L-Carnitine

What Is L-Carnitine?

L-Carnitine is a conditionally essential amino-acid derivative that serves as the obligate carrier for long-chain fatty acids across the inner mitochondrial membrane. Without carnitine, long-chain fatty acyl-CoAs cannot enter the mitochondrial matrix where beta-oxidation takes place, so fat cannot be oxidised for ATP at the mitochondrial level. The mechanism runs through the carnitine palmitoyltransferase shuttle: CPT1 on the outer membrane exchanges the CoA group on a fatty acid for carnitine, the resulting acylcarnitine crosses via carnitine-acylcarnitine translocase, and CPT2 on the inner membrane restores the CoA so beta-oxidation can proceed. Free carnitine is recycled to repeat the cycle.

The body synthesises about 25% of its carnitine requirement in the liver and kidney from lysine and methionine and obtains the rest from dietary red meat and dairy, so tissue stores run lower in plant-based diets. Research interest in the injectable form comes from one pharmacokinetic problem: oral bioavailability of supplemental carnitine is roughly 14 to 18%, because most of an oral dose is fermented by gut bacteria into trimethylamine before absorption, which is also the origin of the cardiovascular TMAO concern. Parenteral administration bypasses gastrointestinal absorption entirely and raises plasma free carnitine 5- to 10-fold higher than oral administration in the published studies. Levocarnitine is FDA-approved for carnitine deficiency, including the dialysis-associated form. Acetyl-L-carnitine is the brain-penetrant form studied in cognition, and propionyl-L-carnitine the form studied in peripheral vascular disease.