Affiliations of authors: M. F. Leitzmann, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; E. L. Giovannucci, Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA.
Correspondence to: Michael F. Leitzmann, MD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd., EPS-MSC 7232, Bethesda, MD 20892 (e-mail: leitzmann{at}mail.nih.gov).
Krone and Harms suggest that the apparent adverse effect of zinc supplements on advanced prostate cancer risk is due to contamination of zinc supplements by cadmium. Cadmium exposure has not been consistently associated with prostate cancer incidence or mortality in epidemiologic studies of cadmium exposure determined by dietary, environmental, blood, or toenail assessment (13). However, because cadmium is a known carcinogen (4), the presence of cadmium in zinc supplements is of potential concern.
Data regarding the cadmium content of zinc supplements are limited to one study (5). That study found that single-mineral, zinc-only supplements contained trace amounts of cadmium (0.049 µg cadmium/15 mg zinc). By contrast, multi-mineral products containing a variety of other minerals in addition to zinc had more than 20 times the amount of cadmium (1.06 µg cadmium/15 mg zinc). As suggested by the authors, one possible reason for the increased cadmium content in multi-mineral supplements is their lower degree of purity than single-mineral products (5). Another possibility is that high cadmium amounts contained in multi-mineral supplements may be attributable to the presence of minerals other than zinc. For example, one study found markedly increased cadmium levels in calcium supplements (6).
Our study lacks data to rule out the possibility that zinc supplement use is positively linked to advanced prostate cancer because of cadmium contamination of supplements. However, excluding subjects who used multivitamin supplements and limiting the analysis to men using zinc-only supplements did not affect the observed positive association between zinc supplement use and risk of advanced prostate cancer in our study. Hence, it is unlikely that the associations we observed can be explained by a higher degree of impurity (i.e., higher cadmium content) of multi-mineral supplements. Notwithstanding, we agree with Krone and Harms that because certain types of dietary supplements may contain nonessential, and potentially harmful, trace elements, further research is warranted to determine the presence of such contaminants in supplements. Such studies may help clarify the riskbenefit trade-offs associated with dietary supplement use.
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