LONGECITY

I am trying to come up with a well-reasoned dosage of ALCAR adjusted to my age (40). This is from the point of view of someone unwilling to risk co-supplementation with ALA. In the absence of dose-ranging studies on healthy humans, I guess we mainly have the Ames rat studies to use a a basis. Lessons from the Ames studies are that too high a dosage not only causes oxidative damage but can be less effective than lower dosages that avoid the oxidative damage side effect.

Specifically, in old rats:

• 1.5% in drinking water (equivalent to about 12g daily in 70 kg humans) is too much. It is the least effective of the three dosages tested and increases markers of oxidative damage.
• 0.5% in drinking water (equivalent to about 4g daily in 70 kg humans) is optimal among the three dosages tested. It is more effective than the higher dosage in ambulatory activity and mitochondrial rehabilitation and does not increase markers of oxidative damage.
• 0.15% in drinking water (equivalent to about 1.2g daily in 70 kg humans), while less effective than the 0.5% dosage, is still significantly more effective than the 1.5% dosage with respect to ambulatory activity.

All this can be found in

Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites
JIANKANG LIU, HANI ATAMNA, HIROHIKO KURATSUNE, AND BRUCE N. AMES

It therefore seems that the optimal dose for a healthy OLD human with the least risk of side effects should lie somewhere between 1g and 4g daily. An old human who wishes to exercise an abundance of caution might restrict to the lower end of this range.

However, for younger individuals, it seems probable that the 1g to 4g range may be too high, be less effective than lower dosages and may in fact cause oxidative harm. For example, from the rat studies, for the same 1.5% dosage of ALCAR, younger rats have a larger absolute decline in cellular ascorbate levels. See for example one of the slides in http://mcb.berkeley......s Lecture.pdf. So, it seems likely that the above range must be adjusted downward depending on age.

Now if aging were linear, this adjustment would presumably be straightforward, from a presumably optimal but potentialy risky (due to lack of human data) dosage of 0g at age 20 to 4g at age 80, or a conservative, less risky dose of 0g at 20 to 1g at 80. This would give an optimal dosage of 1.3 g at age 40, or a more prudent conservative dose of 300mg at age 40.

The problem is, however, that aging is probably not linear. If the falloff is more rapid later than earlier, which seems likely, the dosages at age forty should be less than the linear interpolation would suggest. Maybe much less, depending on the shape of the graph.

Any suggestions?

Edited by andre, 30 November 2008 - 04:07 PM.

Interesting analysis. Unfortunately, I couldn't speak to the question, though I do have another question entirely: Why are you unwilling to co-supplement with ALA? Is it because of the CR issue or is it something else I've missed?

EDIT: While I am at it, does weight play a major factor in determining dosage for ALCAR? I take it you are 70kg or roughly 150 lbs?
Edited by suspire, 30 November 2008 - 04:18 PM.

Interesting analysis. Unfortunately, I couldn't speak to the question, though I do have another question entirely: Why are you unwilling to co-supplement with ALA? Is it because of the CR issue or is it something else I've missed?

Yes, that study scared me off. I am referring to the study that showed that temporary ALA supplementation can block beneficial CR-adaptations in rats after ALA supplementation had been stopped, and that this was essentially a lifelong side effect. I am not at all interested in CR, but I am trying to improve my cardiovascular health through exercise training. There are quite a few studies indicating that various antioxidants can block beneficial exercise-related adaptations. This one in particular addresses cardiovascular health: http://www.imminst.o...xidative stress. ALA in particular seems very risky in this regard, given that its effects may last for very long after stopping supplementation.

EDIT: While I am at it, does weight play a major factor in determining dosage for ALCAR? I take it you are 70kg or roughly 150 lbs?

It plays a role in the law of metabolic scaling. I just copied the ALCAR-related analysis at http://cron-web.org/...ts-guide-5.html. See footnotes 203 and 337.

Hi Guys,
Please bear with me, as I have questions at the end that I hope someone more knowledgable can help me with.

I believe that ALA has a half-life of an hour or so and then is quickly cleared from the body. ALCAR has a half-life of 6.5 hours...
So I take 1.2 grams of ALCAR and 600 mg. of ALA at 11:30AM and then go to the gym at 2:30PM. I am having trouble finding when ALCAR peaks in the blood, but this timing seems to still give me the ALCAR focus and coordination enhancement. My thinking is that the ALA can't have a negative impact as it should be gone by then.

I also take Acetyl-L-Cysteine around 8:30 AM, with Vitamin C and Green tea extract (Acetyl-L-Cysteine and Vitamin C enhance levels of Green Tea polyphenols). The Acetyl-L-Cysteine hangs around for a LONG time in the body and converts to Glutathione. I also take both forms of CoQ10 with breakfast.

I have two questions:

1. Since Acetyl-L-Cysteine and CoQ10 are both anti-oxidants and are certainly present in my blood when I excercise, do you think they could have the same negative effect as ALA?

2. Since Acetyl-L-Cysteine and CoQ10 are also active in the mitochondria, do you think that they can serve the same anti-oxidant function as ALA when taken on the same day as ALCAR?

Thanks.

I take Na-RALA, ALA, ALCAR, Curcumin w/Bioperine, Green Tea extracts, and Resveratrol right before I go to the gym. I think what I do is contradictory to what a lot of people here practice. Personally, I feel vastly more energetic and feel like I get a much better work out in comparison to when I don't supplement those before hand. I suppose I could be getting less bang for the buck in my workout because of them ....but on the flip side, I am working harder than I would otherwise because of them.

I believe that ALA has a half-life of an hour or so and then is quickly cleared from the body. (...) My thinking is that the ALA can't have a negative impact as it should be gone by then.

This may be incorrect. See for example the paper quoted above where, even though ALA supplementation was stopped in rats in middle age, the effects of ALA lasted essentially for the rest of their lives.

Just because a substance is eliminated quickly does not mean that it didn't have time to flip some switches. Lots of drugs have side effects that can last long after elimination or even indefinitely.

1. Since Acetyl-L-Cysteine and CoQ10 are both anti-oxidants and are certainly present in my blood when I excercise, do you think they could have the same negative effect as ALA?

I wouldn't take CoQ10 right before or after exercise.

Here's a blog post I wrote a while ago: Coenzyme Q10, Exercise and Oxidative Stress.

It would be interesting to see a study that measured oxidative stress and performance over a longer time, maybe several months after taking different amounts of anti-oxidants. Obviously we need some oxidative stress to trigger the body to adapt and improve, but I wonder if there would be any advantage to reducing it somewhat?

I wouldn't take CoQ10 right before or after exercise.

The half-life is too long for timing to matter. My anecdotal experience is that CoQ10 has no negative effects up to 100 mg/day, which is as high as I've gone.

Free Radic Res. 2006 May;40(5):445-53.
Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics.
Bhagavan HN, Chopra RK.
Tishcon Corporation, Westbury, NY 11590, USA. hemmi@tishcon.com

Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.

PMID: 16551570

I am referring to the study that showed that temporary ALA supplementation can block beneficial CR-adaptations in rats after ALA supplementation had been stopped, and that this was essentially a lifelong side effect. I am not at all interested in CR, but I am trying to improve my cardiovascular health through exercise training. There are quite a few studies indicating that various antioxidants can block beneficial exercise-related adaptations. This one in particular addresses cardiovascular health: http://www.imminst.o...xidative stress. ALA in particular seems very risky in this regard, given that its effects may last for very long after stopping supplementation.

To add to this, my own personal experience is that ALA supplementation had a negative effect on my exercise performance. The decline was gradual, but after a year or so of using ALA, I felt that I was building up much more lactic acid than I used to when doing my swimming training. As it is supposed to be an insulin mimic, I reasoned that it may be making my body utilise anaerobic rather than aerobic energy, in the same way as consuming high GI food before exercise would. This may be completely incorrect reasoning, but it led to me switching to just taking ALA once each morning, whereas I had been taking it morning, lunch and afteroon. My swimming endurance markedly improved after making this change, with the effects noticeable within just a few days, though it is possible that further improvement has occurred in the following months.

I am referring to the study that showed that temporary ALA supplementation can block beneficial CR-adaptations in rats after ALA supplementation had been stopped, and that this was essentially a lifelong side effect.

Have these sorts of effects been shown to occur with R-Lipoic acid, or just ALA? The S-enantiomer has been shown to have effects that R-Lipoic acid doesn't...

Concerning the ALA controversy:
Im getting 150mg of R(+)-Lipoic Acid spread over the day from my multivitamin (ortho core) anyway. If I now start supplementing 400mg of ALCAR in the morning would the amount of Lipoic Acid I get from the multivitamin be enough to produce the synergistic effects found in the Ames study, thus eliminating the need for further ALA supplementation? And if LA is indeed a risky substance to supplement, has the damage already been done by taking Ortho Core for the past several months? What's your take of this?

IMO opinion this so called ALA controversy is based on a flawed experiment:
http://www.imminst.o...showtopic=23646

IMO opinion this so called ALA controversy is based on a flawed experiment:
http://www.imminst.o...showtopic=23646

Where is it shown that the experiment was flawed?

The criticism on the thread you cited is based on a misunderstanding of the dose, and therefore invalid.

IMO opinion this so called ALA controversy is based on a flawed experiment:
http://www.imminst.o...showtopic=23646

Where is it shown that the experiment was flawed?

The criticism on the thread you cited is based on a misunderstanding of the dose, and therefore invalid.

If you want to criticize my criticism in the linked thread, please do so there. What misunderstanding of the dose?

EDIT: You may refer to an old post by different poster regarding the dose. That was not my criticism at all. See:
http://www.imminst.o...o...st&p=342418

But again, if critical of this criticism, please be so in that thread.
Edited by Blue, 04 October 2009 - 06:17 PM.

IMO opinion this so called ALA controversy is based on a flawed experiment:
http://www.imminst.o...showtopic=23646

Where is it shown that the experiment was flawed?

What misunderstanding of the dose?

EDIT: You may refer to an old post by different poster regarding the dose. That was not my criticism at all.

I read your post in that thread. You do raise some interesting questions and I would also like to see them answered. However, that does not entitle you to state, as if it were fact, that the experiment was "flawed", as you did above.

Edit: Oh sorry, I just noticed the "IMO".

Also, from your post:

Exceptional claims requires exceptional evidence and should be doubted until replicated.

True in the abstract. However, this thinking is backwards where drug safety issues are concerned. Specifically, the responsibility falls on those who would claim that a drug is safe to support their case with evidence. In questions of drug safety, even circumstantial evidence indicating possible harm should be believed until proven wrong. Not the other way around.

P.S. I would like to believe that ALA is safe, since I am currently taking it for a specific condition (sciatic neuropathy due to a botched epidural cortisone injection), for which there is strong evidence for effectiveness in human studies. It is my hope that any harm will be outweighed by the benefit. I would not feel comfortable taking it chronically.
Edited by viveutvivas, 04 October 2009 - 07:11 PM.

Ala has as extensive a safety record as many prescription drugs with multi-years, multi-center, double blind placebo-controlled studies done and decades of use in Germany against neuropathy. A single dubious and most likely incorrect rodent study does not outweigh the numerous human and animal studies finding efficiency against various age-related human diseases and age-related decline.

Further regarding the study, I greatly dislike the fact that the authors makes claim of an astounding discovery, while not mentioning what seems like an obvious flaw in the survival curves and furthermore having an extremely obscure data table which seems to hide the results except those preferred by authors.

If you do believe this study, then everyone on CR should immediately take ALA since it may be the only study showing increased lifespan by combining CR and and substance as compared to CR alone. Bad effects were only seen (in some rodents) when ALA was combined with AL diet.
Edited by Blue, 04 October 2009 - 08:10 PM.

Ala has as extensive a safety record as many prescription drugs with multi-years, multi-center, double blind placebo-controlled studies done and decades of use in Germany against neuropathy.

I hope you are right, since, as I mentioned, I am actually taking it for precisely that.

Further regarding the study, I greatly dislike the fact that the authors makes claim of an astounding discovery, while not mentioning what seems like an obvious flaw in the survival curves and furthermore having an extremely obscure data table which seems to hide the results except those preferred by authors.

Coming from one of the truly hard sciences, I have observed that in the biomedical field, quality research is the exception rather than the rule.

(Slightly off-topic: The recent ridiculous statements, by authorities who should know better, of a 31.2% reduction of HIV infections in the recent vaccine study, are quite revealing.)
Edited by viveutvivas, 05 October 2009 - 12:47 PM.