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

Study Overview
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Brief Summary
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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 Description
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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.

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

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Efamax


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: polyunsaturated<br>5g per day of polyunsaturated fatty acids (3.5g EPA and DHA). | Dietary Supplement: Efamax<br>* 5g daily as capsules for 3 months<br>* Other names: oleic enriched sunflower oil;|
| Placebo Comparator: monounsaturated<br>5g a day of oleic enriched sunflower oil | Dietary Supplement: Efamax<br>* 5g daily as capsules for 3 months<br>* Other names: oleic enriched sunflower oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum liver function tests, lipids, free fatty acids |  | 3 months | 
| Insulin resistance as assessed by HOMA-IR and Adipose Tissue Insulin Resistance Index |  | 3 months | 
| Liver saturated, monounsaturated and polyunsaturated fatty acid indexes as assessed by MR spectroscopy |  | 3 months | 
| Visceral obesity as quantified by MRI, and the adipose derived serum leptin and adiponectin |  | 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 |  | 3 months | 
| Further informative cytokine analyses: GM-CSF, IFN-G, IL-1B, IL-1RA, IL-2, IL-4, IL-5, MCP1 |  | 3 months | 
| Compliance assessed by serum phospholipid fatty acids |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic fatty liver disease, Polyunsaturated fatty acids, Omega-3