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Zinc and copper are so similar in their atomic structure that they can actually compete with one another, not only for absorption, but also for utilization in the body's biochemical pathways. When your intake of zinc is too high relative to your copper intake, the excess zinc actually interferes with the activity of enzymes, which depend on copper for their biological function, by stepping in to copper's proper binding sites in the enzymes.When copper is not properly incorporated into these enzymes, they can't fulfill their biochemical duties.
A high intake of zinc, without a balancing increase in copper intake, can therefore lead to a secondary, functional copper deficiency by competing for absorption and interfering with its metabolism. Research suggests that an excessive ratio of zinc to copper has a negative impact on cardiovascular and skeletal health.
Both animal and human evidence suggests that, for optimal utilization of both minerals, the balance between zinc and copper should be about ten-to-one. But it's common for supplements containing these nutrients to include too much zinc, and little or no copper, with the result that many - perhaps most - zinc supplements and multivitamin multivitamin and multimineral formulas contain potentially harmful zinc imbalances.
This isn't just a theoretical concern. In a series of human studies, putting volunteers on a diet and supplement regimen in which the ratio between zinc and copper was 23.5-to-one (and sometimes lower) - common zinc-to-copper ratios, found in many multivitamins on health food store shelves - resulted in wide-ranging metabolic disturbances, including reduced levels of the copper-based antioxidants enzymes cytosolic superoxide dismutase and ceruloplasmin, increased total and LDL ("bad") cholesterol, anemia, reductions in the body's levels of enkephalins (natural pain-killing molecules), and cardiac dysfunction (including rhythm disturbances and even heart attacks!).
At the extreme, out-of control zinc supplementation impairs immune function, despite the fact that an adequate intake of zinc is necessary for normal immune function. This is especially galling, considering that the most common reason for zinc supplementation is to support healthy immunity. One reason for this may be copper's important role in immune function: one of the classic signs of ‘simple' copper deficiency is depressed levels of important white blood cells (leukocytes and neutrophils).
Over the long term, it seems that other problems linked to long-term, subclinical ‘simple' copper deficiency - such as impaired bone metabolism, poor glucose metabolism, arthritis, neurological dysfunction, and increased levels of Advanced Glycation Endproducts (AGE) - would also manifest from a functional copper deficiency created by excessive zinc intake, leading top copper researcher Dr. Leslie M. Klevay to warn of the "hazards of zinc supplements." The problem, of course, is not zinc supplements - but excessive or unbalanced zinc supplementation.
Excessive Zinc and Prostate Health
The most ironic twist in the tale of overemphasis on zinc has only recently appeared. Many men take zinc supplements to support the health of their prostates, because the prostate has the highest levels of this mineral of any organ of the body, and most studies have found that low levels of zinc in the prostate are associated with benign prostatic hypertrophy (BPH) and prostate cancer. But a large new study, which tracked the health habits of nearly 50 000 American male health professionals for 14 years, found that extreme zinc oversupplementation is associated with a more than doubled risk of developing prostate cancer, especially if continued for more than 10 years.
This doesn't mean that men concerned about prostate health should stop making sure that their zinc intake is adequate: there was no association of zinc supplement use and prostate cancer in men with more reasonable intakes of the mineral. But it does mean that the targets that we should aim for are the kinds of intakes typical of a healthy diet - meaning a supplement designed for sustainable, long-term use should not contain more than about 11 milligrams of zinc.
Copper, Free Radicals, and Heart Health
Aside from an overemphasis on the benefits of zinc and a mysterious tendency to ignore copper's benefits, much of the reason for unbalanced zinc supplementation has come from the myth that copper is a ‘pro-oxidant' mineral, which might accelerate free radical damage in the body. The reason for this concern is the so-called Fenton reaction, whereby "transition metals" (such as iron and copper), when present in their free, ionic form, can catalytically convert the mildly-dangerous hydrogen peroxide into the vicious hydroxyl radical.
But while copper ions can trigger the Fenton reaction in the artificial conditions of the test tube, it's a non-issue from a health perspective - because the body just doesn't contain enough free, ionic copper to be of concern. Test-tube studies showing that ionic copper can accelerate the oxidation of LDL (‘bad') cholesterol, for instance, have used copper ion concentrations that are literally millions of times as high as are found in the body. In fact, controlled human studies have shown that even at high intakes (up to 7 milligrams a day), copper supplements don't increase free radical damage in the body, but actually tend to decrease it, probably because of the nutrient's indispensable role in the body' antioxidant defenses.
Zinc and copper are both key minerals. You need both minerals - and you need them in balance.
References
Sandstead HH. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr. 1995 Mar; 61(3 Suppl): 621S-624S.
Klevay LM. Lack of a recommended dietary allowance for copper may be hazardous to your health. J Am Coll Nutr. 1998 Aug; 17(4): 322-6.
Allen GD, Klevay LM. Copper: an antioxidant nutrient for cardiovascular health. Curr Opin Lipidol. 1994 Feb; 5(1): 22-8.
Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. 2003 Jul 2; 95(13): 1004-7.
Lowe NM, Lowe NM, Fraser WD, Jackson MJ. Is there a potential therapeutic value of copper and zinc for osteoporosis? Proc Nutr Soc. 2002 May; 61(2): 181-5.
Serum zinc and pneumonia in nursing home elderly
American Journal of Clinical Nutrition, Vol. 86, No. 4, 1167-1173
Simin N Meydani, Junaidah B Barnett, Gerard E Dallal, Basil C Fine, Paul F Jacques, Lynette S Leka and Davidson H Hamer
Background: Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied.
Objective: The objective was to determine whether serum zinc concentrations in nursing home elderly are associated with the incidence and duration of pneumonia, total and duration of antibiotic use, and pneumonia-associated and all-cause mortality.
Design: This observational study was conducted in residents from 33 nursing homes in Boston, MA, who participated in a 1-y randomized, double-blind, and placebo-controlled vitamin E supplementation trial; all were given daily doses of 50% of the recommended dietary allowance of essential vitamins and minerals, including zinc. Participants with baseline (n = 578) or final (n = 420) serum zinc concentrations were categorized as having low (<70 µg/dL) or normal (70 µg/dL) serum zinc concentrations. Outcome measures included the incidence and number of days with pneumonia, number of new antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and all-cause mortality.
Results: Compared with subjects with low zinc concentrations, subjects with normal final serum zinc concentrations had a lower incidence of pneumonia, fewer (by almost 50%) new antibiotic prescriptions, a shorter duration of pneumonia, and fewer days of antibiotic use (3.9 d compared with 2.6 d) (P 0.004 for all). Normal baseline serum zinc concentrations were associated with a reduction in all-cause mortality (P = 0.049).
Conclusion: Normal serum zinc concentrations in nursing home elderly are associated with a decreased incidence and duration of pneumonia, a decreased number of new antibiotic prescriptions, and a decrease in the days of antibiotic use. Zinc supplementation to maintain normal serum zinc concentrations in the elderly may help reduce the incidence of pneumonia and associated morbidity.
Requirements and toxicity of essential trace elements, illustrated by zinc and copper.
Am J Clin Nutr. 1995 Mar; 61(3 Suppl): 621S-624S.
Sandstead HH.
Early signs of toxicity of essential trace elements are important. Some trace elements are available over-the-counter (OTC) and/or are present at industrial waste sites. Physicochemically similar trace elements compete for ligands, impairing functions, which is exemplified by the zinc-copper antagonism described long ago by Van Campen, Hill and Matrone, and Klevay. Intestinal absorption of copper is inhibited by zinc. Thus risk of copper deficiency is increased when the molar ratio of zinc to copper (Zn:Cu) is high. As shown by experiments, copper deficiency can occur in humans. Manifestations include decreased erythrocyte copper-zinc superoxide dismutase, increased low-density-lipoprotein cholesterol, decreased high-density-lipoprotein cholesterol, decreased glucose clearance, decreased methionine and leucine enkephalins, and abnormal cardiac function. Calculation of a preliminary reference dose for OTC zinc that assumed high bioavailability and uncertain copper intakes established 9 mg as a safe amount for 60-kg adults.
Lack of a recommended dietary allowance for copper may be hazardous to your health.
J Am Coll Nutr. 1998 Aug; 17(4): 322-6.
Klevay LM.
The 10th edition of Recommended Dietary Allowances (RDA) did not include an RDA for copper; rather a safe and adequate daily intake was suggested. Criteria, history and uses of RDAs were summarized along with data on dietary intakes, balance and depletion experiments, low (fats and oils, skim milk and yogurt) and high (legumes, mushrooms, nuts and seeds) copper foods and hazards of zinc supplements. Bone disease and cardiovascular disease from diets-low in copper have been studied in animals for decades. Men and women fed diets close to 1 mg of copper per day, amounts quite frequent in the US, responded similarly to deficient animals with reversible, potentially harmful changes in blood pressure control, cholesterol and glucose metabolism, and electrocardiograms. Women supplemented with trace elements including copper experienced beneficial effects on bone density. These data exceed similar data on magnesium, selenium and zinc and are sufficient for establishing an RDA. Ischemic heart disease and osteoporosis are likely consequences of diets low in copper. Numerous anatomical, chemical and physiological similarities between animals deficient in copper and people with ischemic heart disease have been noticed. Association between osteoporosis and low copper status deserves further inquiry. Augmenting low copper diets with high copper foods may be beneficial. Committees that establish RDAs should return to the traditions of the first nine editions and make recommendations that promote health and nutritional welfare, meet functional needs, prevent disease and promote public welfare.
Copper: an antioxidant nutrient for cardiovascular health.
Current Opinion in Lipidology. 1994 Feb; 5(1): 22-8.
Allen GD, Klevay LM.
Dietary copper often is low in the Western diet; low intakes may affect all stages of atherosclerosis adversely. Impaired oxidative defense in copper deficiency contributes to hypercholesterolemia, hypertension, and impaired prostaglandin metabolism. Free copper ion does not exist in vivo; some in-vitro experiments are conducted with millions-fold excesses.
Zinc supplement use and risk of prostate cancer.
J Natl Cancer Inst. 2003 Jul 2; 95(13): 1004-7.
Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL.
The high concentration of zinc in the prostate suggests that zinc may play a role in prostate health. We examined the association between supplemental zinc intake and prostate cancer risk among 46 974 U.S. men participating in the Health Professionals Follow-Up Study. During 14 years of follow-up from 1986 through 2000, 2901 new cases of prostate cancer were ascertained, of which 434 cases were diagnosed as advanced cancer. Supplemental zinc intake at doses of up to 100 mg/day was not associated with prostate cancer risk. However, compared with nonusers, men who consumed more than 100 mg/day of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; P(trend) =.003), and men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; P(trend)<.001). Although we cannot rule out residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use, our findings, that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation.
Is there a potential therapeutic value of copper and zinc for osteoporosis?
Proc Nutr Soc. 2002 May; 61(2): 181-5.
Lowe NM, Lowe NM, Fraser WD, Jackson MJ.
Osteoporosis is almost universal in very old age, and is a major cause of morbidity and mortality in the elderly of both sexes. Bone is lost at a rate of 0.2-0.5 %/year in both men and women after the age of 40-45 years. The causes of age-related changes in bone mass are multifactorial and include genetic predisposition, nutritional factors, endocrine changes, habitual exercise levels and body weight. Bone loss is accelerated to 2-5 % year immediately before and for up to 10 years post-menopause (Heaney, 1986). In women hormone-replacement therapy is effective in reducing the rate of bone loss caused by this peri-menopausal decrease in hormone levels (Smith & Studd, 1993); however, in men and older women (>10 years post-menopause) nutrition plays a key role in the rate of bone loss. One factor contributing to bone loss in the elderly may be a subclinical Zn and/or Cu deficiency, due to a reduced dietary intake of micronutrients and reduced absorption (Thomson & Keelan, 1986). Zn and Cu are essential cofactors for enzymes involved in the synthesis of various bone matrix constituents. Paradoxically, Ca supplementation may accentuate the problem of reduced Zn and Cu levels by impairing the absorption of simultaneously-ingested Zn and the retention of Cu (Snedeker et al. 1982; Grekas et al. 1988). The present paper will review the current literature on the potential benefits of Cu and Zn supplementation in reducing bone loss, and present new information on the effect of Ca supplementation on Zn and Cu status in post-menopausal women with osteoporosis.
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