Inflammatory Bowel Disease

Effects of Omega-3 Fatty Acids on Lipids

Introduction

This report was requested and funded by the Office of Dietary Supplements, National Institutes of Health. It is one of several reports focusing on the role of omega-3 fatty acids in the prevention or treatment of various diseases. Three Evidence-based Practice Centers (EPCs) produced this series of reports: the Southern California EPC, based at RAND, the Tufts-New England Medical Center EPC, and the University of Ottawa EPC. This particular report focuses on the effects of omega-3 fatty acids on immune-mediated diseases, bone metabolism, and gastrointestinal/renal diseases.

Over the past 40 years, an increasing number of physiological functions have been attributed to omega-3 fatty acids, including movement of calcium and other substances into and out of cells, relaxation and contraction of muscles, inhibition and promotion of clotting, regulation of secretion of substances that include digestive enzymes and hormones, control of fertility, cell division, and growth.¹ In addition, omega-3 fatty acids may play an important role in brain development and function. Some evidence has suggested that omega-3 fatty acids in the diet may protect against heart attack and stroke, as well as certain inflammatory diseases like arthritis, lupus, and asthma.¹ The major dietary sources of omega-3 fatty acids in the U.S. population are fish, fish oil, vegetable oils (principally canola and soybean), walnuts, wheat germ, and some dietary supplements.

Methods

Key Questions

We consulted with three technical expert panels (TEPs) on this project. The respective panels focused on the following conditions:

Rheumatoid arthritis, systemic lupus erythematosis (SLE), and bone density/osteoporosis.
Renal disease and diabetes.
Gastrointestinal diseases.

The TEPs advised us on refining the preliminary questions posed to us by AHRQ, determining the proper inclusion/exclusion criteria for the study and the populations of interest, establishing the proper outcomes measures, and conducting the appropriate analyses.

Based on the original questions that we received from AHRQ and input from our TEPs, we addressed the following questions in this study:

Diabetes

What is the evidence in adults or children with a) type II diabetes, or b) insulin resistance/the metabolic syndrome for an effect of omega-3 fatty acids on:
- Total cholesterol.
- HDL cholesterol.
- LDL cholesterol.
- Triglycerides.
What is the evidence in adults and children for an effect of omega-3 fatty acids on insulin sensitivity in a) type II diabetes, or b) the metabolic syndrome?

What is the evidence for the efficacy of omega-3 fatty acids in treatment of Crohn's disease and ulcerative colitis?
What is the evidence in adults or children with inflammatory bowel disease that omega-3 fatty acids can replace steroids or other immunosuppressive drugs?
What is the evidence that the benefits of omega-3 fatty acids are influenced by the concomitant administration of various immunosuppressive agents in the treatment of inflammatory bowel disease?

Rheumatoid Arthritis

What is the evidence in adults or children with rheumatoid arthritis that omega-3 fatty acids affect:
- Pain.
- Number of swollen joints.
- Disease activity.
- Patients' global assessment.
- Joint damage.
What is the evidence in adults or children with rheumatoid arthritis that omega-3 fatty acids can replace other more potent anti-inflammatory or immunosuppressive drugs such as steroids and nonsteroidal anti-inflammatory drugs?
What is the evidence that the benefits of omega-3 fatty acids are influenced by the concomitant administration of various immunosuppressive agents in the treatment of rheumatoid arthritis?

Renal Disease

What is the evidence for the efficacy of omega-3 fatty acids in treatment of renal inflammation and glomerulosclerosis?
What is the evidence in adults or children with immune-mediated renal disease that omega-3 fatty acids can replace steroids or other immunosuppressive drugs?
What is the evidence that the benefits of omega-3 fatty acids are influenced by the concomitant administration of various immunosuppressive agents in the treatment of immune-mediated renal disease?

Systemic Lupus Erythematosus

What is the evidence in adults or children with SLE that omega-3 fatty acids affect disease activity, damage, or patient perceptions of outcomes in SLE?
What is the evidence in adults or children with SLE that omega-3 fatty acids can replace steroids or other immunosuppressive drugs?
What is the evidence that the benefits of omega-3 fatty acids in the treatment of SLE are influenced by the concomitant administration of various immunosuppressive agents?

Bone Density/Osteoporosis

What is the evidence that omega-3 fatty acids help maintain bone mineral status?

For each of the study questions, we also assessed:

The effect of omega-3 fatty acids on subpopulations.
The effects of covariates, dose, source, and exposure duration on the outcomes of interest.
The sustainment of effect.

In addition to answering these questions, we evaluated the data on adverse events, including clinical bleeding, gastrointestinal complaints or nausea, diarrhea, headache, dermatological problems, and withdrawal from study due to an adverse event.

Search Strategy

We searched the following online databases to identify literature:

MEDLINE® (1966-July 2003).
PreMEDLINE® (July 8, 2003).
EMBASE (1980-Week 27, 2003).
Cochrane Central Register of Controlled Trials (2nd Quarter, 2003).
CAB Health® (1973-June 2003).
Dissertation Abstracts (1861-December 2002).

We developed a core search strategy and applied it to each relevant disease category:

Rheumatoid arthritis.
Bone density.
SLE.
Renal disease.
Diabetes.
Gastrointestinal diseases.

We also reviewed the reference lists of all applicable articles and contacted our technical expert panel as well as industry experts to identify unpublished data.

Selection Criteria

Two reviewers independently reviewed each article considered for inclusion in the study. Any disagreements between the reviewers were resolved through consensus. We included any articles pertaining to the effects of omega-3 fatty acids on diabetes mellitus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), rheumatoid arthritis, SLE, renal disease, osteoporosis, or bone mineral status. We included only articles that presented research on human subjects and those that reported the results of randomized clinical trials or controlled clinical trials; we accepted observational studies only for bone mineral status. Language was not a barrier to inclusion.

Data Extraction and Analysis

For each article included in the study, two reviewers independently extracted data about:

The trial design.
The outcomes of interest.
The quality of the trial.
The number and characteristics of the patients.
Details on the intervention, such as the dose, frequency, and duration.
The types of outcome measures.
Adverse events.
The elapsed time between the intervention and outcome measurements.

Any disagreements between the reviewers were resolved through consensus. For each article, we then evaluated the quality of the design and execution of trials using a system developed by Jadad; determined a combined applicability grade based on applicability to the U.S. population and health state; performed a meta-analysis of those studies that sufficiently assessed interventions, populations, and outcomes to justify pooling; and performed a qualitative analysis of the remaining studies.