title: Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment in Tanzania. Clinical features and molecular phenotypes of breast cancer in patients with type-2 diabetes mellitus. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Vitamin D status and the risk of cardiovascular disease death. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Randomized clinical trials. Perspectives on some recent ideas. Calcium plus vitamin D supplementation and the risk of colorectal cancer. Obesity, mammography use and accuracy, and advanced breast cancer risk. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals. Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: results of a United States case-control study. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial. Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging.
abstract: BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P < 0.001 ) . CONCLUSION 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations OBJECTIVE To investigate the clinical features , molecular phenotypes and clinical prognosis of breast cancer patients with type-2 diabetes mellitus , thereby providing a basis for individualized therapy of breast cancer . METHODS 105 breast cancer patients with type-2 diabetes mellitus ( DM ) presenting from January 2005 to December 2010 were enrolled in this study . 200 breast cancer non-diabetic patients in the same period were r and omly selected as the control group . The clinical data of DM group and control group were retrospectively analyzed . The SPSS12.0 software was used for statistics and survival analysis . RESULTS The mean age of the patients in DM group were of 57.2∓11.8 years , which was older compared with the control group . The percentage of postmenopausal patients was 71.4 % and the ratio of grade II+III was 98.8 % , which was higher than the control group . The  neoadjuvant chemotherapy response rate of DM group was 67.5 % , which was lower than control group . The patients in DM group had later clinical stage and more lymph metastasis . The proportion of advanced breast cancer was 68.57 % and the ratio of lymph node metastasis was 66.01 % . All the difference was significant ( P<0.05 ) . But there was no significant difference in tumor size and molecular phenotype between the diabetic group with breast cancer and the control group . Disease-free survival and overall survival rates of DM group were 80.2 % and 84.2 % , which were worse than those in the control group . All the differences were significant ( P<0.05 ) . After excluding the patients with other causes of death , results of overall survival still showed worse in DM group , but the difference was not statistically significant ( P>0.05 ) . Serum insulin at fasting and two hours postpr and ial were higher than normal value in DM group , but serum insulin levels in the control group changed in the normal range . CONCLUSION There were older patients , higher proportion of high pathological grade , more lymph node metastasis , later clinical stages in the diabetic group with breast cancer . Breast cancer patients with type-2 diabetes mellitus were at risk of a poor prognosis . Hyperinsulinemia may be the real cause of poor prognosis in breast cancer patients with type-2 diabetes 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 Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline .  Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis In spite of the controversy over the role of r and omized clinical trials  in medical research , the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-r and omized studies such as those relying on the use of historical controls and adjustment technics . Others have suggested that recent statistical innovations for improving clinical trials , including adaptive allocation of treatment to patients and sequential stopping procedures , are underutilized . These innovations , though theoretically interesting , are not easily adapted to large-scale , complex medical trials in which there may be multiple end points and delayed response times . Ethical considerations suggest that r and omized trials are more suitable than uncontrolled experimentation in protecting the interests of patients . R and omized clinical trials remain the most reliable method for evaluating the efficacy of therapies BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer  among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) BACKGROUND Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women , but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear . METHODS We prospect ively collected data during 1996 - 2005 on 287,115 postmenopausal women not using hormone therapy ( HT ) who underwent 614,562 mammography examinations ; 4,446 women were diagnosed with breast cancer within 12 months of a mammography examination . We calculated rates per 1,000 mammography examinations of large ( > 15 mm ) , advanced-stage ( IIb , III , or IV ) , high- grade ( 3 or 4 ) , estrogen receptor (ER)-positive and -negative , and screen-detected and non-screen-detected breast cancer across body mass index ( BMI , kg/m(2 ) ) groups defined as normal ( 18.5 - 24.9 ) , overweight ( 25.0 - 29.9 ) , obese class I ( 30.0 - 34.9 ) , and obese class II/III ( > or = 35.0 ) , adjusting for age , race/ethnicity , and mammography registry and use . All statistical tests were two-sided . RESULTS Adjusted rates per 1000  mammography examinations of overall breast cancer increased across BMI groups ( 6.6 normal , 7.4 overweight , 7.9 obese I , 8.5 obese II/III ; P(trend ) < .001 ) , as did rates of advanced disease , including large invasive ( 2.3 normal , 2.6 overweight , 2.9 obese I , 3.2 obese II/III ; P(trend ) < .001 ) , advanced-stage ( 0.8 normal , 0.9 overweight , 1.3 obese I , 1.5 obese II/III ; P(trend ) < .001 ) , and high nuclear grade ( 1.5 normal , 1.7 overweight , 1.7 obese I , 1.9 obese II/III ; P(trend ) = .10 ) tumors . Rates of ER-positive tumors increased across BMI groups ( P(trend ) < .001 ) ; rates of ER-negative tumors did not . Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women , but rates of non-screen-detected ( false-negative ) cancers were similar . Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use . CONCLUSIONS Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT ; thus , biologic differences in breast tumor development and /or progression may be important BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin CONTEXT The pathogenesis of depression is not fully understood , but studies suggest that low- grade systemic inflammation contributes to the development of depression . OBJECTIVE To test whether elevated plasma levels of C-reactive protein ( CRP ) are associated with psychological distress and depression . DESIGN We performed cross-sectional and prospect i ve analyses of CRP levels in 4 clinical ly relevant categories using data from 2 general population studies . SETTING The Copenhagen General Population and the Copenhagen City Heart studies . PARTICIPANTS We examined 73 131 men and women aged 20 to 100 years . MAIN OUTCOME MEASURES We ascertained psychological distress with  2 single-item self-reports and depression using self-reported antidepressant use , register-based prescription of antidepressants , and register-based hospitalization with depression . RESULTS In cross-sectional analyses , increasing CRP levels were associated with increasing risk for psychological distress and depression ( P = 3 × 10 - 8 to P = 4 × 10 - 105 for trend ) . For self-reported use of antidepressants , the odds ratio was 1.38 ( 95 % CI , 1.23 - 1.55 ) for CRP levels of 1.01 to 3.00 mg/L , 2.02 ( 1.77 - 2.30 ) for 3.01 to 10.00 mg/L , and 2.70 ( 2.25 - 3.25 ) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants , the corresponding odds ratios were 1.08 ( 95 % CI , 0.99 - 1.17 ) , 1.47 ( 1.33 - 1.62 ) , and 1.77 ( 1.52 - 2.05 ) , respectively ; for hospitalization with depression , 1.30 ( 1.01 - 1.67 ) , 1.84 ( 1.39 - 2.43 ) , and 2.27 ( 1.54 - 3.32 ) , respectively . In prospect i ve analyses , increasing CRP levels were also associated with increasing risk for hospitalization with depression ( P = 4 × 10 - 8 for trend ) . CONCLUSIONS Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population OBJECTIVES To test whether accelerated sarcopenia in older persons with high interleukin (IL)-6 serum levels plays a role in the prospect i ve association between inflammation and disability found in many studies . DESIGN Cohort study of older women with moderate to severe disability . PARTICIPANTS Six hundred twenty older women from the Women 's Health and Aging Study in whom information on baseline IL-6 serum level was available . MEASUREMENTS Self-report of functional status , objective measures of walking performance , and knee extensor strength were assessed at baseline and over six semiannual follow-up visits . Potential confounders were baseline age , race , body mass index , smoking , depression , and medical conditions . RESULTS At baseline , women with high IL-6 were more often disabled and had lower walking speed . After adjusting for confounders , women in the highest IL-6 tertile ( IL-6>3.10 pg/mL ) were at higher risk of developing incident mobility disability ( risk ratio ( RR ) = 1.50 , 95 % confidence interval ( CI ) = 1.01 - 2.27 ) , disability in activities of daily living ( RR = 1.41 , 95 % CI = 1.01 - 1.98 ) , and severe limitation in walking ( RR = 1.61 , 95 % CI = 1.09 - 2.38 ) and experienced steeper declines in walking speed ( P < .001 ) than women in the lowest IL-6 tertile ( IL-6 < or = 1.78 pg/mL ) . Decline in knee extensor strength was also steeper , but differences across IL-6 tertiles were not significant . After adjusting for change over time in knee extensor strength , the association between high IL-6 and accelerated decline of physical function was no longer statistically significant . CONCLUSIONS Older women with high IL-6 serum levels have a higher risk of developing physical disability and experience a steeper decline in walking ability than those with lower levels , which are partially explained by a parallel decline in muscle strength Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents . This case-control study was design ed to assess the associations between  cutaneous melanoma ( CM ) and exposure to nonsteroidal anti-inflammatory drugs ( NSAIDs ) and  statins in current users . A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospect ively recruited and interviewed . We assessed participants ' demographic characteristics , CM risk factors , and current and previous use of medications . Multivariable conditional logistic regression models were used to estimate adjusted odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) for associations between  NSAIDs and /or aspirin ( ASA ) , statin exposure , and CM risk .  Half of the subjects were men ( mean age 60 years ) . After adjusting for confounders , use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group ( adjusted OR=0.57 ; 95 % CI=0.43 - 0.77 ) . Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use ( > 5 years adjusted OR=0.51 , 95 % CI=0.35 - 0.75 ) . No significant protective effect was observed with statin exposure ( OR=0.97 , 95 % CI=0.73 - 1.29 ) . Long-term use of NSAIDs , especially ASA , is associated with a significantly decreased risk of CM development . Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM BACKGROUND Calcium and vitamin D ( CaD ) supplementation trials including the Women 's Health Initiative ( WHI ) trial of CaD have shown nonsignificant reductions in total mortality . This report examines intervention effects on total and cause-specific mortality by age and adherence . METHODS The WHI CaD trial was a r and omized , double-blind , placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51 - 82 years from 40 U.S. clinical centers . Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3 ) daily or placebo with average follow-up of 7.0 years . RESULTS The hazard ratio ( HR ) for total mortality was 0.91 ( 95 % confidence interval [ CI ] , 0.83 - 1.01 ) with 744 deaths in women r and omized to CaD versus 807 deaths in the placebo group . HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality , but near unity for coronary heart disease and other causes of death . HRs for total mortality were 0.89 in the 29,942 women younger than 70 years ( 95 % CI , 0.79 - 1.01 ) and 0.95 in the 6,340 women aged 70 and older ( 95 % CI , 0.80 - 1.12 ; p value for age interaction = .10 ) . No statistically significant interactions were observed for any baseline characteristics . Treatment effects did not vary significantly by season . CONCLUSIONS In the WHI CaD trial , supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women . These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality BACKGROUND Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging . The purpose of this investigation was to examine the cross-sectional and prospect i ve relationships between markers of inflammation , interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) , with several measures of physical performance in older persons aged 70 to 79 years . METHODS Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging ( n = 1189 ) , a subset of the Established Population s for Epidemiologic Studies of the Elderly ( n = 4030 ) . Plasma  IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions . Physical function measures included h and grip strength , signature time , chair st and s ( time to complete five repetitions ) , and 6-m walk time . RESULTS Women had lower ( p < .05 ) IL-6 levels than men , but there was no significant difference between blacks and whites . IL-6 and CRP levels were higher ( p < .05 ) in current smokers than in nonsmokers and in those with a greater body mass index ( BMI ) . Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher ( p < .001 ) IL-6 and CRP levels in less active individuals . After adjusting for age , sex , race , BMI , smoking status , use of nonsteroidal anti-inflammatory drugs , and prevalence of morbidity , those in the top two quartiles for walking speed had lower ( p = .012 ) IL-6 levels than those in the bottom quartile . In addition , there was a trend ( p = .038 ) for lower CRP levels in those with higher walking speed . CRP levels were also lower ( p = .04 ) in individuals in the top quartile for grip strength . No significant differences were noted for chair st and s or signature time performance . Repeat performance measures obtained on 405 subjects ( 67 % of those eligible at baseline ) obtained 7 years later had declined significantly ( grip strength , 18 % ; signature time , 21 % ; walking speed , 31 % ; p < .001 ) , except for the chair rise ; however , baseline IL-6 and CRP were not associated with a change in performance . However , those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels ( p < .01 ) and slower walking speed ( p < .05 ) . CONCLUSIONS Although IL-6 has been shown to predict onset of disability  in older persons and both IL-6 and CRP are associated with mortality risk , these markers of inflammation have only limited associations with physical performance , except for walking measures and grip strength at baseline , and do not predict change in performance 7 years later in a high-functioning subset of older adults
target: The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health .
  Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders .
  In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
background: Low serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) have been associated with many non-skeletal disorders .
  However , whether low 25(OH)D is the cause or result of ill health is not known .