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Source: Iso H, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA 2001;285:304-312.
Design/Setting/Subjects: Prospective cohort study of 79,839 women (age 34-59 years in 1988) in the Nurses’ Health Study (NHS) without a prior diagnosis of cardiovascular disease, cancer, diabetes, or hypercholesterolemia, who completed a food frequency questionnaire. Subjects were followed up for 14 years.
Main Outcomes: Relative risk (RR) of stroke in 1980-1994 by quintile of fish intake and category of fish intake.
Results: After 1,086,261 person-years of follow-up, 574 strokes were documented. Women who ate the most fish had a lower risk of stroke than women who ate fish less than once per month. RRs (adjusted for age, smoking, and other cardiovascular risk factors) were 0.93 (95% CI 0.65-1.34) for those consuming fish 1-3 times/month, 0.78 (95% CI, 0.55-1.12) for those who ate fish once a week, 0.73 (95% CI 0.47-1.14) for those who ate fish 2-4 times/week, and 0.48 (95% CI 0.21-1.06) for those who ate fish > 5 times/week (P for trend = 0.06).
Women who ate fish at least twice per week had a significantly reduced risk of thrombotic stroke (RR 0.49, 95% CI 0.26-0.93). The relative risk of total stroke in women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids (PUFAs) was 0.72 (95% CI, 0.53-0.99); the RR for thrombotic infarction was 0.67 (95% CI 0.4-1.07). Hemorrhagic stroke was not associated with fish or omega-3 PUFAs intake. Among stroke subtypes, there is a statistically significant benefit for lacunar infarction, but only a borderline significant for thrombotic infarction. There was no benefit for large-artery occlusive infarction.
Stratified by aspirin use, women ingesting the highest amount of omega-3 PUFAs who were not using aspirin had a significant 49% reduction in the risk of thrombotic stroke.
Comments: A good excuse for splurging on salmon, eating sushi, and for the anchovy-eaters to win out at the pizza parlor.
Herring, sardines, and anchovies have the highest amount of fat and therefore the highest level of omega-3 PUFAs. Other dark meat fish including salmon, mackerel, bluefish, and swordfish are also quite high in PUFAs; tuna also is a good source. Other fish and shellfish contain lesser but significant amounts. Fish oil supplements usually are made from sardines, anchovies, or an inedible fish called menhaden, whose name is derived from a Narraganset Indian word that means "manure," which probably reflects their use as fertilizer.
Most but not all prospective cohort studies have reported an inverse relationship between fish consumption and cardiovascular mortality. In the Physicians’ Health Study, a prospective cohort study of 20,551 U.S. male physicians, dietary fish intake was associated with a reduced risk of sudden death.1
There are fewer data on risk of stroke, so this study is important. Risk reduction was most pronounced among women who did not take aspirin regularly. Aspirin is a much more potent inhibiter of thromboxane A2 synthesis in platelets than are omega-3 PUFAs, but of course aspirin increases bleeding risk. It is reassuring that no increased risk of bleeding was seen in this trial. As the authors point out, bleeding time may be prolonged when the intake of omega-3 fatty acids is more than 3 g/d; however, this corresponds to eating fish tid, a dietary level of intake attained by fewer than 0.1% in this study. (I would add that no increase in bleeding events has been observed in any fish oil clinical trial). Information on fish oil capsule supplementation is not included apparently because information on fish oil supplementation was not requested until 1990, and at that time the prevalence of consumption of fish oil was only 1.6 %. The intake of omega-3 fatty acids through capsules undoubtedly has increased in the last 10 years, and it will be interesting to see if such supplementation is associated with similar reductions in risk in the next report of the NHS.
The authors point out that several known actions of fish oil may be protective. High doses of omega-3 fatty acids are associated with reduced platelet aggregation. Eicosapentaenoic acid, or EPA, (some of which is ingested preformed, and some of which is formed from docosahexaenoic acid) increases the production of thromboxane A3, which then increases prostaglandin I3, a vasodilator. These effects are induced 3-4 days after beginning supplementation and persist for 2-10 weeks after cessation of high-dose supplementation. Dietary supplementation would be expected to have somewhat more modest effects.
1. Albert CM, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998;279:23-28.