It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D 25(OH)D in human subjects was performed and led to the definition of "normal" nutritional vitamin D ...status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing "normal" circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D </= 80 nmol or 32 microg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.
We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 ...years of age. However, neither reached statistical significance.
To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect.
VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry.
The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57-0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33-0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62-1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points.
This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies.
COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The number of assessments of circulating 25-hydroxyvitamin D 25(OH)D for diagnostic purposes has increased significantly during the past 5 y. Over the years, techniques for quantifying 25(OH)D have ...increased and evolved. Some changes have been for the better and some have not. Most current methods appear to provide valid results as long as the operator of the given technique is properly trained and motivated. In addition, any laboratory that assesses circulating 25(OH)D for clinical diagnosis needs to participate in the Vitamin D External Quality Assessment Scheme. Finally, research has shown that circulating 25(OH)D is extremely stable in stored serum or plasma samples; this characteristic makes accurate, long-term epidemiologic studies of circulating 25(OH)D possible. In this article, I provide an overview of the techniques available for measuring 25(OH)D, compare these techniques with one another, and assess their clinical utility. I also briefly discuss the stability of 25(OH)D in biological media and present an overview of the Vitamin D External Quality Assessment Scheme.
Context:
There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation ...process—be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process.
Objective:
In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue.
Conclusions:
Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.
Pregnancy is a time of tremendous growth and physiological changes for mother and her developing fetus with lifelong implications for the child. The concert of actions that must occur so mother does ...not reject the foreign tissue of the fetus is substantial. There must be exquisite balance between maternal tolerance to these foreign proteins of paternal origin but also immune surveillance and function such that the mother is not immunocompromised. When this process goes awry, the mother may experience such pregnancy complications as preeclampsia and infections. Vitamin D deficiency affects these processes. Controversy continues with regard to the optimal daily intake of vitamin D, when sunlight exposure should be taken into account, and how to define sufficiency during such vulnerable and critical periods of development. The importance of vitamin D supplementation during pregnancy in preventing some of the health risks to the mother and fetus appears linked to achieving 25(OH)D concentrations >40 ng/mL, the beginning point of the plateau where conversion of the vitamin D metabolite 25(OH)D, the pre-hormone, to 1,25(OH)
D, the active hormone, is optimized. Throughout pregnancy, the delivery of adequate vitamin D substrate-through sunlight or supplement-is required to protect both mother and fetus, and when in sufficient supply, favorably impacts the epigenome of the fetus, and in turn, long term health. There is a growing need for future research endeavors to focus not only on critical period(s) from pre-conception through pregnancy, but throughout life to prevent certain epigenetic changes that adversely affect health. There is urgency based on emerging research to correct deficiency and maintain optimal vitamin D status. The impact of vitamin D and its metabolites on genetic signaling during pregnancy in both mother and fetus is an area of great activity and still in its early stages. While vitamin D repletion during pregnancy minimizes the risk of certain adverse outcomes (e.g., preterm birth, asthma, preeclampsia, and gestational diabetes), the mechanisms of how these processes occur are not fully understood. As we intensify our research efforts in these areas. it is only a matter of time that such mechanisms will be defined.
Studies have indicated that 25-hydroxyvitamin D (25(OH)D) level in obese is lower than normal weight subjects; however, results of studies that investigated relationship between 25(OH)D and fat mass ...are inconsistent. In addition, several randomized clinical trials (RCTs) have studied the influence of cholecalciferol supplement on percentage fat mass (PFM) but their results are conflicting. The objectives were to investigate the association between vitamin D3 and PFM pooling together observational studies and RCTs. PubMed/MEDLINE, Cochrane, and Scopus were comprehensively searched from inception to September 2016. The Fisher's Z (SE) of correlation coefficient and mean (SD) of changes in PFM from baseline were used to perform meta-analysis in observational studies and RCTs, respectively. To determine potential source of heterogeneity, subgroup and meta-regression analyses were conducted. Pooling correlation coefficients showed an inverse association between PFM (Fisher's Z: - 0.24, 95% CI: - 0.30 to -0 .18) and FM (Fisher's Z: - 0.32, 95% CI: - 0.43 to - 0.22) and 25(OH)D. Subgroup analysis revealed continent but not gender influence on the effect size. Meta-regression analysis indicated that age, latitude, and longitude are not sources of heterogeneity. Combining trials showed vitamin D3 supplementation had a mild but insignificant effect on PFM (- 0.31%, 95% CI: - 1.07 to 0.44). Subgroup analyses indicated that type of cholecalciferol and treatment regimens explain source of heterogeneity. Age, baseline body mass index, dose of cholecalciferol, length of study, female (%), and baseline 25(OH)D are not source of heterogeneity. In conclusion, our results state that 25(OH)D level is inversely correlated with PFM but cholecalciferol supplementation had no effect on PFM.
Abstract
Context
Despite evidence on the association between hypovitaminosis D and adverse pregnancy outcomes and the positive impact of vitamin D supplementation, no evidence exists supporting a ...universal screening program in pregnancy as part of routine prenatal care.
Objective
We sought to determine the effectiveness of a prenatal screening program on optimizing 25-hydroxyvitamin D 25(OH)D levels and preventing pregnancy complications. Also, to identify a safe regimen, we compared several regimens in a subgroup of vitamin D–deficient pregnant women.
Design
Two cities of Masjed-Soleyman and Shushtar from Khuzestan province, Iran, were selected as the screening and nonscreening arms, respectively. Within the screening arm, a randomized controlled trial was conducted on 800 pregnant women.
Setting
Health centers of Masjed-Soleyman and Shushtar cities.
Patients or Participants
Pregnant women aged 18 to 40 years.
Intervention
Women with moderate 25(OH)D, 10 to 20 ng/mL and severe 25(OH)D, <10 ng/mL deficiency were randomly divided into four subgroups and received vitamin D3 (D3) until delivery.
Main Outcome Measure
Maternal concentration of 25(OH)D at delivery and rate of pregnancy complications
Results
After supplementation, only 2% of the women in the nonscreening site met the sufficiency level (>20 ng/mL) vs 53% of the women in the screening site. Adverse pregnancy outcomes, including preeclampsia, gestational diabetes mellitus, and preterm delivery, were decreased by 60%, 50%, and 40%, respectively, in the screening site. A D3 injection in addition to monthly 50,000 IU maintenance therapy contributed the most to achievement of sufficient levels at delivery.
Conclusions
A prenatal vitamin D screening and treatment program is an effective approach in detecting deficient women, improving 25(OH)D levels, and decreasing pregnancy adverse outcomes.
Vitamin D screening policy is beneficial in improving maternal outcomes. A high-dose vitamin D3 administration plus monthly maintenance regimen was efficient in women with baseline levels <20 ng/mL.
Abstract Background Optimal vitamin D intake and its status are important not only for bone and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and ...insufficiency as a global health problem are likely to be a risk for wide spectrum of acute and chronic illnesses. Methods A review of randomized controlled trials, meta-analyses, and other evidence of vitamin D action on various health outcomes. Results Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality. Conclusions Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders. Supplementation guidance and population strategies for the eradication of vitamin D deficiency must be included in the priorities of physicians, medical professionals and healthcare policy-makers.
In a previously published controlled trial, maternal administration of vitamin D during pregnancy was found to protect against wheeze in the offspring at the age of 3 years. In this follow-up study ...involving the same children at the age of 6 years, that supplementation no longer had a protective effect.
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