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.


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

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