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Calcium and Fructose Intake in Relation to Risk of Prostate Cancer¹

Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115 [E. G., E. B. R., M. J. S., W. C. W.]; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115 [E. G., E. B. R., A. A., M. J. S., G. A. C., W. C. W.]; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115 [E. B. R., A. A., M. J. S., G. A. C., W. C. W.]; and Department of Medical Epidemiology, Karolinska Institute, S-171 77 Stockholm, Sweden [A. W.]

Laboratory and clinical data indicate an antitumor effect of 1,25(OH)₂ vitamin D (1,25(OH)₂D) on prostate cancer. High calcium intake suppresses formation of 1,25(OH)₂D from 25(OH)D, thereby decreasing the 1,25(OH)₂D level. Ingestion of fructose reduces plasma phosphate transiently, and hypophosphatemia stimulates 1,25(OH)₂D production. We thus conducted a prospective study among 47,781 men of the Health Professionals Follow-Up Study free of cancer in 1986 to examine whether calcium and fructose intake influenced risk of prostate cancer. Between 1986 and 1994, 1369 non-stage A1 and 423 advanced (extraprostatic) cases of prostate cancer were diagnosed. Higher consumption of calcium was related to advanced prostate cancer [multivariate relative risk (RR), 2.97; 95% confidence interval (CI), 1.61–5.50 for intakes 2000 mg/day versus <500 mg/day; P, trend, 0.002] and metastatic prostate cancer (RR, 4.57; CI, 1.88–11.1; P, trend, <0.001). Calcium from food sources and from supplements independently increased risk. High fructose intake was related to a lower risk of advanced prostate cancer (multivariate RR, 0.51; CI, 0.33–0.80, for intakes >70 versus 40 g/day; P, trend, 0.007). Fruit intake was inversely associated with risk of advanced prostate cancer (RR, 0.63; 95% CI, 0.43–0.93; for >5 versus 1 serving per day), and this association was accounted for by fructose intake. Non-fruit sources of fructose similarly predicted lower risk of advanced prostate cancer. A moderate positive association between energy-adjusted fat intake and advanced prostate cancer was attenuated and no longer statistically significant when controlled for calcium and fructose. Our findings provide indirect evidence for a protective influence of high 1,25(OH)₂D levels on prostate cancer and support increased fruit consumption and avoidance of high calcium intake to reduce the risk of advanced prostate cancer.

¹ Supported by Grants CA 55075 and HL 35464 from the NIH and Special Institution Grant 18 from the American Cancer Society.

² To whom requests for reprints should be addressed, at Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115.

Received 7/10/97. Accepted 11/26/97.

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