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Evidence Analysis Questions related to Fish
Evidence Analysis Questions:
 What is the relationship between fish-derived omega-3 fatty acids and the risk of CHD in individuals without prior heart disease?
Epidemiological studies indicate that regular consumption of an average of two servings of fatty fish per week (about 3.5 oz per serving) [high in long chain n-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] is associated with a 30 – 40% reduced risk of death from cardiac events in subjects without prior disease.
Grade II
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Randomized clinical trials have shown that approximately one gram per day of EPA and DHA from a supplement or fish decreases the risk of death from cardiac events in patients with heart disease.
Grade II
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Two small time series (one neutral and one negative quality) had conflicting results on the effectiveness of EPA as fish oil supplement to reduce weight loss in pancreatic cancer patients. The dosage of EPA as a fish oil supplement and length of supplementation varied among the studies. Larger randomized controlled trials are needed. Sample size was small and there were inconsistencies across the studies.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Five (5) studies had mixed results as to the use of EPA as fish oil supplement and the reduction of weight loss. Three (3) studies (2 + RCTs, 1 – non-randomized trial) found that EPA as fish oil supplement did not have an effect on weight status. Two (2) other studies (1 + before and after study and 1 + RCT) did find EPA as a fish oil supplement to be successful in stabilizing weight in advanced cancer patients. 4/5 studies (2 from each group) are limited by small sample size. In addition, dosing of EPA and length of supplementation was not consistent in these studies. Further trials are needed.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Renal outcomes (proteinuria and rate of GFR decline) were inconsistent among patients with IgA nephropathy who received fish oil supplementation. One 4-year randomized controlled trial indicated a slower decline in renal function and decrease in proteinuria in patients with IgA nephropathy who received 6 grams of fish oil (1.43 grams EPA+DHA) per day in comparison to the control group. Trials of 2 years in duration or less that prescribed 3-4 grams fish oil supplements (1.35-3.35 grams EPA+DHA) per day did not report a consistent significant effect on renal outcomes. In addition, a meta-analysis of 5 earlier trials suggested similar results. Despite such findings, there were various positive effects on other study parameters (e.g., lipid profiles, homocysteine levels).
Grade II
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Subjects with elevated triglycerides (mean values ranged 250-919 mg/dL) taking 2.6-3.6g of commercial EPA/DHA fish oil (approximately 48-60% EPA/ 33-40% DHA) with varied dietary intakes without cholesterol lowering medicines, for 6 weeks to 1 year* had 22-45% reductions in triglyceride values compared to baseline values. Lower doses of fish oil (1.72g; 59% EPA/41% DHA) also resulted in 22-25% reductions in triglycerides vs. baseline values after 6 months to 1 year.
*One study was of 1 year duration and was a 6-month open label extension of a 6 month study.
Grade II
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
The triglyceride lowering benefit of EPA/DHA fish oil with HMG-Co A reductase inhibitors (statins) was reported in three studies of varied patient populations. Studies provided 1.68-3.2g EPA/DHA daily for 5-48 weeks in patients receiving statin therapy with diet and lifestyle changes. This resulted in a 0-35% reduction in triglycerides vs. baseline values. Two of the studies found a 32-35% reduction and one study found no reduction in triglycerides. In these three studies there appears to be no dose response. No dietary adherence data were reported.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
In studies of patients with high triglycerides, not following specific dietary advice and not on concurrent statin therapy, fish oil was associated with a 8-44% increase in LDL-C. In studies of people taking fish oil capsules and statins, LDL-C decreased 0-20%.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Fish oil capsule intake in addition to MNT according to current evidence-based nutrition practice guidelines provided by an RD has not been evaluated in the hypertriglyceridemic patient.
Grade V
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
Four positive quality studies (two cohort studies, one cross-sectional study, and one meta-analysis) provide evidence of a protective effect of consumption of fish and fish-derived omega-3 fatty acids on the risk of CVD events in patients with known CHD. In patients with CHD, higher plasma levels of DHA and EPA are associated with a reduction in arrhythmias and fatal heart disease. In post-menopausal women, regular weekly fish consumption is associated with reduced progression of coronary atherosclerosis.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
There is insufficient evidence to support fish oil therapy to improve renal function and patient or graft survival for kidney transplant patients. Limited evidence shows potential benefit of fish oil in reducing oxidative stress and improving lipid profiles.
Grade III
Overall strength of the available supporting evidence: Grade I - good; Grade II - fair; Grade III - limited; Grade IV - expert opinion; Grade V: not assignable
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