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
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
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 .