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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Efamax

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Wolfson Digestive Diseases Centre, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age greater than 18 years
2. Liver biopsy diagnosis of NAFLD

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Nottingham
• Investigators: Study Chair: Ian A Macdonald, PhD, Biomedical Sciences, University Hospital, Nottingham

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 8, 2009
• First Submitted That Met QC Criteria: January 8, 2009
• First Posted (Estimate): January 9, 2009

Study Record Updates

• Last Update Posted (Estimate): July 4, 2012
• Last Update Submitted That Met QC Criteria: July 3, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; Omega-3; Polyunsaturated fatty acids
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NottinghamNHST1; REC 08/H0403/14; R&D 08GA001