Carnitine plays an essential role in cellular energy metabolism. It primarily serves as a transport molecule, ushering long-chain fatty acids across the mitochondrial membrane and into the mitochondria for energy production via β-oxidation. Known as the carnitine shuttle, the first step involves binding the fatty acid carboxyl group to the thiol group of coenzyme A (CoA) to yield a fatty acyl-CoA. Next, the “activated” fatty acids attach to the hydroxyl group of carnitine to form a fatty acyl-carnitine, which is then transported into the mitochondrial matrix by a carrier protein. Once inside the matrix, the carnitine palmitoyltransferase system exchanges the carnitine for CoA to produce fatty acyl-CoA which can be oxidized for energy. The carnitine is transported back out to the cytoplasmic pool of carnitine so the transfer can occur again.
Carnitine also transports small-chain and medium-chain fatty acids out of the mitochondria in order to maintain normal coenzyme A levels within the mitochondria. Disorders of fatty acid metabolism can result in an accumulation of acyl-Co A, which is associated with apoptosis and inflammation in vital organs such as the heart. However, carnitine conjugation helps to decrease the number of acyl residues available to attach to coenzyme A, thereby decreasing the risks of acyl-coA accumulation. Finally, carnitine does function to bind and remove organic acids.
Carnitine is most often delivered in its acetylated form, acetyl L-carnitine. A majority of the body’s carnitine is found in the heart and skeletal muscle. Nearly 75 percent of the body’s carnitine is supplied through the diet, being found primarily in animal products; especially meat. A small percentage of carnitine can be endogenously synthesized from the amino acids lysine and methionine.
Fatty acid oxidation is most important during exercise, starvation, or when consuming a low-carb diet such as the ketogenic or Paleolithic diets. In fact, β-oxidation is the chief means of energy production for those on a ketogenic diet, making carnitine an important compound for adequate energy production. For those embarking on a ketogenic diet, carnitine may be a helpful adjunct to ensure efficient energy production; however, it may not be a necessary supplement for all, according to one study that sought to understand the impact of a ketogenic diet on carnitine levels. Total carnitine was determined at 0, 1, 6, 12, and 24 months of a ketogenic diet treatment. Even though mild carnitine depletion was noted early in the diet, they were only occasionally on the lower end of normal (or just outside the normal range) throughout the duration of the diet. Therefore, it would seem that most people do not necessarily require extra carnitine when on a ketogenic diet, but it may be helpful to ensure efficient energy production.
Carnitine is, perhaps, most popular among athletes and often taken to reduce muscle fatigue and prolong activity; however, it is also important for promoting exercise among those who are experiencing exercise intolerance due to aging or chronic health problems. Since carnitine targets the two main organ systems that are involved in exercise – the heart and skeletal muscle – it is reasonable to assume it is beneficial in aiding in the supply of adequate energy to these organ systems.
In a small human-based pilot study, the acetyl L-carnitine (or acetylcarnitine) level in the muscle of trained and untrained subjects was measured both before and after 30 minutes of activity on a cycle ergometer at 50% maximal workload. Results showed a dramatic difference in acetylcarnitine metabolism between the groups. Both groups showed an increase in tissue acetylcarnitine content during exercise, but the trained group had a lower peak accumulation immediately after exercise compared to the untrained group, suggesting increased consumption in the trained group. Further, the acetylcarnitine levels continued to rise in the untrained group during recovery, but not in the trained group, indicating this compound is most needed in untrained individuals to prolong exercise fatigue. Low carnitine levels may also be associated with obesity, diabetes, and aging. However, it is also important for these groups to exercise regularly, making carnitine a likely candidate for improving their ability to maintain adequate energy during exercise.
Finally, it is important to mention that there are various inborn errors of metabolism, leading to a primary carnitine deficiency and serious energy depletion. A secondary carnitine deficiency can also arise from organic acidemias and defects of fatty acid oxidation or in the carnitine cycle. Renal failure or dysfunction can inhibit carnitine reabsorption, leading to a carnitine deficiency. A lack of energy from insufficient β-oxidation will be noticeable.
As a key constituent in delivering fatty acids to the mitochondria where they can be oxidized into ATP, carnitine is a crucial compound for energy metabolism, cellular health, and ensuring a sense of vitality and well-being.