Carnitine is a low-molecular-weight, vitamin like compound generally obtained from the diet although it can be biosynthesized from the essential amino acids lysine and methionine. It is stored in limited amounts in skeletal muscle and breakdown products of its metabolism are excreted in the urine.

Carnitine plays an essential role in lipid metabolism as a carrier of activated fatty acids and activated acetate across the mitochondrial membrane. Primary dietary sources are red meat and dairy products, and it is stored in skeletal muscle. Commercially produced supplements are also available.

In addition to its role in normal metabolism, therapy with carnitine has promise in treating patients with altered carnitine homeostasis. In those select individuals, it appears to improve cardiac function, increase exercise capacity, and reduce muscle cramps.

Early research focusing on supplemental L-carnitine's ability to enhance endurance performance provided conflicting results and no changes occurred in muscle carnitine levels. More recent investigations, however, have suggested a beneficial effect of supplemental L-carnitine in training, competition, and recovery from strenuous exercise.

Early articles indicated a lack of toxic side effects and concluded that as a supplement it could be taken with impunity. It now appears that although carnitine itself is not toxic, a product of its metabolism by bacteria in the colon (the microbiome) is highly likely to be a key factor in the development of atherosclerosis. These conclusions are supported by this meta-analysis demonstrating a positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Trimethylamine N-Oxide (TMAO) is a toxic breakdown product from the carnitine in meat (particularly red meat) and phosphatidylcholine from egg yolk. It is likely that TMAO, rather than cholesterol, is the factor that is responsible for the increased risk of heart and vascular disease in non vegetarians. Because it is removed by the kidney, it is particularly important to limit the intake of red meat and egg yolk in patients with renal failure.

We know that the composition of a person's microbiome is influenced by diet. Provide more of any specific food in the diet and the bacteria that thrive on it multiply in the colon. Interestingly, production of TMAO from creatine supplements is minimal in vegans compared to those on unrestricted diets. Presumably their diets, low in carnitine, have limited the number of specific meat (and carnitine) metabolizing bacteria in their colons.

This means those who are vegans for health rather than philosophic reasons can take creatine supplements without worry, as long as it is taken intermittently. Add regular supplements to their training regimen and I suspect their microbiome would change to include more metabolizing bacteria and in turn produce more toxic TMAO from them. These two blogs provide a nice summary of the details on TMAO production and toxicity. Blog 1 and Blog 2.

Should you consider using carnitine as a performance supplement?

For the recreational rider, the health risks of regular carnitine supplements are likely to outweigh any performance benefits. So I'd say no.

For the competitive athlete looking for even a minimal performance edge, the use of a loading dose pre-event (but not in training not on a regular basis) would minimize exposure to TMAO (and cardiovascular risks). .But the risks are not zero, so each athlete will have to make that decision for themselves.

Picking your proteins - the health implications of TMAO

Excessive carbohydrate calories, especially from the simple sugars glucose and fructose, increase the risk for obesity, high blood pressure, heart disease, and even cancer. This is less of a concern when these simple sugars are being used to replace Calories expended by the training or competing athlete. But for the occasional recreational rider, cutting back on carbohydrates is a healthy choice. However that will mean increasing the fat and protein calories in your diet. But what kind of fat? And what kind of protein?

Cholesterol and saturated fats have been tagged as major risk factors for blood vessel disease (atherosclerosis) for decades. But recent work suggests they are not the most important factor in all those heart attacks. Merely a late stage contributor to damage already well under way.

The results of numerous studies and investigations points to Trimethylamine N-Oxide (TMAO) as the real culprit.

There is proof of cause and effect. In an experimental mouse model, raising blood TMAO levels by dietary manipulation increased blood vessel disease in the absence of any changes in the cholesterol or fat content.

Numerous clinical studies of heart disease (chest pain in the ER, progression of known atherosclerotic heart disease) show a direct correlation between increasing blood levels of TMAO and cardiovascular disease.

Carnitine, a protein found in red meat and to a much lesser degree in chicken and fish, is the source of TMAO. Any dietary carnitine not digested and absorbed in the small bowel passes into the colon where bacteria (our microbiome) metabolize it to an intermediate molecule, TMA. TMA is in then absorbed and modified further in the liver to TMAO.

There is a similar pathway for the production of TMAO from lecithin, a protein found in egg yolks.

Solid evidence supports diet as the major determinant of blood TMAO levels. A recent study documented that a diet low in red meat and eggs lowered TMAO levels independent of the amount of cholesterol or saturated fats in those diets.

TMAO production can be reduced with oral antibiotics (which alter the makeup of the microbiome) or by decreasing the dietary intake of carnitine. Vegans as a group have the lowest blood TMAO levels (and the lowest rate of cardiovascular diseases) while those on a regular red meat diet the highest. just replacing red meat with chicken will lower the amount of TMAO excreted in the urine by two thirds.

What does this suggest for your diet?

  1. Carbohydrates should be limited, and this means daily caloric requirements will be replaced by increasing total protein and fat.
  2. Saturated fats, found in butter, cheese, red meat and other animal-based foods, do play a role in the development of cardiovascular disease, but there risk has been overstated.
  3. Your decision on the source of the third component of the daily diet, protein, has considerable impact on your health. We know that vegetarians have the lowest levels of blood vessel disease, and your goal should be a move toward a meat free diet. But that does not mean you have to become a vegan. You can add one or two meat free dinners a week. Or decrease red meat portion sizes. And now we know that your choice of protein, substituting chicken or fish for red meat, adds a third option.

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