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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Effect of n-3 Polyunsaturated Fatty Acid Supplementation in Patients With Non-alcoholic Fatty Liver Disease

Brief Summary: The principal purpose of this study is to determine whether increased intakes of n-3 polyunsaturated (omega-3) fatty acids will reduce the amount of fat stored in the liver in patients with non-alcoholic fatty liver disease.

Detailed Summary:

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.


Sponsor: University of Nottingham

Current Primary Outcome: Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy [ Time Frame: 3 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Serum liver function tests, lipids, free fatty acids [ Time Frame: 3 months ]
  • Insulin resistance as assessed by HOMA-IR and Adipose Tissue Insulin Resistance Index [ Time Frame: 3 months ]
  • Liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy [ Time Frame: 3 months ]
  • Visceral obesity as quantified by MRI, and the adipose derived serum leptin and adiponectin [ Time Frame: 3 months ]
  • Primary assessment of the fibrotic and inflammatory status of the liver with serum TGF beta, TNF a, IL-6, IL-8, IL-8, IL-10 [ Time Frame: 3 months ]
  • Further informative cytokine analyses: GM-CSF, IFN-G, IL-1B, IL-1RA, IL-2, IL-4, IL-5, MCP1 [ Time Frame: 3 months ]
  • Compliance assessed by serum phospholipid fatty acids [ Time Frame: 3 months ]


Original Secondary Outcome:

  • Changes in plasma biochemistry, insulin resistance, lipids, inflammatory cytokines [ Time Frame: 3 months ]
  • change in liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy [ Time Frame: 3 months ]
  • changes in blood pressure, abdominal obesity and anthropometry as assessed clinically and by MR spectroscopy [ Time Frame: 3 months ]
  • changes in diet as assessed historically [ Time Frame: 3 months ]


Information By: University of Nottingham

Dates:
Date Received: January 8, 2009
Date Started: January 2009
Date Completion:
Last Updated: July 3, 2012
Last Verified: July 2012