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With the emergence of the COVID-19 pandemic, the absence of established evidence-based treatment protocols led healthcare professionals and the public to explore experimental treatments, including high doses of vitamin D supplements. This study aimed to assess changes in serum 25-hydroxyvitamin D levels during the pandemic, employing a retrospective cohort analysis of data from Charleston Area Medical Center (CAMC). The study analyzed serum 25-hydroxyvitamin D levels in a cohort of 35,556 patients treated at CAMC in 2019, a representative pre-pandemic period, to 2021, a representative pandemic period. Our findings revealed a significant increase in mean serum 25-hydroxyvitamin D levels as compared with 2019 (37 ± 21 vs. 31 ± 15 ng/mL, p ≤ 0.001). Additionally, in 2021, there were significantly more patients exhibiting serum levels in the highest quintiles, specifically >100 ng/mL (1.6% vs. 0.2%), 75-100 ng/mL (4.6% vs. 1.2%), and 50-75 ng/mL (16.0% vs. 8.4%), p ≤ 0.001. This upsurge suggests increased intake of vitamin D supplements, potentially fueled by widespread discussions that were taking place largely on the internet regarding the efficacy of vitamin D against COVID-19. Our findings underscore the critical need for evidence-based public health messaging, especially during health crises, to prevent unnecessary health risks and ensure patient safety.

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., Competing Interests: Declaration of competing interest We declare that we have no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: The prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association., Methods: The study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death., Results: During a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; P interaction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (P interaction = 0.216)., Conclusions: Lower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Prehypertension affects 25-50% of adults worldwide and no prior study has examined the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality risk in individuals with prehypertension. This study aims to investigate the association of serum 25(OH)D concentrations with all-cause and CVD mortality among prehypertensive adults by utilizing data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2014 and linked 2019 mortality file., Methods: We included 4345 prehypertensive adults who participated in the NHANES between 2007 and 2014 and were followed up until 31 December 2019. Weighted Cox proportional hazards models were used with adjustments for multiple covariates to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risks of dying from any cause and CVD., Results: During a median follow-up of 8.8 years, 335 deaths from any causes were documented, of which 88 participants died from CVD. Compared with participants with sufficient 25(OH)D (≥ 75 nmol/L), the multivariate-adjusted HRs and 95% CIs for participants with severe deficiency (< 25 nmol/L), moderate deficiency (25-49.9 nmol/L), and insufficient concentrations (50-74.9 nmol/L) of serum 25(OH)D for all-cause death were 2.83 (1.46-5.52), 1.17 (0.74-1.86), and 1.36 (0.93-1.98), respectively. Similarly, the multivariable-adjusted HRs and 95%CIs for CVD death were 4.14 (1.10-15.51), 1.23 (0.46-3.28), and 1.73 (0.96-3.14), respectively. We found that there was a 9% reduction in the risk of death from all causes and a 14% reduction in the risk of death from CVD for every 10 nmol/L increase in serum 25(OH)D concentrations., Conclusion: Severe serum 25(OH)D deficiency among prehypertensive adults was associated with increased risk of mortality from all causes as well as from CVD. Our work suggests that supplementing with vitamin D may prevent premature death in severely deficient individuals with prehypertension., (© 2024. The Author(s).)

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., Competing Interests: All authors have disclosed no conflicts of interest

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., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

The purpose of this meta-analysis was to evaluate the relationship between serum 25-hydroxyvitamin D[25(OH)D] levels and gastric cancer. PubMed, Embase, Cochrane Library, Web of Science, The China Academic Journals full-text database, Wanfang Database of Chinese Academic Journals, VIP Chinese Science and Technology Periodicals database, and Chinese Biomedical Literature database were systematically searched. Case-control studies on the correlation between serum 25-hydroxyvitamin D levels and gastric cancer were retrieved, and the data extracted were analyzed. The results of 9 case-control studies containing 671 patients showed that serum 25(OH)D levels in the gastric cancer group were lower than those in the control group (weighted mean difference (WMD) = -8.90, 95% confidence interval (CI): -11.5, -6.32, p < 0.01); the risk of vitamin D deficiency in the gastric cancer group was higher than that in the control group (Odds ratio = 3.09, 95% CI: 1.96, 4.87, p < 0.01). The serum 25(OH)D levels in patients with well and moderately differentiated gastric cancer were higher than those in patients with poorly differentiated gastric cancer (WMD = -3.58, 95% CI: -6.41, -0.74, p = 0.01). Thus, low levels of vitamin D may increase the risk of gastric cancer. Systematic review registration: PROSPERO CRD42022327942.

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., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

One in five Canadians are first-generation immigrants. Evidence suggests the baseline risk for vitamin D (vitD) deficiency is increased among immigrants who move from equatorial to northern countries. We investigated the prevalence and determinants of vitD deficiency/insufficiency among first-generation immigrants compared with native-born Canadians and identified explanatory covariables. We used a cross-sectional design with data from the national Canadian Health Measures Survey (Cycles 3 and 4) (11,579 participants aged 3-79 years). We assessed serum 25-hydroxyvitamin D (S-25(OH)D) levels, sociodemographic and environmental factors, immigration status, length of time in Canada, vitD-rich food intake, ethnicity, and place of birth. Immigrants had lower mean S-25(OH)D than non-immigrants (51.23 vs. 62.72 nmol/L, p < 0.001). Those with younger age at the time of immigration (<18 years) had a high risk for low vitD, and S-25(OH)D levels increased with the length of time they had lived in Canada. The highest deficiency levels were in immigrants born in Morocco, India, and Lebanon compared with native-born Canadians. Ethnicity was the factor most strongly associated with S-25(OH)D. Compared with the white ethnic grouping, the Japanese had the highest level of vitD deficiency, followed by Arabs and Southeast Asians. Ethnic variations, dietary intake, and lifestyle factors are the main predictors of/explanatory factors for vitD status among Canadian immigrants.

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.

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.

Background : During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2-24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants' serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of -6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2-6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant-mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p < 0.05), after mutual adjustment. The cumulative risk model displayed a dose-response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Background: Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable., Methods: A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels., Results: A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8-30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31-43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%-53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls. Similarly, 67.44% (95% CI 48.32%-86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls., Conclusion: A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Recent studies have identified an association between low vitamin D levels and hypertension. We investigated the association between vitamin D levels and hypertension in the general population. We recruited 400 hypertensive subjects and compared them with 400 age- and sex-matched normotensive subjects. This study was carried out at Yashoda Hospital, Hyderabad, India from January 2015 to December 2017. Both groups underwent risk factor evaluation, estimation of serum 25-hydroxyvitamin D levels, and C-reactive protein (CRP) and liver function tests. Out of the 400 hypertensive subjects, 164 (40.2%) had serum 25-hydroxyvitamin D deficiency, compared with 111 (27.7%) normotensive subjects (p = 0.0001). Deficiency of serum 25-hydroxyvitamin D in hypertensive subjects was significantly associated with CRP positivity, low levels of mean serum calcium, low levels of mean serum phosphorous, high levels of mean alkaline phosphatase (p < 0.0001), and abnormal alanine transaminase (ALT) (p = 0.0015) compared with the same parameters in the normotensive subjects. After adjustment in the multiple logistic regression analysis, serum 25-hydroxyvitamin D deficiency (odds: 1.78; 95% CI: 1.31-2.41), CRP positivity (odds: 1.48; 95% CI: 1.48-2.32) and abnormal ALT (odds: 1.2; 95% CI: 0.98-1.94) were significantly associated with hypertension. Serum 25-hydroxyvitamin D deficiency was significantly associated with hypertension.

Objective: To investigate whether vitamin D status predicts weight gain or increase in waist circumference during the 11-year follow-up in general adult population., Design: A population-based longitudinal study., Setting: The study was conducted using data from the nationally representative Health 2000/2011 Survey. The analyses were based on regression models adjusted for sociodemographic and lifestyle factors., Participants: Weight, waist circumference and vitamin D status (serum 25-hydroxyvitamin D concentration analysed with radioimmunoassay) were measured from 2924 participants aged 30-64 years at baseline., Results: In men, low vitamin D status at baseline predicted ≥10 % increase in waist circumference during the follow-up when adjusted for age only (OR for sufficient v. deficient S-25(OH)D 0·41; 95 % CI 0·25, 0·67; P for trend <0·01), but the association with weight gain was only borderline significant. After adjustment for potential confounders, low vitamin D status remained a significant predictor of increase in waist circumference, but the association with weight gain was further attenuated. In women, vitamin D status at baseline did not predict weight gain or increase in waist circumference., Conclusions: Our results suggest that vitamin D insufficiency may be a risk factor of abdominal obesity among men but not among women. In men, it may also increase the risk of weight gain. Further studies are required to confirm these findings and examine potential mechanisms behind them. There is also a possibility that vitamin D is a biomarker of healthy lifestyle rather than an independent risk factor for obesity.

Smell and taste decline with aging, and markedly deteriorate when nutritional deficiencies occur. This study aims to examine the associations between Vitamin D (VD) deficiency and smell and taste impairments among adults. This paper details a cross-sectional study utilizing data from the US National Health and Nutrition Examination Survey (NHANES, 2013-2014.). Smell impairment was assessed by the Pocket Smell Test and defined as failing to correctly identify six or more of the eight odors. Taste impairment was defined as failing to correctly identify quinine or sodium chloride. VD was measured as serum 25-hydroxyvitamin. Multivariable weighted logistic regressions were utilized. Adjusted odds ratio (OR) and 95% confidence interval (CI) were presented. Overall, 2216 (smell sample) and 2636 (taste sample) participants were included, aged between 40 and 80 years old. Of those, 18.3% had taste impairment, 12.2% had smell impairment, and 20% had VD deficiency (<20 ng/mL). Compared to participants with sufficient VD (>30 ng/mL), those with VD deficiency were more likely by 39% to report a higher prevalence of smell impairment (OR = 1.39, 95%CI: 1.02-1.89); and only participants aged 70-80 years with VD inadequacy (20-30 ng/mL) were more likely by 96% to report a higher prevalence of taste impairment (OR = 1.96, 95%CI: 1.35-1.85). VD may have a significant role in age-related smell impairment in adults aged 40 years or older, and in age-related taste impairment in the elderly aged 70-80 years.

Background: The incidence of osteoporotic fractures has increased rapidly, and because of the poor prognosis and high mortality associated with osteoporotic fractures, they remain a prospective research area globally. One way to reduce their incidence is to investigate their intervention risk factors in the elderly. Hence, this study explores the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and osteoporotic fractures in elderly patients through a meta-analysis., Methods: We conducted our literature search mainly in PubMed and Embase for identifying studies that investigated the relationship between serum 25(OH)D levels and the risk for osteoporotic fractures. We performed categorical analysis, heterogeneity checks, publication bias analysis, and subgroup analyses., Results: In total, 20 studies were included, of which 4 were case-cohort studies and 16 were cohort studies. A total of 41,738 patients from 20 studies were included in the meta-analysis, of which 5916 had fractures, including 3237 hip fractures. By combining the lowest and highest categories of relative risks (RRs) and 95% confidence intervals (CIs), it was suggested that lower serum 25-hydroxyvitamin D levels may be a risk factor for fractures. RR (95% CI) for total and hip fractures were 1.11 (0.99, 1.24) and 0.89 (0.80, 0.98) after adjustments., Conclusions: Our study showed that compared to low serum 25(OH)D levels, high serum 25(OH)D levels reduce the risk of hip fractures in the patients aged 60 years or older. In contrast, serum 25(OH)D has no significant relationship with total fracture risk.

Background: This study examined the association between serum 25-hydroxyvitamin D (25(OH)D) and pulmonary function, among Korean adults, from 2010 to 2014., Methods: The data were obtained from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 5), and the first and second year (2013-2014) of KNHANES 6. The study population comprised 14,378 individuals. The variable of interest was serum 25(OH)D, and the dependent variable, pulmonary function., Results: All people with vitamin D levels below 30 ng/ml had lower lung functions, which was significant in lower forced expiratory volume in the first second (FEV1) (serum 25(OH)D < 10 ng/ml, 20 to <30 ng/ml: P = .001, 10 to <20 ng/ml: P = 0) and forced vital capacity (FVC) (serum 25(OH)D level <10 ng/ml: P = .01, 10 to < 20 ng/ml: P = .001, 20 to <30 ng/ml: P = .008). The lower the serum 25(OH)D, the lower the levels of FEV1 in men and this was significant. (serum 25(OH)D < 10 ng/ml: P = .007, 10 to <20 ng/ml: P = .002, 20 to <30 ng/ml: P = .007). The values of FEV1 and FVC were lower in people aged 50-69 years when vitamin D was lower than 30 ng/ml which were all significant. Among participants with BMI values < 23 kg/m 2 , lower vitamin D levels were significantly associated with lower pulmonary function., Conclusions: We found a significant association between serum 25(OH)D and pulmonary function, and this was related to sex, age and body mass index., (Copyright © 2018. Published by Elsevier Ltd.)

Background and Objective: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample., Methods: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C)., Results: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C)., Conclusion: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function., (© 2018 Asian Pacific Society of Respirology.)

Vitamin D deficiency is more common in Blacks, yet Blacks have lower prevalence of bone fragility fractures or osteoporosis than Whites. Broadband ultrasound attenuation (BUA) has been used to explore the association between serum 25(OH)D levels and bone quality in White and non-white populations. We investigated serum 25(OH)D status with corresponding BUA measurements assessed cross sectionally in a cohort of 232 Blacks and 260 Whites, aged 30-95 years who were part of the calibration study of the large Adventist Health Study-2 (AHS-2). At the calibration clinics, calcaneal BUA was measured and blood drawn for serum 25(OH)D assessment. In multivariable analyses, BUA was negatively associated with age (β-coefficient = -0.38; p < 0.0001) and positively associated with body mass index (BMI) (p (trend)  < 0.0001) and positively, but non-significantly, associated with serum 25(OH)D levels. Also, as expected, females had lower BUA (β-coefficient = -5.19; p < 0.05) and Blacks had higher BUA (β-coefficient = 4.26; p < 0.05). Gender and race modified the relationship of serum 25(OH)D on BUA with a positive association in males (p (trend)  ≤ 0.05), but no significant association in females after also controlling for menopausal status and hormone therapy. After also controlling for serum 25(OH)D levels, Black males had higher BUA than White men, but such differences were not found among the females. When stratifying on race, a positive association between serum 25(OH)D levels and BUA (p (trend)  ≤ 0.05) was found in Blacks, but not among Whites. Further studies are needed to understand how racial/ethnic differences in serum 25(OH)D levels influence bone health.

Background and Aims: Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults., Methods and Results: 19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF., Conclusion: Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Dark skin and low exposure to sunlight increase the risk of vitamin D insufficiency in children. Objective: The aim of the study was to evaluate the amount of vitamin D needed to ascertain that most children >4 y of age attain sufficient serum 25-hydroxyvitamin D [S-25(OH)D; i.e., ≥50 nmol/L] during winter regardless of latitude and skin color. Design: In a longitudinal, double-blind, randomized, food-based intervention study, 5- to 7-y-old children from northern (63°N) and southern (55°N) Sweden with fair ( n = 108) and dark ( n = 98) skin were included. Children, stratified by skin color by using Fitzpatrick's definition, were randomly assigned to receive milk-based vitamin D 3 supplements that provided 2 (placebo), 10, or 25 μg/d during 3 winter months. Results: Mean daily vitamin D intake increased from 6 to 17 μg and 26 μg in the intervention groups supplemented with 10 and 25 μg, respectively. In the intention-to-treat analysis, 90.2% (95% CI: 81.1%, 99.3%) of fair-skinned children randomly assigned to supplementation of 10 μg/d attained sufficient concentrations, whereas 25 μg/d was needed in dark-skinned children to reach sufficiency in 95.1% (95% CI: 88.5%, 100%). In children adherent to the study product, 97% (95% CI: 91.3%, 100%) and 87.9% (95% CI: 76.8%, 99%) of fair- and dark-skinned children, respectively, achieved sufficient concentrations if supplemented with 10 μg/d. By using 95% prediction intervals for 30 and 50 nmol S-25(OH)D/L, intakes of 6 and 20 μg/d are required in fair-skinned children, whereas 14 and 28 μg/d are required in children with dark skin. Conclusion: Children with fair and dark skin require vitamin D intakes of 20 and 28 μg/d, respectively, to maintain S-25(OH)D ≥50 nmol/L, whereas intakes of 6 and 14 μg/d, respectively, are required to maintain concentrations ≥30 nmol/L during winter. This trial was registered at clinicaltrials.gov as NCT01741324., (© 2017 American Society for Nutrition.)

Vitamin D is a modulator of both the innate and adaptive immune system. As vitamin D deficiency was a risk factor for some autoimmune diseases, we aimed to evaluate the serum vitamin D levels in autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) and investigated the association between serum vitamin D levels and AITD. 175 AITD patients including 51 GD, 61 euthyroid HT (mild HT), 63 euthyroid HT patients with hypothyroidism receiving hormone therapy (treated HT) were recruited from the outpatient department. 51 controls were from the physical checkup center of the hospital. 25-Hydroxyvitamin D levels, thyroid function, antithyroid antibodies, IL-4, IL-17, and TNF-α were determined. Compared with the controls, treated and mild HT patients had significantly lower 25(OH)D levels (45.77±3.48 vs. 83.49±6.24 nmol/L, p<0.001) and (55.25±3.88 vs. 83.49±6.24 nmol/L, p<0.001), respectively. However, GD patients had similar 25(OH)D levels (81.77±5.60 vs. 83.49±6.24 nmol/L, p=0.808). Compared to 24.1% controls with prevalent vitamin D deficiency, mild HT and treated HT patients were significantly different (55.4%, p<0.001) and (70.3%, p<0.001), respectively; no difference was seen in the GD patients (22.9%, p=0.797). Serum 25(OH)D levels were not associated with thyroid function, antithyroid antibodies, and serum cytokines IL-4, IL-17, and TNF-α in patients with AITD. We observed relatively low vitamin D level in mild and treated HT patients, while GD patients had similar 25(OH)D levels to those of healthy individuals. Further studies are imperative to explore the complex etiology of vitamin D deficiency in AITD.

Objective: To obtain the serum 25-hydroxyvitamin D status for women of child-bearing age aged 18-44 years from rural areas in China Health and Nutrition Survey2010-2012( CHNS 2010-2012)., Methods: We randomly selected the 1520 representative women of childbearing age from the 75 monitoring spots derived in the CNHS 2010-2012. The information of study population were collected using questionnaires and the serum 25-hydroxyvitamin D concentration was determinedusing the RIA kits. The vitamin D nutritional status was classified by the standards suggested by the America Endocrine Society. Multiple Logistic regression analysis was explored therelationship between vitamin D status with the potential relevant factors., Results: The median serum 25-hydroxyvitamin D concentration was 22. 7 ng/m L ranged from 8. 2 to42. 0 ng/m L. The prevalence of vitamin D deficiency was 38. 7%, insufficiently 39. 5%and sufficiently 21. 8%. Multiple Logistic regression analysis showed that nationality, geographical regions and income per capita was the significant., Conclusion: s The nutritional status of vitamin D in women of child bearing-age is not better in the CNHS2010-2012. We suggest that it should be pay more attention on the women of childbearing age for the minority, north China, family income per year between 10000 and 30000 Yuan.

African American men have higher incidence rates of aggressive prostate cancer, where high levels of calcium and serum vitamin D deficient levels play a role in the racial differences in incidence. In this study, we examined associations of serum vitamin D with aggressive prostate cancer to improve our understanding of higher susceptibility of aggressive disease in this racial cohort. From Howard University Hospital, 155 African American men with clinically-identified prostate cancer were identified; 46 aggressive cases, and 58 non-aggressive cases. Serum vitamin D was assessed from fasting blood samples, and total calcium intake was assessed using the Block Food Frequency Questionnaire. Vitamin D receptor polymorphisms from three different loci were genotyped; rs731236 , rs1544410 , and rs11568820 . Multivariate logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) comparing aggressive to non-aggressive prostate cancer. Vitamin D deficiency (<20 ng/mL) significantly increased risk of aggressive disease (OR: 3.1, 95% CI: 1.03-9.57, p -value = 0.04). Stratification by total calcium showed high calcium levels (≥800 mg/day) modified this association (OR: 7.3, 95% CI: 2.15-47.68, p -interaction = 0.03). Genetic variant rs11568820 appeared to increase the magnitude of association between deficient serum vitamin D and aggressive prostate cancer (OR: 3.64, 95% CI: 1.12-11.75, p -value = 0.05). These findings suggest that high incidence of aggressive prostate cancer risk in African American men may be due in-part to deficient levels of serum vitamin D. Other factors, including genetics, should be considered for future studies., Competing Interests: The authors declare no conflicts of interest.

Unlabelled: This study aimed to compare the vitamin D status in healthy Moroccan men and women aged 50 years and older. A total of 186 Moroccan women and 68 men, who had no previous diagnosis of osteoporosis, were recruited prospectively. We found in this study a high prevalence of hypovitaminosis D with no difference between men and women., Purpose: The main purpose of this study was to describe and compare the vitamin D status, parathormone, calcium, and phosphate of healthy Moroccan men and women aged 50 years and older., Methods: We conducted two cross-sectional studies, in postmenopausal women from October 2008 to November 2009 and in men over 50 years old, from December 2009 to August 2010. A total of 186 Moroccan women and 68 men, who had no previous diagnosis of osteoporosis, were recruited prospectively. For the definition of hypovitaminosis D, the preferred level for 25-hydroxyvitamin D (25(OH)D) insufficiency, which is now recommended by many experts, is 30 ng/mL (75 nmol/L), and the levels below 10 ng/ml (25 nmol/L) indicate deficiency., Results: The prevalence of vitamin D deficiency in men and women was 4.4 and 8.6 %, respectively, and the prevalence of vitamin D(25(OH) D) insufficiency in men and women were 85.2 and 77.4 %, respectively. In men and women, no correlations were found between intact parathormone (PTHi) and 25(OH) D (r = 0.056)., Conclusions: Despite a sunny environment, we found in this study a high prevalence of hypovitaminosis D (insufficiency + deficiency) in Moroccan men over 50 years old and postmenopausal women.

Purpose: To investigate the relationship between vitamin D and glaucoma., Methods: This retrospective, cross-sectional study included subjects who underwent a health screening at the Health Screening Center of Kangbuk Samsung Hospital from August 2012 to July 2013. All fundus photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye was glaucomatous based on the criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and by the appearance of the retinal nerve fiber layer and optic disc. If the subjects previously underwent an ophthalmologic examination, they were enrolled based on the documented history. In addition to fundus photographs, each participant underwent a systemic examination including blood sampling and sociodemographic and behavioral questionnaires. The subjects were divided into five groups according to serum 25-hydroxyvitamin D (25(OH)D) level. Multivariate logistic regression models were constructed to assess possible associations between elevated glaucoma risk and systemic factors with a p < 0.2 on univariate analysis., Results: Of the 169,208 subjects older than 20 years, 123,331 were eligible for the study. There was no difference in the prevalence of glaucoma according to quintile of serum 25(OH)D level based on sex ( p = 0.412 for males, p = 0.169 for females). According to the multivariable-adjusted logistic analysis, the odds ratio of glaucoma for the fourth quintile was significantly lower than that of the first quintile in females (odds ratio, 0.713; 95% confidence interval, 0.520 to 0.979)., Conclusions: Lower 25(OH)D level was significantly associated with an elevated risk of glaucoma in females compared with higher 25(OH)D level. Further evaluation is needed to investigate the relationship between glaucoma and vitamin D., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults., Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530)., Results: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R 2 =0.29), vitamin D intake (R 2 =0.24), and genes (R 2 =0.28) explained 35% (R 2 =0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185)., Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Obesity is associated with lower concentrations of serum 25-hydroxyvitamin D; however, uncertainty exists as to the direction of causation. To date, meta-analyses of randomized controlled vitamin D-supplementation trials have shown no effect of raising circulating vitamin D on body weight, although several weight-loss-intervention trials have reported an increase in circulating vitamin D after weight reduction., Objective: We undertook a systematic review and meta-analysis of randomized and nonrandomized controlled trials to determine whether weight loss compared with weight maintenance leads to an increase in serum 25-hydroxyvitamin D., Design: A systematic search for controlled weight-loss-intervention studies published up to 31 March 2016 was performed. Studies that included participants of any age with changes in adiposity and serum 25-hydroxyvitamin D as primary or secondary outcomes were considered eligible., Results: We identified 4 randomized controlled trials (n = 2554) and 11 nonrandomized controlled trials (n = 917) for inclusion in the meta-analysis. Random assignment to weight loss compared with weight maintenance resulted in a greater increase in serum 25-hydroxyvitamin D with a mean difference of 3.11 nmol/L (95% CI: 1.38, 4.84 nmol/L) between groups, whereas a mean difference of 4.85 nmol/L (95% CI: 2.59, 7.12 nmol/L) was observed in nonrandomized trials. No evidence for a dose-response effect of weight loss on the change in serum 25-hydroxyvitamin D was shown overall., Conclusions: Our results indicate that vitamin D status may be marginally improved with weight loss in comparison with weight maintenance under similar conditions of supplemental vitamin D intake. Although additional studies in unsupplemented individuals are needed to confirm these findings, our results support the view that the association between obesity and lower serum 25-hydroxyvitamin D may be due to reversed causation with increased adiposity leading to suboptimal concentrations of circulating vitamin D. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015023836., (© 2016 American Society for Nutrition.)

Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57°), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12·6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0·207, P=0·003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0·004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l.

Summary: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown., Introduction: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N)., Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models., Results: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) μg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort., Conclusion: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

A significant decline of serum 25-hydroxyvitamin D concentration [25(OH)D] with increasing latitude has been reported only for Caucasians. To determine the association between serum 25(OH)D and geographic location and its impact on bone mineral density (BMD) in an Asian population, a total of 17,508 subjects (8910 men and 8598 women) from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) were stratified into four age groups and analyzed for 25(OH)D and BMD according to geographic location (South, 33° N-35° N; Middle, 36° N; North, 37° N-38° N). Mean 25(OH)D were 47.7 and 41.2 nmol/L; calcium intake, 564.9 & 442.3 mg/d; femoral neck BMD, 0.829 & 0.721 g/cm²; and lumbar spine BMD, 0.960 & 0.918 g/cm² for men and women, respectively. Both men and women living in the South had significantly higher 25(OH)D and femoral neck BMD for those ≥50 years old. Lumbar spine BMD was significantly higher in men ≥50 years old, and for women 10-29 & 50-69 years old living in the South. A 1 or 2 degree difference in latitude has a significant effect on serum 25(OH)D and BMD in this low vitamin D status population. Thus, consideration of geographic location for a recommendation of vitamin D intake may be necessary.

Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Maternal vitamin D deficiency has been associated with a number of fetal and neonatal health problems. Preterm birth is one of the most detrimental, and the role of maternal vitamin D deficiency in preterm births has not been universally acknowledged. There had been limited epidemiological studies of vitamin D deficiency on the Chinese population., Subjects and Methods: 1103 women delivered in Shengjing Hospital, China Medical University from January 1(st), 2012 to January 1(st), 2013. Finally, 821 mother-newborn pairs which contained 143 mother-newborn pairs who were preterm delivery were recruited for analysis., Results: There was significant difference between spring and summer (P<0.0001) as well as spring and autumn (P<0.01). Compared to those in summer and autumn, the 25 (OH) D level was significantly lower in winter (summer vs winter P<0.0001, autumn vs winter P<0.0001). Maternal vitamin D level showed obvious variation with months and seasons, with higher level in summer months and lower level in winter months. There were significant difference between the vitamin D level of the very preterm group and the mildly preterm groups (P<0.01), as well as the very preterm group and the in-term groups (P<0.001). Prevalence of Vitamin D deficiency occurred in 63.04% of pregnant women in very preterm group, compared with 36.61% in in-term group., Conclusion: Vitamin D nutritional status of pregnant women and their newborns in Shenyang were relatively good compared to cities in similar latitudes. Vitamin D deficiency was most severe in late spring and least in summer. Severe preterm births before 31 weeks of gestation was associated with maternal vitamin D deficiency.

This review and meta-analysis assessed the relationship between vitamin D levels and the risk of breast and endometrial cancers, and the efficacy of vitamin D supplementation as a preventive strategy. We searched PubMed and the Cochrane Library using "vitamin D" and "breast and endometrial cancer," focusing on human studies in English. Ten high-quality studies were selected based on robust design and data integrity. We analyzed effect sizes--odds ratios, risk ratios, and hazard ratios with 95% confidence intervals--using a random-effects model. Our findings suggest that higher vitamin D levels are linked to a lower risk of these cancers, especially in premenopausal women and those with greater sun exposure. Although some studies found no significant links, the overall evidence supports vitamin D's protective potential. Further randomized trials are necessary to confirm these results and define vitamin D deficiency standards in cancer risk assessment. [ABSTRACT FROM AUTHOR]

A study published in the Clinical & Experimental Allergy journal found that low levels of vitamin D in early childhood were associated with aeroallergen-specific IgE in children with a history of severe bronchiolitis. However, there was no association between vitamin D levels and total, food-specific, or outdoor-aeroallergen-specific IgE. The study suggests that vitamin D plays a role in immune modulation and may be involved in allergic diseases. The study had limitations, such as a small sample size and not accounting for geographic factors and individual allergen exposure. Further research is needed to fully understand the relationship between vitamin D and allergic sensitization. [Extracted from the article]

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Objective: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. Methods: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). Conclusions: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. Methods: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). Conclusions: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

Background: Vitamin D deficiency in Saudi Arabia is alarmingly high and can affect all human ages. However, the characteristic hormonal and metabolic features, and the systemic Vitamin D levels, among Saudi women with polycystic ovarian syndrome (PCOS) remain largely unknown. Aims: This retrospective study aimed to identify the hormonal, metabolic, and Vitamin D status variabilities among infertile Saudi women with PCOS versus those of non-PCOS fertile women as controls. Materials and Methods: The medical records of a total of 99 women (49 PCOS and 50 controls), with matched age and body mass index, were analyzed in this study. For each woman who met the study inclusion criteria, the analyzed parameters included the serum levels of 25-hydroxyvitamin D (25(OH) D), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), androgen, total testosterone (TT), estradiol, progesterone, thyroid hormones, the fasting plasma glucose (FPG), and lipid profile concentrations. Results: Compared to the controls, women with PCOS had significantly lower levels of 25(OH) D, SHBG, FSH, and estradiol, but they had significantly higher levels of LH, androgen, TT, FPG, total cholesterol, and low-density lipoprotein cholesterol. There were no differences between the two groups regarding the other parameters. Conclusions: The present findings highlight the prevalence of sex hormones, metabolic, and Vitamin D status disturbances among Saudi women with PCOS. Large-scale retrospective and prospective studies are therefore essential to realize these findings.

Background: Alopecia areata (AA) has been postulated to be an autoimmune disease affecting the hair follicles. Because vitamin D receptors are present in the immune system and hair follicles, vitamin D has been hypothesized to affect the disease. Objective: The aim of this study was to determine serum 25-hydroxyvitamin D levels and the percentage of vitamin D deficiency in AA patients and compare them with those in healthy controls in a Philippine tertiary hospital. Methods: This cross-sectional study included 29 AA patients and 29 healthy controls. The serum 25-hydroxyvitamin D levels were determined using the chemiluminescent immunoassay method. Results: There was no significant difference in the mean vitamin D levels between AA patients (24.41 ± 6.87 ng/mL) and healthy controls (24.68 ± 6.68 ng/mL) (P = .88). The percentage of patients with vitamin D deficiency, defined as

Background: Vitamin D deficiency in Saudi Arabia is alarmingly high and can affect all human ages. However, the characteristic hormonal and metabolic features, and the systemic Vitamin D levels, among Saudi women with polycystic ovarian syndrome (PCOS) remain largely unknown. Aims: This retrospective study aimed to identify the hormonal, metabolic, and Vitamin D status variabilities among infertile Saudi women with PCOS versus those of non-PCOS fertile women as controls. Materials and Methods: The medical records of a total of 99 women (49 PCOS and 50 controls), with matched age and body mass index, were analyzed in this study. For each woman who met the study inclusion criteria, the analyzed parameters included the serum levels of 25-hydroxyvitamin D (25(OH) D), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), androgen, total testosterone (TT), estradiol, progesterone, thyroid hormones, the fasting plasma glucose (FPG), and lipid profile concentrations. Results: Compared to the controls, women with PCOS had significantly lower levels of 25(OH) D, SHBG, FSH, and estradiol, but they had significantly higher levels of LH, androgen, TT, FPG, total cholesterol, and low-density lipoprotein cholesterol. There were no differences between the two groups regarding the other parameters. Conclusions: The present findings highlight the prevalence of sex hormones, metabolic, and Vitamin D status disturbances among Saudi women with PCOS. Large-scale retrospective and prospective studies are therefore essential to realize these findings. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations between serum 25-hydroxyvitamin D (25(OH)D) levels and serum liver enzymes in a representative sample of US adults.Design: The cross-sectional study sample consisted of 24 229 adults with data on serum 25(OH)D levels and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transaminase (GGT) concentrations, in addition to data on other potential confounders. Multivariate logistic regression and linear regression were applied to assess the associations between serum 25(OH)D levels and ALT, AST, ALP and GGT concentrations.Setting: The National Health and Nutrition Examination Survey, 2001-2006.Participants: The cross-sectional study sample consisted of 24 229 adults.Results: We found a significant association between low serum 25(OH)D levels (<30 nmol/l) and ALP levels in all participants (OR 2·67; 95 % CI 1·98, 3·59; P < 0·001), a confirmed healthy population (OR 3·02; 95 % CI 2·25, 4·07; P < 0·001) and individuals with viral hepatitis (OR 2·87; 95 % CI 1·52, 5·44; P = 0·006) compared with those who had normal 25(OH)D levels (>50 nmol/l). Moreover, in both the logistic regression and linear regression, the associations between 25(OH)D levels and ALP levels were stronger in the subgroups with obesity. No association was present between ALT, AST or GGT levels and serum 25(OH)D levels in this population.Conclusions: The results of the present study provide epidemiological evidence that vitamin D deficiency is associated with liver ALP levels in humans. This finding suggests a potential adverse effect of low 25(OH)D levels on human liver function. However, the underlying mechanisms still need further investigation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate serum 25-hydroxyvitamin D levels in patients with keratoconus (KC) and its association with disease severity and to compare vitamin D levels with those of age- and sex-matched healthy individuals.Methods: This study included 100 patients with KC and 100 non-atopic healthy controls. Serum vitamin D levels were measured using liquid chromatography-tandem mass spectrometry and compared between the study groups. KC severity was graded as mild (K = 43.1-46.9 D), moderate (K = 47-50 D), and severe (K > 50 D). Vitamin D levels were classified as deficient (≤10 ng/mL), insufficient (11-20 ng/mL), and optimal (>20 ng/mL).Results: The mean serum vitamin D level was significantly lower in the KC group than in the control group (12.18 ± 5.05 ng/mL vs 15.18 ± 5.81 ng/mL; p < .001). Vitamin D deficiency (≤10 ng/mL) was observed in 54.0% of the KC patients and 34.0% of the controls (p = .011). Multivariable logistic regression analysis revealed that having deficient vitamin D level increased the presence of KC 2.9 fold (p = .021, 95% confidence interval, 1.17-6.95). Decreasing serum vitamin D levels were not significantly associated with increasing severity of KC (p = .311). Although the rate of patients with deficient vitamin D was the highest in the severe KC group, distribution of vitamin D levels were not significantly different among KC groups (p = .326).Conclusion: The patients with KC had lower serum vitamin D levels than those of age- and sex-matched healthy controls. The present study could be a valuable entry point for further researches investigating the potential link between vitamin D and KC. [ABSTRACT FROM AUTHOR]

Current guidelines provide a universal recommendation on vitamin D intake to prevent insufficiency. However, the relative influence of food, UVB and other factors on serum 25-hydroxyvitamin D (25(OH)D) insufficiency has been poorly investigated in preschool children. We assessed serum 25(OH)D quantities and their association with vitamin D intake using a brief-type self-administered diet history questionnaire for children aged 3–6 years (BDHQ3y), outdoor playing time and background UVB radiation level among 574 36-month-old Japanese children living at latitude 35°N. The average serum 25(OH)D concentration was 23·5 (sd 6·1) ng/ml, and 170 (29·6 %) children had vitamin D insufficiency (<20 ng/ml) despite high consumption of fish. Multiple logistic regression adjusting for social factors showed that when background UVB radiation level was <15 kJ/m2 (monthly average), there was a 1·89 (95 % CI 1·31, 2·74) times higher risk of vitamin D insufficiency, to which vitamin D intake nor time spent outdoors were significantly associated. ANOVA showed that the contribution of the variability in vitamin D intake on the variability of serum 25(OH)D level was 1·8 % of that of UVB exposure. The correlation between vitamin D intake and serum 25(OH)D level was not stronger when limited to measurements in winter. We found that nearly 30 % of 3-year-old Japanese children had vitamin D insufficiency despite high consumption of fish and living at relatively low latitude. We failed to observe an association between vitamin D intake and the risk of vitamin D insufficiency. This may be due to the extremely limited access to vitamin D-fortified food and supplements for children in Japan. [ABSTRACT FROM AUTHOR]

Abstract Although vitamin D is essential for bone health, little is known about prevalence of vitamin D deficiency and low bone mineral density (BMD) among children, especially those in developing countries. It also remains unclear whether serum 25-hydroxyvitamin D [25(OH)D] is associated with BMD among children. We investigated these questions among children and adolescents in Yinchuan (latitude: 38° N), Ningxia, an economically underdeveloped province in Northwest China. A total of 1582 children (756 boys and 826 girls), aged 6–18 years, were recruited from schools using the stratified random sampling method in fall 2015. Serum 25(OH)D concentrations were measured by enzyme-linked immunosorbent assay, and BMD was quantified by dual-energy X-ray absorptiometry. Vitamin D deficiency (defined as serum 25(OH)D ≤ 37.5 nmol/L) was present in 35.5% of study subjects. There were no clear patterns of differences in serum 25(OH)D concentrations across the four age groups compared (6–9 years, 10–13 years, 14–16 years, and 17–18 years). The prevalence of low total body less head (TBLH) BMD (defined as a Z -score of ≤ −2.0 standard deviations away from the mean BMD values of the Chinese pediatric reference population) among children examined was 1.8% and was not significantly different among the four age groups considered. Linear regression analysis revealed that age, weight, and height were significantly and positively associated with TBLH BMD and that the strongest determinant of TBLH BMD was age in boys and weight in girls. There were no significant correlations between serum 25(OH)D concentrations and BMD obtained for total body and at various skeletal sites (r ranged from −0.005 to 0.014) regardless of whether children evaluated were sufficient, insufficient, or deficient in vitamin D. In conclusion, more than one-third of children and adolescents in a Northwest Chinese city were deficient in vitamin D but only <2% of them developed low BMD. Highlights • Vitamin D deficiency (serum 25(OH)D ≤37.5 nmol/L) existed in 35.5% of 1582 school children in a Northwest Chinese city. • The prevalence of low total body less head (TBLH) bone mineral density (BMD) among school children examined was 1.8%. • Age, weight, and height were positively associated with TBLH BMD among this pediatric Chinese population in both sexes. • The strongest determinant of TBLH BMD was age in boys and weight in girls. • Serum 25(OH)D was overall not associated with BMD (total body and various skeletal sites) regardless of vitamin D status. [ABSTRACT FROM AUTHOR]

Background: Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals.Objective: We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes.Methods: Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes.Results: 25(OH)D concentrations were <30 nmol/L in 15% of maternal and 45% of umbilical cord sera and <50 nmol/L in 42% of mothers and 80% of cords. At age 5 y, the mean ± SD KBIT-2 intelligence quotient (IQ) composite score was 104.6 ± 8.6; scores were 107.2 ± 10.0 in verbal and 99.8 ± 8.8 in nonverbal tasks. Developmental delay (scores <85) was seen in <3% of children across all domains. The mean ± SD CBCL total problem score was 21.3 ± 17.5; scores in the abnormal/clinical range for internal, external, and total problem scales were present in 12%, 4%, and 6% of participants, respectively. KBIT-2 and CBCL subscale scores at 5 y were not different between children exposed to low antenatal vitamin D status, either at 30 or 50 nmol/L 25(OH)D thresholds. Neither maternal nor cord 25(OH)D (per 10 nmol/L) were associated with KBIT-2 IQ composite scores [adjusted β (95% CI): maternal -0.01 (-0.03, 0.02); cord 0.01 (-0.03, 0.04] or CBCL total problem scores [maternal 0.01 (-0.04, 0.05); cord 0.01 (-0.07, 0.09)].Conclusion: In this well-characterized prospective maternal-infant cohort, we found no evidence that antenatal 25(OH)D concentrations are associated with neurodevelopmental outcomes at 5 y. The BASELINE Study was registered at www.clinicaltrials.gov as NCT01498965; the SCOPE Study was registered at http://www.anzctr.org.au as ACTRN12607000551493. [ABSTRACT FROM AUTHOR]