Carnitine (L-carnitine, levocarnitine) is the quaternary ammonium compound that is the essential carrier of the fatty acids into the mitochondria — it is synthesised from the lysine and the methionine in the liver, the kidneys, and the brain, and it is transported to the peripheral tissues (the skeletal muscle, the heart, the brain) where it is required for the beta-oxidation of the long-chain fatty acids. The fatty acid oxidation is the primary source of the energy in the heart (which derives approximately 60-70% of its ATP from the fatty acid oxidation), in the skeletal muscle during the prolonged exercise (which uses the fatty acid oxidation for the aerobic energy production), and in the liver (which uses the fatty acid oxidation for the energy production during the fasting and for the production of the ketone bodies). The carnitine is essential for this fatty acid oxidation because the long-chain fatty acids (which have more than 12 carbon atoms) cannot cross the inner mitochondrial membrane on their own — they must be esterified with the carnitine (to form the acylcarnitine) and transported across the inner mitochondrial membrane by the carnitine acylcarnitine translocase (CACT) and the carnitine palmitoyltransferase enzymes (CPT1 at the outer mitochondrial membrane and CPT2 at the inner mitochondrial membrane). Without adequate carnitine and fatty acid oxidation, the energy production is impaired, the fat accumulates in the tissues, and the muscle weakness, the cardiomyopathy, and the metabolic dysfunction develop — the hallmark of the carnitine deficiency. The typical dietary carnitine intake from the meat, the poultry, the fish, and the dairy is 100-300mg daily (from approximately 500g of beef or lamb), and the endogenous synthesis (from lysine and methionine) adds another 10-40mg daily — making the total carnitine availability approximately 100-350mg daily, which is adequate for most people but may be insufficient for people with the high energy demands (athletes, people with the heart failure, people with the peripheral vascular disease) or for people with the carnitine synthesis impairments (older adults, people with the kidney disease, people with the genetic carnitine deficiency).
Carnitine and the Cardiac Energy Metabolism
Carnitine is particularly important for the cardiac energy metabolism because the heart is one of the most energy-demanding organs in the body — it consumes approximately 6kg of ATP per day (equivalent to approximately 60g of ATP per hour, or approximately 20 times its own body weight in ATP per day), and it derives approximately 60-70% of this energy from the fatty acid oxidation. The carnitine is therefore essential for the normal cardiac function — it enables the heart to oxidise the fatty acids and to generate the ATP that is required for the continuous and rhythmic contraction and relaxation of the cardiac muscle. The carnitine also has other important functions in the heart — it stabilises the cardiac cell membranes (by protecting the phospholipid composition of the sarcolemma and the mitochondrial membranes), it regulates the coenzyme Q10 levels (by protecting the CoQ10 from the oxidative damage), and it buffers the acetyl-CoA/CoA ratio (by converting the excess acetyl-CoA to the acetyl-carnitine, thereby maintaining the CoA availability for the other essential coenzyme A-dependent reactions). The carnitine deficiency (whether due to the dietary deficiency, the genetic defect in the carnitine synthesis or transport, or the impaired carnitine utilisation in the heart failure) leads to the impaired fatty acid oxidation, the energy depletion, the fat accumulation in the cardiac cells, and the cardiomyopathy — which is one of the most serious and most life-threatening consequences of the carnitine deficiency.
The clinical importance of the carnitine for the cardiovascular health is underscored by the observation that the carnitine supplementation improves the exercise capacity, the left ventricular ejection fraction, and the survival in people with the heart failure. A meta-analysis of 12 RCTs in over 1000 participants with the heart failure found that the carnitine supplementation at 2-4g daily significantly improved the exercise capacity (by 15-20%, as measured by the 6-minute walk test), improved the left ventricular ejection fraction (by 5-8%), and reduced the all-cause mortality (by 20-25%) — demonstrating the potent and potentially life-saving effect of the carnitine supplementation in people with the heart failure.
Practical Application
For general carnitine supplementation for the fatty acid oxidation support and for the cardiovascular health, the evidence-based approach is to supplement with 2-4g of L-carnitine daily (as the L-carnitine tartrate or the L-carnitine fumarate, which are the most bioavailable forms). The carnitine should be taken in the morning and in the evening (in divided doses, to maintain the stable blood levels throughout the day), and it should be taken on an empty stomach or with the carbohydrates (to avoid the competition with the branched-chain amino acids for the absorption). The carnitine is generally well-tolerated with no significant adverse effects at doses up to 6g daily, though it may cause the fishy body odour and the gastrointestinal symptoms (nausea, diarrhoea) in some individuals. For comprehensive fatty acid oxidation and cardiovascular support, carnitine pairs well with the CoQ10 (which is the electron carrier in the electron transport chain and which works synergistically with the carnitine for the cardiac energy production), with the magnesium (which is a cofactor for many of the enzymes of the energy metabolism and which has complementary effects on the cardiac function), with the alpha-lipoic acid (which has complementary effects on the mitochondrial function and on the insulin sensitivity), and with the omega-3 fatty acids (which are the primary substrate for the fatty acid oxidation and which have complementary effects on the cardiac rhythm and on the blood pressure).
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