Statement Of Gabriel Fernandes
Environmental Protection Agency
Aging Initiative Public Listening Session
San Antonio, Texas
April 8, 2003
Professor of Medicine
Is fish intake safe from mercury toxicity?Both genetic and environmental factors are known to cause a decline of the immune system during aging (1). Attempts to prevent the loss of genome integrity and damage to cellular DNA in immune cells during aging are of vital importance. With age, cumulative damage caused by both exogenous and endogenous agents such as increased air pollution, UV or ionizing radiation and reactive oxygen species generated by respiration could further increase the damage to DNA resulting in impairment of immune function. Loss of various immunological functions in the elderly includes both changes in innate (rapid) and adaptive (delayed) immune responses which are regulated closely by various lymphocyte subsets. With age, the loss of T cell function, particularly changes in the na´ve/memory T-cell ratio, occurs earlier than the loss of B cell function which causes an imbalance in Th-1 (IL-2, IFN-g) and Th-2 (IL-4, IL-6, IL-10) cytokines (2). These changes may promote either organ-specific or systemic inflammation and an increase in autoimmune disorders in the elderly, including susceptibility to viral and bacterial infection. Inadequate nutrition and/or selective dietary deficiency in the elderly could also cause immune deficiency. Furthermore, early loss of immune function may lead to failure to ward off diseases of aging such as cardiovascular disease, cancer, and various autoimmune disorders such as arthritis and osteoporosis. Thus there is a growing interest among the elderly population in maintaining a healthy lifestyle and finding ways to maintain optimal immune function in order to prevent an increase in infection and diseases of aging.
There is a major concern regarding the various environmental factors involved in inducing autoimmune disease during aging. We have been studying the role of dietary factors such as excess calories, particularly those derived from dietary fats. We have established that feeding autoimmune disease prone mice a diet enriched in vegetable oils such as corn oil promotes more severe renal disease and shortens life span, whereas feeding n-3 fatty acids such as fish oil delays the disease process by suppressing the immune system. We also noted that feeding fewer calories - particularly when those calories include fish oil - significantly delays the onset of disease by enhancing antioxidant enzymes and lowering proinflammatory cytokines (3, 4).
In recent years there have been several favorable reports on fish consumption which have described protection against cardiovascular disease, some cancers, arthritis, etc. The use of fish or fish oil as supplements is growing among the elderly in the USA. However, there is also concern regarding accumulation of mercury in various large fish, which can be toxic to the immune system or during pregnancy (5-9). There is a large amount of literature describing the adverse effects of mercury on the immune system which can cause autoimmune disease or malignancy (10-15). Thus more attention to and more frequent examination of the level of mercury and other heavy metal contaminants present in various kinds of fish is also needed to prevent cumulative toxicity in the elderly population in Texas. This is particularly true of swordfish, mackerel, tuna, shark, etc. in Gulf coastal waters, and other species in lakes and rivers. At least frequent random measurement of mercury levels in various native fish in Gulf waters will assure the elderly that the level of mercury in the fish and/or even in fish capsules is within safe levels. Methyl mercury beyond 0.5-1.5 ppm can cause acute neurotoxicity, depressed immune function and damage to DNA, which could cause malignancy. Much research is needed to establish the adverse effects of mercury, not only in children but also in the elderly, particularly in those who are genetically susceptible and at risk of developing chronic diseases of aging such as diabetes, heart disease, hypertension, osteoporosis, etc.
Besides possible pesticide contaminants in fish, it may be necessary to undertake adequate safety research on genetically modified foods (such as oil seeds, grains, corn, soybeans, canola, tomatoes, potatoes etc.) to be used as animal feed and for human consumption. It is important to determine if the genetically modified fruits and seeds will affect human health due to harmful gene products such as toxic or allergenic modified proteins. Although it is reassuring to know they are safe, some products may be allergenic to the elderly due to their impaired immune systems. Public awareness in Europe has led to strict safety concerns regarding many foods in recent years. However, the long-term effects are still unknown. More research is needed before these modified food products are introduced for human consumption (16-18).
1. Hodes, R. J., The effects of aging on lymphocyte development and function: introduction. Springer Semin Immunopathol 24, 1-5, 2002.
2. Gardner, E. M. and Murasko, D. M., Age-related changes in Type 1 and Type 2 cytokine production in humans. Biogerontology 3, 271-90, 2002.
3. Jolly, C., Muthukumar, A., Reddy Avula, C., Troyer, D. and Fernandes, G., Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr 131, 2753-2760, 2001.
4. Muthukumar, A., Zaman, K., Lawrence, R., Barnes, J. L. and Fernandes, G., Food restriction and fish oil suppress atherogenic risk factors in lupus prone (NZB x NZW)F1 mice. J Clin Immunol 23, 23-33, 2003.
5. Hooked on fish? There might be some catches. Health-conscious people eat it three, even four times a week. But farm-raised fish and worries about mercury contamination are churning the waters. Harv Health Lett 28, 4-5, 2003.
6. Gerstenberger, S. L. and Dellinger, J. A., PCBs, mercury, and organochlorine concentrations in lake trout, walleye, and whitefish from selected tribal fisheries in the Upper Great Lakes region. Environ Toxicol 17, 513-9, 2002.
7. Watanabe, K. H., Desimone, F. W., Thiyagarajah, A., Hartley, W. R. and Hindrichs, A. E., Fish tissue quality in the lower Mississippi River and health risks from fish consumption. Sci Total Environ 302, 109-26, 2003.
8. Evans, E. C., The FDA recommendations on fish intake during pregnancy. J Obstet Gynecol Neonatal Nurs 31, 715-20, 2002.
9. Yoshizawa, K., Rimm, E. B., Morris, J. S., Spate, V. L., Hsieh, C. C., Spiegelman, D., Stampfer, M. J. and Willett, W. C., Mercury and the risk of coronary heart disease in men. N Engl J Med 347, 1755-60, 2002.
10. Bagenstose, L. M., Salgame, P. and Monestier, M., IL-12 down-regulates autoantibody production in mercury-induced autoimmunity. J Immunol 160, 1612-7, 1998.
11. Bagenstose, L. M., Salgame, P. and Monestier, M., Cytokine regulation of a rodent model of mercuric chloride-induced autoimmunity. Environ Health Perspect 107 Suppl 5, 807-10, 1999.
12. Bagenstose, L. M., Salgame, P. and Monestier, M., Murine mercury-induced autoimmunity: a model of chemically related autoimmunity in humans. Immunol Res 20, 67-78, 1999.
13. Pollard, K. M., Pearson, D. L., Hultman, P., Hildebrandt, B. and Kono, D. H., Lupus-prone mice as models to study xenobiotic-induced acceleration of systemic autoimmunity. Environ Health Perspect 107 Suppl 5, 729-35, 1999.
14. Mayes, M. D., Epidemiologic studies of environmental agents and systemic autoimmune diseases. Environ Health Perspect 107 Suppl 5, 743-8, 1999.
15. Bigazzi, P. E., Metals and kidney autoimmunity. Environ Health Perspect 107 Suppl 5, 753-65, 1999.
16. Cockburn, A., Assuring the safety of genetically modified (GM) foods: the importance of an holistic, integrative approach. J Biotechnol 98, 79-106, 2002.
17. Goldman, R. and Shields, P. G., Food mutagens(). J Nutr 133, 965S-73S, 2003.
18. Verhoeyen, M. E., Bovy, A., Collins, G., Muir, S., Robinson, S., de Vos, C. H. and Colliver, S., Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway. J Exp Bot 53, 2099-106, 2002.