L-Carnitine Retakes Spotlight, Hints at Survival Benefit in Acute MI: Meta-analysis

April 12, 2013

ROCHESTER, MN — A meta-analysis of 13 controlled trials concludes that including L-carnitine among the other therapies given in the acute setting for MI appears to significantly cut all-cause mortality and lead to fewer angina symptoms and ventricular arrhythmias[1].

In some of the studies, L-carnitine therapy was subsequently given for six months to a year, suggesting a possible role not only in acute management but also secondary prevention, according to the authors, led by Dr James J DiNicolantonio (Wegmans Pharmacy, Ithaca, NY)

The apparent survival gains from L-carnitine, which were only modestly significant, seemed to come from infarct-size limitation and cardiomyocyte membrane stabilization, with chronic improvements in cellular energy metabolism, according to their report published online today in the Mayo Clinic Proceedings.

"The trials showed that with reduction in infarct size, there was improvement in myocardial salvage and myocardial viability," DiNicolantonio told heartwire . "That's probably where a lot of the benefit in mortality is driven in the acute setting," he said, and it could "be driving a reduction in arrhythmias as well."

He and his colleagues propose that the analysis "supports the potential use of L-carnitine in acute myocardial infarction and possibly in secondary coronary prevention and treatment, including angina."

In a red-letter week for L-carnitine, an amine derived in vivo primarily from two amino acids and frequently included in dietary supplements and commercial energy drinks, two journals have separately released a pair of studies with what may seem contradictory conclusions.

On April 7, Nature Medicine published a prospective series of experiments in mice and human subjects that together suggest, according to the authors, that high levels of dietary carnitine, especially in red meat but also in supplements, may indirectly accelerate atherosclerosis. The proposed idea was that gut microbes convert L-carnitine to trimethylamine-N-oxide (TMAO), which in turn promotes cholesterol transport to vessel walls.

"But if carnitine is the problem, certainly high carnitine would be worse than low carnitine," proposed DiNicolantonio. The previous study pointed at TMAO as a driver of atherosclerosis progression, "but only if certain bacteria form TMAO. And it was formed in meat eaters, so maybe it's the meat and not the L-carnitine within the meat that that's promoting TMAO. It's really hard to tease out." Not all of the findings in the Nature Medicine study were consistent with their conclusions, he said.

"L-carnitine may potentially promote plaque; we need those studies for sure. But we're pretty certain that in the acute setting going out to up to a year, L-carnitine had no signal of harm in any of the trials. And when we combined them all, there was a significant reduction in all-cause mortality."

Relative Risk (95% CI) for Outcomes After Treatment of Acute MI With L-Carnitine, Meta-analysis

End point Number of trials (n) RR (95% CI) p
All-cause mortality 11 (3579) 0.78 (0.60–1.00) 0.05
Ventricular arrhythmia 5 (229) 0.35 (0.21–0.58) <0.0001
MI 4 (829) 0.78 (0.41–1.48) NS
Incident HF 6 (3214) 0.85 (0.67–1.09) NS
Angina 2 (261) 0.60 (0.50–0.72) <0.00001

The group's analysis showed L-carnitine with an all-cause mortality odds ratio of 0.73 (95% CI 0.54–0.99, p=0.05) compared with placebo or other controls in >3500 patients across 11 trials. Computed as a relative risk, the ratio was 0.78 (95% CI 0.60–1.00, p=0.05). Outcomes for the other end points were based on fewer trials and patients.

The group speculates that the short- and longer-term CV benefits relate primarily to the ability of L-carnitine to promote elimination of toxic fatty-acid metabolites and facilitate the transport of long-chain fatty acids into the mitochondria, improving glucose oxidation.

They acknowledge that most of the trials had small patient numbers "and did not have a robust number of hard end points" and that the largest trial contributed 62% of the mortality events.

The authors "advocate for a larger trial to be performed in the acute-MI setting to confirm these results in the modern era of routine revascularization and other intensive medical therapies."

But even lacking such a trial, they write, "considering its low cost and excellent safety profile, L-carnitine therapy could be currently considered in selected patients with high-risk or persistent angina after AMI who cannot tolerate ACE inhibitors or beta-blocker therapy."

DiNicolantonio said he has no relevant disclosures; no disclosures for other authors are in the report.


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