Oral supplementation with 25(OH)D3 versus vitamin D3: Effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

Abstract

To test the effect of 25(OH)D 3 (HyD) compared to vitamin D 3 on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 AE 3.9 ng/mL (mean AE SD) and a mean age of 61.5 AE 7.2 years were randomized to either 20 mg of HyD or 20 mg (800 IU) of vitamin D 3 per day in a double-blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]-8, IL-12, interferon gamma-induced protein 10 kDa , monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta , and ''Regulated upon Activation, Normal T-cell Expressed, and Secreted'' [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D 3 group. Women on HyD compared with vitamin D 3 had a 2.8-fold increased odds of maintained or improved lower extremity function (odds ratio [OR] ¼ 2.79; 95% confidence interval [CI], 1.18-6.58), and a 5.7-mmHg decrease in systolic blood pressure ( p ¼ 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1, and MIP-1 b. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 mg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D 3 . ß

Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens

“…The ADDI-D study extends previous observations on the efficacy of calcidiol when employed in vitamin D supplementation for vitamin D inadequacy in postmenopausal women with mean serum 25(OH)D levels below 20 ng/ml [15][16][17]. Moreover, for the first time, the effects of three different calcidiol regimens on core parameters of bone and mineral homeostasis in postmenopausal women with vitamin D inadequacy (i.e., serum 25(OH)D levels less than 30 ng/ml) have been assessed.…”

“…Several pharmacokinetic studies performed in the last four decades have demonstrated its hydrophilic properties, leading to higher solubility in organic solvents, lower trapping in the adipose tissues, smaller distribution volume, and shorter half-life (10-13 days), when compared to the parental compound cholecalciferol (30-45 days) [13,26,28]. The good predictability of achieved 25(OH)D levels in the short term, along with the effective PTH suppression and manageability in case of intoxication, may confirm the advantages of calcidiol supplementation versus cholecalciferol [14,16]. Moreover, greater affinity of calcidiol for vitamin D binding protein (VDBP) allows a more efficient internalization in cells expressing the megalin-cubilin system of endocytic receptors, such as the parathyroids and the renal tissue [29].…”

“…Thus, group 3 received on a weekly basis a similar dose as compared to group 1, taking calcidiol over 7 days. The 20 μg dosage was chosen because of the equivalence (in μg) to 800 IU of cholecalciferol, which is still considered the standard daily dose of vitamin D 3 [15][16][17]. It was decided not to exceed 125 μg for safety reason and possible side effects, since previous studies [15] showed that the administration of 140 μg/week in a single dose, although safe in terms of hypercalciuria and hypercalcemia, was followed by peaks in serum concentration of 25(OH)D nearly approaching 50 ng/ml possibly linked to non-classical side effects such as falls or increase in bone turnover markers [15,23,24].…”

“…Supplementation with vitamin D inactive precursors of the biologically active vitamin D metabolite (i.e., 1,25(OH) 2 D or calcitriol) is an efficient way to correct a poor vitamin D status and restore an optimal mineral homeostasis [1,[13][14][15][16][17].…”

“…Calcidiol administered daily, weekly, or in single bolus has been shown to be more effective and rapid in rising serum 25(OH)D levels with respect to cholecalciferol given at comparable doses daily (20 μg/day), weekly (140 μg/ week for 15 weeks), or in single bolus (140 μg), with no risk of vitamin D intoxication [15]. Notably, the authors assessed also several clinical endpoints providing evidence that calcidiol given daily or weekly may be more effective in maintaining or improving lower extremity function and lowering systolic blood pressure among young postmenopausal women [16].…”