Dairy, calcium, and vitamin D intakes and prostate cancer risk

Nutrition Research Newsletter, June, 2005

Both ecologic and epidemiologic studies have fairly consistently found an increase in prostate cancer risk with intake of dairy foods. A strong ecologic correlation between milk intake and prostate cancer mortality was noted as early as 1975, and in a more recent ecologic analysis, the correlation was stronger for milk and prostate cancer mortality than for any other dietary factor, including red meat. Among epidemiologic studies, 7 of 10 prospective studies found a positive association between dairy intake and prostate cancer risk. Studies that examined individual types of dairy products show more consistent findings for milk, probably because milk is the most commonly consumed form of dairy. Although initial explanations for the observed dairy effect related to the fat content in dairy foods, the hypothesis that 1,25-dihydroxyvitamin D (1,25-D) might protect against prostate cancer suggests another possible mechanism: that at sufficiently high amounts, dietary calcium suppresses production of 1,25-D, thereby increasing risk of prostate cancer.

The observation that dairy may increase risk of prostate cancer is troubling, given current dietary recommendations for calcium intake, aggressive promoting of dairy as a source of calcium, and the possibility that calcium intake may protect against colon cancer. The objective of this analysis was to examine the associations of dairy food, calcium, and vitamin D intake with prostate cancer risk, to determine whether previous findings can be confirmed, and to assess the extent to which associations observed for dairy might be due to their calcium content, possibly through a vitamin D-related pathway.

In a prospective study of 3612 men, followed from 1982 to 1984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study, 131 prostate cancer cases were identified. Dietary intake was estimated from questionnaires completed in 1982 to 1984. Relative risk (RR) and 95% CIs were estimated, by using Cox proportional hazards models adjusted for age, race, and other covariates. Mean age of the men was 57.8 years, 11% were African American, and their usual residence was roughly equally distributed among the 4 regions of the United States. The men consumed dairy foods almost twice a day on average. The most commonly consumed dairy items were low-fat and whole milk, cheese, and ice cream, whereas cottage cheese, cream, and yogurt were generally eaten less than once a week.

In Cox proportional hazards models, dairy food intake was strongly associated with prostate cancer risk. When each dairy food was examined individually, the increase in risk was observed for total milk intake, but for low-fat milk in particular. No elevation was observed for whole milk or for any other dairy food item. Dietary calcium was also strongly associated with risk. In addition, when the researchers looked at calcium from different food sources, only calcium from low-fat milk was clearly associated with risk, although the association was not as strong as that for total calcium. Calcium from all other dietary sources, including calcium from whole milk, from all other dairy besides milk, and from nondairy sources, was not positively associated with risk. There was elevation in risk for the 151 men (4%) who reported use of calcium supplements or for the 846 men (23%) who reported use of multivitamins. Risk was also not especially elevated among 312 men in the highest tertile of calcium intake who were also users of multivitamins or calcium supplements, relative to 1067 nonusers in the lowest tertile of calcium intake.

These findings are consistent with most studies that observed an elevated risk of prostate cancer with greater dairy or milk intake, and with several, but not all studies that observed an elevated risk with greater calcium intake. Dairy foods may increase prostate cancer risk by raising circulating concentrations of insulin-like growth factor I, but such a mechanism would not explain why this is observed in association with low-fat milk only. Alternatively, calcium in dairy may increase risk by suppressing concentrations of circulating 1,25-D. Possibly, this mechanism is more applicable to low-fat milk than to other calcium sources. In the United States, milk is likely the most important source of bioavailable calcium because of its frequency of consumption and the ready absorption of calcium, especially in the presence of vitamin D, added in fortification. Whereas, the suppressive effects of calcium from whole milk may be countered by high intake of vitamin D, a similar reversal of calcium's effects may not occur with low-fat milk because fat-reduced milk products tend to have a lower vitamin D content. Vitamin D, a fat-soluble vitamin, may also be less well absorbed from fat-reduced milk.

In summary, the researchers found that prostate cancer risk was significantly elevated with higher intake of dairy foods and calcium, particularly calcium from low-fat milk. These findings suggest that dairy intake increases risk of prostate cancer, probably through its calcium content. Reasons for the elevated risk with low-fat milk are unclear, although the reduced content and bioavailability of vitamin D in low-fat milk may play a role. Although 1,25-D has been postulated to reduce risk of prostate cancer and calcium may increase risk by suppressing circulating concentrations of 1,25-D, the researchers failed to see any direct evidence for a protective effect of vitamin D intake in this cohort. Calcium is thought to protect against osteoporosis and colon cancer, and dairy is the primary source of calcium in the US diet. Given the implications of these findings with respect to recommendations to increase both calcium intake and low-fat milk consumption, the mechanisms by which calcium and low-fat milk might increase prostate cancer risk should be clarified and confirmed, to verify that calcium is indeed the critical risk factor.