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

J Bone Miner Res. 2012 Jan;27(1):160-9. doi: 10.1002/jbmr.551.


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 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (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 [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta [MIP-1β], 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] = 2.79; 95% confidence interval [CI], 1.18-6.58), and a 5.7-mmHg decrease in systolic blood pressure (p = 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 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) 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).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects*
  • Calcifediol / administration & dosage
  • Calcifediol / pharmacology*
  • Calcium / blood
  • Calcium / urine
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / pharmacology*
  • Dietary Supplements*
  • Female
  • Humans
  • Immunity, Innate / drug effects*
  • Insulin / blood
  • Lower Extremity / physiology*
  • Middle Aged
  • Parathyroid Hormone / blood
  • Systole / drug effects
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Parathyroid Hormone
  • Vitamin D
  • Cholecalciferol
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • Calcifediol
  • Calcium