Should L-Carnitine Be Used to Treat Chest Pain?
Should L-Carnitine Be Used to Treat Chest Pain?
Does evidence support use of L-carnitine for angina pectoris? If so, what is the optimal daily dose?
Levocarnitine or L-carnitine is a naturally occurring amino acid essential for the transport of fatty acids into the mitochondria. L-carnitine is one of several endogenous carnitines that make up the "carnitine pool," which also includes acetyl-L-carnitine and propionyl-L-carnitine.
L-carnitine is absorbed from dietary sources including red meat ("carnitine" is derived from the Latin word for meat), dairy products, and, in much smaller amounts, beans and avocado. It is also synthesized endogenously in the liver and kidney from lysine and methionine. Absorption of oral L-carnitine occurs passively and by carrier transport mechanisms. Active transport also occurs in tissues such as cardiac and skeletal muscle that require high fatty acid oxidation.
Bioavailability from dietary sources is about 75%. Supplements are less efficiently absorbed with a bioavailability of 5%-18%.The kidney maintains L-carnitine homeostasis, reabsorbing > 90% of filtered L-carnitine. With decreased dietary intake of L-carnitine, renal tubular reabsorption increases.
L-carnitine is approved by the US Food and Drug Administration (FDA) for secondary carnitine deficiency associated with inborn errors of metabolism. In addition, intravenous L-carnitine is FDA approved for secondary carnitine deficiency in patients with end-stage renal disease on hemodialysis.
L-carnitine has attracted interest for treatment of a range of cardiovascular disorders, for the prevention or treatment of drug-induced myopathies in patients with HIV infection, and for the treatment of valproate toxicity. The list of disparate conditions purported to benefit from L-carnitine treatment also includes anorexia, chronic fatigue, male infertility, and diphtheria, as well as treatment for weight loss and athletic performance improvement.
Cardiac muscle normally contains very high levels of L-carnitine. In the setting of myocardial ischemia, L-carnitine levels are reduced, leading to impairment of the electrical and contractile activities of the heart. Investigations published from 1984 to 2000 examined the effects of supplemental L-carnitine on exercise tolerance in chronic stable angina pectoris. One of the first trials showing a potential efficacy of L-carnitine for this indication was a small trial of 44 men with stable angina randomized to L-carnitine 2 g/day or placebo. After 4 weeks, workload capacity increased in the L-carnitine group compared with the placebo group, objectively assessed by a cycloergometer. Subjectively, 22.7% of patients taking L-carnitine self-reported resolution of anginal episodes, compared with 9.1% in the placebo group.
In a larger study of 200 patients that was randomized but not blinded, half of the patients received L-carnitine 2 g/day and half received placebo for 6 months in addition to angina medications previous to the study. In the patients receiving L-carnitine, ergometric exercise performance improved and consumption of cardioactive medications decreased.
More recently, Iyer and colleagues studied the safety and efficacy of 2 g/day L-carnitine combined with standard treatment in 47 patients with chronic, stable angina. After 3 months, an increase occurred in exercise duration (P = .006) and time to recovery of ST changes (P = .019) in patients in the L-carnitine group compared with the placebo group. No additional studies have been published within the last decade, and, to date, no studies of L-carnitine for angina have been performed in North America.
L-carnitine 2 g/day has been used with apparent safety in patients with angina for up to 6 months. Products containing D-carnitine or the racemic mixture should be avoided. The D-isomer is biologically inactive and acts as a competitive inhibitor of L-carnitine and may cause symptoms of L-carnitine deficiency. L-carnitine should be avoided in patients with hypothyroidism. L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting triiodothyronine (T3) and thyroxine (T4) entry into cell nuclei.
Although initial research on L-carnitine for angina was encouraging, interest in its use for this indication seems to have dwindled for unknown reasons. Small study size and poor study design limit the reliability of available research. L-carnitine appears to be safe for most patients in doses less than 2 g/day, but it remains an unproven approach to the treatment of angina.
Question
Does evidence support use of L-carnitine for angina pectoris? If so, what is the optimal daily dose?
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Response from Gayle Nicholas Scott, PharmD Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia |
Levocarnitine or L-carnitine is a naturally occurring amino acid essential for the transport of fatty acids into the mitochondria. L-carnitine is one of several endogenous carnitines that make up the "carnitine pool," which also includes acetyl-L-carnitine and propionyl-L-carnitine.
L-carnitine is absorbed from dietary sources including red meat ("carnitine" is derived from the Latin word for meat), dairy products, and, in much smaller amounts, beans and avocado. It is also synthesized endogenously in the liver and kidney from lysine and methionine. Absorption of oral L-carnitine occurs passively and by carrier transport mechanisms. Active transport also occurs in tissues such as cardiac and skeletal muscle that require high fatty acid oxidation.
Bioavailability from dietary sources is about 75%. Supplements are less efficiently absorbed with a bioavailability of 5%-18%.The kidney maintains L-carnitine homeostasis, reabsorbing > 90% of filtered L-carnitine. With decreased dietary intake of L-carnitine, renal tubular reabsorption increases.
L-carnitine is approved by the US Food and Drug Administration (FDA) for secondary carnitine deficiency associated with inborn errors of metabolism. In addition, intravenous L-carnitine is FDA approved for secondary carnitine deficiency in patients with end-stage renal disease on hemodialysis.
L-carnitine has attracted interest for treatment of a range of cardiovascular disorders, for the prevention or treatment of drug-induced myopathies in patients with HIV infection, and for the treatment of valproate toxicity. The list of disparate conditions purported to benefit from L-carnitine treatment also includes anorexia, chronic fatigue, male infertility, and diphtheria, as well as treatment for weight loss and athletic performance improvement.
Cardiac muscle normally contains very high levels of L-carnitine. In the setting of myocardial ischemia, L-carnitine levels are reduced, leading to impairment of the electrical and contractile activities of the heart. Investigations published from 1984 to 2000 examined the effects of supplemental L-carnitine on exercise tolerance in chronic stable angina pectoris. One of the first trials showing a potential efficacy of L-carnitine for this indication was a small trial of 44 men with stable angina randomized to L-carnitine 2 g/day or placebo. After 4 weeks, workload capacity increased in the L-carnitine group compared with the placebo group, objectively assessed by a cycloergometer. Subjectively, 22.7% of patients taking L-carnitine self-reported resolution of anginal episodes, compared with 9.1% in the placebo group.
In a larger study of 200 patients that was randomized but not blinded, half of the patients received L-carnitine 2 g/day and half received placebo for 6 months in addition to angina medications previous to the study. In the patients receiving L-carnitine, ergometric exercise performance improved and consumption of cardioactive medications decreased.
More recently, Iyer and colleagues studied the safety and efficacy of 2 g/day L-carnitine combined with standard treatment in 47 patients with chronic, stable angina. After 3 months, an increase occurred in exercise duration (P = .006) and time to recovery of ST changes (P = .019) in patients in the L-carnitine group compared with the placebo group. No additional studies have been published within the last decade, and, to date, no studies of L-carnitine for angina have been performed in North America.
L-carnitine 2 g/day has been used with apparent safety in patients with angina for up to 6 months. Products containing D-carnitine or the racemic mixture should be avoided. The D-isomer is biologically inactive and acts as a competitive inhibitor of L-carnitine and may cause symptoms of L-carnitine deficiency. L-carnitine should be avoided in patients with hypothyroidism. L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting triiodothyronine (T3) and thyroxine (T4) entry into cell nuclei.
Although initial research on L-carnitine for angina was encouraging, interest in its use for this indication seems to have dwindled for unknown reasons. Small study size and poor study design limit the reliability of available research. L-carnitine appears to be safe for most patients in doses less than 2 g/day, but it remains an unproven approach to the treatment of angina.
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