The Role of Carnitine and Carnitine Supplementation During Exercise in Man and in Individuals with Special Needs

Abstract

Carnitine is critical for normal skeletal muscle bioenergetics. Carnitine has a dual role as it is required for long-chain fatty acid oxidation, and also shuttles accumulated acyl groups out of the mitochondria. Muscle requires optimization of both of these metabolic processes during peak exercise performance. Theoretically, carnitine availability may become limiting for either fatty acid oxidation or the removal of acyl-CoAs during exercise. Despite the theoretical basis for carnitine supplementation in otherwise healthy persons to improve exercise performance, clinical data have not demonstrated consistent benefits of carnitine administration. Additionally, most of the anticipated metabolic effects of carnitine supplementation have not been observed in healthy persons. The failure to demonstrate clinical efficacy of carnitine may reflect the complex pharmacokinetics and pharmacodynamics of carnitine supplementation, the challenges of clinical trial design for performance endpoints, or the adequacy of endogenous carnitine content to meet even extreme metabolic demands in the healthy state.

In patients with end stage renal disease there is evidence of impaired cellular metabolism, the accumulation of metabolic intermediates and increased carnitine demands to support acylcarnitine production. Years of nutritional changes and dialysis therapy may also lower skeletal muscle carnitine content in these patients. Preliminary data have demonstrated beneficial effects of carnitine supplementation to improve muscle function and exercise capacity in these patients.

Peripheral arterial disease (PAD) is also associated with altered muscle metabolic function and endogenous acylcarnitine accumulation. Therapy with either carnitine or propionylcarnitine has been shown to increase claudication-limited exercise capacity in patients with PAD.

Further clinical research is needed to define the optimal use of carnitine and acylcarnitines as therapeutic modalities to improve exercise performance in disease states, and any potential benefit in healthy individuals.

• carnitine
• exercise
• metabolism
• peripheral arterial disease
• hemodialysis
• propionylcarnitine

Key teaching points:

• Carnitine is required for mitochondrial fatty acid oxidation and to minimize the impact of cellular acyl-CoA accumulation.

• The pharmacokinetics of carnitine are complex due to low oral bioavailability, complex distribution between tissues, intraconversion to acylcarnitines and saturable renal transport systems.

• Theoretically, carnitine supplementation may increase carnitine content, increase fatty acid oxidation and protect from the accumulation of metabolic intermediates.

• Clinical trials do not support the use of carnitine supplementation to improve exercise performance in healthy man.

• End-stage renal disease and peripheral arterial disease are both associated with exercise impairment and metabolic alterations which are improved by carnitine supplementation.

Key teaching points:

• Carnitine is required for mitochondrial fatty acid oxidation and to minimize the impact of cellular acyl-CoA accumulation.

• The pharmacokinetics of carnitine are complex due to low oral bioavailability, complex distribution between tissues, intraconversion to acylcarnitines and saturable renal transport systems.

• Theoretically, carnitine supplementation may increase carnitine content, increase fatty acid oxidation and protect from the accumulation of metabolic intermediates.

• Clinical trials do not support the use of carnitine supplementation to improve exercise performance in healthy man.

• End-stage renal disease and peripheral arterial disease are both associated with exercise impairment and metabolic alterations which are improved by carnitine supplementation.

The authors are consultants to Sigma Tau Pharmaceuticals. The authors thank Kathy E. Sietsema, MD for her helpful comments on the manuscript.

Notes

Presented in part at the 38th Annual Meeting of the American College of Nutrition, New York City, NY, September 1997.