Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Fish oil to reduce blood pressure: a meta-analysis

ACP J Club. 1994 Jan-Feb;120:10. doi:10.7326/ACPJC-1994-120-1-010


Source Citation

Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993 Aug;88:523-33.


Abstract

Objective

To determine whether fish oil (omega-3 fatty acids) reduces blood pressure (BP) after adjusting for dose, length of treatment, health of participants, and study design.

Data Sources

Search of Index Medicus to identify studies on omega-3 fatty acids from fish oil, including fish oil supplements and fish diets.

Study Selection

Published and unpublished clinical trials were selected if they used placebo controls and BP was measured before and after treatment.

Data Extraction

Data were extracted on the weighted mean estimates of differences in BP between treatment and control groups, dose levels, type of fish oil, length of treatment, and study design.

Main Results

52 clinical trials were identified; 31 met the inclusion criteria (1356 participants). The overall mean dose of fish oil was 4.8 g/d. 9 studies (29%) showed a statistically significant decrease in systolic BP (SBP); 5 studies (16%), a significant decrease in diastolic BP (DBP); and 1 study (3%), a significant decrease in both BPs. For all 31 studies, the weighted change in SBP for participants taking fish oil compared with participants taking placebo was -3.0 mm Hg (95% CI, -4.5 to -1.5 mm Hg); for DBP the change was -1.5 mm Hg (CI, -2.2 to -0.8 mm Hg). With low doses of fish oil (≥ 15 g/d), the change in SBP was -8.1 mm Hg (CI, -13 to -2.7 mm Hg) and in DBP, -5.8 mm Hg (CI, -10 to -1.2 mm Hg). Fish oil had no effect on BP in studies of patients with normal BP. In studies of patients with hypertension, those who took fish oil compared with those who took placebo had a change in SBP of -3.4 mm Hg (CI, -5.9 to -0.9 mm Hg) and in DBP of -2.0 mm Hg (CI, -3.3 to -0.7 mm Hg). In studies of patients with hypercholesterolemia, those taking fish oil compared with those taking placebo had a change in SBP of -4.4 mm Hg (CI, -6.6 to -2.2 mm Hg) but no change in DBP. BP decreased moderately but nonsignificantly (SBP, -6.3 mm Hg; DBP, -2.9 mm Hg) in 4 studies of patients with cardiovascular disease. In 2 studies of patients with diabetes , changes in BP did not differ between fish oil and placebo groups.

Conclusions

Fish oil reduced blood pressure in a dose-response relation and in participants with hypertension or hypercholesterolemia. Fish oil did not change blood pressure in participants with normal blood pressure.

Source of funding: Harvard School of Public Health.

For article reprint: Dr. M.C. Morris, Center for Research on Health and Aging, Rush-Presbyterian-St Luke's Medical Center, 710 S. Paulina, Chicago, IL 60612. FAX 312-942-2861.


Commentary

Pharmacies, supermarkets, and health food stores sell fish oil capsules for prevention of cardiovascular disease. Has this therapy proved effective? These 3 meta-analyses and 1 other (1) provide some answers. Gapinski and colleagues reported that fish oil was associated with a significant reduction in angiographically defined restenosis after angioplasty. The studies by Appel and Morris and their colleagues showed that fish oil was associated with small reductions in BP in persons with hypertension and hypercholesterolemia.

Before fish oil supplementation is recommended routinely for such disorders, several issues should be considered. As is often the case, the numbers of participants involved in the reported trials have been small and have represented very selected groups. Few women, nonwhites, elderly persons, and patients with comorbidities have been studied. The trials assessing BP have been short; few have lasted more than 3 months. Most studies have compared fish oil supplementation, rather than high fish diets, with placebo capsules.

The doses that have been associated with positive effects have been on the order of 3.5 to 5 grams daily. This is equivalent to 8 to 10 fish oil capsules that are available commercially. (This is roughly equivalent to the following numbers of 100-gram servings of fish daily: mackerel, 1 to 2; salmon, 3 to 4; tuna, 6 to 10; and flounder, 15 to 25 [2, 3].) It is unclear whether benefits can be achieved through supplementations with small amounts of commercially prepared fish oil.

It is also unclear whether high doses of fish oil (> 6 g/d) have detrimental effects, such as higher restenosis rates or major bleeding risks. Even doses of 4 to 5 grams daily may produce side effects, such as elevated low-density lipoprotein cholesterol, belching, bad taste, and diarrhea (3). It may be difficult to achieve high compliance with the prescription of a large number of pills that are associated with socially undesirable side effects. Finally, the trials reviewed have assessed physiologic or intermediate outcomes, such as angiographic lesions and BP, rather than the clinical outcomes of angina or myocardial infarction.

Looking at fish consumption, rather than fish oil supplementation, several prospective studies and 1 randomized controlled trial have suggested that modest dietary fatty fish consumption is associated with decreases in all-cause and ischemic heart disease mortality (4, 5). The randomized trial evaluated 3 dietary interventions (low fat, high fatty fish, and high fiber) in 2033 men with recent myocardial infarction (5). The fatty fish diet consisted of at least 2 weekly portions of fish such as mackerel, herring, or sardines. 22% of participants in the fatty fish group also took very low doses of fish oil supplementation. The rate of all-cause mortality among the men on the fish diet decreased significantly from 12.8% to 9.3% (relative risk reduction, 29%). Ischemic heart disease mortality also fell significantly from 11.4% to 7.7% (relative risk reduction, 33%). No clinically significant side effects were seen with the fish diet, and serum cholesterol was not significantly increased at the end of the 2-year trial.

Although these 3 well-designed meta-analyses show that fish oil supplementation lowers BP in patients with hypertension and that it prevents restenosis after angioplasty, it is premature to adopt fish oil supplementation as routine clinical practice for several reasons. The information available may not be generalizable to most patients. The therapeutic window for fish oil is not well defined, and side effects occur. The long-term clinical outcomes are unknown. Finally, the feasibility of achieving compliance with multiple pills without adversely affecting compliance with other clinically proved regimens (e.g., diuretics for hypertension) is not clear.

Despite these deficiencies in our knowledge regarding fish oil supplementation, current findings are promising. Clinicians should look for results of ongoing multicenter trials that will better establish the safety, tolerability, and efficacy of palatable doses of fish oils. Whether fish oil supplementation is superior to dietary fish intake should also be evaluated. Meanwhile, it is prudent to routinely recommend modest dietary intake of fatty fish, especially for persons who have had a myocardial infarction.

Cynthia D. Mulrow, MD
Audie L. Murphy Memorial Veterans Hospital San Antonio, Texas, USA