94 replies to this topic

[health_nutty]

http://www.nytimes.c...?pagewanted=all

What is the implication of for ALCAR and other carnitine supplements?

[freeman]

I was reading earlier this week of a correlation between phosphatidylcholine and raised TMAO levels in mice with gut flora, but not in mice without gut flora. Really quite similar to this study. Here's another thread discussing this phosphatidylcholine/TMAO study.

Anyhow, seems like ALCAR and phosphatidylcholine, on the balance, are positives for one's health but that there's some bacterial culture (that meat eaters are more likely to have) that spoils the party. Might be a couple of cultures, even.

To me more than anything this suggests we (life extensionsists, scientists, etc.) really need to get a handle on the functional roles of the various bacterial communities living in our bodies.

Obviously wide spectrum antibiotics aren't much of a solution -- on the balance stripping your gut flora is probably far worse than it is good, but maybe veganism is a good solution -- so the thing I'd like to see come in the next stages of investigation are ideas on who bacterial culprits are and if we can eliminate them from our bodies and food sources without undesirable side effects.

[alecnevsky]

+1

"The researchers’ theory, based on their laboratory studies, is that TMAO enables cholesterol to get into artery walls and also prevents the body from excreting excess cholesterol."


Could this be a non-factor for those with low LDL ?

Edited by alecnevsky, 07 April 2013 - 09:05 PM.

[Dorian Grey]

Chris Masterjohn touched on the carnitine/TMAO issue in his rebuttal to the Phosphatidylcholine/TMAO study on heart disease.

In the studies he quotes, it seems carnitine and phosphatidylcholine may generate limited amounts of TMAO, but this is small potatoes compared to the amount of TMAO found in urine after eating SEAFOOD!

http://www.westonapr...-heart-disease/

Does Dietary Choline Contribute to Heart Disease?

by Chris Masterjohn

"these authors even fed 46 different foods to humans and looked at the subsequent excretion of trimethylamine and TMAO. Choline-rich foods like liver and eggs did not produce any increase in urinary trimethylamine or TMAO over control levels. In fact, even carnitine-rich meats failed to increase excretion of these compounds. The only foods that increased excretion of TMAO were seafoods, which naturally contain some trimethylamine, giving them their “fishy” smell.

Here we see that only seafoods, naturally contaminated with trimethylamine, increase the urinary excretion of trimethylamine and TMAO in humans. Liver, eggs, and meat do not.
These authors explained their results by citing research showing that the enzyme phospholipase A cleaves phosphatidylcholine, or lecithin, into a compound called lysolecithin in the small intestine where it is efficiently absorbed. By contrast, other forms of choline travel to the colon where gut bacteria make enzymes that convert them to trimethylamine."

This would seem to indicate if red meat is bad, fish may be even worse!

Edited by synesthesia, 07 April 2013 - 08:55 PM.

[bkaz]

I wonder if ALCAR, &| Alpha GPC, can be absorbed sublingually, to bypass the stomach altogether?

[alecnevsky]

I wonder if ALCAR, &| Alpha GPC, can be absorbed sublingually, to bypass the stomach altogether?

I wouldn't do ALCAR sublingually. GPC and Uridine would not be a problem. I may start doing that from now on and avoid ALCAR.


Edit: I wouldn't do ALCAR sublingually just in view of its acidic taste and what it may do to teeth enamel.

Edited by alecnevsky, 08 April 2013 - 12:37 AM.

[bkaz]

I wonder if ALCAR, &| Alpha GPC, can be absorbed sublingually, to bypass the stomach altogether?

I wouldn't do ALCAR sublingually. GPC and Uridine would not be a problem. I may start doing that from now on and avoid ALCAR.

Thanks, but could you explain why?

[niner]

I wonder if ALCAR, &| Alpha GPC, can be absorbed sublingually, to bypass the stomach altogether?

Now that you mention it, both ALCAR and carnitine are very water soluble, and I'd expect them to be pretty well absorbed before they hit the lower intestine and colon. Isn't that where the bacteria hang out? Meat is a complex substance that would take some time to fully digest, so maybe it carries carnitine further down the digestive tract where the bugs can get at it.

Some things that might help the TMAO situation in general would be to eat meat and fish irregularly, and maybe use probiotics. It might also make sense to cycle ALCAR along with meat- maybe a couple days off a week would be enough to keep the carnitine-eating bacteria from gaining a major foothold.

[alecnevsky]

I wonder if ALCAR, &| Alpha GPC, can be absorbed sublingually, to bypass the stomach altogether?

Now that you mention it, both ALCAR and carnitine are very water soluble, and I'd expect them to be pretty well absorbed before they hit the lower intestine and colon. Isn't that where the bacteria hang out? Meat is a complex substance that would take some time to fully digest, so maybe it carries carnitine further down the digestive tract where the bugs can get at it.

Some things that might help the TMAO situation in general would be to eat meat and fish irregularly, and maybe use probiotics. It might also make sense to cycle ALCAR along with meat- maybe a couple days off a week would be enough to keep the carnitine-eating bacteria from gaining a major foothold.

That makes my 6 months of daily ALCAR somewhat reconcilable. Thanks.

Still, I was recently inducted into a keto diet and find the choline/alcar questions on TMAO very concerning. Did the other thread come to the conclusion that A-GPC is not safe in supplement form but fine when derived from eggs and meats while ALCAR seems to be safer when it's from a water soluble source?

[nightlight]

Linking (via non-randomized statistical associations with TMAO) heart disease and obesity to intestinal flora sets stage for 'second hand obesity' and social isolation of fat people (as always, to protect children, this time from the bad intestinal bugs), as it was done with smokers once the 'second hand smoke' hysteria was whipped up by the same big bucks foundations (e.g. RWJF) that financed antismoking propaganda and legislations. Since obesity (like smoking) has strong racial and class biases, it's yet another a convenent excuse to practice politically correct forms of racial and class discrimination (e.g. a guilt free way to rid towns and cities of the wrong kind of people and be proud of doing it, for the chidren). Bans of marijuana (and other non-pharma drugs/medicinal herbs) used to serve similar discriminatory objectives in early 20th century, albeit back then the racial and class motivation behind the prohibitions was overt. Today we use junk science as a form of self-decepetion to hide those same underlying motivations.

[alecnevsky]

Linking (via non-randomized statistical associations with TMAO) heart disease and obesity to intestinal flora sets stage for 'second hand obesity' and social isolation of fat people (as always, to protect children, this time from the bad intestinal bugs), as it was done with smokers once the 'second hand smoke' hysteria was whipped up by the same big bucks foundations (e.g. RWJF) that financed antismoking propaganda and legislations. Since obesity (like smoking) has strong racial and class biases, it's yet another a convenent excuse to practice politically correct forms of racial and class discrimination (e.g. a guilt free way to rid towns and cities of the wrong kind of people and be proud of doing it, for the chidren). Bans of marijuana (and other non-pharma drugs/medicinal herbs) used to serve similar discriminatory objectives in early 20th century, albeit back then the racial and class motivation behind the prohibitions was overt. Today we use junk science as a form of self-decepetion to hide those same underlying motivations.

Are you in the right section of the forum?

[bkaz]

Niner:

Now that you mention it, both ALCAR and carnitine are very water soluble, and I'd expect them to be pretty well absorbed before they hit the lower intestine and colon. Isn't that where the bacteria hang out? Meat is a complex substance that would take some time to fully digest, so maybe it carries carnitine further down the digestive tract where the bugs can get at it.

bkaz:

Interesting, but these studies showed TMAO increase after carnitine supplementation? Or they took them with fatty meals? TMAO threat does seem to be tenuous, - seafood didn't hurt Okinawans.

BTW, I tried A-GPC sublingually, - it doesn't dissolve. ALCAR is too sour, might do something to the teeth. L-Carnitine is sour too?

Niner:

Some things that might help the TMAO situation in general would be to eat meat and fish irregularly, and maybe use probiotics. It might also make sense to cycle ALCAR along with meat- maybe a couple days off a week would be enough to keep the carnitine-eating bacteria from gaining a major foothold.


bkaz:
Good idea.

Edited by bkaz, 08 April 2013 - 12:55 PM.

[nightlight]

Are you in the right section of the forum?

The link to heart disease via TMAO is weak (correlations on non-randomized samples), hence the whole conjecture is likely a junk science (heart disease is "linkable" to almost anything, it correlates with dozens, perhaps over hundred, of risk factors). Their main assertion also contradicts known protective effects of carnitines which are more solid, being based on hard science (animal experiments). The rest of my post merely speculates on possible agenda behind it (it's always about money, but which money in this case). The main point is -- I wouldn't rush to dump ALCAR and choline supplies into trash just because of this paper.

[Deeviant]

"Researchers, led by Stanley Hazen, chief of cellular and molecular medicine at the Cleveland Clinic's Lerner Research Institute, tested the carnitine and TMAO levels of omnivores, vegans and vegetarians, and examined records of 2,595 patients undergoing cardiac evaluations. In patients with high TMAO levels, the more carnitine in their blood, the more likely they were to develop cardiovascular disease, heart attacks, stroke and death."

I can't post a link, but a quick google search will get you right to several articles citing the study. The research specifically talks about L-Carnitine and I'm not 100% sure that it's acetylated form will cause the same problems, nevertheless, I think it warrents further research.

Thoughts?

[Mind]

Are you in the right section of the forum?

The link to heart disease via TMAO is weak (correlations on non-randomized samples), hence the whole conjecture is likely a junk science (heart disease is "linkable" to almost anything, it correlates with dozens, perhaps over hundred, of risk factors). Their main assertion also contradicts known protective effects of carnitines which are more solid, being based on hard science (animal experiments). The rest of my post merely speculates on possible agenda behind it (it's always about money, but which money in this case). The main point is -- I wouldn't rush to dump ALCAR and choline supplies into trash just because of this paper.

I have to kind-of agree with nightlight on the tenuous nature of this research. The safety and health benefits of carnitine were previously well accepted, so much so that entire supplement lines were based upon it. The multi-step nature of this possible mechanism of heart disease also makes it more tenuous in my mind.

Also remember that mouse studies rarely translate very well into humans - as is documented extensively in these forums. Being neurotic about health, LongeCity members tend to "jump on" both positive and negative research results, no matter if it is in yeast, worms, mice, or even in vitro. Overall, I think it is a positive thing, in that you will find some of the most critique-laden discussions on the most up-to-date research at LongeCity, however, stress is a well-known killer in humans so....don't freak out just yet.

In addition, there are some traditional human populations which have nearly zero incidence of heart disease (maasai, intuit, some native amarican cultures), despite having a diet almost exclusively comprised of meat/fish/milk and fat. There are many caveats with this point (genetics, lifestyle, quality of food-organic, etc...) but if this carnitine connection to heart disease was STRONG, one would expect god-awful levels of heart disease in these populations (back in the day when they lived traditionally).

Outside of traditional meat eating sub-cultures, almost all of the longest lived populations in the world, are omnivorous (except the 7th day adventists in California). However, they typically eat less animal-based proteins than found in the SAD (which is a great abbreviation for the "sad" state of the American diet - too much low quality protein and waaaaay too many empty carbs). Seeing this research makes me glad that I eat a lot of vegetables. Most research would point to more vegetables and less meat as a good way to stay healthy. Of course, different people have success with different diets, and genetics rule supreme (based on super-centenarian research).

In the end, I spent too much time commenting on this subject, because carnitine is a miniscule consideration in the whole scheme of curing aging. Much, much, much, much more important is supporting rejuvenation research. Be sure to save a couple extra dollars to donate to LongeCity, SENS, and Methuselah Foundation research later this year!

[nowayout]

Carnitine may be nice for certain conditions, but given that carnitine is not for the average person an essential supplement for quality of life, I plan to stop taking carnitine for now until this is sorted out.

We can argue all we want to make ourselves feel better about past consumption, but I think a proper abundance of caution puts the onus on proponents of a substance to disprove any evidence of harm that may arise.

In simple terms, the smarter algorithm is "stop until suspicions of harm disproved", and not "continue until suspicions of harm verified."

Edited by viveutvivas, 08 April 2013 - 07:21 PM.

[spermidine]

i think its mostly related to the supplementation of carnitine that can be bad. meat doesnt have as much carnitine per 100 grams that can either be beneficial or detrimental. you will probably need to consume 5 steaks every day for weeks before if anything beneficial or detrimental occurs. people on this thread do act like kids freaking out so easily over one study having negative input on carnitine when there are dozen studies before it that show carnitine being beneficial for variety of other problems.

[Mind]

Carnitine may be nice for certain conditions, but given that carnitine is not for the average person an essential supplement for quality of life, I plan to stop taking carnitine for now until this is sorted out.

We can argue all we want to make ourselves feel better about past consumption, but I think a proper abundance of caution puts the onus on proponents of a substance to disprove any evidence of harm that may arise.

In simple terms, the smarter algorithm is "stop until suspicions of harm disproved", and not "continue until suspicions of harm verified."

I understand your point here and it is good to bring it up, but if that was my guiding principle, I would not be eating much of anything because there is "negative" research/theory on almost every food and supplement. Even the most well known super-food correlated with the healthiest long-lived disease-free of human populations (epidemiologically known for centuries) - olive oil(olives) - is "forbidden" to eat by Dean Ornish, because it is "bad".

[niner]

We can argue all we want to make ourselves feel better about past consumption, but I think a proper abundance of caution puts the onus on proponents of a substance to disprove any evidence of harm that may arise.

In simple terms, the smarter algorithm is "stop until suspicions of harm disproved", and not "continue until suspicions of harm verified."

But you can't prove a negative. We can't really prove that there is no harm. Any random academic can publish a misleading study that makes something look bad. I don't really think there is a simple algorithm here. We need to consider the totality of the evidence, expected harms, expected benefits, probabilities on all of these. It's complicated. This particular study is not much more than a data point, as far as I'm concerned. I'd love to see blood levels of trimethylamine and TMAO in humans after normal oral doses of acetyl carnosine. I'll probably have to wait a long time for that...

[nowayout]

We can argue all we want to make ourselves feel better about past consumption, but I think a proper abundance of caution puts the onus on proponents of a substance to disprove any evidence of harm that may arise.

In simple terms, the smarter algorithm is "stop until suspicions of harm disproved", and not "continue until suspicions of harm verified."

But you can't prove a negative. We can't really prove that there is no harm. Any random academic can publish a misleading study that makes something look bad.

Sure, we cannot prove that there is no harm, but sometimes a study can raise a legitimate suspicion of possible harm. When this happens, I personally think it is a risky strategy to continue consumption. It is better to stop and wait for contradictory evidence, especially in the case of a supplement like carnitine that is not that much of a miracle anyway. The way some people are going on about continuing carnitine you would think it was the fountain of youth or something, when the truth is that it doesn't do all that much to justify taking risks for.

But I am not trying to convince anybody else, just explaining my own reasoning as applied to my own choices.

Edited by viveutvivas, 08 April 2013 - 09:58 PM.

[alecnevsky]

If it were not for some earlier studies suggesting NGF increase with ALCAR, I probably would not be taking it (the effect on energy is marginal.) My neck is really loving the first day off of it in a while. I did try A-GPC sublingually and it was not as easy as Uridine. I used to be able to do a-gpc sublingually when Smart powders had it at 99% instead of washed out 50% at most.

[zorba990]

Or could it be that increased blood levels of carnitine are the result of the problem and not causal. Carnitine is specific for supporting heart mitochondria so would be a reasonable backup system for a failing heart.

[niner]

This paper shows that oral L-carnitine in humans does lead to an increase in trimethylamine. However, they said that the levels of TMAO only increased for the largest dose, a total of 6g/d.

J Clin Pharmacol. 2006 Oct;46(10):1163-70.
Disposition and metabolite kinetics of oral L-carnitine in humans.
Bain MA, Milne RW, Evans AM.

Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.

The pharmacokinetics of L-carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose interval increased significantly (P < .05) from a baseline of 54.2 +/- 9.3 microM to 80.5 +/- 12.5 microM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P < .001) in the renal clearance of L-carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L-carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine-N-oxide from baseline was evident only for the 2-g dose of L-carnitine (from 34.5 +/- 2.0 to 149 +/- 145 microM), and its renal clearance decreased with increasing dose (P < .05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a dose of 0.5 g 3 times a day.

PMID: 16988205

The next two papers show that there is ready interconversion between ALCAR, PLCAR, and L-Carnitine. One thing that I don't know is whether or not either ALCAR or PLCAR represent trimethylamine sources. I'd imagine they would, but it's also possible that being acylated would prevent that from happening. Therefore, at this point it's not obvious whether a typical 1g/d dose of ALCAR is dangerous or safe, but on the basis of the first paper showing no increase in TMAO until the highest dose of Carnitine, I would guess that a low dose of ALCAR is ok.

Br J Clin Pharmacol. 2000 Nov;50(5):441-8.
Pharmacokinetics of propionyl-L-carnitine in humans: evidence for saturable tubular reabsorption.
Pace S, Longo A, Toon S, Rolan P, Evans AM.

Sigma Tau Industrie Farmaceutiche Riunite s.p.a., Pomezia, Rome, Italy.

AIMS:

Propionyl-L-carnitine (PLC) is an endogenous compound which, along with L-carnitine (LC) and acetyl-L-carnitine (ALC), forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC is currently under investigation for the treatment of peripheral artery disease, and the present study was conducted to assess the pharmacokinetics of intravenous propionyl-L-carnitine hydrochloride.
METHODS:

This was a placebo-controlled, double-blind, parallel group, dose-escalating study in which 24 healthy males were divided into four groups of six. Four subjects from each group received propionyl-L-carnitine hydrochloride and two received placebo. The doses (1 g, 2 g, 4 g and 8 g) were administered as a constant rate infusion over 2 h and blood and urine were collected for 24 h from the start of the infusion. PLC, ALC and LC in plasma and urine were quantified by h.p. l.c.
RESULTS:

All 24 subjects successfully completed the study and the infusions were well tolerated. In addition to the expected increase in PLC levels, the plasma concentrations and urinary excretion of LC and ALC also increased above baseline values following intravenous propionyl-L-carnitine hydrochloride administration. At a dose of 1 g, PLC was found to have a mean (+/- s.d.) half-life of 1.09 +/- 0.15 h, a clearance of 11.6 +/- 0.24 l h-1 and a volume of distribution of 18.3 +/- 2.4 l. None of these parameters changed with dose. In placebo-treated subjects, endogenous PLC, LC and ALC underwent extensive renal tubular reabsorption, as indicated by renal excretory clearance to GFR ratios of less than 0.1. The renal-excretory clearance of PLC, which was 0.33 +/- 0.38 l h-1 under baseline condition, increased (P < 0. 001) from 1.98 +/- 0.59 l h-1 at a dose of 1 g to 5.55 +/- 1.50 l h-1 at a dose of 8 g (95% confidence interval for the difference was 2.18,4.97). As a consequence, the percent of the dose excreted unchanged in urine increased (P < 0.001) from 18.1 +/- 5.5% (1 g) to 50.3 +/- 13.3% (8 g). The renal-excretory clearance of LC and ALC also increased substantially after PLC administration and there was evidence for renal metabolism of PLC to LC and ALC.
CONCLUSIONS:

Intravenous administration of propionyl-L-carnitine hydrochloride caused significant increases in the renal excretory clearances of PLC, LC and ALC, due to saturation of the renal tubular reabsorption process - as a consequence there was a substantial increase with dose in the fraction excreted unchanged in urine. Despite the marked increase in the renal clearance of PLC, total clearance remained unchanged, suggesting a compensatory reduction in the clearance of the compound by non excretory routes.

PMID: 11069438 PMCID: PMC2014409

Clin Invest Med. 2009 Feb 1;32(1):E13-9.
Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers.
Cao Y, Wang YX, Liu CJ, Wang LX, Han ZW, Wang CB.

The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.

PURPOSE:

To investigate the pharmacokinetics of L-carnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy volunteers after single L-carnitine administration.
METHODS:

Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC.
RESULTS:

The maximum plasma concentration (Cmax) and area under the curve (AUC 0-infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3 micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08 micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01). The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively.
CONCLUSION:

L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC.

PMID: 19178874

[spermidine]

isnt ALCAR supported for heart health ? there have been few studies i read from the past supporting it for heart health but now with this new study, all those past claims its good for the heart are canceled ?

[TheFountain]

Are you in the right section of the forum?

The link to heart disease via TMAO is weak (correlations on non-randomized samples), hence the whole conjecture is likely a junk science (heart disease is "linkable" to almost anything, it correlates with dozens, perhaps over hundred, of risk factors). Their main assertion also contradicts known protective effects of carnitines which are more solid, being based on hard science (animal experiments). The rest of my post merely speculates on possible agenda behind it (it's always about money, but which money in this case). The main point is -- I wouldn't rush to dump ALCAR and choline supplies into trash just because of this paper.

I have to kind-of agree with nightlight on the tenuous nature of this research. The safety and health benefits of carnitine were previously well accepted, so much so that entire supplement lines were based upon it. The multi-step nature of this possible mechanism of heart disease also makes it more tenuous in my mind.

Also remember that mouse studies rarely translate very well into humans - as is documented extensively in these forums. Being neurotic about health, LongeCity members tend to "jump on" both positive and negative research results, no matter if it is in yeast, worms, mice, or even in vitro. Overall, I think it is a positive thing, in that you will find some of the most critique-laden discussions on the most up-to-date research at LongeCity, however, stress is a well-known killer in humans so....don't freak out just yet.

In addition, there are some traditional human populations which have nearly zero incidence of heart disease (maasai, intuit, some native amarican cultures), despite having a diet almost exclusively comprised of meat/fish/milk and fat. There are many caveats with this point (genetics, lifestyle, quality of food-organic, etc...) but if this carnitine connection to heart disease was STRONG, one would expect god-awful levels of heart disease in these populations (back in the day when they lived traditionally).

Outside of traditional meat eating sub-cultures, almost all of the longest lived populations in the world, are omnivorous (except the 7th day adventists in California). However, they typically eat less animal-based proteins than found in the SAD (which is a great abbreviation for the "sad" state of the American diet - too much low quality protein and waaaaay too many empty carbs). Seeing this research makes me glad that I eat a lot of vegetables. Most research would point to more vegetables and less meat as a good way to stay healthy. Of course, different people have success with different diets, and genetics rule supreme (based on super-centenarian research).

In the end, I spent too much time commenting on this subject, because carnitine is a miniscule consideration in the whole scheme of curing aging. Much, much, much, much more important is supporting rejuvenation research. Be sure to save a couple extra dollars to donate to LongeCity, SENS, and Methuselah Foundation research later this year!

What about this then?

"They evaluated 2,595 patients undergoing heart exams, and found increasing carnitine levels increased risks for stroke, heart attacks and other cardiac events in subjects with high levels of TMAO. Vegans and vegetarians had significantly lower baseline levels of TMAO than meat-eating omnivores, the researchers found. Vegetarians and vegans given carnitine did not show major increases in TMAO levels, however, when compare with meat-eaters who consumed the same amount of carnitine, which suggests vegetarians may possess different gut bacteria."

[niner]

Now that you mention it, both ALCAR and carnitine are very water soluble, and I'd expect them to be pretty well absorbed before they hit the lower intestine and colon. Isn't that where the bacteria hang out? Meat is a complex substance that would take some time to fully digest, so maybe it carries carnitine further down the digestive tract where the bugs can get at it.

Looks like the supplemental forms are not so well absorbed, and are metabolized by gut bacteria. OTOH, meat carnitine is absorbed a lot better. Maybe because there's less of it? Anyone know how much carnitine there is in 100g of beef? (or other sources)

Ann N Y Acad Sci. 2004 Nov;1033:30-41.
Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism.
Rebouche CJ.

Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA. charles-rebouche@uiowa.edu

In mammals, the carnitine pool consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary L-carnitine is 54-87% and is dependent on the amount of L-carnitine in the meal. Absorption of L-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose. Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues). At normal dietary L-carnitine intake, whole-body turnover time in humans is 38-119 h. In vitro experiments suggest that acetyl-L-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-L-carnitine concentration was increased 43% after oral acetyl-L-carnitine supplements of 2 g/day, indicating that acetyl-L-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-L-carnitine is rapidly, but not completely hydrolyzed, and acetyl-L-carnitine and L-carnitine concentrations return to baseline within 12 h. At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating L-carnitine concentration increases (as after high-dose intravenous or oral administration of L-carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating L-carnitine concentration to baseline. Elimination kinetics for acetyl-L-carnitine are similar to those for L-carnitine. There is evidence for renal tubular secretion of both L-carnitine and acetyl-L-carnitine. Future research should address the correlation of supplement dosage, changes and maintenance of tissue L-carnitine and acetyl-L-carnitine concentrations, and metabolic and functional changes and outcomes.

PMID: 15591001

[TheFountain]

This paper shows that oral L-carnitine in humans does lead to an increase in trimethylamine. However, they said that the levels of TMAO only increased for the largest dose, a total of 6g/d.

J Clin Pharmacol. 2006 Oct;46(10):1163-70.
Disposition and metabolite kinetics of oral L-carnitine in humans.
Bain MA, Milne RW, Evans AM.
PMID: 16988205

So the miniscule 500 mgs or 1 gram dosage most of us are taking should not increase the risk? But presumably the people in the study were not supplementing? Do people get that much carnitine from diet? Are does this have more to do with the way gut flora differs from those consuming red meat vs vegetarians?

Edited by Michael, 12 April 2013 - 06:38 PM.

[Blankspace]

Anyone know how much carnitine there is in 100g of beef? (or other sources)

The Linus Pauling Institute has a chart:
http://lpi.oregonsta...tml#performance

Three ounces of beef steak contains 81mg of l-carnitine.

[spermidine]

lol 81mg and you need what, like 3 grams regularly or something for anything bad to occur. enough said

[bobz1lla]

http://www.jnutbio.c...0151-0/abstract
http://www.sciencedi...02191509405460Z
http://www.sciencedi...043661801908527