Letter by Wallis and Penckofer Regarding Article, “Calcium/Vitamin D Supplementation and Cardiovascular Events”
To the Editor:
We read with interest the article by Dr Hsia and colleagues.1 We concur that the null finding was primarily caused by inadequate replacement. Dietary vitamin D supplements were never meant to replace the daily requirements needed to achieve the physiological levels of 25-hydroxyvitamin D levels (>40 ng/mL).2 There is little assurance that over-the-counter vitamin D supplements are biologically active or even contain what the package labeling asserts. Age- or drug-induced hypochlorhydria may interfere with the absorption of calcium-complexed supplements.3 There is evidence that approximately half of patients who take supplements remain severely deficient in vitamin D.4
States of calcium and vitamin D deficiency are also associated with changes in parathyroid hormone, the counterregulatory hormone. Hyperparathyroidism, regardless of whether it is primary or secondary, has been causally linked to increased cardiovascular morbidity and mortality, hypertension, hypertensive heart disease diastolic dysfunction, myocardial fibrosis, and calcification of the aortic valve and annulus.5 In our opinion, no conclusions can be drawn on lack of efficacy of vitamin D replacement without evidence that maximal parathyroid hormone suppression has occurred and that adequate calcium absorption is present (24-hour urinary calcium levels of 100 to 300 mg/d).6 We have found no studies where “treat to target” has been performed. Thus, we believe that it is important to complete studies that use adequate vitamin D and calcium replacement and demonstrate normalization of parathyroid hormone before it can be concluded that such therapy is ineffective.
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.
Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999; 69: 842–856.
Symons C, Fortune F, Greenbaum RA, Dandona P. Cardiac hypertrophy, hypertrophic cardiomyopathy, and hyperparathyroidism: an association. Br Heart J. 1985; 54: 539–542.