Is L-Carnitine the Link between Red Meat and Heart Disease?

Abstract

A recent article in Nature Medicine (2013) suggests that the nutrient L-carnitine, found in red meat and nutritional supplements, promotes atherosclerosis as a result of enteric bacteria in the gut forming a toxin called trimethylamine (TMA), which is further metabolized to trimethylamine-N-oxide (TMAO) [1]. Two other articles by many of the same authors similarly argue that gut bacteria transform dietary choline and phosphatidylcholine to yield TMA with negative cardiovascular consequences [2,3]. Furthermore, omnivorous human subjects produce more TMAO than do vegans or vegetarians; this difference is possibly related to the higher dietary L-carnitine intake of the non-vegetarians. We argue that the conclusions from these studies relating TMO/TMAO to dietary L-carnitine, whether from food or dietary supplements, are misleading and, in fact, L-carnititne is cardioprotective. L-Carnitine and Human Studies Cardiac metabolism needs L-carnitine for normal functioning. In fact, as much as 95% of the L-carnitine stores are in the heart and skeletal muscles. The adult heart normally derives 50-70% of its ATP from fatty acid β-oxidation, which requires L-carnitine to be able to metabolize fatty acids for fuel [4]. The benefits of L-carnitine are well established. Of the more than 2,000 entries on PubMed under the search terms, "carnitine" and "heart, " none appear to be linked to direct evidence of harm. Just the opposite-studies typically show positive and protective effects for the heart. For example, a randomized, double-blind, placebo-controlled trial, using L-carnitine in patients with suspected acute myocardial infarction, found that total cardiac events in the carnitine-supplemented group (2 grams/day for 28 days) were 15.6% versus 26.0% with placebo (p ≤ 0.05) [5]. Similarly, 2 grams/day of oral L-carnitine improved the three-year survival rate of patients with heart failure caused by dilated cardiomyopathy [6]. In another study, investigators randomly provided 4 g/day of L-carnitine to 81 patients for 12 months, in addition to the usual pharmacological treatment [7]. After 12 months, compared to controls, improvements were observed in heart rate (p<0.005), systolic arterial pressure (p<0.005) and diastolic arterial pressure (NS); there were decreases in angina attacks (p<0.005), in rhythm disorders (NS) and in clinical signs of impaired myocardial contractility (NS). Mortality was significantly different between the two groups in favor of the L-carnitine patients (1.2% vs. 12.5%; p<0.005). A meta-analysis of L-carnitine and cardiovascular disease (CVD) found analogous results [8]. Compared with placebo or control, increased dietary L-carnitine is associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in angina symptoms in patients experiencing acute myocardial infarction. Thus, based on the totality of the clinical evidence, as much as 4 grams L-carnitine per day administered up to 12 months not only improved cardiac function, but also increased life expectancy. It is, therefore, difficult to understand how others have linked dietary L-carnitine to worsening CVD outcomes [1]. TMA/TMAO under Normal Diets Fears of possible negative health consequences from ingested L-carnitine due to its role as a precursor to TMA are not new. Researchers for several decades have been exploring possible relationships between TMA and various pathological conditions, including CVD and cancer. Individuals with normal kidney function have no difficulty in excreting TMA/TMAO [9]. The rapid clearance of these compounds under normal circumstances suggests that dietary intake of L-carnitine-containing food is not sufficient to produce toxic levels of TMA/TMAO. Also, it is likely that the association between CVD and elevated blood concentrations of L-carnitine and related compounds such as choline are indicative of dysfunction(s) elsewhere and not causal.