Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a Bayesian network meta-analysis of randomized controlled trials.

Background: Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels. Methods: Three databases including Medline, EMBASE, and the Cochrane Library were systematically searched up to 10 November 2020. The risk of bias was evaluated according to Cochrane Collaboration's tool for rating methodological quality assessment. Direct and indirect comparisons between interventions and controls were performed by a Bayesian network meta-analysis (NMA), where the mean difference (MD) and its 95% confidence interval (CI) were used to indicate the efficacy. Results: This NMA analysis included 116 RCTs with a total of 11,376 participants. Generally, we observed that 25(OH)D concentrations were significantly elevated regardless of vitamin D supplementation frequency. Although the findings of SUCRA indicated that daily vitamin D supplementation had a higher rank value than intermittent supplementation when the supplement dosage was similar, no statistically significant pooled mean differences of 25(OH)D concentration were noted between the daily supplementation group and intermittent supplementation group. Additionally, weekly supplementation with a total of 600,000 IU vitamin D supplementation during 3 months had the best efficacy in elevating 25(OH)D concentration (pooled MD = 63 nmol/L, 95%CI: 49-77). To achieve optimal 25(OH)D concentration (>75 nmol/L), we recommend 60,000 IU vitamin D supplementation monthly (~2,000 IU/day). Conclusion: The efficacy of intermittent vitamin D supplementation was similar to daily supplementation. Coupled with its convenience, the frequency and dosage of intermittent vitamin D supplements were recommended to reach the optimal 25(OH)D level.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257257, PROSPERO CRD42021257257.

Association of Vitamin D in Different Trimester with Hemoglobin during Pregnancy.

The association between vitamin D and hemoglobin has been suggested. Vitamin D can affect erythropoiesis by the induction of erythroid progenitor cell proliferation and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes. However, this relationship in pregnant women is scarce. The purpose of this study was to investigate the association between plasma vitamin D levels with hemoglobin concentration in pregnant women considering each trimester and iron supplementation. The data were obtained from Zhoushan Pregnant Women Cohort, collected from 2011 to 2018. Plasma 25(OH)D was measured in each trimester using liquid chromatography−tandem mass spectrometry. Generalized estimating equations and multiple linear regressions were performed. Finally, 2962 pregnant women and 4419 observations in the first trimester were included in this study. Plasma 25(OH)D in first trimester (T1) (ß = 0.06, p = 0.0177), second trimester (T2) (ß = 0.15, p < 0.0001), and third trimester (T3) (ß = 0.12, p = 0.0006) were positively associated with Hb. Association between plasma 25(OH)D levels in T1 and Hb concentration was positively associated with gestational age (ß = 0.005, p = 0.0421). Pregnant women with VD deficiency in T1 (OR = 1.42, 95% CI: 1.07−1.88) or T2 (OR = 1.94, 95% CI: 1.30−2.89) presented an increased risk of anemia, compared with women without VD deficiency. Moreover, the significant relationship between VD and Hb was only observed among women with iron supplementation during pregnancy. Plasma 25(OH)D levels in each trimester were positively associated with Hb concentration. Iron supplementation might be an important factor affecting the relationship between VD and Hb.

Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement.

BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS: A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS: The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS: The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.

Hemoglobin concentration and iron supplement during pregnancy were associated with an increased risk of gestational diabetes mellitus.

BACKGROUND: Hemoglobin (Hb) measurement is a conventional test during perinatal visits. Hb concentration is related to iron supplement. However, studies focusing on Hb levels, iron supplement, and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels and iron supplement were associated with the risk of gestational diabetes mellitus (GDM). METHODS: A running hospital-based cohort was conducted from August, 2011. The demographic data and medical information were collected individually through questionnaires and patient medical records. Multiple linear regression was applied for the association between Hb levels, iron supplement, and blood glucose. Multiple logistic regression was used for evaluating odds ratios between Hb levels, iron supplement, and GDM. RESULTS: Hb levels during first (T1) and second trimester (T2) of pregnancy were significantly and positively associated with blood glucose and GDM risk. After adjusting for age, prepregnancy body mass index, and other risk factors, pregnant women with Hb ≥ 11 g/dL and iron supplement had higher postprandial blood glucose at 1 hour (Hb ≥ 11 g/dL in T2 and iron supplement in T1: ß = 0.860，P = <0.001; Hb ≥ 11 g/dL in T2 and iron supplement in T2: ß = 0.960，P < 0.001; Hb ≥ 11 g/dL in T1 and iron supplement in T2: ß = 1.133, P = 0.033) and GDM risks (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.05-2.24; OR = 1.92, 95% CI: 1.13-3.35; OR = 2.15, 95% CI: 1.07-4.34, respectively), compared with those with Hb < 11 g/dL and without iron supplement. CONCLUSION: High Hb concentration and iron supplements without anemia increased postprandial blood glucose and risks for GDM. It indicates that pregnant women with good Hb levels should not be advised to take iron supplements during pregnancy.

Vitamin D nutrient status during pregnancy and its influencing factors.

BACKGROUND: Little is known about variation of vitamin D (VD) status during pregnancy among Chinese women. This study is to assess the change of VD status during pregnancy and its influencing factors among Chinese women. METHODS: A running cohort study has being conducted in southeast China. The pregnant women were interviewed and the peripheral blood samples were collected at the first (T1), second (T2) and third trimester (T3), respectively. 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography tandem-mass spectrometry. Multiple linear and logistic regression models were applied to explore the associations of VD supplement with 25(OH)D concentration and VD deficiency, respectively. RESULTS: There were 4368 pregnant women enrolled in the current study. The 25(OH)D concentration increased notably with gestational week. The average plasma 25(OH)D concentration in T1, T2 and T3 was 18.94 ± 8.74, 23.05 ± 11.15, and 24.65 ± 11.59 ng/mL, respectively. Correspondingly, VD deficiency (25(OH)D < 20 ng/mL) rate was 65.26%, 33.56% and 32.12%. In T1 phase, higher pre-pregnancy BMI, more parity, sampling in summer/autumn were related to higher 25(OH)D level, and similar patterns were observed in T2 and T3 phase. There was positive dose-response effect between VD supplement frequency and 25(OH)D concentration during pregnancy, adjusting for potential confounders (T1: ß(SE) = 3.907 (0.319), P < 0.001; T2: ß(SE) = 2.780 (0.805), P < 0.001; T3: ß(SE) = 3.640 (1.057), P = 0.006). Not surprisingly, supplementing VD > 3 times/week reduced the risk of VD deficiency during pregnancy significantly, compared to without VD supplement (T1: OR = 0.30, 95% CI: 0.24-0.37; T2: 0.56, 0.38-0.82; T3: 0.67, 0.44-0.96). CONCLUSION: VD level increased with gestational week among Chinese pregnant women. High frequency of VD supplement during pregnancy is an effective way to reduce risk of VD deficiency, especially among the pregnant women with younger age, low prepregnancy BMI and primipara, and during winter and spring season.

A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe.

BACKGROUND/OBJECTIVES: Optimal doses of vitamin D (VitD) supplement in different populations are unclear. We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [25(OH)D] concentration, to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different populations. SUBJECTS/METHODS: Literature search was conducted in Embase, etc. Randomized controlled trials about VitD supplemental intakes and their effect on 25(OH)D concentration were enrolled. The effect on 25(OH)D concentration between different supplementation doses in each population group was compared by meta-analysis. Multivariate meta-regression model is utilized to establish reference intake dosage of VitD. RESULTS: A total of 136 articles were included about children (3-17 years), adults (18-64 years), postmenopausal women, the elderly ( >64 years), pregnant, or lactating women. Overall, intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose-response effect between intake dose and 25(OH)D concentration. Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration. To reach sufficient 25(OH)D concentration (75 nmol/L), the recommended VitD supplemental intakes was 1340 and 2250 IU/day for children and pregnant women, 2519 and 797 IU/day for European adults aged 18-64 and 65-85 years, 729, 2026, and 1229 IU/day for adults in North America, Asia and Middle East and Africa, respectively. CONCLUSIONS: Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested.

Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women.

AIMS: To explore the relationship between vitamin D pathway genes, gene-environment interactions and vitamin D level among southeast Chinese pregnant women. METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester. Information on demographics, lifestyle, and health behavior were collected using a questionnaire. Multilinear regression and logistic regression models were performed to estimate the associations between SNPs and 25(OH)D level. RESULTS: Mean plasma 25(OH)D concentrations were 15.6 ng/mL among the pregnant women. Variants of GC rs16846876, rs17467825, rs2282679, rs3755967, rs2298850, rs4588, rs7041 and rs1155563, CYP3A4 rs2242480 and CYP24A1 rs2209314 were significantly associated with both 25(OH)D concentrations and vitamin D deficiency (25(OH)D < 15 ng/mL). Variants of NADSYN1/DHCR7 were significantly associated with 25(OH)D concentrations among pregnant women without vitamin D supplements. Pregnant women with vitamin D binding protein (Gc) Gc-1f (P = 0.02) and Gc-1s (P = 0.005) had higher plasma 25(OH)D levels compared to women with Gc-2. Genotype risk score (GRS) calculated from rs7041, rs2242480 and rs2209314 shown a significantly negative association with 25(OH)D levels. Participants with GRS > 3 had a higher risk for vitamin D deficiency than individuals with GRS ≤ 3 (OR = 1.71, 95% CI = 1.25-2.35). Interactions between seasons and CYP27A1 rs933994, CYP3A4 rs2246709 on plasma 25(OH)D concentrations were also observed. Haplotypes of GC and LRP2 genes shown significant associations with 25(OH)D levels among pregnant women, respectively. CONCLUSIONS: Genetic mutants in vitamin D pathway (GC, CYP3A4, CYP24A1, and NADSYN1/DHCR7) had significant associations with 25(OH)D levels among pregnant women in southeast China. Furthermore, their associations were modified by vitamin D supplementation and season.

Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children and White-Collar Workers.

OBJECTIVE: Our study aimed to investigate the nutritional vitamin D status of school children aged 9-15 years and white-collar workers in Zhejiang province, and evaluate the efficacy of low-dose-oral vitamin D supplementation in both populations. METHODS: We conducted a prospective controlled trial during March 2014 to November 2015, comparing the efficacy of vitamin D supplements (400 IU/day) with non-intervention for 18 months in school children aged 9-15 years. Meanwhile, a before-after study was conducted among white-collar workers for 1 year. Serum 25(OH)D concentration was measured at baseline and after vitamin D supplementation, respectively. RESULTS: At the baseline, 95% of school children and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school children, no difference was observed between the intervention and control groups with regard to anthropometric data. Serum 25(OH)D concentrations of the school children intervention group, school children control group and white-collar workers were 12.77 ± 3.01 ng/mL, 14.17 ± 3.59 ng/mL and 16.58 ± 3.66 ng/mL at baseline and increased to 17.34 ± 3.78 ng/mL, 18.04 ± 4.01 ng/mL and 17.75 ± 5.36 ng/mL after vitamin D supplementation, respectively. Although, after adjusting for potential confounders, the 400 IU oral vitamin D supplementation increased serum 25(OH)D concentration in school children (ß = 0.81, p = 0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of vitamin D deficiency was still very high among school children (79.23% in intervention group and 72.38% in control group) and white-collar workers (76.00%). CONCLUSIONS: High prevalence of vitamin D deficiency was common in these two study populations. Daily doses of 400 IU oral vitamin D supplementation was not able to adequately increase serum 25(OH)D concentrations. A suitable recommendation regarding the level of vitamin D supplementation is required for this Chinese population.