Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.

Setting: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21°). Participants: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).

Overall, D(3) is slightly, but significantly, more effective than D(2) to increase serum 25(OH)D. One year of D(2) or D(3) 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 D(2) or D(3) is observed.

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D3 (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D2 (ergocalciferol) and D3. An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D [25(OH)D] concentration. Though controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be ~30-32 ng/ml or above. Using this definition, it has been is estimated that approximately three quarters of all adults in the United States are low. Classically, low vitamin D status has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with “high” amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D3 may be preferable to vitamin D2.

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.Trial RegistrationClinicalTrials.gov NCT00690417 Trial RegistrationClinicalTrials.gov NCT01049048