Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.
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ABSTRACT:
SUBMITTER: Akhtar E
PROVIDER: S-EPMC4979151 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
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Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.
Akhtar Evana E Mily Akhirunnesa A Haq Ahsanul A Al-Mahmud Abdullah A El-Arifeen Shams S Hel Baqui Abdullah A Roth Daniel E DE Raqib Rubhana R
Nutrition journal 20160809 1
<h4>Background</h4>Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear.<h4>Method</h4>To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 w ...[more]
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Project description:Clinical trials are scant and equivocal on whether vitamin D can ameliorate arterial stiffness, particularly in populations at high risk for vitamin D deficiency and cardiovascular disease (CVD). This study determined the dose-response effects of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency.Seventy overweight African Americans (aged 13-45 years) with serum 25-hydroxyvitamin D [25(OH)D] levels ? 20 ng/mL were randomized to monthly oral supplementation of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), or 120,000 IU (~4000 IU/day, n = 18) of vitamin D3 or placebo (n = 17) for 16-weeks. The arterial stiffness measurements, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV, were assessed by applanation tonometry at baseline and 16 weeks.Vitamin D3 supplementation demonstrated a dose-response increase in serum 25(OH)D concentrations between groups (P<0.01). A significant downward linear trend was observed for carotid-femoral PWV (P<0.01), as the mean changes in carotid-femoral PWV across the four treatment groups were 0.13 m/s (95% CI: -0.24, 0.51 m/s) for placebo, 0.02 m/s (95% CI: -0.34, 0.38 m/s) for 600 IU/day group, -0.11 m/s (95% CI: -0.50, 0.27 m/s) for the 2,000 IU/day group, and -0.70 m/s (95% CI: -1.07, -0.32 m/s) for the 4,000 IU/day group. Findings were similar for carotid-radial PWV (P = 0.03), as the mean changes in carotid-radial PWV across the four treatment groups were 0.24 m/s (95% CI: -0.45, 0.92 m/s) for placebo, 0.09 m/s (95% CI: -0.54, 0.73 m/s) for 600 IU/day group, -0.57 m/s (95% CI: -1.20, 0.07 m/s) for the 2,000 IU/day group, and -0.61 m/s (95% CI: -1.25, 0.02 m/s) for the 4,000 IU/day group.Arterial stiffness was improved by vitamin D3 supplementation in a dose-response manner in overweight African Americans with vitamin D deficiency.
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Project description:OBJECTIVE:Supplementing lactating mothers with high doses of vitamin D3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D3 dosing in lactating mothers on vitamin D3 catabolism. We hypothesized that catabolism of 25(OH)D3 to 24,25(OH)2D3 would be greater in the bolus than in the daily dose group. DESIGN, SETTING AND PATIENTS:Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women. INTERVENTIONS:Subjects were randomized to receive vitamin D3 orally, either a single dose of 150,000IU or 5000IU daily for 28days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28days. MAIN OUTCOME MEASURE:Temporal changes in the serum 24,25(OH)2D3/25(OH)D3 ratio. RESULTS:The concentration of serum 24,25(OH)2D3 was directly related to that of 25(OH)D in both groups (r2=0.63; p<0.001). The mean (±SD) 24,25(OH)2D3/25(OH)D3 ratio remained lower at all time points than baseline values in the daily dose group (0.093±0.024, 0.084±0.025, 0.083±0.024, 0.080±0.020, 0.081±0.023, 0.083±0.018 at baseline, 1, 3, 7, 14, and 28days, respectively). In the single dose group, the increase in 24,25(OH)2D3 lagged behind that of 25(OH)D, but the 24,25(OH)2D3/25(OH)D3 values (0.098±0.032, 0.067±0.019, 0.081±0.017, 0.092±0.024, 0.103±0.020, 0.106±0.024, respectively) exceeded baseline values at 14 and 28days and were greater than the daily dose group at 14 and 28days (p=0.003). The 24,25(OH)2D3/25(OH)D3 ratio remained in the normal range with both dosing regimens. Greater breast milk vitamin D3 values in the single dose group were inversely associated with the 24,25(OH)2D3/25(OH)D3 ratio (r2=0.14, p<0.001), but not with daily dosing. CONCLUSIONS:After a 14-day lag, a single high dose of vitamin D led to greater production of 24,25(OH)2D3, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D3 value than did daily vitamin D supplementation, and this effect persisted for at least 28days after vitamin D administration. A daily dose of vitamin D may have more lasting effectiveness in increasing 25(OH)D3 with lesser diversion of 25(OH)D3 to 24,25(OH)2D3 than does larger bolus dosing.
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Project description:BackgroundHypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D(3) administered to apparently healthy schoolchildren.MethodsTo assess short-term safety, 25 subjects randomly received placebo or vitamin D(3) at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D(3) as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study.ResultsIn both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (+/- 11) to 54 (+/- 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 +/- 8 to 19 +/- 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 +/- 7 to 36 +/- 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication.ConclusionVitamin D(3) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels.
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Project description:Anti-Müllerian hormone (AMH) is a paracrine regulator of ovarian follicles. Vitamin D (Vit D) regulates AMH production in vitro, but its role as a regulator of ovarian AMH production is contentious. If Vit D influences ovarian AMH production, then an acute rise in Vit D level should lead to an acute rise in circulating AMH levels. This hypothesis was tested with a randomized double-blind design, with 18-25-year-old women recruited from the community. The study was conducted in early spring, when the marker of Vit D level (25-hydroxyvitamin D, 25(OH)D) tends to be at its nadir. The women consumed either an oral dose of 50,000 IU of Vit D3 (n = 27) or placebo (n = 22). The initial 25(OH)D ± SD value was 53.6 ± 23.3 nmol/L, with 42 of the 49 women having a value below 75 nmol/L, consistent with seasonal nadir. All women receiving Vit D3 treatment exhibited a robust increase in serum 25(OH)D within 1 day (15.8 ± 1.1 nmol/L (n = 27), p < 0.0001), with the increase sustained over the study week. Circulating levels of AMH in the women receiving Vit D3 progressively rose during the following week, with a mean increase of 12.9 ± 3.7% (n = 24, p = 0.001). The study supports the hypothesis that Vit D's positive effects on the fertility of woman may involve the regulation of ovarian AMH levels.
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Project description:BACKGROUND:A critical need exists to better understand the physiological sequel of vitamin D supplementation in obese individuals and African Americans. The aim was to comprehensively evaluate dose- and time-responses of a panel of vitamin D biomarkers to vitamin D supplements in this population. METHODS:We conducted a 16-week randomized, double-blinded, and placebo-controlled clinical trial. Seventy overweight/obese African Americans (age 13-45 years, 84 % females) with 25-hydroxyvitamin D [25(OH)D] concentrations ?20 ng/mL were randomly assigned to receive a supervised monthly oral vitamin D3 of 18,000 IU (~600 IU/day, n?=?17), 60,000 IU (~2000 IU/day, n?=?18), 120,000 IU (~4000 IU/day, n?=?18), or placebo (n?=?17). RESULTS:There were significant dose- and time-responses of circulating 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and intact parathyroid hormone (iPTH), but not fibroblast growth factor-23 (FGF-23), phosphorus and urine calcium to the vitamin D supplements. The mean 25(OH)D concentrations in the 2000 IU and 4000 IU groups reached ?30 ng/mL as early as 8-weeks and remained at similar level at 16-weeks. The increase of 25(OH)D was significantly higher in the 4000 IU group than all the other groups at 8-weeks. The increase of 1,25(OH)2D was significantly higher in the 2000 IU and 4000 IU groups than the placebo at 8-weeks. Only the 4000 IU compared to the placebo significantly reduced iPTH at 8- and 16-weeks. CONCLUSIONS:Our RCT, for the first time, comprehensively evaluated time- and dose- responses of vitamin D supplementation in overweight/obese African Americans with suboptimal vitamin D status. Circulating 25(OH)D, 1,25(OH)2D, and iPTH, but not FGF-23, phosphorus and urine calcium, respond to vitamin D supplementation in a time- and dose-response manner. By monthly dosing, 2000 IU appears to be sufficient in achieving a 25(OH)D level of 30 ng/mL in this population. However, importantly, 4000 IU, rather than 2000 IU, seems to suppress iPTH. If replicated, these data might be informative in optimizing vitamin D status and providing individualized dosing recommendation in overweight/obese African Americans. TRIAL REGISTRATION:ClinicalTrials.gov number: NCT01583621, Registered on April 3, 2012.
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Project description:Objectives:Obese, African-American (AA) adolescents are at increased risk for vitamin D deficiency. The primary objective of this pilot study was to examine the effect of vitamin D supplementation upon 25-hydroxy vitamin D (25OHD) levels in obese, AA adolescents. Methods:A randomized, double-blinded, controlled pilot study included 26 obese (BMI???95%ile), vitamin D deficient (25OHD?<?20?ng/mL), pubertal AA adolescents (ages 12-17). Subjects received cholecalciferol 1000?IU or 5000?IU daily for 3?months. Serum 25OHD, vitamin D binding protein, parathyroid hormone, and cardiometabolic risk markers were obtained at baseline and post-treatment. Results:Of 39 subjects enrolled, 26 (67%) were vitamin D deficient (mean 25OHD 12.0?±?3.8?ng/mL) at baseline and were randomized, with 22 completing the study. Sex, age, season, pubertal stage, BMI, insulin resistance (HOMA-IR) and 25OHD were similar at baseline between the 1000?IU and 5000?IU groups. Post-treatment, 25OHD increased less in the 1000?IU group (5.6?ng/mL, p?=?0.03) vs. the 5000?IU group (15.6?ng/mL, p?=?0.002). 83% of the 5000?IU group and 30% of the 1000?IU group reached post-treatment 25OHD???20?ng/mL (p?=?0.01); 50% of the 5000?IU group, but no subject from the 1000?IU group, achieved 25OHD???30?ng/mL (p?=?0.009). We detected no group differences in mineral metabolites or cardiometabolic risk markers following supplementation. Conclusions:Cholecalciferol dosing in excess of the current Institute of Medicine dietary reference intakes was required to achieve 25OHD levels ?20?ng/mL in obese, AA adolescents. Supplementation of 5000?IU may be required to achieve the desired goal.
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