Carnitine Shows Promise Against Risk Factor for Cardiovascular Disease

Abstract & Commentary

By Dónal P. O'Mathúna, PhD

Synopsis: Carnitine supplementation produced beneficial changes in endothelial function as measured by flow-mediated dilation (FMD) after a high-fat meal. No significant differences were found for other biomarkers of inflammation and oxidative stress. Carnitine may have a role in reducing risk factors for cardiovascular disease, although this research is still at a very early stage.

Source: Volek JS, et al. Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults. Am J Cardiol 2008;102:1413-1417.

Because carnitine has been shown to decrease oxidative stress and improve endothelial cell functioning, the investigators examined the effects of carnitine supplementation on postprandial flow-mediated dilation (FMD) and circulating biomarkers of inflammation and oxidative stress after a high-fat meal. A randomized, double-blind, placebo-controlled, crossover study design was used. Thirty men and women (age 30 ± 8 years, body mass 72.9 kg ± 17.1 kg, body fat 13.0% ± 6.4%) participated in two vascular testing days, each preceded by three weeks of supplementation with either 2 g/d of L-carnitine (L-carnitine L-tartrate) or placebo with a three- to five-week washout period between trials. Brachial artery FMD in response to 5 minutes of upper arm occlusion and circulating markers of oxidative stress and inflammation were measured in the fasting state and after a standardized high-fat meal. After three weeks of supplementation, peak FMD in the fasting state was similar between the carnitine and placebo trials, averaging 6.6%. Peak FMD during the postprandial period decreased to 5.8% at 1.5 hours during placebo and increased to 7.7% during the carnitine trial (n = 30: P = 0.043 for supplement by time interaction effect). This improvement in postprandial vascular function was most dramatic in subjects who showed a decrease in peak FMD in response to the meal (n = 15: P = 0.003 for supplement by time interaction effect). There was a significant increase in postprandial lipemia and plasma interleukin-6 but no effect of supplementation. There were no significant postprandial changes or supplement effects for plasma tumor necrosis factor-alpha and malondialdehyde. In conclusion, consistent with other work showing a beneficial effect of carnitine on vascular function, these findings indicate that carnitine supplementation in healthy individuals improves postprandial FMD after a high-fat meal.

Commentary

Carnitine is a quaternary amine found primarily in meat and fish. It was once thought to be a vitamin, but is now regarded as a conditionally essential nutrient (CEN).1 A CEN is a compound normally produced in sufficient quantities in the body, but which can be required in the diet under certain conditions. Carnitine is required for transport of long-chain fatty acids into the mitochondria of muscle cells where they are oxidized to release their energy. Carnitine is concentrated in tissues that utilize fatty acids as their primary dietary fuel, which includes skeletal and cardiac muscle.2

The physiological basis for the study reviewed here is that myocardial ischemia leads to loss of carnitine from endothelial cells. Reduced tissue levels of carnitine are associated with increased oxidative stress and compromised blood flow. Earlier studies showed that intravascular carnitine administration can counteract oxidative stress and improve blood flow via several mechanisms that impact endothelial function. Several other studies showed that oral carnitine supplementation has beneficial effects on cardiovascular risk factors and in patients with different forms of cardiovascular disease, including angina, dysrhythmia, chronic heart failure, myocardial infarction, or peripheral vascular disease.1

Flow mediated dilation (FMD) is a method used to quantify endothelial function.3 Impaired endothelial function is involved in the pathophysiology of atherosclerotic cardiovascular disease. FMD represents endothelium-dependent vascular relaxation, and is typically measured at the brachial artery due to ease of access. As such it is a marker for increased risk of cardiovascular disease. Various stimuli can be used to elicit flow-dependent dilation of the arteries, with a single high-fat meal being used in this trial.4

The study used a randomized, double-blind crossover design. However, no details were given about the method of randomization or how well the allocation was concealed. The crossover design allows participants to serve as their own controls, but must ensure an adequate washout period between interventions. This trial used three weeks for men and about five weeks for women. Women were given a longer time to ensure they would be tested in each phase in the same menstrual phase. Using the same washout period for all participants would have been preferable. No discussion of the adequacy of either time period for complete washout was given. Neither was there discussion of the rationale for three weeks of supplementation vs any other period. Such details would have provided important background for the design of the study. Compliance with protocol was stated to be 100% based on signed log sheets. Collection of unused capsules would have provided an additional objective method of assessing compliance.

Great detail was given, however, on the procedures used, including how FMD was measured. Recent calls have been made to standardize these procedures before FMD can be usefully applied in research and clinical practice.3

The results showed a clear difference in vascular reactivity between those taking carnitine compared to placebo. Not only was the difference numerically significant, but the direction of change was opposite. At 1.5 hours after the meal, peak dilation decreased to 5.8% in the placebo group, but increased to 7.7% in the carnitine group (P = 0.043). A subgroup analysis was conducted on those found to have greater postprandial vascular impairment. It was not stated if this analysis was pre-planned or conducted ad hoc. Those with greater impairment were identified as having a decrease in peak dilation 1.5 hours after the meal when taking the placebo (n = 15). Their average peak dilation decreased from 7.2% pre-meal to 3.3% 1.5 hours postprandial. When taking carnitine, the average peak dilation increased from 5.5% to 6.9% (P = 0.003). However, significant differences were not found at 3 and 4.5 hours post- prandial. None of the other outcomes measured showed significant differences between placebo and carnitine supplementation.

The clinical and research implications of this study are difficult to assess, and were not discussed by the authors. Other research has demonstrated that increased FMD is most likely associated with improved nitric oxide metabolism. While this study demonstrates that carnitine supplementation improves endothelial vasodilation after a high-fat meal, further research is needed to demonstrate the clinical relevance of this finding.

References

1. Kendler BS. Supplemental conditionally essential nutrients in cardiovascular disease therapy. J Cardiovasc Nurs 2006;21:9-16.

2. Karlic H, Lohninger A. Supplementation of L-carnitine in athletes: Does it make sense? Nutrition 2004;20: 709-715.

3. Peretz A, et al. Flow mediated dilation of the brachial artery: An investigation of methods requiring further standardization. BMC Cardiovasc Disord 2007;7:11.

4. Kelm M. Flow-mediated dilatation in human circulation: Diagnostic and therapeutic aspects. Am J Physiol Heart Circ Physiol 2002;282:H1-H5.