The carnitine in red meat -- and the action of gut bacteria on it -- may be more of a threat to heart health than the saturated fat and cholesterol, a combination human and preclinical study suggests.
In a cohort of 2,595 patients undergoing elective cardiac evaluation, there were significant "dose-dependent associations between carnitine concentration and risks of prevalent coronary artery disease, peripheral artery disease, and overall cardiovascular disease" (P<0.05 for all), according to Stanley Hazen, MD, PhD, chief of cellular and molecular medicine at the Cleveland Clinic, and colleagues.
The significance remained even after researchers adjusted for traditional cardiovascular disease risks (P<0.05), they reported online in Nature Medicine.
Hazen and colleagues noted that individuals with the highest plasma concentration of carnitine also had angiographic evidence of coronary disease, "regardless of the extent (for example, single- versus multivessel) of coronary artery disease, as revealed by diagnostic cardiac catheterization."
However, it is not necessarily the carnitine that is harmful but rather the enzyme TMAO, which is produced by gut bacteria from carnitine, they noted: In the multivariate adjusted analysis, the association of carnitine with cardiovascular risk was only evident among individuals with high plasma TMAO concentrations (P<0.001).
"Thus, although plasma concentrations of carnitine seem to be associated with both prevalent and incident cardiovascular risks, these results suggest that TMAO, rather than carnitine, is the primary driver of the association of carnitine with cardiovascular risks," researchers stated.
It appeared that the volume of red meat consumed was linked with the gut's ability to break down carnitine and produce TMAO.
A volunteer who consumed red meat (beef, venison, lamb, mutton, duck, or pork) on a daily basis was challenged with carnitine ingestion and exhibited increased plasma and urine levels of TMAO compared with baseline levels.
In contrast, a vegan who had not consumed any meat for 5 years revealed no change in TMAO levels from baseline following carnitine ingestion and had "virtually no capacity to generate TMAO in plasma after the carnitine challenge," Hazen and colleagues found.
Expanding the research to more vegans and vegetarians, the investigators noted that this group had significantly lower levels of fasting baseline TMAO than those who ate meat.
This is the first time that such a nutritional pathway involving the ingestion of carnitine and its metabolism by intestinal microbiota into the "proatherosclerotic metabolite TMAO" has been revealed, researchers wrote.
Carnitine is not an essential nutrient, as the body naturally produces all a person needs. Also, there are positive aspects of carnitine. It also has a role in energy production because it helps move fatty acids into cells for storage to be used as energy later.
Carnitine is also found in small amounts of nuts and beans, is available as a dietary supplement, and is a common ingredient in energy drinks, which may or may not be a good thing.
"We need to examine the safety of chronically consuming carnitine supplements as we've shown that, under some conditions, it can foster the growth of bacteria that produce TMAO and potentially clog arteries," Hazen said in a statement.
In the preclinical portion of the study, researchers found that previously germ-free mice fed oral carnitine for several weeks developed the requisite gut microbiota and the ability to generate TMAO.
In addition, they found that mice that were not germ free and who were given an antibiotic to suppress intestinal bacteria could not generate TMAO.
These findings "confirm in mice an obligatory role for gut microbiota" in the production of TMAO from dietary carnitine, Hazen and colleagues concluded.
Mice studies also showed that a diet supplemented with carnitine produced 10 times the amount of TMAO as a carnitine-free diet.
In addition, the carnitine-enhanced diet revealed an increased burden of aortic plaque compared with those not given carnitine.
"Of note, the increase in atherosclerotic plaque burden with dietary carnitine occurred in the absence of proatherogenic changes in plasma lipid, lipoprotein, glucose, or insulin levels," Hazen and colleagues pointed out.