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Context: Whether ergocalciferol (D2) and cholecalciferol (D3) are equally effective to increase and maintain serum 25-hydroxyvitamin D [25(OH)D] concentration is controversial. Objective: The aim of the study was to evaluate the effect of daily and once monthly dosing of D2 or D3 on circulating 25(OH)D and serum and urinary calcium. Design, Setting and Participants: In a university clinical research setting, 64 community dwelling adults age 65+ were randomly assigned to receive daily (1,600 IU) or once-monthly (50,000 IU) D2 or D3 for 1 yr. Main Outcome Measures: Serum 25(OH)D, serum calcium, and 24-h urinary calcium were measured at months 0, 1, 2, 3, 6, 9, and 12. Serum PTH, bone-specific alkaline phosphatase, and N-telopeptide were measured at months 0, 3, 6, and 12. Results: Serum 25(OH)D was less than 30 ng/ml in 40% of subjects at baseline; after 12 months of vitamin D dosing, levels in 19% of subjects (n = 12, seven receiving daily doses and five monthly doses) remained low, despite compliance of more than 91%. D2 dosing increased 25(OH)D2 but produced a decline (P < 0.0001) in 25(OH)D3. Substantial between-individual variation in 25(OH)D response was observed for both D2 and D3. The highest 25(OH)D observed was 72.5 ng/ml. Vitamin D administration did not alter serum calcium, PTH, bone-specific alkaline phosphatase, N-telopeptide, or 24-h urine calcium. Conclusions: Overall, D3 is slightly, but significantly, more effective than D2 to increase serum 25(OH)D. One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals. Substantial between-individual response to administered vitamin D2 or D3 is observed.

Measurement of circulating 25-hydroxy-vitamin D [25(OH)D]) is the accepted clinical indicator of vitamin D status. However, between-laboratory differences in measurement of this analyte exist, which may confound clinical care.We investigated the current agreement of 25(OH)D measurement in clinical laboratories and explored the possibility that simple calibration would improve between-laboratory agreement.Serum obtained from healthy volunteers (age 20-60 yr) and one "calibrator," selected to have a 25(OH)D value near 30 ng/ml, were sent for 25(OH)D measurement in four clinical laboratories (laboratories A-D) using HPLC, liquid chromatography tandem mass spectroscopy, and RIA methodologies.Serum 25(OH)D. Based upon self-report, the laboratory with the lowest interassay percent coefficient of variation was assigned as the reference to which the others were compared using linear regression and Bland-Altman analyses (Analyse-it; Analyse-it Software, Ltd., Leeds, UK).Good correlation was observed for 25(OH)D measurement between laboratory A and laboratories B-D (R(2) = 0.99, 0.81, and 0.95, respectively). Modest between-laboratory variation was noted; the mean bias ranged from 2.9-5.2 ng/ml. Consistent with a systematic offset, each value in laboratory B was higher than in laboratory A, and 89% of values from laboratories B-D were higher than laboratory A. The use of a single calibrator and correction factor reduced mean between-laboratory bias for laboratories B and D.Measurement of 25(OH)D by clinical laboratories yields similar results. The use of even a single calibrator will improve, but not resolve, between-laboratory variability. Based upon these data, in combination with reported within-individual variability, we recommend that clinicians aim for values greater than 30 ng/ml in their patients.

Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used.The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure.This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21 degrees ).The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m(2) (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7).Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml.Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml.These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.