Choline has been around as a dietary supplement for a long time. Its use as a treatment for the accumulation of fat in the liver is well recorded in the nutritional literature from both animal and human studies. In the past the most likely form of damage to the liver was through the use of drugs, which could damage the liver through the build up of toxin which causes free radical damage, oxidative stress and inflammation. Alcohol is particularly problematic in this regard and is associated with the accumulation of fatty acids in the liver leading to the development of alcoholic fatty liver disease (AFLD) which can in turn develop to cirrhosis of the liver. More recently however, the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing and this has rekindled interest in choline as a possible treatment. Non-alcoholic fatty liver disease is thought to be caused by consumption of a typical Western diet, and is considered part of the cluster of metabolic changes that occur during the development of the metabolic syndrome.
Low intakes of choline are thought to contribute to pathological changes, such as steatosis (triglyceride accumulation in the liver cells), steatohepatitis (steatosis with associated inflammation and fibrosis) and cirrhosis (replacement of metabolically active liver cells with non-active scar tissue). Choline may prevent these pathological changes because it is required for the correct metabolism and export of fatty acids from the liver to the circulation through their incorporation into the very low density lipoprotein (VLDL) particle. Animal models have been used to show the effects of choline deficiency on the accumulation of fatty acids in the liver of mammals. For example, in one study1, genetic knockout mice absent the enzyme phosphatidylethanolamine N-methyltransferase which converts phosphatidylethanolamine to phosphatidylcholine, were used to assess the effects of choline on liver health. Because the mice cannot synthesise choline endogenously they are reliant of dietary choline.
Feeding the mice a high fat diet caused them to develop steatohepatitis, hepatomegaly and they also lost significant body weight. These detrimental changes were accompanied by significant increases in hepatic triglyceride, cholesterol and cholesteryl ester concentrations. However, the high fat diet did not affect control mice that retained the activity of the phosphatidylethanolamine N-methyltransferase enzyme. However, when the knockout mice were fed choline, it was able to normalise the hepatic cholesterol concentrations in the liver and significantly and dramatically improve liver function. This was measured biochemically by an increase in the expression of enzymes involved in the export and transport of cholesterol. Therefore choline is able to reverse the detrimental changes caused by fatty acid accumulation in the liver suggesting it might be an effective treatment for nonalcoholic fatty liver disease. Supplemental choline is available commercially as dietary lecithin from soybean.
RdB
