Fish Oil and Hypertension (High Blood Pressure)

A meta-analysis of controlled trials published in Circulation in 1993 reported that fish oil may reduce high blood pressure. EPA and DHA, the omega-3 fatty acids found in fish oil, lower blood pressure, according to the analysis. The effect was dependent on the amount of omega-3 oil used.

Trials using over 3 grams per day of omega-3 reported significant reductions in blood pressure. One of the double-blind studies reported that DHA had greater effects on blood pressure than EPA or mixed fish oil supplements.

Abstracts of Published Studies
Indicating Fish Oil's Potential Efficacy to Lower High Blood Pressure

Effects of Docosahexaenoic Acid (DHA) on Vascular Pathology and Reactivity in Hypertension

Experimental Biology and Medicine 228:299-307 (2003)

Marguerite M. Engler*,1, Mary B. Engler*, Diane M. Pierson,2, Loredana Brizio Molteni and Agostino Molteni

Laboratory of Cardiovascular Physiology, Department of Physiological Nursing, University of California, San Francisco, California 94143-0610; and Department of Pathology and Pharmacology, University of Missouri, School of Medicine, Kansas City, Missouri 64108

Previous studies have shown that docosahexaenoic acid (DHA) has an antihypertensive effect in spontaneously hypertensive rats (SHR). To investigate possible mechanisms for this effect, vascular pathology and reactivity were determined in SHR treated with dietary DHA. SHR (7 weeks) were fed a purified diet with either a combination of corn/soybean oils or a DHA-enriched oil for 6 weeks. Histological evaluation of heart tissue, aorta, coronary, and renal arteries was performed. Vascular responses were determined in isolated aortic rings. Contractile responses to agonists, including norepinephrine (10-9 to 10-4 M), potassium chloride (5-55 mM), and angiotensin II (5 x 10-7 M) were assessed. Vasorelaxant responses to acetylcholine (10-9 to 10 -4 M), sodium nitroprusside (10-9 to 10-6 M), papaverine (10-5 to 10-4 M), and methoxyverapamil (D600, 1-100 µM) were determined. DHA-fed SHR had significantly reduced blood pressure (P < 0.001) and vascular wall thicknesses in the coronary, thoracic, and abdominal aorta compared with controls (P < 0.05) Contractile responses to agonists mediated by receptor stimulation and potassium depolarization were not altered in DHA-fed SHR. Endothelial-dependent relaxations to acetylcholine were not altered which suggests endothelial-derived nitric oxide production/release is not affected by dietary DHA. Other mechanisms of vascular relaxation, including intracellular cyclic nucleotides, cGMP, and cAMP were not altered by dietary DHA because aortic relaxant responses to sodium nitroprusside and papaverine were similar in control and DHA-fed SHR. No significant differences were seen in relaxant responses to the calcium channel blocker, D600, or contractile responses to norepinephrine in the absence of extracellular calcium. These results suggest that dietary DHA does not affect mechanisms related to extracellular calcium channels or intracellular calcium mobilization. Moreover, the contractile and vasorelaxant responses are not differentially altered with dietary DHA in this in vivo SHR model. The findings demonstrate that dietary DHA reduces systolic blood pressure and vascular wall thickness in SHR. This may contribute to decrease arterial stiffness and pulse pressure, in addition to the antihypertensive properties of DHA. The antihypertensive properties of DHA are not related to alterations in vascular responses.

Does fish oil lower blood pressure? A meta-analysis of controlled trials.

Circulation. 1993 Aug;88(2):523-33.

Morris MC, Sacks F, Rosner B.

Department of Epidemiology, Harvard School of Public Health.

BACKGROUND. In a meta-analysis of 31 placebo-controlled trials on 1356 subjects, we examined the effect of omega-3 fatty acids in fish oil on blood pressure by grouping studies that were similar in fish oil dose, length of treatment, health of the subjects, or study design. METHODS AND RESULTS. The mean reduction in blood pressure caused by fish oil for the 31 studies was -3.0/-1.5 mm Hg (95% confidence intervals: systolic blood pressure: -4.5, -1.5; diastolic blood pressure: -2.2, -0.8). There was a statistically significant dose-response effect when studies were grouped by omega-3 fatty acid dose: -1.3/-0.7 mm Hg at doses < or = 3 g/d, -2.9/-1.6 mm Hg at 3.3 to 7 g/d, and -8.1/-5.8 mm Hg at 15 g/d. Both eicosapentaenoic acid and docosahexaenoic acid were significantly related to blood pressure response. There was no effect on blood pressure in eight studies of "healthy" persons (mean reduction, -0.4/-0.7 mm Hg) at an overall mean dose of 4.2 g omega-3 fatty acids/d. By contrast, there was a significant effect of -3.4/-2.0 mm Hg in the group of hypertensive studies with a mean fish oil dose of 5.6 g/d and on systolic blood pressure only in six studies of hypercholesterolemic patients (-4.4/-1.1 mm Hg) with a mean dose of 4.0 g/d. A nonsignificant decrease in blood pressure was observed in four studies of patients with atherosclerotic cardiovascular disease (-6.3/-2.9 mm Hg). Variations in the length of treatment (from 3 to 24 weeks), type of placebo, and study design (crossover or parallel groups) did not appear to account for inconsistent findings among studies. CONCLUSIONS. There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease or hypercholesterolemia.

PMID: 8339414 [PubMed - indexed for MEDLINE]

Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials.

Arch Intern Med. 1993 Jun 28; 153(12): 1429-38.

Appel LJ, Miller ER 3rd, Seidler AJ, Whelton PK.

Welch Center for Prevention, Epidemiology, and Clinical Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.

BACKGROUND: Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids (omega-3 PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of omega-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 omega-3 PUFA supplementation. To estimate an overall effect of omega-3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP delta in omega-3 PUFA group minus BP delta 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), omega-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 omega-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 omega-3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in omega-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 omega-3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP reductions in individuals with untreated hypertension. However, use of omega-3 PUFA as antihypertensive therapy will require demonstration of long-term efficacy and patient acceptability of lower doses.

PMID: 8141868 [PubMed - indexed for MEDLINE]

The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial.

Am J Clin Nutr. 1993 Jan;57(1):59-64.

Morris MC, Taylor JO, Stampfer MJ, Rosner B, Sacks FM.

Center for Research on Health and Aging, Chicago, IL 60612.

We conducted a double-blind, crossover trial with 18 healthy, untreated mildly hypertensive subjects to test the effect on blood pressure of 6 or 12 g fish oil/d (50% n-3 fatty acids) as compared with an olive oil placebo. Blood pressure was measured every 6 wk in the clinic and three times daily by subjects using a semiautomated device in their homes. Compliance was determined biochemically. No significant changes in home or clinic blood pressure measurements were noted for either dose after 6 or 12 wk of treatment. Clinic blood pressure after 12 g fish oil/d was slightly lower than after placebo treatment by -0.8/-0.4 mm Hg [95% CI: systolic blood pressure (-4.4, +2.8); diastolic blood pressure (-3.2, +2.4)]. Blood pressure changes were not correlated with compliance, baseline dietary fish consumption, or blood pressure. Moderate doses of fish oil did not have a substantial effect on blood pressure. We conclude that fish oil is not a practical treatment for mild hypertension.

PMID: 8416666 [PubMed - indexed for MEDLINE]

The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension

New England Journal of Medicine - Volume 320:1037-1043 April 20, 1989 Number 16

HR Knapp, and GA FitzGerald

Both n-3 and n-6 polyunsaturated fats have been suggested to lower blood pressure, an effect ascribed to altered biosynthesis of eicosanoids. To test these hypotheses, we studied blood pressure and eicosanoid production during supplementation of dietary fat for four weeks in 32 men with mild essential hypertension. Supplementation was preceded and followed by four-week run-in and recovery periods. Groups of eight subjects received either 10 ml or 50 ml of fish oil (3 or 15 g of n-3 fatty acids) daily, 50 ml of safflower oil (39 g of n-6 fatty acids), or 50 ml of a mixture of oils that approximated the types of fat present in the American diet. The biosynthesis of eicosanoids was assessed by the measurement of urinary metabolites. Blood pressure decreased in the men who received the high dose of fish oil (systolic pressure by a mean of 6.5 mm Hg [P less than 0.03] and diastolic pressure by 4.4 mm Hg [P less than 0.015]), but not in the other groups. Although the formation of vasodilatory prostacyclins (prostaglandins I2 and I3) increased initially, this increase was not maintained as blood pressure fell. The level of thromboxane A2 metabolites fell; metabolites of thromboxane A3 were detected in the groups receiving fish oil. The formation of prostaglandin E2 increased during supplementation with safflower oil and tended to decrease with fish oil; no prostaglandin E3 metabolite was detected. Our data indicate that high doses of fish oil can reduce blood pressure in men with essential hypertension. However, the clinical usefulness and safety of fish oil in the treatment of hypertension will require further study.

Docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) lowers ambulatory blood pressure and heart rate in humans.

Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ.

Hypertension. 1999 Aug;34(2):253-60.

Department of Medicine, University of Western Australia, and the West Australian Heart Research Institute, Perth, Australia. tmori@cyllene.uwa.edu.au

Animal studies suggest that the 2 major omega3 fatty acids found in fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects on blood pressure (BP) and heart rate (HR). The aim of this study was to determine whether there were significant differences in the effects of purified EPA or DHA on ambulatory BP and HR in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to 4 g/d of purified EPA, DHA, or olive oil (placebo) capsules and continued their usual diets for 6 weeks. Fifty-six subjects completed the study. Only DHA reduced 24-hour and daytime (awake) ambulatory BP (P<0.05). Relative to the placebo group, 24-hour BP fell 5.8/3.3 (systolic/diastolic) mm Hg and daytime BP fell 3.5/2.0 mm Hg with DHA. DHA also significantly reduced 24-hour, daytime, and nighttime (asleep) ambulatory HRs (P=0. 001). Relative to the placebo group, DHA reduced 24-hour HR by 3. 5+/-0.8 bpm, daytime HR by 3.7+/-1.2 bpm, and nighttime HR by 2. 8+/-1.2. EPA had no significant effect on ambulatory BP or HR. Supplementation with EPA increased plasma phospholipid EPA from 1. 66+/-0.07% to 9.83+/-0.06% (P<0.0001) but did not change DHA levels. Purified DHA capsules increased plasma phospholipid DHA levels from 4.00+/-0.27% to 10.93+/-0.62% (P<0.0001) and led to a small, nonsignificant increase in EPA (1.52+/-0.12% to 2.26+/-0.16%). Purified DHA but not EPA reduced ambulatory BP and HR in mildly hyperlipidemic men. The results of this study suggest that DHA is the principal omega3 fatty acid in fish and fish oils that is responsible for their BP- and HR-lowering effects in humans. These results have important implications for human nutrition and the food industry.

PMID: 10454450 [PubMed - indexed for MEDLINE]

Blood pressure lowering effect of eicosapentaenoic acid (EPA)-rich diet in normotensive, hypertensive and hyperlipemic subjects.

Experientia. 1985 Apr 15;41(4):462-4.

Singer P, Wirth M, Godicke W, Heine H.

A mackerel diet or a herring diet in which two cans of fish fillet were consumed daily over 2 weeks within a prescribed regimen, in a crossover design, were given to 15 normotensive volunteers, 14 patients with mild essential hypertension and eight patients with type IV and V hyperlipoproteinemia (HLP). In normotensives a markedly lower systolic and diastolic blood pressure at the end of the period on the mackerel diet could be observed, whereas in hypertensive and hyperlipemic subjects only systolic blood pressure was significantly decreased. After the herring diet, which served as control, changes in blood pressure were of a minor degree.

PMID: 2985425 [PubMed - indexed for MEDLINE]