title: Baseline Serum 25-Hydroxy Vitamin D Is Predictive of Future Glycemic Status and Insulin Resistance High-Dose Vitamin D Supplementation in People With Prediabetes and Hypovitaminosis D C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. 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 Calcium plus vitamin D3 supplementation facilitated Fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Vitamin D supplementation during exercise training does not alter inflammatory biomarkers in overweight and obese subjects A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity. Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults. Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year. Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.
abstract: OBJECTIVE —Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks . However , prospect i ve data using the biomarker serum 25-hydroxyvitamin D [ 25(OH)D ] are limited and therefore examined in the present study . RESEARCH DESIGN AND METHODS —A total of 524 r and omly selected nondiabetic men and women , aged 40–69 years at baseline , with measurements for serum 25(OH)D and IGF-1 in the population -based Ely Study , had glycemic status ( oral glucose tolerance ) , lipids , insulin , anthropometry , and blood pressure measured and metabolic syndrome risk ( metabolic syndrome z score ) derived at baseline and at 10 years of follow-up . RESULTS —Age-adjusted baseline mean serum 25(OH)D was greater in men ( 64.5 nmol/l [ 95 % CI 61.2–67.9 ] ) than women ( 57.2 nmol/l [ 54.4,60.0 ] ) and varied with season ( highest late summer ) . Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia ( fasting glucose : β = −0.0023 , P = 0.019 ; 2-h glucose : β = −0.0097 , P = 0.006 ) , insulin resistance ( fasting insulin β = −0.1467 , P = 0.010 ; homeostasis model assessment of insulin resistance [ HOMA-IR ] : β = −0.0059 , P = 0.005 ) , and metabolic syndrome z score ( β = −0.0016 , P = 0.048 ) after adjustment for age , sex , smoking , BMI , season , and baseline value of each metabolic outcome variable . Associations with 2-h glucose , insulin , and HOMA-IR remained significant after further adjustment for IGF-1 , parathyroid hormone , calcium , physical activity , and social class . CONCLUSIONS —This prospect i ve study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance . These associations are potentially important in underst and ing the etiology of abnormal glucose metabolism and warrant investigation in larger , specifically design ed prospect i ve studies and r and omized controlled trials of supplementation OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels < 30 ng/mL were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes  compared with placebo administration BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events OBJECTIVE The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume , serum TNF-alpha , soluble TNF-receptor-2 ( sTNFR-2 ) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons . DESIGN A cross-sectional case-control study was used . PATIENTS Twenty-eight overweight/obese prob and s with normal glucose tolerance ( BMI > 27 kg/m(2 ) ) and 15 lean people ( BMI < 25 kg/m(2 ) ) , all of them undergoing planned surgical operation , participated in the study . METHODS Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein . Serum TNF-alpha , sTNFR-2 ( ELISA ) and fasting C-peptide ( RIA )  were measured . RESULTS TNF-alpha protein was expressed in adipocytes of both depots . The expression was evaluated visually and found to be greater in the obese patients . Significantly higher serum TNF-alpha ( 5.58+/-0.87 pg/ml vs 4.21+/-0.55 , mean+/-s.d . , P<0.01 , Mann-Whitney ) and sTNFR-2 levels ( 7.84+/-3.56 ng/ml vs 4.59+/-1.35 , P=0.005 ) were found in the obese subgroup in correlation with the fasting C-peptide level ( r=0.49 , P=0.003 ; and r=0.74 , P=0.001 ) and the C-peptide/ blood glucose ratio ( r=0.47 , Spearman , P=0.005 ; and r=0.70 , P=0.001 ) . The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients ( subcutaneous : r=0.52 , P=0.0003 ; r=0.69 , P<0.0001 ; visceral : r=0.65 , P<0.0001 ; r=0.63 , P<0.0001 ) and in both subgroups . CONCLUSIONS Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha , sTNFR-2 production and obesity-linked insulin resistance 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 Background Recent evidence suggests that higher calcium and /or vitamin D intake may be associated with lower body weight and better metabolic health . Due to contradictory findings from intervention trials , we investigated the effect of calcium plus vitamin D3 ( calcium+D ) supplementation on anthropometric and metabolic profiles during energy restriction in healthy , overweight and obese adults with very-low calcium consumption . Methods Fifty-three subjects were r and omly assigned in an open-label , r and omized controlled trial to receive either an energy-restricted diet ( −500 kcal/d ) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks . Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight , BMI , body composition , waist circumference , and blood pressures , as well as in plasma TG , TC , HDL , LDL , glucose and insulin concentrations . Results Eighty-one percent of participants completed the trial ( 85 % from the calcium + D group ; 78 % from the control group ) . A significantly greater decrease in fat mass loss was observed in the calcium + D group ( −2.8±1.3 vs.-1.8±1.3 kg ; P=0.02 ) than in the control group , although there was no significant difference in body weight change ( P>0.05 ) between groups . The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area ( P<0.05 for both ) . No significant difference was detected for changes in metabolic variables ( P>0.05 ) . Conclusion Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction . Trial registration Clinical Trials.gov ( NCT01447433 , http:// clinical trials.gov/ ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The purpose of this study was to examine the effects of vitamin D supplementation on inflammatory biomarkers in overweight and obese adults participating in a progressive resistance exercise training program . Twenty-three ( 26.1 ± 4.7 years ) overweight and obese ( BMI 31.3 ± 3.2 kg/m2 ) adults were r and omized into a double-blind vitamin D supplementation ( Vit D 4,000 IU/day ; female 5 , male 5 ) or placebo ( PL , female 7 ; male 6 ) intervention trial . Both groups performed 12 weeks ( 3 days/week ) of progressive resistance exercise training ( three sets of eight exercises ) at 70–80 % of one repetition maximum . Whole-blood lipopolysaccharide (LPS)-stimulated tumor necrosis factor ( TNF ) α production as well as circulating C-reactive protein ( CRP ) , TNFα , interleukin 6 ( IL-6 ) , and alanine aminotransferase ( ALT ) were assessed at baseline and after the 12-week intervention . No main effects of group or time were detected for circulating CRP , TNFα , IL-6 , and ALT . As expected , when PL and Vit D groups were combined , there was a significant correlation between percent body fat and CRP at baseline ( r = 0.45 , P = 0.04 ) , and between serum 25OHD and CRP at 12 weeks ( r = 0.49 , P = 0.03 ) . The PL group had a significant increase in 25 μg/ml LPS + polymixin B-stimulated TNFα production ( P = 0.04 ) , and both groups had a significant reduction in unstimulated TNFα production ( P < 0.05 ) after the 12-week intervention . Vitamin D supplementation in healthy , overweight , and obese adults participating in a resistance training intervention did not augment exercise-induced changes in inflammatory biomarkers AIMS Vitamin D deficiency may increase the risk for type 2 diabetes . African Americans tend to have poor vitamin D status and increased risk of diabetes , but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group . This study was conducted to determine whether vitamin D supplementation improves insulin secretion , insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes . METHODS In this r and omized , placebo-controlled trial , we examined the effect of 4000 IU/day vitamin D(3 , ) on glycaemia and contributing measures including insulin secretion , insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes . Outcome measures were derived from oral glucose tolerance testing . RESULTS Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation . Insulin sensitivity decreased by 4 % in the vitamin D group compared with a 12 % increase in the placebo group ( p = 0.034 ) . Insulin secretion increased by 12 % in the vitamin D group compared with a 2 % increase in the placebo group ( p = 0.024 ) , but changes in the disposition index were similar across groups . There was no effect of supplementation on post-load glucose or other measures of glycaemia . CONCLUSIONS Supplementation with 4000 IU/day vitamin D(3 ) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia . In this study , vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans Insufficient vitamin D status has been linked to autoimmune diseases , cancer and metabolic disorders , like obesity and insulin resistance . In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation . The relation between vitamin D and pro-inflammatory cytokines is not completely established . Furthermore , it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers . The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha ( TNF-α ) , interleukin 6 ( IL-6 ) and high sensitive C-reactive protein ( hs-CRP ) in patients with overweigh and obesity . We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance ( HOMA-IR and QUICKI ) . Serum levels of IL-6 , TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year r and omised intervention with either 40,000 IU vitamin D ( cholecalciferol ) per week or 20,000 IU vitamin D per week  ,  or placebo .  We found significant associations between IL-6 , TNF-α , vitamin D and insulin resistance indices at baseline . One year intervention with vitamin D  decreased serum IL-6 levels ; however hs-CRP levels were significantly increased . Neither measures of insulin resistance , nor TNF-α were influenced by a 1-year vitamin D supplementation The aims of the present study was to examine how overweight and obesity affect serum concentrations  nitric oxide ( NO ) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors ( sTNF-R ) in subjects with overweight and obesity . The study groups involved 154 women : 102 obese ( 81 obese with body mass index [ BMI ] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2 ) , 24 overweight patients , and 28 lean controls .  Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors ( sTNF-R1 , sTNFR-2 ) were measured by enzyme-linked immunosorbent assay ( ELISA ) kits .  Serum concentration of insulin was measured by radioimmunoassay ( RIA ) .  Plasma glucose , cholesterol , high-density lipoprotein (HDL)-cholesterol , and triglicerydes were determined by enzymatic procedure . Body composition was determined by impedance analysis using Bodystat ( Douglas , British Isles ) . Serum concentrations of NO in the overweight group ( 35.1 + /- 12.1 micromol/L ) and the obese groups with BMI 30 to 40 kg/m2 ( 32.8 + /- 9.3 micromol/L ) and with BMI greater than 40 kg/m2 ( 33.3 + /- 8.5 micromol/L ) were significantly higher when compared to controls ( 28.2 + /- 8.1 micromol/L ) : P < .05 ; P < .01 , and P < .01 , respectively . There was no difference in levels of NO between the overweight group and both obese groups . Serum concentration of TNF-alpha was also significantly higher in the group with overweight ( 6.5 + /- 3.1 pg/mL ) , in the obese group with BMI 30 to 40 kg/m2 ( 6.8 + /- 3.1 pg/mL ) , and in the obese group with BMI greater than 40 kg/m2 ( 7.4 + /- 2.6 pg/mL ) when compared to controls ( 2.9 + /- 2.2 pg/mL ) : P < .00005 ; P < .00005 , and P < .0000001 , respectively . However , serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group , both obese groups , and controls . In conclusion , we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women . It seems that there is an association between serum concentrations of TNF-alpha and NO ; however , this relationship depends on the degree of obesity BACKGROUND & AIMS The impact of vitamin D supplementation in overweight and obese adults during resistance training on body composition , muscle function , and glucose tolerance was investigated . METHODS Twenty-three overweight and obese ( age : 26.1±4.7 y ; BMI : 31.3±3.2 kg/m(2 ) ; 25-hydroxyvitamin D : 19.3±7.2 ng/mL ) adults were recruited for participation in a double-blind , placebo-controlled trial . Participants were r and omly divided into vitamin D ( VitD , 4000 IU/d ; 5 females , 5 males ) and placebo ( PL ; 7 females , 6 males ) groups . Both groups completed 12 weeks of resistance training . 25-hydroxyvitamin D , parathyroid hormone , body composition , and glucose tolerance were assessed at baseline and 12 weeks . Muscle function ( strength and power ) was assessed at baseline , 4 , 8 , and 12 weeks . RESULTS During the intervention , 25-hydroxyvitamin D increased and parathyroid hormone decreased in the VitD group ( P<0.05 ) . Peak power was significantly increased at 4 weeks in the VitD group only ( P<0.05 ) . Regression analysis revealed an inverse association between the change in 25-hydroxyvitamin D with the change in waist-to-hip ratio ( R(2)=0.205 , P=0.02 ) . No other improvements were observed with supplementation . CONCLUSIONS Vitamin D supplementation in overweight and obese adults during resistance training induced an early improvement in peak power , and elevated vitamin D status was associated with reduced waist-to-hip ratio . CLINICAL TRIAL REGISTRATION NUMBER NCT01199926 OBJECTIVE Adiponectin inhibits vascular inflammation and increases IL-10 mRNA expression in human macrophages . Thus , we investigated the possible relationship between plasma adiponectin and IL-10 levels and the effects of a diet-induced moderate weight loss on both cytokines . PATIENTS AND STUDY DESIGN  Plasma adiponectin and IL-10 levels were analyzed in 64 and roid [ body mass index ( BMI ) , > 28 kg/m2 ; waist to hip ratio ( WHR ) , > or = 0.86 ] and 20 gynoid [ BMI , > 28 kg/m2 ; WHR , < 0.86 ] obese healthy women . And roid obese women ( 49 + /- 14 yr ) had a mean BMI of 37.1 + /- 5.3 kg/m2 , similar to that of gynoid obese women ( 49 + /- 11 yr ; BMI , 33.4 + /- 2.6 kg/m2 ) . Twenty nonobese control women ( 46 + /- 11 yr ; BMI , 25.2 + /- 2.2 kg/m2 ) were also studied . In 15 and roid obese women , measurements were repeated after a 12-wk diet period ( 1200 kcal/d ) . RESULTS Median adiponectin [ 5.2 ( range , 3.3 - 7.8 ) vs. 12.1 ( 9.7 - 13.9 ) vs. 15.0 ( 12.6 - 18.2 ) microg/ml ; P < 0.0001 ] and IL-10 [ 1.8 ( 1.2 - 3.3 ) vs. 3.5 ( 2.9 - 4.3 ) and vs. 4.1 ( 3.5 - 4.8 ) pg/ml ; P < 0.0001 ] levels were lower in and roid vs. gynoid vs. nonobese women . Among and roid obese women , low adiponectin levels were independently related ( P < 0.0001 ) to decreased IL-10 levels , independently of BMI , WHR , or insulin resistance . No significant change in either median adiponectin or IL-10 levels was observed after body weight reduction ( 8 + /- 4 kg ; P < 0.01 ) , although percent changes in adiponectin paralleled those in IL-10 ( P < 0.05 ) . CONCLUSIONS And roid obesity is associated with a concomitant reduction of IL-10 and adiponectin levels . However , the antiinflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo .  Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment AIM To determine the short-term effect of vitamin D(3 ) supplementation on insulin sensitivity in apparently healthy , middle-aged , central ly obese men . SUBJECTS AND METHODS A double-blind r and omized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3 ) ( 120,000 IU each ; supplemented group ) fortnightly or placebo ( control group ) . Hepatic fasting insulin sensitivity [ homeostasis model assessment ( HOMA ) , quantitative insulin-sensitivity check index , HOMA-2 ] , postpr and ial insulin sensitivity [ oral glucose insulin sensitivity ( OGIS ) ] , insulin secretion ( HOMA%B , HOMA2-%B ) , lipid profile and blood pressure were measured at baseline and at 6 weeks ' follow-up . RESULTS Seventy-one of the recruited subjects completed the study ( 35 in supplemented group , 36 in control group ) . There was an increase in OGIS with supplementation by per protocol analysis ( P = 0.038 ; intention-to-treat analysis P = 0.055 ) . The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant ( mean difference 41.1 + /- 15.5 ; P = 0.01 ) . No changes in secondary outcome measures ( insulin secretion , basal indices of insulin sensitivity , blood pressure or lipid profile ) were found with supplementation . CONCLUSION The trial indicates that vitamin D(3 ) supplementation improves postpr and ial insulin sensitivity ( OGIS ) in apparently healthy men likely to have insulin resistance ( central ly obese but non-diabetic ) BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475 CONTEXT Vitamin D receptors are present in many tissues . Hypovitaminosis D is considered to be a risk factor for atherosclerosis . OBJECTIVE This study explores the effects of vitamin D replacement on insulin sensitivity , endothelial function , inflammation , oxidative stress , and leptin in vitamin D-deficient subjects . DESIGN , SETTING , AND PATIENTS Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [ 25(OH)D ] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter . The vitamin D-deficient group received 300,000 IU i m monthly for 3 months . The following parameters were evaluated before and after treatment : vitamin D metabolites , leptin , endothelial function by brachial artery flow mediated dilatation ( FMD ) , insulin sensitivity index based on oral glucose tolerance test , and lipid peroxidation as measures of thiobarbituric acid reactive substances ( TBARS ) . RESULTS FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls ( P = 0.001 ) and improved after replacement therapy ( P = 0.002 ) . Posttreatment values of TBARS were significantly lower than pretreatment levels ( P < 0.001 ) . A positive correlation between FMD and 25(OH)D ( r = 0.45 ; P = 0.001 ) and a negative correlation between FMD and TBARS ( r = -0.28 ; P < 0.05 ) were observed . There was a significant increase in leptin levels after therapy , and the leptin levels were positively correlated with 25(OH)D levels ( r = 0.45 ; P < 0.05 ) . CONCLUSIONS This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation . Replacement of vitamin D has favorable effects on endothelial function . Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis . Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter BACKGROUND AND AIM Cross-sectional studies indicate vitamin D to be of importance for glucose tolerance , blood pressure and serum lipids , but whether supplementation with vitamin D would improve cardio-vascular risk factors is not known . DESIGN AND SETTING The study was a 1 year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway from November 2005 to October 2007 . Subjects . A total of 438 overweight or obese subjects , 21 - 70 years old , were included and 330 completed the study . INTERVENTIONS The subjects were r and omized to vitamin D ( cholecalciferol , vitamin D(3 ) ) 40 000 IU per week ( DD group ) , vitamin D 20 000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . MAIN OUTCOME MEASURES Fasting serum lipids and blood pressure were measured and an oral glucose tolerance test performed at start and end of the study . RESULTS At baseline the mean serum 25(OH)D levels were 58 nmol L(-1 ) ( all subjects ) and increased to 140 and 101 nmol L(-1 ) in the DD and DP groups , respectively . No significant differences were found between the three groups regarding change in measures of glucose metabolism or serum lipids . In the DP group , there was a slight but significant increase in systolic blood pressure compared with the placebo group . CONCLUSIONS Our results do not support a positive effect of vitamin D on glucose tolerance , blood pressure or serum lipids . Further studies in subjects with low serum 25(OH)D levels combined with impaired glucose tolerance , hypertension or dyslipidaemia are needed CONTEXT We previously showed that a single high dose of oral ( po ) cholecalciferol ( D₃ ) sharply increases serum 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We evaluated the long-term bioavailability and metabolism of a single po or intramuscular ( i m ) high dose of ergocalciferol ( D₂ ) or D₃. DESIGN This was a prospect i ve intervention study . SETTING The study was conducted in an ambulatory care setting . PATIENTS Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS A single dose of 600,000 IU of po or i m D₂ or D₃ was administered . MAIN OUTCOME MEASURES Serum 25(OH)D and 1,25-dihydroxyvitamin D [ 1,25(OH)₂D ] were measured at baseline and at days 30 , 60 , 90 , and 120 by RIA . Serum 1,25(OH)₂D₂ , 1,25-dihydroxyvitamin D₃ [ 1,25(OH)₂D₃ ] , 24,25-hydroxyvitamin D₂ [ 24,25(OH)D₂ ] , and 24,25-hydroxyvitamin D₃ [ 24,25(OH)D₃ ] were measured by liquid chromatography-t and em mass spectrometry in a subgroup of patients receiving the po formulations . RESULTS The areas under the curve of 25(OH)D after D₃ were significantly higher than those after D₂ ( P < .0001 ) . Serum 25(OH)D basal difference significantly increased at day 30 with po D₂ and D₃ ( P < .01 and P < .0001 ) and up to day 90 with po D₃ ( P < .01 ) . The i m formulations produced a slow increased , and values peaked at day 120 relative to the other time points ( P < .0001 ) . We found a decrease in 1,25(OH)₂D at day 30 ( P < .05 ) and up to day 120 ( P < .001 ) and an increase in 1,25(OH)₂D₂ at day 30 ( P < .01 ) and up to day 120 ( P < .01 ) after po D₂. Oral D₂ and D₃ produced increases in 24,25(OH)D₂ and 24,25(OH)D₃ , respectively , at day 30 ( P < .001 ) . CONCLUSIONS A po dose of 600,000 IU of D₂ or D₃ is initially more effective in increasing serum 25(OH)D than the equivalent i m dose and is rapidly metabolized . Our RIA assay for 1,25(OH)₂D may not recognize
target: Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers .
  Risk of bias was present in most studies , thus supporting the need for higher quality studies in this area to more conclusively underst and the role VD supplementation has on inflammatory pathways
background: BACKGROUND Obesity induced low- grade chronic inflammation disrupts proper immune and metabolic function .
  Vitamin D deficiency increases inflammation , which is associated with cardiometabolic risk .
  This systematic review examines the association between oral vitamin D ( VD ) supplementation and circulating inflammatory biomarkers and glycemic outcomes from r and omized controlled trials ( RCTs ) of overweight and /or obese adults .