Nutrition and Immunity

RESEARCHERS studying the often-surprising effects of nutrition on immunity report that dietary manipulation can become a promising new tool to foster recovery or prevent disease in millions of people.

"We are discovering that some nutriments can be used, not so much as foods, but as modulators, manipulators or stimulators of the immune system," said Dr. Robert A. Good, a pediatrician and immunologist at All Childrens Hospital in St. Petersburg, Fla. "This could turn out to be pretty powerful medicine if we can understand it better."

In recent years, scientists have been teasing out the immunological effects of such nutrients as dietary fats, amino acids, vitamins A, E and B-6 and the minerals zinc, iron, copper and selenium. They are finding, for example, that the amino acid arginine can help prevent postoperative infections and that common polyunsaturated fats can impair immune responses that protect against cancer. The findings are expected to help design diets to prevent heart disease that also boost, rather than suppress, immunity.

At the same time, based on this new knowledge, physicians are increasingly using tests of immunological competence to help determine the nutritional status of patients.

Potential beneficiaries of immune-modifying nutrient adjustments include young children and the elderly, certain cancer patients, patients suffering from severe burns or autoimmune diseases, and people undergoing major surgery, organ transplants or treatments that inadvertently suppress immune responses.

There are even hints that dietary measures might eventually be used to slow the aging of the immune system and to extend the human lifespan by delaying the onset of diseases that result from immunological decline. There is no reason to believe, however, that special diets or specific nutrients can counter the virally induced suppression of immune responses in AIDS patients.

"As we learn more, we should be able to tailor-make diets to the needs of the moment, for example, using one diet to down-regulate the immunological response that leads to rejection of a transplanted organ and another diet to foster rejection of a cancer," Dr. Good said.

Preliminary research has already indicated that nutrient changes in formulas given by tube or vein to surgical and burn patients may significantly decrease their risk of life-threatening infections. If such changes prove beneficial in more definitive studies, this measure alone could save thousands of lives and millions of dollars each year.

For example, Dr. J. Wesley Alexander and Michelle A. Gottschlich at the Shriners' Burn Institute in Cincinnati studied 57 burn patients, who usually are not fed for a day or so after injury. They showed, however, that immediate administration of a special liquid diet by gastric tube could reduce the risk of infections in severely burned patients by 50 percent. The nutritious diet also shortened the patients' hospital stay and reduced death rates when compared with patients fed standard formulas. The special diet was rich in protein, vitamins A and E, iron and other vitamins and trace elements and derived half its fat from omega-3 fatty acids, or fish oil.

Other research at Albany Medical Center has shown that highly refined fish oil supplements can suppress the symptoms of rheumatoid arthritis, an autoimmune diseases in which the body's immune system mistakenly attacks its own tissues. And studies are under way by Dr. George Blackburn at New England Deaconess Hospital in Boston in patients with early stage cancers of the breast, colon and prostate to test the ability of fish oils to prevent metastasis, or spread of cancer cells beyond the site of origin.

Animal studies have already shown that fish oil in the diet can increase the activity of white blood cells called macrophages, which detect and attack foreign cells.

Both deficiences and excesses of the same nutrients can be harmful to immunological defenses. For example, a deficiency of the trace element zinc depresses the activity of immunological cells, but Canadian studies have shown that an excess of zinc (20 times the recommended daily amount of 15 milligrams) also causes an immunological decline in otherwise healthy people.

The studies by dozens of scientists also show that polyunsaturated fats, which have been widely recommended as replacements for artery-clogging saturated fats, can, when consumed in amounts now common in American diets, impair normal immunological responses. This impairment, in turn, might increase the risk of developing certain infections or even cancer. This observation, made in animal studies, may account in part for the finding in some large studies that diets high in polyunsaturated vegetable oils diminished heart attacks but not overall death rates. Researchers say that polyunsaturates, even when consumed at the recommended level of 10 percent of total calories, could be hazardous.

"Moderation remains the key to a health-promoting diet and a healthy immune system," said Dr. Ranjit K. Chandra, pediatrician and immunologist at the Memorial University of Newfoundland. Dr. Chandra, who studies both children and the elderly, was editor of "Nutrition and Immunology," a text summarizing the state of the science published this winter by Alan R. Liss Inc.

Dr. Chandra and his colleagues were among the first to uncover the devastating immunological consequences of severe malnutrition, which renders people highly susceptible to life-threatening infections. Among seriously malnourished children in India, they found impaired function of the immunological cells that carry memory of what should be attacked, a depressed ability of macrophages to kill bacteria and fungi and a sluggish response of the complement system that normally magnifies the immune response to infection or injury. They also found a failure of mucous membranes to block attachment of harmful microorganisms and an impairment of antibodies that normally prevent microorganisms from sticking to cells.

In industrialized countries like the United States and Canada, Dr. Chandra said, immune responses may malfunction as a result of nutrient derangements in such people as hospital patients malnourished because of their disease or its treatment, premature infants, the elderly and the obese.

Among the nutrients found thus far to have significant immunological effects are these:

Fatty acids: Diets high in the kinds of polyunsaturated fatty acids prominent in corn, safflower and soybean oils disrupt the immune system. In excess amounts these fatty acids, known as N-6, delay the maturation of suppressor cells, which act as brakes on the immune system. They also inhibit the formation of lymphocytes, primary cells of the immune response, resulting in an overall blunting of immune responses.

While high levels of polyunsaturates in the diet may help prevent rejection of organ transplants, they may also foster the growth of tumors, according to Dr. John E. Kinsella, a lipid biochemist at Cornell University. He said a better approach from an immunological standpoint would be to consume less N-6 fatty acid and more omega-3 fatty acid, prominent in fish and canola oil, as well as in many dark-green leafy vegetables. An alternative, he said, is to eat a very low-fat diet without any particular increase in omega-3's.

Nucleotides: These substances, derived from genetic material and present in ordinary diets, are missing from liquid formula diets administered to patients who cannot eat normally. Dr. Charles E. Van Buren of the University of Texas, Houston, and his collaborator, Dr. Fred Rudolph of Rice University, have shown that diets free of nucleotides sharply suppress immune functions and, in laboratory animals, enhance the survival of transplanted organs but also increase the risk of fungal and bacterial infections.

Arginine: In animal studies, adding this "nonessential" amino acid to the diet enhanced immune responses and preserved immune function in the face of malnutrition and advancing cancers. Arginine is an ordinary component of protein that is available as a concentrated dietary supplement from health food stores. Dr. John M. Daly, a surgeon at the University of Pennsylvania in Philadelphia, showed that arginine can stimulate immune function in patients whose immune systems are undermined by disease or surgery. He is now studying 60 to 100 surgical patients to determine whether postoperative infections can be suppressed by adding arginine to the diet.

Trace Elements: Zinc, the most widely studied essential mineral with respect to immunity, is often deficient in diets that derive most of their protein from grains. But many Americans also have marginal or low intakes of zinc, which could result in depressed immune responses. Especially at risk are the elderly and people who eat little or no meat and lots of fiber. Zinc is essential to the production of thymic hormones, needed to foster maturation of immune cells. A deficiency of zinc during prenatal or early life can permanently damage immunological function.

On the other hand, Dr. Chandra and colleagues in Newfoundland showed that excessive zinc - 300 milligrams a day, a popular megadose - depressed cellular immunity and macrophage activity, primarily by raising blood and cell levels of low-density lipoprotein, the substance that carries artery-clogging cholesterol.

Iron deficiency, especially during prenatal and early life when growth is rapid, can result in long-term immunological deficiences that are not correctable by subsequent iron supplements. Iron is a critical ingredient in a number of enzymes that are involved in the killing of infectious organisms. An estimated 10 to 15 percent of Americans are iron-deficient.

But high levels of iron in the blood are also known to foster the growth of such organisms, expecially in people who are otherwise malnourished. For example, in several studies, iron given by injection to malnourished women in Africa and Asia rendered them highly susceptible to malaria. Thus, in correcting a iron deficiency, total nutrition must be taken into account and blood levels of iron kept moderate.

Deficiencies of selenium, needed for the formation of antibodies and enzymes that take part in immunity, are not common in industrialized countries. But excessive intake of selenium, such as some health-food enthusiasts recommend, can impair immune responses. As little as four times the recommended intake of 0.05 to 0.2 milligram can have adverse effects, Dr. Chandra said.

Vitamins: Deficiency of vitamin A can increase the risk of infections, particularly infections of the eyes and respiratory and gastrointestinal tracts. Dr. Chandra's studies have shown that when vitamin A is deficient, bacteria can bind more readily to the cells lining the respiratory tract. Since even a small excess of vitamin A can be toxic, Dr. Chandra and others recommend that to avoid an overdose it is best to consume its chemical parent, beta-carotene, which is prominent in most dark-green and deep-yellow vegetables and fruits. In converting beta-carotene to vitamin A, the body does not produce toxic amounts.

Deficiency of vitamin B-6, which occurs in about 6 to 8 percent of elderly Americans, impairs cellular immunity and the activity of thymic hormone, which is vital to the maturation of immune cells. Similarly, cellular immunity is depressed by a deficiency of folic acid, a B vitamin needed for cell division. Pregnant women, the elderly and inner city children are most likely to be deficient in folic acid.