Early biochemical observations point to nutritional strategies to manage non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease globally. The first stage of NAFLD is steatosis, the accumulation of triacylglycerols within hepatocytes. Inflammation and oxidative stress both contribute to progression to more severe disease. In 2004 Clinical Science published two papers reporting on fatty acids and oxidative stress markers in the livers of patients with NAFLD; both these papers are highly cited. One paper reported an altered pattern of fatty acids within the livers of patients with NAFLD; there was a lower contribution of polyunsaturated fatty acids (PUFAs) including both n - 6 and n - 3 PUFAs and an altered balance between n - 6 and n - 3 PUFAs in favour of the former. Ratios of precursor PUFAs to their long chain more unsaturated derivatives were altered in NAFLD and were interpreted to indicate a reduced activity of the pathway of synthesis of long chain highly unsaturated PUFAs. The authors interpreted their findings to indicate that a low hepatic content of n - 3 PUFAs has a causal role in NAFLD. The second paper reported lower hepatic antioxidant defences and increased markers of oxidative stress in NAFLD, consistent with a role for oxidative stress in the disease. Many studies have now explored the effect of supplemental n - 3 PUFAs or antioxidants, including vitamin E, in patients with NAFLD with some benefits being reported. There remains much interest in n - 3 PUFAs and antioxidants as preventive and therapeutic strategies in NAFLD and therefore it seems likely that citation of the two papers from 2004 will be sustained.