Effect of Dietary Carnitine Isomers and γ-Butyrobetaine on L-Carnitine Biosynthesis and Metabolism in the Rat

Abstract

Oral supplementation with L-carnitine or DL-carnitine for treatment of primary and secondary carnitine deficiency syndromes is becoming increasingly popular, yet little is known about the systemic manifestations of oral intake of large doses of those compounds, particularly the D-isomer of carnitine. To determine the possible beneficial and/or toxic effects or oral carnitine isomers and the carnitine precursor, γ-butyrobetaine, in the rat, groups of male, weanling rats were fed a carnitine-free diet (control) supplemented with various amounts of L-carnitine, D-carnitine, DL-carnitine or γ-butyrobetaine for 32 days. Rats fed diets supplemented with L-carnitine (0.1–1.0%) had increased L-carnitine concentrations in serum and all tissues studied. Mean L-carnitine concentrations in serum and tissues (except liver) from rats fed equivalent amounts of L-carnitine, as the racemic mixture DL-carnitine, were greater than controls but were consistently lower than in rats fed L-carnitine alone. D-Carnitine (1% of diet) significantly reduced serum and heart L-carnitine concentrations from control levels, and the effects of γ-butyrobetaine depended on the level of dietary supplementation. Dietary L-carnitine, D-carnitine and γ-butyrobetaine (1%) reduced carnitine biosynthesis from ε-N-trimethyl-L-lysine in vivo. However, this decrease probably resulted from effects on transport of γ-butyrobetaine into tissues, rather than on the biosynthetic pathway per se. Other than mild diarrhea with high levels of some supplements, no toxic effects of these compounds were observed under the conditions employed and within the time frame of the study. However, the negative effects of high levels of dietary γ-butyrobetaine and D-carnitine on tissue L-carnitine concentrations observed in this study may presage more severe systemic alterations over a longer period of time.