title: Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Dose-Dependent Short-Term Effects of Single High Doses of Oral Vitamin D3 on Bone Turnover Markers 1,25-Dihydroxyvitamin D fluctuations in cardiac surgery are related to age and clinical outcome* Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the serum of healthy adults. Dose Response to Vitamin D Supplementation in Postmenopausal Women
abstract: 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 BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin AIMS A significant proportion of cardiac surgical patients develop critical post-operative complications . We aim ed to investigate the association of pre-operative 25-hydroxyvitamin D ( 25(OH)D ) levels with major cardiac and cerebrovascular events ( MACCE ) in cardiac surgical patients . METHODS AND RESULTS From January 2010 to August 2011 , we consecutively measured circulating 25(OH)D in 4418 operated patients . Of the study cohort , 38.0 % had deficient 25(OH)D values ( < 30 nmol/L ) and additional 32.3 % had insufficient values ( 30 - 49.9 nmol/L ) , whereas only 3.1 % had values > 100 nmol/L. The incidence of MACCE was 11.5 % . In multivariable-adjusted logistic regression models , the odds ratio of MACCE at deficient , inadequate , and high 25(OH)D levels was 2.23 [ 95 % confidence interval ( CI ) : 1.31 - 3.79 ] , 1.73 ( 95 % CI : 1.01 - 2.96 ) and 2.34 ( 95 % CI : 1.12 - 4.89 ) , respectively , compared with 25(OH)D levels of 75 - 100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay . Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75 - 100 nmol/L. CONCLUSION Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE . Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels > 100 OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 We investigated the short-term effects on bone turnover markers of high doses of vitamin D3 in order to identify what initial therapeutic dose can be safely administered in vitamin D-deficient subjects . Thirty-seven elderly subjects [ mean age 75 ± 3 ( SD ) years ] were consecutively r and omized to the administration of a single oral bolus of 600000 , 300000 , or 100000 IU vitamin D3 . Blood sample s were taken at baseline and 1 , 3 , 7 , 14 , 30 , 60 , and 90 days after vitamin D3 administration . Twenty-four subjects served as controls . No relevant changes in bone turnover markers [ C-terminal telopeptides of type I collagen ( sCTX ) and bone-specific alkaline phosphatase ( BAP ) ] were observed in the controls . In treated patients a dose-dependent effect on sCTX was observed . With the administration of 600,000 IU vitamin D3 a significant increase of sCTX was observed already at day 1 , and it was sustained for 2 months . The changes in sCTX with smaller doses were considerably lower and reached statistical significance only within the first 3 days with the 300,000 IU dose . BAP remained unchanged in patients given 300,000 and 600,000 IU vitamin D3 , while it significantly rose by 15–23 % throughout the observation period in patients given 100,000 IU . Our results indicate that the use of a vitamin D bolus exceeding 100,000 IU may be associated with acute increases of sCTX Objective : To investigate the interrelationship between cardiac surgery , age , circulating concentrations of the vitamin D hormone 1,25-dihydroxyvitamin D , and clinical outcome . Design : Prospect i ve , monocentric , two-arm parallel study . Setting : Tertiary Heart and Diabetes Center in the Federal State of North Rhine-Westphalia , Germany . Patients : Twenty-nine cardiac surgical patients aged ⩽65 yrs and 30 patients ≥75 yrs . Measurements : We assessed  1,25-dihydroxyvitamin D and other biochemical parameters of mineral metabolism ( calcium , phosphate , 25-hydroxyvitamin D , and parathyroid hormone ) , various inflammatory markers ( C-reactive protein , interleukin-6 and 8) , and different immunological parameters ( CD4 and CD8 cells , monocyte HLA-DR expression ) . We collected blood sample s preoperatively , immediately after surgery , and on postoperative days 1 , 5 , and 30 . In addition , we assessed adverse outcome until discharge as a composite of myocardial infa rct ion , low cardiac output syndrome , infection , stroke , or in-hospital death . Results : There were significant transient cardiac surgery-related fluctuations in 1,25-dihydroxyvitamin D and the aforementioned parameters of mineral metabolism , inflammation , and immune status . Compared to younger patients , older patients had consistently lower 1,25-dihydroxyvitamin D and phosphate levels ( p = .013 and p = .036 , respectively ) and significantly higher interleukin 6 and 8 levels ( p = .008 and p < .001 , respectively ) . Circulating 1,25-dihydroxyvitamin D was directly related to glomerular filtration rate ( R2 = .227 ; p < .001 ) and inversely related to interleukin 6 ( R2 = .105 ; p = .012 ) . The rate of adverse outcome tended to be higher in older than in younger patients ( 20.0 % vs. 3.5 % ; p = .081 ) . In risk score-adjusted logistic regression analysis , adverse outcome risk decreased by 7.7 % ( SE : 3.7 % ) for each pmol/L increment in 1,25-dihydroxyvitamin D ( p = .037 ) . Conclusions : Circulating 1,25-dihydroxyvitamin D levels fluctuate in relation to cardiac surgery . Low 1,25-dihydroxyvitamin D levels are associated with inflammatory processes and age-related differences in clinical outcome . Future studies should determine whether therapies aim ed at treating low 1,25-dihydroxyvitamin D levels can improve the outcome in older cardiac surgery patients Few foods contain ergocalciferol or cholecalciferol . Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms ( Agaricus bisporus ) on the vitamin D status of healthy adults . Thirty-eight volunteers were r and omized to 4 treatments consumed with a st and ard meal for 6 wk : the control ( C ) group received untreated mushrooms providing 0.85 μg/d ergocalciferol ( n = 10 ) ; groups M1 and M2 received UV-treated mushrooms providing 8.8 ( n = 10 ) and 17.1 μg/d ( n = 9 ) , respectively ; and the supplement ( S ) group received purified ergocalciferol plus untreated mushrooms , providing a total of 28.2 μg/d ( n = 9 ) . Serum total 25-hydroxyvitamin D [ 25(OH)D ] and 25-hydroxyergocalciferol [ 25(OH)D2 ] were 83 ± 38 and 2.4 ± 2.0 nmol/L , respectively , at baseline ( mean ± SD ) . At wk 6 , 25(OH)D2 had increased and was higher in all treatment groups than in the C group , whereas 25-hydroxycholecalciferol [ 25(OH)D3 ] had decreased and was lower in the M2 and S groups than in the C group . Increases in 25(OH)D2 for groups C , M1 , M2 , and S were 1.2 ± 5.2 , 13.8 ± 7.3 , 12.7 ± 3.7 , and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3 , -10.4 ± 6.4 , -20.6 ± 14.6 , and -29.5 ± 15.9 nmol/L , respectively . Concentrations did not change in group C. In summary , ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status , because 25(OH)D3 decreased proportionally BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( < 25 kg/m(2 ) ) , obese women ( ≥30 kg/m(2 ) ) had a 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging
target: 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
background: 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 .