Serum 25-Hydroxyvitamin D Concentrations and Depressive Symptoms among Young Adult Men and Women Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) Vitamin D status has a linear association with seasonal infections and lung function in British adults. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Predicted 25-hydroxyvitamin D in relation to incidence of breast cancer in a large cohort of African American women Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography Prospective Population-Based Study of the Association between Serum 25-Hydroxyvitamin-D Levels and the Incidence of Specific Types of Cancer Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Are Hill's criteria for causality satisfied for vitamin D and periodontal disease? High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial Calcium plus vitamin D supplementation and the risk of breast cancer. Vitamin D Status and the Risk of Lung Cancer: A Cohort Study in Finland
There has been an increased interest in the role of vitamin D in depression ; however , there have been few studies conducted in younger population groups . Our aim was to investigate the association between vitamin D status and depressive symptoms in a non- clinical young adult sample living in Dunedin , New Zeal and . A cross-sectional sample of 615 young adults completed a question naire including demographics and the  Centre  for Epidemiological Studies Depression Scale ( CES-D ) . Height , weight and a blood sample for 25-hydroxyvitamin D [ 25(OH)D ] was obtained . Serum 25(OH)D was used to predict depression scores , adjusting for potential confounders including time spent outdoors for 13 consecutive days , BMI , age , sex and ethnicity . Prevalence of low vitamin D was high even in this age group , and serum 25(OH)D was negatively associated with depression symptoms before and after adjustment . When investigating the relationship between the presence versus absence of depressive symptoms and quartiles of 25(OH)D , participants in the lowest quartile were more likely to report depressive symptoms compared with those in the highest quartile . Although our findings suggest that vitamin D is a predictor of depression symptomatology , even when controlling for time spent outdoors , a r and omised controlled trial in this young adult target group is needed to confirm the association Background Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p<0.0001 ) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese AIMS To compare depressive symptoms in participants with low and high serum 25-hydroxyvitamin D ( 25(OH)D ) levels and to examine whether supplementation with vitamin D(3 ) would improve symptoms in those with low serum 25(OH)D levels . METHOD Participants with low 25(OH)D levels were r and omised to either placebo or 40 000 IU vitamin D(3 ) per week for 6 months . Individuals with high serum 25(OH)D levels were used as nested controls . Depressive symptoms were evaluated with the Beck Depression Inventory , Hospital Anxiety and Depression Scale , Seasonal Pattern Assessment Scale and Montgomery-Åsberg Depression Rating Scale . The study was registered at Clinical Trials.gov ( NCT00960232 ) . RESULTS Participants with low 25(OH)D levels ( n = 230 ) at baseline were more depressed ( P<0.05 ) than participants with high 25(OH)D levels ( n = 114 ) . In the intervention study no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo . CONCLUSIONS Low levels of serum 25(OH)D are associated with depressive symptoms , but no effect was found with vitamin D supplementation BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with  respiratory infections and lung function .  We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research Background Vitamin D deficiency , which has been linked to an increased risk of colorectal cancer , is particularly common among African Americans . Previous studies of vitamin D status and breast cancer risk , mostly conducted in white women , have had conflicting results . We examined the relationship between predicted  vitamin D status and incidence of breast cancer in a cohort of 59,000 African American women . Methods Participants in the Black Women ’s Health Study have been followed by biennial mail question naires since 1995 , with self-reported diagnoses of cancer confirmed by hospital and cancer registry records . Repeated five-fold cross-validation with linear regression was used to derive the best 25-hydroxyvitamin D ( 25(OH)D ) prediction model based on measured 25(OH)D in plasma specimens obtained from 2856 participants in 2013–2015 and question naire-based variables from the same time frame . In the full cohort , including 1454 cases of incident invasive breast cancer , Cox proportional hazards models were used to compute the incidence rate ratio ( IRR ) for each quartile of predicted vitamin D score relative to the highest quartile . Predicted vitamin D score for each two-year exposure period was a cumulative average of predicted scores from all exposure periods up to that time . Results Twenty-two percent of women with measured 25(OH)D were categorized as “ deficient ” ( < 20 ng/mL ) and another 25 % as “ insufficient ” ( 20–29 ng/mL ) . The prediction model explained 25 % of variation in measured 25(OH)D and the correlation coefficient for predicted versus observed 25(OH)D averaged across all cross-validation runs was 0.49 ( SD 0.026 ) . Breast cancer risk increased with decreasing quartile of predicted 25(OH)D , p for trend 0.015 ; the IRR for the lowest versus highest quartile was 1.23 ( 95 % confidence interval 1.04 , 1.46 ) . Conclusions In prospect i ve data , African American women in the lowest quartile of cumulative predicted 25(OH)D were estimated to have a 23 % increased risk of breast cancer relative to those with relatively high levels . Preventing vitamin D deficiency may be an effective means of reducing breast cancer incidence in African American women PURPOSE A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma . METHODS A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma . We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort ( median follow-up , 4.7 years ) . RESULTS In the retrospective study , self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse ( odds ratio = 0.6 ; 95 % CI , 0.4 to 1.1 ; P = .09 ) . Nonrelapsers had higher mean 25-hydroxyvitamin D(3 ) levels than relapsers ( 49 v 46 nmol/L ; P = .3 ; not statistically significant ) . In the cohort ( prospect i ve ) study , higher 25-hydroxyvitamin D(3 ) levels were associated with lower Breslow thickness at diagnosis ( P = .002 ) and were independently protective of relapse and death : the hazard ratio for relapse-free survival ( RFS ) was 0.79 ( 95 % CI , 0.64 to 0.96 ; P = .01 ) for a 20 nmol/L increase in serum level . There was evidence of interaction between the vitamin D receptor ( VDR ) BsmI genotype and serum 25-hydroxyvitamin D(3 ) levels on RFS . CONCLUSION Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome . The cohort study tests this hypothesis , providing evidence that higher 25-hydroxyvitamin D(3 ) levels , at diagnosis , are associated with both thinner tumors and better survival from melanoma , independent of Breslow thickness . Patients with melanoma , and those at high risk of melanoma , should seek to ensure vitamin D sufficiency . Additional studies are needed to establish optimal serum levels for patients with melanoma Accumulating evidence suggests that vitamin D may protect against cancer , but results from epidemiologic studies are inconclusive so far , and other studies looking into the prospect i ve association of total cancer mortality and serum 25-hydroxyvitamin D [ 25(OH)D ] levels , which are considered to be the best indicator of vitamin D status , are scarce . We measured 25(OH)D and 1,25-dihydroxyvitamin D in 3,299 patients from the Ludwigshafen Risk and Cardiovascular Health study . The baseline examination was done between July 1997 and January 2000 and included a fasting blood sampling in the morning before coronary angiography . During a median follow-up period of 7.75 years , 95 patients died due to cancer . After adjustment for possible confounders , the Cox proportional hazard ratio ( 95 % confidence interval ) of the fourth 25(OH)D quartile was 0.45 ( 0.22 - 0.93 ) when compared with the first quartile and the hazard ratio per increase of 25 nmol/L in serum 25(OH)D concentrations was 0.66 ( 0.49 - 0.89 ) . We found no association between serum 1,25-dihydroxyvitamin D levels and fatal cancer . In summary , our data suggest that low levels of 25(OH)D are associated with increased risk of fatal cancer in patients referred to coronary angiography and that the maintenance of a sufficient vitamin D status might therefore be a promising approach for the prevention and /or treatment of cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(5):1228–33 Background : Observational studies have suggested an inverse association between vitamin D status and  cancer  . We investigated the prospect i ve associations between vitamin D status and the total and specific type of cancer in three cohorts from the general Danish population . Methods : A total of 12,204 individuals 18 to 71 years old were included . The level of 25-hydroxyvitamin D was measured at baseline , and information about cancer was obtained from the Danish Cancer Registry . Results : During the 11.3-year median follow-up time , there were 1,248 incident cancers . HRs [ 95 % confidence intervals ( CI ) ] per 10 nmol/L higher baseline vitamin D level were : for all cancers ( HR = 1.02 ; 95 % CI , 0.99–1.04 ) , all cancers excluding non-melanoma skin cancer , NMSC ( HR = 1.00 ; 95 % CI , 0.97–1.03 ) , head and neck cancer ( HR = 0.97 ; 95 % CI , 0.84–1.12 ) , colorectal cancer ( HR = 0.95 ; 95 % CI , 0.88–1.02 ) , cancer of bronchus and lung ( HR = 0.98 ; 95 % CI , 0.91–1.05 ) , breast cancer ( HR = 1.02 ; 95 % CI , 0.96–1.09 ) , cancer of the uterus ( HR = 1.10 ; 95 % CI , 0.95–1.27 ) , prostate cancer ( HR = 1.00 ; 95 % CI , 0.93–1.08 ) , cancer of the urinary organs ( HR = 1.01 ; 95 % CI , 0.90–1.14 ) , NMSC ( HR = 1.06 ; 95 % CI , 1.02–1.10 ) , and malignant melanoma ( HR = 1.06 ; 95 % CI , 0.95–1.17 ) . Conclusions : Apart from a significantly higher risk for NMSC with higher vitamin D status , we found no statistically significant associations between vitamin D status and total or specific cancers . Impact : Our results do not indicate that there is an impact of vitamin D on total cancer incidence . Cancer Epidemiol Biomarkers Prev ; 23(7 ) ; 1220–9 . © 2014 AACR BACKGROUND R and omized controlled trials testing the association between vitamin D status and upper respiratory tract infection ( URTI ) have given mixed results . During a multicenter , r and omized controlled trial of colorectal adenoma chemoprevention , we tested whether 1000 IU/day vitamin D(3 ) supplementation reduced winter episodes and duration of URTI and its composite syndromes , influenza-like illness ( ILI ; fever and ≥2 of sore throat , cough , muscle ache , or headache ) and colds ( no fever , and ≥2 of runny nose , nasal congestion , sneezing , sore throat , cough , swollen or tender neck gl and s ) . METHODS The 2259 trial participants were aged 45 - 75 , in good health , had a history of colorectal adenoma , and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were r and omized to vitamin D(3 ) ( 1000 IU/day ) , calcium ( 1200 mg/day ) , both , or placebo . Of these , 759 participants completed daily symptom diaries . Secondary data included semiannual surveys of all participants . RESULTS Among those who completed symptom diaries , supplementation did not significantly reduce winter episodes of URTI ( rate ratio [ RR ] , 0.93 ; 95 % confidence interval [ CI ] , .79 - 1.09 ) including colds ( RR , 0.93 ; 95 % CI , .78 - 1.10 ) or ILI ( RR , 0.95 ; 95 % CI , .62 - 1.46 ) , nor did it reduce winter days of illness ( RR , 1.13 ; 95 % CI , .90 - 1.43 ) . There was no significant benefit according to adherence , influenza vaccination , body mass index , or baseline vitamin D status . Semiannual surveys of all participants ( N = 2228 ) identified no benefit of supplementation on ILI ( odds ratio [ OR ] , 1.14 ; 95 % CI , .84 - 1.54 ) or colds ( OR , 1.03 ; 95 % CI , .87 - 1.23 ) . CONCLUSIONS Supplementation with 1000 IU/day vitamin D(3 ) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 There is mounting evidence that periodontal disease ( PD ) is linked to low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations in addition to recognized risk factors like diet and smoking . This paper review s this evidence using Hill 's criteria for causality in a biological system . Evidence for strength of association , consistency , cohesion and ' dose-effects ' [ biological ' gradients ' ] include strong inverse correlations between serum 25(OH ) and both PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength ; induces formation of cathelicidin and other defensins that combat bacterial infection ; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms . Experimental evidence from limited supplementation studies [ using calcium and vitamin D ] shows that supplementation reduces tooth loss . Thus , existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill 's criteria for causality in a biological system . Further experimental evidence for effectiveness and temporality , preferably from r and omized controlled trials of vitamin D supplementation [ adjusting for other PD risk factors including diet and smoking to reduce confounding ] are necessary to confirm causality . If confirmed , dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and on how to avoid deficiency OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking < 400 IU/d as part of usual care ) . MEASUREMENTS The primary outcome was incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P < .001 ) . Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures BACKGROUND Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk , no r and omized trial has evaluated these relationships . METHODS Postmenopausal women ( N = 36 282 ) who were enrolled in a Women 's Health Initiative clinical trial were r and omly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3 ) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture . Mammograms and breast exams were serially conducted . Invasive breast cancer was a secondary outcome . Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects . A Cox proportional hazards model was used to estimate the risk of breast cancer associated with r and om assignment to calcium with vitamin D(3 ) . Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake , body mass index ( BMI ) , recreational physical activity , and breast cancer risks were evaluated using logistic regression models . Statistical tests were two-sided . RESULTS Invasive breast cancer incidence was similar in the two groups ( 528 supplement vs 546 placebo ; hazard ratio = 0.96 ; 95 % confidence interval = 0.85 to 1.09 ) . In the nested case-control study , no effect of supplement group assignment on breast cancer risk was seen . Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake ( diet and supplements ) ( r = 0.19 , P < .001 ) and were higher among women with lower BMI and higher recreational physical activity ( both P < .001 ) . Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity ( P(trend ) = .20 ) . CONCLUSIONS Calcium and vitamin D supplementation did not reduce invasive breast  cancer incidence in postmenopausal women . In addition , 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk . These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk Experimental data support the suppressing effect of vitamin D on lung carcinogenesis , but epidemiologic evidence is limited . The aim of the present study was to evaluate whether serum 25-hydroxyvitamin D [ 25(OH)D ] level is associated with the risk of  lung cancer  in a prospect i ve cohort study in Finl and . 25(OH)D levels were measured by RIA from serum collected at baseline ( 1978 - 1980 ) from 6,937 men and women . During a maximum follow-up of 24 years , 122 lung cancers were identified . After adjustment for potential confounders , no overall significant association between  vitamin D and lung cancer risk was observed [ relative risk ( RR ) for the highest versus lowest tertile , 0.72 ; 95 % confidence interval ( 95 % CI ) , 0.43 - 1.19 ; Ptrend = 0.22 ] . There was a statistically significant interaction between vitamin D and sex ( P = 0.02 ) and age ( P = 0.02 ) : serum 25(OH)D level was inversely associated with lung cancer incidence for women ( RR , 0.16 ; 95 % CI , 0.04 - 0.59 ; Ptrend < 0.001 ) and younger participants ( RR , 0.34 ; 95 % CI , 0.13 - 0.90 ; Ptrend = 0.04 ) but not for men ( RR , 1.03 ; 95 % CI , 0.59 - 1.82 ; Ptrend = 0.81 ) or older individuals ( RR , 0.92 ; 95 % CI , 0.50 - 1.70 ; Ptrend = 0.79 ) . In conclusion , although there was no overall association between vitamin D and lung cancer risk , women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk . Although experimental data support the suppressing effect of vitamin D on the development of lung cancer , large epidemiologic studies from different population s with repeated measurements of vitamin D are warranted to confirm this finding . ( Cancer Epidemiol Biomarkers Prev 2008;17(11):3274–8
The evidence shows that vitamin D supplementation provides some benefit in fracture prevention ( likely ∼10–15 % relative reduction ) , particularly at a dose ≥800 IU and with calcium ; a likely benefit in the rate of falls , though it is less clear whether the number of fallers changes ; and a possible small ( ∼5 % ) relative reduction in mortality .
Evidence does not support the use of vitamin D supplementation for the prevention of cancer , respiratory infections or rheumatoid arthritis .
Similarly , evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being .
Regular testing of 25-hydroxyvitamin D is generally not required , and mega-doses ( ≥300,000 IU ) appear to increase harms .
Over the past decade , a large body of observational evidence has suggested an association between  lower vitamin D status ( 25-hydroxyvitamin D ) and multiple acute and chronic disorders , including cancer , multiple sclerosis , depression and respiratory tract infections .
This evidence has fostered the hypothesis that increasing vitamin D intake may treat and prevent such disorders .
Our objective was to perform a critical analysis of the highest-level evidence for ten common beliefs regarding vitamin D for the prevention of falls , fractures and respiratory tract infections , the reduction of cancer incidence/mortality and overall mortality , and the prevention or treatment of depression/mental well-being , rheumatoid arthritis and multiple sclerosis , as well as maximum dosing and regular testing .