Abstract
Vitamin D deficiency is a common condition with significant musculoskeletal and non-musculoskeletal effects. Controversy exists regarding the efficacy of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) therapy in increasing circulating 25(OH) vitamin D (25(OH)D) concentration. Furthermore, little attention has been given to evaluating how high-dose intermittent therapy should be monitored. The study evaluated the effect of daily and monthly D2 or D3 on circulating 25(OH)D concentration.
After excluding pre-existing abnormal calcium or vitamin D metabolism, 64 community dwelling participants were randomly double-blinded and placebo-matched to equivalent doses of either D2 or D3, taken daily or monthly. They were monitored at nine visits over a 12-month prospective period. At each visit, pills were counted and fasting serum samples collected for determination of 25(OH)D2/D3, calcium, bone specific alkaline phosphatase (BSALP) and parathyroid hormone (PTH), while urine samples were collected for n-telopeptide (NTx) and 24 h calcium excretion. 25(OH)D was measured by reverse-phase high-performance liquid chromatography.
Compliance was >91% in the four groups. Total 25(0H)D concentration increased with all regimens, though the absolute increase at 12 months was greater for D3 than D2 for both daily (23 versus 15 nmol/L P = 0.05) and monthly (22 versus 9 nmol/L P = 0.11) dosing. Frequency of dosing did not significantly alter serum 25(OH)D concentration (daily versus monthly, 5% P = 0.29). Substantial between-individual variability was noted and demonstrated to be non-dependent on baseline 25(OH)D concentration. Dosing with D2 led to a substantial reduction in 25(OH)D3 concentration (30 nmol/L at 12 months P<0.0001). Monthly dosing with D2 or D3 produced a peak in 25(OH)D of 7.5–18.3 nmol/L after three days, which diminished to only 3.8–5.0 nmol/L after 30 d. Vitamin D administration did not alter serum calcium, PTH, BSALP, NTx concentrations or 24 h urine calcium excretion.
The authors concluded that D3 is more effective than D2 at increasing serum 25(OH)D concentration. One year of D2 or D3 dosing (1600 IU daily or 50,000 IU monthly) does not result in toxicity. Substantial variability in response to equal doses of vitamin D exists and warrants careful monitoring. Limitations of this study include the lack of vitamin D-deficient participants and the relatively small sample size.