Serum calcium normal range in 1000 term newborns.

INTRODUCTION: Serum calcium rapidly declines at birth because of the sudden interruption of the maternal-fetal calcium influx. Several factors are known to influence serum calcium in the first days of life, including circulating concentrations of maternal vitamin D. Objective was to establish the normal range variations of neonatal serum calcium according to the French current vitamin D supplementation during pregnancy, i.e. 100,000 IU of cholecalciferol during the third trimester. METHODS: We included in our prospective cohort study 1002 mother-newborn dyads from, with recruitments from April 2012 to July 2014 in France, in two recruiting centers located in Paris neighborhoods. RESULTS: Total serum calcium at 3 days of life in neonates varied from 2.06 to 2.73 mmol/L [2.5 and 97.5 percentiles], with a mean of 2.45 mmol/L. Serum calcium was similar between babies born from vitamin D supplemented mothers and those born from the non-supplemented ones. Univariate and multivariable analyses demonstrated the importance of maternal and cord blood 25(OH)D concentrations for newborn serum calcium maintenance. CONCLUSION: We established that the expected serum calcium in neonates ranges between 2.06 and 2.73 mmol/L which is significantly wider than the adult range. This finding should help physicians in the diagnosis of hypo- or hypercalcemia. In addition, our study supports the importance of vitamin D supplementation and 25(OH)D status for neonatal serum calcium maintenance.

Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.

OBJECTIVES: Inherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations. DESIGN: Retrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13). METHODS: We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth. RESULTS: Overall final height (n = 69) was below target height (TH): -0.9(1.4) vs. -0.1(0.9) SD, p < 0.001. Final height was ≤ TH-2SD in 12 (21%) patients. Height ≤ - 2SD was more frequent during puberty than during early-infancy and pre-puberty: 23.5% vs. 6.9%, p = 0.002; and vs. 10.7%, p < 0.001. Pubertal delay was frequent (26.7%). Height (SD) was positively associated with isoleucine concentration: ß, 0.008; 95%CI, 0.003 to 0.012; p = 0.001. In the pubertal subgroup, height (SD) was lower in patients with vs. without AAM supplementation: -1.22 (1.40) vs. -0.63 (1.46) (p = 0.02). In OA, height and median (IQR) isoleucine and valine concentrations(µmol/L) during puberty were lower in patients with vs. without AAM supplementation: -1.75 (1.30) vs. -0.33 (1.55) SD, p < 0.001; and 40 (23) vs. 60 (25) (p = 0.02) and 138 (92) vs. 191 (63) (p = 0.01), respectively. No correlation was found with IGF1. Lean-mass index was lower than fat-mass index: -2.03 (1.15) vs. -0.44 (0.89), p < 0.001. CONCLUSIONS: In IAAMDs, growth retardation worsened during puberty which was delayed in all disease subgroups. Height seems linked to the disease, AAM composition and lower isoleucine concentration, independently of the GH-IGF1 pathway. We recommend close monitoring of diet during puberty.

Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial.

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).

Cholecalciferol (vitamin D3) must not be considered as an endocrine disruptor / Le cholécalciférol (la vitamine D3) ne doit pas être inclus dans la liste des perturbateurs endocriniens

A French ministerial decree planning to include cholecalciferol, i.e. vitamin D3 (VD3), in the endocrine disruptors (ED) list has generated a lot of concerns in French physicians and scientists. The aim of the present article was to discuss the scientific rationale that may support or not this decision, which seems to be due to the use of VD3 overdose as a rodenticide in some European countries. First, it is noticeable that cholecalciferol is not an "exogenous substance", a term used in all the definitions of ED, as it is largely synthesized in the skin after UVB rays exposure. Second, we did not find any published article that may support the inclusion of VD3 in the ED list. The request "vitamin D AND endocrine disruptor" reported 33 references in the PubMed database on March, 10, 2022, most of them discussing disturbances of vitamin D metabolism by EDs. Third, a large amount of studies conclude that VD3 has or may have beneficial effects on many functions that are known to be altered by EDs. In addition, we warn that learning that VD3 could be legally considered as a PE may cause the general public to mistrust vitamin D supplementation, which is not desirable in terms of public health as it may increase the already too high prevalence of vitamin D deficient individuals. We consider the aberrant decision of including cholecalciferol in the ED list should be rapidly invalidated before being effective in France and possibly disseminated in the European Union.

Un projet d'arrêté ministériel inscrivant le cholécalciférol, c'est-à-dire la vitamine D3 (VD3), dans la liste des perturbateurs endocriniens (PE) est à l'origine de débats en France. L'objectif de notre article était de préciser les arguments scientifiques pour et contre l'inscription de la VD3 dans la liste des PE, qui semble être initialement due à son utilisation à très forte dose comme raticide/rodenticide dans certains pays. Premièrement, le cholécalciférol ne peut être défini comme une substance exogène, terme utilisé dans les différentes définitions des PE, car il est largement synthétisé dans la peau suite à l'exposition aux UVB. Deuxièmement, il n'existe aucune publication dans la base de données PubMed en faveur d'une inscription de la VD3 dans la liste des PE. La requête « vitamin D AND endocrine disruptor ¼ retrouvait 33 références au 10 mars 2022, la plupart évoquant des perturbations du métabolisme de la vitamine D par les PE. Troisièmement, un grand nombre d'études concluent, au contraire, que la VD3 a des effets bénéfiques sur de nombreuses fonctions altérées par les PE. Plus largement, nous alertons sur le fait qu'apprendre que la VD3 pourrait être règlementairement considérée comme un PE pourrait occasionner, auprès du grand public, une défiance vis-à-vis de la supplémentation en vitamine D, ce qui n'est pas souhaitable en termes de santé publique car de nature à aggraver la prévalence déjà trop élevée des individus carencés en vitamine D. Il est encore temps d'éviter cette décision aberrante et non fondée.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation.

Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients.

Vitamin D supplementation and COVID-19: expert consensus and guidelines.

After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. Given the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives some hope of curbing the pandemic. Vitamin D is a possible candidate drug which is discussed in a high number of publications. Randomised clinical trials have shown that vitamin D supplementation significantly reduces the risk of respiratory infections. There is also a great deal of evidence that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D, present in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.

[Vitamin D supplementation and COVID-19: expert consensus and guidelines]. / Supplémentation en vitamine D et Covid-19 : consensus d'experts et recommandations.

After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. With the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Vitamin D is a possible candidate discussed in a high amount of publications. Randomized clinical trials show that vitamin D supplementation significantly reduces the risk of respiratory infections. There are also many evidences that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D found in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.

Vitamin D and pregnancy outcomes: Overall results of the FEPED study.

Vitamin D insufficiency is highly prevalent in children and adults including pregnant women. During pregnancy, maternal vitamin D insufficiency could increase risks of several pregnancy complications and adverse birth outcomes. The FEPED study was designed to assess the effects of maternal vitamin D status in the first trimester during pregnancy on risks of preeclampsia, gestational diabetes mellitus (GDM), preterm birth and small-for-gestational age (SGA) at birth. This observational prospective cohort included 3129 women with a singleton pregnancy between April 2012 and July 2014 in six maternity units in France and Belgium. The aim of this review is to summarize the results of the FEPED study. At the first trimester the mean 25(OH)D concentration was 21.9 ± 10.4 ng/mL and 25(OH)D concentration was <20 ng/mL in 46.5 % of patients. After matching 83 cases of preeclampsia with 319 controls, a significant decrease in the risk of preeclampsia was associated with maternal vitamin D levels ≥ 30 ng/mL in the third trimesters (OR = 0.34; 95 % CI: 0.13-0.86. P = 0.023). In the first trimester, the risk for preeclampsia was decreased in these patients, but did not achieve statistical significance (OR = 0.57 95 % CI, 0.30-1.01; p = 0.09). For the 250 cases with GDM matched with 941 controls, no linear relationship was found between GDM and 25OHD levels in the first trimester of pregnancy. Finally, 2813 pregnant women were included in analyses of risks of preterm and SGA birth. No association was found between low maternal vitamin D levels in the first trimester and the risks of preterm birth (aOR = 1.53; 95 % CI: 0.97-2.43) or SGA (aOR = 1.07; 95 % CI: 0.75-1.54). Further investigation is needed to understand the mechanisms behind the association between vitamin D and birth outcomes.

Vitamin D Supplementation in France in patients with or at risk for osteoporosis: Recent data and new practices.

With intermittent vitamin D supplementation, serum 25-hydroxyvitamin D (25OHD) levels may remain stable only if the dosing interval is shorter than 3 months, the ideal perhaps being about 1 month. Recent data support moderate daily vitamin D doses instead of high intermittent doses, notably in elderly patients prone to falls. The level of evidence is low, however, with no head-to-head comparisons of clinical outcomes such as fractures and falls in groups given identical dosages daily versus intermittently. A challenge to daily vitamin D supplementation in France is the absence of a suitable pharmaceutical formulation. In addition, daily dosing carries a high risk of poor adherence. Until suitable vitamin D3 formulations such as tablets or soft capsules each containing 1000 or 1500 IU become available, we suggest intermittent supplementation according to 2011 GRIO guidelines. Among the available dosages, the lowest should be preferred, with the shortest possible interval, e.g., 50,000 IU monthly rather than 100,000 every two months.

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE).

OBJECTIVE: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). METHODS: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 µg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]). RESULTS: The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups. CONCLUSIONS: Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01198132. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.

Vitamin D, bone alkaline phosphatase and parathyroid hormone in healthy subjects and haemodialysed patients from West Africa: impact of reference ranges and parathyroid hormone generation assays on the KDIGO guidelines.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend targets based on multiples of the upper limit of normal (ULN) of parathyroid hormone (PTH) concentration. However, the ULN has not always been correctly established by manufacturers. While it is known that the ULN is supposed to be higher in African Americans than in Caucasians, it is largely unknown in Africans. METHODS: We established the ULN of PTH concentration in a population of 240 healthy Ivorians using second- and third-generation PTH assays before and after supplementation with 100 000 IU of cholecalferol. We measured the levels of PTH, bone alkaline phosphatase, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 100 haemodialysed Ivorian patients. RESULTS: The prevalence of vitamin D deficiency in Ivory Coast is low. The ULN obtained using the third-generation PTH assay was similar to that obtained in Caucasians but was higher when PTH was measured using the second-generation PTH assay. According to the KDIGO guidelines, ∼20% of the haemodialysed patients were below twice the ULN and 30% were above nine times the ULN. Approximately 25% of the patients were even >12 times the ULN. We observed a discrepancy in the results between the two PTH assays (14%) that was relatively more important than what we observed from previous studies in Caucasians using the same strategy. CONCLUSIONS: We found a low prevalence of vitamin D deficiency in a tropical country like Ivory Coast. We also established the PTH reference range, which could prove useful for the follow-up of haemodialysed patients, particularly for the large number of patients suffering from secondary hyperparathyroidism who are at high risk of adverse bone events.

Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule.

Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint was the area under the curve (AUC) of serum 25-hydroxyvitamin-D (25(OH)D) concentrations on Day 112. This study was conducted in France from February to June 2014 in 53 young adults with a mean age of 26.9 years. At baseline, low mean serum 25(OH)D levels were observed in both groups (10.6 ng/mL in Group 1 and 9.0 ng/mL in Group 2). On Day 112, the AUC of serum 25(OH)D concentration was 2499.4 ± 463.8 nmol/mL (7.8 ± 0.2 for LogAUC) for Group 1 and 2152.3 ± 479.8 nmol/mL (7.6 ± 0.2 for LogAUC) for Group 2. Bioequivalence of the two treatments was not demonstrated. Superiority of vitamin D3 100,000 IU soft capsule was observed with p = 0.029 for AUC and p = 0.03 for LogAUC using a non-parametric Wilcoxon test. The profile of the serum 25(OH)D concentration showed a significant difference in favor of Group 1 on Days 1, 3, 7, 14 and 90. Mean serum 25(OH)D concentrations in Group 1 were between 20 and 30 ng/mL during the four-month period and under 20 ng/mL throughout the study in Group 2, except on Day 112. Mean Cmax for Group 1 was significantly higher (p = 0.002). Fourteen days were needed to reach Tmax by more than half the subjects in Group 1 compared to 45 days in Group 2. Both treatments were well tolerated, with no severe or related adverse events reported. In conclusion, the pharmacokinetic profile of the new formulation of vitamin D3 100,000 IU soft capsule is superior to that of the oral solution in ampoule. The new formulation increased serum 25(OH)D levels to above 20 ng/mL and maintained levels from 20 ng/mL to 30 ng/mL for four months in late winter and spring.

Vitamin D status during pregnancy and in cord blood in a large prospective French cohort.

BACKGROUND & AIMS: Vitamin D status during pregnancy and in newborns has never been studied in France. This study aims at determining the vitamin D status during the first and third trimesters of pregnancy (T1, T3) and in cord blood (CB) in the middle-north of France. METHODS: We conducted a prospective cohort study in five French centers (latitude 47.22 to 48.86°N). Serum 25(OH)-vitamin D (25(OH)D) concentrations were measured using a radioimmunoassay during T1, T3 and in CB. According to the French guidelines, pregnant women received cholecalciferol, 100,000 IU, in the seventh month. RESULTS: Between April 2012 and July 2014, 2832 women were included, of whom 2803 were analyzed (mean ± SD age: 31.5 ± 5.0 years; phototypes 5-6: 21.8%). Three and 88.6% of participants received supplementation during the month before inclusion and in the seventh month, respectively. At T1, T3, and CB, mean 25(OH)D concentrations were 21.9 ± 10.4, 31.8 ± 11.5, and 17.0 ± 7.2 ng/mL, respectively, and 25(OH)D was <20 ng/mL in 46.5%, 14.0%, and 68.5%, respectively. At T1, body mass index ≥25 kg/m2, dark phototypes, sampling outside summer, and no supplementation before inclusion were independently associated with vitamin D insufficiency (25(OH)D < 20 ng/mL). Women who received cholecalciferol supplementation in month 7 had higher 25(OH)D at T3 than non-supplemented women (32.5 ± 11.4 versus 25.8 ± 11.4 ng/mL, p = <0.001) and marginally higher 25(OH)D in CB (17.2 ± 7.2 versus 15.5 ± 7.1 ng/mL, p = 0.004). CONCLUSIONS: Despite the recommended supplementation, vitamin D insufficiency is frequent during pregnancy and in newborns in France.

A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D3 Supplementation.

We aimed to determine whether a cumulative dose of vitamin D3 produces the same effects on the serum concentration of 25(OH)D3 if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D3 daily or 50,000 IU monthly. The same cumulative dose of vitamin D3 was given to each treatment group (150,000 IU). The 25(OH)D3 serum concentrations from baseline to day 75 were 14.3 ± 3.7 to 27.8 ± 3.9 ng/mL in the monthly group and 14.1 ± 3.4 to 28.8 ± 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D3, as expected, serum 25(OH)D3 and 1,25(OH)2D3 increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D3 provides an effective tool for a rapid normalization of 25(OH)D3 in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL.

Vitamin D in adults: update on testing and supplementation.

Hypovitaminosis D, a frequent condition in adults, is accompanied by adverse skeletal and non-skeletal events. The objective of the present article was to propose an update on the indications and use of vitamin D testing and supplementation in adults. Among healthy middle-aged adults, the serum 25-hydroxyvitamin D (25(OH)D) target concentration is 50 nmol/L. Natural intakes (sun exposure and diet) are sufficient, and there is no indication for systematic blood test or supplementation. In middle-aged adults who are either sick or dependent or frail, natural intakes are generally insufficient but should be encouraged. In this population, the loading phase of the supplementation targets a 25(OH)D concentration of 75 nmol/L, and the pattern of supplementation (200,000 to 400,000 IU orally over 2 months) depends on the measure of circulating 25(OH)D (which is not reimbursed outside the scope defined by the French national authority for health). In adults over 65 years of age, the loading phase of the supplementation should be systematic and targets a concentration of 75 nmol/L (pattern of 300,000 IU orally over 3 months). Regardless of age, the loading phase should be followed by a long-term maintenance phase of supplementation to maintain the 25(OH)D concentration above the target. A measure of serum 25(OH)D is useful after 9 months of supplementation to adjust the frequency or dosage of supplements if necessary.

Vitamin D and multiple sclerosis: An update.

The most recent findings linking exposure to sun and vitamin D insufficiency to multiple sclerosis (MS) are reviewed. Due to insufficient sunshine and changing lifestyles, hypovitaminosis D is widespread in temperate countries. Numerous epidemiological studies have strongly suggested that sunshine and vitamin D insufficiency contributes to MS risk in these countries. Moreover, several large genetic studies in MS patients have recently stated unequivocally that diverse abnormalities involving vitamin D metabolism are related to the risk of the disease. The important implications of such results are discussed here. Then, the interactions of hypovitaminosis D with the other genetic and environmental protective and risk factors, such as the allele HLA DRB1*1501, Epstein-Barr virus infection, obesity, smoking and sexual hormones, are summarized. Vitamin D insufficiency and sufficiency could be a risk and a protective factor, respectively, among many other factors possibly continuously modulating the global MS risk from the mother's pregnancy to the triggering of MS in adulthood. However, many interactions between these different factors occur more particularly between conception and the end of adolescence, which corresponds to the period of maturation of the immune system and thymus and may be related to the dysimmune nature of the disease. The main mechanisms of action of vitamin D in MS appear to be immunomodulatory, involving the various categories of T and B lymphocytes in the general immune system, but neuroprotector and neurotrophic mechanisms could also be exerted at the central nervous system level. Furthermore, several controlled immunological studies performed in MS patients have recently confirmed that vitamin D supplementation has multiple beneficial immunomodulatory effects. However, there is still an enduring absence of major conclusive randomized clinical trials testing vitamin D supplementation in MS patients because of the quasi-insurmountable practical difficulties that exist nowadays in conducting and completing over several years such studies involving the use of a vitamin. Nevertheless, it should be noted that similar robust statistical models used in five different association studies have already predicted a favorable vitamin D effect reducing relapses by 50-70%. If there is now little doubt that vitamin D exerts a beneficial action on the inflammatory component of MS, the results are as yet much less clear for the progressive degenerative component. Lastly, until more information becomes available, vitamin D supplementation of MS patients, using a moderate physiological dose essentially correcting their vitamin insufficiency, is recommended.