Fish consumption, cancer, and Alzheimer disease

12 Sir Francis Wyatt Place, Newport News, VA 23692, E-mail: wbgrant{at}norfolk.infi.net

Dear Sir:

The recent article in the Journal by Fernandez et al (1), pointing out that fish consumption reduces the risk of several types of cancer, is an important work that opens the door to increased prevention of such cancers. Chronic inflammation is one of the risk factors for cancer (2). The results of a recent study suggest that nonsteroidal antiinflammatory drugs may prevent colon cancer by suppressing the expression of hepatocyte growth factor (3).

Cancers for which risk is not reduced by fish consumption are likely not influenced by inflammation. Breast cancer, for example, is related to high concentrations of estrogen and progesterone (2). Prostate cancer is strongly associated with consumption of calcium and the nonfat portion of milk and inversely associated with consumption of tomatoes (4). The hypothesis proposed to explain the link between calcium and prostate cancer is that calcium reduces the amount of circulating vitamin D (5), which has been shown to inhibit prostate cancer cell growth (6).

In addition to cancer, fish consumption has been found to reduce the risk of developing Alzheimer disease (7). The hypothesized mechanism is a reduction in inflammation in the cerebral vascular system. The classic ß-amyloid deposits of Alzheimer disease tend to coincide with blood vessels in the brain (8). Thus, the inflammation caused by most fatty acids, which are the highest dietary risk factor for Alzheimer disease (7), can be opposed by the n-3 fatty acids in fish oils. This hypothesis is supported by studies showing that frequent consumption of nonsteroidal antiinflammatory drugs reduces the risk of Alzheimer disease (9). Given that fish tend to bioaccumulate toxins, including heavy metals and pesticides, and that the world's fish stocks are being depleted rapidly, plant-derived alternatives to fish would be desirable. Although a report by Harris (10) indicates that these plant-derived alternatives are not yet equivalent to fish, it is hoped that research will continue on this important topic. Thus, our understanding of Alzheimer disease, cancer, and heart disease (1) will benefit from a better understanding of the causes, prevention, and role of inflammation in these chronic diseases.

REFERENCES

1. Fernandez E, Chatenoud L, La Vecchia C, Negri E, Franceschi S. Fish consumption and cancer risk. Am J Clin Nutr 1999;70:85–90.
2. Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc Natl Acad Sci U S A 1995;92:5258–65.
3. Ota S, Tanaka Y, Bamba H, Kato A, Matsuzaki F. Nonsteroidal anti-inflammatory drugs may prevent colon cancer through suppression of hepatocyte growth factor expression. Eur J Pharmacol 1999; 367:131–8.
4. Grant WB. An ecologic study of dietary links to prostate cancer. Alt Med Rev 1999;4:162–9.
5. Giovannucci E. Dietary influences of 1,25(OH)2 vitamin D in relation to prostate cancer: a hypothesis. Cancer Causes Control 1998; 9:567–82.
6. Elstner E, Campbell MJ, Munker R, et al. Novel 20-epi-vitamin D3 analog combined with 9-cis-retonoic acid markedly inhibits colony growth of prostate cancer cells. Prostate 1999;40:141–9.
7. Grant WB. Dietary links to Alzheimer's disease. Alzheimer Dis Rev 1997;2:42–55.
8. Armstrong RA, Cairns NJ, Lantos PL. Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease. Alzheimer Dis Assoc Disord 1998;12:378–83.
9. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997;48:626–32.
10. Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65(suppl):1645S–54S.