Hi Loren,
Here I go again with the question of the week. I love my job!
What do you think about carnitine found in high levels in red meat ( and in other products- other meats, sports drinks, etc) and its potential association with the formation of coronary plaque?
I appreciate your response to my questions. Feel free to answer when you have time. No rush.
Thanks for your time and expertise.
- Pam
Dr. Cordain's Response:
Hi Pam,
Good to hear from you. General practitioners such as yourself are responsible to your patients for giving them proper dietary advice, particularly whether or not they should avoid red meat to protect against heart disease. The most recent commotion about red meat, carnitine and formation of coronary plaque (atherosclerosis) comes from the paper1 listed below from Stanley Hazen’s group at the Cleveland Clinic.
My colleague, Chris Masterjohn, has done a superb job of critiquing this paper and it’s scientific shortcomings in "Does Carnitine From Red Meat Contribute to Heart Disease Through Intestinal Bacterial Metabolism to TMAO?"
I am in complete agreement with Chris’s conclusion that, "The bottom line here is that the popular interpretation of this study as an indictment of red meat makes no sense." I have a few additional comments that corroborate Chris’s conclusion.
Although intriguing, Hazen's model doesn’t fit well with the bigger picture of atherosclerosis etiology, particularly the two large meta analyses by Key's group2, 3 showing cardiovascular disease (CVD) mortality in vegans and vegetarians to be no better than the general population. Vegans/vegetarian data from India actually show high mortality from CVD and an earlier disease progression/mortality.4
Another point worth considering are the well studied polymorphisms disrupting FMO3 activity in trimethylaminuria patients causing inefficient conversion of TMA to TMAO. Hence in these patients tissue concentrations of TMAO are severely reduced. Given this metabolic scenario, one would expect that any of the polymorphisms disrupting the FMO3 gene would be highly protective for CVD (if the Hazen hypothesis is correct). No CVD epidemiologic evidence supports this evidence. In fact, a recent study5 shows that heterozygote genotypes (158Glu/Lys and 308Glu/Gly) increase the risk of stroke six times in hypertensives.
Cordially,
Loren Cordain, Ph.D., Professor Emeritus
References
1. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85
2. Key TJ, Fraser GE, Thorogood M, Appleby PN, Beral V, Reeves G, Burr ML, Chang-Claude J, Frentzel-Beyme R, Kuzma JW, Mann J, McPherson K. Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Am J Clin Nutr. 1999 Sep;70(3 Suppl):516S-524S.
3. Key TJ, Appleby PN, Spencer EA, Travis RC, Roddam AW, Allen NE. Mortality in British vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Am J Clin Nutr. 2009 May;89(5):1613S-1619S
4. Kumar J, Garg G, Sundaramoorthy E, Prasad PV, Karthikeyan G, Ramakrishnan L, Ghosh S, Sengupta S. Vitamin B12 deficiency is associated with coronary artery disease in an Indian population. Clin Chem Lab Med. 2009;47(3):334-8.
5. Türkanoğlu Özçelik A, Can Demirdöğen B, Demirkaya S, Adalı O. Flavin containing monooxygenase 3 genetic polymorphisms Glu158Lys and Glu308Gly and their relation to ischemic stroke. Gene. 2013 Mar 17. pii: S0378-1119(13)00244-8. doi: 10.1016/j.gene.2013.03.010. [Epub ahead of print]
