Carnitine: A Highly Promising Biomarker and Proven Treatment for Cardiac Disease and a Case against It as a Cause of Atherosclerosis

Stephen L. DeFelice, M.D., Founder and Chairman of FIM, The Foundation for Innovation in Medicine, who brought carnitine into the United States, speaks out on the current carnitine controversy.

L-carnitine is a natural substance found in high concentrations in the heart. It transports fatty acids into mitochondria, the furnaces of the cell, to be metabolized and produce energy. Because the heart requires high levels of energy it primarily uses fat which has more calories per unit than sugar.

I’m the physician who brought L-carnitine into the United States in 1965 to conduct the first clinical trial in patients with hyperthyroidism. Later on, I was stationed at WRAIR, the Walter Reed Army Institute of Research, and, for certain reasons, believed that L-carnitine could both prevent and treat myocardial ischemia, a lack of oxygen supply to the heart, even during a heart attack. At the institute I was fortunate to meet an expert cardiovascular pharmacologist, Major James Vick. Together we conducted a number of animal studies supporting my hypothesis. When hearts were made ischemic, arrthymias and cardiac arrest ensued. When given before, during or after the ischemic phase, L-carnitine dramatically prevented and reversed these events. We also found that L-carnitine reversed hearts that were in congestive failure.  Subsequent laboratory studies by other investigators confirmed these findings. In other animal studies, including monkeys, we showed that L-carnitine protects the heart against a number of toxins including the septicemia- producing bacterium, E.coli, and the anti-cancer drug, doxorubicin.

In an animal experiment, scientist Austin Shug of the University of Wisconsin,  as a member of a research team, discovered that L-carnitine leaks out from the ischemic portion of the myocardium. He and I then met with cardiologist James Thomsen of the same university and planned a clinical protocol in patients with coronary artery disease. The study was conducted and demonstrated that L-carnitine protects the human heart against myocardial ischemia (The American Journal of Cardiology in 1979). Then Dr. Shug teamed up with physician, Vera Regitz, at the German Heart Institute. In a series of clinical studies conducted in patients with congestive heart failure, cardiomyopathy and coronary artery disease they discovered that, in these conditions of cardiac stress, cardiac muscle levels of L-carnitine are very low while blood levels are significantly higher than normal. (View the publication here.). This indicates that the high blood levels are due to leakage from the myocardium or heart muscle. Elevated L-carnitine blood levels, therefore, is a highly promising biomarker for of serious cardiac distress and due to and not a cause of atherosclerosis as misinterpreted in the Cleveland clinical study. (This offers an interesting opportunity for an innovative medical device company). From a medical therapeutic point of view, high doses of L-carnitine should have been administered to these patients. In animal studies Vick and I first showed that much higher than normal blood levels of L-carnitine are needed to prevent and reverse ischemia as well as having other beneficial cardiac effects. This observation has been subsequently confirmed by other investigators in multiple animal and clinical studies.

On April 13 of this year- last week- the findings of a multicenter clinical study were published in Mayo Clinic Proceedings reporting that L-carnitine, when administered after a heart attack, significantly reduces death from all causes as well as causing a significant reduction of ventricular arrthymias and angina attacks when compared to placebo or a control group.

You may wonder with the abundance of published laboratory and clinical studies reporting the cardiac benefits of L- carnitine, why does it remain a “secret” to doctors particularly since it is approved for such uses in other countries. Generally speaking, doctors learn about pharmaceuticals after FDA approval which is followed by promotional-educational programs by pharmaceutical companies. In the early 70’s I did make an attempt to launch a clinical program with L-carnitine to obtain FDA approval for coronary artery disease. The Thomsen study was part of that effort. It was my first lesson of medical economics; L-carnitine lacked a patent. In addition, since it is a natural substance, it is difficult to obtain a strong patent. But based on  laboratory studies which I sponsored, I managed to obtain use or methods patents for a number of cardiac conditions. Though such patents are not strong ones, I did manage to obtain initial interest of support until D,L carnitine appeared in the health food stores freely available for purchase by the consumer. Understandably, the support was withdrawn. Later on L-carnitine distribution in these stores shortly followed which was the final nail in the coffin.

Because of the Orphan Drug Act, however, I teamed with the late Dr. Claudio Cavazza, the proprietor of Sigma tau, Inc. and a good man, to obtain two FDA approvals – Primary Carnitine Deficiency, a fatal disease in children and for patients undergoing renal dialysis. So both the intravenous and oral forms of pharmaceutical quality are now available to physicians by prescription to administer to patients for heart conditions.  But there is still that dilemma that no company is permitted to launch an educational program without FDA approval. On the other hand, doctors are permitted to prescribe without such approval. Bottom line, the cardiac promise of L-carnitine is too important to be withheld from the medical community.

(There is confusion regarding whether L-carnitine is a dietary supplement or FDA approved pharmaceutical. It’s both).

Getting back to carnitine as a cause of atherosclerosis, children with Primary Carnitine Deficiency experience life-threatening heart failure which is reversed by L-carnitine which restores its cardiac levels. Many of these children have been on very high doses of L-carnitine for long periods of time without any signs of atherosclerosis. It is FDA approved as a drug and also in many other countries where long-term animal safety studies at high doses are required . These studies show no signs of atherosclerosis. The FDA approved package insert lists no serious side effect of L-carnitine.

Many parents of children who are being treated with L-carnitine are now legitimately concerned about the safety of carnitine. Hopefully, this brief review will lighten their burden. Its efficacy and safety have long been established.