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 High-dose oral vitamin D3 supplementation in the elderly Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and postoperative outcome in cardiac surgery. Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study. Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Vitamin D Supplementation and Hemoglobin Levels in Hypertensive Patients: A Randomized Controlled Trial Plasma Vitamin D and 25OHD Responses of Young and Old Men to Supplementation with Vitamin D3 Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Milk fortified with the current adequate intake for vitamin D (5 microg) increases serum 25-hydroxyvitamin D compared to control milk but is not sufficient to prevent a seasonal decline in young women. Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women Vitamin D supplementation in young White and African American women. Inverse relation between vitamin D and serum total immunoglobulin G in the Scandinavian Cystic Fibrosis Nutritional Study Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study. Maternal plasma 25-hydroxyvitamin D concentration and birthweight, growth and bone mineral accretion of Gambian infants Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women Prophylactic vitamin D in healthy infants: assessing the need. Evaluation of Vitamin D Supplementation Doses during Pregnancy in a Population at High Risk for Deficiency Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men.
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 Summary Daily dosing with vitamin D often fails to achieve optimal outcomes , and it is uncertain what the target level of 25-hydroxyvitamin D should be . This study found that large loading doses of vitamin D3 rapidly and safely normalize 25OHD levels , and that monthly dosing is similarly effective after 3–5 months . With baseline 25OHD > 50 nmol/L , vitamin D supplementation does not reduce PTH levels . Introduction There is concern that vitamin D supplementation doses are frequently inadequate , and that compliance with daily medication is likely to be suboptimal . Methods This r and omized double-blind trial compares responses to three high-dose vitamin D3 regimens and estimates optimal 25-hydroxyvitamin D ( 25OHD ) levels , from changes in parathyroid hormone ( PTH ) , and procollagen type I amino-terminal propeptide ( P1NP ) in relation to baseline 25OHD . Sixty-three elderly participants were r and omized to three regimens of vitamin D supplementation : a 500,000-IU loading dose ; the loading dose plus 50,000 IU/month ; or 50,000 IU/month . Results The Loading and Loading + Monthly groups showed increases in 25OHD of 58 ± 28 nmol/L from baseline to 1 month . Thereafter , levels gradually declined to plateaus of 69 ± 5 nmol/L and 91 ± 4 nmol/l , respectively . In the Monthly group , 25OHD reached a plateau of ~80 ± 20 nmol/L at 3–5 months . There were no changes in serum calcium concentrations . PTH and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD levels < 50 and < 30 nmol/L , respectively . Conclusions Large loading doses of vitamin D3 rapidly and safely normalize 25OHD levels in the frail elderly . Monthly dosing is similarly effective and safe , but takes 3–5 months for plateau 25OHD levels to be reached CONTEXT Observational studies relating circulating 25-hydroxyvitamin D ( 25OHD ) and dietary vitamin D intake to cardiovascular disease ( CVD ) have reported conflicting results . OBJECTIVE Our objective was to investigate the association of 25OHD , dietary vitamin D , PTH , and adjusted calcium  with  CVD and mortality in a Scottish cohort . DESIGN AND SETTING The MIDSPAN Family Study is a prospect i ve study of 1040 men and 1298 women from the West of Scotl and recruited in 1996 and followed up for a median 14.4 yr . PARTICIPANTS Locally resident adult offspring of a general population cohort were recruited from 1972 - 1976 . MAIN OUTCOME MEASURES CVD events ( n = 416 ) and all-cause mortality ( n = 100 ) were evaluated . RESULTS 25OHD was measured using liquid chromatography-t and em mass spectrometry in available plasma ( n = 2081 ) . Median plasma 25OHD was 18.6 ng/ml , and median vitamin D intake was 3.2 μg/d ( 128 IU/d ) . Vitamin D deficiency ( 25OHD < 15 ng/ml ) was present in 689 participants ( 33.1 % ) . There was no evidence that dietary vitamin D intake , PTH , or adjusted calcium were associated with CVD events or with mortality . Vitamin D deficiency was not associated with CVD ( fully adjusted hazard ratio = 1.00 ; 95 % confidence interval = 0.77 - 1.31 ) . Results were similar after excluding patients who reported an activity-limiting longst and ing illness at baseline ( 18.8 % ) and those taking any vitamin supplements ( 21.7 % ) . However , there was some evidence vitamin D deficiency was associated with all-cause mortality ( fully adjusted hazard ratio = 2.02 ; 95 % confidence interval = 1.17 - 3.51 ) . CONCLUSION Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD . Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD CONTEXT Several cohort studies have reported U-shaped or inverse J-shaped associations between circulating 25-hydroxyvitamin D [ 25OHD ] and clinical outcomes . OBJECTIVE We aim ed to investigate in cardiac surgical patients the association of preoperative 25OHD and 1,25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ] levels with the risk of major adverse cardiac and cerebrovascular events ( MACCE ) . DESIGN A prospect i ve cohort study of adult cardiac surgical patients in 2012 - 2013 was used . SETTING The study was conducted at the Heart and Diabetes Center North Rhine-Westphalia , Germany . PATIENTS A total of 3371 adult patients participated in the study . INTERVENTION None Measurements : The main outcome measure was MACCE until discharge . We categorized vitamin D metabolite levels into subgroups and performed multivariable-adjusted logistic regression analysis to estimate odds ratios ( ORs ) of MACCE . Moreover , we performed multiple regression analysis to assess the association of 25OHD and circulating 1,25(OH)2D3 with preoperative parameters . RESULTS As compared with patients in the 25OHD reference category ( 75 - 100 nmol/L ) , the multivariable-adjusted odds ratios ( OR ) of MACCE was significantly higher in patients with deficient 25OHD levels ( < 30 nmol/L ) ( OR = 2.06 [ 95%CI : 1.24 - 3.43 ] ) , but was comparable in patients with 25OHD levels > 100 nmol/L ( OR = 1.16 [ 95 % CI : 0.56 - 2.37 ] ) . Poor kidney function was an important predictor of high 25OHD ( > 100 nmol/L ) and low 1,25(OH)2D3 levels . 1,25(OH)2D3 was not independently associated with the incidence of MACCE . CONCLUSIONS In cardiac surgical patients , deficient but not high 25OHD levels are independently associated with the risk of MACCE . Cohort studies should consider potential interrelationships between kidney function , circulating vitamin D metabolite levels , and clinical outcome PURPOSE Vitamin D deficiency and cardiometabolic risk factors are common in obese adolescents . Observational studies demonstrate an inverse relationship among serum 25-hydroxyvitamin D ( 25OHD ) and obesity , insulin resistance , and inflammatory cytokines . This pilot study explores if vitamin D supplementation could reduce serum concentrations of inflammatory cytokines ( interleukin [ IL ] 6 , IL-10 , tumor necrosis factor α ) , adiponectin , lipids , hemoglobin A1C , and high-sensitivity C-reactive protein ( hs-CRP ) . A secondary aim was to determine the associations between baseline serum 25OHD concentrations and body mass index ( BMI ) , hs-CRP , inflammatory cytokines , and lipids . METHODS Overweight and obese adolescents enrolled in this 24-week , r and omized , double-blind study were given 150,000 IU ergocalciferol or placebo at baseline and 12 weeks . Outcome measurements included serum 25OHD , inflammatory cytokines , adiponectin , hs-CRP , lipids , hemoglobin A1C , and BMI at baseline , 12 , and 24 weeks . RESULTS Of 40 participants , 31 ( 78 % ) completed the study . Mean ± st and ard error 25OHD levels were similar in vitamin D and placebo groups at baseline ( 19.6 ± 5.3 vs. 25.8 ± 10.8 ng/mL ) and 24 weeks ( 20.1 ± 3.4 vs. 24.6 ± 8.4 ng/mL ) . Inflammatory and cardiovascular markers were not significantly different between groups at 24 weeks . Serum 25OHD at baseline was associated with BMI ( r = -.44 [ 95 % confidence interval , -.66 to -.15 ] ) but not with other outcome measures . CONCLUSIONS Supplementation with vitamin D at 150,000 IU every 3 months failed to increase serum 25OHD or alter inflammatory markers and lipids in overweight and obese youth . Further studies are needed to establish the dose of vitamin D required to increase 25OHD and determine potential effects on metabolic risk factors in obese teens Aims Circulating 25-hydroxyvitamin D ( 25OHD ) levels < 75 nmol/L are associated with a nonlinear increase in mortality risk . Such 25OHD levels are common in heart failure ( HF ) . We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF . Methods and results Four hundred HF patients with 25OHD levels < 75 nmol/L were r and omized to receive 4000 IU vitamin D daily or matching placebo for 3 years . Primary endpoint was all-cause mortality . Key secondary outcome measures included hospitalization , resuscitation , mechanical circulatory support ( MCS ) implant , high urgent listing for heart transplantation , heart transplantation , and hypercalcaemia . Initial 25OHD levels were on average < 40 nmol/L , remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D ( 19.6 % ; n = 39 ) or placebo ( 17.9 % ; n = 36 ) with a hazard ratio ( HR ) of 1.09 [ 95 % confidence interval ( CI ) : 0.69 - 1.71 ; P = 0.726 ] . The need for MCS implant was however greater in patients assigned to vitamin D ( 15.4 % , n = 28 ) vs. placebo [ 9.0 % , n = 15 ; HR : 1.96 ( 95 % CI : 1.04 - 3.66 ) ; P = 0.031 ] . Other secondary clinical endpoints were similar between groups . The incidence of hypercalcaemia was 6.2 % ( n = 10 ) and 3.1 % ( n = 5 ) in patients receiving vitamin D or placebo ( P = 0.192 ) . Conclusion A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants . Data indicate caution regarding long-term supplementation with moderately high vitamin D doses . Trial Registration Information clinical trials.gov Idenitfier : NCT01326650 Vitamin D insufficiency is commonly associated with hip fracture . However , the equipotency of ergocalciferol and cholecalciferol supplementation in this patient group has not been studied in a r and omized trial using high-performance liquid chromatography ( HPLC ) measurement of serum 25-hydroxyvitamin D ( 25OHD ) . The objective of this study was to determine if ergocalciferol and cholecalciferol are equipotent therapies in vitamin D-insufficient hip fracture patients . Ninety five hip fracture in patients with vitamin D insufficiency ( 25OHD<50 nmol/L ) were r and omized , double-blind , to treatment with ergocalciferol 1000 IU/day ( n=48 ) or cholecalciferol 1000 IU/day ( n=47 ) for three months . All participants were also given a placebo matching the alternative treatment to maintain blinding of treatment allocation . The primary endpoint was total serum 25OHD measured by HPLC . Secondary endpoints included 25OHD measured by radioimmunoassay ( RIA ) , intact parathyroid hormone ( iPTH ) , and bioactive ( 1 - 84 ) whole PTH ( wPTH ) .  Seventy patients ( 74 % ) completed the study with paired sample s for analysis . Cholecalciferol supplementation result ed in a 31 % greater increase in total HPLC-measured 25OHD ( p=0.010 ) and 52 % greater rise in RIA-measured 25OHD ( p<0.001 ) than supplementation with an equivalent dose of ergocalciferol . Changes in iPTH and wPTH were not significantly different between calciferol treatments ( p>0.05 ) . In vitamin D-insufficient hip fracture patients , supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol . However , the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation Epidemiological evidence suggests that circulating 25-hydroxyvitamin D ( 25OHD ) levels are inversely associated with hemoglobin ( Hb ) levels and anemia risk . We evaluated whether vitamin D supplementation improves Hb levels and reduces anemia risk in hypertensive patients . Two hundred patients with 25OHD levels < 75 nmol/L who attended the Styrian Vitamin D Hypertension Trial were included , of whom 188 completed the trial . Patients r and omly received 2800 IU vitamin D3 daily or a matching placebo for eight weeks . Initially , the prevalence of anemic status ( Hb levels < 12.5 g/dL ) and deficient 25OHD levels ( < 30 nmol/L ) was 6.5 % and 7.5 % , respectively . All anemic patients had 25OHD levels > 50 nmol/L. The mean ( 95 % confidence interval ) vitamin D effect on Hb levels was 0.04 ( −0.14 to 0.22 ) g/dL ( P = 0.661 ) . Moreover , vitamin D treatment did not influence anemic status significantly ( P > 0.999 ) . Likewise , vitamin D had no significant effect on Hb levels in the subgroups of anemic patients or in patients with initial 25OHD levels < 30 nmol/L. In conclusion , a daily vitamin D supplement of 2800 IU for eight weeks did not improve Hb levels or anemic status  in hypertensive patients . Future trials should focus on anemic patients with deficient 25OHD levels ( e.g. , < 30 nmol/L ) . This trial is registered with clinical trials.gov [ NCT02136771 ] Objectives : This study was conducted to determine whether there are age differences in the plasma parent vitamin D and 25-hydroxyvitamin D ( 25OHD ) responses to eight weeks of supplementation with 20 μg/day of vitamin D3 . Methods : Twenty-five healthy young men ( age 18–35 ) and 25 healthy older men ( 62–79 ) were r and omly assigned to supplementation with 20 μg/day of vitamin D3 or to no intervention and followed for eight weeks . Plasma vitamin D3 was measured by high performance liquid chromatography and 25OHD was measured by competitive protein binding . Results : Both young and old men in the supplemented group had pronounced , rapid and similar increases in plasma vitamin D3 , whereas vitamin D3 concentrations were stable in the control group . By the end of the eight-week adaptation period , plasma vitamin D3 of young and old men had increased by 4.3 and 6.2 nmol/L respectively . In the supplemented group , mean 25OHD concentrations of both the young and old men increased during the study , and the magnitude of the change after eight weeks was nearly identical in the two age groups ( 22.5 and 22.1 nmol/L in the young and the old men , respectively ) . In the control group there was a modest decrease in 25OHD of both the young and old men . Conclusions : There appears to be no age-related impairment among men in the absorption or metabolism of 20 μg/day of vitamin D3 taken orally for at least eight weeks 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 Low vitamin D status in women of childbearing age may have implication s for health . Vitamin D status of New Zeal and ers ( NZ ) , based on low serum 25-hydroxyvitamin D ( 25OHD ) is suboptimal . Vitamin D status may be improved with supplements and /or fortified foods . Recently an Adequate Intake ( AI ) for Australia and NZ was set at 5 microg/d vitamin D. We aim ed to determine the effect of daily consumption of milk powder fortified with 5 microg vitamin D3 on serum 25OHD concentration over 12 wks . 73 non-pregnant women ( 18 - 47 y ) living in Dunedin , NZ ( 46 degrees S ) were r and omised to receive either unfortified ( control ) or fortified ( 5 microg vitamin D3 ) milk for 12 wks from January to April . Mean 25OHD was similar between groups at week 0 ( control 74 vs 76 nmol/L ) and fell significantly in both groups over the 12 weeks ( control 53 nmol/L , fortified 65 nmol/L ; p < 0.001 ) . After 12 wks the fortified milk group had a serum 25OHD 19 % ( 95 % CI ; 7 , 32 % ) higher ( 10 nmol/L ) than the control group after adjusting for baseline levels ( p < 0.001 ) . Daily consumption of fortified milk providing the current AI of 5 microg day vitamin D3 for 12 weeks result ed in higher 25OHD concentrations than control milk . This dose was not sufficient to prevent the seasonal decline in 25OHD . This study suggests an AI of 5 microg may be inadequate for New Zeal and ers to allow for seasonal changes in sunlight exposure , and is unlikely sufficient for other population s with low sunlight exposure Purpose This study aim ed to determine whether there is a relationship between iron status and bone metabolism , and to compare the effects of the consumption , as part of the usual diet , of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women . Methods Young healthy iron-deficient or iron-sufficient women ( serum ferritin ≤30 ng/mL or > 30 ng/mL , respectively ) were recruited . Iron-deficient women were assigned to a nutritional intervention consisting of a r and omised , controlled , double-blind , parallel design trial of 16 weeks during winter . They consumed , as part of their usual diet , an iron ( Fe group , n = 54 ) or iron and vitamin D-fortified ( Fe+D group , n = 55 ) flavoured skimmed milk ( iron , 15 mg/day ; vitamin D3 , 5 μg/day , 200 IU ) . The iron-sufficient women followed their usual diet without supplementation ( R group , n = 56 ) . Dietary intake , body weight , iron biomarkers , 25-hydroxyvitamin D ( 25OHD ) , parathyroid hormone ( PTH ) , procollagen-type 1 N-terminal propeptide ( P1NP ) , and aminoterminal telopeptide of collagen I ( NTx ) were determined . Results Negative correlations were found between baseline log-ferritin and log-NTx ( p < 0.001 ) , and between transferrin and P1NP ( p = 0.002 ) . Serum 25OHD increased ( from 62 ± 21 to 71 ± 21 nmol/L , mean ± SD , p < 0.001 ) while P1NP and NTx decreased in Fe+D during the assay ( p = 0.004 and p < 0.001 , respectively ) . NTx was lower in Fe+D compared to Fe at week 8 ( p < 0.05 ) and was higher in Fe and Fe+D compared to R throughout the assay ( p < 0.01 ) . PTH did not show changes . Conclusions Iron deficiency is related with higher bone resorption in young women . Consumption of a dairy product that supplies 5 μg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status , defined as 25OHD over 75 There is limited information on the effects of vitamin D on serum 25 hydroxyvitamin D ( 25OHD ) in young people and none on African Americans . The main objective of this trial was to measure the effect of different doses of vitamin D3 on serum 25OHD and serum parathyroid hormone ( PTH ) in young women with vitamin D insufficiency ( serum 25OHD ≤ 20 ng/mL ( 50 nmol/L ) . A r and omized double-blind placebo-controlled trial of vitamin D3 was conducted in young white and African American women , age 25 to 45 years . A total of 198 healthy white ( 60 % ) and African American ( 40 % ) women were r and omly assigned to placebo , or to 400 , 800 , 1600 , or 2400 IU of vitamin D3 daily . Calcium supplements were added to maintain a total calcium intake of 1000 to 1200 mg daily . The primary outcomes of the study were the final serum 25OHD and PTH levels at 12 months . The absolute increase in serum 25OHD with 400 , 800 , 1600 , and 2400 IU of vitamin D daily was slightly greater in African American women than in white women . On the highest dose of 2400 IU/d , the mixed model predicted that mean 25OHD increased from baseline 12.4 ng/mL ( 95 % confidence interval [ CI ] , 9.2 - 15.7 ) to 43.2 ng/mL ( 95 % CI , 38.2 - 48.1 ) in African American women and from 15.0 ng/mL ( 95 % CI , 12.3 - 17.6 ) to 39.1 ng/mL ( 95 % CI , 36.2 - 42.0 ) in white women . There was no significant effect  of vitamin D dose on serum PTH in either race but there was a significant inverse relationship between final serum PTH and serum 25OHD . Serum 25OHD exceeded 20 ng/mL in 97.5 % of whites on the 400 IU/d dose and between 800 and 1600 IU/d for African Americans . The recommended dietary allowance ( RDA ) suggested by the Institute of Medicine for young people is 600 IU daily . The increase in serum 25OHD  after vitamin D supplementation was similar in young and old , and in white and African American women Background / Objectives : The hallmark of cystic fibrosis ( CF ) is chronic lung inflammation . The severity of lung disease is closely correlated with immunoglobulin G ( IgG ) levels . Beyond its contribution to the bone health , the importance of vitamin D has not been fully recognized owing to the lack of human studies providing evidence of its benefit . In the context of the recently described immunomodulatory functions of vitamin D , we aim ed to assess the relationship between vitamin D and IgG levels . Subjects/ Methods : Eight hundred and ninety-six CF patients were included ( 0.53–65.9 years ) from seven centers in Denmark , Norway and Sweden . Serum 25-hydroxyvitamin D ( 25OHD ) and total IgG were measured , spirometry was carried out and vitamin D intake data were gathered using a 7-day dietary food record . Multiple linear regression analyses were performed for IgG and forced expiratory volume in 1λs ( FEV1 ) as dependent variables , and serum 25OHD , daily food and supplemented vitamin D sources of intake as independent variables . The model was controlled for age , gender , genotype , CF-related diabetes , season , infection/colonization status , long-term oral corticosteroid treatment , long-term treatment with macrolide antibiotics , pancreatic insufficient phenotype and body mass index z-score . Results : Serum total IgG levels were negatively associated with serum 25OHD ( adjusted R 2=0.376 ; beta=−0.02 ; P<0.001 ) , supplemented vitamin D intake per kg bodyweight ( adjusted R 2=0.375 ; beta=−0.82 ; P<0.001 ) and total vitamin D intake per kg bodyweight ( adjusted R 2=0.398 ; beta=−0.60 ; P=0.002 ) . Serum 25OHD was positively associated with FEV1 ( adjusted R 2=0.308 ; beta=0.0007 ; P=0.025 ) . Conclusions : Increasing vitamin D intake may positively modulate inflammation in CF . This study supports the proposed role of vitamin D in the immune system during infection and substantiates prospect i ve studies Summary The effects of higher than recommended vitamin D doses on bone mineral density ( BMD ) and quality are not known . In this study , higher intakes , in postmenopausal women undergoing weight control over 1 year , had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry . Introduction Studies examining how bone responds to a st and ard dose of vitamin D supplementation have been inconsistent . In addition , the effects of higher doses on BMD and quality are not known . Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance . Methods This 1-year-long , r and omized , double-blind controlled study addresses whether vitamin D supplementation , in healthy overweight/obese older women , affects BMD and bone structural parameters . In addition , bone turnover and serum total , free , and bioavailable 25-hydroxyvitamin D ( 25OHD ) responses to one of three daily levels of vitamin D3 ( 600 , 2000 , 4000 IU ) with 1.2 Ca g/day during weight control were examined . Results Fifty-eight women ( age , 58 ± 6 years ; body mass index , 30.2 ± 3.8 kg/m2 , serum 25OHD , 27.3 ± 4.4 ng/mL ) were r and omized to treatment . After 1 year , serum 25OHD concentrations increased to 26.5 ± 4.4 , 35.9 ± 4.5 , and 41.5 ± 6.9 ng/mL , in groups 600 , 2000 , and 4000 IU , respectively , and differed between groups ( p < 0.01 ) . Weight change was similar between groups ( −3.0 ± 4.1 % ) . Cortical ( Ct ) thickness of the tibia changed by −1.5 ± 5.1 % , + 0.6 ± 3.2 % , and + 2.0 ± 4.5 % in groups 600 , 2000 , and 4000 IU , respectively , and each group was significantly different from each other ( p < 0.05 ) . Conclusion The decline in Ct thickness was prevented with higher vitamin D3 supplementation , but there were no other significant changes due to treatment over 1 year . Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies CONTEXT Public health authorities around the world recommend widely variable supplementation strategies for adults , whereas several professional organizations , including The Endocrine Society , recommend higher supplementation . METHODS We analyzed published r and omized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health . CONCLUSIONS The extraskeletal effects of vitamin D are plausible as based on pre clinical data and observational studies . However , apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly , causality remains yet unproven in r and omized controlled trials ( RCTs ) . The greatest risk for cancer , infections , cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D ( 25OHD ) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis , estimated from serum 1,25-dihydroxyvitamin D and PTH , calcium absorption , or bone mass , can be normalized by 25OHD levels above 20 ng/mL. Moreover , vitamin D supplementation ( 800 IU/d ) in combination with calcium can reduce fracture incidence by about 20 % . Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women . Based on calculations of the metabolic clearance of 25OHD , a daily intake of 500 - 700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL. Therefore , the recommendations for a daily intake of 1500 - 2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects , as suggested by The Endocrine Society Task Force , are premature . Fortunately , ongoing RCTs will help to guide us to solve this important public health question Background : Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency , but the vitamin D status that fully normalizes absorption is not known for humans . Objective : To quantify calcium absorption at two levels of vitamin D repletion , using pharmacokinetic methods and commercially marketed calcium supplements . Design : Two experiments performed in the spring of the year , one year apart . In the first , in which participants were pretreated with 25-hydroxyvitamin D ( 25OHD )  , mean serum 25OHD concentration was 86.5 nmol/L ; and in the other , with no pretreatment , mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a st and ard low calcium breakfast . A low calcium lunch was provided at mid-day . Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter . Methods : Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve ( AUC ) for the load-induced increment in serum total calcium . Results : AUC9 ( ± SEM ) , was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD  and 2.20 ± 0.240 in those not pretreated ( P < 0.001 ) . In brief , absorption was 65 % higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L ( both values within the nominal reference range for this analyte ) . Conclusions : Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges , calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus , individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake . We conclude that the lower end of the current reference range is set too low Severe vitamin D deficiency is common among Muslim immigrants . The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants . The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants . This 1-year-long r and omised double-blinded placebo-controlled intervention with vitamin D3 ( 10 and 20 microg/d ) included girls ( 10.1 - 14.7 years ) , women ( 18.1 - 52.7 years ) and men ( 17.9 - 63.5 years ) of Pakistani origin living in Denmark . The main endpoints were serum 25-hydroxyvitamin D ( S-25OHD ) , parathyroid hormone , bone turnover markers and bone mass . The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women ( 4-fold ) , and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men . S-25OHD concentrations increased at 6 months and were stable thereafter . Baseline S-25OHD concentrations tended to be lower in girls and women than in men ; females achieved about 46 nmol/l and men 55 nmol/l after supplementation . Serum intact parathyroid hormone concentrations decreased at 6 months , but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine Maternal vitamin D deficiency during pregnancy is a recognized risk factor for rickets and osteomalacia in infancy ( 1 ) . The circulating plasma concentration of 25-hydroxyvitamin D ( 25OHD ) , a long-lived metabolite of vitamin D , is used to judge vitamin D status ; values below 25 nmol/L are associated with an increased risk of rickets and osteomalacia ( 1 ) . There is evidence that a low maternal plasma 25OHD in pregnancy may influence the growth and bone mineral accrual of the offspring during foetal life , infancy and childhood . Positive associations have been reported between maternal  vitamin D  status in pregnancy and birthweight , birth length , length at 1 year and bone mineral accretion at 9 years ( 2–6 ) , although evidence is conflicting ( 7,8 ) . These relationships have been observed at concentrations of 25OHD higher than those associated with rickets and osteomalacia , and there are calls to raise the accepted lower threshold of vitamin D sufficiency for pregnant women , most recently to 80 nmol/L ( 9 ) . On a population basis , plasma 25OHD concentrations above 80 nmol/L are relatively uncommon in countries at temperate latitudes but are more common among people living in the tropics who have abundant skin sunshine exposure ( 10 ) . To contribute to the debate on the definition of vitamin D sufficiency in pregnancy , we have investigated the influence of maternal plasma 25OHD concentration on foetal and infant growth in a rural area of The Gambia , West Africa ( 13 ° N ) . In this region , there is tropical sunshine all year , the women are farmers who work out-of-doors for much of each day , and local female dress does not restrict regular sunshine exposure to the face , neck , shoulders , arms and feet , especially during farm work and gardening . The study was a secondary analysis of biochemical , anthropometric and bone data from a subset of 125 women and infants collected during a calcium supplementation study of blood pressure in pregnant Gambian women ( International Trial Registry : IS RCT N96502494 ) . No significant benefits for foetal and infant growth of maternal calcium supplementation were identified despite the low customary calcium intake in The Gambia ( 11 ) . The protocol , methods , maternal characteristics and infant data from the detailed study have been published ( 11 ) . Briefly , women from the rural villages of Keneba and M and uar , West Kiang , The Gambia were recruited at 20 weeks of pregnancy ( P20 ) and r and omized to a daily calcium supplement or a matching placebo tablet until parturition ( 1500 mg Ca as calcium carbonate and microcellulose-lactose , respectively ; Nycomed Pharma AS , Asker , Norway ) . Fasting , early morning blood was collected and anthropometry performed at P20 and 36 weeks of pregnancy ( P36 ) . The mean ( ± SD ) age , weight , height and dietary calcium intake of the women at P20 were 27.4 ± 7.5 years , 56.3 ± 6.7 kg , 1.61 ± 0.05 m and 356 ± 190 mg/day , respectively . The median parity ( range ) was 3 ( 0–10 ) . Infant birthweight was measured within 24 h of delivery . Weight , crown-heel length and head circumference were measured at 2 , 13 and 52 weeks postpartum . In addition , infant bone mineral content ( BMC ) , bone mineral density ( BMD ) and bone width ( BW ) or bone area ( BA ) , were measured by single photon absorptiometry of the midshaft radius ( Lunar SP2 , Lunar Corporation , Madison , WI , USA ) and , for a subset ( n = 44 , 47 and 52 at 2 , 13 and 52 weeks , respectively ) , by whole-body dual-energy X-ray absorptiometry ( Lunar DPX+ , software version 4.7b , Lunar Corporation ) . Plasma 25OHD was measured a using radioimmunometric assay ( Diasorin Ltd , Wokingham , Berks , UK ) , with assay performance monitored through the Vitamin D External Quality Assessment Scheme ( DEQAS ; Endocrine/Oncology Laboratory , Charing Cross Hospital , London , UK ) . The intra- and inter-assay coefficients of variation were 4 % and 100 ) ; possible trends in the data with p = 0.01–0.1 were noted . The analysis was conducted on 123 mother – infant pairs ; blood sample s from two subjects were not available . Mean ± SD 25OHD ( range ) was : P20 = 103 ± 25 ( 53–167 ) nmol/L ; P36 = 111 ± 27 ( 51–189 ) nmol/L. No subject had a 25OHD value < 50 nmol/L , 20 % and 16 % had 25OHD < 80 nmol/L , at P20 and P36 , respectively . There was a high degree of within-subject consistency in 25OHD at P20 and P36 ( 25OHDP36 = 33.2 + [ 0.79 ± 0.07] × 25OHDP20 , p ≤ 0.001 , R2 adjusted 51.5 % , n = 121 ) ; 11 % of women had 25OHD < 80 nmol/L at both P20 and P36 . The mean birthweight of the infants was 2.99 ± 0.36 kg . The infant anthropometric and bone measures during the first year are given in Table 1 . No significant relationships or trends in the data were observed between maternal 25OHD concentration using the values at P20 , P36 or the mean of the two and any of the following infant measures : birthweight , infant weight , length , head circumference , BMC , BW ( or BA ) , BMD and size-adjusted BMC of the midshaft radius and whole body at any time postpartum . This is illustrated in Figure 1 for birthweight as a function of maternal 25OHD concentration at P20 . Comparing the results for mothers with 25OHD above and below 80 nmol/L did not alter this finding . Table 1 Anthropometric and bone measures  of Gambian infants Figure 1 Lack of a significant relationship between infant birthweight and maternal vitamin D status at 20 weeks of pregnancy ( p = 0.8 ) . Multiple regression model included season , maternal height , weight , weight gain , supplement group and sex of the infant . No significant interaction between supplement group and maternal 25OHD concentration was observed for any infant variable . Trends in the data were observed in a few instances for a supplement group × 25OHD interaction among the bone measures but no consistent picture emerged and they were considered to have arisen by chance . We conclude that there is no evidence for an influence of vitamin D status during pregnancy on infant growth and bone mineral accrual in the conditions prevailing in The Gambia . The children in this study , as is common in this region of The Gambia ( 13 ) , were born small , grew well for the first months of life but experienced growth faltering during later infancy compared to Western children ( 11,14 ) , as demonstrated by their weight and length SDS . The 25OHD concentrations of the women were > 50 nmol/L in the second half of pregnancy , and no distinction could be drawn in infant outcomes between mothers with concentrations above or below 80 nmol/L. Thus , our study suggests that , for women with regular , adventitious UVB sunshine exposure and in situations where foetal and infant growth may be constrained by multiple factors , there would be no benefit for foetal and infant growth or bone mineral accrual in aim ing to increase the vitamin D status of individual mothers during pregnancy above 50 or 80 Objective : Assessment of the effectiveness and safety of high daily 125 μg ( 5000 IU ) or 250 μg ( 10 000IU ) doses of vitamin D2 during 3 months , in rapidly obtaining adequate 25 hydroxyvitamin D ( 25OHD ) levels . Design : Longitudinal study .Subjects : Postmenopausal osteopenic/osteoporotic women ( n=38 ) were studied during winter and spring . Median age ( 25–75th percentile ) was 61.5 ( 57.00–66.25 ) years , and mean bone mineral density ( BMD ) was 0.902 (0.800–1.042)g/cm2 . Subjects were r and omly divided into three groups : control group ( n=13 ) : no vitamin D2 , 125 μg/day ( n=13 ) and 250 μg/day ( n=12 ) of vitamin D2 groups , all receiving 500 mg calcium/day . Serum calcium , phosphate , bone alkaline phosphatase ( BAP ) , C-telopeptide ( CTX ) , 25OHD , mid-molecule parathyroid hormone ( mmPTH ) , daily urinary calcium and creatinine excretion were determined at baseline and monthly . Results : For all subjects ( n=38 ) , the median baseline 25 hydroxyvitamin D ( 25OHD ) level was 36.25 ( 27.5–48.12 ) nmol/l . After 3 months , 8 % of the patients in the control group , 50 % in the 125 μg/day group and 75 % in the 250 μg/day group had 25OHD values above 85 nmol/l ( 34 ng/ml ) . Considering both vitamin D2 groups together , mmPTH and BAP levels diminished significantly after 3 months ( P<0.02 ) , unlike those of CTX . Serum calcium remained within normal range during the follow-up . Conclusions : The oral dose of vitamin D2 required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D3 dose ( 20 μg/day ) . During 3 months , 250 μg/day of vitamin D2 most effectively raised 25OHD levels to 85 nmol/l in 75 % of the postmenopausal osteopenic/osteoporotic women treated The objective was to evaluate the need for vitamin D prophylaxis in healthy infants . This was a prospect i ve and r and omized study performed at primary care clinics . Eighty-eight full-term 1-month-old healthy infants were r and omly assigned to receive ( n = 41 ) or not ( n = 47 ) 402 IU/d of vitamin D for 1 year . Primary outcome measures were serum 25-hydroxyvitamin D ( 25OHD ) and parathyroid hormone ( PTH ) concentrations at 3 , 6 , and 12 months of age ; secondary measures included data on feeding , habitat , season of birth , sun exposure , and physical examination . At 3 and 6 months of age , serum 25OHD levels ( ±SD ) were significantly higher ( P < .001 ) in the prophylaxis group . In the group without prophylaxis , serum 25OHD increased with age ; and breast-fed infants aged 3 months had the lowest value ( 20.2 ± 9.4 ng/mL ) , which was significantly ( P = .001 ) lower than that of formula-fed infants ( 35.0 ± 9.7 ng/mL ) . The PTH levels were not influenced by the prophylaxis or feeding . No influence of either the habitat or season of birth on serum 25OHD concentrations was demonstrated . No infant had clinical signs of vitamin D deficiency . Serum 25OHD and PTH concentrations were weakly but significantly correlated ( r = -0.29 , P = .009 ) at 3 months of age . Healthy infants  without vitamin D prophylaxis had lower circulating concentrations of 25OHD at 3 and 6 months of age , the lowest value being found in 3-month breast-fed infants . The clinical relevance of these findings is probably negligible because serum 25OHD levels spontaneously increased with age and were not associated with high serum PTH . Clinical manifestations of rickets were not observed Aim / Background : Vitamin D supplementation during pregnancy is a well-accepted recommendation worldwide ; however , the debate about the correct dose is ongoing . We aim ed to compare daily doses of 600 , 1,200 , and 2,000 IU in this r and omized , controlled study . Methods : The study group consisted of 91 pregnant women aged 16 - 42 years admitted to Kocaeli Maternity and Children Hospital between April 2011 and April 2012 . The participants were r and omly divided into 3 groups . 600 , 1,200 , and 2,000 IU/day of vitamin D was supplemented to group 1 ( control group , n = 31 ) , group 2 ( n = 31 ) , and group 3 ( n = 32 ) , respectively . Serum calcium , 25-hydroxyvitamin D ( 25OHD ) , and the calcium/creatinine ratio in spot urine sample s were measured in the follow-up period . The serum calcium and 25OHD levels of the mothers ' infants were measured as well . Results : The frequency of vitamin D sufficiency after supplementation was 80 % in group 3 and it was significantly higher than in groups 1 ( 42 % ) and 2 ( 39 % ) ( p = 0.03 ) . The frequency of vitamin D sufficiency in the infants of the participants was 91 % in group 3 and it was significantly higher than in groups 1 ( 36 % ) and 2 ( 52 % ) ( p = 0.006 ) . Conclusions : At least 2,000 IU/day of vitamin D is needed to ensure adequate vitamin D status in pregnancy and early infancy OBJECTIVES To study the effects of vitamin D supplementation in healthier population s of men . DESIGN : R and omized , controlled trial . SETTING General clinical research center . PARTICIPANTS Sixty-five healthy , community-dwelling men ( mean age+/-st and ard deviation=76+/-4 , range 65 - 87 ) . INTERVENTION Cholecalciferol ( 1,000 IU/d ) or placebo supplementation for 6 months ; all received 500 mg supplemental calcium . MEASUREMENTS Upper and lower extremity muscle strength and power , physical performance and activity , health perception , calcium and vitamin D intake , and biochemical assessment , including 25-hydroxyvitamin D ( 25OHD ) , parathyroid hormone ( PTH ) , and ionized calcium levels . RESULTS The levels of 25OHD increased and PTH decreased in the cholecalciferol group , whereas there were no significant changes in the control group ( P<.001 ) . Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score . Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score . No significant difference in strength , power , physical performance , or health perception was found between groups . CONCLUSION The 25OHD or PTH levels correlated with physical activity and physical performance in older , community-dwelling men with normal 25OHD status . Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy , older men . Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin
Conclusions This systematic review demonstrates that body weight is an important predictor of variation in circulating 25OHD in cohorts on vitamin D supplements .
Our model provides an estimate of the daily vitamin D dose that is necessary for achieving adequate circulating 25OHD levels in vitamin D-insufficient or vitamin D-deficient individuals/cohorts with different body weights and ages
Purpose There is considerable variation in incremental circulating 25-hydroxyvitamin D ( 25OHD ) levels on vitamin D supplements , even when similar age groups and identical vitamin D doses are compared .
We therefore aim ed to investigate the importance of body weight for the dose – response relation in circulating 25OHD .