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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)

Author Affiliations
From the Welch Center for Prevention, Epidemiology, and Clinical Research (Drs Appel, Seidler, and Whelton), Department of Medicine, The Johns Hopkins University School of Medicine (Drs Appel and Whelton), and Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health (Drs Appel and Whelton), Baltimore, Md; and Medical University of South Carolina, Charleston (Dr Miller).

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