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
