Total,Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

Epidemiological studies suggest a relationship between total 25-hydroxyvitamin D [25(OH)D], adiposity, and metabolic traits. The bioavailability of 25(OH)D is regulated by the albumin, vitamin D binding protein (VDBP), and variants of the GC gene. Therefore, it is not clear if bioavailable or free 25(OH)D offer additional benefits compared to total 25(OH)D when estimating the magnitude of these associations. Our aim was to evaluate the association between 25(OH)D (total, free and bioavailable) with adiposity and metabolic traits. This was a cross-sectional study of 1904 subjects from the Health Workers Cohort Study from Mexico. Free and bioavailable 25(OH)D were calculated based on VDBP and albumin determinations, using a formula adjusted for the GC gene diplotypes. Adiposity and metabolic traits were measured with standardized procedures. Free and bioavailable 25(OH)D levels correlated with total 25(OH)D, r = 0.71 and 0.70, respectively (p < 0.001). Total, bioavailable and free 25(OH)D levels were negatively associated with the adiposity marker (visceral adiposity index) and metabolic traits (metabolic syndrome, type 2 diabetes, triglycerides, triglycerides/HDL-c ratio, and triglycerides/glucose index) in multivariate regression models (ORs = 0.73 to 0.96). Our findings suggest that free and bioavailable 25(OH)D do not offer additional advantages over total 25(OH)D regarding its association with adiposity and several metabolic traits in Mexican adults.     

High Prevalence of Vitamin D Deficiency in Infertile Women Referring for Assisted Reproduction

A comprehensive analysis of the vitamin D status of infertile women is the first step in understanding hypovitaminosis impact on reproductive potential. We sought to determine vitamin D profiles of women attending an infertility center and to investigate non-dietary determinants of vitamin D status in this population. In this cross-sectional analysis, a cohort of 1072 women (mean age ± standard deviation 36.3 ± 4.4 years) attending an academic infertility center was used to examine serum 25-hydroxy-vitamin D (25(OH)D) levels in relation to demographic characteristics, seasons and general health risk factors. Both unadjusted and adjusted levels of serum 25(OH)D were examined. Median 25(OH)D concentration was below 30 ng/mL for 89% of the entire year. Over the whole year, 6.5% of patients had 25(OH)D levels ≤10 ng/mL, 40.1% ≤20 ng/mL, and 77.4% ≤30 ng/mL. Global solar radiation was weakly correlated with 25(OH)D levels. At multivariable analysis, 25(OH)D levels were inversely associated with BMI; conversely, 25(OH)D levels were positively associated with height and endometriosis history. Serum 25(OH)D levels are highly deficient in women seeking medical help for couple’s infertility. Levels are significantly associated with body composition, seasonal modifications and causes of infertility. Importantly, this deficiency status may last during pregnancy with more severe consequences.     

A Prospective Cohort Study of Bioavailable 25-Hydroxyvitamin D Levels as a Marker of Vitamin D Status in Nontuberculous Mycobacterial Pulmonary Disease

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years; 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration <50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.     

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)₂D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)₂D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites.     

Prevalence and Determinants of Vitamin D Deficiency in 9595 Mongolian Schoolchildren: A Cross-Sectional Study

Population-based data relating to vitamin D status of children in Northeast Asia are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 9595 schoolchildren aged 6–13 years in Ulaanbaatar (UB), the capital city of Mongolia. Risk factors for vitamin D deficiency were collected by questionnaire, and serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using an enzyme-linked fluorescent assay, standardized and categorized as deficient (25[OH]D <10 ng/mL) or not. Odds ratios for associations between independent variables and risk of vitamin D deficiency were calculated using multivariate analysis with adjustment for potential confounders. The prevalence of vitamins D deficiency was 40.6% (95% CI 39.7% to 41.6%). It was independently associated with female gender (adjusted odds ratio [aOR] for girls vs. boys 1.23, 95% CI 1.11–1.35), month of sampling (aORs for December–February vs. June–November 5.28 [4.53–6.15], March–May vs. June–November 14.85 [12.46–17.74]), lower levels of parental education (P for trend <0.001), lower frequency of egg consumption (P for trend <0.001), active tuberculosis (aOR 1.40 [1.03–1.94]), household smoking (aOR 1.13 [1.02 to1.25]), and shorter time outdoors (P for trend <0.001). We report a very high prevalence of vitamin D deficiency among Mongolian schoolchildren, which requires addressing as a public health priority.     

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case–Control Study

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.     

Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21–93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.     

Associations between Maternal Selenium Status and Cord Serum Vitamin D Levels: A Birth Cohort Study in Wuhan,China

Serum selenium (Se) has been reported to be associated with serum 25-hydroxyvitamin D [25(OH)D], but epidemiological findings are limited in pregnant women. We aimed to assess the associations between maternal urinary Se concentrations and cord serum 25(OH)D levels. We measured urinary concentrations of Se in the first, second, and third trimesters and cord serum 25(OH)D of 1695 mother-infant pairs from a prospective cohort study in Wuhan, China. The results showed that each doubling of urinary Se concentrations in the first, second, third trimester, and whole pregnancy (average SG-adjusted concentrations across three trimesters) were associated with 8.76% (95% confidence interval (CI): 4.30%, 13.41%), 15.44% (95% CI: 9.18%, 22.06%), 11.84% (95% CI: 6.09%, 17.89%), and 21.14% (95% CI: 8.69%, 35.02%) increases in 25(OH)D levels. Newborns whose mothers with low (<10 μg/L) or medium (10.92–14.34 μg/L) tertiles of urinary Se concentrations in whole pregnancy were more likely to be vitamin D deficient (<20 ng/mL) compared with those with the highest tertile (>14.34 μg/L). Our study provides evidence that maternal Se levels were positively associated with cord serum vitamin D status.     

Association between Maternal Serum 25-Hydroxyvitamin D Concentrations and the Risk of Preterm Birth in Central Sudan: A Case–Control Study

There are few published studies on the association between vitamin D concentrations and preterm birth (PB) in sub-Saharan Africa. The current study aimed to assess the association between 25-hydroxyvitamin D (25[OH)] D) levels and PB. A matched case–control study (60 women in each arm) was conducted in Medani maternity hospital in central Sudan. The cases were women with spontaneous PB, and healthy women with term deliveries were the controls. The clinical/medical and obstetric history was gathered using a questionnaire. The enzyme-linked immunosorbent assay was used to measure the serum 25(OH)D levels. Women with PB had significantly lower median (interquartile range) 25(OH)D concentrations compared with the controls (18.4 (7.3) ng/mL vs. 20.2 (16.5) ng/mL, p = 0.001). Forty-two (70.0%) women with PB and 29 (48.3%) women in the control group had vitamin D deficiency (25(OH)D level ≤ 20 ng/mL). The results of the multivariable logistic regression showed that the 25(OH)D concentrations were negatively associated with PB (adjusted odds ratio (aOR) = 0.92, 95% confidence interval (CI) = 0.87–0.97). Vitamin D-deficient pregnant women were at a higher risk of PB (aOR = 2.69, 95% CI = 1.17–6.23). Low 25(OH)D concentrations were found at the time the variable was determined in women with spontaneous PB and were an independent risk factor for PB.     

Vitamin D Status Is Associated with Modifiable Lifestyle Factors in Pre-Adolescent Children Living in Urban Kuala Lumpur,Malaysia

Studies on vitamin D status and its determinants in growing children in countries with ample sunshine such as Malaysia have been limited. The aim of our study was to determine factors associated with serum 25(OH)D concentrations such as lifestyle, dietary intake, anthropometry, and body composition in 243 pre-adolescent Malaysian children from low-income families living in Kuala Lumpur. This cross-sectional study measured bone density and body composition using dual-energy X-ray absorptiometry (DXA), while serum 25(OH)D was measured using LC–MS/MS. Time spent outdoors, body surface area exposed to sunlight, dietary intake, and physical activity level were assessed using questionnaires. Multiple linear regression and stepwise analysis were performed to identify significant predictors for serum 25(OH)D. About 69.4% had 25(OH)D < 50 nmol/L, and 18.9% were vitamin-D-deficient with 25(OH)D < 30 nmol/L. Girls had a nine-fold higher prevalence of vitamin D deficiency than boys. Body surface area exposed to sunlight, Sun Index, and fat mass were significant predictors of 25(OH)D concentrations in this population. Modifiable lifestyle factors such as sun exposure and reducing obesity are important public health guidance to ensure optimal vitamin D status in these children.     

Vitamin D Status in Spanish Elite Team Sport Players

Low vitamin D is usual; however, data are limited for elite team players. The aim was to investigate the vitamin D levels in Football Club Barcelona (FCB) first division players of six sport modalities. Ninety-five elite male players (27.3 ± 4.6 y) belonging to FCB provided data for vitamin D throughout a season. In this study, 25(OH)D was measured in serum by chemiluminescent immunoassay. Outdoor/indoor training and supplementation were also considered. Total mean 25(OH)D concentrations were 91.9 ± 23.1 nmol/L in all players, with higher mean levels among supplemented players (94.7 ± 24.3 nmol/L). Around 25% of the team players were below optimal levels (<75 nmol/L), but none were below 50 nmol/L. Caucasian, supplemented football and handball players had the highest mean vitamin D concentrations over the whole year, whereas basketball players (indoor training) had the lowest ones. The highest rate of vitamin D insufficiency was found in spring (40%). A positive significant effect was observed for the interaction between indoor/outdoor training and supplementation with 25(OH)D concentrations (p < 0.05). Those team players training outdoors with supplementation had higher total vitamin D concentrations than those with indoors training and/or supplementation. A positive interaction of outdoor training with supplementation exists to determine 25(OH)D concentrations in team players.     

Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels ≤17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18–28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25–0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (≤17 ng/mL) or with high (≥29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.     

Plasma 25(OH)D Concentrations and Gestational Diabetes Mellitus among Pregnant Women in Taiwan

Vitamin D’s function in the development of gestational diabetes mellitus (GDM) is not consistent in the literature. We examined the association between maternal plasma 25(OH)D concentration and GDM risk. A national cross-sectional study (1497 pregnant women) was conducted between 2017 and 2019 across Taiwan. Blood samples were drawn at recruitment to assess 25(OH)D concentrations, including vitamin D deficiency (VDD) (<20 ng/mL), insufficiency (<32 ng/mL), and sufficiency (≥32 ng/mL). GDM was detected from 24 to 28 weeks of gestation with the results extracted from the antenatal visit records. The prevalence of GDM was 2.9%. Logistic model analysis showed that 25(OH)D concentrations were not significantly associated with the risk of GDM (adjusted odds ratio (AOR) = 0.97, p = 0.144). However, subjects with VDD had a significantly greater risk of GDM (AOR = 2.26, p = 0.041), but not in those with vitamin D insufficiency (AOR = 1.20, p = 0.655). Furthermore, cubic piecewise spline regression was used to explore the relationship between five-unit intervals of 25(OH)D and the predicted probability of GDM. As the proportion of GDM increased for low 25(OH)D concentrations, it decreased at moderate concentrations and increased again at higher concentrations. These findings revealed a nonlinear relationship between 25(OH)D and GDM risk. VDD would be risky for GDM occurrence.     

The Importance of Dose,Frequency and Duration of Vitamin D Supplementation for Plasma 25-Hydroxyvitamin D

The importance of dose, frequency and duration of vitamin D supplementation for plasma 25(OH)D levels is not well described and rarely reported for supplementation that exceeds 2000 IU per day. The objective is to examine dose, frequency and duration of supplementation in relation to plasma 25(OH)D in a large population-based sample. We accessed data on 2714 volunteers that contributed to 4224 visits and applied multilevel regression. Compared to not using supplements, a minimum regimen of 1000–2000 IU once or twice per week for one month was not effective in raising 25(OH)D. Compared to this minimum regimen, higher doses of 2000–3000, 3000–4000, and 5000 IU or more were associated with a 7.49, 13.19 and 30.22 nmol/L 25(OH)D increase, respectively; frequencies of three to four, five to six and seven times/week were associated with a 5.44, 16.52 and 30.69 nmol/L increase, respectively; and supplementation of five months or longer was associated with an increase of 6.68 nmol/L (p < 0.01 for all). Age, body weight, physical activity, smoking, and self-rated health were significantly associated with 25(OH)D. Whereas dose, frequency and duration of supplementation are important to healthy subjects committed to optimizing their nutritional status, to the design of clinical trials, individual characteristics and lifestyle contribute substantially to 25(OH)D.     

Vitamin D Status and Severity of Clostridium difficile Infections

Background: Clostridium difficile is the most common cause of nosocomial diarrhea, affecting up to 10% of hospitalized patients. Preliminary studies suggest an association between vitamin D status and C difficile infections (CDIs). Our goal was to investigate whether serum 25‐hydroxyvitamin D (25(OH)D) levels are associated with CDI severity. Methods: We prospectively enrolled patients diagnosed with CDI and divided them into 2 severity groups: group A (positive toxin A/B enzyme immunoassay only) and group B (positive toxin A/B enzyme immunoassay with abdominal computed tomography scan findings consistent with colitis). Serum 25(OH)D levels (25(OH)D₃, 25(OH)D₂, and total 25(OH)D) were measured on all patients after diagnosis of CDI. We performed multivariable logistic regression analyses to investigate the association between 25(OH)D levels and CDI severity, while adjusting for age, Deyo‐Charlson Comorbidity Index, recent hospitalization, and vitamin D supplementation. Results: One hundred patients were enrolled between July 2011 and February 2013. The mean (standard deviation) cohort age and Deyo‐Charlson Comorbidity Index were 62 (19) years and 4 (3), respectively; 54% of patients were male. Mean serum total 25(OH)D level was 22 (10) ng/mL. Mean 25(OH)D₃ level was significantly higher in group A (n = 71) than in group B (n = 29): 21 (1) vs 15 (2) ng/mL, respectively (P = .005). There was no observed difference in mean 25(OH)D₂ levels and total 25(OH)D levels between the 2 groups. Multivariable logistic regression analysis demonstrated an association between 25(OH)D₃ levels and CDI severity (adjusted odds ratio, 0.92; 95% confidence interval, 0.87–0.98). Conclusions: We found a significant inverse association between 25(OH)D₃ levels and CDI severity. Further studies are needed to determine whether vitamin D supplementation can improve outcomes in patients with CDI.     

Screening for Vitamin D Deficiency in Black Americans: Comparison of Total,Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density

Objectives

There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP].

Design

Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort.

Setting

The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri.

Participants

122 men and 206 women, age 60.2 ± 4.3 years.

Intervention

Retrospective analysis.

Measurements

Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes.

Results

Serum total 25(OH) D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD.

Conclusion

Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

     

Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population

Introduction

Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency.

Objective

To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength.

Design and methods

Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants.

Results

53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p = <0.001). Chinese had the lowest level of VDBP (169.6ug/ml) followed by Malay (188.8 ug/ml) and Indian having the highest (220.1 ug/ml). Calculated bioavailable and free 25(OH)D levels were significantly higher in Chinese, followed by Malays and Indians, which also correlated with better grip strength measures amongst the Chinese.

Conclusion

The Malays and Indians had overall lower free, bioavailable and total 25(OH)D compared with ethnic Chinese. Chinese ethnic group also had the lowest VDBP and better overall grip strength.

     

Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)₂D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D₃ in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D₃ or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.     

Temporal Association of Reduced Serum Vitamin D with COVID-19 Infection: Two Single-Institution Case–Control Studies

(1) Background: Vitamin D supplementation has been proposed for the prevention and treatment of COVID-19, but it is not clear if reduced serum vitamin D predisposes individuals to COVID-19 and/or is a secondary consequence of infection. This study assessed the temporal association between serum vitamin D and COVID-19 with two single-institution case–control studies through the University of California San Diego (UCSD) Health System. (2) Methods: This study included patients who tested positive for COVID-19 from 1 January to 30 September 2020 with serum 25-hydroxy-vitamin D (25(OH)D) measured within 180 days of diagnosis. Patients were separated based on whether 25(OH)D was measured before (n = 107 cases, 214 controls) or after (n = 203 cases, 406 controls) COVID-19 diagnosis. COVID-19 infection status was the outcome variable in the pre-diagnosis study, whereas serum 25(OH)D level was the outcome variable in the post-diagnosis study. (3) Results: Serum 25(OH)D levels were not associated with the odds of subsequent COVID-19 infection (OR 1.0, 95% CI: 1.0 to 1.0, p = 0.98). However, COVID-19-positive individuals had serum 25(OH)D measurements that were 2.7 ng/mL lower than the controls (95% CI: −5.2 to −0.2, p = 0.03). (4) Conclusions: In our study population, serum 25(OH)D levels were not associated with the risk of acquiring COVID-19 infection but were reduced in subjects after COVID-19 infection. These results support the possibility that reduced serum 25(OH)D is a consequence and not a cause of COVID-19 infection.     

Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study

(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4–11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25–50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.