Should we drop Carnitine?

http://www.bbc.co.uk/news/health-22042995

Maybe just dissolving carnitine in a topical would be a safer way.

Its not about carnitine itself ,its about pathogenic gut bacteria(which use carnitine as a fuel).
Get some TMAO blood tests.
Injecting also surpass this issue.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3145.html

here is the study

I forgot to ask if ALC is different than regular Carnitine in this matter?

This is also on the front page of Foxnews.com right now...

http://www.foxnews.com/health/2013/04/08/new-health-worry-in-red-meat/?test=latestnews

So once again, like rdk has been saying for years, it all goes back to the pathogenic organisms.

To me these sound like commensals, and the problem is disproportionate levels of them. I think the meta-genome is something we've only begun to scratch the surface of and in the next decade or so we'll probably begin to trace almost every aspect of health (in some way) back to the interactions between host and bacterial genomes. This is just one example. For me though, I always take these alarmist reports with a grain of salt. Again, we can probably assume this is the result of an imbalance, one that would not be problematic in a healthy gut environment.

Secondly, I think its ignoring the complexity of the gut microbiome. In balance, a series of other species might produce compounds that neutralize this one. Perhaps other strains are capable of metabolizing it themselves. I'm just spitballing, obviously the research isn't there yet. But I don't think its justification to stop eating red meat or force yourself to reduce it to once a week or anything.

Many bacteria contain enzymes for conversion of alcohol into acetaldehyde, which is a carcinogen. Or Pyruvate into alcohol. But other species degrade these or transform them with their own enzymes. The point is its much more complex with gut bacteria than "produce chemical A, get this effect on a macro scale", the dynamics of their metabolisms are something science is still exploring.

http://circres.ahajournals.org/content/109/2/127.full

Another study linking TMAO to bacterial metabolism of phosphatidylcholine, something present in every cell in our body in large amounts. Something protective must be occurring to offset this or we'd all be developing atherosclerotic plaque at age 3. It is interesting to consider what changes in the body might lead to this as we age though.

http://jn.nutrition.org/content/119/5/800.full.pdf

"These observations support the hypothesis that it is only when intestinal transport systems for the absorption of choline are overloaded that appreciable amounts of this nutrient reach the large bowel and are metabolized to form TMA by intestinal bacteria. DMA formation did not increase in pro portion to TMA excretion, suggesting that there is no simple product-precursor relationship between these two amines."

It appears that gut bacteria produce the FMO3 enzyme in order to metabolize nitrogen-containing compounds (including choline and amino acids). Choline and carnitine are both converted by this enzyme into TMAO so they can be excreted in the urine. When this does not occur, TMA builds up and is released in sweat. TMAO is the natural excretory form of methylamines. I suppose the problem is that its getting out of control.

But is TMAO a cause of increased atherosclerotic plaque/heart attack or just associated with it? TMAO is common in many forms of life as a cellular solute that opposes uric acid. The interplay between TMAO and uric acid is crucial for protein folding and unfolding. When uric acid rises, which is correlated with insulin resistance and heart disease, TMAO also rises. A rise in lactic acid, increasing kidney burden of acids, indirectly increases uric acid and TMAO. The kidneys are how the body reduces excess acidic compounds. Also, a lack of alkaline minerals like potassium/magnesium/calcium increase acidosis, so maybe supplementing these would be beneficial.

It seems then like only a high intake of carnitine COMBINED with a hampered ability to absorb it (percentage of utility varies amongst people) and also dysbiosis favoring strains that metabolize carnitine must all be present for this to be a problem. If these aren't present then I'd expect kidney function to handle TMAO burden properly. But I imagine there are a few things we can do to mitigate all of this:

- Daily intake of a good sea salt or multimineral supplement featuring potassium/magnesium.
- Keep kidneys in good shape, stay hydrated (perhaps alkaline water)
- Keep gut healthy (daily garlic or something to moderate flora)
- Keep red meat/organ meat intake to a reasonable amount (not every day)
- Supplement with a powerful flavanoid like quercetin (shown to reduce uric acid levels)

And perhaps supplementation of l-carnitine is something we should be questioning the safety of. Are the sugar metabolism/mitochondrial benefits outweighed by the negatives? I suppose without having a full profile of your own gut bacteria, it is risky to supplement in high doses of a specific bacterial metabolite. Although the body does manufacture it on its own from lysine and methionine (?).

I supplement 2gr ALC with 200gr R-ALA every day...Should i stop using Acetyl l carnitine?

Steve_Gr wrote:I supplement 2gr ALC with 200gr R-ALA every day...Should i stop using Acetyl l carnitine?

I supplement with actey l carnitine too, wondering the same thing now.

Urg, I supplement with 800 mg L-carnitine tartrate daily. Should I get a TMAO blood test or something?

Would normal cholesterol levels indicate things are ok?

TMAO? LMAO


http://eathropology.com/2013/04/10/tmao-lmao/


TMAO? LMAO.
Apr10 by Adele Hite, MPH RD

Move over saturated fat and cholesterol. There’s a new kid on the heart disease block: TMAO.

TMAO is not, as I first suspected, a new internet acronym that I was going to have to get my kids to decipher for me, while they snickered under their collective breaths. Rather, TMAO stands for Trimethylamine N-oxide, and it is set to become the reigning king of the “why meat is bad for you” argument. Former contenders, cholesterol and saturated fat, have apparently lost their mojo. After years of dominating the heart disease-diet debate, it turns out they were mere poseurs, only pretending to cause heart disease, the whole time distracting us from the true evils of TMAO.

The news is, the cholesterol and saturated fat in red meat can no longer be held responsible for clogging up your arteries. TMAO, which is produced by gut bacteria that digest the carnitine found in meat, is going to gum them up instead. This may be difficult to believe, especially in light of the fact that, while red meat intake has declined precipitously in the past 40 years, prevalence of heart disease has continued to climb. However, this is easily accounted for by the increase in consumption of Red Bull—which also contains carnitine—even though it is not, as some may suspect, made from real bulls (thank you, BW).

So should we stop supplementing with it? CS? Anyone else?

While I preface this with a disclaimer of I don't know for sure....

But I think it's BS.

Acetly L carnitine is very helpful. So IS CHOLESTEROL if you are low in Lysine, Proline and Mg Ascorbate...

read Linus Pauling and you may well see why that reaction they are complaining about is good for you.

Definitely looking to hear from CS/anthonyspencer on this?

I really don't think you are going to have a problem taking carnitine unless you have a severe dysbiosis of the gut. A sample of 6 people in the human study tells us almost nothing (5 meat eaters vs. one vegan is not representative of anything). The body has adequate systems for dealing with TMAO. Here are situations where I would perhaps lay off on lots of carnitine supplementation for the time being:

- any type of kidney malfunction or dysfunction
- fatty liver/cirrhosis (or medically elevated liver enzymes)

Its important to note there isn't a causal line drawn between TMAO and heart disease. I know CS has been taking carnitine for quite some time now, and I doubt he's a guy we'll see topple over from CVD any time soon.

http://chriskresser.com/red-meat-and-tmao-its-the-gut-not-the-meat

Thanks for that insightful reply. Ok so to clarify, there has been no direct causal relationship between TMAO and heart disease. So if TMAO levels would rise to harmful levels, if the body is healthy, would be broken down and eliminated?

[WARNING: Rant)
Yes, the big key here is that no direct causitive mechanism has been shown connecting TMAO to heart disease. Its correlative. TMAO tends to be above normal levels in people with advanced athersclerosis. But there could be something else causing this and TMAO rises secondarily.

TMAO testing is not a routine test to my knowledge so even trying to track one's levels isn't realistic.

TMA is produced through metabolism of choline and carnitine by bacteria in the gut. TMA must then be processed by the liver or kidney, which both contain various isoforms of the FMO enzyme group. FMO3 oxygenates TMA into TMAO, making it soluble for excretion in the urine.

So let's look at the players. FMO enzymes are really important for detoxing xenobiotics so we don't want to lower them. Carnitine is incredibly important for fatty acid metabolism in the mitochondria. TMA isn't so bad in low levels, but can become toxic and very excitatory. So what's left to put the blame on? TMAO right...and by association choline and carnitine .

Now here is my theory on the whole thing. No proof whatsoever, but its my thought. TMAO in an important ozmolyte in marine species. In counteracts the effects of high uric acid and moderates the kinetics of enzymes by altering the Urea:TMAO ratio. There have been studies to show that TMAO has this property in land mammals regardless of whether the protein or the solute evolved in tandem.
http://www.cell.com/biophysj/abstract/S0006-3495(98)77972-X

I believe one aspect of the co-evolution of land mammals and their gut microbiome was a means of producing TMAO through consumption of fatty fish, eggs, other meats and certain vegetables. Marine life also hydrolizes phosphatidylcholine to produce TMAO, whether or not this is bacterially driven I don't know.
http://www.ncbi.nlm.nih.gov/pubmed/11854367

TMAO is a solute that has a protein-stabilizing effect in the presence of uric acid. Our bodies are engines for the buldup and breakdown of protein, its what we do. Now, its well understood how uric acid is a metabolite of the breakdown of protein. Perhaps we co-evolved with our gut bacteria to produce TMAO from choline/protein consumption as a means of stabilizing concentrations of uric acid in the cell environment. It makes more logical sense to me that TMAO has some biological role (rather than zero) when it is a metabolite of two very important energy molecules in the human body.

Because of its relationship with choline, we'd expect TMAO levels to be proportional to the body's fat stores. That's one reason why TMAO might rise with heart disease. http://qjmed.oxfordjournals.org/content/93/11/707.full Human beings are one of the only species that does not produce enzymes to oxidize urea, which suggests some evolutionary advantage to higher uric acid levels (and TMAO as an offshoot), but the evidence for a correlation between uric acid levels and heart disease is strong. The evolutionary advantage of meat and fish consumption is obvious, and the interaction between the two osmolytes TMAO and uric acid is probably like evolutionary reconciliation for these eating behaviors.

But here's the rub: uric acid tends to rise as a result of underlying cardiovascular conditions (not cause them). Let's connect uric acid to heart disease and diabetes. Pre-atherosclerotic conditions are largely characterized by high levels of oxidants. These lower the ability of vascular cells to produce nitric oxide, which decreases vascular flexibility. Uric acid is one of the body's main antioxidants and so uric acid rises to offset high levels of oxidation. Oxidative processes also confer insulin resistance, but this resistance tends not to apply to the kidneys, where chronic high insulin causes the body to hold onto sodium (water) AND uric acid. Hypoxic conditions in the veins and heart muscle also raise circulating adenosine levels: increased uric acid.

So to me, the problem of atherosclerosis starts at a damaged cellular sugar metabolism. This confers a deranged fatty acid metabolism, disrupts fatty acid composition of cell membrane, and increases intracellular concentrations of energy molecules and oxidants. This disrupts insulin sensitivity. Solvents in the blood buildup, blood pressure increases. All of this leads to INCREASED URIC ACID.

TMAO is the balancer of uric acid and helps keep enzymes functioning properly when cell pH gets too low. I wouldn't be surprised if it was discovered we produce it endogenously from our own fat stores.

Anyway, I think the incresaed TMAO found along with heart disease is just correlative, its a protection mechanism FOR the protection mechanism (uric acid). We also have to consider that the gut microbiota tends to adapt to the diet, so a diet consistently high in protein would create consistently higher uric acid concentrations, and should also produce the bacterial populations that would produce the most TMAO (Co-Evolution!). This would incraese survivability of both: bacteria get to eat, we balance cell ozmolytes.

TL;DR: heart disease is and always will be the result of damaged cell carbohydrate metabolism. High uric acid and TMAO come secondary. Moral of the story: don't worry about carnitine.

theseeker86 wrote:So should we stop supplementing with it? CS? Anyone else?

It's junk science pure and simple. Cholesterol is a healing substance....however "they" still think it's a bad substance.

Taking L-Carnitine or in the way I prefer, ALC (Acetyl L-Carnitine), when taken with lipoic acid will produce longevity effects, plus enhance other things. I never recommend to take ALC alone, due to the elevation in free-radicals...however, lipoic acid negates this effect and enhances the other benefits.

Also, nice analysis anthonyspencer54.

CS, 100 mg Stabilized R Lipoic Acid + 1000mg ALC two times/day after meals you think is a safe combo?

Question for Anthony and CS:

Anthony: didn't it say in the study that TMAO directly effected the body's ability to release harmful fatty deposits from arteries as well as effect the body's ability to metabolize cholesterol? Your thoughts on this? (Direct vs correlative here)

CS: I have been taking 800 mg l-carnitine tartrate (carnipure) now for a year now. I definitely believe it has helped in my hair maintenance regimen. I also take a number of other supplements like magnesium, ginkgo, and vit c (won't go into all of them). Is it not safe for me to be taking this 800mg carnitine because of raising free radicals? (Haven't noticed any negative health effects so far)

Steve_Gr wrote:CS, 100 mg Stabilized R Lipoic Acid + 1000mg ALC two times/day after meals you think is a safe combo?

Before or during meals is better.

sizzlinghairs wrote:Question for Anthony and CS:

Anthony: didn't it say in the study that TMAO directly effected the body's ability to release harmful fatty deposits from arteries as well as effect the body's ability to metabolize cholesterol? Your thoughts on this? (Direct vs correlative here)

CS: I have been taking 800 mg l-carnitine tartrate (carnipure) now for a year now. I definitely believe it has helped in my hair maintenance regimen. I also take a number of other supplements like magnesium, ginkgo, and vit c (won't go into all of them). Is it not safe for me to be taking this 800mg carnitine because of raising free radicals? (Haven't noticed any negative health effects so far)

This article will help a little on why I add the lipoic acid. Keep in mind that L-Carnitine does act as a free radical scavenger, however it can also boost more ATP, which in itself can produce some free-radicals. ALC is absorbed better and will likely produce more of this effect. This is why lipoic acid will help.

http://www.life-enhancement.com/magazine/article/989-can-acetyl-l-carnitine-and-lipoic-acid-slow-the-aging-process

Here's an article that adds weight to the questionable facts of the so-called study about red meat being harmful. So called dietitians have literally destroyed the health of millions of people with such abysmal advice (such as limiting red meat).

http://suppversity.blogspot.com/2013/04/meaty-news-choline-carnitine-bacteria.html

Nice posts, CS.

http://www.westonaprice.org/blogs/cmasterjohn/2013/04/10/does-carnitine-from-red-meat-contribute-to-heart-disease-through-intestinal-bacterial-metabolism-to-tmao/

Let Chris Masterjohn debunk any study. I love the way this guy handles these types of things. He's a fountain of knowledge.

Anyhow, note the portion on ApoE mice. I think the standing level of oxidative stress is important here. These mice were unable to use glutathione in the normal fashion, and I think it contributed. I'd guess their uric acid levels were high from the get go and it would be interesting to know that.

Also interesting: "The authors provide no evidence that the variation of plasma carnitine in these subjects primarily reflects variations in dietary carnitine intake, and there is no particular reason to assume this. To offer one counter-example, in guinea pigs, one of the few experimental animals that have a dietary vitamin C requirement like humans do, vitamin C deficiency leads to a loss of carnitine from muscle and an increase in plasma carnitine. Vitamin C probably protects against heart disease by preventing lipoprotein oxidation in the blood and by promoting collagen synthesis in arterial plaques, which protects them from rupture. Perhaps plasma carnitine is an inverse marker of vitamin C status."

http://www.metabolomics.ca/News/publications/MetabolomicsInMonitoringKidneyTransplants.pdf

The absence of blood oxygenation creates a condition in which restored circulation results in inflammation and oxidative damage from the oxygen rather
than restoration of normal function. This damage is caused by white blood cells, inflammatory proteins andfree radicals flowing back into the tissue during the reperfusion process....It was also noted that ischemia–repurfusion injury was highly correlated with increased levels of allantoin (50–100 times normal) and TMAO in the blood. Allantoin, which is an oxidative product of uric acid, is a common marker of oxidative cell stress. On the other hand, TMAO is a homeostatic ‘rescue’ compound that allows blood proteins to handle increased concentrations of urea and guanidine (both strong protein denaturants)
that arise during renal failure or renal stress..."

Again there was something adverse already happening cardiovascularly with the subjects, most likely. Uric acid levels and uric acid metabolites were probably already elevated. If all of the different metabolic risk factors had been accounted for, we probably wouldn't have a headline here.

Let's take a look at an example...

Firstly rubbish science always gets a "front seat" in the media. They love scare tactics.
For decades have have promoted a diet of grains and carbohydrates, which never existed 10,000 years ago.

Here's a study published on L-Carnitine at around the same week as the other study: It revealed that testosterone in hemodialysis patients is typically low...as well as L-Carnitine levels.

Testosterone is inversely correlated with heart disease. In the study conclusion, it added that treatment of L-carnitine could help raise testosterone levels. Something like this would never be published on the news. I could produce hundreds of similar studies showing benefit with L-Carnitine with respect to improve cardiovascular disease.

In fact, it's been used in integrative medicine as part of a heart treatment of well over a decade.

Rejuvenation Res. 2013 Mar 14. [Epub ahead of print]
Evidence for a positive association between serum carnitine and free testosterone levels in uremic men with hemodialysis.
Sakai K, Fukami K, Yamagishi SI, Kaida Y, Adachi T, Ando R, Manabe R, Otsuka A, Sugi K, Ueda S, Okuda S.

Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan; fujita_kazuko@med.kurume-u.ac.jp.

Background and Aims: Low free testosterone levels are associated with sexual dysfunction and an increased risk of cardiovascular disease in male hemodialysis patients. Carnitine deficiency is frequently observed in hemodialysis patients as well. However, relationship between carnitine and testosterone levels remains unknown. In this study, we examined whether carnitine deficiency was independently associated with low free testosterone levels in male hemodialysis patients. Methods: Nineteen male hemodialysis patients underwent determinations of blood chemistries, including serum levels of free testosterone, carnitine and pentosidine, one of the well-characterized advanced glycation end products. Results: Mean free testosterone levels in hemodialysis patients were significantly lower than those in healthy controls (4.67 ± 2.69 vs 9.50 ± 3.67 pg/ml, p<0.001). Univariate analysis revealed that carnitine (p=0.023), pentosidine (inversely, p=0.027), blood glucose (inversely, p=0.032), creatinine (p=0.026) levels and statin use (inversely, p=0.034) were correlated with free testosterone values. Multiple stepwise regression analysis revealed that carnitine (p=0.001) and statin use (inversely, p=0.002) were the independent determinants of age-adjusted free testosterone levels in hemodialysis patients (r2=0.612). Conclusions: The present study gives the first evidence that decreased carnitine levels were independently associated with low free testosterone values in male hemodialysis patients. Our study suggests that decreased carnitine levels may be a novel therapeutic target for uremic men with hemodialysis.