Vitamin D in Cancer Patients: Above All, Do No Harm
Authors: Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2009)

In this issue of Journal of Clinical Oncology, Crew et al report results of an examination of vitamin D in 103 premenopausal breast cancer patients who participated in a 1-year trial of zoledronate compared with placebo, in which all women received daily vitamin D (400 IU) and calcium (1,000 mg). Seventy-four percent of women were vitamin D deficient at study entry shortly after diagnosis; deficiency was more common in black and Hispanic women than in white women. After 1 year, less than 15% of the white women (but no Hispanic or black women) who had been vitamin D deficient at baseline achieved sufficient levels in their blood. The authors conclude, “...our study suggests that a dose of 400 IU daily is inadequate in breast cancer patients even to maintain skeletal health, and is probably too low for meaningful anticancer effects.” They go on to comment that controversy exists as to the upper safe daily limit of vitamin D supplementation and suggest “...it may be prudent to follow serum levels of 25-OHD [25-hydroxyvitamin D]...” This carefully conducted study echoes results recently reported by Neuhouser et al (that approximately three fourths of patients with breast cancer from Los Angeles had inadequate blood levels of vitamin D) and by our group (that the same proportion of patients with breast cancer in Toronto had inadequate levels). A search on PubMed using the terms “vitamin D,” “vitamin D and cancer,” or “vitamin D and breast cancer” from 1990 to November 2008 yielded the results shown in Table 1. The total number of articles relating to vitamin D published annually during that period has more than doubled, the number relating to cancer and vitamin D has almost tripled, and the number relating to breast cancer and vitamin D has increased almost six-fold. It is likely this increase reflects both a desire to generate evidence on effects of vitamin D that are now recognized to extend beyond bone health and calcium metabolism (including effects on neuromuscular and cardiovascular health, autoimmunity, infection, and cancer) and a belief, not fully supported by evidence, that vitamin D deficiency is a cause of ill health in the general population that should be treated with increasingly high doses of vitamin D. A recent meta-analysis of nine studies of vitamin D supplementation showing that vitamin D supplementation in doses that ranged from 300 to 2,000 IU/d (mean, 528 IU/d) was associated with a modest but significant reduction in mortality (relative risk, 0.93; 95% CI, 0.87 to 0.99) provides some support for this belief; however, evidence for other health effects is weaker, and the authors recommended further study. When one looks at the association of vitamin D with cancer, the evidence is intriguing. For breast cancer, the strongest evidence is obtained from ecological studies that concluded that higher cancer rates in northern (v southern) latitudes were due to vitamin D deficiency. Observational studies examining the association between vitamin D intake or blood levels in relation to cancer risk in general, and breast cancer risk in particular, have yielded inconsistent results. Evidence of an adverse effect of vitamin D deficiency in colorectal cancer has been most consistent. Randomized trials, designed primarily for bone end points, have also yielded inconsistent results. Lappe et al reported a reduction of overall cancer risk (a secondary end point) in postmenopausal women randomly assigned to receive calcium alone or calcium plus vitamin D (1,100 IU/d) versus placebo; there was no vitamin D–only arm and cancer risk did not differ between the two calcium-containing arms. In contrast, a recent report from the Women’s Health Initiative failed to identify a beneficial effect of vitamin D supplementation (at a lower dose of 400 IU/d) on breast cancer risk compared with placebo. A note of caution is injected by reports that higher blood levels of vitamin D (well below