Vitamin and Mineral Supplement Use Is Associated with Reduced
Risk of Prostate Cancer1
Alan R. Kristal,2Janet L. Stanford, Jennifer H. Cohen,
Kristine Wicklund, and Ruth E. Patterson
Cancer Prevention Research Program, Fred Hutchinson Cancer Research
Center, Seattle, Washington 98109 [A. R. K., J. H. C., R. E. P.]; Department of
Epidemiology, University of Washington, Seattle, Washington 98195 [A. R. K.,
J. L. S., J. H. C., R. E. P.]; and Epidemiology Program, Fred Hutchinson
Cancer Research Center, Seattle, Washington 98109 [J. L. S., K. W.]
This population-based, case-control study in King
County, Washington examined supplement use in 697
incident prostate cancer cases (ages 40–64) identified
from the Puget Sound Surveillance, Epidemiology and
End Results program registry and 666 controls recruited
from the same overall population using random-digit
dialing sampling. Participants reported their frequency of
use of three types of multivitamins and single
supplements of vitamins A, C, and E, calcium, iron, and
zinc over the 2 years before diagnosis. Logistic regression
analyses controlled for age, race, education, family
history of prostate cancer, body mass index, number of
prostate-specific antigen tests in the previous 5 years, and
dietary fat intake. Adjusted odds ratios (95% confidence
limits) for the contrast of >7/week versus no use were as
follows: multivitamins, 0.96 (0.73, 1.26); vitamin A, 0.59
(0.32, 1.06); vitamin C, 0.77 (0.57, 1.04); vitamin E, 0.76
(0.54, 1.08); calcium, 1.04 (0.61, 1.78); iron, 0.50 (0.13,
1.76); and zinc, 0.55 (0.30, 1.00). Odds ratios differed
little when cases were stratified by stage of disease at
diagnosis or by histopathological grade. There were
significant dose-response effects for zinc and ordered
dose-response trends for vitamins C and E. Overall, these
results suggest that multivitamin use is not associated
with prostate cancer risk, but use of individual
supplements of zinc, vitamin C, and vitamin E may be
protective. Further study is needed to investigate the
direct role of these dietary supplements, as well as the
role of lifestyle variables associated with supplement use,
on prostate cancer risk.
In the United States, prostate cancer is the most common cancer
among men and second only to lung cancer as the leading cause
of cancer-related mortality (1). Control of prostate cancer is
based primarily on early detection and treatment, because
known risk factors for prostate cancer are either not modifiable
(increasing age and a family history of prostate cancer) or not
well understood (black race). However, there is increasing
evidence that dietary patterns and use of dietary supplements
are associated with prostate cancer risk (2, 3). Further research
on dietary supplements is of considerable importance, because
supplementation could be an inexpensive and easily imple-
mented means for primary prevention.
Few epidemiological studies have reported on associations
between supplement use and prostate cancer risk (4). The
strongest evidence for a protective effect of dietary supplements
comes from two large, randomized controlled trials. In the
ATBC3trial, which tested 50 mg of ?-tocopherol and 20 mg of
?-carotene for the prevention of lung cancer among smokers,
there was an unexpected 30% reduction in prostate cancer
incidence among participants randomized to receive ?-tocoph-
erol compared to placebo (5). In the Dietary Prevention of
Cancer Trial, which tested 100 ?g of organic selenium for the
prevention of skin cancer, there was an unexpected 60% re-
duction among prostate cancer incidence in participants ran-
domized to receive the active agent (6). The only other signif-
icant finding of supplement use with prostate cancer risk was
from the Health Professionals Follow-Up Study, which found
an approximate 3-fold increase for advanced disease associated
with calcium supplementation of greater than 900 mg (7). No
associations of supplementation were found in three random-
ized trials of ?-carotene (8–10) or in a cohort study of the
elderly examining vitamins A, C, and E (11).
This report gives results from a large population-based
case-control study of middle-aged men and examines associa-
tions of dietary supplement use with prostate cancer risk.
Participants and Methods
Data are from a subset of participants in a study of risk factors
for prostate cancer. Eligible participants were white and black
male residents of King County (Seattle) Washington, ages
40–64 years, who were newly diagnosed with histologically
confirmed prostate cancer between January 1, 1993, and De-
cember 31, 1996. Cases were identified from the Seattle-Puget
Sound SEER cancer registry. Only cases with a residential
telephone were eligible, because controls were selected using
Furthermore, because the emphasis was on recruiting
younger men, only a random 75% sample of cases ages 60–64
were recruited. Of 917 cases selected for participation, 753
(82.1%) were interviewed. Reasons for nonresponse were phy-
sician refusal to allow contact (2.6%), case refusal (12.5%),
Received 3/22/99; revised 6/23/99; accepted 7/21/99.
The costs of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked advertisement in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1Supported by NIH Grants R01-CA56678, P30-CA15704, T32-CA09661, and
2To whom requests for reprints should be addressed, at Fred Hutchinson Cancer
Research Center, MP-702, 1100 Fairview Avenue North, Seattle, WA 98109-
3The abbreviations used are: ATBC, ?-Tocopherol, ?-Carotene; PSA, prostate-
specific antigen; SEER, Surveillance, Epidemiology and End Results program.
887Vol. 8, 887–892, October 1999
Cancer Epidemiology, Biomarkers & Prevention
17. Agresti, A. An Introduction to Categorical Data Analysis. New York: John
Wiley & Sons, 1996.
18. Zaichick, V. Y., Sviridova, T. V., and Zaichick, S. V. Zinc in the human
prostate gland: normal, hyperplastic and cancerous. Int. Urol. Nephrol., 29:
19. Whelan, P., Walker, B. E., and Kelleher, J. Zinc, vitamin A, and prostate
cancer. Br. J. Urol., 55. 525–528, 1983.
20. Lekili, M., Ergen, A., and Celebi, I. Zinc plasma levels in prostatic carcino-
mas and BPH. Int. Urol. Nephrol., 23: 151–154, 1991.
21. Cousins, R. J. Zinc. In: E. E. Ziegler and L. J. Filer (eds.), Present Knowledge
in Nutrition, pp. 293–306. Washington, DC: ILSI Press, 1996.
22. Eichholzer, M., Stahelin, H. B., Ludin, E., and Bernasconi, F. Smoking,
plasma vitamins D, E, retinol, and carotene, and fatal prostate cancer: seventeen-
year follow-up of the prospective Basel study. Prostate, 38: 189–198, 1999.
23. Knekt, P., Aromaa, A., Maatela, J., Ritva-Kaarina, A., Nikkari, T., Hakama,
M., Hakulinen, T., Peto, R., Saxen, E., and Teppo, L. Serum vitamin E and risk
of cancer among Finnish men during a 10-year follow-up. Am. J. Epidemiol.,
127: 28–40, 1988.
24. Hartman, T. J., Albanes, D., Pietinen, P., Hartmen, A. M., Rautalahti, M.,
Tangrea, J. A., and Taylor, P. R. The association between baseline vitamin E,
selenium, and prostate cancer in the ?-tocopherol, ?-carotene cancer prevention
study. Cancer Epidemiol., Biomarkers Prev., 7: 335–340, 1998.
25. Nomura, A. M., Stemmermann, G. N., Lee, J., and Craft, N. Serum micro-
nutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epide-
miol., Biomarkers Prev., 6: 487–491, 1997.
26. Hsing, A. W., Comstock, G. W., Abbey, H., and Polk, B. F. Serologic
precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate
cancer. J Natl. Cancer Inst., 82: 941–946, 1990.
27. Gann, P., Ma, J., Giovannucci, E., Willett, W., Sacks, F., Hennekens, C., and
Stampfer, M. Lower prostate cancer risk in men with elevated plasma lycopene
levels: results of a prospective analysis. Cancer Res., 59: 1225–1230, 1999.
28. Willett, W. C., Polk, B. F., Morris, J. S., Stampfer, M. J., Pressil, S., Rosner,
B., Taylor, J. O., Schneider, K., and Hames, C. G. Prediagnostic serum selenium
and risk of cancer. Lancet, 2: 130–134, 1983.
29. Levine, M., Rumsey, S., Wang, Y., Park, J., Kwon, O., Xu, W., and Amano,
N. Vitamin C. In: E. E. Ziegler and L. J. Filer (eds.), Present Knowledge in
Nutrition, pp. 146–159. Washington, DC: ILSI Press, 1996.
30. Lee, M. M., Wang, R. T., Hsing, A. W., Gu, F. L., Wang, T., and Spitz, M.
Case-control study of diet and prostate cancer in China. Cancer Causes Control,
9: 545–552, 1998.
31. Carter, B. S., Bova, G. S., Beaty, T. H., Steinberg, G. D., Childs, B., Issacs,
W. B., and Walsh, P. C. Hereditary prostate cancer: epidemiologic and clinical
features. J. Urol., 150: 797–802, 1993.
32. Woold, S. H. Screening for prostate cancer with prostate-specific antigen: an
examination of the evidence. N. Engl. J. Med., 333: 1041–1405, 1995.
33. Close, D., Kristal, A., Patterson, R., and White, E. Associations of demo-
graphic and health-related characteristics with prostate cancer screening in Wash-
ington State. Cancer Epidemiol., Biomarkers Prev., 7: 627–630, 1998.
34. Patterson, R. E., Neuhouser, M. L., White, E., Hunt, J. R., and Kristal, A. R.
Cancer-related behavior of vitamin supplement users. Cancer Epidemiol., Bi-
omarkers Prev., 7: 79–81, 1998.
35. Block, G., Sinha, R., and Gridley, G. Collection of dietary-supplement data
and implications for analysis. Am. J. Clin. Nutr., 59: 232S–239S, 1994.
36. Patterson, R. E., Kristal, A. R., Levy, L., McLerran, D., and White, E.
Validity of methods used to assess vitamin and mineral supplement use. Am. J.
Epidemiol., 148: 643–649, 1998.
37. Psaty, B. M., Lee, M., and Savage, P. J. Assessing the use of medications in
the elderly: methods and initial experience in the Cardiovascular Health Study.
J. Clin. Epidemiol., 45: 683–692, 1992.
38. Patterson, R. E., Neuhouser, M. L., White, E., Kristal, A. R., and Potter, J. D.
Measurement error from assessing use of vitamin supplements at one point in
time. Epidemiology, 9: 567–569, 1998.
39. Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., Wang, G. Q., Yang,
C. S., Zheng, S. F., Gail, M., Li, G. Y., Yu, Y., Liu, B. Q., Tangrea, J., Sun, Y. H.,
Liu, F., Fraumini, J. F., Zhang, Y. H., and Li, B. Nutrition intervention trials in
Linxian, China: supplementation with specific vitamin/mineral combinations,
cancer incidence, and disease-specific mortality in the general population. J. Natl.
Cancer Inst., 85: 1483–1492, 1993.
Vitamin and Mineral Supplements and Prostate Cancer