Residential Greenness and Frailty Among Older Adults: A Longitudinal Cohort in China

ObjectivesFrailty is an accumulation of deficits characterized by reduced resilience to stressors and increased vulnerability to adverse outcomes. There is evolving evidence on the health benefits of residential greenness, but little is known about its impact on frailty.DesignA longitudinal cohort study.Setting and participantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with a 12-year follow-up.MethodsWe assessed residential greenness by calculating the Normalized Difference Vegetation Index (NDVI) in the 500 m radius around participants' residence. We used 39 self-reported health items to construct a frailty index (FI) as a proportion of accumulated deficits. We defined an FI of ≤0.21 as nonfrail and prefrail, and an FI of >0.21 as frail. We used the mixed effects logistic regression models to examine the association between residential greenness and frailty, adjusted for a number of covariates.ResultsWe had 16,238 participants, with a mean age of 83.0 years (standard deviation: 11.5). The mean baseline NDVI and FI were 0.40, and 0.12, respectively. Compared to the participants living in the lowest quartile of residential greenness, those in the highest quartile had a 14% [odds ratio (OR): 0.86, 95% confidence interval (CI): 0.77, 0.97] lower odds of frailty. The association was stronger among urban vs rural residents. Additionally, each 0.1-unit increase in annual average NDVI was related to a 2% higher odds of improvement in the frailty status (OR: 1.02, 95% CI: 1.00, 1.04).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are related to a lower likelihood of frailty, specifically in urban areas.     

Prevalence and Predictors of Vitamin D Deficiency and Insufficiency among Pregnant Rural Women in Bangladesh

Although adequate vitamin D status during pregnancy is essential for maternal health and to prevent adverse pregnancy outcomes, limited data exist on vitamin D status and associated risk factors in pregnant rural Bangladeshi women. This study determined the prevalence of vitamin D deficiency and insufficiency, and identified associated risk factors, among these women. A total of 515 pregnant women from rural Bangladesh, gestational age ≤ 20 weeks, participated in this cross-sectional study. A separate logistic regression analysis was applied to determine the risk factors of vitamin D deficiency and insufficiency. Overall, 17.3% of the pregnant women had vitamin D deficiency [serum 25(OH)D concentration <30.0 nmol/L], and 47.2% had vitamin D insufficiency [serum 25(OH)D concentration between 30–<50 nmol/L]. The risk of vitamin D insufficiency was significantly higher among nulliparous pregnant women (OR: 2.72; 95% CI: 1.75–4.23), those in their first trimester (OR: 2.68; 95% CI: 1.39–5.19), anaemic women (OR: 1.53; 95% CI: 0.99–2.35; p = 0.056) and women whose husbands are farmers (OR: 2.06; 95% CI: 1.22–3.50). The risk of vitamin deficiency was significantly higher among younger pregnant women (<25 years; OR: 2.12; 95% CI: 1.06–4.21), nulliparous women (OR: 2.65; 95% CI: 1.34–5.25), women in their first trimester (OR: 2.55; 95% CI: 1.12–5.79) and those with sub-optimal vitamin A status (OR: 2.30; 95% CI: 1.28–4.11). In conclusion, hypovitaminosis D is highly prevalent among pregnant rural Bangladeshi women. Parity and gestational age are the common risk factors of vitamin D deficiency and insufficiency. A husband’s occupation and anaemia status might be important predictors of vitamin D insufficiency, while younger age and sub-optimal vitamin A status are risk factors for vitamin D deficiency in this population.     

Vitamin D Intake and Status in 6-Year-Old Icelandic Children Followed up from Infancy

High serum 25-hydroxyvitamin D (25(OH)D) levels have been observed in infants in Nordic countries, likely due to vitamin D supplement use. Internationally, little is known about tracking vitamin D status from infancy to childhood. Following up 1-year-old infants in our national longitudinal cohort, our aims were to study vitamin D intake and status in healthy 6-year-old Icelandic children (n = 139) and to track vitamin D status from one year of age. At six years, the mean 25(OH)D level was 56.5 nmol/L (SD 17.9) and 64% of children were vitamin D sufficient (25(OH)D ≥ 50 nmol/L). A logistic regression model adjusted for gender and breastfeeding showed that higher total vitamin D intake (Odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.08–1.49), blood samples collected in summer (OR = 8.88, 95% CI = 1.83–43.23) or autumn (OR = 5.64, 95% CI = 1.16–27.32) compared to winter/spring, and 25(OH)D at age one (OR = 1.02, 95% CI = 1.002–1.04) were independently associated with vitamin D sufficiency at age six. The correlation between 25(OH)D at age one and six was 0.34 (p = 0.003). Our findings suggest that vitamin D status in infancy, current vitamin D intake and season are predictors of vitamin D status in early school age children. Our finding of vitamin D status tracking from infancy to childhood provides motivation for further studies on tracking and its clinical significance.     

Association Between Plasma 25-hydroxyvitamin D Concentrations and Incident Activities of Daily Living Disability: A Longitudinal Community-Based Cohort Study

ObjectivesA few studies of Western populations have found inconsistent results regarding the associations between vitamin D status and physical function. We explored the association between circulating vitamin D status [plasma 25-hydroxyvitamin D, 25(OH)D] and incident activities of daily living (ADL) disability among Chinese older adults.DesignCommunity-based longitudinal cohort study.Setting and ParticipantsA total of 2453 men and women (median age 84.0 years) in 7 Chinese longevity areas were included.MeasuresCox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident ADL, with adjustments for potential sociodemographic, and lifestyle confounders and biomarkers. Because there was a statistically significant interaction between plasma 25(OH)D and sex in relation to incident ADL, men and women were analyzed separately.ResultsThe median concentrations of plasma 25(OH)D were 46.6 nmol/L and 36.4 nmol/L for men and women, respectively. Compared with the lowest quartile in the fully adjusted model, the HR for incident ADL disability for the highest quartile was 0.55 (95% CI 0.36–0.85) for women; for men, a null association was indicated (HR_{highest vs lowest} 0.61, 95% CI 0.37–1.00). However, when using the recommended circulating 25(OH)D thresholds by the US Institute of Medicine, those with vitamin D sufficiency (≥50 nmol/L) had better ADL disability prognoses than those with vitamin D deficiency (<30 nmol/L) in both sexes (men HR 0.45, 95% CI 0.28–0.72; women HR 0.58, 95% CI 0.37–0.90).Conclusions and ImplicationsThe relationship between plasma 25(OH)D concentration and incident ADL disability was sex-specific among Chinese older adults. However, participants with recommended vitamin D sufficiency may have better disability prognoses in both sexes, suggesting that the recommended 25(OH)D concentration for bone health may extend to functional outcomes such as ADL disability in Chinese older adults.     

Risk factors for vitamin D deficiency in women aged 20–50 years consulting in general practice: a cross-sectional study

Abstract

Objective: Vitamin D deficiency is often unidentified, although treatment is simple and inexpensive. Our objective was to estimate the influence of concealing clothes and other risk factors for vitamin D deficiency in women aged 20 to 50 years consulting general practitioners. Methods: 13 GPs in the Rhone Alps area planned to recruit 300 women (100 veiled and 200 non-veiled) from January to March 2008. Serum 25(OH)D and PTH were measured in one single laboratory (Biomnis^®) by a radio-immunoassay method. A survey was administered about dietary habits, sun exposure, and quality of life. Results: Among 247 women enrolled, 196 were analysed: 61 wearing concealing clothes (31.2%) and 135 without (68.8%). As expected, 25(OH)D serum level was significantly lower in covered women (20.1 versus 38.9 nmol/l P < 0.001). Of women who did not wear concealing clothing, 39.3% had severe hypovitaminosis D (25(OH)D concentration < 30 nmol/l). Women wearing concealing clothes had more often other known risk factors such as dark skin (P < 0.001), less sunlight exposure, or a higher Body Mass Index (P = 0.009). Besides concealing clothing (OR 6.37, 95% CI: 1.35–30.09), multivariate analyses revealed two independent risk factors for vitamin D deficiency: no full-body sun exposure (OR: 3.06, 95% CI: 1.18–7.94) and no outdoor sports (OR: 2.81, 95% CI: 1.11–7.12) for threshold 52 nmol/l.

Conclusion: Young women consulting their GP had hypovitaminosis D more often than expected. Besides concealing clothing, absence of full body sun exposure during summer and of outdoor sports practice could suggest a possible vitamin D deficiency.     

Serum 25(OH)D response to vitamin D3 supplementation: A meta-regression analysis

ObjectiveThe aim of this study was to review factors that influence serum 25(OH)D when patients are given vitamin D supplements.MethodsFrom a comprehensive search of all randomized controlled clinical trials with vitamin D₃ supplementation available on PubMed up to November 2011, we selected 33 with 43 treatment arms that included at least 30 adult participants. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses were performed for prespecified factors, including dose, duration, baseline serum 25(OH)D, and age.ResultsWith a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37 nmol/L (95% CI, 33–41) with significant heterogeneity among studies. Dose (slope: 0.006; P < 0.001), trial duration (slope: 0.21; P < 0.001), baseline serum 25(OH)D (slope: −0.19; P < 0.001), and age (slope: 0.42; P < 0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In subgroup analyses, the PMD was higher with doses ≥800 IU/d (39.3 nmol/L) after 6 to 12 mo (41.7 nmol/L), with baseline 25(OH)D <50 nmol/L (39.6 nmol/L), and in adults aged >80 y (40.5 nmol/L).ConclusionThis meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of ≥800 IU/d, after at least 6 to 12 mo, and even when baseline 25(OH)D is low and in adults >80 y.     

Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth.     

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case–control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82–1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83–1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78–1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.     

Multinutrient-Fortified Juices Improve Vitamin D and Vitamin E Status in Children: A Randomized Controlled Trial

BackgroundProvision of fortified juices may provide a convenient method to maintain and increase blood fat-soluble vitamins.ObjectiveTo determine whether children consuming orange juice fortified with calcium and combinations of vitamins D, E, and A could increase serum 25-hydroxyvitamin D [25(OH)D], α-tocopherol, and retinol levels.DesignA 12-week randomized, double-blind, controlled trial.Participants/settingOne hundred eighty participants (aged 8.04±1.42 years) were recruited at Tufts (n=70) and Boston University (n=110) during 2005-2006. Of those recruited, 176 children were randomized into three groups: CaD (700 mg calcium+200 IU vitamin D), CaDEA (700 mg calcium+200 IU vitamin D+12 IU vitamin E+2,000 IU vitamin A as beta carotene), or Ca (700 mg calcium). Children consumed two 240-mL glasses of CaD, CaDEA, or Ca fortified orange juice daily for 12 weeks.Main outcome measuresSerum 25(OH)D, α-tocopherol, and retinol concentrations.Statistical analysesChanges in 25(OH)D, α-tocopherol, retinol, and parathyroid hormone concentrations were examined. Covariates included sex, age, race/ethnicity, body mass index, and baseline 25(OH)D, α-tocopherol, retinol, or parathyroid hormone levels. Multivariate models and repeated measures analysis of variance tested for group differences with pre–post measures (n=141).ResultsBaseline 25(OH)D was 68.4±27.7 nmol/L (27.4±11.10 ng/mL) ), with 21.7% of participants having inadequate 25(OH)D (<50 nmol/L [20.03 ng/mL]). The CaD group's 25(OH)D increase was greater than that of the Ca group (12.7 nmol/L [5.09 ng/mL], 95% CI 1.3 to 24.1; P=0.029). The CaDEA group's increase in α-tocopherol concentration was greater than that in the Ca or CaD groups (3.79 μmol/L [0.16 μg/mL], 95% CI 2.5 to 5.1 and 3.09 μmol/L [0.13 μg/mL], 95% CI −1.8 to 4.3), respectively (P<0.0001). Retinol levels did not change, and body weight remained as expected for growth.ConclusionsDaily consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E increased 25(OH)D and α-tocopherol concentrations in young children within 12 weeks.     

Prevalence and Correlates of Vitamin D Deficiency among Young South African Infants: A Birth Cohort Study

Early-life vitamin D deficiency is associated with adverse child health outcomes, but the prevalence of vitamin D deficiency and its correlates in infants remains underexplored, particularly in sub-Saharan Africa. We aimed to investigate the prevalence of vitamin D deficiency and its correlates among young infants in South Africa. This study included 744 infants, aged 6–10 weeks from the Drakenstein Child Health Study, a population-based birth cohort. Infants were categorized into distinct categories based on serum 25(OH)D concentration level including deficient (<50 nmol/L), insufficient (50–74 nmol/L), and sufficient (≥75 nmol/L). Using multivariable Tobit and logistic regression models, we examined the correlates of serum 25(OH)D₃ levels. The overall prevalence of vitamin D deficiency was 81% (95% confidence intervals (CI]) 78–83). Multivariable regression analysis showed that serum 25(OH)D₃ concentration was independently associated with study site, socioeconomic status, and sex. Birth in winter and breastfeeding were the strongest predictors of lower serum 25(OH)D₃ concentration levels. Compared to non-breastfed children, children breastfed were at higher risk of vitamin D deficiency (AOR, 1.96; 95% CI, 1.04–3.67) and breastfeeding for more than one month was associated with greater likelihood of vitamin D deficiency (AOR, 5.40; 95% CI, 2.37–12.32) and lower vitamin D concentrations (−16.22 nmol/L; 95% CI, −21.06, −11.39). Vitamin D deficiency in infants is ubiquitous, under-recognised, and strongly associated with season of birth and breastfeeding in this setting. Nutritional interventions with vitamin D supplementation in national health programs in low- and middle-income countries are urgently needed to improve early-life vitamin D status in infants.     

Vitamin D: Sunshine vs. diet vs. pills

One in five people in the UK is known to have a low serum vitamin D level (25‐hydroxy vitamin D below 25 nmol/l) according to the National Diet and Nutrition Survey. The Summer of 2015 saw publication of a draft report from the government's Scientific Advisory Committee on Nutrition (SACN), which proposes introduction of dietary reference values (DRVs) for all age groups (not just those considered as vulnerable). The health outcome identified as the basis for setting DRVs for vitamin D was musculoskeletal health (based on rickets, osteomalacia, falls, risk of falling and muscle strength). The data were not sufficient to establish a distribution of serum 25(OH)D concentrations or a clear threshold serum 25(OH)D concentration to support musculoskeletal health outcomes, but the evidence overall suggests that the risk of poor musculoskeletal health is increased at serum 25(OH)D concentrations below 25 nmol/l. Therefore, SACN selected a serum 25(OH)D concentration of 25 nmol/l, on a precautionary basis, as the target concentration to protect all individuals from poor musculoskeletal health. This concentration was considered to be a ‘population protective level’ (i.e. the concentration that 97.5% of individuals in the UK should be above, throughout the year, in order to protect musculoskeletal health). After establishing the health outcomes linked with low vitamin D status, the next step in estimating DRVs for vitamin D was translation of the serum 25(OH)D concentration of 25 nmol/l into a dietary intake value that represents the reference nutrient intake (RNI) for vitamin D [i.e. the average daily vitamin D intake that would be sufficient to maintain a serum 25(OH)D concentration of at least 25 nmol/l in 97.5% of individuals in the UK]. The average vitamin D intake refers to the mean or average intake over the long‐term and takes account of day‐to‐day variations in vitamin D intake. It was not possible to quantify the sunlight exposure required in the summer months to maintain a winter serum 25(OH)D concentration of at least 25 nmol/l because of the number of factors that affect endogenous vitamin D synthesis, storage and utilisation. Instead, use was made of a series of three randomised controlled trials, conducted in the winter months, to estimate directly the amount of vitamin D required daily to achieve a serum threshold of 25 nmol/l throughout the year. The RNI proposed by SACN for all people aged 4 and above is 10 μg/day. For younger children, a Safe Intake of 8.5–10 μg/day (depending on age) is proposed. These recommendations bring alignment with many other countries of the world. As dietary intakes from food are typically well below the 10 μg/day proposed by SACN for most age groups, media reports speculated on how this advice might be achieved in practice.     

Relationship between Serum 25OH-Vitamin D2 Level and Vitamin D Status of Children Aged 3–5 Years in China

Background: Vitamin D deficiency is prevalent globally and there is lack of evidence as to how 25(OH)D2 contributes to vitamin D status. The aim of this study was to describe vitamin D status and to assess the role of vitamin D2, a dietary vitamin D source, against the vitamin D status of children aged 3–5 years in China. Methods: Data were extracted from the Chinese National Nutrition and Health Surveillance (CNNHS) in 2013. The concentration of serum 25(OH)D2 and 25(OH)D3 was measured by using LC-MS/MS. Results: A total of 1435 subjects were enrolled and serum 25(OH)D were analyzed. The prevalence of total serum 25(OH)D < 30 nmol/L was 8.9%. Serum 25(OH)D2 was detected in 10.9% of the studied children. After adjusting for confounding factors, total 25(OH)D concentration was 8.48 nmol/L lower and odds ratio of vitamin D deficiency was 4.20 times (OR (95%CI): 4.20 (1.64, 10.77)) in children without 25(OH)D2 than those with 25(OH)D2 detected. Conclusions: Vitamin D deficiency was common among children aged 3–5 years in China. Vitamin D2 may play a role in preventing vitamin D deficiency in Chinese children aged 3–5 years.     

Serum 25-hydroxyvitamin D levels among Boston trainee doctors in winter

As indoor workers, trainee doctors may be at risk for inadequate vitamin D. All trainee doctors (residents) in a Boston pediatric training program (residency) were invited to complete a survey, and undergo testing for serum 25-hydroxyvitamin D [25(OH)D], PTH, and calcium during a 3-week period in March 2010. We examined the association between resident characteristics and serum 25(OH)D using Chi2 and Kruskal-Wallis test and multivariable linear and logistic regression. Of the 119 residents, 102 (86%) participated. Although the mean serum 25(OH)D level was 67 nmol/L (±26), 25 (25%) had a level <50 nmol/L and 3 (3%) residents had levels <25 nmol/L. In the multivariable model, factors associated with 25(OH)D levels were: female sex (β 12.7, 95% CI 3.6, 21.7), white race (β 21.7, 95% CI 11.7, 31.7), travel to more equatorial latitudes during the past 3 months (β 6.3, 95% CI 2.0, 10.5) and higher daily intake of vitamin D (β 1.1, 95% CI 0.04, 2.1). Although one in four residents in our study had a serum 25(OH)D <50 nmol/L, all of them would have been missed using current Centers for Medicare and Medicaid Services (CMS) screening guidelines. The use of traditional risk factors appears insufficient to identify low vitamin D in indoor workers at northern latitudes.     

Vitamin D status and hypertensive disorders in pregnancy

PurposeSeveral studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear.MethodsAmong women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4–36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%).ResultsWe did not detect an association between plasma 25(OH)D concentration (mean 58, standard deviation 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval, 0.77–1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval, 1.01–1.72) per each 25 nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest that this association was not because of reverse causation. Although the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension.ConclusionsThese data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy.     

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka,Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.     

The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D₃ (25(OH)D₃), 25-hydroxyvitamin D₂ (25(OH)D₂) and Epi-25-hydroxyvitamin D₃ (Epi-25(OH)D₃)), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12–25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen’s Kappa test. Serum total 25(OH)D ranged from 33.8–169.8 nmol/L and plasma ranged from 28.6–211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D₃ (7.38 nmol/L; 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D₃ (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.     

A comprehensive genetic and epidemiological association analysis of vitamin D with common diseases/traits in the UK Biobank

Vitamin D has been intensively studied for its association with human health, but the scope of such association and the causal role of vitamin D remain controversial. We aim to comprehensively investigate the links between vitamin D and human health through both epidemiological and Mendelian randomization (MR) analyses. We examined the epidemiological associations between serum 25‐hydroxyvitamin D (25(OH)D) concentration and 90 diseases/traits in 326,409 UK Biobank (UKBB) Europeans. The causal relations between 25(OH)D and 106 diseases/traits were investigated by performing MR analysis using genome‐wide significant 25(OH)D‐associated variants (N = 143) from the largest UKBB GWAS to date. In epidemiological analysis, we found 25(OH)D was associated with 45 diseases/traits across cardiovascular/metabolic diseases, psychiatric/neurological diseases, autoimmune/inflammatory diseases, cancer, musculoskeletal diseases, and quantitative traits. In MR‐analysis, we presented evidence suggesting potential causal role of 25(OH)D in increasing height (β = .064, 95% confidence interval [CI] = 0.019–0.11) and preventing the risk of ovarian cancer (odds ratio [OR] = 0.96, 95% CI = 0.93–0.99), multiple sclerosis (OR = 0.96, 95% CI = 0.94–0.98), leg fracture (OR = 0.60, 95% CI = 0.45–0.80) and femur fracture (OR = 0.53, 95% CI = 0.32–0.84). These findings confirmed associations of vitamin D with a broad spectrum of diseases/traits and supported the potential causal role of vitamin D in promoting health.     

Effect of Vitamin D Supplementation on Depressive Symptoms in Patients With Knee Osteoarthritis

ObjectivesTo determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency.DesignA prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D₃ (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups.Setting and ParticipantsThis clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia.MeasuresThe primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27).ResultsOf 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: ?0.66, 95% confidence interval (CI): ?1.22 to ?0.11, P for difference = .02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: ?0.73, 95% CI: ?1.41 to ?0.05, P for difference = .04) over 24 months.Conclusions/ImplicationsThese findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA.     

The effect of body mass index on adequacy of serum 25-hydroxyvitamin D levels in US adults: the National Health and Nutrition Examination Survey 2001 to 2006

PurposeTo investigate the relationship between body mass index (BMI) and vitamin D adequacy among US adults.MethodsWe used data for US adults aged 18 years or older (n = 12,927) who participated in the 2001 to 2006 United States National Health and Nutrition Examination Survey. Log-binomial regression was used to estimate the strength of association between BMI categories and the prevalence of serum 25-hydroxyvitamin D [25(OH)D] greater than or equal to 20 ng/mL before and after controlling for selected characteristics. An interaction term between race or ethnicity and BMI categories was tested.ResultsAmong US adults, 67.2% had serum 25(OH)D greater than or equal to 20 ng/mL, a cut point suggested by the Office of Dietary Supplements for adequate bone and general health. Overweight and obese adults were 8% (95% confidence interval, 0.89–0.95) and 26% (95% confidence interval, 0.71–0.78), respectively, less likely to have serum 25(OH)D greater than or equal to 20 ng/mL than their normal weight counterparts after controlling for age, gender, race/ethnicity, nativity and marital status, as well as education and income. No heterogeneity of the association between BMI categories and the prevalence of 25(OH)D greater than or equal to 20 ng/mL was observed by race or ethnicity.ConclusionsThe low prevalence of 25(OH)D greater than equal to 20 ng/mL among overweight and obese adults in the US population underscores the need to comparatively assess vitamin D intakes across different BMIs.     

Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08–6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11–2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.