Response to comment on: Davidson et al. High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D. Diabetes Care 2013;36:260-266.

This letter is in response to Pilz et al. (1) who are concerned about the possible long-term effects of high levels of vitamin D on mortality. In a sense, our study was a “proof of concept” one. As noted in our article (2) and in its Supplementary Table 3, there have been a number of studies evaluating the effect of vitamin D supplementation on diabetes, insulin secretion, and insulin sensitivity, almost all of which have been negative. There are five possible reasons for these negative results: 1) some subjects did not have hypovitaminosis D; 2) the dose of vitamin D was too low; 3) relatedly, achieved serum vitamin D levels were not high enough; 4) duration of treatment was too short; or 5) vitamin D supplementation was truly ineffective. We chose conditions to meet the first four situations, i.e., subjects with hypovitaminosis D at high risk for developing diabetes and treated them for 1 year with very high doses of vitamin D (88,865 IU per week or 12,695 per day) quickly achieving serum levels of nearly 70 ng/mL. Thus, our negative results strongly support the fifth reason, i.e., vitamin D supplementation is simply ineffective in delaying the development of diabetes in people at high risk who have low levels of vitamin D or in their ability to secrete or respond to insulin.

Pilz et al. (1) point out that in a meta-analysis of 14 prospective cohort studies evaluating serum vitamin D levels and mortality, a few suggested a U-shaped relationship (3). However, this suggestion was not confirmed in a recently published National Health and Nutrition Examination Survey study (4). Although our study was certainly not intended to help establish acceptable vitamin D doses, the lack of hypercalcemia and hypercalciuria while ingesting nearly 13,000 IU of vitamin D per day for a year may help meet potential reservations concerning the recommendations of The Endocrine Society that a tolerable dose of vitamin D is 10,000 IU per day.