Letter by Zitterman et al Regarding Article, “Calcium/Vitamin D Supplementation and Cardiovascular Events”
To the Editor:
We read with interest the paper by Hsia and colleagues1 in which the authors demonstrated that a daily vitamin D supplement of 400 IU (10 μg) in combination with 1000 mg calcium has no beneficial effects on cardiovascular risk. In our opinion, the data interpretation is complicated by the lack of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (calcitriol) measurements. It may be that the vitamin D dose was too low to influence circulating calcitriol concentrations. It may also be that baseline 25-hydroxyvitamin D concentrations were already sufficient enough to produce adequate amounts of calcitriol. Calcitriol is the only vitamin D metabolite with known physiological actions. Experimental data demonstrate that calcitriol has important protective vascular effects such as suppression of renin activity, inhibition of vascular calcification, and reduction of thrombogenicity.2 Several retrospective studies already indicate that calcitriol and other active vitamin D analogs reduce all-cause and cardiovascular mortality in calcitriol-deprived patients with end-stage renal failure.2 In elderly vitamin D–deficient patients and in immobilized subjects, measures that result in a meaningful rise in plasma 25-hydroxyvitamin D also increase plasma calcitriol very rapidly.3,4 Interestingly, advanced age and immobilization are associated with high cardiovascular morbidity. Moreover, physical activity is not only able to prevent cardiovascular disease, but is also associated with significantly higher 25-hydroxyvitamin D and calcitriol plasma concentration compared with sedentary lifestyle.5 For the interpretation of vitamin D effects on cardiovascular health, it is therefore necessary to measure plasma calcitriol in future interventional studies.
Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M; for the Women’s Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007; 115: 846–854.
Bouillon RA, Auwerx JH, Lissens WD, Pelemans WK. Vitamin D status in the elderly: seasonal substrate deficiency causes 1,25-hydroxycholecalciferol deficiency. Am J Clin Nutr. 1987; 45: 755–763.
Scheld K, Zittermann A, Heer M, Herzog B, Mika C, Drummer C, Stehle P. Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest. Clin Chem. 2000; 47: 1688–1695.