understanding of vitamin d role in optimal health has expanded greatly in the past few years .
grant indicated that increasing western europeans serum 25(oh)d levels to at least 100 nmol / l all year could significantly reduce rates and economic burdens of several types of diseases whereas the reduction in healthcare expenditures was estimated to be 187,000 million euro per year .
the most important benefits would come for cancer , cardiovascular disease , diabetes mellitus , respiratory infections , dental / periodontal diseases and other .
for these reasons the polish consensus on vitamin d supplementation and standards were published on the beginning of 2010 and implemented into practice .
it negatively affects effectiveness of expensive pharmacotherapies in infectious diseases ( chronic hepatitis c , tuberculosis ) , osteoporosis , multiple sclerosis , epilepsy , chronic kidney diseases and atopic dermatitis .
it is estimated that more than 1 billion people of all ages worldwide have serum 25(oh)d values < 75 nmol / l .
nmol / l ] increased in 1015 y from 22% to 33% ( nhanes iii 19881994 ) to 36% and 41% ( nhanes 20012004 ) respectively .
recent surveys performed in poland evidenced more frequent vitamin d deficiency in the polish population than in the united states .
table 1 displays prevalence of serum 25-hydroxyvitamin d ( 25[oh]d ) level of less than 50 nmol / l in the broad ages spectrum of polish population .
it was found that in winter 83% of polish newborns started their lives in a state of vitamin d deficiency because 78% of their mothers were also deficient .
evaluation of vitamin d status during childhood and adolescence indicated marked improvement up to the 6th month of life . from the 12th month of life ( or even slightly earlier )
at least 80% of the whole polish population , including children and adolescents , adults and seniors , were vitamin d deficient ( 25(oh)d <
the prevalence is much higher of vitamin d deficiency and insufficiency . in small studies from polish hospitals
more than 90% of hypertension adolescents and women with ovary cancer are vitamin d deficient . in these patients
generally major determinants of vitamin d status are latitude , seasonality , skin pigmentation , clothing and use of sunscreens , and also supplement use and eating vitamin d fortified foods . in poland sunlight exposure is the primary determinant of vitamin d status because there are no vitamin d fortified foods .
recent evidence suggests that vitamin d may impact on clinical outcomes and treatment response in some diseases .
the current body of evidence supports the view that vitamin d supplementation holds promises as risk - modifying intervention in tuberculosis ( tb ) , influenza and viral upper respiratory illnesses .
there has been a particular interest on the possible role of vitamin d supplementation as adjunctive therapy in settings of infection .
a clear benefit of adjunctive vitamin d therapy in tb treatment , chronic hepatitis c ( chc ) infection and acute lower respiratory infections ( alri ) was observed .
interferon ( ifn)-based treatment for hepatitis c virus ( hcv ) infection has a therapeutic limitation and side effects , a more efficient therapeutic strategy is desired .
two small prospective randomized controlled studies showed that those patients who received vitamin d3 supplementation of 2000 iu / day , targeting a 25(oh)d level > 80 nmol / l , in addition to peg - ifn / rbv combination therapy , had higher rates of rapid virologic response ( rvr ; 44% vs. 17% , p < 0.001 ) , complete early virologic response ( cevr ; 94% vs. 48% , p < 0.001 ) and sustained virological response svr ( 86% vs. 42% ; or 2.5 , 95% ci 2.04.9 , p < 0.001 ) in hcv-1   and svr ( 95% vs. 77% , p < 0.001 ) in hcv-2/3 infection compared with subjects treated with standard therapy .
moreover , recipients of vitamin d3 supplementation were less likely to relapse or non - respond to antiviral therapy .
similarly , a small retrospective study showed vitamin d3 supplementation improved svr rate in the treatment of recurrent hepatitis c post liver transplantation ( 53.3% vs. 18.5% , p = 0.02 ) .
logistic regression analysis identified vitamin d supplement [ odds ratio ( or ) 3.0 , 95% ci 2.04.9 , ] and the serum 25(oh)d levels ( < 15 or > 15 ng / ml , or 2.2 , ) as an independent predictor of viral response indicating that adding vitamin d3 to conventional peg / rbv therapy significantly improved viral response .
lange reported that cyp27b11260 rs10877012 was an independent predictor of sustained virologic response ( svr ) in patients with poor - response il28b genotypes , but not in patients with favorable il28b genotype .
patients with chronic hepatitis c showed a high prevalence of vitamin d defficiency [ 25(oh)d < 20 ng / ml ] during all seasons , but 25(oh)d serum levels were not associated with treatment outcomes .
this study suggested a role of 1,25-dihydroxyvitamin d [ 1,25(oh)2d , calcitriol ] produced in macrophages s important to enhance the therapeutic efficacy of medications to treat hepatitis c. however , the serum concentration of the 1,25-dihydroxyvitamind precursor , 25(oh)d was not a suitable predictor of treatment outcome in this study because its concentration was too low .
terrier investigated the association between serum vitamin d status and the presence of hcv extra - hepatic manifestations .
84 of 94 patients ( 89% ) were vitamin d deficient or insufficient (  30 ng / ml ) .
low 25(oh)d levels correlate with the presence of mixed cryoglobulinaemia and systemic vasculitis in chronic hcv infection .
these findings suggest the potential multifaceted benefits of vitamin d supplementation in hcv - infected patients . low serum 25(oh)d level is associated with a high risk of developing active tuberculosis ( tb ) .
sato investigated the relationships between serum 25(oh)d levels and clinical course of tb after standard therapy in hospitalized patients with tb .
drug sensitivity testing was performed for all the subjects and those not showing drug resistances for the first - line anti - tb drugs were included in the study .
nmol / l ] . in 23 patients treated with the standard first - line 4-drug regimen serum 25(oh)d levels showed significant negative correlation with time taken to obtain 3 consecutive negative sputum smears or tb bacteria cultures and indicated that low serum 25(oh)d level was a good predictor of a prolonged clinical course in patients with active pulmonary tb .
ganmaa examined the effect of vitamin d supplementation on tuberculin skin test ( tst ) conversion .
this double - blind , placebo - controlled study was conducted in 120 mongol schoolchildren ( 25(oh)d < 50
vitamin d supplementation ( 800 iu / day ) for 6 mo had significant favorable effects on serum 25(oh)d concentrations and on growth in stature .
leis documented that in children < 5 y old whose vitamin d intake was less than 80 iu / kg / d were greater than 4 times more likely to have alri compared with children with a vitamin d intake exceeding 80 iu / kg / day ( or 4.9 , ci : 1.5 , 16.4 ) .
therefore increased vitamin d supplementation could prevent bronchiolitis and pneumonia the most common reasons for hospitalization in young children . in the polish atopic dermatitis interventional study vitamin d supplementation of 2000 iu / day for 3 mo in deficient patients led to two - fold increase in 25(oh)d and 2 fold decrease in disease symptoms ( table 2 ) . in pierrot - deseilligny observational , uncontrolled study vitamin d3 supplementation ( 3010 iu / day on average ) was given to 156 patients with relapsing  remitting multiple sclerosis , under first - line immunomodulatory therapy and with initial 25(oh)d serum level lower than 100 nmol / l .
relapses were determined for 29.1  8.4 and 29.8  10.1 mo during and before vitamin d supplementation , respectively .
every 10 nmol increase in 25(oh)d level was associated with a reduction in the relapse incidence rate of 13.7% . according to the 25(oh)d levels , the relapse incidence rate ratio decreased as the 25(oh)d level increased up to 110 nmol / l .
extra - renal cells , such as parathyroid cells , smooth muscle cells , endothelial cells , pancreatic cells and immunomodulatory cells , contain the machinery to locally produce 1,25(oh)2d .
this may explain the associations of adequate vitamin d status with lower chronic disease risk .
thus , the ability to maintain sufficient serum concentrations of 25(oh)d , the substrate for extra - renal 1-hydroxylase for the local production of 1,25(oh)2d , is particularly important in ckd .
shroff verified the hypothesis in rct study that ergocalciferol supplementation in 47 vitamin d deficient children with ckd stages 24 delayed the onset of secondary hyperparathyroidism . in this randomized , double - blinded , placebo - controlled study in children with ckd24 who had vitamin d deficiency ( median follow - up was 12 mo ) the time to development of hyperparathyroidism was significantly longer with ergocalciferol treatment compared with placebo ( hazard ratio , 0.30 ; 95% confidence interval , 0.090.93 , p = 0.05 ) .
with ergocalciferol treatment , normal 25(oh)d levels were achieved in all 8 children with ckd2 , 8 of 11 children with ckd3 , but not in the single patient with ckd4 .
nmol / l were required to achieve normal levels of 1,25(oh)2 d. therefore ergocalciferol was an effective treatment that delayed the development of secondary hyperparathyroidism in children with ckd23 .
alvarez documented that vitamin d3 ( cholecalciferol ) treatment reduced parathyroid hormone levels in 46 adult patients with early chronic kidney disease in 1 y rct study .
subjects with early ckd ( stages 23 ) were supplemented with oral vitamin d3 ( vitamin d group ; 50,000 iu / wk for 12 wk followed by 50,000 iu every other week for 40 wk ) .
serum 25(oh)d increased in the vitamin d group only [ 26.7  6.8 to 42.8  16.9 ng / ml ; ] and remained elevated at 1 y. pth decreased from baseline only in the vitamin d group ( baseline : 89.1  49.3 to 70.1  24.8 pg / ml ; p = 0.01 ) at 12 weeks , but values were not significantly different from baseline at 1 y. blood pressure and fgf23 did not change in either group .
thus serum pth levels improved after vitamin d3 treatment in adult ckd patients who had secondary hyperparathyroidism .
vitamin d supplementation as adjunctive therapy in osteoporosis why only some osteoporotic patients maintain a positive response to prolonged bisphosphonate therapy is unknown .
carmel examined bisphosphonate response and its association with serum 25(oh)d level in a  real world  setting .
serum 25(oh)d level was strongly associated with maintaining bisphosphonate response arguing that vitamin d may be involved in optimizing prolonged bisphosphonate therapy .
postmenopausal women with low bone mineral density ( bmd ) treated with bisphosphonates were categorized . a favorable response to biphosphonate therapy
the definition of non - response to bisphosphonate therapy was based on the eurofors study , which identified patients for teriparatide therapy after  failing  anti - resorptive agents ( median duration of bisphosphonate treatment was 36 mo ) .
non - response included any of the following : ( 1 ) t - score of < 3.0 at the lumbar spine , femoral neck , total hip , or trochanter despite > 24 mo of bisphosphonates therapy ; ( 2 ) decrease of > 3.0% in bmd at the lumbar spine , bilateral femoral neck , total hip , or trochanter between the baseline and follow - up dexa scans ; ( 3 ) incident low - trauma fracture despite > 12 mo of bisphosphonate therapy .
patients with a mean 25(oh)d  33 ng / ml had a 4.5-fold greater odds of a favorable response . patients with a mean 25(oh)d  33 ng / ml had a substantially greater likelihood of maintaining bisphosphonate response .
the probability of inadequate response to bisphosphonate therapy measured as bmd increase was 4-fold higher in patients with 25(oh)d < 30 ( or , 4.42 ; 95% ci , 1.2215.97 , p = 0.02 ) . in patients with vitamin d deficiency response to
bisphosphonate therapy measured by bone turnover markers indicated that ctx decreased only by 48% in patient treated with alendronate in comparison to 61% in patient supplemented with cholecalciferol ( 0.266 mg / wk for 3 mo ; final vitamin d status - serum 25(oh)d 82 ng / ml ) .
bertoldo reported that serum 25(oh)d levels modulate the acutephase response associated with the first nitrogencontaining bisphosphonate infusion .
body temperature and crp decreased when vitamin d status was normalized . in longitudinal clinical trial
( 40 individuals with severe chronic periodontitis ) bashutski evidenced that placebo patients with baseline vitamin d deficiency [ serum 25(oh)d , 1619 ng / ml ] had significantly less clinical attachment loss ( cal ) gain ( -0.43 mm vs. 0.92 mm , p < 0.01 ) and probing depth ( ppd ) reduction ( 0.43 mm vs. 1.83 mm , p < 0.01 ) than vitamin - d - sufficient individuals . vitamin d deficiency at the time of periodontal surgery negatively affects treatment outcomes for up to 1 y and indicated that vitamin d status may be critical for post - surgical healing .
these data are supported by work of hokugo who described increased prevalence of bisphosphonate - related osteonecrosis of the jaw with vitamin d deficiency in rats .
necrotic bone in the oral cavity has recently been reported in patients treated with nitrogen - containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone .
similar to human patients , rat onj lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia . it was suggested that the pathophysiologic mechanism(s ) underpinning onj may involve the interaction between bisphosphonates and compromised vitamin d functions in the realm of skeletal homeostasis and innate immunity .
bischoff - ferrari evaluated the effect of 8002000 iu daily cholecalciferol and extended physiotherapy ( pt ) on complications after hip fracture . at baseline ,
50.9% of participants had 25(oh)d levels of less than 12 ng / ml and 97.7% of less than 30 ng / ml .
extended pt was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 iu / d , was successful in reducing hospital readmission but not falls .
thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture .
hgberg evidenced amelioration of depression by vitamin d supplementation in swedish adolescents . in 54 swedish depressed adolescents increasing mean serum 25(oh)d from 41
nmol / l at baseline to 91 nmol / l after supplementation led to decreased symptoms of depression : well - being increased ( p < 0.001 ) and there was a significant improvement in eight of the nine items : depressed feeling ( p < 0.001 ) , irritability ( p < 0.05 ) , tiredness ( p < 0.001 ) , mood swings ( p < 0.01 ) , sleep difficulties ( p < 0.01 ) , weakness ( p < 0.01 ) , ability to concentrate ( p < 0.05 ) and pain ( p < 0.05).vitamin d supplementation alone has therapeutic effect in vitamin d deficient depressed patients .
huang described patients with multiple areas of chronic pain and supplemented with vitamin d3 1200 iu daily ( if serum 25(oh)d was 20 to 29 ng / ml ) or 50,000 iu weekly ( if serum 25(oh)d was < 20 ng / ml ) improved their pain levels , sleep , and various aspects of qol .
khoraminya reported therapeutic effects of vitamin d3 ( 1500 iu / day ) as adjunctive therapy to fluoxetine ( 20 mg ) in 42 patients with major depressive disorder . in the 8-weeks , double - blind , randomized , placebo - controlled trial depression severity based on hamilton depression rating scale hdrs and beck depression inventory bdi decreased significantly after intervention , with a significant difference between the two groups - the vitamin d + fluoxetine combination was significantly better than fluoxetine alone from the 4th week of treatment .
the exact mechanism by which vitamin d exerts its beneficial effect in epilepsy is still to be explored .
vitamin d receptors as well as the 1-hydroxylase , the enzyme that produces 1,25(oh)2d , are distributed widely in the brain .
vitamin d deficiency is known to be highly prevalent among epilepsy patients , but only one study , published nearly 40 y ago , documented that administration of vitamin d2 resulted in a seizure reduction of 30% on average .
in small study of hollo vitamin d3 supplementation ( oral dose of 40,000200,000 iu bolus in order to normalize vitamin d deficiency , and then a daily maintenance dose of 20002600 iu ) results in improved seizure control in patients with pharmacoresistant epilepsy .
ten ( of 13 ) patients showed decreased seizure numbers during the 90 d following treatment onset as compared with the baseline period . among all patients ,
the median seizure reduction was 40% , and there was a non - significant tendency for patients with larger proportional elevation of 25(oh)d levels exhibiting a larger proportional reduction in seizure numbers .
median serum 25(oh)d level at baseline was 11.8 ng / ml ( range : 4.034.2 ng / ml ) and rose close to the normal range in all patients ( median : 38.0 ng / ml , range : 23.345.0 ng / ml ) .
the current body of evidence supports the view that vitamin d supplementation holds promises as risk - modifying intervention in tuberculosis ( tb ) , influenza and viral upper respiratory illnesses .
there has been a particular interest on the possible role of vitamin d supplementation as adjunctive therapy in settings of infection . a clear benefit of adjunctive vitamin d therapy in tb treatment , chronic hepatitis c ( chc ) infection and acute lower respiratory infections ( alri ) was observed . interferon ( ifn)-based treatment for hepatitis c virus
( hcv ) infection has a therapeutic limitation and side effects , a more efficient therapeutic strategy is desired .
two small prospective randomized controlled studies showed that those patients who received vitamin d3 supplementation of 2000 iu / day , targeting a 25(oh)d level > 80 nmol / l , in addition to peg - ifn / rbv combination therapy , had higher rates of rapid virologic response ( rvr ; 44% vs. 17% , p < 0.001 ) , complete early virologic response ( cevr ; 94% vs. 48% , p < 0.001 ) and sustained virological response svr ( 86% vs. 42% ; or 2.5 , 95% ci 2.04.9 , p < 0.001 ) in hcv-1   and svr ( 95% vs. 77% , p < 0.001 ) in hcv-2/3 infection compared with subjects treated with standard therapy .
moreover , recipients of vitamin d3 supplementation were less likely to relapse or non - respond to antiviral therapy .
similarly , a small retrospective study showed vitamin d3 supplementation improved svr rate in the treatment of recurrent hepatitis c post liver transplantation ( 53.3% vs. 18.5% , p = 0.02 ) .
logistic regression analysis identified vitamin d supplement [ odds ratio ( or ) 3.0 , 95% ci 2.04.9 , ] and the serum 25(oh)d levels ( < 15 or > 15 ng / ml , or 2.2 , ) as an independent predictor of viral response indicating that adding vitamin d3 to conventional peg / rbv therapy significantly improved viral response .
lange reported that cyp27b11260 rs10877012 was an independent predictor of sustained virologic response ( svr ) in patients with poor - response il28b genotypes , but not in patients with favorable il28b genotype .
patients with chronic hepatitis c showed a high prevalence of vitamin d defficiency [ 25(oh)d < 20 ng / ml ] during all seasons , but 25(oh)d serum levels were not associated with treatment outcomes .
this study suggested a role of 1,25-dihydroxyvitamin d [ 1,25(oh)2d , calcitriol ] produced in macrophages s important to enhance the therapeutic efficacy of medications to treat hepatitis c. however , the serum concentration of the 1,25-dihydroxyvitamind precursor , 25(oh)d was not a suitable predictor of treatment outcome in this study because its concentration was too low .
terrier investigated the association between serum vitamin d status and the presence of hcv extra - hepatic manifestations .
84 of 94 patients ( 89% ) were vitamin d deficient or insufficient (  30 ng / ml ) .
low 25(oh)d levels correlate with the presence of mixed cryoglobulinaemia and systemic vasculitis in chronic hcv infection .
these findings suggest the potential multifaceted benefits of vitamin d supplementation in hcv - infected patients . low serum 25(oh)d level is associated with a high risk of developing active tuberculosis ( tb ) .
sato investigated the relationships between serum 25(oh)d levels and clinical course of tb after standard therapy in hospitalized patients with tb .
drug sensitivity testing was performed for all the subjects and those not showing drug resistances for the first - line anti - tb drugs were included in the study .
nmol / l ] . in 23 patients treated with the standard first - line 4-drug regimen serum 25(oh)d levels showed significant negative correlation with time taken to obtain 3 consecutive negative sputum smears or tb bacteria cultures and indicated that low serum 25(oh)d level was a good predictor of a prolonged clinical course in patients with active pulmonary tb .
ganmaa examined the effect of vitamin d supplementation on tuberculin skin test ( tst ) conversion .
this double - blind , placebo - controlled study was conducted in 120 mongol schoolchildren ( 25(oh)d < 50
vitamin d supplementation ( 800 iu / day ) for 6 mo had significant favorable effects on serum 25(oh)d concentrations and on growth in stature .
leis documented that in children < 5 y old whose vitamin d intake was less than 80 iu / kg / d were greater than 4 times more likely to have alri compared with children with a vitamin d intake exceeding 80 iu / kg / day ( or 4.9 , ci : 1.5 , 16.4 ) .
therefore increased vitamin d supplementation could prevent bronchiolitis and pneumonia the most common reasons for hospitalization in young children .
in the polish atopic dermatitis interventional study vitamin d supplementation of 2000 iu / day for 3 mo in deficient patients led to two - fold increase in 25(oh)d and 2 fold decrease in disease symptoms ( table 2 ) . in pierrot - deseilligny observational , uncontrolled study vitamin d3 supplementation ( 3010 iu / day on average ) was given to 156 patients with relapsing  remitting multiple sclerosis , under first - line immunomodulatory therapy and with initial 25(oh)d serum level lower than 100 nmol / l .
relapses were determined for 29.1  8.4 and 29.8  10.1 mo during and before vitamin d supplementation , respectively .
every 10 nmol increase in 25(oh)d level was associated with a reduction in the relapse incidence rate of 13.7% . according to the 25(oh)d levels , the relapse incidence rate ratio decreased as the 25(oh)d level increased up to 110 nmol / l .
extra - renal cells , such as parathyroid cells , smooth muscle cells , endothelial cells , pancreatic cells and immunomodulatory cells , contain the machinery to locally produce 1,25(oh)2d .
this may explain the associations of adequate vitamin d status with lower chronic disease risk .
thus , the ability to maintain sufficient serum concentrations of 25(oh)d , the substrate for extra - renal 1-hydroxylase for the local production of 1,25(oh)2d , is particularly important in ckd .
shroff verified the hypothesis in rct study that ergocalciferol supplementation in 47 vitamin d deficient children with ckd stages 24 delayed the onset of secondary hyperparathyroidism . in this randomized , double - blinded , placebo - controlled study in children with ckd24 who had vitamin d deficiency ( median follow - up was 12 mo ) the time to development of hyperparathyroidism was significantly longer with ergocalciferol treatment compared with placebo ( hazard ratio , 0.30 ; 95% confidence interval , 0.090.93 , p = 0.05 ) .
with ergocalciferol treatment , normal 25(oh)d levels were achieved in all 8 children with ckd2 , 8 of 11 children with ckd3 , but not in the single patient with ckd4 .
25(oh)d levels > 100 nmol / l were required to achieve normal levels of 1,25(oh)2 d. therefore ergocalciferol was an effective treatment that delayed the development of secondary hyperparathyroidism in children with ckd23 .
alvarez documented that vitamin d3 ( cholecalciferol ) treatment reduced parathyroid hormone levels in 46 adult patients with early chronic kidney disease in 1 y rct study .
subjects with early ckd ( stages 23 ) were supplemented with oral vitamin d3 ( vitamin d group ; 50,000 iu / wk for 12 wk followed by 50,000 iu every other week for 40 wk ) .
serum 25(oh)d increased in the vitamin d group only [ 26.7  6.8 to 42.8  16.9 ng / ml ; ] and remained elevated at 1 y. pth decreased from baseline only in the vitamin d group ( baseline : 89.1  49.3 to 70.1  24.8 pg / ml ; p = 0.01 ) at 12 weeks , but values were not significantly different from baseline at 1 y. blood pressure and fgf23 did not change in either group . thus serum pth levels improved after vitamin d3 treatment in adult ckd patients who had secondary hyperparathyroidism .
vitamin d supplementation as adjunctive therapy in osteoporosis why only some osteoporotic patients maintain a positive response to prolonged bisphosphonate therapy is unknown .
carmel examined bisphosphonate response and its association with serum 25(oh)d level in a  real world  setting .
serum 25(oh)d level was strongly associated with maintaining bisphosphonate response arguing that vitamin d may be involved in optimizing prolonged bisphosphonate therapy .
postmenopausal women with low bone mineral density ( bmd ) treated with bisphosphonates were categorized .
the definition of non - response to bisphosphonate therapy was based on the eurofors study , which identified patients for teriparatide therapy after  failing  anti - resorptive agents ( median duration of bisphosphonate treatment was 36 mo ) .
non - response included any of the following : ( 1 ) t - score of <
3.0 at the lumbar spine , femoral neck , total hip , or trochanter despite > 24 mo of bisphosphonates therapy ; ( 2 ) decrease of > 3.0% in bmd at the lumbar spine , bilateral femoral neck , total hip , or trochanter between the baseline and follow - up dexa scans ; ( 3 ) incident low - trauma fracture despite > 12 mo of bisphosphonate therapy . patients with a mean 25(oh)d  33 ng / ml had a 4.5-fold greater odds of a favorable response . patients with a mean 25(oh)d  33 ng / ml had a substantially greater likelihood of maintaining bisphosphonate response . the probability of inadequate response to bisphosphonate therapy measured as bmd increase was 4-fold higher in patients with 25(oh)d < 30 ( or , 4.42 ; 95% ci , 1.2215.97 , p = 0.02 ) . in patients with vitamin d deficiency response to
bisphosphonate therapy measured by bone turnover markers indicated that ctx decreased only by 48% in patient treated with alendronate in comparison to 61% in patient supplemented with cholecalciferol ( 0.266 mg / wk for 3 mo ; final vitamin d status - serum 25(oh)d 82 ng / ml ) .
bertoldo reported that serum 25(oh)d levels modulate the acutephase response associated with the first nitrogencontaining bisphosphonate infusion . body temperature and
( 40 individuals with severe chronic periodontitis ) bashutski evidenced that placebo patients with baseline vitamin d deficiency [ serum 25(oh)d , 1619
ng / ml ] had significantly less clinical attachment loss ( cal ) gain ( -0.43 mm vs. 0.92 mm , p < 0.01 ) and probing depth ( ppd ) reduction ( 0.43 mm vs. 1.83 mm , p < 0.01 ) than vitamin - d - sufficient individuals .
vitamin d deficiency at the time of periodontal surgery negatively affects treatment outcomes for up to 1 y and indicated that vitamin d status may be critical for post - surgical healing .
these data are supported by work of hokugo who described increased prevalence of bisphosphonate - related osteonecrosis of the jaw with vitamin d deficiency in rats .
necrotic bone in the oral cavity has recently been reported in patients treated with nitrogen - containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone .
similar to human patients , rat onj lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia .
it was suggested that the pathophysiologic mechanism(s ) underpinning onj may involve the interaction between bisphosphonates and compromised vitamin d functions in the realm of skeletal homeostasis and innate immunity .
bischoff - ferrari evaluated the effect of 8002000 iu daily cholecalciferol and extended physiotherapy ( pt ) on complications after hip fracture . at baseline ,
50.9% of participants had 25(oh)d levels of less than 12 ng / ml and 97.7% of less than 30 ng / ml .
extended pt was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000
thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture .
hgberg evidenced amelioration of depression by vitamin d supplementation in swedish adolescents . in 54 swedish depressed adolescents increasing mean serum 25(oh)d from 41
nmol / l at baseline to 91 nmol / l after supplementation led to decreased symptoms of depression : well - being increased ( p < 0.001 ) and there was a significant improvement in eight of the nine items : depressed feeling ( p < 0.001 ) , irritability ( p
< 0.05 ) , tiredness ( p < 0.001 ) , mood swings ( p < 0.01 ) , sleep difficulties ( p < 0.01 ) , weakness ( p < 0.01 ) , ability to concentrate ( p < 0.05 ) and pain ( p < 0.05).vitamin d supplementation alone has therapeutic effect in vitamin d deficient depressed patients .
huang described patients with multiple areas of chronic pain and supplemented with vitamin d3 1200 iu daily ( if serum 25(oh)d was 20 to 29 ng / ml ) or 50,000 iu weekly ( if serum 25(oh)d was < 20 ng / ml ) improved their pain levels , sleep , and various aspects of qol .
khoraminya reported therapeutic effects of vitamin d3 ( 1500 iu / day ) as adjunctive therapy to fluoxetine ( 20 mg ) in 42 patients with major depressive disorder . in the 8-weeks ,
double - blind , randomized , placebo - controlled trial depression severity based on hamilton depression rating scale hdrs and beck depression inventory bdi decreased significantly after intervention , with a significant difference between the two groups - the vitamin d + fluoxetine combination was significantly better than fluoxetine alone from the 4th week of treatment .
the exact mechanism by which vitamin d exerts its beneficial effect in epilepsy is still to be explored .
vitamin d receptors as well as the 1-hydroxylase , the enzyme that produces 1,25(oh)2d , are distributed widely in the brain .
vitamin d deficiency is known to be highly prevalent among epilepsy patients , but only one study , published nearly 40 y ago , documented that administration of vitamin d2 resulted in a seizure reduction of 30% on average . in small study of hollo vitamin d3 supplementation ( oral dose of 40,000200,000 iu bolus in order to normalize vitamin d deficiency , and then a daily maintenance dose of 20002600 iu ) results in improved seizure control in patients with pharmacoresistant epilepsy .
ten ( of 13 ) patients showed decreased seizure numbers during the 90 d following treatment onset as compared with the baseline period . among all patients ,
the median seizure reduction was 40% , and there was a non - significant tendency for patients with larger proportional elevation of 25(oh)d levels exhibiting a larger proportional reduction in seizure numbers .
median serum 25(oh)d level at baseline was 11.8 ng / ml ( range : 4.034.2 ng / ml ) and rose close to the normal range in all patients ( median : 38.0 ng / ml , range : 23.345.0 ng / ml ) .
there is a substantial and growing body of evidence indicating that the lower end of the adequate range is at least 80 nmol / l and , by some criteria , 100 nmol / l .
it was evidenced that transfering patients from vitamin d deficiency to proper vitamin d status ( 75100 nmol / l serum 25(oh)d ) increase effectiveness of therapies in infectious diseases ( chronic hepatitis c , tuberculosis ) , osteoporosis , multiple sclerosis , epilepsy , chronic kidney diseases and atopic dermatitis . for these reasons
doctors should take special attension to vitamin d status in patients suffering for these diseases properly implementing recent vitamin d recommendation .
 at least 80% of the whole polish population , including prepubertal children and adolescents , adults and seniors , are vitamin d deficient , defined as 25(oh)d < 50 
 nmol / l . 
 83% of polish newborns start their lives at the state of vitamin d deficiency because 78% of their mothers are also deficient . 
 it was observed that treating patient vitamin d deficiency to vitamin d status serum 25(oh)d ) 75100 nmol / l increased effectiveness of therapies in infectious diseases ( chronic hepatitis c , tuberculosis ) , osteoporosis , multiple sclerosis , epilepsy , chronic kidney diseases and atopic dermatitis . . 
 for these reasons doctors should take special attension to vitamin d status in patients suffering for these diseases properly implementing recent vitamin d recommendation . 
Introduction
Epidemiology of Vitamin D Deficiency in Poland
Effect of Vitamin D Status on Pharmacological Treatment Efficacy
Vitamin D supplementation and infectious diseases
Vitamin D supplementation as adjunctive therapy in autoimmune diseases
Vitamin D supplementation as adjunctive therapy in CKD
Vitamin D supplementation as adjunctive therapy in neurological disorders
Conclusions