Many people are aware of the damage that long-term ethanol (alcohol) consumption can have on the liver. The reason that ethanol can damage liver tissue is because the metabolism of ethanol can cause the deposition of lipids, mainly triglycerides, in the hepatic tissue which leads to a disease caused alcoholic fatty liver. A high fat diet consumed concomitantly with high intakes of alcohol accentuates the deposition of fat in the liver, but the main cause of alcoholic fatty liver is the endogenous biosynthesis of lipids from ethanol. In addition, the ability of the liver to oxidise fatty acids becomes impaired and this further compromises liver function. If left untreated, alcoholic fatty liver develops into hepatic steatosis, and can then deteriorate to cirrhosis of the liver and eventual death. Use of dietary supplements and diet to treat alcoholic fatty liver is controversial because without withdrawal of the underlying cause, the heavy drinking, nutritional approaches are severely compromised. That being said, carnitine has shown some promise as a treatment.
Carnitine (3-hydroxy-4-trimethylaminobutyrate) is a compound synthesised in the body and required for the intramitochondrial translocation of fatty acids for oxidation. In this role, it has been hypothesised that carnitine may be of benefit in alcoholic fatty liver disease, because it might increase the oxidation of fatty acids. Some evidence suggest that carnitine deficiency can occur during times of increased requirement and this has lead some researchers to assess its hepatic lipid lowering effects. Much of the work performed on carnitine has used animal models, but generally supplements do appear effective at ameliorating the effects of ethanol induced hepatic lipid accumulation in mammals. For example, in one study1, rats were fed a diet comprising of 36 % ethanol which resulted in severe accumulation of lipids including triglycerides, cholesterol, phospholipids and free fatty acids in the hepatic tissue. However, supplementation of carnitine, and its precursor amino acids methionine and lysine, significantly lowered the lipid content of the liver.
Therefore carnitine may be a useful supplement to treat the symptoms of alcoholic fatty liver. Interestingly, the use of the precursor amino acids methionine and lysine (used by the body to synthesise carnitine) did not cause an improvement in the lipid content of the liver over carnitine alone. These results suggest that the accumulation of hepatic lipids might be due to a deficiency of carnitine, but that low precursors levels were not the cause of this. A deficiency of carnitine is plausible because it explains the reduced oxidation of fatty acids that occurs with alcoholic fatty liver, and could be induced by the endogenous synthesis rates falling behind those necessary to remove lipids from the hepatic tissue for oxidation in the mitochondria. Therefore under conditions of excessive lipid accumulation, carnitine may become conditionally essential and a dietary source may be required to prevent the development of alcoholic fatty liver. But is carnitine effective at treating a similar condition called non-alcoholic fatty liver induced by poor quality diet?
Although liver disease is widely known to be caused by alcohol, few are aware that a very similar disease called non-alcoholic fatty liver can be induced by poor diet. Non-alcoholic fatty liver is caused by fructose over consumption, and results in an almost identical pathogenesis to alcoholic fatty liver. This relates to the very similar ways that fructose and ethanol are metabolised (here). Over consumption of either ethanol or fructose will cause a build up of lipids in the liver, and can cause metabolic dysfunction. Diet induced obesity in rats is known to induce a carnitine deficiency, presumably because endogenous synthesis cannot keep pace with the requirement to oxidise fatty acids2. In addition, carnitine levels in rats are associated inversely with the degree of insulin resistance, and mitochondrial dysfunction in β-oxidation is reversed in rats with 8 weeks of carnitine supplementation. These results suggest that carnitine may be an effective treatment for non-alcoholic fatty liver and this may explain some of the reported weight loss effects of carnitine.
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