Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults.

BACKGROUND & AIMS: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. METHODS: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 µg calcifediol or 20 µg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. RESULTS: Supplementation with 20 µg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 µg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 µg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. CONCLUSIONS: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 µg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION NUMBER: NCT01868945.

A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast.

PURPOSE: Past studies have shown that higher macular pigment optical density (MPOD) and lutein (L) and zeaxanthin (Z) supplementation are related to improvements in glare disability, photostress recovery, and chromatic contrast. This study assessed those links using a randomized, double-blind, placebo-controlled design. METHODS: The visual effects of 1 year of supplementing L (10 mg/d) and Z (2 mg/d) were investigated. One hundred fifteen young, healthy subjects were recruited and randomized into the study (58 received placebo, 57 L+Z). Several dependent measures were collected at baseline and then once every 3 months: serum L and Z measured by HPLC chromatography; MPOD measured using customized heterochromatic flicker photometry; photostress recovery assessed by measuring the time needed to recover visual acquisition of a grating target after 30 seconds of an intense xenon white flash exposure; glare disability evaluated as the energy in a surrounding annulus necessary to veil a central grating target; and chromatic contrast assessed by measuring thresholds for a yellow grating target superposed on a 460-nm background. RESULTS: Macular pigment optical density increased significantly versus placebo at all eccentricities (10, 30, 60, and 105 minutes from the center of the macula). Serum L and Z also increased significantly by the first follow-up visit (at 3 months), and remained elevated throughout the intervention period of 1 year. Chromatic contrast and photostress recovery time improved significantly versus placebo. Glare disability was correlated with macular pigment density throughout the study period but did not increase significantly in the treated group. CONCLUSIONS: Daily supplementation with L+Z resulted in significant increase in serum levels and MPOD and improvements in chromatic contrast and recovery from photostress. These results are consistent with past studies showing that increasing MPOD leads to improved visual performance. (ClinicalTrials.gov number, NCT00909090.).