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BackgroundVitamin D deficiency is common in pregnancy. Vitamin D plays an important role in the developing brain, and deficiency may impair childhood behavioral development.ObjectivesThis study examined the relationship between gestational 25(OH)D concentrations and childhood behavior in the Environmental influences on Child Health Outcomes (ECHO) Program.MethodsMother-child dyads from ECHO cohorts with data available on prenatal (first trimester through delivery) or cord blood 25(OH)D and childhood behavioral outcomes were included. Behavior was assessed using the Strengths and Difficulties Questionnaire or the Child Behavior Checklist, and data were harmonized using a crosswalk conversion. Linear mixed-effects models examined associations of 25(OH)D with total, internalizing, and externalizing problem scores while adjusting for important confounders, including age, sex, and socioeconomic and lifestyle factors. The effect modification by maternal race was also assessed.ResultsEarly (1.5-5 y) and middle childhood (6-13 y) outcomes were examined in 1688 and 1480 dyads, respectively. Approximately 45% were vitamin D deficient [25(OH)D < 20 ng/mL], with Black women overrepresented in this group. In fully adjusted models, 25(OH)D concentrations in prenatal or cord blood were negatively associated with externalizing behavior T-scores in middle childhood [-0.73 (95% CI: -1.36, -0.10) per 10 ng/mL increase in gestational 25(OH)D]. We found no evidence of effect modification by race. In a sensitivity analysis restricted to those with 25(OH)D assessed in prenatal maternal samples, 25(OH)D was negatively associated with externalizing and total behavioral problems in early childhood.ConclusionsThis study confirmed a high prevalence of vitamin D deficiency in pregnancy, particularly among Black women, and revealed evidence of an association between lower gestational 25(OH)D and childhood behavioral problems. Associations were more apparent in analyses restricted to prenatal rather than cord blood samples. Interventions to correct vitamin D deficiency during pregnancy should be explored as a strategy to improve childhood behavioral outcomes.

BackgroundMacro- and micronutrients, such as proteins, vitamin D, and calcium (Ca), are important dietary factors that can modify bone mineral density (BMD). Genetic factors can interact with diet, affecting an individual's predisposition to osteoporosis.ObjectivesThis study aimed to evaluate the associations between macro- and micronutrient intakes and BMD in Mexican postmenopausal women, and their interactions with genetic polymorphisms involved in the vitamin D metabolic pathway.MethodsWe analyzed data from 317 postmenopausal women from the Health Workers Cohort Study, a longitudinal cohort studied in Cuernavaca, Mexico. Postmenopausal women participated in 2 data collection waves (2004-2006 and 2010-2011), with a mean time of 6.4 years. Dietary intake was assessed with a semi-quantitative FFQ. BMD (femoral neck, hip, and lumbar spine) was measured by DXA. Hybrid mixed-effects regression models were used to assess the associations of dietary macro- and micronutrients on BMD, after adjusting for confounding factors and for diet and single nucleotide polymorphism interactions.ResultsAt baseline, the median age was 57 years (IQR, 50-64). Mean femoral neck, hip, and lumbar spine BMDs decreased over time. We observed statistically significant longitudinal associations for diet (Ca, vitamin D, magnesium, phosphorus, and protein intake) and BMD. Increases of vitamin D, Ca, and protein intakes by 1 SD were associated with mean increases in the femoral neck BMD (0.083 SD, 0.064 SD, and 0.130 SD, respectively). Multiple significant interactions were identified between several loci (CYP2R1, CYP24A1, CYP27B1, VDR, and DHCR7/NADSYN1) and diet for BMDs (femoral neck, hip, and lumbar spine), mainly for protein intake.ConclusionsOur data support associations of vitamin D, Ca, protein, phosphorous, and magnesium consumption with BMD in Mexican postmenopausal women and suggest possible gene-diet interactions. These results could facilitate future personalized nutrition recommendations to help prevent low BMD.

BackgroundVitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes.ObjectivesWe examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race.MethodsThis study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race.ResultsMean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D

Background: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear.Objectives: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L.Methods: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests.Results: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L.Conclusions: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www.clinicaltrials.gov/ct2/show/NCT02563015) as NCT02563015. [ABSTRACT FROM AUTHOR]

Background: Nonlinear association between serum 25-hydroxyvitamin D [25(OH)D] concentration and all-cause mortality has been widely reported for the general population, but this association has not been quantified for individuals with inflammatory bowel disease (IBD).Objectives: The aim was to explore the association between serum 25(OH)D and all-cause mortality in individuals with IBD.Methods: We identified 2690 females and 2532 males aged 40-69 y with diagnosed IBD at baseline in the UK Biobank. Serum 25(OH)D concentration was measured by direct competitive chemiluminescent immunoassay. The outcome was all-cause mortality, ascertained via the death registry. Cox proportional hazard regression was used to evaluate associations between serum 25(OH)D in quintiles and all-cause mortality among individuals with IBD [Crohn disease (CD; n = 1760) and ulcerative colitis (UC; n = 3462)]. Restricted cubic splines were used to investigate potential nonlinearity.Results: During the mean follow-up period of 11.9 y, 529 deaths (198 in CD and 331 in UC) were documented among 5222 individuals with IBD. Compared with the lowest quintile of serum 25(OH)D, HRs for the second to the highest quintiles were 0.82 (95% CI: 0.63, 1.06), 0.63 (95% CI: 0.47, 0.83), 0.64 (95% CI: 0.48, 0.85), and 0.74 (95% CI: 0.55, 0.99), respectively. Nonlinearity was detected in the dose-response association between serum 25(OH)D concentration and all-cause mortality (P-nonlinearity < 0.001), and 25(OH)D concentrations of 44-78 nmol/L were associated with a 50% lower risk of all-cause mortality (than 10 nmol/L). Subgroup analyses showed that the nonlinear association mostly applied to females (P-nonlinearity < 0.001 compared with 0.080 in males).Conclusions: We observed a nonlinear association, mostly applicable to females, between serum 25(OH)D concentrations and all-cause mortality among individuals with IBD. A 25(OH)D concentration range of 44-78 nmol/L can serve as a starting point for future research to confirm recommended 25(OH)D concentrations for individuals with IBD. [ABSTRACT FROM AUTHOR]

Background: The 2020-2025 Dietary Guidelines for Americans (2020 DGA) recommend 3 dietary patterns for Americans, including a Healthy Vegetarian Dietary Pattern (HVDP).Objectives: The objective of this study was to assess whether nutritionally adequate dairy-free and vegan adaptations to the HVDP can be modeled with foods already in the DGA.Methods: Using similar food pattern modeling procedures as the 2020 DGA, the nutrient composition of 2 alternative models-dairy-free and vegan-of the 1800-, 2000-, 2200-, and 2400-kcal/d HVDPs was assessed. The dairy food group was replaced with a dairy alternative group comprised of soy milk and soy yogurt fortified with calcium, vitamin A, and vitamin D. For the vegan model, eggs were replaced with equal proportions of vegetarian protein foods.Results: Dairy-free and vegan models required minimal changes to the HVDP. Cup-equivalents and/or ounce-equivalents of vegetables, fruits, grains, oils, and discretionary calories remained unchanged. Content of total fat, polyunsaturated fat, linoleic acid (18:2n-6), linolenic acid, iron, copper, vitamin D, riboflavin, vitamin B-12, and vitamin K increased in both models by ≥10% (all comparisons relative to the original HVDP). Choline increased ≥25% in the dairy-free models. Protein decreased 11% in both 1800-kcal/d models and 10% in both 2000-kcal/d models. Sodium, cholesterol, zinc, and phosphorus decreased across all energy levels in both models, and selenium decreased in the vegan model. Carbohydrate, fiber, saturated fat, EPA, DHA, calcium, magnesium, potassium, vitamin A, vitamin E, vitamin C, thiamin, folate, and vitamin B-6 changed ≤10%. Both models contained adequate nutrients to meet Dietary Reference Intakes (DRIs) for most age and sex groups for which 1800-, 2000-, 2200-, and 2400-kcal/d diets are appropriate. Zinc was the only nutrient below the DRI for males.Conclusions: The dairy-free and vegan HVDP models could help adults who do not consume dairy foods and/or other animal products to meet nutrition recommendations. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV.Objectives: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania.Methods: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression.Results: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05).Conclusions: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680. [ABSTRACT FROM AUTHOR]

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

Background: Most pregnant or lactating women in Canada will not meet iodine requirements without iodine supplementation.Objectives: To assess the iodine status of 132 mother-infant pairs based on secondary analyses of a vitamin D supplementation trial in breastfed infants from Montréal, Canada.Methods: Maternal iodine status was assessed using the breastmilk iodine concentration (BMIC). Singleton, term-born infants were studied from 1-36 months of age. Usual (adjusted for within-person variation) iodine intakes were estimated from urinary iodine and creatinine concentrations. Iodine status was assessed using median urinary iodine concentrations (UICs) and by estimating inadequate intakes by the cut-point method using a proposed Estimated Average Requirement for infants 0-6 months of age (72 μg/d).Results: At 1, 3, and 6 months of age, 70%, 63%, and 3% of infants, respectively, were exclusively breastfed. From 1-36 months of age (n = 82-129), the median UICs were ≥100 μg/L (range, 246-403 μg/L), which is the cutoff for adequate intakes set by the WHO for children <2 years. Almost all (98%-99%) infants at 1 and 2 months, 2 and 3 months, and 3 and 6 months of age had usual creatinine-adjusted iodine intakes ≥ 72 μg/d. The median BMIC was higher (P < 0.001) at 1 month compared to 6 months of lactation [1 month, 198 μg/kg (IQR, 124-274; n = 105) and 6 months, 109 μg/kg (IQR, 67-168; n = 78)]. At 1 and 6 months, 96% and 79% of mothers, respectively, had a BMIC ≥ 60 μg/kg, the lower limit of a normal reference range. The percentages of mothers that used a multivitamin-mineral (MVM) supplement containing iodine were 90% in pregnancy and 79% and 59% at 1 and 6 months of lactation, respectively.Conclusions: The iodine status of infants was adequate throughout infancy. These results support a recommendation that all women who could become pregnant, who are pregnant, or who are breastfeeding take a daily MVM supplement containing iodine. [ABSTRACT FROM AUTHOR]

Background: Vitamin D status at birth is reliant on maternal-fetal transfer of vitamin D during gestation.Objectives: We aimed to examine the vitamin D status of newborn infants in a diverse population and to subsequently identify the modifiable correlates of vitamin D status.Methods: In this cross-sectional study, healthy mother-infant dyads (n = 1035) were recruited within 36 h after term delivery (March 2016-March 2019). Demographic and lifestyle factors were surveyed. Newborn serum 25-hydroxyvitamin D [25(OH)D] was measured (standardized chemiluminescence immunoassay) and categorized as deficient [serum 25(OH)D <30 nmol/L] or adequate (≥40 nmol/L). Serum 25(OH)D was compared among categories of maternal characteristics using ANOVA; each characteristic was tested in a separate model. Subgroups (use of multivitamins preconception and continued in pregnancy compared with during pregnancy only) were matched (n = 352/group) for maternal factors (ancestry, age, income, education, parity, and prepregnancy BMI) using propensity scores; logistic regression models were generated for odds of deficiency or adequacy.Results: Infants' mean serum 25(OH)D was 45.9 nmol/L (95% CI: 44.7, 47.0 nmol/L) (n = 1035), with 20.8% (95% CI: 18.3%, 23.2%) deficient and 60.7% (95% CI: 55.2%, 66.2%) adequate. Deficiency prevalence ranged from 14.6% of white infants to 41.7% of black infants. Serum 25(OH)D was higher (P < 0.0001) in infants of mothers with higher income, BMI < 25 kg/m2, exercise and sun exposure in pregnancy, and use of multivitamins preconception. In the matched-subgroup analysis, multivitamin supplementation preconception plus during pregnancy relative to only during pregnancy was associated with lower odds for vitamin D deficiency (ORadj: 0.55; 95% CI: 0.36, 0.86) and higher odds for adequate vitamin D status (ORadj: 1.47; 95% CI: 1.04, 2.07).Conclusions: In this study most newborn infants had adequate vitamin D status, yet one-fifth were vitamin D deficient with disparities between population groups. Guidelines for a healthy pregnancy recommend maternal use of multivitamins preconception and continuing in pregnancy. An emphasis on preconception use may help to achieve adequate neonatal vitamin D status.This trial was registered at clinicaltrials.gov as NCT02563015. [ABSTRACT FROM AUTHOR]

Background: Associations between vitamin D and stroke remain inconsistent. One major risk factor for stroke is high blood glucose, but the role it plays in this association is not well studied.Objectives: We aimed to evaluate the individual association between plasma 25-hydroxyvitamin D [25(OH)D] and risk of first stroke stratified by fasting blood glucose (FBG), and the joint associations between plasma 25(OH)D, glycemic status, and first stroke in hypertensive adults.Methods: This study was a nested, case-control design utilizing data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 591 first stroke cases (of which 475 were ischemic stroke, 114 were hemorrhagic stroke, and 2 were uncertain type) and 591 matched controls. The age range of the study population was 45-75 y. The normal FBG (NFG) group had FBG <5.6 mmol/L,  and the impaired FBG (IFG) group had FBG ≥5.6 mmol/L and <7.0 mmol/L. Diabetes was defined as participants with FBG ≥7 mmol/L or who were receiving treatment with hypoglycemic agents. ORs (95% CIs) were calculated using unconditional logistic regression models.Results: Multivariable adjusted models revealed an inverse association between quartiles of 25(OH)D and risk of first stroke among participants with NFG, but the opposite trend was observed for those with IFG or diabetes. The largest ORs (>2) were observed among patients with diabetes, compared with the reference group of NFG and high 25(OH)D. Those with NFG and low 25(OH)D (OR = 1.73, 95% CI: 1.22 to 2.44) or those with IFG and high 25(OH)D (OR = 1.74, 95% CI: 1.14 to 2.67) both had a higher risk of total stroke. There was a significant interaction between 25(OH)D and a combined group of IFG and diabetes (P = 0.001). Similar results were observed for ischemic stroke.Conclusions: In a hypertensive population, the relation between plasma 25(OH)D and risk of first stroke was significantly modified by FBG. This trial was registered at https://www.clinicaltrials.gov as NCT00794885. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported that dietary and serum concentrations of vitamin D and cholesterol are correlated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about whether 25 hydroxyvitamin D [25(OH)D], lipids, and oxysterols are related to cognitive function.Objective: This study sought to explore the relations between 25(OH)D, lipids, oxysterols, and cognitive function.Methods: In this study, about 209 MCI patients and 209 age- and gender-matched healthy controls were recruited from the Shanxi province of China (49.5% male; median [IQR] age: 63 [59-66] y). Serum concentrations of 25(OH)D, lipids, and oxysterols were measured using ultra-performance LC-MS. Cognitive performance was determined via comprehensive mental, verbal, and auditory cognitive tests. Dietary information was collected using a semiquantitative FFQ and 3 consecutive days of 24-h dietary recalls. Logistic regression analyses, Spearman's correlation, and partial correlation analyses were used to explore correlation between the variables.Results: Participants with vitamin D deficiency [serum 25(OH)D <20.0 ng/mL] were 3 times more likely to develop MCI compared to those with adequate vitamin D (≥30 ng/mL) concentrations. The AUC of 25(OH)D was 0.72 and the cut-off was 16.5 ng/mL (sensitivity:  50.3%,  specificity: 84.4%). Serum 25(OH)D concentrations were negatively correlated with total cholesterol (TC) (r = -0.19, P = 0.02), LDL-cholesterol (r = -0.17, P = 0.04), and 24S,25-epoxycholesterol (24S,25-epoxy-CHO) (r = -0.21, P = 0.01). Conversely, the Montreal Cognitive Assessment (MoCA) (r = 0.185, P < 0.001) and symbol digit modalities test (SDMT) (r = 0.11, P = 0.03) scores were positively correlated with serum 25(OH)D concentrations.Conclusion: The study identified significant differences in serum 25(OH)D concentrations between MCI patients and cognitive healthy controls, and there was a correlation between serum concentrations of 25(OH)D, lipids, and oxysterols and cognitive impairment among people. This study was registered at the Chinese Clinical Trial Registry as ChiCTR1900025452. [ABSTRACT FROM AUTHOR]

Background: The measurement of micronutrient status is essential to understand the health of individuals and populations, but there are limited data on the stability of micronutrients in whole blood.Objectives: The objective was to investigate the effects of delayed processing of whole blood on the stability of 25 micronutrient and selected clinical biomarkers.Methods: Blood from 16 healthy adults was collected into EDTA, lithium heparin (LH), or serum tubes. Samples were processed within 2 hours of collection ("2-hour processed") or mailed overnight (boxed with frozen cold packs) before processing ("24-hour processed"). Micronutrient and clinical biomarker concentrations were quantified with validated methods. The concentration percentage difference between the 2- and 24-hour processed samples was calculated and was compared against quality specifications determined from intra- and interindividual variations.Results: All analytes had a sample type where the percentage difference concentration between 2-hour and 24-hour processed samples was ≤4% and was acceptable based on calculated limits, including for biomarkers of vitamin A, vitamin D, thiamin, folate, vitamin B-12, iron (ferritin), and zinc status and for selected clinical markers, C-reactive protein, HDL and total cholesterol, and triglycerides. EDTA plasma vitamin C was lower compared to the 2-hour processed sample (geometric mean, 43%; 95% CI: 36%-49%). Pyridoxal-5-phosphate (vitamin B-6 biomarker) decreased, with differences from the 2-hour processed samples of -8% (95% CI: -13% to -2%) and -14% (95% CI: -18% to -9%) in LH plasma and serum, respectively.Conclusions: In blood collected from adult participants, delayed processing of chilled whole blood for 24 hours did not materially affect the measured concentrations of the majority of micronutrients and selected clinical biomarkers. This suggests that for these analytes, adherence to a 2-hour processing protocol may be unnecessary. This knowledge is valuable and may help to simplify logistics for sample transport and processing of blood samples for micronutrient status assessment. [ABSTRACT FROM AUTHOR]

Background: Variability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens.Objectives: We aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation.Methods: In a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained.Results: Supplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (<5% increase in R2). Variance in neonatal 25(OH)D was explained mostly by maternal delivery 25(OH)D and prenatal vitamin D intake (R2 = 82%). Variance in 25(OH)D in later infancy could only partly be explained by numerous biological, sociodemographic, and laboratory-related characteristics, including feeding practices (R2 = 43%).Conclusions: Presupplementation 25(OH)D and vitamin D supplemental dose are the major determinants of the response to maternal prenatal vitamin D intake. Vitamin D dosing regimens to prevent maternal and infant vitamin D deficiency should take into consideration the mean 25(OH)D concentration of the target population. [ABSTRACT FROM AUTHOR]

Background: Prospective studies have shown differences in some disease risks between vegetarians and nonvegetarians, but the potential biological pathways are not well understood.Objectives: We aimed to assess differences in concentrations of biomarkers related to disease pathways in people with varying degrees of animal foods exclusion.Methods: The UK Biobank recruited 500,000 participants aged 40-69 y (54.4% women) throughout the United Kingdom in 2006-2010. Blood and urine were collected at recruitment and assayed for more than 30 biomarkers related to cardiovascular diseases, bone and joint health, cancer, diabetes, renal disease, and liver health. In cross-sectional analyses, we estimated adjusted geometric means of these biomarkers by 6 diet groups (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) in 466,058 white British participants and 2 diet groups (meat eaters, vegetarians) in 5535 British Indian participants.Results: We observed differences in the concentrations of most biomarkers, with many biomarkers showing a gradient effect from meat eaters to vegetarians/vegans. Of the largest differences, compared with white British regular meat eaters, white British vegans had lower C-reactive protein [adjusted geometric mean (95% CI): 1.13 (1.03, 1.25) compared with 1.43 (1.42, 1.43) mg/L], lower low-density lipoprotein cholesterol [3.13 (3.07, 3.20) compared with 3.65 (3.65, 3.65) mmol/L], lower vitamin D [34.4 (33.1, 35.9) compared with 44.5 (44.4, 44.5) nmol/L], lower serum urea [4.21 (4.11, 4.30) compared with 5.36 (5.36, 5.37) mmol/L], lower urinary creatinine [5440 (5120, 5770) compared with 7280 (7260, 7300) μmol/L], and lower γ-glutamyltransferase [23.5 (22.2, 24.8) compared with 29.6 (29.6, 29.7) U/L]. Patterns were mostly similar in British Indians, and results were consistent between women and men.Conclusions: The observed differences in biomarker concentrations, including lower C-reactive protein, lower LDL cholesterol, lower vitamin D, lower creatinine, and lower γ-glutamyltransferase, in vegetarians and vegans may relate to differences in future disease risk. [ABSTRACT FROM AUTHOR]

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

Background: Low vitamin D status is a global public health issue that vitamin D food fortification and biofortification may help to alleviate.Objectives: We investigated the effect of vitamin D food fortification and biofortification on circulating 25-hydroxyvitamin D (25(OH)D) concentrations. We expanded the scope of earlier reviews to include adults and children, to evaluate effects by vitamin D vitamer, and investigate linear and nonlinear dose-response relations.Methods: We conducted a systematic review and meta-analysis. We searched CINAHL, MEDLINE, PubMed, Embase, the Cochrane Library, and gray and unpublished literature sites for randomized controlled trials, including people of all ages, with the criteria: absence of illness affecting vitamin D absorption, duration ≥4 wk, equivalent placebo food control, dose quantification, dose ≥5 μg/d, baseline and endpoint or absolute change in 25(OH)D concentrations reported, random allocation, and participant blinding. Quality was assessed using the Jadad Scale.Results: Data from 34 publications (2398 adults: 1345 intervention, 1053 controls; 1532 children: 970 intervention, 562 controls) were included. Random-effects meta-analysis of all studies combined (mean dose 16.2 μg/d) indicated a pooled treatment effect of 21.2 nmol/L (95% CI: 16.2, 26.2), with a greater effect for studies using cholecalciferol than ergocalciferol. Heterogeneity was high (I2  > 75%). Metaregression analyses for all studies combined suggested positive effect differences for baseline circulating 25(OH)D concentrations <50 nmol/L, dose ≥10 μg/d and a negative effect difference when the intervention arm included a calcium dose ≥500 mg/d greater than the control arm. Dose-response rates were found to be nonlinear (Wald test for nonlinearity P < 0.001). For all studies combined, a threshold occurred at ∼26 nmol/L for a dose of ∼21 μg/d.Conclusions: These results support use of vitamin D food fortification to improve circulating 25(OH)D circulations in populations. This work was registered with PROSPERO as CRD42020145497. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is critical to brain health and a promising candidate to prevent cognitive decline and onset of Alzheimer disease (AD), although the underlying brain mechanisms are unclear.Objectives: This study aimed to determine the association between vitamin D intake and brain cortical thickness in older adults.Methods: This was a cross-sectional investigation of 263 cognitively unimpaired participants, aged 65 y and older, participating in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) trial (an ongoing study testing the effects of a 3-y diet intervention on cognitive decline). Vitamin D intake, from diet and supplements, was ascertained from an FFQ. Linear regression analysis, adjusted for age, sex, race, education, income, cognitive and physical activities, and cardiovascular disease risk factors, was used to determine the association between vitamin D intake and cortical thickness of the whole brain, lobes, and AD signature.Results: Total vitamin D intake was associated with cortical thickness of the temporal lobe and AD signature. Compared with individuals in the lowest quartile of total vitamin D intake [median: 140 international units (IU)/d], those in the highest quartile (median: 1439 IU/d) had a 0.038-mm (95% CI: 0.006, 0.069 mm) thicker temporal lobe and 0.041-mm (95% CI: 0.012, 0.070 mm) thicker AD signature. Most vitamin D intake was from supplements, and supplemental intake was also associated with cortical thickness. Compared with those who used no supplement, individuals taking 800-1000 IU/d and >1000 IU/d of supplemental vitamin D had a 0.039-mm (95% CI: 0.013, 0.066 mm) and 0.047-mm (95% CI: 0.013, 0.081 mm) thicker temporal lobe and a 0.037-mm (95% CI: 0.013, 0.061 mm) and 0.046-mm (95% CI: 0.015, 0.077 mm) thicker AD signature, respectively. Dietary vitamin D was not related to brain cortical thickness in our sample.Conclusions: In cognitively unimpaired older adults, total and supplemental vitamin D intakes were associated with cortical thickness in regions vulnerable to AD.This trial was registered at clinicaltrials.gov as NCT02817074. [ABSTRACT FROM AUTHOR]

Background: Data from the 2007-2010 NHANES suggested that vitamin D supplements contributed to increased serum concentrations of 25-hydroxyvitamin D [25(OH)D] in the US population.Objectives: We sought to determine whether 25(OH)D continued to increase during NHANES 2011-2014 and whether associations of 25(OH)D with preselected covariates differed across time periods.Methods: For this study, 25(OH)D was measured in adults (≥20 y) using LC-MS/MS. Descriptive and regression analyses were stratified by survey period to investigate the effects of age, race-Hispanic origin, sex, season, BMI, dietary vitamin D, and vitamin D-containing supplements. A multiple linear regression model was used to assess 25(OH)D changes between two 4-y survey periods, namely 2007-2010 and 2011-2014.Results: We observed several significant concomitant increases between 2007-2010 and 2011-2014: unadjusted mean 25(OH)D increased by 2.7 nmol/L (95% CI: 0, 5.4 nmol/L; P = 0.048), the percentage of persons taking any vitamin D-containing supplements increased 2.9% (95% CI: 0.03, 5.5%; P = 0.0314), and the percentage of persons taking high-dose (≥1000 IU/d) vitamin D-containing supplements increased 8.6% (95% CI: 6.9, 9.9%; P < 0.0001). With covariate adjustment, the increase in 25(OH)D from 2007-2010 to 2011-2014 was no longer statistically significant [1.4 nmol/L (95% CI: -3.0, 0.23 nmol/L; P = 0.09)]. After adjustments, several large differences in 25(OH)D remained, namely non-Hispanic blacks had 25(OH)D 22 nmol/L lower than that of non-Hispanic whites, and users of vitamin D-containing supplements ≥1000 IU/d had 25(OH)D 31 nmol/L higher than that of nonusers.Conclusions: After adjusting for vitamin D supplement dose, the overall adjusted increase in 25(OH)D was no longer statistically significant, suggesting that changes in US adults' 25(OH)D concentrations between NHANES periods 2007-2010 and 2011-2014 may primarily be associated with changes in vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Background: Lactoferrin (LF) has been shown to promote bone anabolism, and the vitamin D receptor (VDR) mediates the effects of vitamin D on bone. We hypothesized that LF improves bone health by increasing VDR expression.Objectives: We sought to determine the role of VDR activation in LF-induced osteogenic activity in vivo and in vitro and the underlying molecular mechanisms.Methods: Sixty male C57BL/6J mice (aged 4 wk) were randomly assigned into 6 groups and fed vitamin D-deficient (VDD; 0 IU/kg) or vitamin D-normal diet (VDN; 1000 IU cholecalciferol/kg) and administered placebo or LF (100 or 1000 mg/kg body weight) by gavage for 24 wk. Trabecular bone structure was analyzed using micro-CT, and VDR expression was assessed by immunohistochemistry. In vitro, MC3T3-E1 cells were treated with 100 μg LF/mL to evaluate its effect on VDR expression. Finally, the direct recruitment of LF to the Vdr promoter was confirmed by chromatin immunoprecipitation assay. In addition, cells were transfected with pGL3-basic Vdr vector for monitoring Vdr promoter activation using luciferase assays.Results: LF supplementation at 100 and 1000 mg/kg revealed an ∼6.5% (P < 0.05) increase in bone mineral density in mice on VDD diet and exhibited an enhanced expression of VDR in bone compared with control. This increased expression of VDR was also observed in the bone of mice on the VDN diet, but the effect was more pronounced in VDD diet. In vitro, compared with the control group, Vdr mRNA expression was 18 times greater (P < 0.05) and peaked at 2 h posttreatment of LF. By cotransfection of the pGL3-basic Vdr vector, LF induced luciferase activity by 30% (P < 0.05) in MC3T3-E1 cells.Conclusions: In vivo and in vitro, LF, a potential activator of VDR, promotes osteogenesis. This suggests that dairy products, which are rich in LF, may serve as a functional food to improve bone health. [ABSTRACT FROM AUTHOR]

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

Background: Previous studies have suggested that insufficient concentrations of vitamin D are associated with dental caries in primary teeth, but evidence remains inconclusive.Objectives: We assessed the longitudinal associations between prenatal, perinatal, and early childhood serum 25-hydroxyvitamin D concentrations [25(OH)D] and the risk of dental caries in 6-year-old children.Methods: This research was conducted within the Generation R Study, a large, multi-ethnic, prospective cohort study located in Rotterdam, the Netherlands. Dental caries were assessed in children using the decayed-missing-filled-primary teeth index at a mean age of 6.1 years (90% range, 4.8-9.1). We measured serum total 25(OH)D concentrations at 3 time points: prenatally (at 18-24 weeks of gestation), perinatally (at birth), and during early childhood (at age 6 years). We performed logistic regression analyses to determine the longitudinal association of serum 25(OH)D concentrations with caries risks in 5257 children. Additionally, we constructed a Genetic Risk Score (GRS) for the genetic predispositions to serum total 25(OH)D concentrations based on 6 vitamin D-related single nucleotide polymorphisms in a subsample of 3385 children.Results: Children with severe prenatal and early childhood serum 25(OH)D deficiencies (<25 nmol/L) were more likely to be diagnosed with caries [OR, 1.56 (95% CI, 1.18-2.06) and 1.58 (95% CI, 1.10-2.25), respectively] than children with optimal concentrations (≥75 nmol/L). After adjustment for residuals of serum 25(OH)D concentrations at other time points, only the early childhood serum 25(OH)D concentration was inversely associated with the caries risk at 6 years (OR, 0.97; 95% CI, 0.95-0.98). However, our GRS analysis showed that children who are genetically predisposed to have lower serum 25(OH)D concentrations do not have a higher risk of developing caries in primary teeth.Conclusions: Our study suggests a weak association between serum 25(OH)D concentrations and risks of caries in primary teeth. Based on our results, we do not recommend vitamin D supplementation for the prevention of dental caries in children. [ABSTRACT FROM AUTHOR]

Background: The evolution of vitamin D status across pregnancy trimesters and its association with prepregnancy body mass index (ppBMI; in kg/m2) remain unclear.Objectives: We aimed to 1) assess trimester-specific serum total 25-hydroxyvitamin D [25(OH)D] concentrations, 2) compare those concentrations between ppBMI categories, and 3) examine associations between 25(OH)D concentrations, ppBMI, and vitamin D intake.Methods: As part of a prospective cohort study, 79 pregnant women with a mean age of 32.1 y and ppBMI of 25.7 kg/m2 were recruited in their first trimester (average 9.3 weeks of gestation). Each trimester, vitamin D intake was assessed by 3 Web-based 24-h recalls and a Web questionnaire on supplement use. Serum total 25(OH)D was measured by LC-tandem MS. Repeated-measures ANOVA was performed to assess the evolution of 25(OH)D concentrations across trimesters of pregnancy and comparisons of 25(OH)D concentrations between ppBMI categories were assessed by 1-factor ANOVAs. Stepwise regression analyses were used to identify determinants of 25(OH)D concentrations in the third trimester.Results: Mean ± SD serum total 25(OH)D concentrations increased across trimesters, even after adjustments for ppBMI, seasonal variation, and vitamin D intake from supplements (67.5 ± 20.4, 86.5 ± 30.9, and 88.3 ± 29.0 nmol/L at mean ± SD 12.6 ± 0.8, 22.5 ± 0.8, and 33.0 ± 0.6 weeks of gestation, respectively; P < 0.0001). In the first and third trimesters, women with a ppBMI ≥30 had lower serum total 25(OH)D concentrations than women with a ppBMI <25 (P < 0.05); however, most had concentrations >40nmol/L by the second trimester. Vitamin D intake from supplements was the strongest determinant of third-trimester serum total 25(OH)D concentrations (r2 = 0.246, β = 0.51; P < 0.0001).Conclusions: There was an increase in serum total 25(OH)D concentrations across trimesters, independent of ppBMI, seasonal variation, and vitamin D intake from supplements. Almost all women had serum total 25(OH)D concentrations over the 40- and 50-nmol/L thresholds, thus our study supports the prenatal use of a multivitamin across pregnancy. [ABSTRACT FROM AUTHOR]

BackgroundKnee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH).ObjectiveThe objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis.MethodsSerum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits.ResultsThe mean concentrations of serum 25(OH)D and PTH were 26.2 μg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 μg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 μg/L] had >2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 μg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4).ConclusionOur results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Background: Identification of nutrients of public health concern has been a hallmark of the Dietary Guidelines for Americans (DGA); however, a formal systematic process for identifying them has not been published.Objectives: We aimed to propose a framework for identifying "nutrients or food components" (NFCs) of public health relevance to inform the DGA.Methods: The proposed framework consists of 1) defining terminology; 2) establishing quantitative thresholds to identify NFCs; and 3) examining national data. The proposed framework utilizes available data from 3 key data sources or "prongs": 1) dietary intakes; 2) biological endpoints; and 3) clinical health consequences such as prevalence of health conditions, directly or indirectly through validated surrogate markers.Results: In identifying potential NFCs of public health concern, the 2020 DGA Committee developed a decision-tree framework with suggestions for combining the 3 prongs. The identified NFCs of public health concern for Americans ≥1 y old included fiber, calcium (≥2 y old), vitamin D, and potassium for low intakes and sodium, added sugars, and saturated fats (≥2 y old) for high intakes that were associated with adverse health consequences. Iron was identified among infants ages 6-12 mo fed human milk. For reproductive-aged and pregnant females, iron (all trimesters) and folate (first trimester) were identified for low intake, based on dietary and biomarker data (iron) or the severity of the consequence (folic acid and neural tube defects). Among pregnant women, low iodine was of potential public health concern based on biomarker data. Other NFCs that were underconsumed, overconsumed, and pose special challenges were identified across the life course.Conclusions: The proposed decision-tree framework was intended to streamline and add transparency to the work of this and future Dietary Guidelines Advisory Committees to identify NFCs that need to be encouraged or discouraged in order to help reduce risk of chronic disease and promote health and energy balance in the population. [ABSTRACT FROM AUTHOR]

Background: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood.Objectives: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice.Methods: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA.Results: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa.Conclusions: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice. [ABSTRACT FROM AUTHOR]

Background: Suboptimal vitamin D (VitD) status has been associated with poor bone health and other adverse health outcomes and is common among children. Various early-life factors are associated with child VitD, yet few studies have examined multiple factors simultaneously in a single study population.Objectives: We aimed to characterize relations of early-life factors with plasma 25-hydroxyvitamin D [25(OH)D] concentrations in early and mid-childhood, and to explore potential differences in these associations between white and black children.Methods: We identified associations of various early-life factors with 25(OH)D concentrations in early and mid-childhood among 961 children in Project Viva using linear regression models. All variables associated with 25(OH)D were included together in final multivariable models at each outcome time point: 1 in the overall sample and additional models for children whose mothers identified them as being white or black.Results: Overall mean ± SD 25(OH)D concentrations were 86 ± 29 nmol/L in early childhood and 68 ± 21 nmol/L in mid-childhood. After accounting for other predictors, children who took VitD supplements (compared with those who did not) had 25(OH)D concentrations 5.6 nmol/L (95% CI: 2.0, 9.2 nmol/L) higher in early childhood and 8.2 nmol/L (95% CI: 4.8, 11.6 nmol/L) higher in mid-childhood. Other factors consistently associated with higher 25(OH)D were blood collection in summer or fall, white race, nonfall birth season, prenatal exposure to higher 25(OH)D, and higher dietary intake of VitD. Greater waist circumference was associated with lower 25(OH)D in early childhood (β: -3.8; 95% CI: -7.4, -0.2 per 1-SD increase) among black children only.Conclusions: Our findings may help clinicians better target children at risk of lower 25(OH)D for screening and/or intervention and may inform research focused on associations of 25(OH)D with different exposures and outcomes or causal effects of early-life factors on later VitD status.This trial was registered at clinicaltrials.gov as NCT02820402. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency has been associated with health problems globally, but there is limited information on vitamin D status and associated risk factors among adults in underserved populations.Objective: This study aimed to identify risk factors for vitamin D deficiency/insufficiency among Puerto Rican adults from the Boston Puerto Rican Health Study (BPRHS).Methods: A total of 822 adults (45-75 y, at baseline) were included in these analyses. Deficiency was defined as serum 25-hydroxyvitamin D [25(OH)D] <30 and insufficiency as 30 to <50 nmol/L. Dietary intake was assessed with a validated FFQ. Associations between risk factors, including dietary vitamin D, supplement use, ancestry, skin pigmentation, months in the past year spent in a southern climate, and serum 25(OH)D were assessed with multivariable general linear models.Results: Approximately 13% of participants were deficient in 25(OH)D and another 43% insufficient. Skin pigment was associated with 25(OH)D using 3 measures, greater African ancestry (β ± SE) (-7.74 ± 2.91, P = 0.01); interviewer assessed dark or medium, compared with white, skin tone, (-5.09 ± 2.19, P = 0.02 and -5.89 ± 1.58, P < 0.001, respectively); and melanin index of the upper inner right arm, assessed using a spectrophotometer (-2.04 ± 0.84, P = 0.02). After adjusting for ancestry, factors associated with lower serum 25(OH)D included smoking (-4.49 ± 1.58, P = 0.01); BMI (-0.21 ± 0.10, P = 0.04); and spring compared with autumn blood draw (-4.66 ± 1.68, P = 0.004). Factors associated with higher serum 25(OH)D included female sex compared with male (4.03 ± 1.58, P = 0.01); dietary vitamin D intake μg/d (0.71 ± 0.25, P < 0.004); vitamin D supplement use (4.50 ± 1.87, P = 0.02); income to poverty ratio (0.01 ± 0.01, P = 0.06), and months in a southern climate during the past year (0.96 ± 0.56, P = 0.09).Conclusions: Vitamin D deficiency/insufficiency was prevalent in this Puerto Rican population living in the northeastern USA. Several factors were associated with this, which may assist in identifying those at risk. Interventions are needed to improve serum 25(OH)D concentration, particularly among those with limited exposure to sunlight. [ABSTRACT FROM AUTHOR]

Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for which comprehensive data are lacking in school-aged children. We assessed the micronutrient status of Nepalese children, aged 6 to 8 y, born to mothers who participated in a community-based antenatal micronutrient supplementation trial from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a random sample of 1000 children. Results revealed deficiencies of vitamins A (retinol 2 μg/L, 20%), B-12 (cobalamin 8.3 mg/L, 40.1%; TfR:ferritin >500 μg/μg, 14.3%], iodine (thyroglobulin >40 μg/L, 11.4%), and selenium (plasma selenium 1 g/L, C-reactive protein >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of deficiency as assessed by retinol, β-carotene, PLP, ferritin, TfR, selenium, copper, or having any or multiple deficiencies. For any nutrient, population deficiency prevalence estimates were altered by ≤5.4% by the presence of inflammation, suggesting that the majority of deficiencies exist regardless of inflammation. Multiple micronutrient deficiencies coexist in school-aged children in rural Nepal, meriting more comprehensive strategies for their assessment and prevention.

Few detailed data are available on the wide range of determinants of vitamin D status among postmenopausal women, and it is also unclear whether there may be undiscovered determinants. The objective of this study was to comprehensively evaluate determinants of serum 25-hydroxyvitamin D [25(OH)D] concentrations in a large cohort of postmenopausal women. Data from a subset of the Women's Health Initiative Observational Study were analyzed (50-79 y; n = 3345). Information on diet, lifestyle behaviors, secondhand smoke, use of dietary supplements and medication, chronic diseases, and anthropometry was collected at baseline (1993-1998) and on sun exposure at year 4 follow-up. Linear regression was performed to estimate regression coefficients (β). Significant determinants were total vitamin D intake (food plus supplements per 100 IU/d, β = 2.08), years of supplemental vitamin D use (β = 0.15), total fat intake (grams per day, β = -0.03), smoking status (β = -2.64, current vs. never), regional solar irradiance (β = 6.26, 475-500 vs. 300-325 Langleys), daylight time spent outdoors in summer (β = 5.15, >2 h vs.

Background: Calcium plus vitamin D supplementation of pregnant Brazilian adolescents with habitually low calcium intake (∼600 mg/d) reduced bone loss during the first 20 wk postpartum.Objective: We investigated maternal bone mass changes during the first year postpartum as a follow-up of the clinical trial.Methods: Pregnant adolescents (14-19 y) received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition. Bone area and bone mineral content and bone mineral density (BMD) at total body, lumbar spine, and hip (total and femoral neck) were assessed by DXA at 3 time points postpartum (5 wk, 20 wk, and 56 wk). Intervention group, time postpartum, and group × time interaction effects were tested by repeated-measures mixed-effects models adjusting for calcium intake, return of menses, breastfeeding practices, and body weight.Results: Time (P < 0.05) but not group affected several absolute bone measurements. There was a group × time interaction for femoral neck BMD (P = 0.045). Mean ± SE values (g/cm2) at 5 wk, 20 wk, and 56 wk were, respectively, 1.025 ± 0.026, 0.980 ± 0.026, and 1.022 ± 0.027 for the placebo group and 1.057 ± 0.025, 1.030 ± 0.024, and 1.055 ± 0.025 for the supplemented group. An interaction also was observed for percentage change in femoral neck BMD relative to 5 wk (P = 0.049), with a more pronounced decrease in the placebo group (-4.58 ± 0.42%) than in the supplemented group (-3.15% ± 0.42%) at 20 wk (P = 0.019), and no difference between groups at 56 wk (-0.44% ± 0.71% in the placebo and -0.76% ± 0.62% in the supplemented group; P = 0.65).Conclusions: Calcium plus vitamin D supplementation of the adolescent mothers reduces the magnitude of bone loss at the femoral neck from 5 to 20 wk postpartum without an effect on bone changes after 1 y postpartum, indicating that there is no sustained effect of the supplement tested. [ABSTRACT FROM AUTHOR]

We summarize here lessons learned from studies on skeletal and extra-skeletal functions of vitamin D in hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) patients with a mutant, nonfunctioning vitamin D receptor (VDR). During childhood, HVDRR patients are dependent on intestinal VDR, demonstrate low intestinal fraction calcium absorption, and have a bone calcium accretion rate that leads to hypocalcemia and rickets. After puberty, there is recovery in intestinal calcium absorption and in bone calcium accretion and structure. HVDRR monocytes and lymphocytes show impairment in the expression of antimicrobial proteins and demonstrate a proinflammatory cytokine profile. However, HVDRR patients do not exhibit increased rates of infections or inflammatory diseases. Vitamin D deficiency is associated with asthmatic exacerbations. Surprisingly, HVDRR patients do not usually develop asthma. They have normal allergic tests and lung functions and are protected against provoked bronchial hyperactivity. HVDRR patients have decreased IL-5 levels in their exhaled breath condensate. Given that IL-5 is a key cytokine in the development of airway inflammation and hyperactivity and that VDR is important for IL-5 generation, it is plausible that low lung IL-5 protects HVDRR patients from asthma. Vitamin D metabolites have suppressive effects on the renin angiotensin system. However, no HVDRR patient showed hypertension or echocardiographic pathology, and their renin angiotensin metabolites were normal. The VDR is expressed throughout the reproductive system, suggesting a role in reproduction. However, the reproductive history of HVDRR patients is normal despite the lack of a normal VDR. HVDRR patients provide a unique opportunity to study the role of the VDR and the role of vitamin D in various human systems. [ABSTRACT FROM AUTHOR]

Background: Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D.Objectives: We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration.Methods: We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere.Results: GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 × 10-6) and serum 25(OH)D concentration from 64.4 ± 20.9 nmol/L to 68.5 ± 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063).Conclusions: We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries. [ABSTRACT FROM AUTHOR]

Background: Vitamins D and K, which are present in human brain, may have a role in neurodegenerative disease.Objectives: Given the interest in measuring nutrient concentrations in archived brain samples, it is important to evaluate whether freezer storage time affects these concentrations. Therefore, we evaluated differences in vitamin D and vitamin K concentrations in human brain samples stored for various lengths of time.Methods: Postmortem brain samples were obtained from 499 participants in the Rush Memory and Aging Project (mean age 92 y, 72% female). Concentrations of vitamins D and K and their metabolites were measured in 4 regions (midtemporal cortex, midfrontal cortex, cerebellum, anterior watershed white matter) using LC-MS/MS and HPLC, respectively. The predominant forms were 25-hydroxycholecalciferol [25(OH)D3] and menaquinone-4 (MK4). ANOVA was used to determine if concentrations differed according to storage time.Results: The geometric mean of the mean 25(OH)D3 concentration (across 4 regions) in brains stored for 1.1 to 6.0 y did not differ from that in brains stored ≤1.0 y (all P ≥ 0.37), whereas 25(OH)D3 in brains stored >6.0 y was 31-40% lower (P ≤ 0.003). MK4 had similar results, with the geometric mean MK4 concentration in the brains stored ≥9.0 y being 48-52% lower than those in brains stored ≤1.0 y (P ≤ 0.012). The 25(OH)D3 and MK4 concentrations were positively correlated across all 4 regions (all Spearman ρ ≥ 0.79, P < 0.001).Conclusions: 25(OH)D3 and MK4 appear to be stable in brain tissue from older adults stored at -80°C for up to 6 and 9 y, respectively, but not longer. Freezer storage time should be considered in the design and interpretation of studies using archived brain tissue. [ABSTRACT FROM AUTHOR]

Background: Vitamin D might have beneficial potential in influencing the natural history of the coronavirus disease 2019 (COVID-19) due to its immunomodulatory and anti-inflammatory properties.Objective: The aim was to investigate whether vitamin D deficiency is associated with COVID-19 incidence and disease severity in Chinese people.Methods: In a cross-sectional study we retrospectively analyzed 335 COVID-19 patients (median: 56.0; IQR: 43.0-64.0 y) who were admitted to the Wuhan Tongji Hospital between 27 February and 21 March 2020. We also included an age- and sex-matched population of 560 individuals (median: 55; IQR: 49.0-60.0 y) who underwent the physical examination program. Their serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during the same period from 2018-2019. Serum 25(OH)D concentrations were measured for all COVID-19 patients on admission. Severity of COVID-19 was determined based on the level of respiratory involvement. A general linear model with adjustment for covariates was used to compare 25(OH)D concentrations between the COVID-19 and 2018-2019 control groups. Adjusted ORs with 95% CIs for associations between vitamin D status and COVID-19 severity were estimated via multivariable logistic regression.Results: In the general linear model adjusted for age, sex, comorbidities, and BMI, serum 25(OH)D concentrations were significantly lower among COVID-19 patients than the 2018-2019 controls [ln transformed values of 3.32 ± 0.04 vs. 3.46 ± 0.022 ln (nmol/L), P = 0.014]. Multivariable logistic regression showed that male sex (OR: 2.26; 95% CI: 1.06, 4.82), advanced age (≥65 y) (OR: 4.93; 95% CI: 1.44, 16.9), and vitamin D deficiency (<30 nmol/L) (OR: 2.72; 95% CI: 1.23, 6.01) were significantly associated with COVID-19 severity (all P < 0.05).Conclusions: These findings suggested that vitamin D deficiency impacts COVID-19 hospitalization and severity in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Plant-based diets may reduce the risk of chronic diseases, but can also lead to low calcium and vitamin D intakes, posing a risk for bone health.Objectives: We investigated whether partial replacement of animal proteins with plant-based proteins using a whole-diet approach affects bone and mineral metabolism in healthy adults in 3 groups fed diets differing in protein composition.Methods: This 12-week clinical trial was comprised of 107 women and 29 men (20-69 years old; BMI mean ± SD, 24.8 ± 3.9) randomly assigned to consume 1 of 3 diets designed to provide 17 energy percent (E%) protein: "animal" (70% animal protein, 30% plant protein of total protein intake), "50/50" (50% animal, 50% plant), and "plant" (30% animal, 70% plant) diets. We examined differences in bone formation [serum intact procollagen type I amino-terminal propeptide (S-iPINP)], bone resorption [serum collagen type 1 cross-linked C-terminal telopeptide (S-CTX)], mineral metabolism markers (primary outcomes), and nutrient intakes (secondary outcomes) by ANOVA/ANCOVA.Results: S-CTX was significantly higher in the plant group (mean ± SEM, 0.44 ± 0.02 ng/mL) than in the other groups (P values < 0.001 for both), and differed also between the animal (mean ± SEM, 0.29 ± 0.02 ng/mL) and 50/50 groups (mean ± SEM, 0.34 ± 0.02 ng/mL; P = 0.018). S-iPINP was significantly higher in the plant group (mean ± SEM, 63.9 ± 1.91 ng/mL) than in the animal group (mean ± SEM, 55.0 ± 1.82 ng/mL; P = 0.006). In a subgroup without a history of vitamin D supplement use, plasma parathyroid hormone was significantly higher in the plant than in the animal group (P = 0.018). Vitamin D and calcium intakes were below recommended levels in the plant group (mean ± SEM, 6.2 ± 3.7 μg/d and 733 ± 164 mg/d, respectively).Conclusions: Partial replacement of animal proteins with plant-based proteins for 12 weeks increased the markers of bone resorption and formation among healthy adults, indicating a possible risk for bone health. This is probably caused by lower vitamin D and calcium intakes from diets containing more plant-based proteins, but it is unclear whether differences in protein intake or quality play a major role. This trial was registered at clinicaltrials.gov as NCT03206827. [ABSTRACT FROM AUTHOR]

Background: A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited.Objectives: Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians.Methods: We performed an observational prospective study on 601 participants of the Hoorn Study (mean ± SD age: 70 ± 6 y, 50.4% women, BMI: 27.2 ± 4.0 kg/m2), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D (stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders.Results: Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m2.7; 95% CI: 1.8, 10.0 g/m2.7). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status.Conclusions: A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk. [ABSTRACT FROM AUTHOR]

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

Background: Vitamin D deficiency compromises muscle function and is related to the etiology of several clinical conditions that can contribute to the development of disability. However, there are few epidemiological studies investigating the association between vitamin D deficiency and the incidence of disability.Objectives: We aimed to assess whether vitamin D deficiency is associated with the incidence of disability in basic activities of daily living (BADL) and to verify whether there are sex differences in this association.Methods: A 4-y follow-up study was conducted involving individuals aged 50 y or older who participated in ELSA (English Longitudinal Study of Ageing). The sample consisted of 4814 participants free of disability at baseline according to the modified Katz Index. Vitamin D was assessed by serum 25-hydroxyvitamin D [25(OH)D] concentrations and the participants were classified as sufficient (>50 nmol/L), insufficient (>30 to ≤50 nmol/L), or deficient (≤30 nmol/L). Sociodemographic, behavioral, and clinical characteristics were also investigated. BADL were re-evaluated after 2 and 4 y of follow-up. The report of any difficulty to perform ≥1 BADL was considered as an incident case of disability. Poisson models stratified by sex and controlled for sociodemographic, behavioral, and clinical characteristics were carried out.Results: After 4-y follow-up, deficient serum 25(OH)D was a risk factor for the incidence of BADL disability in both women (IRR: 1.53; 95% CI: 1.16, 2.03) and men (IRR: 1.44; 95% CI: 1.02, 2.02). However, insufficient serum 25(OH)D was not a risk factor for the incidence of BADL disability in either men or women.Conclusions: Independently of sex, deficient serum 25(OH)D concentrations were associated with increased risk of incidence of BADL disability in adults >50 y old and should be an additional target of clinical strategies to prevent disability in these populations. [ABSTRACT FROM AUTHOR]

Background: Hong Kong faces several public health problems including malnutrition and osteoporosis. Considering the typical Chinese diet and overall low physical activity levels of Chinese adults, timely interventions to improve nutritional status and bone health are needed.Objectives: We examined the effects of a nutrition plus exercise intervention on serum vitamin B-12 and 25-hydroxyvitamin D [25(OH)D], bone turnover markers, and parathyroid hormone (PTH) concentrations in apparently healthy Chinese middle-aged and older adults.Methods: In this 24-wk randomized controlled trial, 180 Chinese adults (85 women, mean ± SD age: 61 ± 6 y) were randomly assigned to receive a fortified milk supplement (2 × 30 g/d) and an exercise program (2 × 1 h/wk including resistance, balance, and aerobic training) or no intervention. The primary outcome was physical performance. In this article we analyzed the secondary outcomes serum vitamin B-12 and 25(OH)D concentrations, assessed at baseline, 12 wk, and 24 wk. Also, bone turnover markers and PTH concentrations were studied. Linear mixed models evaluated group differences over time.Results: A significant time × group interaction (P < 0.001) was found for serum vitamin B-12 and 25(OH)D concentrations and the bone turnover markers, but not for serum PTH concentrations (P = 0.09). The intervention increased mean ± SD vitamin B-12 concentrations from baseline (345 ± 119 pmol/L) to 24 wk (484 ± 136 pmol/L), whereas concentrations remained stable within the control. For 25(OH)D concentrations, the intervention group had a greater increase from baseline (54.7 ± 14.2 nmol/L) to 24 wk (80.1 ± 19.2 nmol/L) than the control (60.6 ± 15.2 compared with 65.6 ± 14.6 nmol/L). The ratio of the net effect of bone formation and resorption was greater in the intervention group, suggesting less bone remodeling, irrespective of sex.Conclusions: A fortified milk supplement and exercise intervention successfully improved vitamin B-12 and 25(OH)D concentrations as well as the balance of bone turnover markers of Chinese middle-aged and older adults.This trial was registered at trialregister.nl as NTR6214. [ABSTRACT FROM AUTHOR]

Background: Many cancer patients initiate dietary supplement use after cancer diagnosis. How dietary supplement use contributes to the total nutrient intake among cancer survivors as compared with individuals without cancer needs to be determined.Objectives: We aimed to evaluate nutrient intakes from dietary supplements among cancer survivors in relation to their total nutrient intake and compare those with individuals without cancer.Methods: We evaluated the prevalence, dose, and reason for using dietary supplements among 2772 adult cancer survivors and 31,310 individuals without cancer who participated in the NHANES 2003-2016.Results: Cancer survivors reported a higher prevalence of any (70.4% vs. 51.2%) and multivitamin/mineral (48.9% vs. 36.6%) supplement use and supplement use of 11 individual vitamins and 8 minerals than individuals without cancer. Overall, cancer survivors had significantly higher amounts of nutrient intake from supplements but lower nutrient intakes from foods for the majority of the nutrients. Compared with individuals without cancer, cancer survivors had a higher percentage of individuals with inadequate intake (total nutrient intake Conclusions: Cancer survivors reported a higher prevalence and dose of dietary supplement use but lower amounts of nutrient intake from foods than individuals without cancer. The inadequate nutrient intake from foods and the short-term and long-term health impact of dietary supplement use, especially at high doses, need to be further evaluated among cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Accurate and reliable methods to assess prevalence of use of and nutrient intakes from dietary supplements (DSs) are critical for research, clinical practice, and public health monitoring. NHANES has been the primary source of DS usage patterns using an in-home inventory with a frequency-based DS and Prescription Medicine Questionnaire (DSMQ), but little is known regarding DS information obtained from 24-h dietary recalls (24HRs).Methods: The objectives of this analysis were to compare results from 4 different methods for measuring DS use constructed from two data collection instruments (i.e., DSMQ and 24HR) and to determine the most comprehensive method for measuring the prevalence of use and estimating nutrient intakes from DS for selected nutrients. NHANES 2011-2014 data from US adults (aged ≥19 y; n = 11,451) were used to examine the 4 combinations of methods constructed for measuring the prevalence of use of and amount of selected nutrients from DSs (i.e., riboflavin, vitamin D, folate, magnesium, calcium): 1) DSMQ, 2) 24HR day 1, 3) two 24HRs (i.e., mean), and 4) DSMQ or at least one 24HR.Results: Half of US adults reported DS use on the DSMQ (52%) and on two 24HRs (mean of 49%), as compared with a lower prevalence of DS use when using a single 24HR (43%) and a higher (57%) prevalence when combining the DSMQ with at least one 24HR. Mean nutrient intake estimates were highest using 24HR day 1. Mean supplemental calcium from the DSMQ or at least one 24HR was 372 mg/d, but 464 mg/d on the 24HR only. For vitamin D, the estimated intakes per consumption day were higher on the DSMQ (46 μg) and the DSMQ or at least one 24HR (44 μg) than those on the 24HR day 1 (32 μg) or the mean 24HR (31 μg). Fewer products were also classed as a default or reasonable match on the DSMQ than on the 24HR.Conclusions: A higher prevalence of use of DSs is obtained using frequency-based methods, whereas higher amounts of nutrients are reported from a 24HR. The home inventory results in greater accuracy for products reported. Collectively, these findings suggest that combining the DSMQ with at least one 24HR (i.e., DSMQ or at least one 24HR) is the most comprehensive method for assessing the prevalence of and estimating usual intake from DSs in US adults.This trial was registered at clinicaltrials.gov as NCT03400436. [ABSTRACT FROM AUTHOR]

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

Background: Vitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in low- and middle-income countries and response to cholecalciferol supplementation in pregnancy are sparse.Objective: We characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.Methods: This study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation [iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN]; MMN included 10 μg/d cholecalciferol. Plasma 25-hydroxycholecalciferol [25(OH)D3], 24,25-dihydroxycholecalciferol [24,25(OH)2D3], and C3-epimer-25-hydroxycholecalciferol [3-epi-25(OH)D3] were measured by LC-MS/MS in 863 women [aged 30 ± 7 y (mean ± SD)] in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3 and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.Results: Early pregnancy 25(OH)D3 concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) (P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3 was positively associated with maternal age and gestational age. Change in 25(OH)D3 was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3 mirrored that of 25(OH)D3 and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3 concentration increased across pregnancy.Conclusion: This study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa. [ABSTRACT FROM AUTHOR]

Background: Evidence is lacking to determine whether there have been any changes in dietary or total usual intakes of vitamin D among Canadians, in the light of recent evidence of beneficial health effects beyond bone.Objective: We aimed to examine trends in dietary and total usual intake of vitamin D among Canadians aged ≥1 y.Methods: This study used nationally representative nutrition data from the Canadian Community Health Survey Cycle 2.2 (CCHS 2004) and CCHS Nutrition in 2015. Dietary intake data were collected with use of two 24-h dietary recalls and dietary supplement use was determined by questionnaire. The National Cancer Institute method was used to estimate the usual intake of vitamin D as well as the prevalence of vitamin D inadequacy among Canadians aged ≥1 y.Results: From 2004 to 2015, the usual intake of vitamin D from food significantly decreased (P < 0.05) by 1 μg/d only in vitamin D supplement nonusers. The contribution of Milk and Alternatives food group (i.e., fluid milk, fortified soy beverages, powdered milk, and other milk alternatives) to dietary vitamin D intake significantly decreased (P < 0.05) in both supplement users (by 7.1%) and nonusers (by 5.8%). Prevalence of vitamin D supplement use and percentage contribution of vitamin D from supplemental sources significantly increased (P < 0.05) by 5.0% and 14.9%, respectively, from 2004 to 2015. Total usual intake of vitamin D (food + supplement) significantly increased (P < 0.05) from 15.1 ± 0.3 μg/d in 2004 to 31.5 ± 1.8 μg/d in 2015 in vitamin D supplement users. In contrast to vitamin D supplement nonusers, the prevalence of vitamin D inadequacy significantly decreased (P < 0.05) from 20.6% to 14.1% among users of vitamin D supplements.Conclusions: The prevalence of vitamin D supplement use and the percentage contribution of vitamin D from supplemental sources has increased in the Canadian population over an 11-y period. [ABSTRACT FROM AUTHOR]

Background: Breakfast consumption has declined over the past 40 y and is inversely associated with obesity-related diet and health outcomes. The breakfast pattern of food pantry clients and its association with diet is unknown.Objective: The objective is to investigate the association of breakfast consumption with diet quality and usual nutrient intakes among food pantry clients (n = 472) living in rural communities.Methods: This was an observational study using cross-sectional analyses. English-speaking participants ≥18 y (or ≥19 y in Nebraska) were recruited from 24 food pantries in rural high-poverty counties in Indiana, Michigan, Missouri, Nebraska, Ohio, and South Dakota. Participants were surveyed at the pantry regarding characteristics and diet using 24-h recall. A second recall was self-completed or completed via assisted phone call within 2 wk of the pantry visit. Participants were classified as breakfast skippers when neither recall reported breakfast ≥230 kcal consumed between 04:00 and 10:00; breakfast consumers were all other participants. The Healthy Eating Index-2010 was modeled with breakfast pattern using multiple linear regression. Mean usual intake of 16 nutrients was estimated using the National Cancer Institute Method and compared across breakfast pattern groups. Usual nutrient intake was compared with the Estimated Average Requirement (EAR) or Adequate Intake (AI) to estimate the proportion of population not meeting the EAR or exceeding the AI.Results: A total of 56% of participants consumed breakfast. Compared with breakfast skippers, breakfast consumers had 10-59% significantly higher usual mean intakes of all nutrients (P ≤ 0.05), and had 12-21% lower prevalence of at-risk nutrient intakes except for vitamin D, vitamin E, and magnesium.Conclusions: Adult food pantry clients living in rural communities experienced hardships in meeting dietary recommendations. Breakfast consumption was positively associated with usual nutrient intakes in this population. This trial was registered at clinicaltrials.gov as NCT03566095. [ABSTRACT FROM AUTHOR]

Background: 25-Hydroxycholecalciferol [25(OH)D] is the predominant circulating metabolite of vitamin D and serves as the precursor for 1α,25-dihydroxycholecalciferol [1,25(OH)2D], the hormonally active form. The presence of 1α-hydroxylase (1α-OHase) in the intestine suggests that 1,25(OH)2D can be produced from 25(OH)D, but the effects of oral 25(OH)D on the intestine have not been determined.Objectives: We investigated the acute intestinal response to orally consumed 25(OH)D in mice by assessing mRNA induction of cytochrome p450 family 24 subfamily A member 1 (Cyp24), a vitamin D-dependent gene. The mechanism of action then was determined through in vitro analyses with Caco2 and HT-29 cells.Methods: Adult male C57BL6 mice were given a single oral dose of 40, 80, 200, or 400 ng 25(OH)D (n = 4 per dose) or vehicle (n = 3), and then killed 4 h later to evaluate the duodenal expression of Cyp24 mRNA by qPCR and RNA in situ hybridization. The 25(OH)D-mediated response was also evaluated with Caco2 and HT-29 cells by inhibition assay and dose-response analysis. A cytochrome p450 family 27 subfamily B member 1 (CYP27B1) knockdown of HT-29 was created to compare the dose-response parameters with wild-type HT-29 cells.Results: Oral 25(OH)D induced expression of Cyp24 mRNA in the duodenum of mice with 80 ng 25(OH)D by 3.3 ± 0.8 ΔΔCt compared with controls (P < 0.05). In vitro, both Caco2 and HT-29 cells responded to 25(OH)D treatment with 200-fold and 175-fold greater effective concentration at 50% maximal response than 1,25(OH)2D, yet inhibition of 1α-OHase and knockdown of CYP27B1 had no effect on the responses.Conclusions: In mice, orally consumed 25(OH)D elicits a vitamin D-mediated response in the duodenum. In vitro assessments suggest that the response from 25(OH)D does not require activation by 1α-OHase and that 25(OH)D within the intestinal lumen acts as a vitamin D receptor agonist. [ABSTRACT FROM AUTHOR]

Background: There are few studies directly comparing the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D3] to cholecalciferol (D3).Objectives: The primary objectives were to compare the effectiveness of D3 and 25(OH)D3 in raising 25-hydroxyvitamin D [25(OH)D] serum concentrations and achieving steady state.Methods: This was a randomized, double-blind, active comparator trial of 91 participants (53 females, 38 males), aged 63.3 ± 7.9 y. 25(OH)D3 (10, 15, and 20 µg) and D3 (20 µg) were dosed daily for 6 mo followed by 6 mo of washout. Frequent measurements of serum 25(OH)D were performed. Pharmacokinetic parameters were fitted for each individual and the treatment average was modeled with linear regression using the individual baseline level, sex, and gender as covariates.Results: Mean baseline 25(OH)D was similar in all groups (47.1-49.5 nmol/L). Increases in 25(OH)D to steady state were higher in the 25(OH)D3 groups than in the D3 group [least squares (LS) means (95% CI): 50.1 (43.3-58.0), 72.5 (64.3-81.7), 97.4 (86.6-109.6) nmol/L in 10, 15, and 20 µg/d and 38.7 (33.1-45.2) nmol/L in the D3 group; P = 0.0173, P < 0.0001, P < 0.0001]. The rate to reach steady state was similar in all groups, but the time to reach 25(OH)D concentrations of 75 nmol/L was faster in the higher-dosed 25(OH)D3 groups than in the D3 group (7 and 10 d compared with 40 d, P < 0.0001 and P < 0.0001 for 15 and 20 µg/d). The rate of elimination was 59-109% higher in the 25(OH)D3 groups than in the D3 group. The area under the curve (AUC)/µg dose demonstrated that 25(OH)D3 was 3 times as effective as D3 at raising 25(OH)D concentrations.Conclusions: 25(OH)D3 is ∼3 times as effective as D3 at raising 25(OH)D concentrations. Once supplementation is discontinued, the elimination rate of 25(OH)D3 is faster than D3. This trial was registered at clinicaltrials.gov as NCT02333682. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency (VDD) is associated with depression and schizophrenia in adults. The effect of VDD in childhood on behavioral development is unknown.Objectives: We aimed to study the associations of VDD and vitamin D binding protein (DBP) in middle childhood with behavior problems in adolescence.Methods: We quantified plasma total 25-hydroxyvitamin D [25(OH)D] and DBP in 273 schoolchildren aged 5-12 y at recruitment into a cohort study in Bogota, Colombia. Externalizing and internalizing behavior problems were assessed after a median 6-y follow-up by parental report [Child Behavior Checklist (CBCL)] and self-report [Youth Self-Report (YSR)]. We estimated mean problem score differences with 95% CIs between exposure categories using multivariable linear regression. We also compared the prevalence of clinical behavior problems (score >63) between exposure groups. We assessed whether the associations between DBP and behavior problems were mediated through VDD.Results: Mean ± SD CBCL and YSR externalizing problems scores were 56.5 ± 9.3 and 53.2 ± 9.5, respectively. Internalizing problems scores averaged 57.1 ± 9.8 and 53.7 ± 9.8, respectively. VDD [25(OH)D <50 nmol/L] prevalence was 10.3%. VDD was associated with an adjusted 6.0 (95% CI: 3.0, 9.0) and 3.4 (95% CI: 0.1, 6.6) units higher CBCL and YSR externalizing problems scores, respectively, and an adjusted 3.6 (95% CI: 0.3, 6.9) units higher CBCL internalizing problems scores. The prevalence of clinical total externalizing problems was 1.8 (95% CI: 1.1, 3.1) times higher in children with VDD than that in children without VDD. DBP concentration below the population median was related to higher YSR aggressive behavior and anxious/depressed subscale scores and to higher prevalence of clinical total externalizing problems. The associations between DBP and behavior problems were not mediated through VDD.Conclusions: VDD and low DBP in middle childhood are related to behavior problems in adolescence. [ABSTRACT FROM AUTHOR]