Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial. Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults. Response to Vitamin D3 Supplementation in Obese and Non-Obese Caucasian Adolescents The serum 25-hydroxyvitamin D response to vitamin D supplementation is related to genetic factors, BMI, and baseline levels. Vitamin D supplementation has no major effect on pain or pain behavior in bedridden geriatric patients with advanced dementia The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. Supplementation with High Doses of Vitamin D to Subjects without Vitamin D Deficiency May Have Negative Effects: Pooled Data from Four Intervention Trials in Tromsø Vitamin D status predicts physical performance and its decline in older persons. A randomized, controlled trial of vitamin D supplementation upon musculoskeletal health in postmenarchal females. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation.
CONTEXT Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status . OBJECTIVE Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3 . SUBJECTS AND DESIGN This was a r and omized , placebo-controlled , double-blinded study of healthy adults ages 18 - 84 yr who received placebo , 1000 IU vitamin D3 , 1000 IU vitamin D2 , or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter . RESULTS Sixty percent of the healthy adults were vitamin D deficient at the start of the study . The circulating levels of 25-hydroxyvitamin D ( mean+/-sd ) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 ( baseline 16.9+/-10.5 ng/ml ; 11 wk 26.8+/-9.6 ng/ml ) , vitamin D3 ( baseline 19.6+/-11.1 ng/ml ; 11 wk 28.9+/-11.0 ng/ml ) , or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 ( baseline 20.2+/-10.4 ng/ml ; 11 wk 28.4+/-7.7 ng/ml ) . The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily . The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml . CONCLUSION A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels . Therefore , vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status CONTEXT Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection , particularly among those receiving the antiretroviral drug efavirenz . Optimal vitamin D dosing for treatment is unclear . OBJECTIVE Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D ( 25-OHD ) concentration from baseline to study wk 4 and 12 during treatment with vitamin D(3 ) , 50,000 IU monthly . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized double-blind , placebo-controlled multicenter trial of HIV-infected youth ages 18 - 24 yr , with viral load below 5000 copies/ml , on stable antiretroviral therapy . INTERVENTION INTERVENTION included vitamin D(3 ) , 50,000 IU ( n = 102 ) , or matching placebo ( n = 101 ) administered in three directly observed oral doses at monthly intervals . RESULTS At baseline , mean ( sd ) age was 20.9 ( 2.0 ) yr ; 37 % were female and 52 % African-American , and 54 % were vitamin D deficient/insufficient ( 25-OHD < 20 ng/ml ) , with no r and omized group differences . Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D , 43 of 46 ( 93 % ) had sufficient 25-OHD by wk 12 . Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 ( 13.3 ) to 35.9 ( 19.1 ) ng/ml at wk 12 ( P < 0.001 ) with no change for placebo . Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration , efavirenz did not diminish the response to vitamin D supplementation . There was no treatment-related toxicity . CONCLUSIONS Supplementation with vitamin D(3 ) 50,000 IU monthly for three doses was safe . Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l .  Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l . Thirty-four subjects completed the study , with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l .  Vitamin D supplementation  increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure .  Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency CONTEXT Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption . OBJECTIVE The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D ( 25OHD ) after supplementation with vitamin D(3 ) . DESIGN , SETTING , AND PARTICIPANTS This analysis was conducted in the active treatment arm of a r and omized , double-blind , placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture . Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3 ) and 500 mg/d calcium .  Intakes of monounsaturated fatty acids ( MUFA ) , polyunsaturated fatty acids ( PUFA ) , and saturated fatty acids ( SFA ) were estimated by food frequency question naire . MAIN OUTCOME MEASURE The change in plasma 25OHD during 2 yr  vitamin D and calcium supplementation was assessed . RESULTS The change in plasma 25OHD ( nanograms per milliliter ) during vitamin D supplementation was positively associated with MUFA , ( β = 0.94 ; P = 0.016 ) , negatively associated with PUFA , ( β = -0.93 ; P = 0.038 ) , and positively associated with the MUFA/PUFA ratio ( β = 6.46 ; P = 0.014 ) . CONCLUSION The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3 ) . Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3 ) supplements in healthy older adults . More studies are needed to confirm these findings BACKGROUND Hypovitaminosis D is prevalent in youth worldwide , but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group . We assessed the safety of high doses of vitamin D(3 ) administered to apparently healthy schoolchildren . METHODS To assess short-term safety , 25 subjects r and omly received placebo or vitamin D(3 ) at doses of 14,000 IU/wk for 8 wk . To assess long-term safety , 340 subjects r and omly received placebo , vitamin D(3 ) as 1,400 IU/wk or 14,000 IU/wk for 1 yr . Biochemical variables were monitored at 0 , 2 , 4 , 6 , and 8 wk and 8 wk off therapy in the short-term study and at 0 , 6 , and 12 months in the long-term study . RESULTS In both the short- and long-term studies , mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group . In the short-term study , mean 25-hydroxyvitamin concentrations increased from 44 ( + /- 11 ) to 54 ( + /- 19 ) ng/ml in the treated groups ( P = 0.033 ) . In the long-term study , mean 25-hydroxyvitamin D levels increased from 15 + /- 8 to 19 + /- 7 ng/ml ( P < 0.0001 ) in subjects receiving 1,400 IU/wk and from 15 + /- 7 to 36 + /- 22 ng/ml ( P < 0.0001 ) in the group receiving 14,000 IU/wk . No subject developed vitamin D intoxication . CONCLUSION Vitamin D(3 ) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) OBJECTIVE Low vitamin D levels and risk factors for vascular disease are both common in South Asian women . This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels . METHODS Parallel-group , double-blind , r and omised placebo-controlled trial . Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of < 75 nmol/L were r and omised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo . Outcomes were measured at baseline , 4 and 8 weeks . The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation . Secondary outcomes included blood pressure , arterial stiffness , microvascular function measured using laser Doppler iontophoresis , insulin resistance , serum lipids , circulating markers of inflammation , thrombosis and adipokines . RESULTS 50 women were r and omised , 25 to each group . Mean age was 41 years ; mean baseline 25-hydroxyvitamin D level was 27 nmol/L.  25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks ( 16 nmol/L , 95 % CI 11 to 21 , p < 0.001 ) . There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks ( 0.1 % , 95 % CI -0.9 to 1.1 , p = 0.84 ) or 8 weeks ( 0.0 % , 95 % CI -1.4 to 1.4 , p = 0.98 ) . There was no improvement in cholesterol , insulin resistance or markers of inflammation . Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks . CONCLUSION A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels . TRIAL REGISTRATION IS RCT N75081811 CONTEXT The benefits of high serum levels of 25-hydroxyvitamin D [ 25(OH)D ] are unclear . Trials are needed to establish an appropriate evidence base . OBJECTIVE We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design . DESIGN Pilot D-Health was a r and omized trial carried out in a general community setting with 12 months intervention and follow-up . PARTICIPANTS Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day . A total of 644 participants were r and omized , and 615 completed the study ( two persons withdrew because of nonserious adverse events ) . INTERVENTIONS The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D(3 ) . MAIN OUTCOMES The main outcomes were the recruitment rate and changes in serum 25(OH)D. RESULTS Ten percent of those approached were recruited . At baseline , the mean 25(OH)D was 42 nmol/liter in all three study arms . The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter , compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups , respectively . CONCLUSIONS The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level CONTEXT Whether ergocalciferol ( D(2 ) ) and cholecalciferol ( D(3 ) ) 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 D(2 ) or D(3 ) 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 r and omly assigned to receive daily ( 1,600 IU ) or once-monthly ( 50,000 IU ) D(2 ) or D(3 ) 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 % . D(2 ) dosing increased 25(OH)D(2 ) but produced a decline ( P < 0.0001 ) in 25(OH)D(3 ) . Substantial between-individual variation in 25(OH)D response was observed for both D(2 ) and D(3 ) . 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 , 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 OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( < 30 ng ml(-1 ) ) ; of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P < 0.001 ) , with wide variations between single patients ; in the placebo group vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation  increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions CONTEXT AND OBJECTIVE Suboptimal vitamin D status can be corrected by vitamin D supplementation , but individual responses to supplementation vary . We aim ed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D ( 25(OH)D ) after supplementation . DESIGN AND PARTICIPANTS We used data from a pilot r and omized controlled trial in which 644 adults aged 60 to 84 years were r and omly assigned to monthly doses of placebo , 30 000 IU , or 60 000 IU vitamin D3 for 12 months . Baseline characteristics were obtained from a self-administered question naire . Eighty-eight single-nucleotide polymorphisms ( SNPs ) in 41 c and i date genes were genotyped using Sequenom MassArray technology . Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay . We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels . RESULTS Supplement dose and baseline 25(OH)D level explained 24 % of the variability in response to supplementation . Body mass index , self-reported health status , and ambient UV radiation made a small additional contribution . SNPs in CYP2R1 , IRF4 , MC1R , CYP27B1 , VDR , TYRP1 , MCM6 , and HERC2 were associated with change in 25(OH)D level , although only CYP2R1 was significant after adjustment for multiple testing . Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors . CONCLUSION Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation , perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of Background / Aims : Vitamin D deficiency is highly prevalent in obese children , and obese children tend to respond poorly to vitamin D supplementation . The objective of the study was to compare the response to vitamin D3 supplementation ( 2,000 IU once daily for 12 weeks ) between obese and non-obese Caucasian adolescents . Methods : The study design was open label non-r and omized . It was carried out at a single center . Eighteen obese adolescents ( aged 12–18 years ) and the same number of age- , gender- and season-matched non-obese adolescents received vitamin D3 ( 2,000 IU/day ) orally for 12 weeks . Total serum 25-hydroxyvitamin D [ 25(OH)D ] , parathyroid hormone , calcium and phosphorus were measured at baseline and at the end of the 12-week period . Results : The mean baseline 25(OH)D level was higher in the non-obese compared to the obese subjects ( mean 28.9 vs. 25.2 ng/ml ; p = 0.029 ) . The increment in 25(OH)D levels following  vitamin D supplementation was significantly lower in the obese adolescents ( mean change 5.8 vs. 9.8 ng/ml ; p = 0.019 ) . Conclusions : Higher doses of vitamin D are required to treat vitamin D deficiency in obese adolescents compared to their non-obese peers OBJECTIVE The serum 25-hydroxyvitamin D ( 25(OH)D ) level is not only dependent on vitamin D intake and production in the skin but also dependent on genetic factors . Thus , in large genome-wide association studies , it has been shown that single nucleotide polymorphisms ( SNPs ) in the vitamin D binding protein ( DBP ) , as well as in enzymes related to activation or degradation of vitamin D and its metabolites , are as important for the serum 25(OH)D level as the effect of season . How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain . DESIGN AND METHODS Data were pooled from three r and omized controlled trials where 40 , 000 IU vitamin D/week was given for 6 months . Serum 25(OH)D was measured before and at the end of the intervention , and the subjects were genotyped for SNPs related to the serum 25(OH)D level . RESULTS Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2R1 genes . Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase ( delta ) after supplementation . Those with the lowest baseline serum 25(OH)D ( without regard to genotypes ) had the highest increase ( delta ) after supplementation . Subjects with high BMI had lowest baseline 25(OH)D levels and also the smallest increase ( delta ) after supplementation . CONCLUSIONS The serum 25(OH)D response to supplementation depends on genes , baseline level , and BMI . However , whether this is clinical ly important or not depends on the therapeutic window of vitamin D , an issue that is still not settled Background and aims : In a few , earlier , uncontrolled trials , alleviation of  chronic pain  has been documented by vitamin D supplementation . This r and omized double-blind placebo controlled trial addressed the association between pain and vitamin D deficiency and the effects of vitamin D supplementation on pain in institutionalized aged patients . Methods : 216 long-term care patients were enrolled in Helsinki , Finl and . Pain was assessed by three tools : Resident Assessment Instrument ( RAI ) , Discomfort Behavior Scale , and Pain Assessment in Advanced Dementia Scale . Scores for Cognitive Performance Scale ( CPS ) and other clinical assessment s were also collected from the RAI- data base . Levels of 25-hydroxyvitamin D ( 25-OHD ) and parathyroid hormone were also determined . Patients in pain ( n=202 ) were r and omized into three treatment groups , each receiving 0 , 400 , or 1200 IU cholecalciferol per day , respectively . Assessment s were repeated after six-month vitamin D supplementation . Results : Patients were aged ( 84.5±7.5 yrs ) , demented ( CPS= 4.9±1.4 , range 1–6 ) , and chronically bedridden .  Pain was present in 38.4 % to 83.8 % of patients depending on assessment tool . Low 25-OHD levels ( < 50 nmol/L ) were very common ( 98.1 % ) . However , vitamin D deficiency was not associated with pain or pain behavior . The supplementation result ed in a marked increase in 25-OHD levels . However , neither prevalence of painlessness nor pain scores changed significantly after vitamin D supplementation . Conclusions : We were not able either to show an association between vitamin D deficiency and pain or to observe alleviation of pain by vitamin D supplementation . The independent role of vitamin D in the etiology of pain remains controversial Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol  increased mean plasma 25OHD from 35 to 110 nmol/L ( p < 0.00001 ) and significantly decreased PTH ( p < 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [ 25(OH)D ] and high-density lipoprotein cholesterol ( HDL-C ) in subjects with high waist circumference . Subjects were r and omly assigned a daily multivitamin and mineral ( MVM ) supplement or a MVM supplement plus vitamin D 1,200 IU/day ( MVM+D ) for 8 weeks . There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( − 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l , respectively ; P = 0.003 ) . Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l ) in 61 % of participants . There were no significant changes in cardiovascular disease risk markers . Thus , vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation CONTEXT Vitamin D deficiency is associated with insulin resistance and risk of future diabetes . OBJECTIVE The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus ( T2DM ) . DESIGN This was a r and omized controlled trial performed in 2008 through 2015 . SETTING The study was conducted at the clinical research unit at a teaching hospital . PATIENTS Five hundred eleven subjects ( mean age 62 y , 314 males ) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included . A total of 256 were r and omized to vitamin D and 255 to placebo .  Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events . INTERVENTIONS Interventions included vitamin D ( cholecalciferol ) 20 000 IU/wk vs placebo for 5 years . Annual oral glucose tolerance tests were performed . MAIN OUTCOME MEASURE Progression to T2DM was the main outcome measure . Secondary outcomes were change in glucose levels , insulin resistance , serum lipids , and blood pressure . RESULTS The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L ( 24 ng/mL ) . One hundred three in the vitamin D and 112 in the placebo group developed T2DM ( hazard risk 0.90 ; 95 % confidence interval 0.69–1.18 , Cox regression , P = .45 , intention to treat analysis ) . No consistent significant effects on the other outcomes were seen . Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results . No serious side effects related to the intervention were recorded . CONCLUSIONS In subjects without vitamin D deficiency , vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes . Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect . This study tested if supplementation with  vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes ( T2DM ) Data were pooled from four r and omized clinical trials with vitamin D performed in Tromsø with weight reduction , insulin sensitivity , bone density , and depression scores as endpoints . Serum lipids , glycated hemoglobin ( HbA1c ) , and high sensitivity C-Reactive Protein , ( HS-CRP ) were measured at baseline and after 6–12 months of supplementation with vitamin D 20 000 IU–40 000 IU per week versus placebo .  A total of 928 subjects who completed the interventions were included . At baseline the mean serum 25-hydroxyvitamin D ( 25(OH)D ) level in those given vitamin D was 55.9 ( 20.9 ) nmol/L and the mean increase was 82.4 ( 40.1 ) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight , but significant , increase in HbA1c of 0.04 % , an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D < 50 nmol/L , and in those with low baseline HDL-C and serum 25(OH)D < 50 nmol/L a slight decrease serum HDL-C of 0.08 mmol/L ( P < 0.05 ) . No serious side-effects were seen . In conclusion , in subjects without vitamin D deficiency , there is no improvement in serum lipids , HbA1c , or HS-CRP with high dose vitamin D supplementation . If anything , the effect is negative CONTEXT Vitamin D deficiency is common among older people and can cause mineralization defects , bone loss , and muscle weakness . OBJECTIVE The aim of this study was to investigate the association of serum 25-hydroxyvitamin D ( 25-OHD ) concentration with current physical performance and its decline over 3 yr among elderly . DESIGN The study consisted of a cross-sectional and longitudinal design ( 3-yr follow-up ) within the Longitudinal Aging Study Amsterdam . SETTING An age- and sex-stratified r and om sample of the Dutch older population was used . OTHER PARTICIPANTS Subjects included 1234 men and women ( aged 65 yr and older ) for cross-sectional analysis and 979 ( 79 % ) persons for longitudinal analysis . MAIN OUTCOME MEASURE(S ) Physical performance ( sum score of the walking test , chair st and s , and t and em st and ) and decline in physical performance were measured . RESULTS Serum 25-OHD was associated with physical performance after adjustment for age , gender , chronic diseases , degree of urbanization , body mass index , and alcohol consumption . Compared with individuals with serum 25-OHD levels above 30 ng/ml , physical performance was poorer in participants with serum 25-OHD less than 10 ng/ml [ regression coefficient ( B ) = -1.69 ; 95 % confidence interval ( CI ) = -2.28 ; -1.10 ] , and with serum 25-OHD of 10 - 20 ng/ml ( B = -0.46 ; 95 % CI = -0.90 ; -0.03 ) . After adjustment for confounding variables , participants with 25-OHD less than 10 ng/ml and 25-OHD between 10 and 20 ng/ml had significantly higher odds ratios ( OR ) for 3-yr decline in physical performance ( OR = 2.21 ; 95 % CI = 1.00 - 4.87 ; and OR = 2.01 ; 95 % CI = 1.06 - 3.81 ) , compared with participants with 25-OHD of at least 30 ng/ml . The results were consistent for each individual performance test . CONCLUSIONS Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women . Because almost 50 % of the population had serum 25-OHD below 20 ng/ml , public health strategies should be aim ed at this group CONTEXT There has been a resurgence of vitamin D deficiency rickets throughout the developed world , with infants and adolescents being primarily affected . Adolescence is a crucial period for muscle and bone mineral accumulation . OBJECTIVE The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system . DESIGN AND SETTING We conducted a community-based , double-blind , r and omized controlled trial in a secondary school . PARTICIPANTS Postmenarchal 12- to 14-yr-old females participated in the trial . Ninety-nine were screened , 73 were included in r and omized controlled trial , and 69 completed the trial . There were no adverse events . INTERVENTION Four doses of 150,000 IU vitamin D(2 ) ( ergocalciferol ) were given over 1 yr . MAIN OUTCOME MEASURES Dual-energy x-ray absorptiometry , peripheral quantitative computed tomography , and jumping mechanography were used . RESULTS At follow-up , 25-hydroxyvitamin D [ 25(OH)D ] status was 56.0 ± 8.9 nmol/liter in the intervention group and 15.8 ± 6.6 nmol/liter in controls . There were no effects of supplementation on bone ; however , for muscle function , efficiency of movement improved in the vitamin D-treated group . There was an interaction between baseline 25(OH)D concentration and response to vitamin D supplementation for muscle jump velocity . CONCLUSIONS Despite improvements in 25(OH)D status , treatment with vitamin D(2 ) was not shown to increase mineral accretion , bone geometry or strength , muscle force , or power . There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations . Lack of effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is required Public health recommendations do not distinguish between vitamin D2 and vitamin D3 , yet disagreement exists on whether these two forms should be considered equivalent . The objective of the present study was to evaluate the effect of a daily physiological dose of vitamin D2 or vitamin D3 on 25-hydroxyvitamin D ( 25(OH)D ) status over the winter months in healthy adults living in Dunedin , New Zeal and ( latitude 46 ° S ) . Participants aged 18 - 50 years were r and omly assigned to 25 μg ( 1000 IU ) vitamin D3 ( n 32 ) , 25 μg ( 1000 IU ) vitamin D2 ( n 31 ) or placebo ( n 32 ) daily for 25 weeks beginning at the end of summer . A per- protocol approach , which included ≥ 90 % supplement compliance , was used for all analyses . Serum 25-hydroxyvitamin D3 ( 25(OH)D3 ) , 25-hydroxyvitamin D2 ( 25(OH)D2 ) and parathyroid hormone ( PTH ) were measured at baseline and at 4 , 8 , 13 and 25 weeks . Geometric mean total serum 25(OH)D concentrations ( sum of 25(OH)D2 and 25(OH)D3 ) at baseline was 80 nmol/l . After 25 weeks , participants r and omised to D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over the winter months compared with vitamin D3-supplemented participants ( both P < 0.001 ) . Supplementation with vitamin D2  increased serum 25(OH)D2 but produced a 9 ( 95 % CI 1 , 17 ) nmol/l greater decline in the 25(OH)D3 metabolite compared with placebo ( P < 0.036 ) . Overall , total serum 25(OH)D concentrations were 21 ( 95 % CI 14 , 30 ) nmol/l lower in participants receiving vitamin D2 compared with those receiving D3 ( P < 0.001 ) , among whom total serum 25(OH)D concentrations remained unchanged . No intervention-related changes in PTH were observed . Daily supplementation of vitamin D3 was more effective than D2 ; however , the functional consequence of the differing metabolic response warrants further investigation The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density ( BMD ) after calcium ( 500 mg ) and vitamin D ( 400 IU ) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency ( 25-hydroxyvitamin D , < 12 ng/ml ) . One hundred and ninety-two women ( mean age , 75 + /- 7 yr ) were r and omized to receive either the supplementation ( n = 95 ) or a placebo ( n = 97 ) in a double-blind , controlled clinical trial for 1 yr . In comparison with the placebo group , supplementation significantly increased BMD , normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers . The initial values of telopeptide cross-links were correlated with improvement in total body BMD [ urinary N-telopeptides ( NTX ) , r = 0.38 ; C-telopeptides ( CTX ) , r = 0.32 ; serum CTX , r = 0.28 ] , and the 3-month changes in the same markers were correlated with improvement in total body ( urinary N-telopeptides , r = -0.29 ; serum CTX , r = -0.26 ) and vertebral BMD ( CTX , r = -0.26 ; all P < 0.05 ) . We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium  and vitamin D supplementation
Dietary recommendations and r and omized trials on vitamin D supplementation should evaluate whether increases in circulating 25-hydroxyvitamin D levels match expectations -- for instance , the average increases obtained by trials on vitamin D3 without concomitant calcium supplements
CONTEXT Few studies in subjects over 50 yr of age have evaluated the influence of variable doses of vitamin D supplementation on serum 25-hydroxyvitamin D levels .
OBJECTIVE We performed a meta- analysis of changes in circulating 25-hydroxyvitamin D level associated with vitamin D supplementation in Caucasian subjects over 50 yr old .