likely the same holds true for acetyl-l-carnitine.

FASEB J. 2001 Mar;15(3):700-6. Related Articles, Links

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ®-(alpha)-lipoic acid.

Suh JH, Shigeno ET, Morrow JD, Cox B, Rocha AE, Frei B, Hagen TM.

Linus Pauling Institute, Department of Biochemistry, Oregon State University, Corvallis, Oregon 97331, USA.
PMID: 11259388

Abstract and full paper availabe through pub med at http://www.ncbi.nlm....8&dopt=Abstract

[kenj]

I found this study among those on Morelife that indicates that, while ALA is beneficial in old rats, it has little effect on young ones. Conclusion: you needn't use this supplement if you are under perhaps 30 or 40, and your need for it will increase with age. You're only wasting your money unless you're an old rat like me. Likely the same holds true for acetyl-l-carnitine.

Maxwatt,

I think R-Lipoic Acid is an excellent sup, and one you can start with at a fairly young age (early/mid 20s), for *protecting* the mitochondria from oxidative damage.
Protecting the insulin system against aging is also a +. And, modulating inflammation level in the body, it is a truly *must-take* sup for any adult, interestet in optimal health.
And RLA is one sup that has a noticable effect on me (more energy from food), starting in my mid 20s.
BTW, the usual no brainer: yes, I would never rely on the SLA form, when we have the natural RLA.

[chrisp2]

Can anyone recommend a good place to buy AOR's R-LA? (In the US)

The only place I've been recommended to purchase from (by AOR) was somewhere that I bought their LA from before... And I don't feel that even though they claimed to keep it refrigerated when asked... I'm not so sure they do, as the color was off compared to the same brand/type I bought from iHerb previously. (Only switched from iHerb b/c they don't offer AOR products anymore - such a shame... They were people you could trust)

[Athanasios]

Agree with kenj.

I think R-Lipoic Acid is an excellent sup, and one you can start with at a fairly young age (early/mid 20s), for *protecting* the mitochondria from oxidative damage.
Protecting the insulin system against aging is also a +. And, modulating inflammation level in the body, it is a truly *must-take* sup for any adult, interestet in optimal health.
And RLA is one sup that has a noticable effect on me (more energy from food), starting in my mid 20s.
BTW, the usual no brainer: yes, I would never rely on the SLA form, when we have the natural RLA.

[ageless]

yeah, it does have some multi-positive effects that seem sometimes too good to be true... it is a powerful anti-inflammatory, improves insulin function, powerful mitochondria antioxidant, etc...

[maxwatt]

yeah, it does have some multi-positive effects that seem sometimes too good to be true... it is a powerful anti-inflammatory, improves insulin function, powerful mitochondria antioxidant, etc...

Even so, unless one has a specific condition (eg diabetes) that it can treat, if one is young enough that one's mitochondria still have their normal membrane potential, then it is unlikely to be more helpful than other plentiful and cheaper antioxidants.

[Athanasios]

Even so, unless one has a specific condition (eg diabetes) that it can treat, if one is young enough that one's mitochondria still have their normal membrane potential, then it is unlikely to be more helpful than other plentiful and cheaper antioxidants.

I can see that argument with something such as NAC, that boosts glutathione, but for any ol' antioxidant, I wouldnt agree.

[robert v]

Does anyone know how much Biotin is in the Juvenon product?  I've been only adding 300mcg of Biotin to the mix.

I bought some of the Juvenon product a while ago. The label says that "per serving" there is Biotin 200 mcg, Calcium 154 mg, Acetyl-l-Carnitine 1000 mg, Alpha Lipoic Acid 400 mg, and serving size is two tablets.

-Robert

[kenj]

R-Lipoic Acid and DiHydroLipoic Acid is truly an amazing, multifunctional duo, - besides it "mimicking" insulin, interesting for all healthy folk (CR people may "benefit" less), it can modulate inflammatory activities in the body: inhibiting COX-2 activity/PGE2 production;
I note in myself that I have to megadose the GLA fatty acid when on RLA, as it causes very dry skin and cracked heels after a few days,
possibly displacing Arachidonic Acid from cell membranes (?), - I'm not sure, - at least it is performing *some* prostaglandin regulation. In this regard the RLA/DHLA/GLA super protecting trio is so interesting, working (along with the EPA fatty acid) to knock inflammation down hard, also possibly (?) reducing certain proteins within multiple cancer forms.
I speculate: Raising both the PGE1 and E3 series, while "silencing" the infalmmatory-promoting PGE2 is a GREAT strategy to claim yourself invincible...

Chrisp2, I take both R-Lipoic Acid and R-DiHydroLipoic Acid; - GeroNova's R-PLUS is THE top dog available, IMO.
While Alpha Lipoic Acid is an antioxidant, - and does not kill you, - the R-Lipoic/DiHydroLipoic forms are so. much. more. potent for mitochondrial health (the basis for success with other antioxidants (like vit C and E).

[niner]

While Alpha Lipoic Acid is an antioxidant, - and does not kill you, - the R-Lipoic/DiHydroLipoic forms are so. much. more. potent for mitochondrial health (the basis for success with other antioxidants (like vit C and E).

It makes sense that dihidrolipoic acid is "better" than lipoic acid; but is there any evidence of that? Does it have adequate stability, bioavailability, and pharmacokinetics?

Given that the half life of lipoic acid is about 25 minutes, it is nearly all gone in a few hours. If we are relying on it to deal with the greater free radical load of ALCAR supplementation, shouldn't we be using sustained release dosage forms? AOR and Jarrow both have them. AOR's is R, Jarrow's is racemic.

[chrisp2]

Still looking to find a good US supplier for AOR's SR R-Lipoic... (At a decent price of course)

Any recommendations?

[makoss]

Chrisp, I get my AOR sustained release ALA from egetbetter.com. They're a company from Vermont.

[ryan1113]

Still looking to find a good US supplier for AOR's SR R-Lipoic...  (At a decent price of course)

Any recommendations?

http://www.bcn4life....y_Code=10155000


Are there any other sustained release R-ALA products other than this and the Geronova. It's all very over-priced.