The low death rate from coronary heart disease among the Greenland Eskimos has been ascribed to their high fish consumption. We therefore decided to investigate the relation between fish consumption and coronary heart disease in a group of men in the town of Zutphen, the Netherlands. Information about the fish consumption of 852 middle-aged men without coronary heart disease was collected in 1960 by a careful dietary history obtained from the participants and their wives. During 20 years of follow-up 78 men died from coronary heart disease. An inverse dose-response relation was observed between fish consumption in 1960 and death from coronary heart disease during 20 years of follow-up. This relation persisted after multiple logistic-regression analyses. Mortality from coronary heart disease was more than 50 per cent lower among those who consumed at least 30 g of fish per day than among those who did not eat fish. We conclude that the consumption of as little as one or two fish dishes per week may be of preventive value in relation to coronary heart disease.

The inverse relation between fish consumption and 20-year mortality from coronary heart disease.

Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.

Divide and conquer—the strategy that science uses to cope with the mountains of printed matter it produces—appears on the surface to serve us well. Science organizes itself into manageable units—scientific specialties—and so its literature is created and assimilated in manageable chunks or units. But a few clouds on the horizon ought not to go unexamined. First, most of the units are no doubt logically related to other units. Second, there are far more combinations of units, therefore far more potential relationships among the units, than there are units. Third, the system is not organized to cope with combinations. I suggest that important relationships might be escaping our notice. Individual units of literature are created to some degree independently of one another, and, insofar as that is so, the logical connections among the units, though inevitable, may be unintended by and even unknown to their creators. Until those fragments, like scattered pieces of a puzzle, are brought together, the relationships among them may remain undiscovered—even though the isolated pieces might long have been public knowledge. My purpose in this essay is to show, by means of an example, how this might happen. I shall identify two units of literature that are logically connected but noninteractive; neither seems to acknowledge the other to any substantial degree. Yet the logical connections, once apparent, lead to a potentially useful and possibly new hypothesis.

Fish oil, Raynaud's syndrome, and undiscovered public knowledge.

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.

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

Background Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. Objectives To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. Search methods We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. Selection criteria Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. Data collection and analysis Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. Main results We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. Authors' conclusions The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

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Reduction in saturated fat intake for cardiovascular disease

Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study, with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil Each oil containing approx 40% of n-3 and n-6 polyunsaturated fatty acids (PUFA) respectively During the n-3 PUFA period, systolic blood pressure, plasma total lipids, triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III (AT-III) rose Cutaneous bleeding time increased significantly In contrast only AT-III rose during the n-6 PUFA feeding, however, more marked than during the n-3 oil period It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases It is in this respect superior to that of n-6 PUFA, stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted

J.Z. Mortensen

Papers

The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure.

n-3 POLYUNSATURATED FATTY ACIDS AND ISCHAEMIC HEART DISEASE