The calcium and vitamin D controversy.

Areas of the world where vitamin D levels are low for months of the year and intakes of calcium are high have a high prevalence of osteoporosis and cardiovascular disease. This suggests a public health message of avoiding calcium supplements and increasing vitamin D intake. No message could be more welcome as vitamin D can be given as a bolus while calcium must be taken daily and may be poorly tolerated. This approach is based on no evidence from intervention studies. Randomized controlled trials (RCTs) suggest that vitamin D given with calcium elicits a small reduction in fracture risk and deaths. This has not been demonstrated for D given alone. The cardiovascular safety of calcium and vitamin D (CaD) supplements is difficult to ascertain due to weaknesses in RCT designs and adjudication that cannot be remedied by subanalysis. Moreover, no major new RCTs are in process to provide better evidence. It remains unclear that calcium from dietary sources has health advantages over supplements. Benefits may be confined to patients with poor nutritional intake and the small effects at societal levels may be derived from large effects in a small number of patients. This has been impossible to confirm given the limited information about baseline vitamin D and calcium status at entry into trials. Future intervention studies should carefully capture baseline characteristics as these may determine the strength of the response, and make more efficient use of randomization strategies allowing subsequent disassembly or subanalyses while maintaining balancing. Though large clinical RCTs currently evaluate the effects of higher vitamin D doses (equivalent to 50-83 µg/d) there is no current research effort regarding the calcium controversy. In the absence of such studies it is not possible to provide clinicians with evidence-based recommendations regarding the best use of CaD supplementation.