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A Meta-analysis of Controlled Clinical Trials

Lawrence J. Appel, MD, MPH; Edgar R. Miller III, MD, PhD; Alexander J. Seidler, PhD; Paul K. Whelton, MD, MSc

Arch Intern Med. 1993;153(12):1429-1438.

Abstract

Background
Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids (-3) PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of -3 PUFA supplementation have been of insufficient size to detect relevant BP changes.

Methods
We conducted a meta-analysis of 17 controlled clinical trials of -3 PUFA supplementation. To estimate an overall effect of -3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP A in -3 PUFA group minus BP A in control group), which was then weighted according to the inverse of the variance.

Results
In the 11 trials that enrolled normotensive individuals (n=728), -3 PUFA supplementation led to significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one trials, respectively. In the six studies that enrolled untreated hypertensives (n=291), significant reductions of SBP and DBP were present in two and four trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg) with 95% confidence intervals were —1.0 (—2.0 to 0.0) and —0.5 (—1.2 to +0.2) in the trials of normotensives, and —5.5 (—8.1 to —2.9) and —3.5 (—5.0 to —2.1) in the trials of untreated hypertensives. In 13 of 17 studies, trial duration was less than 3 months. Doses of -3 PUFA tended to be high (average dose >3 g/d in 11 trials). The magnitude of BP reduction was greatest at high BP but was not significantly associated with dose of -3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in -3 PUFA participants than in control participants (28% vs 13%, P<.001).

Conclusions
Our analyses indicate that diet supplementation with a relatively high dose of -3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP reductions in individuals with untreated hypertension. However, use of -3 PUFA as antihypertensive therapy will require demonstration of long-term efficacy and patient acceptability of lower doses.

(Arch Intern Med. 1993;153:1429-1438)

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