2004Q-0097 - Qualified Health Claim (QHC): Calcium and various cancers
FDA Comment Number : EC1
Submitter : Dr. Edward Giovannucci Date & Time: 05/27/2004 06:05:58
Organization : Harvard Medical School
Academia
Category :
Issue Areas/Comments
GENERAL
GENERAL
The epidemiologic evidence presented for a benefit of calcium on prostate cancer risk grossly mischaracterizes the existing evidence. One case- control study that found an inverse association is mentioned but the rather large body of non-supportive evidence is ignored or readily discounted. In fact, a strong case can be made that higher calcium intake is associated with an increased rather than a decreased risk of prostate cancer. Several case-control (1, 2) and prospective cohort (3-6) studies have found positive associations between calcium intake and prostate cancer risk. Other studies do not support (7-10) or are only weakly supportive of this association (11, 12). In addition, in many case-control studies, men consuming relatively high levels of milk and other dairy products, the main sources of calcium, are at an either statistically significant increased risk (2, 13-18) or suggestively increased risk of prostate cancer (11, 12, 19, 20) compared to low or non-consumers, although several studies have not supported an association (21, 22). Most prospective cohort studies (4, 6, 8, 23-25), but not all (7, 26-28), support an association between higher intake of milk or dairy products and risk of prostate cancer. In addition, countries with greater per capita consumption of milk have higher prostate cancer mortality rates (r=0.7) (29-31).

The petitioners mischaracterize the results from the Physicians? Health Study, claiming that an observed association between calcium and prostate cancer risk is due to correlation between calcium and dairy fat, the presumed true risk factor for prostate cancer. However, as reported in that study, (4) dairy fat was not associated with risk of prostate cancer (relative risk of 1.06 between high and low quartiles). In addition, calcium from skim milk, which contains essentially no fat, was associated with an increased risk of prostate cancer. Thus, although this study does not prove an effect of calcium, the observed association is clearly not due to dairy fat. The Health Professionals Follow-Up Study, based on 1369 incident cases of prostate cancer and 201 cases of metastatic prostate cancer in 8 years of follow-up (3), also reported an association with calcium independent of dairy fat. Interestingly, in three recent prospective studies that found evidence of an inverse association between calcium intake and colorectal cancer (32-34), a positive association was observed for prostate cancer risk.(3-5). These studies were able to detect the expected reduced risk of colorectal cancer related to their measure of calcium intake; it is thus of concern that they all found an increased risk of prostate cancer associated with high calcium intake.

Thus, far from making a case for a protective effect of calcium on prostate cancer risk, the current epidemiologic data are strongly suggestive of a positive association. Out of 29 studies, 1 found an inverse association with calcium but 17 found statistically significant positive associations with calcium or milk intake, and 4 found suggestive positive associations. It is premature to conclude that this is a causal association, but if anything, the data suggest the need for careful further study of this potential downside of increased calcium intake in men instead of encouraging greater intakes.

See attached file for references.