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Department of Medicine
Toronto General Hospital
University Health Network
200 Elizabeth Street
Toronto, ON
Canada M5G 2C4
E-mail: msood99{at}gmail.com
Faculty of Pharmacy
University of Toronto
Toronto, ON
Canada
Dear Sir:
It was with great interest and concern that we read the recent article in the Journal by Lappe et al (1). The subsequent events of their trial and other evidence have now led to the new national recommendations by the Canadian Cancer Society (CCS) for supplementation with 1000 IU vitamin D/d either year-round or during the winter months, depending on risk (2). Thus, Canadians have now become a global experiment for vitamin D supplementation, but the question remains—is it too soon?
There is no question that vitamin D has shown considerable promise in the primary prevention of cancer, but recent evidence raises significant concerns about the generalizability of these results. In patients with renal impairment, phosphate retention due to a declining glomerular filtration rate has long been recognized as a risk factor for cardiovascular disease (3). It was a long-held belief that a uremic environment coupled with hyperphosphatemia was necessary to cause vascular calcification and to increase cardiovascular events, but this belief has recently been challenged. Dhingra et al (4) investigated the relation between serum phosphorus and the incidence of cardiovascular disease in 3368 patients with normal renal function. The Framingham Offspring study group was analyzed according to serum phosphorus concentrations by quartiles. Those in the highest quartile had a multivariate-adjusted risk of cardiovascular disease 1.55 times that of persons in the lowest serum phosphorus quartile (P = 0.004). This risk remained after the exclusion of a small number of patients with serum phosphorus concentrations >4.5 mg/dL (1.45 mmol/L). The fact that vitamin D intake increases gastrointestinal absorption of both calcium and phosphate raises the question of whether a higher vitamin D intake will be associated with greater cardiovascular risk.
The results of Lappe et al, although impressive, fail to report serum phosphate and calcium concentrations in patients taking vitamin D supplementation. Furthermore, Lappe et al made no mention of cardiovascular events or of the incidence of kidney stones in the study population. Finally, as they clearly stated, the incidence of cancer is a secondary outcome. The study was neither designed nor powered to definitively answer the question of whether vitamin D supplementation reduces cancer risk. The unfortunate outcome of all of this is a premature recommendation by the CCS. As Canadians, we ask the question—have we just traded one problem for another?
ACKNOWLEDGMENTS
Neither of the authors had a personal or financial conflict of interest.
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