Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Cardiovascular and microvascular outcomes according to vitamin D level and genetic variants among individuals with prediabetes: a prospective study.

BACKGROUND: Whether serum vitamin D mediate vascular diseases in prediabetic populations remains unclear. This study aimed to determine the associations between circulating 25-hydroxyvitamin D [25(OH)D] levels and vitamin D receptor (VDR) polymorphisms with the risk of macrovascular complications, including myocardial infarction and stroke, and microvascular complications such as diabetic nephropathy and retinopathy, among adults with prediabetes. METHODS: Participants with prediabetes in UK Biobank were included (N = 56,387). Multivariable dose-response and Cox proportion models were used to explore the relationship of serum 25(OH)D status and the risks of vascular complications. The interaction of VDR polymorphisms with serum 25(OH)D level on risks of vascular events was also assessed. RESULTS: During a median follow-up of 12 years, higher levels of 25(OH)D were significantly and nonlinearly associated with a lower risk of macrovascular diseases among prediabetic individuals. The adjusted hazard ratios (95% confidential interval) of serum 25(OH)D levels of ≥ 75.0 nmol/L versus < 25 nmol/L were 0.75 (0.63-0.88) for myocardial infarction, 0.74 (0.55-1.00) for stroke, 1.02 (0.60-1.74) for diabetic nephropathy, and 1.30 (0.92-1.84) for diabetic retinopathy, respectively. The rs2228570 (FokI) polymorphisms significantly interacted with 25(OH)D on incident myocardial infarction (P-interaction = 0.042) and stroke (P-interaction = 0.033). The individuals with serum 25(OH)D level of 50.0-74.9 nmol/L and rs2228570 (FokI) homozygotes had the lowest risks of vascular complications. CONCLUSIONS: Lower serum 25(OH)D levels are significantly and nonlinearly associated with an increased risk of cardiocerebrovascular diseases in prediabetic individuals, with VDR polymorphisms of rs2228570 (FokI) modify such associations. Monitoring a safe 25(OH)D concentration is suggested to prevent the vascular complications for prediabetes.

The link between serum 25-hydroxyvitamin D, inflammation and glucose/insulin homoeostasis is mediated by adiposity factors in American adults.

We used an established mediation analysis to investigate the role of adiposity in the relation between serum 25(OH)D with markers of inflammation and glucose and insulin metabolism. We used data from National Health and Nutrition Examination Survey (2005-2010), to evaluate the associations between serum 25(OH)D and markers of insulin resistance (IR) or inflammation, and whether these associations are mediated by adiposity factors. Analysis of co-variance and conceptual causal mediation analysis were conducted taking into consideration the survey design and sample weights. BMI was found to have significant mediation effects (to varied extent) on the associations between serum 25(OH)D and CRP, apo-B, fasting glucose, insulin, HOMA-IR, HOMA-B and HbA1c (all P < 0·05). Both WC and apVAT were also found to partly mediate the associations between serum 25 25(OH)D with CRP, FBG, HbA1c, TAG and HDL-cholesterol (all P < 0·05). These findings support the importance of optimising 25(OH)D status in conditions with abnormal adiposity (i.e. obesity) and treatments for the prevention of cardiometabolic diseases affecting adipose tissue metabolism (i.e. weight loss).

Relationship between vitamin D, iron, and hepcidin in premenopausal females, potentially confounded by ethnicity.

PURPOSE: To investigate the associations between vitamin D, hepcidin, and iron status in premenopausal females of different ethnic cohorts residing in Auckland, New Zealand (NZ). METHODS: A total of 160 females aged 18-45 years participated in a cross-sectional study. Demographics, body composition, serum 25(OH)D, inflammatory markers (C-reactive protein and interleukin-6, IL-6), and iron biomarkers (serum ferritin, haemoglobin, soluble transferrin receptor, and hepcidin) were measured. Comparisons between parametric, non-parametric, and categorical variables were completed by using one-way ANOVA, Kruskal-Wallis, and Chi-squared tests, respectively. ANCOVA was used to compare serum 25(OH)D across iron parameter categories. RESULTS: Of the 160 participants, 60 were NZ European, 67 were South Asian, and 33 were from the 'other' ethnic groups. South Asians had significantly higher body fat percentage (BF%) and IL-6 concentration (38.34% and 1.66 pg·mL-1, respectively), compared to NZ Europeans (27.49% and 0.63 pg·mL-1, respectively, p < 0.001). South Asians had significantly lower 25(OH)D concentrations compared to NZ Europeans (33.59 nmol·L-1 vs 74.84 nmol·L-1, p < 0.001). In NZ Europeans, higher 25(OH)D concentration was seen in those with lower (≤ 3.5 nM) hepcidin concentration, p = 0.0046. In South Asians, higher 25(OH)D concentration was seen in those with higher (> 3.5 nM) hepcidin concentrations, p = 0.038. There were no associations between serum 25(OH)D and serum ferritin. CONCLUSION: Within South Asian women, an unexpected positive relationship between 25(OH)D and hepcidin concentration was observed which may be due to significantly higher IL-6 concentrations, BF%, and lower 25(OH)D concentrations. Future research is required to confirm these observations in this ethnic cohort.

Dose-Response Effect of Consuming Commercially Available Eggs on Wintertime Serum 25-Hydroxyvitamin D Concentrations in Young Australian Adults: a 12-Week Randomized Controlled Trial.

BACKGROUND: Vitamin D deficiency is a common health concern during winter. Eggs are one of the few rich dietary sources of vitamin D, containing cholecalciferol (vitamin D-3) and 25-hydroxyvitamin D-3 [25(OH)D3], with the latter reported to be 5 times more potent at increasing serum 25(OH)D concentrations, the major circulating form of vitamin D. However, whether there is an optimal dose of eggs to increase or maintain 25(OH)D concentrations during wintertime is not known. OBJECTIVES: To evaluate the dose-response effect of consuming 2, 7, or 12 commercially available eggs per week on serum 25(OH)D concentrations during the autumn-winter months in young adults. Secondary aims were to investigate changes in serum lipids, and the feasibility (adherence) and acceptability to consuming the eggs. METHODS: In a 12-wk randomized controlled trial, 51 adults aged 25-40 y were randomly assigned to consume 2 eggs/wk (control, n = 17), 7 eggs/wk (n = 17), or 12 eggs/wk (n = 17). Change in serum 25(OH)D was the primary outcome as assessed by LC/MS/MS. Serum lipids were assessed using standard techniques, and acceptability to consuming the eggs was assessed via a questionnaire. RESULTS: Forty-two (82%) participants completed the study. Mean adherence to the eggs was 83% for controls, 86% for 7 eggs/wk, and 83% for 12 eggs/wk. Mean serum 25(OH)D concentrations did not change significantly in either the 7-eggs/wk (-8.3 nmol/L; 95% CI: -17.0, 0.4 nmol/L) or 12-eggs/wk (-7.2 nmol/L; 95% CI: -18.6, 4.3 nmol/L) groups, but decreased by 28.6 nmol/L (95% CI: -38.1, -18.9 nmol/L) in controls, which led to a significant (P = 0.003) between-group difference for the change after 12 wk. Serum lipids did not differ between the groups, and acceptability profiles to consuming the eggs were positive and similar for all 3 groups. CONCLUSIONS: Consuming 7 commercially available eggs per week for 12 wk was effective for attenuating the wintertime decline in circulating vitamin D concentrations in young Australian adults, with 12 eggs/wk not providing any additional benefits.

Maternal vitamin D status in early pregnancy and its association with gestational diabetes mellitus in Shanghai: a retrospective cohort study.

BACKGROUND: There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. METHODS: The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24-28 weeks of gestation. Participants' demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. RESULTS: In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. CONCLUSIONS: In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

The Relationship of 25(OH)D3 with Diabetes Mellitus and the Mediation Effect of Lipid Profile in Chinese Rural Population of Henan Province.

Background and Objectives: Studies suggest that vitamin D is involved in the development of type 2 diabetes mellitus (T2DM) and influences serum lipids levels, while lipid disorders are also closely related to T2DM. This study attempts to explore the complex relationship of serum 25(OH)D3, serum lipids, and T2DM among Chinese population. Materials and Methods: A cross-sectional study was carried out among 2326 subjects. The chi-square (χ2) test was applied to compare the prevalence of T2DM or dyslipidemia between two serum 25(OH)D3 levels. Linear regression was applied to analyze the correlation between serum lipids and 25(OH)D3 contents. Univariate and logistic analysis were used to explore the relationship between two lipid levels and T2DM. Mediation analysis was used to explore whether serum lipids mediate the relationship between two serum 25(OH)D3 levels and T2DM. Results: Compared to subjects with 25(OH)D3 ≥ 30 ng/mL, subjects with 25(OH)D3 < 30 ng/mL were higher in the prevalence of T2DM. The occurrences of high TG and low HDL-C were significantly higher in vitamin D deficiency and insufficiency than those in vitamin D sufficiency. Serum 25(OH)D3 content showed a reverse correlation with TC, TG, and LDL-C, but positive correlation with HDL-C. The odds ratios (ORs) (95% confidence intervals, 95%CI) of T2DM by comparing TG ≥ 2.26 mmol/L vs. TG < 2.26 mmol/L and HDL-C < 1.04 mmol/L vs. HDL-C ≥ 1.04 mmol/L in all participants were 2.48 (1.94-3.18) and 1.37 (1.07-1.75), respectively. Serum TG or HDL-C level partially mediated the relationship between two 25(OH)D3 level and T2DM. Conclusions: Serum 25(OH)D3 < 30 ng/mL seems to be associated with T2DM or dyslipidemia (high TG and low HDL-C) in our study, but there is still no proof of a cause-effect relationship. Moreover, serum TG or HDL-C level partially mediated the relationship between 25(OH)D3 levels and T2DM.

Association of Serum Vitamin D level and COVID-19 infection: A Case-control Study.

BACKGROUND: Vitamin D is considered a potent modulator of the immune system, albeit its role in COVID-19 infection is a matter of debate. The present study aimed to estimate the association between serum vitamin D levels and COVID-19 among people in Qatar. METHODS: This case-control study, approved by the Institutional Review Board of Primary Health Care Corporation (PHCC) Qatar, retrospectively evaluated the principal public healthcare sector population data repository retrieved from the cloud-based Electronic Health Record (EHR) software-Cerner, during April 2020-2021. The health records of all adult patients aged >18 years who had undergone the reverse transcription-polymerase chain reaction (RT-PCR) test and whose medical records had documented serum 25-hydroxyvitamin D [25 (OH)D] levels were analyzed. RESULTS: A total of 924,173 EHRs were extracted, of which 62,451 EHR comprised of 16,446 (26.3%) COVID-19 patients and 46,005 (73.7%) negative-control group patients met the inclusion criteria. The odds ratio (OR) among different categories of vitamin D deficiency (VDD) revealed that people with mild/moderate VDD were 1.18 times (95% CI 1.126-1.258) and those with severe VDD were 1.90 times (95% CI 1.116-1.251) more likely to have COVID-19 infection when compared to the people with optimal serum vitamin D level. On applying multiple logistic regression, the odds of having COVID-19 infection were found to be 1.27 times (95% CI 1.184-1.371) higher among those with mild/moderate VDD and 1.32 times (95% CI 1.206-1.405) higher among those with severe VDD when compared to people with optimal vitamin D level (p < 0.001). CONCLUSION: Our findings demonstrated a significant association between the suboptimal serum vitamin D level and COVID-19 infection. Further studies are required to determine the effects of VDD on the severity and outcomes of COVID-19 infections.

Vitamin D Supplementation and Sunlight Exposure on Serum Vitamin D Concentrations in 2 Parallel, Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Vitamin D concentrations are a function of sunlight exposure and dietary intake. However, current dietary vitamin D recommendations do not consider differences in country-specific sunlight availability or spontaneous individual exposure. OBJECTIVES: We aimed to investigate the effects of vitamin D supplementation and sunlight exposure on vitamin D concentrations in Brazilian women living in high compared with low latitudes. METHODS: In 2 parallel, double-blind, randomized placebo-controlled trials, Brazilian women living in England (51°N) composed "without ultraviolet B (UVB) exposure" groups and those living in Brazil (16°S) composed the "with UVB exposure" groups (mean age, 31.39 ± 8.7 years). Participants received 15 µg cholecalciferol or placebo daily for 12 weeks during wintertime. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, the primary outcome, were assessed by HPLC-MS/MS, vitamin D intakes were assessed by 4-day diet diaries, and sunlight exposure was assessed by UVB dosimeters. The effects of supplementation and UVB exposure were tested by the intention to treat with a linear mixed model. RESULTS: The 25(OH)D concentrations increased in both supplemented groups [from 75.1 ± 22.0 to 84.8 ± 21.0 nmol/L (P = 0.004) in the group with UVB exposure; from 38.1 ± 15.9 to 55.1 ± 12.2 nmol/L (P < 0.001) in the group without UVB exposure], with no significant changes in either placebo group. Concentrations in both supplemented groups were higher than those in the placebo group without UVB exposure (P = 0.0002 in the group with UVB exposure; P = 0.0035 in the group without UVB exposure). Postintervention 25(OH)D concentrations were significantly affected by serum 25(OH)D concentrations at baseline (P < 0.0001) and by intervention (placebo or supplement; P > 0.0001), with a large effect size (Cohen's D = 0.768), but were not affected by UVB exposure (with or without; P = 0.1386), nor by the interaction between the intervention (placebo or supplement) and UVB exposure (with or without; P = 0.9845). CONCLUSIONS: Moderate supplementation of 15 ug/d cholecalciferol, in accordance with current recommendations, supports an adequate vitamin D status in adult women, irrespective of latitude, and might concomitantly prevent an increase in parathyroid hormone. The Interaction Between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes (D-SOL) study was registered at clinicaltrials.gov as NCT03318029.

Low Circulating Vitamin D in Intensive Care Unit-Admitted COVID-19 Patients as a Predictor of Negative Outcomes.

BACKGROUND: Vitamin D deficiency has been associated with an increased risk of respiratory infections. OBJECTIVES: The study aimed to evaluate the serum 25-hydroxyvitamin D [25(OH)D] concentration in patients admitted to the intensive care unit (ICU) as a predictor of coronavirus disease 2019 (COVID-19) mortality. METHODS: A single-center retrospective observational study was conducted. Forty adult patients (50% men) with confirmed COVID-19 who were admitted to the ICU were enrolled. The primary endpoint was mortality at day 60. Serum 25(OH)D concentration was measured on the day of admission to the ICU. We used the Mann-Whitney test, Fisher's exact test, Kaplan-Meier analysis, and receiver operator characteristic (ROC) analysis to assess serum 25(OH)D concentration as a predictor of COVID-19 mortality. RESULTS: All 40 patients had a low median (IQR) serum 25(OH)D concentration at admission [12 (9-15) ng/mL]. The median (IQR) serum 25(OH)D concentration was greater in survivors [13.3 (10.0-17.1) ng/mL, n = 22] than in nonsurvivors [9.6 (7.9-14.2) ng/mL; n = 18], P = 0.044. The area under the ROC curve was 0.69 (95% CI: 0.52, 0.86; P = 0.044). The 60-d mortality rate of those with serum 25(OH)D concentrations ≤9.9 ng/mL (n = 14, 71%) tended to be greater than that of those with concentrations >9.9 ng/mL (n = 26, 31%) (P = 0.065), and they had a 5.6-fold higher risk of death (OR: 5.63; 95% CI: 1.35, 23.45; P = 0.018). CONCLUSIONS: The ICU patients had a low serum 25(OH)D concentration. Serum 25(OH)D concentrations ≤9.9 ng/mL on admission can be used to predict in-hospital mortality in patients with COVID-19.This trial was registered at clinicaltrials.gov as NCT04450017.

The application value of serum 25(OH)D3, uric acid, triglyceride, and homeostasis model assessment of insulin resistance in male patients with hyperuricemia combined with hypogonadism.

BACKGROUND: The purpose of this study was to investigate the application value of serum 25(OH)D3, uric acid, triglyceride (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) in male patients with hyperuricemia combined with hypogonadism. METHODS: From August 2018 to August 2020, a total of 198 male patients with primary hyperuricemia were prospectively enrolled in our hospital for inpatient treatment in the department of Metabolism and Endocrinology. They are divided into normal gonadal function group (normal group, n = 117) and hypogonadal function group (hypogonadism group, n = 81), according to free testosterone (FT) level, International Index of Erectile Function (IIEF-5), and androgen deficiency in the aging male (ADAM) questionnaires. Laboratory indexes were compared between two groups. Multivariate logistic regression was applied to analyze the influencing factors of hypogonadism. RESULTS: Among the 198 hyperuricemia patients, 40.91 % were hypogonadism. Compared with the normal group, the BMI, waist circumference (WC), and the prevalence of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia (HLP), and obesity (OB) in the hypogonadism group were higher, and the difference was statistically significant (P < 0.05, respectively). The levels of fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), serum uric acid (SUA), alanine transaminase (ALT) of hypogonadism group were higher than those of normal group, while the levels of TT, FT, E2, 25(OH)D3 of hypogonadism group were lower than those of normal group (P < 0.05, respectively). Pearson's linear correlation was used to analyze the correlation between the indicators with significant differences in general data and laboratory indicators and hypogonadism. BMI, WC, HOMA-IR, TG, SUA, TT, FT, 25(OH)D3, E2 were positively correlated with hypogonadism (r = 0.556, 0.139, 0.473, 0.143, 0.134, 0.462, 0.419, 0.572, 0.601, P = 0.012, 0.027, 0.018, 0.019, 0.028, 0.029, 0.030, 0.009, 0.003, respectively). Taking the above indicators as independent variables and hypogonadism as the dependent variable, logistic regression analysis found that the risk factors for hypogonadism were SUA, WC, BMI, HOMA-IR, TG, TT, FT, E2, and 25(OH) D3. CONCLUSIONS: Serum 25(OH)D3, SUA, HOMA-IR, TG levels were positively correlated with male hyperuricemia patients with hypogonadism. They have important application value in the diagnosis of male hyperuricemia patients with hypogonadism.

Serum 25-hydroxyvitamin D, frailty, and mortality among the Chinese oldest old: Results from the CLHLS study.

BACKGROUND AND AIMS: In this study, the aim is to explore whether frailty status modified the associations of serum 25(OH)D levels with all-cause and cause-specific mortality in the oldest old Chinese population. METHODS AND RESULTS: A total of 1411 participants aged at least 80 years were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Information on serum 25(OH)D level, frailty status, and covariates were examined at baseline. All-cause and cause-specific mortality status were ascertained during the follow-up survey conducted in 2017-2018 by using the ICD-10 codes. Cox proportional hazard models with stratified analyses were performed to evaluate potential associations. Over a median follow-up of 3.2 years, 722 (51.2%) participants were deceased, including 202 deaths due to circulatory diseases, and 520 deaths due to noncirculatory causes. After multivariable adjustment, the lowest quartile of serum 25(OH)D levels (Hazard Ratios (95% Confidence Intervals), 1.85 (1.45-2.36), 1.85 (1.45-2.36), 1.73 (1.31-2.29), respectively) and frailty (Odd Ratios (95% Confidence Intervals), 1.91 (1.60-2.29), 2.67 (1.90-3.74), 1.64 (1.31-2.05)) were associated with significantly higher risk of all-cause mortality, circulatory mortality, and noncirculatory mortality, respectively. In addition, we observed significant interactions among 25(OH)D and frailty on the risk of all-cause and cause-specific mortality (all P-interaction < 0.001). Similar results were found in sensitivity analyses by excluding participants who died in the first year of follow-up and using clinical cutoffs of serum 25(OH)D levels. CONCLUSION: Low serum 25(OH)D levels were associated with higher risk of all-cause and cause-specific mortality among the oldest old of the Chinese population, and the associations were significantly stronger in individuals with frailty.

Serum Vitamin D and Depressive Symptomatology among Boston-Area Puerto Ricans.

BACKGROUND: Low vitamin D status, assessed using serum 25-hydroxyvitamin D [25(OH)D] concentration, has been associated with depression, but research among minority populations, such as Puerto Ricans is limited. We examined the association between serum 25(OH)D and self-reported depressive symptomatology across 3 waves of follow-up in a cohort of Puerto Rican adults residing in Massachusetts. OBJECTIVES: We evaluated the cross-sectional and longitudinal associations between serum 25(OH)D and self-reported depressive symptoms in the Boston Puerto Rican Health Study (BPRHS) cohort. METHODS: Participants of the BPRHS were evaluated for depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). Serum 25(OH)D was measured at baseline (n = 1434), year 2 (n = 1218), and year 5 (n = 914). We categorized serum 25(OH)D concentration as sufficient (≥20 ng/mL), insufficient (12 to <20 ng/mL), and deficient (<12 ng/mL). Multivariable linear regression was used for cross-sectional analyses at baseline, and repeated measures mixed effects modeling was used over 3 waves of follow-up for longitudinal analyses. We conducted sensitivity analyses in vitamin D supplement nonusers and participants with complete data on baseline serum 25(OH)D and CES-D at all 3 visits. RESULTS: Serum 25(OH)D concentration was not associated with CES-D score in cross-sectional analysis [ß = -0.85; 95% CI: -2.80, 1.10 for deficient compared with sufficient 25(OH)D; P-trend = 0.59] or in longitudinal analyses over 5 y [ß = -0.41; 95% CI: -1.95, 1.13 for deficient compared with sufficient 25(OH)D; P-trend = 0.93]. Results were similar in sensitivity analyses restricted to vitamin D supplement nonusers (n = 1371) and in analyses conducted in participants with complete measures of baseline serum 25(OH)D and CES-D score at all 3 visits (n = 887) [ß = -0.12; 95% CI: -1.98, 1.74 for deficient compared with sufficient 25(OH)D; P-trend = 0.93]. CONCLUSIONS: We did not observe a significant association between serum 25(OH)D and depressive symptomatology in the BPRHS cohort.

Summer Season and Recommended Vitamin D Intake Support Adequate Vitamin D Status throughout Pregnancy in Healthy Canadian Women and Their Newborns.

BACKGROUND: Vitamin D deficiency in pregnancy is reported as a prevalent public health problem. OBJECTIVES: We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D. METHODS: Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured. RESULTS: Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (<30 nmol/L) occurred. Serum 1,25(OH)2D concentrations were significantly higher in late pregnancy (101.1 ± 26.9 pmol/L) than in early pregnancy (82.2 ± 19.2 pmol/L, P < 0.001, n = 84). Cord serum 25(OH)D concentrations averaged 55% of maternal concentrations. In adjusted multivariate analyses, maternal vitamin D status in early pregnancy was positively associated with summer season (est.ß: 13.07; 95% CI: 5.46, 20.69; P < 0.001) and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P < 0.001); and in late pregnancy with summer season (est.ß: 24.4; 95% CI: 15.6, 33.2; P < 0.001), nonmilk dairy intake (est.ß: 0.17; 95% CI: 0.02, 0.32; P = 0.029), and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P = 0.04). CONCLUSIONS: Summer season and recommended vitamin D intakes supported adequate vitamin D status throughout pregnancy and in cord blood at >50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.

Associations of vitamin D with novel and traditional anthropometric indices according to age and sex: a cross-sectional study in central southern China.

PURPOSE: Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. METHODS: Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. RESULTS: In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. CONCLUSION: A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Is vitamin D deficiency a public health concern for low middle income countries? A systematic literature review.

PURPOSE: Vitamin D deficiency has been receiving increasing attention as a potential public health concern in low and lower-middle income countries (LMICs), of which there are currently 83. We aimed to conduct a comprehensive systematic literature review (SLR) of available data on vitamin D status and prevalence of vitamin D deficiency in all 83 LMICs. METHODS: We followed the general methodology for SLRs in the area of serum 25-hydroxyvitamin D. Highest priority was placed on identifying relevant population-based studies, followed by cross-sectional studies, and to a lesser extent case-control studies. We adopted the public health convention that a prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D < 25/30 nmol/L) at > 20% in the entire population and/or at-risk population subgroups (infants, children, women of child-bearing age, pregnancy) constitutes a public health issue that may warrant intervention. RESULTS: Our SLR revealed that of the 83 LMICs, 65% (n = 54 countries) had no published studies with vitamin D data suitable for inclusion. Using data from the remaining third, a number of LMICs had evidence of excess burden of vitamin D deficiency in one or more population subgroup(s) using the above convention (Afghanistan, Pakistan, India, Tunisia and Mongolia) as well as possibly other LMICs, albeit with much more limited data. Several LMICs had no evidence of excess burden. CONCLUSION: Vitamin D deficiency is a public health issue in some, but certainly not all, LMICs. There is a clear need for targeting public health strategies for prevention of vitamin D deficiency in those LMICs with excess burden.

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome. METHODS: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used. RESULTS: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen. CONCLUSION: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007.

Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation.

BACKGROUND & AIMS: Fatty liver disease is an important complication associated with liver transplantation, and the cytochrome P-450 system of the donor liver may be involved in its pathogenesis. To explore the effects of the CYP27A1, CYP27B1, CYP2R1, and vitamin D receptor pathways on vitamin D maintenance after living donor liver transplantation, we investigated the interplay between serum 25(OH)D and common variants in 60 paired donors and recipients who underwent living donor liver transplantation. METHODS: We prospectively collected 60 donor/recipient pairs from our liver transplantation programmes and extracted serum DNA to evaluate single nucleotide polymorphisms in CYP27A1 rs4674344, CYP27B1 rs10877012, CYP2R1 rs10741657, and VDR rs2228530 alleles using real-time polymerase chain reaction. We measured serum 25(OH)D concentrations of donors (D-D0) and recipients before (R-D0) and after (R-D30) living donor liver transplantation for comparison with repeated-measures analysis of variance in generalized estimating equations analysis. RESULTS: Fatty liver disease was noted in 28.3% of the cases after living donor liver transplantation, and the graft rejection rate was 25%. There were significant differences in low serum 25(OH)D concentrations between D-D0 and R-D0 and between R-D0 and R-30 groups. Significant associations were observed for serum CYP27A1 rs4674344 in recipients and donors as well as for graft liver tissue with VDR rs2228530. There was no significant relationship with serum CYP27B1 rs10877012 in recipients and donors or with graft liver tissue with CYP2R1 rs10741657. CONCLUSIONS: Donor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.

Expression and Clinical Significance of Serum 25-OH-D in pregnant women with SCH (Subclinical Hypothyroidism) and GDM (Gestational Diabetes Mellitus).

OBJECTIVE: To analyze the level and clinical significance of serum 25-hydroxyvitamin D (25-OH-D) levels in pregnant women with subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM). METHOD: One hundred pregnant women of 24-28 weeks' pregnancy with SCH combined GDM were selected into the observation group, and 100 healthy pregnant women were selected into the control group during the corresponding period. Examined the thyroid stimulating hormone (TSH), free thyroxine (FT4), 25-OH-D, serum calcium (Ca2+), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbAIc) levels and thyroid peroxide antibody (TPOAb), Thyroglobulin antibody (TgAb) status. Examine and compare TSH, FT4, Ca2+, FPG, HbAIc, TPOAb, and TgAb at different levels of serum 25-OH-D in the observation group. Compared the 25-OH-D levels and the ratio of different contents of 25-OH-D of TPOAb-positive and TgAb-positive SCH pregnant women. RESULT: The levels of TSH, FPG and HbAIc in the observation group were significantly higher than those in the control group (P<0.01). Through comparison of FT4 levels between the two groups, the difference had no statistical significance (P>0.05). The levels of 25-OH-D and Ca2+ in the observation group was significantly lower than those in the control group, and the difference had statistical significance (P<0.01). Through comparison of TSH, Ca2+, FPG and HbAIc in groups with different serum 25-OH-D levels, the difference had statistical significance (P<0.01). The positive rates of TPOAb and TgAb of pregnant women in the observation group were higher than in the control group (P<0.05). The vitamin D deficiency rate of TPOAb or TgAb positive pregnant women in the observation group was higher than those in the TPOAb or TgAb negative pregnant women, the difference had statistical significance (P < 0.05). CONCLUSION: blood glucose level in pregnant women with GDM and SCH increased significantly, blood calcium level decreased significantly. This group of people are more likely to have VitD deficiency. Thyroid stimulating hormone and blood glucose levels in pregnant women are negatively correlated with VitD levels. Therefore, serum 25-OH-D level can be used as an important reference index for gestational diabetes mellitus with subclinical hypothyroidism, and it has great clinical significance to maintain it at a normal level.