Correspondence
Fish Intake and the Risk of Coronary Disease
N Engl J Med 1995; 333:937-938October 5, 1995
- Article
To the Editor:
Ascherio and coworkers (April 13 issue)1 reported findings on dietary fish intake and the risk of coronary heart disease and concluded that there was no relation. There was, however, an increased risk of coronary-artery bypass grafting in the two groups with the highest fish intake. Selection bias appears an unlikely explanation.
In our study of 1833 Eastern Finnish men with a high fish intake, men in the upper half of the fish-intake distribution (≥30 g per day in four-day food records) had 1.9 times the risk (adjusted for risk factors; 95 percent confidence interval, 1.1 to 3.1) of acute myocardial infarction of men who ate less fish.2 Men who had high hair mercury values (≥2.0 μg per gram) had 1.7 times the risk (adjusted for risk factors; 95 percent confidence interval, 1.03 to 2.8) of acute myocardial infarction.2 Both fish intake and hair mercury values had direct, approximately linear associations with the risk of acute myocardial infarction. Elevated hair mercury values were associated with increased lipid peroxidation.2 As has not previously been reported, we also measured 19 serum fatty acids with a capillary gas chromatographic system (Hewlett–Packard 5890 with flame ionization detector). After adjustment in a Cox model for the same covariates as in the earlier analysis,2 the risk of acute myocardial infarction in patients whose values for the n-3 fatty-acid index (the ratio of the sum of values for eicosapentaenoate and docosahexaenoate to the sum of values for all saturated fatty acids) were in the highest quarter was 2.1 times the risk in patients with values in the lowest three quarters.
Thus, in our cohort, a high intake of fish was associated with an increased risk of acute myocardial infarction, whether fish intake was assessed through diet records or by direct measurement of hair mercury or serum n-3 fatty acids. Epidemiologic studies have a limited ability to distinguish the effects of beneficial and harmful substances in the same foodstuffs. Fish is not merely a source of n-3 fatty acids but also of methyl mercury.3 Dietary fish may be either protective or harmful, depending on its contents of n-3 fatty acids and mercury.
3 ReferencesJukka T. Salonen, M.D., Ph.D., M.Sc.P.H.
Kristiina Nyyssönen, M.Sc.
Riitta Salonen, M.D., Ph.D.
University of Kuopio, 70211 Kuopio, Finland1
Ascherio A ,Rimm EB ,Stampfer MJ ,Giovannucci EL ,Willett WC . Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977-982
Full Text | Web of Science | Medline2
Salonen JT ,Seppanen K ,Nyyssonen K , et al. Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 1995;91:645-655
Web of Science | Medline3
Clarkson TW . Environmental contaminants in the food chain. Am J Clin Nutr 1995;61:Suppl:682S-686S
Web of Science | Medline
To the Editor:
It is unfortunate that the article by Ascherio et al. received such widespread and exaggerated media coverage, which went beyond the authors' own qualified interpretation of their findings. Beyond the possible claim that high levels of fish consumption may be no better than low levels, it contributes nothing to the important question of whether n-3 fatty acids can reduce the risk of coronary heart disease.
In this study, as the authors recognized, the lowest quintile of the health-conscious health professionals comprising the study cohort were eating 0.7 fish serving on average per week. Previous studies1,2 have indicated that one or two meals of fish per week already afford considerable protection from death due to coronary heart disease. Thus, the difference between their lowest and highest quintiles of intake may not add further benefit. Furthermore, the n-3 fatty acids have now been shown to have antiarrhythmic effects,3,4 which account for over 50 percent of deaths from acute myocardial infarctions, and we know that the n-6 as well as the n-3 fatty acids share this effect.5 All their subjects were receiving similar amounts of total polyunsaturated fatty acid daily, which would dampen the benefits from added fish intake.
Finally, their subjects with the highest intake of n-3 fatty acids were both the most health conscious and the most at risk for coronary heart disease, as indicated by their family histories and past histories of hypertension, high cholesterol, and diabetes. It is the higher mortality in this group that appears to vitiate a possible beneficial dose response of fish intake to coronary heart disease.
5 ReferencesAlexander Leaf, M.D.
Harvard Medical School, Boston, MA 021151
Kromhout D ,Bosschieter EB ,de Lezenne Coulander C . The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209
Full Text | Web of Science | Medline2
Dolecek TA . Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. Proc Soc Exp Biol Med 1992;200:177-182
Web of Science | Medline3
McLennan PL ,Bridle TM ,Abeywardena MY ,Charnock JS . Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey. Am Heart J 1992;123:1555-1561
CrossRef | Web of Science | Medline4
Billman GE ,Hallaq A ,Leaf A . Prevention of ischemia-induced ventricular fibrillation by ω3 fatty acids. Proc Natl Acad Sci U S A 1994;91:4427-4430
CrossRef | Web of Science | Medline5
Kang JX ,Leaf A . Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes. Proc Natl Acad Sci U S A 1994;91:9886-9890
CrossRef | Web of Science | Medline
To the Editor:
Although the data of Ascherio et al. on the risk of coronary heart disease according to the calculated intake of n-3 fatty acids (their Table 2) do not indicate a protective effect of n-3 fatty acids in this cohort of subjects, data on the relative risk of coronary heart disease according to fish intake do indeed suggest a protective effect of low-to-moderate fish intake on “nonfatal myocardial infarction,” “fatal CHD [coronary heart disease],” and “any myocardial infarction.” 1,2 Passing from the first category of fish intake (<1 serving per month) to the second category (1 to 3 servings per month) involves — in the multivariate analysis performed — a reduction of 38 percent, 26 percent, and 34 percent in the relative risk of these three end points, respectively, with confidence intervals suggesting statistically significant effects for “nonfatal myocardial infarction” and “any myocardial infarction.” Quintiles of higher consumption are associated with variable changes in risk. Thus, data on the relation of fish intake to the risk of coronary heart disease could fit a U-shaped model.
The difference between these trends and that seen with n-3 fatty acids would suggest that as-yet-unidentified substances in fish, other than n-3 fatty acids, may have protective effects. This supports the speculation arising from the analysis of the Zutphen study,3 in which most of the protection was observed passing from the category of “no fish intake” to that of “low fish intake” (1 to 14 g per day, corresponding to one to two fish dishes per week). At such levels of intake, as pointed out by Ascherio et al., it is unlikely that the reduction in coronary heart disease can be explained by the known effects of n-3 fatty acids. In addition, the Zutphen study reported that protection from coronary heart disease was also seen with consumption of lean fish containing extremely low amounts of n-3 fatty acids.3
My colleagues and I,4 as well as others, have worked toward understanding the biologic effects of n-3 fatty acids as a probable explanation for existing epidemiologic data. The consistency of the low-fish-intake data of Ascherio et al. with the Zutphen study should be highlighted, since it could foster research on potentially beneficial components of fish other than n-3 fatty acids.
4 ReferencesRaffaele De Caterina, M.D., Ph.D.
Institute of Clinical Physiology, 56100 Pisa, Italy1
Ascherio A ,Rimm EB ,Stampfer MJ ,Giovannucci EL ,Willett WC . Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977-982
Full Text | Web of Science | Medline2
Katan MB . Fish and heart disease. N Engl J Med 1995;332:1024-1025
Full Text | Web of Science | Medline3
Kromhout D ,Bosschieter EB ,de Lezenne Coulander C . The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209
Full Text | Web of Science | Medline4
De Caterina R, Endres S, Kristensen SD, Schmidt EB. n-3 Fatty acids and vascular disease. New York: Springer, 1993.
Author/Editor Response
The authors reply:
To the Editor: It is possible, as Salonen and colleagues suggest, that consumption of fish contaminated with methyl mercury increases the risk of myocardial infarction; this deserves further investigation. As Leaf correctly states, our study indicates that increasing fish intake from low to high levels is unlikely to reduce the risk of coronary heart disease. We believe that this result has important implications, especially for men who, feeling that eating fish several times per week would afford substantial protection against coronary heart disease, may have ignored the avoidance of other risk factors. The cardiovascular effects of n-3 fatty acids mentioned by Leaf have been observed at high levels of intake and are therefore unlikely to explain the beneficial effects of small amounts of fish suggested by previous epidemiologic investigations.1,2 We agree that a high intake of polyunsaturated fats from other sources may have dampened the benefits of fish intake, and in fact we noted that the previously observed benefits of fish intake may have been related to the low amounts of polyunsaturated fats consumed at that time. Concerning the high coronary risk among men with the highest intake of n-3 fatty acids, we adjusted data for family history of myocardial infarction, as well as history of hypertension, hypercholesterolemia, and diabetes. As we described in detail in our article, the lack of an inverse association between fish intake and the risk of coronary heart disease persisted after adjustment for these factors, and it is unlikely that residual confounding would offset a substantial beneficial effect of high fish intake. Finally, we have emphasized the lack of an overall trend between fish intake and the risk of coronary heart disease because this was the primary hypothesis addressed by the study. Observations on different shapes of dose response, however, such as the U-shaped relation suggested by De Caterina, can provide useful insights and deserve some consideration, especially if they can be supported by a plausible biologic mechanism.
2 ReferencesAlberto Ascherio, M.D.
Walter C. Willett, M.D.
Harvard School of Public Health, Boston, MA 021151
Kromhout D ,Bosschieter EB ,de Lezenne Coulander C . The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209
Full Text | Web of Science | Medline2
Shekelle RB ,Missell LV ,Paul O ,Shryock AM ,Stamler J . Fish consumption and mortality from coronary heart disease. N Engl J Med 1985;313:820-820
Full Text | Web of Science | Medline
- Citing Articles (5)
Citing Articles
1
Jusheng Zheng, Tao Huang, Yinghua Yu, Xiaojie Hu, Bin Yang, Duo Li. (2011) Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies. Public Health Nutrition1-13
CrossRef2
Ka He. (2009) Fish, Long-Chain Omega-3 Polyunsaturated Fatty Acids and Prevention of Cardiovascular Disease—Eat Fish or Take Fish Oil Supplement?. Progress in Cardiovascular Diseases 52:2, 95-114
CrossRef3
Baukje de Roos, Yiannis Mavrommatis, Ingeborg A Brouwer. (2009) Long-chain n-3 polyunsaturated fatty acids: new insights into mechanisms relating to inflammation and coronary heart disease. British Journal of Pharmacology 158:2, 413-428
CrossRef4
Kimberly M Smith, Leila M Barraj, Mark Kantor, Nadine R Sahyoun. (2009) Relationship between fish intake, n-3 fatty acids, mercury and risk markers of CHD (National Health and Nutrition Examination Survey 1999–2002). Public Health Nutrition 12:08, 1261
CrossRef5
Gandham Bulliyya. (2002) Influence of fish consumption on the distribution of serum cholesterol in lipoprotein fractions: comparative study among fish-consuming and non-fish-consuming populations. Asia Pacific Journal of Clinical Nutrition 11:2, 104-111
CrossRef
