human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units ( IU ) to achieve 25-hydroxyvitamin D ( 25(OH)D ) levels of at least 50 nmol/L , even when endogenous vitamin D synthesis is minimal such as in winter . We aim ed to evaluate this recommendation in women of childbearing age . This is a single-center , r and omized , open trial conducted from 8 January to 9 May 2016 in Esslingen , Germany . We r and omized 201 apparently healthy women to receive for 8 weeks a daily multimicronutrient supplement containing either 200 IU ( n = 100 ) or 800 IU vitamin D3 ( n = 101 ) . Primary outcome measure was serum 25(OH)D.  196 participants completed the trial .  Increases in 25(OH)D ( median with interquartile range ) from baseline to study end were 13.2 ( 5.9 to 20.7 ) nmol/L in the 200 IU group , and 35.8 ( 18.2 to 52.8 ) nmol/L in the 800 IU group ( p < 0.001 for the between group difference ) . At study end , levels of ≥50 nmol/L were present in 70.4 % of the 200 IU group and in 99 % of the 800 IU group . Participants on hormonal contraceptives had higher baseline levels and a stronger increase in 25(OH)D. In conclusion , daily supplementation of 800 IU vitamin D3 during wintertime in Germany is sufficient to achieve a 25(OH)D level of at least 50 nmol/L in almost all women of childbearing age , whereas 200 IU are insufficient Highlights • Pregnancy vitamin D and cord blood DNA methylation compared in 1416 infants.• Associations tested in two large prospect i ve cohort studies , MoBa and ALSPAC.• Similarly for offspring health outcomes and vitamin D  , no convincing associations Introduction Preeclampsia is a pregnancy-specific syndrome . One of the hypotheses concerning the etiology of preeclampsia is vitamin D deficiency during pregnancy . Method and Material s The present study is a r and omized controlled clinical trial which aims to determine the effect of vitamin D supplement on reducing the probability of recurrent preeclampsia .  72 patients were placed in control group while 70 patients were r and omized to the intervention group . The intervention group received a 50000 IU pearl vitamin D3 once every two weeks . The control group was administered placebo . Vitamin D or placebo was given until the 36th week of pregnancy . Results The patients in intervention group have significantly lower ( P value = 0.036 ) probability of preeclampsia than patients in the control group . The risk of preeclampsia for the control group was 1.94 times higher than that for the intervention group ( 95 % CI 1.02 , 3.71 ) . Conclusion The intended intervention ( i.e. , prescription of vitamin D ) has a protective effect against recurrent preeclampsia .  Vitamin D supplementation therapy in pregnancy could help in reducing the incidence of gestational hypertension/preeclampsia . Registration This study has been registered in Iranian Registry of Clinical Trials ( I RCT ) site with ID number I RCT 2017010131695N1 Summary On September 29 , 2011 , acknowledged experts in the field of vitamin D , mainly European , were brought together in order to discuss the recent scientific advances in relation to vitamin D : the current requirements and associations with various health outcomes . In this article , the discussion s result ing from the meeting are summarized . Introduction Several groups at risk for developing vitamin D insufficiency have been identified . Accordingly , review s indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l . In addition to the role of vitamin D in bone health , recent studies suggest that it may play a pivotal role in other systems , e.g. , the cardiovascular system , pancreas , muscle , immune system and brain . Most evidence , however , is obtained from observational studies and yet inconclusive . Methods To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes , a workshop entitled “ Vitamin D Expert Meeting : Do we get enough ? ” , was organized . Results Despite low vitamin D levels worldwide , consensus on the definition of deficiency is not yet reached . In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects , r and omized controlled trials in these fields are warranted . The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation , in most studies co-administered with calcium , reduces fracture risk in the senior population . Conclusion To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg ( 800 IU ) , which is best achieved with a supplement Context : Available evidence shows an association of vitamin D with and rogen levels in men . However , results from preliminary r and omized controlled trials ( RCTs ) are conflicting . Objective : To evaluate whether vitamin D supplementation increases total testosterone ( TT ) levels in healthy men . Design : The Graz Vitamin D&TT‐ RCT is a single‐center , double‐blind , r and omized , placebo‐controlled trial conducted between December 2012 and January 2017 . Setting : Endocrine outpatient clinic at the Medical University of Graz , Austria . Participants : Ninety‐eight healthy men with TT levels ≥10.4 nmol/L and 25‐hydroxyvitamin D [ 25(OH)D ] levels < 75 nmol/L completed the study . Intervention : Subjects were r and omly assigned to receive 20,000 IU/wk of vitamin D3 ( n = 50 ) or placebo ( n = 50 ) for 12 weeks . Main Outcome Measures : Primary outcome was TT measured using mass spectrometry . Secondary outcomes were free testosterone , sex hormone‐binding globulin , estradiol , follicle‐stimulating hormone , and luteinizing hormone levels ; free and rogen index ; metabolic characteristics ; and body composition . Results : In healthy men [ mean values ± st and ard deviation : age , 39 years ( ±13 years ) ; 25(OH)D level , 53.3 nmol/L ( ±18.3 nmol/L ) ; TT , 19.1 nmol/L ( ±5.6 nmol/l ) ] , no significant treatment effect on TT was found ; however , there were significant effects on quantitative insulin sensitivity check index ( QUICKI ) and a trend toward decreased Matsuda index . In the treatment group , median ( interquartile range ) changes for TT , QUICKI , and Matsuda index were 0.5 nmol/L ( −0.63 to 0.63 nmol/L ; P = 0.497 ) , −0.02 ( −0.04 to 0.01 ; P = 0.034 ) , and −0.9 ( −3.2 to 0.8 ; P = 0.051 ) , respectively . Conclusion : Vitamin D treatment had no effect on TT levels in middle‐aged healthy men with normal baseline TT , but it significantly decreased QUICKI . Additional studies investigating vitamin D effects on TT and insulin sensitivity in healthy men are required Context Results of animal models and cross-sectional cohort studies have suggested a beneficial role for vitamin D in male reproduction . Objective Determine the effect of vitamin D and calcium supplementation on semen quality in infertile men with serum 25-hydroxyvitamin-D ( 25OHD ) levels ≤50 nmol/L. Design A single-center , triple-blinded , r and omized clinical trial . Participants A total of 1427 infertile men were screened to include 330 ; 1002 men did not meet inclusion criteria and 95 did not wish to participate . Intervention The active group received cholecalciferol 300,000 IU initially , then 1400 IU cholecalciferol and 500 mg of calcium daily for 150 days ; the other group received placebo .  Results Serum concentrations of 25OHD and 1,25-dihydroxyvitamin D3 were significantly higher in men in the treatment group compared with the placebo group . Vitamin D supplementation was not associated with changes in semen parameters , although spontaneous pregnancies tended to be higher in couples in which the man was in the treatment group [ 7.3 % vs 2.4 % , Δ5.0 % ( -0.6 % ; 10.5 % ) ] . Vitamin D treatment in a subgroup of oligozoospermic men increased the chance for a live birth compared with placebo [ 35.6 % vs 18.3 % , Δ17.3 % ( 1.6 % ; 32.9 % ) ] . Moreover , serum inhibin B levels were higher in men deficient in vitamin D who were r and omly assigned to receive high-dose vitamin D [ 193 pg/mL vs 143 pg/mL , Δ49 pg/mL ( 8 ; 91 pg/mL ) ] ; however , the increase in sperm concentration was not significantly higher than in the placebo group ( P = 0.07 ) . Conclusion High-dose vitamin D supplementation did not improve semen quality in vitamin D-insufficient infertile men . The positive impact of vitamin D supplementation on live birth rate and serum inhibin B in oligozoospermic and vitamin D-deficient men may be of clinical importance and warrant verification by others Context : Single-nucleotide polymorphisms ( SNPs ) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , but these relationships have not been examined following antenatal cholecalciferol supplementation . Objective : To determine whether SNPs in DHCR7 , CYP2R1 , CYP24A1 , and GC are associated with the response to gestational cholecalciferol supplementation . Design : Within-r and omization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation . Setting : Hospital antenatal clinics . Participants : In total , 682 women of white ethnicity ( 351 placebo , 331 cholecalciferol ) were included . SNPs at rs12785878 ( DHCR7 ) , rs10741657 ( CYP2R1 ) , rs6013897 ( CYP24A1 ) , and rs2282679 ( GC ) were genotyped . Interventions : 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery . Main Outcome Measure : 25(OH)D at r and omization and 34 weeks of gestation were measured in a single batch ( Liaison ; Diasorin , Dartford , UK ) . Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [ β represents the change in 25(OH)D per additional common allele ] . Results : Only rs12785878 ( DHCR7 ) was associated with baseline 25(OH)D [ β = 3.1 nmol/L ; 95 % confidence interval ( CI ) , 1.0 to 5.2 nmol/L ; P < 0.004 ] . In contrast , rs10741657 ( CYP2R1 ) ( β = −5.2 nmol/L ; 95 % CI , −8.2 to −2.2 nmol/L ; P = 0.001 ) and rs2282679 ( GC ) ( β = 4.2 nmol/L ; 95 % CI , 0.9 to 7.5 nmol/L ; P = 0.01 ) were associated with achieved 25(OH)D status following supplementation , whereas rs12785878 and rs6013897 ( CYP24A1 ) were not . Conclusions : Genetic variation in DHCR7 , which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D bio synthesis pathway , appears to modify baseline 25(OH)D. In contrast , the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1 , which may alter 25-hydroxylase activity , and GC , which may affect vitamin D binding protein synthesis or metabolite affinity BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta . Recent research es have shown that low level of vitamin D3 " 25-hydroxyvitamin D ( 25[OH]D ) " in serum is a risk factor for pre-eclampsia . Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia . The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-ec 
    Output:
    
agent
Meta-analyses of r and omized controlled trials ( RCTs ) document that physiological vitamin D supplementation during pregnancy is safe and improves vitamin D and calcium status , thereby protecting skeletal health .
Although certain RCTs and /or meta-analyses reported some other beneficial effects , it is still not clear whether vitamin D supplementation  improves fertility or decreases the risk of adverse pregnancy outcomes such as low birth weight , pre-eclampsia and neonatal mortality , or reduces wheeze/asthma in the infants .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units ( IU ) to achieve 25-hydroxyvitamin D ( 25(OH)D ) levels of at least 50 nmol/L , even when endogenous vitamin D synthesis is minimal such as in winter . We aim ed to evaluate this recommendation in women of childbearing age . This is a single-center , r and omized , open trial conducted from 8 January to 9 May 2016 in Esslingen , Germany . We r and omized 201 apparently healthy women to receive for 8 weeks a daily multimicronutrient supplement containing either 200 IU ( n = 100 ) or 800 IU vitamin D3 ( n = 101 ) . Primary outcome measure was serum 25(OH)D.  196 participants completed the trial .  Increases in 25(OH)D ( median with interquartile range ) from baseline to study end were 13.2 ( 5.9 to 20.7 ) nmol/L in the 200 IU group , and 35.8 ( 18.2 to 52.8 ) nmol/L in the 800 IU group ( p < 0.001 for the between group difference ) . At study end , levels of ≥50 nmol/L were present in 70.4 % of the 200 IU group and in 99 % of the 800 IU group . Participants on hormonal contraceptives had higher baseline levels and a stronger increase in 25(OH)D. In conclusion , daily supplementation of 800 IU vitamin D3 during wintertime in Germany is sufficient to achieve a 25(OH)D level of at least 50 nmol/L in almost all women of childbearing age , whereas 200 IU are insufficient Highlights • Pregnancy vitamin D and cord blood DNA methylation compared in 1416 infants.• Associations tested in two large prospect i ve cohort studies , MoBa and ALSPAC.• Similarly for offspring health outcomes and vitamin D  , no convincing associations Introduction Preeclampsia is a pregnancy-specific syndrome . One of the hypotheses concerning the etiology of preeclampsia is vitamin D deficiency during pregnancy . Method and Material s The present study is a r and omized controlled clinical trial which aims to determine the effect of vitamin D supplement on reducing the probability of recurrent preeclampsia .  72 patients were placed in control group while 70 patients were r and omized to the intervention group . The intervention group received a 50000 IU pearl vitamin D3 once every two weeks . The control group was administered placebo . Vitamin D or placebo was given until the 36th week of pregnancy . Results The patients in intervention group have significantly lower ( P value = 0.036 ) probability of preeclampsia than patients in the control group . The risk of preeclampsia for the control group was 1.94 times higher than that for the intervention group ( 95 % CI 1.02 , 3.71 ) . Conclusion The intended intervention ( i.e. , prescription of vitamin D ) has a protective effect against recurrent preeclampsia .  Vitamin D supplementation therapy in pregnancy could help in reducing the incidence of gestational hypertension/preeclampsia . Registration This study has been registered in Iranian Registry of Clinical Trials ( I RCT ) site with ID number I RCT 2017010131695N1 Summary On September 29 , 2011 , acknowledged experts in the field of vitamin D , mainly European , were brought together in order to discuss the recent scientific advances in relation to vitamin D : the current requirements and associations with various health outcomes . In this article , the discussion s result ing from the meeting are summarized . Introduction Several groups at risk for developing vitamin D insufficiency have been identified . Accordingly , review s indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l . In addition to the role of vitamin D in bone health , recent studies suggest that it may play a pivotal role in other systems , e.g. , the cardiovascular system , pancreas , muscle , immune system and brain . Most evidence , however , is obtained from observational studies and yet inconclusive . Methods To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes , a workshop entitled “ Vitamin D Expert Meeting : Do we get enough ? ” , was organized . Results Despite low vitamin D levels worldwide , consensus on the definition of deficiency is not yet reached . In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects , r and omized controlled trials in these fields are warranted . The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation , in most studies co-administered with calcium , reduces fracture risk in the senior population . Conclusion To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg ( 800 IU ) , which is best achieved with a supplement Context : Available evidence shows an association of vitamin D with and rogen levels in men . However , results from preliminary r and omized controlled trials ( RCTs ) are conflicting . Objective : To evaluate whether vitamin D supplementation increases total testosterone ( TT ) levels in healthy men . Design : The Graz Vitamin D&TT‐ RCT is a single‐center , double‐blind , r and omized , placebo‐controlled trial conducted between December 2012 and January 2017 . Setting : Endocrine outpatient clinic at the Medical University of Graz , Austria . Participants : Ninety‐eight healthy men with TT levels ≥10.4 nmol/L and 25‐hydroxyvitamin D [ 25(OH)D ] levels < 75 nmol/L completed the study . Intervention : Subjects were r and omly assigned to receive 20,000 IU/wk of vitamin D3 ( n = 50 ) or placebo ( n = 50 ) for 12 weeks . Main Outcome Measures : Primary outcome was TT measured using mass spectrometry . Secondary outcomes were free testosterone , sex hormone‐binding globulin , estradiol , follicle‐stimulating hormone , and luteinizing hormone levels ; free and rogen index ; metabolic characteristics ; and body composition . Results : In healthy men [ mean values ± st and ard deviation : age , 39 years ( ±13 years ) ; 25(OH)D level , 53.3 nmol/L ( ±18.3 nmol/L ) ; TT , 19.1 nmol/L ( ±5.6 nmol/l ) ] , no significant treatment effect on TT was found ; however , there were significant effects on quantitative insulin sensitivity check index ( QUICKI ) and a trend toward decreased Matsuda index . In the treatment group , median ( interquartile range ) changes for TT , QUICKI , and Matsuda index were 0.5 nmol/L ( −0.63 to 0.63 nmol/L ; P = 0.497 ) , −0.02 ( −0.04 to 0.01 ; P = 0.034 ) , and −0.9 ( −3.2 to 0.8 ; P = 0.051 ) , respectively . Conclusion : Vitamin D treatment had no effect on TT levels in middle‐aged healthy men with normal baseline TT , but it significantly decreased QUICKI . Additional studies investigating vitamin D effects on TT and insulin sensitivity in healthy men are required Context Results of animal models and cross-sectional cohort studies have suggested a beneficial role for vitamin D in male reproduction . Objective Determine the effect of vitamin D and calcium supplementation on semen quality in infertile men with serum 25-hydroxyvitamin-D ( 25OHD ) levels ≤50 nmol/L. Design A single-center , triple-blinded , r and omized clinical trial . Participants A total of 1427 infertile men were screened to include 330 ; 1002 men did not meet inclusion criteria and 95 did not wish to participate . Intervention The active group received cholecalciferol 300,000 IU initially , then 1400 IU cholecalciferol and 500 mg of calcium daily for 150 days ; the other group received placebo .  Results Serum concentrations of 25OHD and 1,25-dihydroxyvitamin D3 were significantly higher in men in the treatment group compared with the placebo group . Vitamin D supplementation was not associated with changes in semen parameters , although spontaneous pregnancies tended to be higher in couples in which the man was in the treatment group [ 7.3 % vs 2.4 % , Δ5.0 % ( -0.6 % ; 10.5 % ) ] . Vitamin D treatment in a subgroup of oligozoospermic men increased the chance for a live birth compared with placebo [ 35.6 % vs 18.3 % , Δ17.3 % ( 1.6 % ; 32.9 % ) ] . Moreover , serum inhibin B levels were higher in men deficient in vitamin D who were r and omly assigned to receive high-dose vitamin D [ 193 pg/mL vs 143 pg/mL , Δ49 pg/mL ( 8 ; 91 pg/mL ) ] ; however , the increase in sperm concentration was not significantly higher than in the placebo group ( P = 0.07 ) . Conclusion High-dose vitamin D supplementation did not improve semen quality in vitamin D-insufficient infertile men . The positive impact of vitamin D supplementation on live birth rate and serum inhibin B in oligozoospermic and vitamin D-deficient men may be of clinical importance and warrant verification by others Context : Single-nucleotide polymorphisms ( SNPs ) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , but these relationships have not been examined following antenatal cholecalciferol supplementation . Objective : To determine whether SNPs in DHCR7 , CYP2R1 , CYP24A1 , and GC are associated with the response to gestational cholecalciferol supplementation . Design : Within-r and omization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation . Setting : Hospital antenatal clinics . Participants : In total , 682 women of white ethnicity ( 351 placebo , 331 cholecalciferol ) were included . SNPs at rs12785878 ( DHCR7 ) , rs10741657 ( CYP2R1 ) , rs6013897 ( CYP24A1 ) , and rs2282679 ( GC ) were genotyped . Interventions : 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery . Main Outcome Measure : 25(OH)D at r and omization and 34 weeks of gestation were measured in a single batch ( Liaison ; Diasorin , Dartford , UK ) . Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [ β represents the change in 25(OH)D per additional common allele ] . Results : Only rs12785878 ( DHCR7 ) was associated with baseline 25(OH)D [ β = 3.1 nmol/L ; 95 % confidence interval ( CI ) , 1.0 to 5.2 nmol/L ; P < 0.004 ] . In contrast , rs10741657 ( CYP2R1 ) ( β = −5.2 nmol/L ; 95 % CI , −8.2 to −2.2 nmol/L ; P = 0.001 ) and rs2282679 ( GC ) ( β = 4.2 nmol/L ; 95 % CI , 0.9 to 7.5 nmol/L ; P = 0.01 ) were associated with achieved 25(OH)D status following supplementation , whereas rs12785878 and rs6013897 ( CYP24A1 ) were not . Conclusions : Genetic variation in DHCR7 , which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D bio synthesis pathway , appears to modify baseline 25(OH)D. In contrast , the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1 , which may alter 25-hydroxylase activity , and GC , which may affect vitamin D binding protein synthesis or metabolite affinity BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta . Recent research es have shown that low level of vitamin D3 " 25-hydroxyvitamin D ( 25[OH]D ) " in serum is a risk factor for pre-eclampsia . Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia . The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-ec 
    Output:
    