Zinc & Immune System Function

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DietaryTipsForHBP , From: JoAnn Guest Fri, 9 Jul 2004 18:12:16 -0700 (PDT) Zinc & Immune System FunctionZinc & Immune System Function http://www.willner.com/References/webref19.htm It is clearly established that adequate supplies of zinc are essential to the development and maintenance of a healthy immune system and that aging is associated with immune impairment that can be partially repaired with zinc supplementation. There are many groups in our population at increase risk of at least marginal zinc deficiency. We now know that the elderly may be getting insufficient zinc in their diets. Another problem related to zinc is macular degeneration. "Because this disorder affect parts of the eyes in

which zinc is known to have an important impact on the metabolic function of enzymes crucial in vision, investigators hypothesized that zinc deficiencies might play a role in the disease. to test this idea they constructed a double-blind, placebo-controlled trial involving 151 patients afflicted by this condition. In a 12 to 24 month follow-up they found that the patients given zinc supplements had significantly less visual loss than the group that got placebos. The zinc was given in 100 mg tablets, twice a day with meals. Side effects were minimal." (Sheldon Saul Hendler, Md, Phd, The Doctors’ Vitamin & Mineral Encyclopedia, Simon & Shuster) The following study provides another cause for concern about adequate zinc levels: Zinc deficiency may increase arterial oxidative stress The starting point of this study was the observation that zinc deficiency severely impairs endothelial cell function, an effect reversed by zinc supplementation. To determine

how zinc affects cytokine production, the activation of a nuclear transcription factor (NF-kB)was examined in endothelial cell cultures. NF-kB was chosen because this transcription factor activates genes directing the synthesis of proinflammatory cytokines and to increased oxidative stress. Cells deprived of zinc were triggered by tumor necrosis factor (TNF). TNF signals a cascade of events leading to the synthesis of proteins that regulate oxidative stress and promote free radicals. Zinc supplementation reversed the activation by TNF in these cells: zinc inhibited activation of oxidative stress transcription factors and the synthesis of Interleukin 8 and promoted a return to homoeostatic balance. Comment: Arteries are vulnerable to ongoing oxidative stress due to exposure to oxidizing agents such as drugs and free radicals, including superoxide and lipid peroxyl radicals. Blood contains an elaborate array of antioxidants, including ascorbic acid, uric acid and defensive

serum proteins to limit this damage. However, antioxidant defenses are not 100% efficient. Zinc participates in these defenses by serving as a cofactor for the antioxidant enzyme, superoxide dismutase. Other aspects of zinc Metabolism must be involved, since zinc deficiency causes profound oxidative damage to proteins, lipids and DNA. As one example of a nonenzymatic function, zinc is a cell membrane stabilizer. In addition, this paper shows that zinc deficiency seems to regulate cytokine-mediated activation of transcription factors, especially those triggering inflammation and oxidative stress. If zinc deficiency promotes activation of oxidative stress and inflammatory cytokines by endothelial cells, thenzinc status may be important in the development of atherosclerosis. Zinc is removed by food processing and subclinical deficiencies are-likely with compromised diets. Connell P et al. Zinc attenuates tumor necrosis factor-mediated activation of transcription factors in

endothelial cells. J Am College Nutr 1997; 16: 411-417. To provide more information on zinc, we are excerpting an article from the magazine, Health & Nutrition Breakthroughs, published by New Hope Natural Media, written by Dr. Michael Janson: Zinc— Immune System’s Missing Link? by Michael Janson, M.D. To the general public, minerals are far less understood or valued than vita mins, though both are equally important to physiological functions. Among minerals themselves, calcium, magnesium and iron receive a disproportionate amount of attention, even though other minerals are equally necessary. Actually, all nutrients work in concert in our tissues to keep us healthy. One may well wonder, therefore, why some minerals are held in so much higher esteem than others. Well, calcium’s popularity, for example, is due largely to advertising by the dairy industry to underscore the importance of milk, and iron is well known because its deficiencies are so

easy to detect. Mineral nutrients can be found in varying quantities in both our diets and our bodies. When they are present in our bodies in large amounts (measured in grams), they’re called major minerals and include calcium, chlorine, magnesium, phosphorus, potassium, sodium and sulfur. Those that occur in smaller quantities (measured in milligrams or micrograms) are called trace minerals and include boron, chromium, cobalt, copper, iodine, iron, manganese, selenium, silicon and zinc. Deficiencies of either major or trace minerals can be as devastating to one’s health as a lack of other better-known nutrients such as vitamins A, C, E and B complex. . A Zinc Deficiency Can Be Devastating to Overall Health Though zinc gets little attention, it is critical to a healthy body. Without it, more than 300 enzymes including trypsin and alcohol dehydrogenase cannot work properly, and physiological functions such as digestion and alcohol metabolism break down. The

human body generally contains 1.4 g to 2.5 g of zinc.1 Much of this zinc is found in muscle and bone. It is also present in skin, hair and nails, as well as in the retina of the eye and in the prostate gland. One of zinc’s most essential roles is for the white blood cells of the immune system, where it helps the body fight off a range of viral infections—from strep and influenza to herpes and the common cold. Some white blood cells produce antibodies (humoral immunity), while others are phagocytes that attack and destroy invaders, thereby providing cellular immunity. The thymus gland, located just under the sternum, controls some of our immune functions and is affected by the amount of zinc in the body. For instance, the thymus produces thymulin, a thymic peptide that is responsible for cell-mediated immunity. As we age, the thymus gland diminishes in function and size-from nearly the same size as the heart in infants to almost undetectable in elderly people. This

happens in both humans and animals. Although long considered a normal process, it appears related to zinc nutritional status. A zinc supplement given to aging mice restored the function of their thymus glands and led to the glands’ regrowth.2 Researchers thus concluded that the usual involution of the thymus gland is not inevitable and can be reversed with zinc supplements. Thymus-derived cells (T-cells) andnatural killer cells likewise depend on zinc. Both T-cells and natural killer cells support a variety of immune-system functions such as destroying foreign cells, vitally infected cells and cancer cells. An in vitro study showed that zinc increased the response of T-cells to all immune stimuli by 100 percent.3 The authors concluded that "treatment with zinc may have immunotherapeutic relevance, particularly in the aged and stressed organism." Zinc has been linked to the body’s ability to resist viruses, especially respiratory infections.4 In a group of

malnourished children in Ecuador, supplementation with zinc significantly reduced the incidence of cough, fever and respiratory secretions compared to placebo. However, after supplementation ceased, the symptoms returned to previous levels. In addition, two Italian doctors concluded that zinc deficiencies in elderly people may lead to depression of both humoral and cellular immunity, a significant increase of susceptibility to infections, and an increase in morbidity and mortality.5 Zinc deficiency is often the result of a poor diet-it is one of the hallmarks of malnourishment-but it can also be caused by poor intestinal absorption or excessive zinc loss resulting from trauma, bums, stress, bleeding, diabetes or chelation therapy (proper protocol for chelation includes zinc supplements). It is difficult to evaluate the body’s level of zinc because no single laboratory test is ideal. Physicians must therefore rely on the signs and symptoms of zinc deficiency as well as lab

tests. Supplementing with zinc is quite safeits only significant side effect is lowered copper levels in the body tissues, since the two minerals compete for absorption. Considering zinc’s safety, people should consider taking zinc supplements, especially as they age-being sure to include copper in the proper balance. Most practitioners who supplement their patients’ diets with zinc also recommend taking copper at a ratio of 10 mg to 15 mg zinc for each milligram of copper. Zinc And The Common Cold Despite research showing that zinc improves immunity, clinicians still don’t know for certain if zinc supplements can help treat a common cold in people who are not grossly malnourished. (Studies on malnourished people may not accurately reflect how supplements affect a healthy person.) A number of studies, however, suggest that supplementation can help. A 1989 in vitro study showed that zinc chloride can inhibit growth of rhinoviruses, which along with

coronaviruses and adenoviruses are responsible for most colds.6 A 1984 clinical trial demonstrated that the duration of colds was cut in half in the subjects taking zinc (23 mg every two hours) compared to those taking a placebo.7 After seven days, 86 percent of the zinc group were free of symptoms, compared to only 46 percent of the placebo group. In a 1987 clinical study, it was shown that zinc gluconate lozenges reduced the symptom score from 8.2 to 5.7 (a 30 percent reduction) in subjects. who developed upper respiratory infections after being exposed to an infecting dose of rhinovirus.8 However, several investigators in early controlled studies did not find zinc helpful for treating colds.9,10 They suggested that the controls in previous studies (other than the ones mentioned above) were inadequate because the , intensely bitter taste of zinc would have made blinding difficult. The researchers also described side effects in the zinc-treated groups, but these were mainly

due to the taste of the zinc leading to nausea and temporarily altered taste buds. I I Yet even in this purportedly negative study, the authors admitted that the zinctreated group had reduced symptom severity-a statistically significant 7 percent to 9 percent. The dose of zinc and the specific zinc compounds used varied from study to study, and this may account for the discrepancies. Most recently, researchers demonstrated a significant reduction in cold symptoms in a group of 50 patients given zinc gluconate lozenges compared to a placebo group of 50 controls.12 The colds were significantly shorter in the zinc group than in the placebo group (4.4 days versus 7.6 days). The zinc group also had significantly fewer days of coughing, headache, hoarseness, nasal congestion, nasal drainage and sore throat. Recognizing that zinc lozenges apparently do help treat viral respiratory infections, other researchers attempted to identify some of the mechanisms at work, concluding

that the interruption of viral binding sites was most likely a factor.13 Supplements That Are Easy To Swallow One problem associated with zinc is no longer an issue-its bitter taste is easily masked in lozenge-type supplements. The supportive research cited suggests that lozenges are worth taking at the onset of a cold because of their potential to help treat viral upper respiratory infections. But zinc itself is by no means a cure-all nor an isolated magic bullet. Zinc supplements are best considered as part of a comprehensive immune-enhancing program that includes other nutrients such as vitamins A, B6, C and E. Essential fatty acids and Co-Q10 are also important to a healthy immune system and should be taken routinely. Immune stimulating herbs such as Echinacea angustifolia or E. purpurea and Oregon graperoot (Mahonia aquifolium) also help build immunity and reduce the symptoms of respiratory infection. Add a whole-foods diet low in sugar (sugar inhibits white

cell function), regular exercise and a stress -management program and you have a true prescription for a strong immune system. Michael Janson, M.D., is president of the American Preventive Medical Associ . ati . on and a fellow and president-elect of the American College for Advancement in Medicine. Janson is the author of The Vitamin Revolution in Health Care. He practices nutrition therapy, chelation therapy and preventive medicine at the Center for Preventive Medicine in Barnstable, Mass. REFERENCES 1. Under, M. ed. Nutritional Biochemistry and Metabolism New York: Elsevier Science Publishing 1991. 2. Mocchegiani, E., et. al aL Reversibility of the thymic involution and of age-related peripheral immune dys functions by zinc upplementation in old mice." Int J Immunopharmacol 17(9): 703-18, September 1995. Saba, A.R_ et at. "Zinc induces thymulin secretion from human thymic epithelial cells in vitro and augments splenocyte and thymocyte responses in

vivo." Int J Immunopharmacol 17(9): 729-33, September 1995. 4. Sempertegui, F, et at. "Effects of short-term zinc sup, plementation cm cellular immunity, respiratory symptoms and growth of malnourished Equadorian children 1~ Eur J Clin Nutr 50(1): 42-46, January I 5 Ripa, S. & Ripa, R., "Zinc and the elderly." Minerva Med 1995, (6): 275-8, June 1995. 6. Merluzzi, %’J., et at. "Evaluation of zinc complexes on replication of rhinovirus 2 in vitro." Res Commim Chem Pathol Pharmacol 66(3):425-40, December 1989. 7 Eby, G.A., et in duration of common cold, by zinc gluconate lozenges in a double-blind study." Antimicrob Agents Che 25(l): 20-24, January 1984. 8. Al-Nak ib, W, et al. "Prophylaxis and treatment of rhino virus colds with zinc gluconate lozenges." J. anamicrob Chemother 20(6):893,901, December 1987. 9. Douglas’ R.M., "Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract

infection., in Australian adult,.- Antimicrob Agents Chemother 31(: 1263-65, August 1987. 10. Fair, B.M., et al. "Two randomized controlled trials of zinc gluconate lozenge therapy of experimentally induced hin.,i... colds." Antimicrob Agents Chemother, 31(: 1183-87, August 1987. 11. Smith, D.S., et al. "Failure of zinc gluconate in treatment of acute upper respiratory tract infection,." Antimicrob Agents chemother, 33 (5): 646-48, May 1989. 12. Mossad S.B., et al. "Zinc gluconate lozenges for treat, ing the common cold. A randomized, double-blind placebocontrolled study." Ann Intern Med 15;125(2): 81-88. July 1996. 13.Novick, S G., t al. "How does zinc modify the com- cold! Clinical observations and implications regarding mechanisms of action." Med Hypotheses 46(3): 295-302, March 1996. [excerpted from Health & Nutrition Breakthroughs, December 1997, New Hope Natural Media. (303) 939-8440.] Willner Chemists - The

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