CORRESPONDENCE

Re: Zinc Supplement Use and Risk of Prostate Cancer

Cheryl A. Krone, Louis C. Harms

Affiliations of authors: C. A. Krone, Applied Research Institute, Palmerston North, New Zealand; L. C. Harms, Applied Research Institute, Evanston, IL.

Correspondence to: Cheryl A. Krone, PhD, Applied Research Institute, P.O. Box 1969, Palmerston North, New Zealand (e-mail: cakrone{at}u.washington.edu).

Although the etiology of prostate cancer is still virtually unknown, some epidemiologic, experimental, and dietary supplement studies have provided evidence of a protective role for zinc in the development and progression of prostate malignancy. However, results of other studies have suggested that high intraprostatic zinc levels may increase prostate cancer risk. The recent study in the Journal by Leitzmann et al. (1) amplifies this concern by reporting that an increased risk of advanced prostate cancer is associated with zinc intake of greater than 100 mg/day, as well as with the long-term (i.e., >10 years) use of supplemental zinc. However, no strong evidence could be identified in support of specific mechanisms for the observed associations. We suggest that the presence of cadmium in some zinc supplements could contribute to the observed association between zinc supplement use and prostate cancer risk (2).

Contrary to the physiologic and potentially beneficial effects of zinc, cadmium has been implicated epidemiologically and experimentally in the etiology of prostate cancer (3). Cadmium induces conformational changes in p53, presumably by replacing zinc atoms that normally bind this protein, and impairs the DNA-binding activity of p53 and the subsequent induction of cell cycle arrest after DNA damage (4). Malignant transformation of human prostate epithelial cells in vitro was associated with exposure to a cadmium concentration at the low end of the concentration range found in human prostates of men who do not have occupational cadmium exposure (5).

Zinc and cadmium have very similar chemical properties and are invariably found together in nature. All commercially available zinc supplements that we analyzed (2) contained detectable levels of cadmium; however, the amounts varied by almost 40-fold when based on a fixed amount of zinc (e.g., 15 mg, the recommended daily allowance for zinc). We estimate that consumption of approximately 140 mg/day of zinc [the median daily level of zinc supplement intake among the high-intake group studied by Leitzmann et al. (1)] in the zinc supplement that we found contains the highest cadmium-to-zinc ratio would yield a cadmium dose of approximately 19 µg/day. This dose is nearly double the total mean daily exposure to cadmium from foods, excluding shellfish, as estimated in the U.S. Food and Drug Administration Total Diet Study (i.e., 10 µg cadmium/person/day). For members of the general public that are not occupationally exposed to cadmium, food is the major route of cadmium uptake. Humans accumulate cadmium with age; the biologic half-life of cadmium is on the order of decades. It has been suggested that even small repeated low doses of cadmium could accumulate in the body and mimic the activities of zinc, leading to the adverse effects on prostate health associated with cadmium intake (5).

Our results suggest that zinc supplements with relatively low cadmium levels can and should be produced [e.g., supplements containing the gluconate form of zinc uniformly had lower levels of cadmium than those containing zinc sulfate or zinc as an amino acid chelate (2)]. The risks and benefits associated with dietary supplements deserve further study because dietary supplementation could be an inexpensive and easy way to prevent various malignancies and other disorders. However, it is necessary to use caution when adopting dietary supplement regimens. Not only can there be undetected or unknown toxic chemicals in such supplements, but the action of pure dietary components such as zinc at pharmacologic doses does not always produce the expected effects. A further example of this is the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial, in which an unanticipated and undesirable increase in lung cancers was observed among the cigarette smokers given pharmacologic doses of beta-carotene (6). Indeed, one could also ask of zinc supplements: are they friend or foe?

REFERENCES

1 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;95:1004–7.[Abstract/Free Full Text]

2 Krone CA, Wyse E, Ely JT. Cadmium in zinc-containing mineral supplements. Int J Food Sci Nutr 2001;52:379–8.[CrossRef][ISI][Medline]

3 Waalkes MP, Rehm S, Coogan TP, Ward JM. Role of cadmium in the etiology of cancer of the prostate. In: Thomas JA, Colby HD, editors. Endocrine toxicology. 2nd ed. Washington (DC): Taylor & Francis; 1997. p. 227–43.

4 Meplan C, Mann K, Hainaut P. Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells. J Biol Chem 1999;274:31663–70.[Abstract/Free Full Text]

5 Achanzar WE, Diwan BA, Liu J, Quader ST, Webber MM, Waalkes MP. Cadmium-induced malignant transformation of human prostate epithelial cells. Cancer Res 2001;61:455–8.[Abstract/Free Full Text]

6 Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996;88:1560–70.[Abstract/Free Full Text]



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