Supplementation with High Doses of Vitamin D to Subjects without Vitamin D Deficiency May Have Negative Effects: Pooled Data from Four Intervention Trials in Troms？

Data were pooled from four randomized clinical trials with vitamin D performed in Troms？ with weight reduction, insulin sensitivity, bone density, and depression scores as endpoints. Serum lipids, glycated hemoglobin ( ), and high sensitivity C-Reactive Protein, (HS-CRP) were measured at baseline and after 6–12 months of supplementation with vitamin D？20？000？IU–40？000？IU per week versus placebo. A total of 928 subjects who completed the interventions were included. At baseline the mean serum 25-hydroxyvitamin D (25(OH)D) level in those given vitamin D was 55.9 (20.9)？nmol/L and the mean increase was 82.4 (40.1)？nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight, but significant, increase in of 0.04%, an increase in HS-CRP of 0.07？mg/L in those with serum 25(OH)D <？50？nmol/L, and in those with low baseline HDL-C and serum 25(OH)D <？50？nmol/L a slight decrease serum HDL-C of 0.08 mmol/L ( ). No serious side-effects were seen. In conclusion, in subjects without vitamin D deficiency, there is no improvement in serum lipids, , or HS-CRP with high dose vitamin D supplementation. If anything, the effect is negative. 1. Introduction In recent years there has been a great interest in the relation between vitamin D and health outcomes [1]. As the vitamin D receptor (VDR) is found in tissues throughout the body it is reasonable to assume that effects of vitamin D are not restricted to its classical effects on calcium metabolism [2]. Thus, the levels of serum 25-hydroxyvitamin D (25(OH)D), which is the metabolite used to evaluate a subject’s vitamin D status [2], are in cross-sectional studies associated with risk factors for type 2 diabetes (T2DM) and cardiovascular disease [3–7] and in prospective studies associated with increased risk of these diseases and also cancer and even death [1, 8–11]. One would therefore expect that it should be easy to demonstrate a positive effect of vitamin D supplementation on health, but so far the evidence from properly performed randomized clinical trials (RCTs) is lacking. We have previously performed four large RCTs with high dose vitamin D intervention in Troms？, northern Norway, studying specifically the effects on weight [12], insulin sensitivity [13], bone density [14], and depression scores [15]. In addition to these endpoints we have also included other measures of glucose and lipid metabolism and inflammation markers. We have included more than 900 subjects in these studies, a number high enough to disclose an effect on these secondary endpoints, if present.