Serum 25-Hydroxyvitamin D Levels and Risk of Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND & AIMS: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults. METHODS: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders. RESULTS: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals. CONCLUSIONS: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease.

The Relationship Between Vitamin D Intake and Serum 25-hydroxyvitamin D in Young Children: A Meta-Regression to Inform WHO/FAO Vitamin D Intake Recommendations.

BACKGROUND: This work was commissioned by the World Health Organization and Food and Agriculture Organization to inform their update on the vitamin D requirements for children aged <4 y. OBJECTIVES: The objective of this work was to undertake multilevel and multivariable dose-response modeling of serum 25-hydroxyvitamin D (25OHD) to total vitamin D intake in children aged <4 y with the goal of deriving updated vitamin D requirements for young children. METHODS: Systematically identified randomized controlled trials among healthy children from 2 wk up to 3.9 y of age provided with daily vitamin D supplements or vitamin D-fortified foods were included. Linear and nonlinear random effects multilevel meta-regression models with and without covariates were fitted and compared. Interindividual variability was included by simulating the individual serum 25OHD responses. The percentage of individuals reaching set minimal and maximal serum 25OHD thresholds was calculated and used to derive vitamin D requirements. RESULTS: A total of 31 trials with 186 data points from North America, Europe, Asia, and Australasia/Oceania, with latitudes ranging from 61°N to 38°S, and with participants of likely mostly light or medium skin pigmentation, were included. In 29 studies the children received vitamin D supplements and in 2 studies the children received vitamin D-fortified milk with or without supplements. The dose-response relationship between vitamin D intake and serum 25OHD was best fitted with the unadjusted quadratic model. Adding additional covariates, such as age, did not significantly improve the model. At a vitamin D intake of 10 µg/d, 97.3% of the individuals were predicted to achieve a minimal serum 25OHD threshold of 28 nmol/L. At a vitamin D intake of 35 µg/d, 1.4% of the individuals predicted to reach a maximal serum 25OHD threshold of 200 nmol/L. CONCLUSIONS: In conclusion, this paper details the methodological steps taken to derive vitamin D requirements in children aged <4 y, including the addition of an interindividual variability component.

Serum 25-hydroxyvitamin D threshold and risk of rickets in young children: a systematic review and individual participant data meta-analysis to inform the development of dietary requirements for vitamin D.

PURPOSE: The objective of this systematic review was to determine a minimum serum 25-hydroxyvitamin D (25OHD) threshold based on the risk of having rickets in young children. This work was commissioned by the WHO and FAO within the framework of the update of the vitamin D requirements for children 0-3 years old. METHODS: A systematic search of Embase was conducted to identify studies involving children below  4 years of age with serum 25OHD levels and radiologically confirmed rickets, without any restriction related to the geographical location or language. Study-level and individual participant data (IPD)-level random effects multi-level meta-analyses were conducted. The odds, sensitivity and specificity for rickets at different serum 25OHD thresholds were calculated for all children as well as for children with adequate calcium intakes only. RESULTS: A total of 120 studies with 5412 participants were included. At the study-level, children with rickets had a mean serum 25OHD of 23 nmol/L (95% CI 19-27). At the IPD level, children with rickets had a median and mean serum 25OHD of 23 and 29 nmol/L, respectively. More than half (55%) of the children with rickets had serum 25OHD below 25 nmol/L, 62% below 30 nmol/L, and 79% below 40 nmol/L. Analysis of odds, sensitivities and specificities for nutritional rickets at different serum 25OHD thresholds suggested a minimal risk threshold of around 28 nmol/L for children with adequate calcium intakes and 40 nmol/L for children with low calcium intakes. CONCLUSION: This systematic review and IPD meta-analysis suggests that from a public health perspective and to inform the development of dietary requirements for vitamin D, a minimum serum 25OHD threshold of around 28 nmol/L and above would represent a low risk of nutritional rickets for the majority of children with an adequate calcium intake.

Causal association between serum 25-hydroxyvitamin D levels and right ventricular structure and function: A Mendelian randomization study.

BACKGROUND AND AIM: Deficient concentrations of vitamin D have been linked to several cardiovascular conditions, but the causal relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and right ventricular structure and function remains unclear. Mendelian randomization (MR) was employed to inspect this association. METHODS AND RESULTS: Genetic instrumental variables associated with 25(OH)D levels were acquired from genome-wide association studies (GWAS) analyses. Summary statistics for right ventricular structure and function, including right ventricular end diastolic volume, right ventricular end systolic volume, right ventricular stroke volume, and right ventricular ejection fraction, were acquired from publicly available GWAS datasets. For the primary analysis, the inverse variance weighted (IVW) method was utilized in performing the MR analysis. Additionally, secondly analyses were conducted to estimate the robustness and consistency of the attained conclusions. The MR analysis did not reveal a considerable causal association between serum 25(OH)D levels and right ventricular end diastolic volume (ß: 0.112, 95% confident interval [CI]: -0.006 to 0.230, p = 0.063), right ventricular end systolic volume (ß: 0.102, 95% CI: -0.021 to 0.226, p = 0.105), right ventricular stroke volume (ß: 0.095, 95% CI: -0.018 to 0.207, p = 0.099), or right ventricular ejection fraction (ß: -0.005, 95% CI: -0.123 to 0.112, p = 0.928). CONCLUSIONS: Our findings did not reveal any substantial evidence supporting a causal relationship between serum 25(OH)D levels and the structure and function of the right ventricle. These findings suggest that serum 25(OH)D levels may not directly influence right ventricular parameters assessed.

Association of serum 25-hydroxyvitamin D concentration with all-cause and cause-specific mortality in hypertensive patients.

BACKGROUND AND AIMS: To examine the association of serum 25-hydroxyvitamin D [25(OH)D] with all-cause mortality and disease-specific mortality in patients with hypertension. METHODS AND RESULTS: This cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by association with National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cause-specific mortality and 95% confidence intervals (CIs) for serum 25(OH)D concentrations. The cohort included 10,325 adult participants. The mean serum 25(OH)D level was 65.87 nmol/L, and 32.2% of patients were vitamin D deficient (<50 nmol/L). During a mean follow-up of 77 months, 1290 deaths were recorded, including 345 cardiovascular deaths and 237 cancer deaths. Patients with higher serum 25(OH)D were more likely to have lower all-cause mortality and cardiovascular mortality than those with serum 25(OH)D < 25.00 nmol/L. For cancer mortality in hypertensive patients, vitamin D may not have a predictive role in this. CONCLUSIONS: This study shows that higher 25(OH)D levels are significantly associated with lower all-cause mortality and cardiovascular disease (CVD) mortality. These findings suggest that maintaining adequate vitamin D status may reduce the risk of death in patients with hypertension.

U-shaped association between serum 25-hydroxyvitamin D concentrations and urinary leakage among adult females aged 45 years and over in the United States: a cross-sectional study.

BACKGROUND: The relationship between serum vitamin D status and urinary leakage (UL) among middle-aged females needs to be further studied. The aim of this study was to evaluate the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with UL among American females ages 45 years and over. METHODS: Seven cycles of the National Health and Nutrition Examination Survey (NHANES) with self-report UL data, were used. A total of 9525 women aged 45 years and older were enrolled in this study. Univariate and multivariate logistic regression models and the smooth curve fitting were utilized to analyze the association between clinical UL and serum 25-hydroxyvitamin D [25(OH)D] concentrations. RESULTS: A non-linear relationship between serum 25(OH)D concentrations and clinical ULwas observed. When serum 25(OH)D concentration was higher than the inflection point 63.5 nmol/L, a positive correlation was observed between serum 25(OH)D concentrations and clinical UL ([OR]: 1.007, 95%CI: 1.005-1.009, P < 0.01). However, when serum 25(OH)D concentration was below the inflection point 63.5 nmol/L, a negative correlation was observed between serum 25(OH)D concentrations and clinical UL ([OR]: 0.993, 95%CI: 0.989-0.996, P < 0.01). CONCLUSIONS: The association between serum vitamin D and the risk of UL exhibited a U-shaped pattern among US middle-aged females, with an inflection point occurring at a serum 25(OH)D concentration of 63.5 nmol/L.

Serum 25-hydroxyvitamin D mediates the association between heavy metal exposure and cardiovascular disease.

BACKGROUND: Mediation analysis aims to determine how intermediate variables affect exposure to disease. In this study, 25-hydroxyvitamin D (25(OH)D) was evaluated to assess its role in mediating heavy metal exposure and cardiovascular disease (CVD). METHODS: A total of 9,377 participants from the National Health and Nutrition Examination Survey (NHANES) for the years 2011-2018 were included. Firstly, restricted cubic spline (RCS), and multivariable logistic regression model were performed to estimate the association between heavy metal exposure (Cadmium, Lead, Mercury, Manganese, and Selenium), as well as serum 25(OH)D and CVD. Secondly, using generalized linear regression model and generalized additive models with smooth functions, we investigated the correlation between heavy metal exposure and serum 25(OH)D. Finally, the mediation effect of serum 25(OH)D in the associations between heavy metal exposure and CVD was explored. RESULTS: The RCS plots revealed that Cadmium, and Lead were positively and linearly associated with CVD, while Mercury, and Manganese were inversely and linearly associated with CVD. Additionally, a roughly L- and U-shaped relationship existed between Selenium, as well as 25(OH)D and CVD. When potential confounding factors were adjusted for, serum 25(OH)D had negative associations with Cadmium, Lead, and Manganese, while serum 25(OH)D had positive relationship with Selenium. There was a mediation effect between Manganese exposure and CVD, which was mediated by 25(OH)D. CONCLUSION: According to the mediation analysis, the negative association between Manganese exposure and incident CVD was increased by 25(OH)D. The increasing dietary intake of Vitamin D could increase the protective effect of manganese intake on CVD.

Association between Serum 25-Hydroxyvitamin D Concentrations and Respiratory Infection among United States Adults.

BACKGROUND: Vitamin D plays an essential role in immune responses to infections. However, the association between serum 25(OH)D concentrations and respiratory infection remains unclear. OBJECTIVES: The current study aimed to examine the association between serum 25(OH)D concentrations and respiratory infection among the United States adults. METHODS: This cross-sectional study used data from the NHANES 2001-2014. Serum 25(OH)D concentrations were measured by radioimmunoassay or liquid chromatography-tandem mass spectrometry and were classified as ≥75.0 nmol/L (sufficiency), 50.0-74.9 nmol/L (insufficiency), 30.0-49.9 nmol/L (moderate deficiency), and <30 nmol/L (severe deficiency). The respiratory infections included self-reported head or chest cold as well as influenza, pneumonia, or ear infection within the last 30 d. The associations between serum 25(OH)D concentrations and respiratory infections were examined using weighted logistic regression models. Data are presented as ORs and 95% CIs. RESULTS: This study included 31,466 United States adults ≥20 y of age (47.1 y, 55.5% women) with a mean serum 25(OH)D concentration of 66.2 nmol/L. After adjusting for sociodemographic characteristics, season of examination, lifestyle and dietary factors, and body mass index, compared with participants with a serum 25(OH)D concentration ≥75.0 nmol/L, those with a serum 25(OH)D concentration <30 nmol/L had higher risk of head or chest cold (OR: 1.17; 95% CI: 1.01, 1.36) and other respiratory diseases, including influenza, pneumonia, and ear infections (OR: 1.84; 95% CI: 1.35, 2.51). In the stratification analyses, lower serum 25(OH)D concentrations were associated with a higher risk of head or chest cold in obese adults but not in nonobese adults. CONCLUSIONS: Serum 25(OH)D concentrations are inversely associated with respiratory infection occurrence among United States adults. This finding may shed light on the protective effect of vitamin D on the respiratory health.

Association between food intake patterns and serum vitamin D concentrations in US adults.

The objective of this study was to investigate the association between food patterns and serum vitamin D concentrations in US adults. Data from two cycles of National Health and Nutrition Examination Surveys, 2003-2004 and 2005-2006, were used (n 6637). Three major food patterns were derived using factor analysis. These three patterns were labeled as meat and processed meat foods (MPF), vegetables, fruit, nuts, and whole grains (VFNW), and sweet, snack, and beverage pattern (SSB). Serum vitamin D was measured with RIA and later standardized to reflect the assay changes over time. In multivariate-adjusted regression analysis, the MPF pattern was significantly, inversely associated with serum vitamin D concentrations (P < 0·001). However, the relation between the VFNW pattern and serum vitamin D was non-linear (P < 0·001). There was no relationship between SSB pattern and serum vitamin D in US adults. In conclusion, persons with a high intake of meat and processed meats are associated with lower serum vitamin D concentrations. Reducing processed foods and emphasizing VFNW will be beneficial from a health perspective.

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Relatively low and moderate pre-fracture serum 25-hydroxyvitamin D levels associated with the highest survival in elderly hip fracture patients in Finland: a minimum 3-year follow-up.

The association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L. PURPOSE: To explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland. METHODS: A prospectively collected cohort of hip fracture patients (n = 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified: < 50, 50-74, 75-99, and ≥ 100 nmol/L. Survival was analyzed with a Bayesian multivariate model. Relative survival was explored with the life table method according to serum 25-hydroxyvitamin D. Mortality according to serum 25-hydroxyvitamin D level and to the hospital was calculated. RESULTS: Mortality in the patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L was significantly lower than in all other patients together at every post-fracture year. The most important factors for survival were age under 85 years; living in an actual/private home; serum 25-hydroxyvitamin D level of 50-74 nmol/L, followed by 75-99 nmol/L; ASA classes 1-2 and 3; and female sex. The mean age of patients with serum 25-hydroxyvitamin D level of 50-99 nmol/L was significantly higher than in other levels. Relative survival was highest in men, women, and patients in hospital B with serum 25-hydroxyvitamin D level of 50-74 nmol. CONCLUSION: The highest 3-year survival and the lowest mortality in this cohort appeared in patients with pre-fracture serum 25-hydroxyvitamin D level of 50-74 nmol/L. This result differs from similar studies and is lower than the recommended level of 25-hydroxyvitamin D among hip fracture patients. The results should be examined in future research with larger data.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 1 liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays - impact of 3-epi-25-hydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays used for the determination of serum total 25-hydroxyvitamin D (25(OH)D), which is the sum of 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3). A set of 50 single-donor samples was assigned target values for concentrations of 25(OH)D2, 25(OH)D3, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) using isotope dilution liquid chromatography - tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 1 includes results from 14 laboratories using 14 custom LC-MS/MS assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 53% of the LC-MS/MS assays met the VDSP criterion of mean % bias ≤ |±5%|. For the LC-MS/MS assays not meeting the ≤ |±5%| criterion, four assays had mean % bias of between 12 and 21%. Based on multivariable regression analysis using the concentrations of the four individual vitamin D metabolites in the 50 single-donor samples, the performance of several LC-MS/MS assays was found to be influenced by the presence of 3-epi-25(OH)D3. The results of this interlaboratory study represent the most comprehensive comparison of LC-MS/MS assay performance for serum total 25(OH)D and document the significant impact of the lack of separation of 3-epi-25(OH)D3 and 25(OH)D3 on assay performance, particularly with regard to mean % bias.

Adequacy of calcium and vitamin D nutritional status in a nationally representative sample of Irish teenagers aged 13-18 years.

CONTEXT AND PURPOSE: In light of the key roles of vitamin D and calcium in adolescent bone health, there is a critical need for representative data on nutritional status for both micronutrients in teenagers. The present work used data from the recent representative National Teens' Food Survey II (2019-2020) to assess calcium and vitamin D intakes of teenagers in Ireland, including adequacy of such intakes, as well as, for the first time, to characterise serum 25-hydroxyvitamin D (25(OH)D) concentrations and their determinants. METHODS: Usual calcium and vitamin D intake estimates were generated using food intake data (via 4-day weighed food records) from a nationally representative sample of teenagers aged 13-18 years in Ireland (n 428). Serum 25(OH)D was measured (via LC-MS/MS) in the 57.5% (n 246) who provided a blood sample. RESULTS: Sixty-seven and 94% of Irish teenagers had intakes of calcium and vitamin D below the respective Estimated Average Requirements values, reflecting a high degree of inadequacy of intake for both micronutrients (and higher in girls than boys; P < 0.001). In addition, 21.7% and 33.1% of teenagers had serum 25(OH)D < 30 nmol/L (risk of vitamin D deficiency) and 30-49.9 nmol/L (inadequacy), respectively. Extended winter sampling, being aged 16-18 years, low total vitamin D intake, being overweight/obese or being of non-white skin type were significant (P < 0.05) predictors of serum 25(OH)D < 30 nmol/L. CONCLUSIONS: There was a high prevalence of inadequacy of intake of calcium and vitamin D in Irish teenagers, and a fifth were at increased risk of vitamin D deficiency.

Vitamin D metabolites, D3 and D2, and their independent associations with depression symptoms among adults in the United States.

Background: The two metabolites of vitamin D; serum 25-hydroxyvitamin D3 (25(OH)D3) and D2 (25(OH)D2), and their independent roles in mood regulation are unexplored. This study aims to examine 25(OH)D3 and 25(OH)D2 and their interplay with depression symptoms.Materials and Methods: Utilizing data from the U.S. National Health and Nutrition Examination Survey (2007-2011, 2013-2014), a cross-sectional study was conducted. Depression was assessed using the 9-item Patient Health Questionnaire, and those with total score ≥5 were considered as having mild to severe depression symptoms. 25(OH)D3 and 25(OH)D2, the clinical markers of vitamins D3 and D2, were measured. Weighted logistic regressions were utilized to examine the adjusted association between 25(OH)D3 and depression, and the effect modification of 25(OH)D2.Results: The sample included 11,471 participants aged 20-80 years. Of those, 23.4% reported symptoms of depression, 28.9% had 25(OH)D3 deficiencies(<20 ng/mL), and 21.5% exhibited presence of 25(OH)D2(>0.6 ng/mL). After adjustment, among participants with presence of 25(OH)D2, those who had 25(OH)D3 deficiencies were more likely by 54% to report depression symptoms (OR = 1.54,95%CI:1.14-2.07). In fact, among participants with nearly no 25(OH)D2 presence, a significant effect estimate between 25(OH)D3 deficiency and depression symptom was not observed(OR = 1.11,95%CI:0.94-1.31).Conclusions: Both vitamin D metabolites retain an independent and significant role in mood regulation. The study provides valuable insights on vitamin D3 and its significant relationship with depression symptoms in the presence of vitamin D2. Further research is required to elucidate the distinct mechanisms of these two vitamin D metabolites on depression.

Clinical correlates of serum 25-hydroxyvitamin D in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent. MATERIALS AND METHODS: We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (N = 100) was included as a control group. RESULTS: PD patients had lower 25(OH)D serum levels than controls. Deficiency status (<20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (P = .002) and vitamin D intake (P = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, P = .035), worse clinical symptoms (UPDRS Part-III total score [P = .006] and dopaminergic [P = .033] and non-dopaminergic subscores [P = .001]) and greater global cognitive function impairment (P = .041). Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure. CONCLUSION: : Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.

The relationship between serum 25-hydroxyvitamin-D level and sweat function in patients with type 2 diabetes mellitus.

AIMS: The objective of this study is to explore the relationship between serum 25-hydroxyvitamin-D(25-(OH)2D3) level and sweat function in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study of 1021 patients with T2DM who underwent 25-(OH)2D3 level detections and sweat function tests was carried out. These individuals were divided into deficient groups (n = 154 cases), insufficient groups (n = 593 cases) and sufficient groups (n = 274 cases). Spearman correlation analysis and multivariate stepwise linear regression analysis were implemented to determine the association of 25-(OH)2D3 level and sweat function. RESULTS: The total presence of sweating dysfunction was 38.59%. Patients with a lower level of serum 25-(OH)2D3 had more severe sweat secretion impairment (P < 0.05). As the decrease of serum 25-(OH)2D3 level, the presence of sweating dysfunction increased (P < 0.05). 25-(OH)2D3 level was positively correlated with sweat function parameters, age and duration of T2DM were negatively correlated with sweat function parameter (P < 0.05). Multivariate stepwise linear regression analysis explored a significant association between serum 25-(OH)2D3 level with sweat function (P < 0.05). CONCLUSIONS: Serum 25-(OH)2D3 level was positively correlated with sweat function in patients with T2DM.

High-Intensity Physical Activity with High Serum Vitamin D Levels is Associated with a Low Prevalence of Osteopenia and Osteoporosis: A Population-Based Study.

We found that combination of high-intensity PA and high 25(OH)D levels was associated with low prevalence of osteoporosis/osteopenia. In addition, the prevalence of osteoporosis was lower in the low PA with high 25(OH)D levels than in the moderate or high PA with low 25(OH)D levels. INTRODUCTION: The aim of this study was to explore the association of physical activity (PA) and serum 25-hydroxyvitamin D (25[OH]D) levels with osteopenia/osteoporosis. METHODS: The Korean National Health and Nutrition Examination Survey data from 2008 to 2011 were used in this study. Data from 6868 individuals were selected. Each individual's level of PA was classified as 'low', 'moderate', or 'high'. Serum 25(OH)D levels were classified as 'low' or 'high'. Accordingly, the combined PA and 25(OH)D groups were divided into 6 groups. Bone mineral density (BMD) was classified as 'normal (T score ≥ - 1.0)', 'osteopenia (- 2.5 < T score < - 1.0)' or 'osteoporosis (T score ≤ - 2.5)'. Crude and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated using multinomial logistic regression models. RESULTS: The AORs (95% CIs) for osteopenia were 0.64 (0.50-0.83) in the high PA with high 25(OH)D group and 0.69 (0.53-0.88) in the moderate PA with high 25(OH)D group. The AORs (95% CIs) for osteoporosis were increased in the groups in ascending order as follows: high PA with high 25(OH)D (0.40 [0.28-0.57]) < moderate PA with high 25(OH)D (0.47 [0.33-0.66]) < low PA with high 25(OH)D (0.59 [0.42-0.83]) < high PA with low 25(OH)D (0.70 [0.49-1.00]) < moderate PA with low 25(OH)D (0.76 [0.53-1.07]) < low PA with low 25(OH)D. This result was consistent in males but not evident in females. CONCLUSION: We suggest that the combination of high-intensity PA and high 25(OH)D levels is positively associated with high BMD.

The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study.

BACKGROUND: To investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach. METHODS: Genetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses. RESULTS: Six, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 - 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 - 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses. CONCLUSIONS/INTERPRETATION: Serum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.

Vitamin D supplementation does not enhance resistance training-induced gains in muscle strength and lean body mass in vitamin D deficient young men.

PURPOSE: Vitamin D (Vit-D) supplementation has been shown to increased muscle strength in young adults. It remains unclear if Vit-D supplementation enhances the efficacy of resistance training (RT). This study tested the hypothesis that Vit-D supplementation would enhance the RT-induced increases in muscle strength and lean body mass (LBM) in Vit-D deficient young men. METHODS: Thirty-nine men (baseline serum 25(OH)D < 50 nmol L‒1) were quasi-randomly assigned to one of the two groups that performed a 12-week supervised RT program concomitant with either Vit-D (8000 IU daily; VD) or placebo (PLC) supplementation. RESULTS: During 12-week RT, energy and nutrient (except Vit-D) intake and training loads did not differ in the two groups. Serum 25(OH)D levels increased from 36.3 ± 9.2 to 142.4 ± 21.9 nmol L‒1 (P < 0.05) in VD group and remained unchanged between 36.3 ± 8.9 and 29.4 ± 6.6 nmol L‒1 (P > 0.05) in PLC group. Muscle strength (1-repetition maximum) increased (P < 0.05) to an equal extent in the two groups in 5 exercises performed on RT equipment, whereas strength gains in chest press and seated row were greater (P < 0.05) in PLC compared to VD group. Total and regional LBM (measured by DXA scan) increased (P < 0.05) equally in the two groups. Android fat mass decreased (P < 0.05) in VD group only. CONCLUSION: Vit-D supplementation does not enhance the efficacy of RT in terms of muscle strength and LBM gains in Vit-D deficient young healthy men.

Serum 25-hydroxyvitamin-D and nonalcoholic fatty liver disease: Does race/ethnicity matter? Findings from the MESA cohort.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25(OH)D) is associated with higher nonalcoholic fatty liver disease (NAFLD) risk in studies of mainly white participants. Significant racial/ethnic differences exist in serum 25(OH)D and NAFLD prevalence questioning extending this association to other racial/ethnic groups. We tested whether the association between serum 25(OH)D and NAFLD vary by race/ethnicity. METHODS AND RESULTS: This was a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) that included 3484 participants (44% male; 38.4% Whites, 27.8% African-Americans, 23.5% Hispanics, and 10.3% Chinese-Americans) who had serum 25(OH)D and upper abdominal CT images available at baseline. Serum 25(OH)D was measured by high-performance liquid chromatography-tandem mass spectrometry. NAFLD was identified if liver-to-spleen Hounsfield-Unit ratio was <1. Whites had the highest 25(OH)D level and African-Americans had the lowest level (mean ± SD: 29.5 ± 10.4 vs.19.9 ± 9.1, respectively). Six hundred and eleven (17.5%) participants had NAFLD; Hispanics had the highest prevalence (26.2%) followed by Chinese-Americans (19.8%), Whites (15.8%) and African-Americans (11.7%), P < 0.0001. In adjusted model, the association of 25(OH)D with NAFLD differed by race/ethnicity (P < 0.0001). Negative association was only evident in Causations (OR (95% CI):1.23 (1.03, 1.47) per 1 SD lower serum 25(OH)D). For other racial/ethnic groups, BMI, triglycerides, diabetic status and/or smoking, but not serum 25(OH)D, were common independent risk factors for NAFLD. CONCLUSIONS: The negative association between serum 25(OH)D and NAFLD in Whites may not be broadly generalizable to other racial/ethnic groups. Modifiable risk factors including BMI, triglycerides, diabetic status and/or smoking associate with NAFLD risk in non-white racial/ethnic groups beyond 25(OH)D.