A Randomized Clinical Trial of Vitamin D Supplementation in Healthy Adolescents

PurposeThe most safe and effective dose of vitamin D supplementation for healthy adolescents is currently unknown. The aim of this study was to compare the efficacy of 200 IU versus 1,000 IU of daily vitamin D₃ for supplementation in healthy adolescents with baseline vitamin D sufficiency.MethodsWe conducted a double-blind, randomized clinical trial. Fifty-six subjects, ages 11–19 years, with baseline vitamin D sufficiency received 1,000 IU or 200 IU of daily vitamin D₃ for 11 weeks. Compliance was assessed using MEMS6 Trackcaps and pill counts.ResultsFifty-three subjects completed the clinical trial. Subjects in the two treatment arms were similar in terms of age, race, gender, body mass index, and dietary calcium and vitamin D intake. Serum 25(OH)D level in the 200 IU treatment arm was 28.1 ± 6.2 ng/mL at baseline (mean ± SD) and 28.9 ± 7.0 ng/mL at follow-up. In the 1,000 IU treatment arm, 25(OH)D levels were 29.0 ± 7.3 and 30.1 ± 6.6 at baseline and follow-up, respectively. Mean change in 25(OH)D level did not differ significantly between treatment arms (p = .87), nor did mean change in parathyroid hormone, calcium, phosphate, bone turnover markers, fasting glucose, or fasting insulin.ConclusionsIn healthy adolescents with baseline vitamin D sufficiency, supplementation with vitamin D₃ doses of 200 and 1,000 IU for 11 weeks did not increase serum 25(OH)D levels, with no significant difference observed between treatment arms.     

Effects of Vitamin D3 and Calcium Supplementation on Serum Levels of Tocopherols,Retinol, and Specific Vitamin D Metabolites

γ-Tocopherol (γT) protects against DNA-damaging effects of nitrogen oxides, yet its physiologic regulation in vivo is unknown. Observational studies indicate inverse associations of 25[OH]-vitamin D with γT and leptin. To determine whether vitamin D₃ supplementation alters levels of lipid-soluble micronutrients, serum samples (N = 85 subjects) from a randomized, double-blind, placebo-controlled clinical trial of vitamin D₃ (800 IU) and calcium (2 g), alone and in combination, were analyzed for lipid micronutrients and specific vitamin D metabolites at baseline and after 6 mo of supplementation. Serum 25[OH]-vitaminD₃ levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas 25[OH]-vitaminD₂ levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the vitamin D₃ and vitamin D₃ plus calcium groups, respectively. At baseline, γT levels were inversely associated with 25[OH]D (r = ?0.31, P = 0.004). With vitamin D₃ plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), whereas similar changes in γT (19% lower, P = 0.14) were observed. No significant effects were observed for D₃ supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D₃ ± calcium affects serum tocopherol and 25[OH]D₂ levels; however, studies using larger, more homogeneous populations are warranted.     

Safety and Efficacy of Early Vitamin D Supplementation in Critically Ill Extremely Preterm Infants: An Ancillary Study of a Randomized Trial

BackgroundDespite substantial evidence that vitamin D deficiency is highly prevalent among infants born extremely preterm (≤28 weeks’ of gestation), several consensus statements do not recommend vitamin D doses >400 IU/day for these infants. Safety remains a concern.ObjectiveThe study aim was to determine safety and efficacy profiles of enteral vitamin D in Black and White infants randomized to three different vitamin D doses soon after birth.DesignAncillary study of a masked randomized clinical trial.Participants/settingSeventy-three infants born extremely preterm between 2012 and 2015 at a southern US academic neonatal unit (33’ latitude) who had >90% compliance with the assigned intervention were included.InterventionInfants were randomized to receive placebo (placebo group), 200 IU/day vitamin D (200 IU group), or 800 IU/day vitamin D (800 IU group) during the first 28 days after birth.Main outcome measuresSafety outcomes included serum 25-hydroxy vitamin D (25[OH]D) and calcium concentrations. Efficacy outcomes included the predictive risk of bronchopulmonary dysplasia.Statistical analysisPer-protocol analysis using unadjusted, repeated-measures mixed models.ResultsMean birth weight was 815 ± 199 g. Half were male and 56% were Black. Of 58 infants with 25(OH)D measurements at birth, 40 (69%) had vitamin D deficiency (<20 ng/mL). The mean difference in 25(OH)D in nanograms per milliliter between Postnatal Day 28 and Postnatal Day 1 was +9 in the placebo group, +23 in the 200 IU group, and +62 in the 800 IU group (P < 0.0001). The increase observed in 25(OH)D was more significant among Black infants. The predictive risk of severe bronchopulmonary dysplasia in the 200 IU and 800 IU groups was lower, but this difference did not reach statistical significance. No vitamin D or calcium toxicity was observed.ConclusionsA vitamin D dose of 800 IU/day safely corrected vitamin D deficiency by Postnatal Day 14.     

Low Vitamin D Status Among Obese Adolescents: Prevalence and Response to Treatment

PurposeTo explore the prevalence of low vitamin D status among obese adolescents and to examine the effect of current management of low vitamin D status in these patients.MethodsA retrospective chart review of obese adolescents who had been screened for vitamin D status by serum total 25-hydroxyvitamin D (25(OH)D) level. Vitamin D deficiency was defined as 25(OH)D level of <20 ng/mL, vitamin D insufficiency as 25(OH)D level of 20–30 ng/mL, and vitamin D sufficiency as 25(OH)D level of >30 ng/mL. Adolescents with vitamin D deficiency were treated with 50,000 IU of vitamin D once a week for 6–8 weeks, whereas adolescents with vitamin D insufficiency were treated with 800 IU of vitamin D daily for 3 months. Repeat 25(OH)D was obtained after treatment.ResultsThe prevalence rate of low vitamin D status among 68 obese adolescents (53% females, 47% males, age: 17 ± 1 years, body mass index: 38 ± 1 kg/m², Hispanic: 45%, African American: 40%, Caucasian: 15%) was 100% in females and 91% in males. Mean (±SE) 25(OH)D level was significantly higher in summer (20 ± 8 ng/mL) than in spring (14 ± 4 ng/mL, p < .02), and significantly lower in winter (15 ± 7 ng/mL) than in fall (25 ± 15 ng/mL, p < .05). Although there was a significant (p < .00001) increase in mean 25(OH)D after the initial course of treatment with vitamin D, 25(OH)D levels normalized in only 28% of the participants. Repeat courses with the same dosage in the other 72% did not significantly change their low vitamin D status.ConclusionsIncreased surveillance and possibly higher vitamin D doses are warranted for obese adolescents whose total 25(OH)D levels do not normalize after the initial course of treatment.     

Body Size and Serum 25 Hydroxy Vitamin D Response to Oral Supplements in Healthy Older Adults

Background: Vitamin D insufficiency is prevalent in the northeast United States. Since vitamin D insufficiency is readily amenable to supplementation, it is important to understand what factors are associated with serum 25 hydroxy vitamin D (25(OH)D) response to vitamin D supplementation.

Objective: In this study we examined the association of serum 25(OH)D response to vitamin D supplementation with body size in a population of elderly subjects.

Methods: 257 healthy, ambulatory men and women 65 years of age or older were randomly assigned to treatment with either 700 IU/day (17.5 μg/d) of supplemental vitamin D₃ and 500 mg/day (12.5 mmol/d) of supplemental calcium, or to placebo.

Results: In multivariate regression analyses, after adjusting for baseline 25(OH)D, season, and sex, we found change in 25(OH)D to be inversely associated with baseline BMI (p = 0.01) in subjects treated with supplements for one year. Change in 25(OH)D was also negatively associated with other baseline anthropometric measurements in these subjects.

Conclusion: Our study implies that body size should be taken into account when estimating the amount of vitamin D intake needed to raise 25(OH)D to the desired level.     

Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health

BACKGROUND: Fortification of milk with vitamin D may not be adequate for satisfying the vitamin D requirement because of variability in vitamin D content after fortification and because many persons have milk allergy or lactose intolerance. Additional foods need to be fortified with vitamin D. OBJECTIVE: We determined whether vitamin D, a fat-soluble vitamin, is bioavailable in orange juice and skim milk, 2 nonfat beverages. DESIGN: On 3 separate occasions, 18 adults ingested 25 000 IU vitamin D(2) in 240 mL whole milk or skim milk or in 0.1 mL corn oil applied to toast. A separate, double-blind, randomized, controlled trial investigated whether the consumption of orange juice fortified with vitamin D(3) would increase serum 25-hydroxyvitamin D [25(OH)D] concentrations: 14 subjects ingested 240 mL orange juice fortified with 1000 IU vitamin D, and 12 subjects ingested a control orange juice daily for 12 wk. RESULTS: Peak serum vitamin D(2) concentrations did not differ significantly after the ingestion of vitamin D(2) in whole milk, skim milk, or corn oil on toast. After subjects consumed orange juice fortified with 1000 IU vitamin D(3) daily for 12 wk, serum 25(OH)D(3) concentrations increased by 150%, and serum parathyroid hormone concentrations decreased by 25% compared with baseline; control subjects had a seasonal increase of 45% in 25(OH)D and no significant change in serum parathyroid hormone. CONCLUSIONS: The fat content of milk does not affect vitamin D bioavailability. Vitamin D fortification at 1000 IU/240 mL orange juice for 12 wk safely increased 25(OH)D(3) concentrations in adults.     

Breakfast Skipping Is Associated with Vitamin D Deficiency among Young Adults entering Initial Military Training

BackgroundVitamin D deficiency (VDD), defined as serum 25-hydroxyvitamin D (25[OH]D) levels < 20 ng/mL [to convert 25[OH]D ng/mL to nmol/L, multiply by 2.5]) is prevalent in young adults and has been associated with adverse health outcomes, including stress fracture during periods of increased physical activity such as military training. Foods commonly consumed at breakfast provide an important source of vitamin D, yet breakfast skipping is common among young adults. However, whether breakfast skipping is associated with VDD in young adults is unclear.ObjectivesThis study aimed to determine whether breakfast skipping is associated with odds of VDD among recruits entering initial military training (IMT), and with changes in serum 25(OH)D during IMT. In addition, whether diet quality and vitamin D intake mediated these associations was determined.DesignSecondary analysis of individual participant data collected during five IMT studies. Breakfast skipping (≥ 3 times/week) was self-reported. Dietary intake was determined using food frequency questionnaires, and vitamin D status was assessed using circulating 25(OH)D concentrations pre- and post-IMT.Participants and settingParticipants were healthy US Army, US Air Force, and US Marine recruits (N = 1,569, 55% male, mean ± standard deviation age 21 ± 4 years) entering military service between 2010 and 2015 at Fort Jackson, SC; Fort Sill, OK; Lakeland Air Force Base, TX; or the Marine Corps Recruit Depot, Parris Island, SC.Main outcome measuresPrimary outcomes were VDD pre-IMT and change in 25(OH)D from pre- to post-IMT.Statistical analysis performedAssociations were determined using multivariate-adjusted logistic and linear regression and mediation models.ResultsForty-six percent of military recruits were classified as breakfast skippers pre-IMT, and 30% were VDD. Breakfast skipping was associated with a higher odds of pre-IMT VDD (odds ratio 1.5, 95% CI 1.1 to 1.9), and lower vitamin D intake and diet quality were partial mediators of the association. Serum 25(OH)D concentrations improved (P = 0.01) among habitual breakfast skippers versus nonskippers during IMT; however, regression to the mean could not be ruled out. Neither change in diet quality nor vitamin D intake were associated with change in 25(OH)D concentrations during IMT.ConclusionsBreakfast skipping is prevalent among incoming military recruits and is associated with VDD. This relationship may be mediated by lower diet quality and vitamin D intake.     

Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers

For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose-response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12-20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0-10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children.     

Vitamin D deficiency is associated with poor response to active hepatitis B immunisation in patients with chronic kidney disease

Vitamin D deficiency is highly prevalent in patients suffering from chronic kidney disease. At present it is not known whether this condition is associated with poor response to hepatitis B vaccination in these patients. We performed a retrospective analysis of 200 patients with chronic kidney disease stages 3-5D, who had undergone hepatitis B vaccination with three 40 μg recombinant hepatitis B vaccine doses in a single centre. Anti-HBs antibody titres and 25-hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence immunoassays. Vitamin D deficiency with serum levels <10 ng/mL was found in 35.5% of patients. These patients had a lower seroconversion rate than did patients with levels ≥10 ng/mL (45% vs 64%; P = 0.011) and their median (25th, 75th percentile) anti-HBs antibody titres were lower (0 (0, 117) IU/L vs 48 (0, 236.5) IU/L). Non-responders had lower 25(OH)D concentrations than did responders (12.9 ± 6.5 ng/mL vs 15.1 ± 7.4 ng/mL; P = 0.034). Treatment with a vitamin D receptor activator had no influence on the immune response. In a multiple logistic regression analysis vitamin D deficiency (OR 0.480; P = 0.023) and diabetes (OR 0.496; P = 0.038) remained independent and significant negative predictors of seroconversion. In conclusion, in patients with chronic kidney disease vitamin D deficiency is associated with a poor antibody formation upon hepatitis B vaccination.     

The bioavailability of vitamin D from fortified cheeses and supplements is equivalent in adults

There is a need to increase the options for vitamin D fortification. We have developed a method to fortify hard cheese with vitamin D. Our aim was to characterize the bioavailability of vitamin D from fortified cheeses. Eighty adults were randomized to weekly servings of fortified cheddar cheese (DC) (34 g; n = 20); fortified low-fat cheese (DLF) (41 g; n = 10); liquid vitamin D supplement (1 mL), taken with food (DS+) (n = 20) or without food (DS-) (n = 10); placebo cheddar cheese (n = 10); or placebo supplement (n = 10). The treatments contained 28,000 IU cholecalciferol (vitamin D3), equivalent to 4000 IU (100 microg/d). The primary outcome was the comparison of vitamin D bioavailability, as measured by the serum 25-hydroxyvitamin D [25(OH)D] response, between fortified cheeses and supplement. In the placebo groups, initial 25(OH)D, 55.0 +/- 25.3 nmol/L, declined over the 8-wk winter protocol, to 50.7 +/- 24.2 nmol/L (P = 0.046). In the vitamin D-treated groups, the mean increases in 25(OH)D over 8 wk were: 65.3 +/- 24.1 (DC), 69.4 +/- 21.7 (DLF), 59.3 +/- 23.3 (DS+), and 59.3 +/- 19.6 nmol/L (DS-); these changes differed from the placebo groups (P < 0.0001) but not from one another (P = 0.62). Compared with baseline, serum parathyroid hormone decreased with both fortification (P = 0.003) and supplementation (P = 0.012). These data demonstrate that vitamin D is equally bioavailable from fortified hard cheeses and supplements, making cheese suitable for vitamin D fortification.     

Cholecalciferol supplementation to improve the hepatitis B vaccination response in hemodialysis patients: A first randomized open label pilot study (DeVitaHep)

BackgroundPatients with advanced chronic kidney disease should be vaccinated against hepatitis B. In observational studies vitamin D insufficiency is associated with a reduced seroconversion rate. The effect of cholecalciferol supplementation on hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency is unknown.MethodsIn this randomized open label pilot study 40 unvaccinated haemodialysis patients with 25(OH)D insufficiency (<30 ng/mL) were enrolled. In the supplementation group, we administered cholecalciferol orally in a dose of 28,000 IU weekly for a maximum of 12 weeks. Hepatitis B vaccination (HBvaxPRO 40 µg i.m. months 0, 1, 6) was performed after achieving a 25(OH)D level >30 ng/mL or after completing three months of supplementation despite failure to achieve the target level. In the control group, patients were vaccinated immediately after randomization. Anti-hepatitis B-antibody titer (anti-HBs) was measured eight weeks after completing the vaccination course.ResultsThirty-seven (26 male, 11 female) patients aged 65 (13.5) years underwent randomization with 17 patients allocated to the control group and 20 patients included in the supplementation group. After 12 weeks of cholecalciferol supplementation, mean (SD) 25(OH)D concentration increased from 15.0 (8.0) to 31.0 (7.1) ng/mL, but remained unchanged in the control group (14.0 (7.1) to 11.6 (7.5) mg/mL). Neither the number of patients with seroconversion (anti-HBs titer ≥ 10 IU/L; n = 6 (35.3%) vs n = 3 (27.3%), p = 0.704), nor the number of patients with seroprotection (anti-HBs titer >100 IU/L; n = 4 (23.5%) vs n = 2 (18.2%) differed between treatment groups. Cholecalciferol supplementation was safe without treatment-related adverse events.ConclusionIn this small pilot study, high-dose oral cholecalciferol supplementation did not improve the hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency.This clinical trial was registered within EudraCT (EudraCT number 2011-004621-26).     

Vitamin D status and its association with adiposity and oxidative stress in schoolchildren

ObjectiveThe aim of this study was to evaluate serum 25-hydroxyvitamin D [25(OH)D] level and its association with adiposity, inflammation, and oxidative stress in schoolchildren.MethodsA total of 1488 schoolchildren ages 7 to 11 y were recruited in Harbin, China (latitude: 44°04′N–46°40′N) in May. Serum 25(OH)D, which is an indicator of vitamin D status, was determined. Anthropometric data were collected following general physical examinations. Serum lipids, glucose metabolism indices, inflammatory molecules, and oxidative stress markers were determined. Dietary intake and physical activity also were assessed.ResultsThe median serum 25(OH)D concentration was 18.4 ng/mL. Of the 1488 schoolchildren included, 839 (56.4%) had vitamin D deficiency [25(OH)D < 20 ng/mL]. Children in the vitamin D deficiency group had significantly higher body weight (34.1 ± 3.8 versus 31.5 ± 3.3 kg; P < 0.001), body mass index (18.4 ± 2.2 versus 16.8 ± 1.7 kg/m²; P < 0.001), waist circumference (60.1 ± 8.5 versus 57.2 ± 7.7 cm; P < 0.001), percentage of body fat (20.2% ± 2.6% versus 19.1% ± 2.4%; P < 0.001), and significantly lower concentrations of serum superoxide dismutase (95.38 ± 12.22 versus 127.62 ± 15.98 U/mL; P < 0.001) compared with those in the vitamin D sufficiency group. After adjusting for sex, age, body mass index, and percentage of body fat, a positive association between serum 25(OH)D and superoxide dismutase was found (β = 0.230; P < 0.001).ConclusionsVitamin D deficiency is common in Harbin schoolchildren. Serum 25(OH)D is closely associated with adiposity and superoxide dismutase in schoolchildren, suggesting that vitamin D deficiency potentially increases the risk for diseases caused by higher adiposity and oxidative stress.     

Vitamin D status and hypertensive disorders in pregnancy

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

Effects of vitamin D3 and calcium supplementation on serum levels of tocopherols, retinol, and specific vitamin D metabolites

γ-Tocopherol (γT) protects against DNA-damaging effects of nitrogen oxides, yet its physiologic regulation in vivo is unknown. Observational studies indicate inverse associations of 25[OH]-vitamin D with γT and leptin. To determine whether vitamin D(3) supplementation alters levels of lipid-soluble micronutrients, serum samples (N = 85 subjects) from a randomized, double-blind, placebo-controlled clinical trial of vitamin D(3) (800 IU) and calcium (2 g), alone and in combination, were analyzed for lipid micronutrients and specific vitamin D metabolites at baseline and after 6 mo of supplementation. Serum 25[OH]-vitamin D(3) levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas 25[OH]-vitamin D(2) levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the vitamin D(3) and vitamin D(3) plus calcium groups, respectively. At baseline, γT levels were inversely associated with 25[OH]D (r = -0.31, P = 0.004). With vitamin D(3) plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), whereas similar changes in γT (19% lower, P = 0.14) were observed. No significant effects were observed for D(3) supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D(3) ± calcium affects serum tocopherol and 25[OH]D(2) levels; however, studies using larger, more homogeneous populations are warranted.     

Vitamin D Deficiency in Cord Plasma from Multiethnic Subjects Living in the Tropics

Background: Vitamin D deficiency is commonly reported in high-latitude areas and in dark-pigmented individuals. However, nothing is known about vitamin D in cord blood from multiethnic subjects living in the tropics.

Objective: Our study objective was to determine the prevalence of vitamin D deficiency in summer and winter in cord blood from multiethnic individuals in Hawai’i where sufficient sun irradiance occurs year-round for cutaneous vitamin D production.

Methods: 25-Hydroxyvitamin D (25(OH)D) levels were quantified by enzyme immunoassay in 100 cord plasma samples from apparently healthy full-term newborns and their mothers. Stratification was performed by birth season and ethnicity.

Results: Mean 25(OH)D levels were 24.5 ng/mL (9.1–68.3 ng/mL). Overall, 28% of samples were vitamin D deficient (<20 ng/mL) and 50% were insufficient (20–30 ng/mL). 25(OH)D levels (ng/mL) were highest in Caucasians (30.5, n = 19), followed by Asians (25.1, n = 43), Hispanics (21.5, n = 3), Pacific Islanders (20.0, n = 25), and African Americans (19.6, n = 2). Differences among groups were significant (p = 0.008). Cord plasmas from summer versus winter were higher overall (p = 0.001) and among Asians (p = 0.0003). Seasonal changes were correlated with sun irradiance overall (r = 0.43, p = 0.0001), among Caucasians (r = 0.45, p = 0.05), and among Asians (r = 0.45, p = 0.0001).

Conclusion: Our results suggest that prenatal supplement recommendations of 400 IU vitamin D/day do not protect against vitamin D deficiency, even in subjects living in the tropics where ample sun irradiance exists for cutaneous vitamin D synthesis. The high prevalence of vitamin D deficiency we observed emphasizes the necessity for regular 25(OH)D monitoring, particularly during pregnancy and lactation, in dark-pigmented individuals, and during winter months.     

Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis

BackgroundGiven the high rates of vitamin D deficiency among pregnant women and possible effects on offspring health, a systematic review on this topic was conducted to help inform future practice guidelines.ObjectiveTo evaluate associations between maternal vitamin D supplementation, maternal 25-hydroxyvitamin D (25(OH)D) concentrations, and health outcomes.MethodsA PubMed literature search was conducted to identify studies that examined the health effects of vitamin D supplementation during pregnancy on maternal and infant health outcomes published from 2000 to 2016. Among 976 identified publications, 20 randomized clinical trials met the inclusion criteria. The initial search was extended to include five studies published between July 2016 and September 2018.Main outcome measuresMaternal and infant 25(OH)D concentrations, gestational diabetes, preeclampsia or gestational hypertension, cesarean section, maternal parathyroid hormone and calcium concentrations, and infant gestational age, birth weight, and birth length.Statistical analysesMean differences, odds ratios, and 95% CIs were calculated, only for the initial search, using separate random-effects meta-analyses for each outcome.ResultsEvidence was good or strong that maternal vitamin D supplementation significantly increased maternal (13 studies, n=18, mean difference, 14.1 ng/mL [35.2 nmol/L]; 95% CI=9.6-18.6 ng/mL [24.0-46.4 nmol/L]) and infant (nine studies, n=12; 9.7, 5.2, 14.2 ng/mL [24.2, 12.9, 35.5 nmol/L]) 25(OH)D concentrations, although heterogeneity was significant (I²=95.9% and I²=97.4, respectively, P<0.001). Evidence was fair that vitamin D supplementation significantly decreases maternal homeostatic model assessment-insulin resistance (five studies, n=7; −1.1, −1.5, −0.7) and increases infant birth weight (nine studies, n=11, 114.2, 63.4, 165.1 g), both had insignificant heterogeneity. A null effect of maternal supplementation on other maternal (preeclampsia, cesarean section) and infant (gestational age, birth length) outcomes was found.ConclusionsResults show vitamin D supplementation during pregnancy improves maternal and infant 25(OH)D concentrations and may play a role in maternal insulin resistance and fetal growth. To further inform practice and policies on the amount of vitamin D, which supports a healthy pregnancy, high quality dose-response randomized clinical trials, which assess pregnancy-specific 25(OH)D thresholds, and appropriately powered clinical outcomes are needed.     

Plasma 25-Hydroxyvitamin D Responses of Younger and Older Men to Three Weeks of Supplementation with 1800 IU/day of Vitamin D

Objective: The objective of this study was to compare changes in plasma 25-hydroxyvitamin D (25(OH)D) levels of younger and older men after three weeks of oral vitamin D supplementation.

Methods: Nine younger men (22 to 28 years) and nine older men (65 to 73 years) with self-reported vitamin D intakes below 200 IU/d were enrolled in February and randomized to 1800 IU/d of ergocalciferol (vitamin D₂, n=11) or to a control group (n=7) and followed for three weeks. Blood was collected at baseline, and after one, two and three weeks for measurement of plasma concentrations of total 25(OH)D, 25(OH)D₂ and 25(OH)D₃.

Results: In both the younger and older supplemented men, 25(OH)D₂ and total 25(OH)D concentrations increased significantly during the study, whereas values of these metabolites did not change in younger or older control subjects. No group showed significant changes in 25-hydroxyvitamin D₃. There was a significant interaction between age group and supplement group, suggesting that the effect of vitamin D₂ supplementation on changes in 25(OH)D₂ changes with age. The mean increase in 25(OH)D₂ was greater in the younger supplemented men than in the older supplemented men (37±9 nmol/L vs. 19.5 nmol/L, p=0.027), and this accounted for their significantly greater increase in total 25(OH)D.

Conclusion: These data are consistent with an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed vitamin D.     

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

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

An updated systematic review and meta-analysis of the efficacy of vitamin D food fortification

Food fortification is a potentially effective public health strategy to increase vitamin D intakes and circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We updated a previous systematic review to evaluate current evidence from randomized controlled intervention studies in community-dwelling adults of the effect of fortified foods on 25(OH)D concentrations. Ovid MEDLINE, PubMed, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled intervention studies with vitamin D-fortified foods in free-living adults and data on circulating 25(OH)D. Two reviewers independently screened 441 papers for eligibility and extracted the relevant data. A meta-analysis of the absolute mean change in circulating 25(OH)D concentrations was conducted using a random effects model. Sixteen studies from 15 publications were included, of which 14 showed a significant effect of fortified foods on 25(OH)D concentrations. Heterogeneity was high (P = <0.0001, I(2) = 89%) and was partly explained by dose, latitude (range, 3-60°), and baseline 25(OH)D (range, 24.0-83.6 nmol/L). When combined in a random effects analysis (n = 1513; 767 treated, 746 controls), a mean individual intake of ~11 μg/d (440 IU/d) from fortified foods (range, 3-25 μg/d) increased 25(OH)D by 19.4 nmol/L (95% CI: 13.9, 24.9), corresponding to a 1.2 nmol/L (95% CI: 0.72, 1.68) increase in 25(OH)D for each 1 μg ingested. Vitamin D food fortification increases circulating 25(OH)D concentrations in community-dwelling adults. Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health.