The Effect of n-3 Polyunsaturated Fatty Acid Supplements in Patients With Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is present in 10-24% of the general adult population. The first step of NAFLD involves the accumulation of fat within the liver (steatosis). Steatosis occurs either due to defective generation, metabolism or excretion of fatty acids by the liver. The next step in NAFLD progression is inflammation, which commonly occurs due to pro-inflammatory stimuli. Persistent inflammation results in end-stage liver disease. NAFLD is associated with the metabolic syndrome, which is characterised by central obesity, insulin resistance, raised triglycerides and hypertension. With the current obesity epidemic, there is predicted to be greater numbers of patients with NAFLD in the future.

Polyunsaturated fatty acids (PUFAs) are essential components of our diet, though standard Western intakes are lower than the recommended amounts. Supplementing the long chain n-3 PUFAs (commonly termed omega-3), EPA and DHA, improves many of the metabolic syndrome features. They lower plasma triglycerides, and may improve insulin resistance.

The diet of NAFLD patients tends to be deficient in n-3 PUFAs and have an excessive intake of the harmful n-6 PUFAs. This pattern is mirrored in their liver lipid content as assessed at biopsy.

Currently there is no proven treatment for NAFLD. Animal studies and limited studies in patients have been supportive of a benefit with n-3 polyunsaturated fatty acids. This needs to be further assessed.

Inclusion criteria

• Age greater than 18 years
• Liver biopsy diagnosis of NAFLD

Exclusion criteria

• Excessive alcohol intake - > 21 units per week in men and > 14 in women
• A further liver disease diagnosis
• Poorly controlled diabetes - HbA1c > 8.0%, or use of insulin sensitisers
• Pregnancy
• Cirrhosis
• Contraindications to MR scanning - pacemaker or metallic foreign body etc.
• Changes in the dose or initiation of lipid altering medication within the preceding three months, such as statins, fibrates or systemic steroids
• Use of n-3 PUFA supplements within the prior 4 months, an adequate washout period
• Significant co-morbid inflammatory illnesses as determined by research team