Mixing: R-ALA & Acetyl-L-Carnitine

Hey everybody:

I was wondering if you could suggest an optimal dose for cognition enhancing purposes of these two substances.
Both daily and per dose suggestions would be greatly appreciated.

Thanks.

Uhh, for cognition enhancing, I would not primarily think of these two compounds. They can support other stronger cognition enhancing substances in the sense that R-ALA is mostly protective and ALC is mostly energetic. There is no such thing as a general optimal dose because every body is unique. So I think the best thing to do is to experiment what the optimal dose for you personally is at this moment in your life. Variables you need to take into account are: other supplements you also take, age, body weight, personal health condition, (chronic) ailments & diseases, allergies/sensitivities, and the expected daily activity (how much physical and mental activity?).
From what I read in the several literature and tests, for ALA, try a dose ranging from 50 mg - 400 mg a day, for ALC ranging from 250 mg - 2 gram a day. If you read the several documentations on the internet, you probably will come to the same conclusion. Do not hold me responsible if you are overdosing yourself.

Edited by shapeshifter, 31 May 2004 - 08:31 AM.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

2-4 g daily is good for ALCAR, if you can afford it. I would take it 3x daily.

Thanks for the reply Dave. I apppreciate it.

Take care,

Adam

Hey everybody:

I was wondering if you could suggest an optimal dose for cognition enhancing purposes of these two substances.
Both daily and per dose suggestions would be greatly appreciated.

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.

R-lipoic acid has a very short half-life in plasma, although there is some evidence that it hangs around in cells for longer; to be safe, it makes sense to take this at least 3 times daily. Taking it on an empty stomach is best for overall absorption, although taking it with food gives a mild sustained-release effect.

ALCAR has a longer half-life, but should still best be taken at least twice daily. It should be taken away from food and from other quaternary amines (including DMAE, choline, and TMG) as they share a transporter system in the brain and GI and will compete for absorption if taken together.

Uhh, for cognition enhancing, I would not primarily think of these two compounds. They can support other stronger cognition enhancing substances in the sense that R-ALA is mostly protective and ALC is mostly energetic.

ALCAR is among the best-documented cognition enhancing nutrients available; the evidence for R-LA mostly comes from animal experiments, but is very compelling (see this full-text article in particular:

Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames
BN.
Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha-lipoic acid.
PNAS. 2002 Feb 19;99(4):2356-61.
http://www.pnas.org/.../full/99/4/2356

The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-L-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-alpha-lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). ... These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

There is no such thing as a general optimal dose because every body is unique. So I think the best thing to do is to experiment what the optimal dose for you personally is at this moment in your life. Variables you need to take into account are: other supplements you also take, age, body weight, personal health condition, (chronic) ailments & diseases, allergies/sensitivities, and the expected daily activity (how much physical and mental activity?).

This is all good advice. However, one does have to start from somewhere. It's best to start one's regimen with doses backed by the primary scientific literature, and play from there.

From what I read in the several literature and tests, for ALA, try a dose ranging from 50 mg - 400 mg a day, for ALC ranging from 250 mg - 2 gram a day. 

Those dosages are often included in multinutrient formulas, but aside from the high end of the ALCAR dose they don't have any real backing in the literature. Supplement manufacturers often include token amounts of ingredients just to be able to list them on the label while making the price look like a bargain, unfortunately.

I wanted to know from those of you who experiment with this substance if it is noticeble subjectively.

If there are effects, please explain them and their duration. 

Thanks in advance for any replies.

Hagen and Ames' studies do certainly suggest that the greatest short-term impact on performance and subjective experience would acrue to older organisms whose mitochondrial function is already somewhat impaired. Personally, I seemed to get a mental lift when I first switched from the racemate to R-LA, but I don't put much stock in my subjective response to supplements: it's too subjective, is of no statistical worth (sample size = 1) and intelligent people are more susceptible to the placebo effect .

In any case, I think R-LA is worth taking as a safe, orthomolecular intervention for neuroprotection and potentially retarded aging, even if it has little obvious short-term effect.

To your health!

AOR

Thank you for the informative response, AORSupport. I sincerely appreciate this.

I tend to think those who are young and healthy should stick on the lower end of the dosage range for ALA, or at least make sure to guage their reaction before moving to higher doses. Reason being many experience symptoms of hypoglycemia at the higher doses. And, a number of healthy people have measured blood sugar with a blood glucose measure before and after ALA under reasonably controlled conditions and found that it decreases blood sugar, which combined with the available research, is enough evidence for me. Beneficial for some but you don't want to take it to far. And of course, there is the dreaded sulfur smell.

@shpongled: What sulphur smell do you speak of?

Thanks.

I am 25; do you think 450 mg RALA per day is a good dosage?

The best dose would be 1000mg of R-ALA. And in addition with GLA/CLA (synergistic effect).

Have we found the solution to ageing?
by Anne Woodham
Two substances found naturally in the body could reverse the ageing process when taken as supplements. Anne Woodham explains the research

LInkage
Can health supplements acetyl-L-carnitine and alpha-lipoic acid do to humans what they did to ageing rats? Californian researchers were amazed when they fed these dietary supplements that can be bought in high street health shops to laboratory animals.
'With the two supplements together, these old rats got up and did the macarena,' said Bruce N. Ames, Professor of Molecular and Cell Biology at the University of California, Berkeley. 'The brain looks better, they are full of energy - everything we looked at looks more like a young animal.'
Within hours of news of Ames' results appearing in the media in February, a Richmond health store had sold out of the supplements. A spokesperson for health shop chain Holland & Barrett reported a nationwide run on stocks.

According to Professor Ames, evidence suggests that the deterioration of mitochondria, our cells' energy power packs, is as an important cause of ageing. Destructive molecules called free radicals that are produced during normal metabolism (chemical processes that convert nutrients into energy and keep us alive) are thought to cause this deterioration.

Acetyl-L-carnitine and alpha-lipoic acid are chemicals found naturally in body cells. Alpha-lipoic acid is an antioxidant that destroys free radicals. Acetyl-L-carnitine is a protein that boosts the action of an enzyme (carnitine acetyltransferase) that fuels mitochondria and becomes less active with age.

Professor Ames and his team reckoned that combining the two as supplements would deliver a two-pronged punch to ageing cells. Their studies, published in the US science journal Proceedings of the National Academy of Sciences in February 2002, showed they were right. 'Each chemical solves a different problem,' said Ames. 'The two together are better than either one alone.'

From old age to middle age
After a month on the supplements, elderly and lethargic rats had more energy, did better on memory tests and their mitochondria worked better. The decline in overall activity typical of aged rats was reversed to that of a middle-aged to young adult rat seven to ten months of age. This is equivalent to making a 75- to 80-year-old person act middle-aged.

'The animals seem to have much more vigour and are much more active than animals not on this diet, signalling massive improvement to these animals' health and well-being,' said Dr. Tory Hagen, a colleague of Ames who is now at the Linus Pauling Institute at Oregon State University.

Professor Ames and Dr. Hagen have formed a company, Juvenon, to patent the combination and are currently carrying out human clinical trials of the treatment. But their experiments with rats are only the first step and other scientists warn against rushing into health shops and self-dosing on the supplements before they have been shown to work in humans or the proper dose is established.

Alpha-lipoic acid
The mitochondria in the cells normally make enough of this chemical compound for energy production purposes. It is only when in excess and circulating in a 'free' state in our cells that alpha-lipoic acid acts as an antioxidant, and the only way to achieve an excess is through supplementation. Most foods, apart from liver and yeast, contain only tiny amounts of the compound.

As an antioxidant, it switches off many fat- and water-soluble free radicals in the body and seems to protect our genetic material, DNA. It also re-processes vitamins C and E and other antioxidants to make them more effective.

Research indicates that it will prove a very special and powerful antioxidant but there is still little known about it. What there is suggests that supplements can help keep nerves healthy and prevent or treat age-related diseases such as heart disease, cataracts and diabetes. Because it is made in the cells by the mitochondria, it is particularly well placed to prevent and even reverse ageing. It appears to be safe, but nobody knows what amounts should be used. If it is so potent, it may also be possible to overdose. Anyone who is on medication for heart disease or diabetes should talk to a doctor before taking it.

Acetyl-L-carnitine
This molecule occurs naturally in the liver, brain and kidney and is similar in form to the amino acid L-carnitine, which carries fatty acids into the mitochondria where they are converted to energy. Acetyl-L-carnitine is involved in the production of a key neurotransmitter acetylcholine, important for cognitive function. Some studies suggest that it may delay the progression of Alzheimer's disease, protect nerve cells from deterioration, increase mental energy and help relieve depression.

The body normally converts L-carnitine, which is made in the liver, into acetyl-L-carnitine. Levels may decrease after the age of 40, but it is not normally considered an essential nutrient because the body can manufacture all it needs. Most research involving acetyl-L-carnitine uses 500mg three times a day. It appears to be safe, although body odour, nausea, vomiting, agitation, skin rash and increased appetite are reported side effects. Because some medications may interact with it, discuss any supplementation with your doctor or pharmacist.

@shpongled:  What sulphur smell do you speak of?

Thanks.

I am 25; do you think 450 mg RALA per day is a good dosage?

If you take a lot of ALA, your breath and body fluids can start to smell like sulfur. Taking it before food helps, although it decreases the total bioavailability. 450 mg daily is good, if you get symptoms of hypoglycemia you can reduce it.

The best dose would be 1000mg of R-ALA. And in addition with GLA/CLA (synergistic effect).

CLA is not a good idea for anyone concerned with health.

The best dose would be 1000mg of R-ALA. And in addition with GLA/CLA (synergistic effect).

CLA is not a good idea for anyone concerned with health.

Why do you say this David? Are you sure we are referring to the same CLA? Conjugated lineolic acid, right?

CLA is not a good idea for anyone concerned with health.

Why do you say this David? Are you sure we are referring to the same CLA? Conjugated lineolic acid, right?

If I may be permitted to read David's mind , I expect that he's thinking of reports like these:

Riserus U, Arner P, Brismar K, Vessby B.
Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome.
Diabetes Care. 2002 Sep;25(9):1516-21.

OBJECTIVE: Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. ...

In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. ... Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P < 0.05).

CONCLUSIONS: These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.


Riserus U, Vessby B, Arnlov J, Basu S.
Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men.
Am J Clin Nutr. 2004 Aug;80(2):279-83.

BACKGROUND: We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations. ...

In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively.

RESULTS: ... Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition. CONCLUSIONS: A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.


Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B.
Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.
Circulation. 2002 Oct 8;106(15):1925-9.

In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF(2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism.

CONCLUSIONS: t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.

Larsen TM, Toubro S, Astrup A.
Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies.
J Lipid Res. 2003 Dec;44(12):2234-41.

Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro.

CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. ...

In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health.

* Rant alert *
Life extensionists have to start taking seriously the fact that supplements are not "inherently safe," and stop popping pills on the basis that "Well, the evidence isn't clear -- but it can't hurt." It most certainly can. Other common examples are increased risk of fracture from preformed vitamin A (retinol/retinyl ester) from diet and supplements at doses > ~3000 IU; lipid disturbances and heart arrhythmia from excessive zinc (> 23 mg without compensatory copper, or >50 mg long-term in any case); the possibility of increased risk of neurological disease from excessive manganese (Institute of Medicine's safe Upper Limit is 11 mg, although the relative impact of Mn from water, inhalation, food, and supplements needs to be worked out); etc.

To go further than this into xenobiotic drugs which have not been tested for long-term use in healthy, normal humans is simply to gamble with one's own life, showing contempt for one's own health and chance at indefinite lifespan -- a real possibilityfor the first time in history, standing as we are at the cusp of engineered negligible senescence. As I've said before, there would be little more bitter than to spend years pursuing extended youth, health, and longevity, only to discover that one has actually been poisoning oneself with the very substances which one has been swallowing in hopes of extended health and longevity.

Read the primary literature, and think critically. The future is glorious -- but you have to live long enough to see it. We get only one shot at endless youth.

AOR

Well now, AOR Support:

That is indeed an information overload. My favorite!

[thumb]

Regarding your comments about endless youth; all too often we find that supplements that are proven to be effective at one thing turn out not to be. I am going to keep this general just to highlight the fact that this happens all the time.

Is this news for you AOR support? There is an inherent danger in ingesting any chemical; proven to be effective at x may be (we later find out) dangerous at y.

That is just the breaks of living on the supplement "edge."

...I don't know about you, Mr. Support, but I like living on the edge...



Thanks for the info on CLA, I appreciate it!

Hey AOLsupport.
You said
"ALCAR has a longer half-life, but should still best be taken at least twice daily. It should be taken away from food and from other quaternary amines (including DMAE, choline, and TMG) as they share a transporter system in the brain and GI and will compete for absorption if taken together."
How many hours appart should they be taken?

Hey AOLsupport.
    You said
"ALCAR has a longer half-life, but should still best be taken at least twice daily. It should be taken away from food and from other quaternary amines (including DMAE, choline, and TMG) as they share a transporter system in the brain and GI and will compete for absorption if taken together."
  How many hours appart should they be taken?

I am not AOR, but I call tell you that 45 minutes should be long enough. One hour may be a little better, but 45 minutes is good enough (assuming you are on an empty stomach to begin with [not eaten for 3-4 hours]).

I recently (two months ago) increased my daily dosage of KRALA to 900 millgrams, with no negative reaction. I am used to it; thanks for everybody's input.

Nootropi,

ALA and biotin are chemically similar. They share the same metabolic pathway. Make sure you're taking atleast 1:1 ALA/biotin. Unless you wanna go bald or something...

(another reason I love Life Extension Mix - 3g of biotin per daily serving)

[thumb]

[:o] Oh sh!t!


I just double checked this. It's 3,000mcg, not 3 grams! That's only 3 milligrams!

I gotta go check on my hair...

Lemon,

I'm aware of the chemical similarity, but do you have a reference for how much biotin one is supposed to take which I gather is 1 mg biotin/gm...ALA? gm R-ala?

Thanks.

Scott,

Dave from Bulk Nutrition says:

http://www.1fast400....and_Health.html

As a supplement, biotin even in large doses is ~100 percent bioavailable [12]. Taking a multivitamin that provides biotin should provide one with enough to avoid suboptimal status. The general recommendation for biotin supplementation to prevent deficiency due to ALA is 1 mg or more per 100 mg of ALA. If one is taking more than a gram of pantothenic acid daily, a biotin supplement providing at least 1 mg is warranted, and 3-5 mg may be best to stay on the safe side (it should also be noted that biotin and pantothenic acid exhibit a synergistic relationship under some circumstances). Because large amounts adminstered at a time might increase renal excretion, biotin is more effective when taken as two or three smaller doses throughout the day [12].

Also, might not a bad idea to take your ALA/RALA/KRALA away from biotin that way they won't have to compete.

Thanks.

Is there any contradiction between these two substances (for example competition for transport receptors etc.) when attempting to administer doses of R-ALA and ALCAR at the same time for convenience?

For example, if one's regimen was:

R-ALA 1g (333mg 3 divided doses )
ALCAR 2g (1000mg 2 divided doses)

Is taking 333mg of R-ALA simultaneously with 1000mg of ALCAR advisable if maximum absorption of both is important?

Edited by beggars_banquet, 15 November 2004 - 08:28 AM.

Is there any contradiction between these two substances (for example competition for transport receptors etc.) when attempting to administer doses of R-ALA and ALCAR at the same time for convenience? 

For example, if one's regimen was:

R-ALA  1g  (333mg 3 divided doses )
ALCAR  2g  (1000mg 2 divided doses)

Is taking 333mg of R-ALA simultaneously with 1000mg of ALCAR advisable if maximum absorption of both is important?

Read the whole thread next time. Your answer is here already!

This might be a little off-topic. Is SMI2LE's RALA have only +R Alpha Lipoic Acid? Or is bad negatively charged ALA in their? What about K-R-Ala? I just got some.

http://www.aor.ca/ma...-october_01.pdf

Pinball

This might be a little off-topic.  Is SMI2LE's RALA have only +R Alpha Lipoic Acid?  Or is bad negatively charged ALA in their?  What about K-R-Ala?  I just got some.

http://www.aor.ca/ma...er_01.pdf<br />

Pinball

Smi2le's KRALA is Gernova's KRALA. Check out geronova.com to find out more about KRALA.

If you got the KRALA, then you need 600 mg KRALA to equal 200 mg RALA. So to get an effective anti aging/cognitive enhancement dose, take 600 mg KRALA 3 times a day. If you got the plain RALA, then 200 mg = 200 mg.

This might be a little off-topic.  Is SMI2LE's RALA have only +R Alpha Lipoic Acid?  Or is bad negatively charged ALA in their?  What about K-R-Ala?  I just got some.

http://www.aor.ca/ma...er_01.pdf<br />

Pinball

Smi2le's KRALA is Gernova's KRALA. Check out geronova.com to find out more about KRALA.

If you got the KRALA, then you need 600 mg KRALA to equal 200 mg RALA. So to get an effective anti aging/cognitive enhancement dose, take 600 mg KRALA 3 times a day. If you got the plain RALA, then 200 mg = 200 mg.

Thanks again Nootropi,

yeah, on the gernova site, they say, it is "(typical RLA content >99.4%, SLA< 0.6%)". My post started because, http://www.aor.ca/ma...summer_2002.pdf said that AOR.CA are the only people that +RLA and no SLA.

Pithetic if it is true.

Pinball

That is a lot of RALA at 600 mgs. That fits into one medium size pill--I just made a batch. I wonder what kind of research is out on the safety of this particular chemical is. I am taking a large stack already... With the safety concerns that AOR put out in their periodical I am debating whether or not I should take it. I will tell you what gernova says.

Pinball

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

A question to anyone tuned in: If I add SAMe to ACAR, ALA, biotin, a full plate of vitamins and minerals, and ginkgo, will anything there cancel out the other or bring about an unwanted metabolic process?