Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease

Background: In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). Objective: We evaluated whether vitamin D-3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. Design: Patients with PD (n = 114) were randomly assigned to receive vitamin D-3 supplements (n = 56; 1200 IU/d) or a placebo = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS). Results: Compared with the placebo, vitamin D-3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean +/- SD change within vitamin D-3 group: +0.02 +/- 0.62 (P = 0.79); change within placebo group: +0.33 +/- 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D-3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D-3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D-3 group: -0.38 +/- 0.48 (P = 0.91); change within placebo group, +0.63 +/- 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D-3 group: +/-0.00 +/- 0.60 (P = 0.78); change within placebo group: +0.37 +/- 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. Conclusion: Vitamin D-3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841. Am J Clin Nutr 2013;97:1004-13.