94 replies to this topic

[niner]

I wonder if one could offset this effect, if it is real, with vitamin K2.

The "if its real" hits it on the head. Just eat real food, not human made crap.

K2 would likely help in the process.

Meat is real food. So's fish. Are you saying don't take any form of supplemental carnitine?

What does K2 have to do with this? I don't see it.

[eddielang]

I wonder if one could offset this effect, if it is real, with vitamin K2.

The "if its real" hits it on the head. Just eat real food, not human made crap.

K2 would likely help in the process.

Meat is real food. So's fish. Are you saying don't take any form of supplemental carnitine?

What does K2 have to do with this? I don't see it.

Agreed, animals are real food, and likely the best.

I just don't see any value to the study as we should be eating food, not food parts.

[misterE]

Animal-foods like meat, cheese, milk and eggs are high in saturated-fat and cholesterol and deficient in fiber and phytonutrients. Saturated-fat plays a key role in insulin-resistance. These animal-foods today are also packed with dioxins and PCB's, which are powerful hormone-disruptors and carcinogens.



The logical choice from reading not only this study, but the bulk of the scientific-data, is that we should be eating more plant-based foods like whole-grains and legumes, and less meat, dairy, eggs, and processed-food. This study posted in the opening-post is just more confirmation.

Edited by misterE, 21 April 2013 - 04:03 PM.

[eddielang]

Animal-foods like meat, cheese, milk and eggs are high in saturated-fat and cholesterol and deficient in fiber and phytonutrients. Saturated-fat plays a key role in insulin-resistance. These animal-foods today are also packed with dioxins and PCB's, which are powerful hormone-disruptors and carcinogens.



The logical choice from reading not only this study, but the bulk of the scientific-data, is that we should be eating more plant-based foods like whole-grains and legumes, and less meat, dairy, eggs, and processed-food. This study posted in the opening-post is just more confirmation.

I don't see it. Sorry, but animal foods minus processed foods are protective, not causative of insulin resistance.

The logical thing would be to eat foods that we were evolutionary designed to eat.

Compare our digestive tract with that of a ruminant and that of a carnivore. Then ask yourself why we store fat not carbs as an endogenous fuel source, what's the benefit there if its going to shorten vs. sustain life?

What foods can you find in nature in winter? Delicious and nutritious animals, and the sea ones are the best for making human brains. You can't do that with veggies, not enough EPA/DHA.

What foods do we have to pre-process or "enrich" to not get sick by eating them raw?
Oh, it's the foods you are advocating, grains, and beans.

[8bitmore]

[,,,]
A question to you: what sort of things are we reliant on our gut flora?

Please use actual, recent, research and not old prevalent 'reasonable' assumptions. <-- I bolded this, because of the wide-spread, long-invalid, misconceptions in this field harbored by many people today, including well educated people.

Just to ran ahead of you in this a bit:
- we do not rely on our gut flora for digestion nor production of essential nutrients. Those who disagree, please show legit research.
- they do not really 'protect' us from pathogens.

The other question: what is normal biota? Isn't it the one that outputs all sort of nasty stuff into the bloodstream of an average person, starting with LPS and ending with TMAO discussed here?

What about after using antibiotics? Common sense would be to dose prebiotics/fiber, with some starter probiotics. At least for a little while after.

That's the right way of using antibiotics, i.e. to follow with good pro- and prebiotics for at least as long as antibiotics were taken.

I don't understand the position you are championing here, first you argue that the gut flora is, at best, inconsequential in relation to our health and then you commence to support the use of probiotics?

[xEva]

I don't understand the position you are championing here, first you argue that the gut flora is, at best, inconsequential in relation to our health and then you commence to support the use of probiotics?

We cannot avoid microbes. Even when we are super-clean and hygienic, all our attempts at sterility are futile in practice. No matter what we do, some bacteria will get in where they do not belong. And they will be take out promptly by the immune sys. So quickly that we won't even notice. In fact, that's what goes on every single day, every minute of our lives. It is when the bacteria that 'got in' are numbered in millions that we notice the intrusion through malaise or fever. It all boils down to the number of bugs that got in. As long as it's low, we have nothing to worry about.

So here is my position on bacteria. Our immune systems manage them. I do not consider them our symbionts, because in my view symbionts do not finish off their host the moment his immune sys goes down, and that's precicely what bacteria that are considered normal part of our gut flora do, when the opportunity presents itself.

Take Bacteroides fragilis. The studies show that mortality due this 'normal' symbiotic bug getting into the bloodstream hovers around 30%, which makes us walking time bombs. When/who knows/how this or some other 'symbiont' ventures out of its niche and takes us out?

There are many publications nowadays in which bacteria are touted as our little friends and helpers. They are largely naive. To keep it short, I will give only one example to show the undisputed truth of my words. That's immune deficiency syndromes, both acquired like AIDS or inborn like in 'plastic bubble boys' stories I'm sure you've read about. When the immune sys is down, it is not some exotic ebola or plague that takes the patient out. It is invariably a mundane, common non-pathogenic 'symbiont' that ventured out of its usual niche. And what keeps it in its niche? The immune sys.

The bottom line is, there is no good bacteria. Some are better than others. How bad they are depends entirely on our immune sys and nothing else. Really. Either it can handle them or it cannot.

Since living without them is impossible, we have to manage them. Actively and aggressively, just like our immune systems do it. That's my position on microbes.


Refs

Clinical significance of and outcomes for Bacteroides fragilis bacteremia http://www.ncbi.nlm....pubmed/19812858

Attributable mortality of bacteremia associated with the Bacteroides fragilis group. http://www.ncbi.nlm..../pubmed/7548498

Edited by xEva, 21 April 2013 - 11:46 PM.

[xEva]

LEF's rebuttal to the recent media-sensationalized carnitine report. They are still down on red meat, but not carnitine supplementation (a vested interest, of course).

The authors of the Mayo Clinic study found carnitine supplementation was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in angina symptoms in patients who had experienced a heart attack. These effects were thought to occur through multiple mechanisms, including improved energy metabolism in the mitochondria, decreased ischemia, and enhanced left ventricle function.2

But these positive Mayo Clinic study results do not deny what registered nurses who manage children on therapeutic ketogenic diets have been reported and advised to parents for years. (I don't know what goes on now, but several years ago carnitine was a regular supplement for the therapeutic ketogenic diet.) The nurses advised parents that bad breath that often arises on the diet is due to bacteria overgrowth fed by carnitine.

So, yes, the carnitine is a good supplement for improved energy metabolism, etc. but still it causes certain bacteria to flourish. My solution is simple: keep the numbers of those bacteria low by blowing them periodically out and keep the goodies carnitine has to offer without the downsides. Why not?

I posted this info in another thread several days ago.
An enteric coated dosage of sorbic acid (maybe a different organic acid would work better) could be helpful in limiting growth of some gut flora that produce TMA.

But IMHO there is a simpler method of adding some acids and that is various types of bifido/lacto and their metabolites delivered via various fermented foods and 'brines' like sauerkraut or pickles 'juice', and yogurts.

[Godof Smallthings]

Interestingly, according to this study: http://www.formatex....ook/773-781.pdf , the ethanol extract of the root bark from the goji berry tree (cortex lycii radicis) was active in vitro against bacterial strains that produce TMAO. It's a long shot, but I wonder if it would counteract the problems with carnitine supplementation in omnivores?

[revenant]

@ xEva: Weak acids are mostly absorbed in the stomach. One would need to protect a weak organic acid so that it can reach the lower GIT where most of the target bacteria species are located. The great thing about this approach, is the fact that the "good" bacteria are not affected by non-ionized acids.

[Michael]

I hope to have more to add to this thread in a while, but for now I'll note a new report on this connection in the New England Journal of Medicine:

Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk

W.H. Wilson Tang, M.D., Zeneng Wang, Ph.D., Bruce S. Levison, Ph.D., Robert A. Koeth, B.S., Earl B. Britt, M.D., Xiaoming Fu, M.S., Yuping Wu, Ph.D., and Stanley L. Hazen, M.D., Ph.D.

N Engl J Med 2013; 368:1575-1584April 25, 2013DOI: 10.1056/NEJMoa1109400

... We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels ... after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics.

We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography.

Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics.

Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups.

The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events.
http://www.nejm.org/...6/NEJMoa1109400

I don't think this adds ENORMOUSLY to the case they had already built -- but add, it does.

[Sillewater]

So, in light of this addition, maybe intermittent carnitine supplementation so that the gut bacteria isn't induced?

[Climactic]

Any info on how exactly TMAO is linked to CVD? What is the mechanism? Maybe there is something else that can be done to break the link.

Edited by Climactic, 28 April 2013 - 10:57 PM.

[Hebbeh]

+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 ?

From post #3

[kismet]

I started reading the paper and found their conclusion to be backed by their data in general, although, some issues remain (can we independently reproduce the results?, sample size, artificial conditions for *some* sub-experiments, secondary prevention, ...).

So, in light of this addition, maybe intermittent carnitine supplementation so that the gut bacteria isn't induced?

The first thing I noticed was that vegans (vegetarians) had no TMAO response. This would be an obvious start, coupled with improving carnitine absorption (reduce and split doses? etc?), possibly also intermittent dosing. That is, if we really want to take carnitine.

Do you remember that creatine also might have unique benefits in veg*ans?

Additionally:
If people are wondering what the hell all these seemingly contradictory studies mean, you can read my summary of recent research. I had the idea to sum it all up after reading this thread and the usual confusion it elicited.

Edited by kismet, 29 April 2013 - 03:40 PM.

[Mind]

I started reading the paper and found their conclusion to be backed by their data in general, although, some issues remain (can we independently reproduce the results?, sample size, artificial conditions for *some* sub-experiments, secondary prevention, ...).

So, in light of this addition, maybe intermittent carnitine supplementation so that the gut bacteria isn't induced?

The first thing I noticed was that vegans (vegetarians) had no TMAO response. This would be an obvious start, coupled with improving carnitine absorption (reduce and split doses? etc?), possibly also intermittent dosing. That is, if we really want to take carnitine.

Do you remember that creatine also might have unique benefits in veg*ans?

Additionally:
If people are wondering what the hell all these seemingly contradictory studies mean, you can read my summary of recent research. I had the idea to sum it all up after reading this thread and the usual confusion it elicited.

Thanks so much for the summary and the links Kismet! Very much appreciated.

[Guardian4981]

So are folks saying the issue is gut bacteria?

Not saying that doesn't play a role, but has anyone considered the thyroid relationship?

Carnitine seems to lower T3, and lowered levels of T3 may be associated with heart disease. I know when I took carnitine after a few days I felt really lethargic!

[Sillewater]

...........
Do you remember that creatine also might have unique benefits in veg*ans?

.......

I take 800mg of creatine a day. Creapure.

[kismet]

I hope to have more to add to this thread in a while, but for now I'll note a new report on this connection in the New England Journal of Medicine:

Meanwhile, to fuel the controversy a little more. It seems that models of longevity are characterized by low choline levels (1):

In terms of metabolic commonality, three metabolites choline, TMA and mobile lipids (mainly VLDL) were significantly altered (decreased) in all three long-lived mice [dietary restriction, Ames dwarf, Irs-/-] relative to their appropriate controls.

So, I would be very careful with choline supplementation given all the data we have. Just try getting the Adequate Intake without any free choline and keep meat intake low for now. The evidence for higher choline dosing is weak anyway.

1. J Proteome Res. 2012 Apr 6;11(4):2224-35. doi: 10.1021/pr2010154. Epub 2012 Feb 27.
Metabotyping of long-lived mice using 1H NMR spectroscopy.
Wijeyesekera A, Selman C, Barton RH, Holmes E, Nicholson JK, Withers DJ.

[Michael]

Meanwhile, to fuel the controversy a little more. It seems that models of longevity are characterized by low choline levels (1):

In terms of metabolic commonality, three metabolites choline, TMA and mobile lipids (mainly VLDL) were significantly altered (decreased) in all three long-lived mice [dietary restriction, Ames dwarf, Irs-/-] relative to their appropriate controls.

So, I would be very careful with choline supplementation given all the data we have. Just try getting the Adequate Intake without any free choline and keep meat intake low for now. The evidence for higher choline dosing is weak anyway.

A very important finding, Kismet -- thanks! Have you seen the full text? I wonder if the study reports one way or the other on carnitine: lab mouse chow is vegetarian and doesn't contain carnitine, so you wouldn't expect it to be there to modulate.

On the one hand, this may mean that CR mice (and people?) are less prone to release free choline into the blood and possibly to convert it to TMA, meaning that CR folk are somewhat protected from this effect. On the other hand, it may mean that this is somehow an important mediator of some CR benefits, and overconsuming phosphatidylcholine or taking 'free' choline or carnitine supplements could nix some of our CR benefits.

It also adds another dimension to my previous comments to the effect that since TMA-induced atherosclerosis could not explain Spindler's finding that carnitine supplementation slightly decreased the LS of AL mice (since mice don't get atherosclerosis without special modifications to alter their cholesterol metabolism), "the sum of the rodent and human evidence seems to imply a double whammy: accelerated atherosclerosis, AND some other, unguessed mechanism of increased mortality to boot."

This new research implies, first, the possibility that suppressing TMA production is somehow important to the BENEFIT of CR even in genetically normal mice (which don't develop atherosclerosis), and that TMA per se may be bad even for AL mice.

(By the way, it's not just Spindler who has reported a deleterious effect of carnitines on lifespan in healthy mice. Weindruch, who is also one of the very few scientific researchers who really runs proper LS studies (ie, where the controls are not obese, or sickly, or genetically fucked-up, or what have you, but have normal, proper survival from the get-go) found that two separate *cocktails* of supplements *including* /acetyl/ -L-carnitine (ALCAR) slightly shortened the lives of otherwise-healthy mice: one cocktail of ALCAR with lipoic acid, lycopene, and alpha-tocopherol, and one cocktail of ALCAR with CoQ10, lipoic acid, and NADH:

(This is the only reporting of these data that I know. These results come from the LEF LifeSpan Project, very little of which have ever seen the light of day ...

Reference
1. J Proteome Res. 2012 Apr 6;11(4):2224-35. doi: 10.1021/pr2010154. Epub 2012 Feb 27.
Metabotyping of long-lived mice using 1H NMR spectroscopy.
Wijeyesekera A, Selman C, Barton RH, Holmes E, Nicholson JK, Withers DJ.

Edited by Michael, 09 September 2013 - 12:56 PM.

[Michael]

"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 ?

No: if anything, it seems like the relative increase in risk is higher for those with low (<70 mg/dL, which is pretty damned low) LDL (adjusted relative risk for Major Adverse Cardiovascular Events (MACE) among patients in the top vs. bottom quartiles of TMAO of 2.5) vs. the same comparison in people with good (RR for persons with >70 mg/dL = 1.6) or high (RR at LDL> 100 mg/dL also = 1.7) LDL.

At a guess, I'm going to hypothesize that this might be because when your LDL is high, it tends to be older and oxidized, so that there's already something triggering arterial macrophages to take it up, whereas when LDL levels are low (and younger and less oxidized), your macrophages may not bother taking up an occasional stray particle unless it gets a little "encouragement" (in the form of TMA) to engulf it.

[Wry]

[/center]

 

From the limited amount information provided, it seems that CoQ10, ALA, or NADH may have acted as a negative force on the red control group. In the pink control group it may have been the Vitamin E, ALA, or Lycopene acting as a negative force. I see no reason to assume that the ALCAR in this study is leading to accelerated death. It should be noted that the control group for ALCAR, NADH, ALA, CoQ10 is above the individualized groups for both ALA and CoQ10.  There's also the dosage to take into account for each of these supplements. In humans a dose of 500 mg or lower of ALCAR I think would be ideal, whereas a higher dosage may bring about more harm than good. Please correct me if I am wrong about any of this.
 

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

Edited by Wry, 29 January 2015 - 08:51 PM.

[nowayout]

(By the way, it's not just Spindler who has reported a deleterious effect of carnitines on lifespan in healthy mice. Weindruch, who is also one of the very few scientific researchers who really runs proper LS studies (ie, where the controls are not obese, or sickly, or genetically fucked-up, or what have you, but have normal, proper survival from the get-go) found that two separate *cocktails* of supplements *including* /acetyl/ -L-carnitine (ALCAR) slightly shortened the lives of otherwise-healthy mice: one cocktail of ALCAR with lipoic acid, lycopene, and alpha-tocopherol, and one cocktail of ALCAR with CoQ10, lipoic acid, and NADH:

(This is the only reporting of these data that I know. These results come from the LEF LifeSpan Project, very little of which have ever seen the light of day ...

Reference
1. J Proteome Res. 2012 Apr 6;11(4):2224-35. doi: 10.1021/pr2010154. Epub 2012 Feb 27.
Metabotyping of long-lived mice using 1H NMR spectroscopy.
Wijeyesekera A, Selman C, Barton RH, Holmes E, Nicholson JK, Withers DJ.

 

 

Those non-CR graphs look indistinguishable to me FAPP. 

 

[nowayout]

Agreed, animals are real food, and likely the best.

 

It should be kept in mind though that the farm animals we eat today are not "real" animals.  

[StevesPetRat]

Hmm, after reading this discussion and the many rebuttals / responses, it seems like TMAO may simply be a proxy for dysbiosis / endotoxemia, then.

[Adaptogen]

Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota

http://www.sciencedi...756464615001735

[tunt01]

Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota

http://www.sciencedi...756464615001735

 

 

Very interesting.  Thank you for this.

[thedarkbobo]

Little off topic I am thinking about my diet - more olive oil, no eggs(damn, I eat a lot of pasta recently as it's easy to prepare for 1 week ahead)->rice, some more vegs, still a lot of meat(but somehow reduce bacteria in gut via allicin or sorbic acid(?)). Find me a cheap source of nuts and I can eat them all day long .

Maybe the point of friday without meat was to reduce the number of TMAO producing bacteria in a gut?

 

2 questions:

- is choline intake bad overall? Like Centrophenoxine powder vs eggs (which is said to increase cholesterol)

- are there some well tested procedures to dispose of not usefull bacteria in a gut? Lets say I want to get rid of TMAO producing bacteria, what then?

 

I wonder if there are some connections to eating meat - TMAO/bacteria and: salt, alcohol and now C60 (as allicin is anti inflamantory so maybe this also helps).

Edited by thedarkbobo, 08 November 2015 - 10:21 AM.

[thedarkbobo]

Ah half of answer is here ...(choline)

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

http://ajcn.nutritio...087692.abstract

"Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake."

[Adaptogen]

Ginger attenuates trimethylamine-N-oxide (TMAO)-exacerbated disturbance in cholesterol metabolism and vascular inflammation

[Adaptogen]

Statin Use is Associated with Lower Trimethylamine-N-oxide (TMAO) Level in Adults at Risk of Atherosclerotic Cardiovascular Disease, Independent of Serum Cholesterol and Renal Function