Fish Story or Food for Thought?

Abstract & Commentary

Synopsis: Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer’s disease.

Source: Morris MC, et al. Arch Neurol. 2003;60:940-946.

This study examined whether consumption of fish had any effect on the risk of developing Alzheimer’s disease. Morris and associates carried out a prospective study of 815 people aged 65-94 in a biracial community in Chicago. Subjects were followed for an average of 4 years for the development of Alzheimer’s disease. The subjects completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. The Alzheimer’s disease was diagnosed using a structured neurological examination and standardized criteria. A total of 131 people in the sample developed Alzheimer’s disease. Participants who consumed fish once per week had a 60% less risk of Alzheimer’s disease as compared to those who rarely or never ate fish (relative risk, 0.4). This was in a model in which other risk factors were statistically adjusted to correct for the effects of age, sex, ethnicity, education, stroke, hypertension, heart disease apolipoprotein E genotype, total caloric intake, and consumption of other fats and vitamin E. The association was particularly marked for intake of long-chain n-3 polyunsaturated fatty acids and docosahexaenoic acid (Omega-3). The intake of a-linolenic acid, which is found in vegetable oil and nuts, was protective only in people with the APOe4 allele. Morris et al suggest that the consumption of Omega-3 fatty acids, which are found in fish, vegetable oils, and nuts, may reduce the risk of Alzheimer’s disease.

Comment by M. Flint Beal, MD

This is an interesting study. It is consistent with other studies from Morris et al in another population. The effect size is very large. Whether this will be reproducible in other epidemiological studies remains to be seen, but it is definitely worthy of further investigation.

Morris et al have also shown recently that intakes of saturated fat and transunsaturated fat are positively associated with risk of Alzheimer’s disease, whereas intakes of W6 polyunsaturated fat and monounsaturated fat are inversely associated. This study was carried out in the same population, and it was shown that persons in the other upper fifth of saturated fat intake had a 2.2-fold increased risk as compared with persons of the lowest fifth in intake of developing Alzheimer’s disease.1

Another study of the intake of total fat, saturated fatty acids, transfatty acids, cholesterol and low-intake monosaturated acids, and N6 polyunsaturated acids and N3 polyunsaturated fatty acids was carried out in the Rotterdam epidemiological study. In this cohort of 5395 subjects there was no association between fat intake and subsequent development of dementia.2

If fish intake is indeed protective against Alzheimer’s disease, what could be the mechanism? It has been shown that long-chain n-3 polyunsaturated fatty acids have an effect on membrane stability, as well as neurite health outgrowth. They could potentially alter b-amyloid processing. Omega-3 fatty acids have previously been shown to be associated with a lower risk of cancer, as well as cardiovascular disease and stroke. A protective dose effect of fish intake against stroke was detected in the Nurse’s Health Study, as well as in the Health Professional Follow-up Study. However, in this study there was no dose effect. It is conceivable that fish intake could have some minor deleterious effects due to methylmercury and the accumulation of PCBs, which occur in some large predatory fish. Nevertheless, the overall evidence suggests that intake of fish may exert protective effects against a number of diseases and further investigation of its role in protecting against Alzheimer’s disease is certainly warranted.

References

1. Morris MC, et al. Arch Neurol. 2003;60:194-200.

2. Engelhart MJ, et al. Neurology. 2002;59:1915-1921.

Dr. Beal is Professor and Chairman, Department of Neurology, Cornell University Medical College, New York, NY.