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Research Newsletter-Fall/Winter 2010


Victoria J. Drake, Ph.D.
LPI Research Associate
Manager, Micronutrient Information Center

Summary: Deficiencies of zinc, selenium, iron, and copper adversely affect immune response. Conversely, too much iron and copper impair immune function. Probiotics—microorganisms often added to dairy products like yogurt—improve immune function in the gastrointestinal system and may help prevent inflammatory bowel disease. Obesity produces chronic inflammation and compromised immunity that may increase the susceptibility to inflections. Moderate, regular exercise may enhance immunity, but prolonged high-intensity exercise may impair it.

Part 1 of this article discussed the differences between the innate and adaptive immune systems and focused on the role of macronutrients (protein and lipids) and vitamins. In part 2, I discuss the role of minerals and other dietary and lifestyle factors in immunity.

Several nutritionally-essential minerals, including zinc, selenium, iron, and copper, play important roles in the development and expression of immune responses. Zinc is required for both innate and adaptive immunity because it has various catalytic, structural, and regulatory functions in the body. Inadequate intake of zinc can lead to a nutritional deficiency of the mineral and compromised immune function. For instance, zinc deficiency impairs the complement system, a biochemical network of more than 30 proteins in plasma and on cell surfaces that functions to kill invading pathogens by direct lysis (cell rupture) or through the promotion of phagocytosis. Phagocytosis is a process by which certain immune cells, such as macrophages, engulf and digest invading microorganisms and foreign particles. Zinc deficiency also impairs other components of innate immunity, including natural killer cell activity and the ability of immune cells to generate oxidants that kill invading pathogens, as well as production and function of lymphocytes—cells that are key to mounting an adaptive response. Adaptive immune responses, which are more complex than innate responses, provide antigen specificity and immunologic "memory" of pathogens; the latter makes subsequent responses to the same pathogen more efficient. For example, vaccines function by this process so that subsequent exposure to the pathogen elicits a fast and efficient immune response. Zinc deficiency results in a heightened vulnerability to several infectious agents. In particular, children with zinc deficiency have increased susceptibility of infectious diarrhea, and zinc supplementation reduces the frequency, severity, and duration of diarrheal episodes in young children. Zinc supplementation in children may also reduce the incidence of lower respiratory infections like pneumonia. However, because of conflicting studies, it is presently not clear whether zinc supplementation has utility in treating childhood malaria.

Selenium is required for normal function of several enzymes important in innate and adaptive immunity, including the glutathione peroxidases—key redox regulators and cellular antioxidants. Inadequate intake of selenium can impair multiple immune responses, such as cytokine (cell-signaling molecules) expression, antibody production, and aspects of cell-mediated immunity. Selenium deficiency has been shown to enhance the virulence or progression of some viral infections. For example, mouse studies have shown that a relatively harmless strain of coxsackievirus becomes more virulent in selenium-deficient mice, resulting in an inflammation of the heart muscle called myocarditis. In humans, concomitant selenium deficiency and coxsackievirus infection may both contribute to the cardiomyopathy in Keshan disease. Additionally, small controlled trials in individuals who were not overtly selenium deficient have found that short-term supplementation with selenium enhances immune cell response to foreign antigens. Other studies have established selenium to be an important regulator of cytokine expression.

Iron is required by the host to mount an effective immune response because the mineral is needed in the differentiation and proliferation of T lymphocytes and in the generation of reactive oxygen species that kill pathogens. Accordingly, iron deficiency—the most prevalent micronutrient deficiency in the world—results in impaired immunity and increased morbidity and mortality from infections. However, iron is required by most infectious agents for replication and survival, and during the early stages of an infection, serum levels of iron decrease and ferritin (a protein that stores iron) levels increase in order to sequester iron from pathogens. Moreover, elevated iron levels, such as in untreated hereditary hemochromatosis (a genetic condition of iron overload despite normal iron intake), can impair phagocytic function, cytokine production, complement system activation, as well as the function of B and T lymphocytes. Further, elevated iron levels may be a risk factor for cancer and death, especially in men. Since iron is very efficiently recycled in the body and lost only in blood and skin sloughing, the Linus Pauling Institute recommends that men and postmenopausal women who are not at risk of iron deficiency take a multivitaminmineral supplement that does not contain iron.

Copper is also important in immunity, but the exact mechanism of its immune action is not yet known. Nutritional deficiency of copper results in an abnormally low number of neutrophils, a condition called neutropenia. Menkes disease is a genetic disorder of intracellular copper transport. Individuals with Menkes disease suffer from severe copper deficiency and frequent, serious infections. It is currently unknown if marginal or mild copper deficiency results in impaired immunity, but high intakes of copper for prolonged periods have been shown to adversely affect immune function.

Dietary factors other than nutrients may affect immunity, as well. For instance, yogurt and other fermented foods may contain probiotics, which are live microorganisms that benefit the overall health of the host when they are administered in sufficient amounts. Bacteria of the Lactobacilli and Bifidobacteria species are common examples. These and other probiotics can transiently inhabit the lower gastrointestinal tract and modulate immune function by interacting with intestinal epithelial cells and immune cells. Studies have shown that probiotics can benefit both innate and adaptive immunity; however, immune modulation requires regular consumption of probiotics since they have not been shown to permanently alter intestinal microflora. Specific immune effects include strengthening the intestinal epithelial barrier and stimulating production of antibodies and T lymphocytes—important mediators of the adaptive immune response. Immune effects of probiotics may depend on the particular strain, as well as the dose, route, and frequency of delivery. While probiotics may have utility in the prevention of various diseases, such as inflammatory bowel disease, diarrheal diseases, allergic diseases, and gastrointestinal infections, more clinical studies are currently needed to elucidate their health effects.

While certain nutritional deficiencies, like some of the mineral deficiencies mentioned above, can compromise immunity, oversupply of nutrients may also be associated with untoward immune effects. Overnutrition is a form of malnutrition where nutrients, especially macronutrients, are supplied in excess of the body's needs. Overnutrition can create an imbalance between energy intake and energy expenditure, leading to excessive energy storage and obesity. Obesity is a major public health problem in the United States and elsewhere because the condition is associated with increased risk of morbidity from a number of chronic diseases, including hypertension and other cardiovascular diseases, type 2 diabetes, liver and gallbladder disease, osteoarthritis, sleep apnea, and various cancers. Moreover, obesity is linked to an increased risk of overall mortality.

Obesity has been shown to alter immunocompetence. In obesity, immune cells called macrophages infiltrate adipose (fat) tissue and accumulate in numbers proportional to the degree of obesity. Macrophages and other immune cells play important roles in the development of inflammation. Inflammatory processes are triggered in part by molecules secreted by adipose tissue. A chronic state of low-grade inflammation exists in obesity. Adipose tissue secretes a number of fatty acids, cytokines, and hormones that are involved in inflammatory and immune processes. The hormone leptin is secreted from adipose tissue and circulates in direct proportion to the degree of fat stores. Leptin is an important regulator of food intake, body weight, and energy homeostasis. Results of animal and in vitro studies indicate that leptin also modulates inflammatory and other immune responses, such as stimulation of proinflammatory cytokine production. Immune modulation that occurs in obesity could increase the susceptibility of obese individuals to infections. Some epidemiological studies have shown that obese patients have a higher incidence of postoperative and other hospital-related infections compared with patients of normal weight. Obese individuals have also been shown to exhibit poor wound healing and increased occurrence of skin infections.

An increased vulnerability, severity, or complications of certain infections in obesity may be related to a number of factors, such as select micronutrient deficiencies. In fact, deficiencies or inadequacies of the B vitamins and vitamins A, C, D, and E have been associated with obesity, probably because energy-dense but micronutrient-poor foods are consumed. Certain mineral deficiencies may also be linked to obesity. For example, one study in obese children and adolescents associated impairments in cell-mediated immunity with deficiencies in zinc and iron. Overall, immune responses appear to be compromised in obesity, but more research is needed to clarify the relationship between obesity and infection-related morbidity and mortality.

In addition to dietary factors, lifestyle choices may play a role in immunity. Moderate, regular physical activity decreases biomarkers of systemic inflammation and may also enhance immune function, especially in sedentary individuals. In contrast, high-intensity exercise for prolonged periods (≥90 minutes) increases levels of C-reactive protein—a biomarker of cardiovascular and systemic inflammation—and may temporarily compromise responses of both innate and adaptive immunity. However, the effects of exercise on immune responses are probably influenced by a number of variables, including a person's age, genetics, overall health and nutritional status, as well as the type, intensity, and duration of exercise. More clinical research is needed to determine whether exercise-induced changes in immune functions translate to altered risk of various infections, such as the common cold and other respiratory tract infections.

For more detailed information on nutrition and immunity, see the article in the Micronutrient Information Center.

This article was underwritten, in part, by a grant from Bayer Consumer Care AG, Basel, Switzerland.

Last updated November 2010