Carnitine Concern?

Posted by on Apr 8, 2013 in Supplement Shelf

The New York Times featured an article Online and in Print on April 7th/8th regarding the possible association between high dietary carnitine intake and risk of cardiovascular disease. More than one patient  has asked about the relevance of this to their regular supplementation with L-carnitine (or its acetyl and propionyl derivatives). The full text  of original study is paywalled but the abstract is available here from Nature 

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.doi:10.1038/nm.3145

 

The following general facts should be reviewed before jumping to conclusions
  • L-Carnitine is synthesized in our bodies and plays important physiological roles especially in beta oxidation of fats and branched chain amino acids in the mirochondria of striped muscle cells i.e. cardiac and skeletal muscle especially.
  • It is available in the diet in animal products, especially red meat, but also milk and dairy.
  • Deficiency of carnitine is unusual, although not unknown in certain pediatric settings.
  • Supplementation of L- carnitine in the cancer setting has  evidential support for counteraction cardiotoxicity induced by the antitumor antibiotics such as Adriamycine, as well as chemo induced neuropathy. IUt can also preovide support in compromised nutritional settings such as cancer related cachexia.
  • Other supplementary uses of  L- Carnitine compounds  – such as for  depression, fatigue, peripheral vascular disease – are typically not well supported by existing data. Intake of large supplementary doses by groups such as body builders or weight loss advocates is totally “experimental”, however no significant toxicities or side effects other than “fishy body odor” have been reported.

 

In addition, the following facts about the study in NAture should be taken into account…

  • The metabolism of Carnitine to the breakdown products TMA and TMAO has been known for sometime. It is what happens to carnitine.
  • The effect of Carnitine breakdown products on atherosclerosis was induced in mice, who were fed a diet excessively high continuos dietary supplement of  Carnitine (1.3% by weight chow)
  • The effect of red meat consumption on blood levels of TMAO in humans is  dependant on whether the subjects were vegan or heavy consumers of red meat, and the state of their gut microbiome.
  • Press release driven reports about dramatic “new study findings” are usually driven more by readership and grant funding concerns than scientific education and knowledge.

At this time, there is nothing at all to suggest that our patients who are supplementing L-Carnitine or derivatives need to make ANY  changes. Our protocols are primarily related to the oncological setting and specify L-Carnitine supplements during neurotoxic chemotherapy, cardiotoxic chemotherapy, and to enhance energy metabolism during recovery from dietary compromise as a result of cancer itself  or conventional treatments. Our patients are usually low consumers of red meats and dairy products, and take wide spectrum probiotics. If you are self supplementing  L-carnitine at high levels for reasons unrelated to these uses, there would still seem to be little reason at this time, especially in vegetarians/vegans, to change. However, the Nature study has raised a preliminary concern in relation to  further links between high red meat consumption and athersclerotic cardiac disease and also  high L- Carnitine suplplementary intake in heavy meat eaters which requires further investigation.