Researchers have investigated for the first time the role of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the development of liver cancer.

The researchers report that carnitine deficiency is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that long-term L-carnitine supplementation prevents the development of liver cancer.

Carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.

The number of liver cancers diagnosed in the US and throughout the world is increasing at an alarming rate. The number of liver cancers will continue to increase over the next few decades. Most of the increase in liver cancer is attributable to patients who became infected with hepatitis B and C viruses.

Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or reversed.

L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from dietary sources such as red meat and dairy products.

L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production.

Despite the liver being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to find any studies investigating the role of long-term endogenous carnitine depletion and/or carnitine deficiency during induction of hepatic carcinogenesis.

The research team led by Professor Sayed-Ahmed used a liver cancer mouse model under conditions of carnitine depletion and carnitine supplementation.

In the carnitine depleted rat model, there was a progressive increase in the activities of liver enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate, diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes compared to normal values, as well as normal liver histology with unremarkable central vein and no evidence of pre-neoplastic lesions in liver tissues.
References:
1. Al-Rejaie SS, Aleisa AM, Al-Yahya AA, Bakheet SA,Alsheikh A, Fatani AG, Al-Shabanah OA, Sayed-Ahmed MM. Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats World J Gastroenterol 2009; 15(11): 1373-1380.