Serum 25(OH)D response to vitamin D3 supplementation: A meta-regression analysis

ObjectiveThe aim of this study was to review factors that influence serum 25(OH)D when patients are given vitamin D supplements.MethodsFrom a comprehensive search of all randomized controlled clinical trials with vitamin D₃ supplementation available on PubMed up to November 2011, we selected 33 with 43 treatment arms that included at least 30 adult participants. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses were performed for prespecified factors, including dose, duration, baseline serum 25(OH)D, and age.ResultsWith a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37 nmol/L (95% CI, 33–41) with significant heterogeneity among studies. Dose (slope: 0.006; P < 0.001), trial duration (slope: 0.21; P < 0.001), baseline serum 25(OH)D (slope: −0.19; P < 0.001), and age (slope: 0.42; P < 0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In subgroup analyses, the PMD was higher with doses ≥800 IU/d (39.3 nmol/L) after 6 to 12 mo (41.7 nmol/L), with baseline 25(OH)D <50 nmol/L (39.6 nmol/L), and in adults aged >80 y (40.5 nmol/L).ConclusionThis meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of ≥800 IU/d, after at least 6 to 12 mo, and even when baseline 25(OH)D is low and in adults >80 y.     

Serum 25-hydroxyvitamin D levels and the risk of depression: A systematic review and meta-analysis

Objective

No quantitative systematic review or meta-analysis of population-based epidemiological studies has been conducted to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of depression. This study aimed to summarize the current evidence from cross-sectional and prospective cohort studies that have evaluated the association between 25(OH)D levels and the risk of depression.

Methods

Relevant studies were identified by systematically searching the PubMed, EMBASE, Web of Science, and PsycINFO databases through April 2012. Cross-sectional and cohort studies that reported adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of interest were included. The reported risk estimates for 25(OH)D categories were recalculated, employing a comprehensive trend estimation from summarized dose-response data. A pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models.

Results

In the meta-analysis, 25(OH)D levels were significantly inversely associated with depression in 5 of 11 case-control studies and 2 of 5 cohort studies. The pooled estimate of the adjusted OR of depression in 11 cross-sectional studies (n = 43,137) was 0.96 (95% CI = 0.94–0.99, I² = 63%) for a 10 ng/ml increase in 25(OH)D levels. The 5 included cohort studies comprised 12,648 participants, primarily elderly individuals, whose serum 25(OH)D levels were measured, and 2,663 experienced depression events during follow-up. The pooled adjusted OR of depression was 0.92 (95% CI = 0.87–0.98, I² = 50%) for a 10 ng/ml increase in 25(OH)D levels.

Conclusions

Our results indicate an inverse association between serum 25(OH)D levels and the risk of depression. Further studies are warranted to establish whether this association is causal.     

A systematic review of vitamin D status in southern European countries

Purpose

Despite an acknowledged dearth of data on serum 25-hydroxyvitamin D (25(OH)D) concentrations from Southern European countries, inter-country comparison is hampered by inconsistent data reporting. The purpose of the current study was to conduct a systematic literature review of available data on serum 25(OH)D concentrations and estimate vitamin D status in Southern European and Eastern Mediterranean countries, both at a population level and within key population subgroups, stratified by age, sex, season and country.

Methods

A systematic review of the literature was conducted to identify and retrieve scientific articles reporting data on serum 25(OH)D concentration and/or vitamin D status following standard procedures.

Results

Data were extracted from 107 studies, stratified by sex and age group, representing 630,093 individuals. More than one-third of the studies reported mean 25(OH)D concentrations below 50 nmol/L and ~?10% reported mean serum 25(OH)D concentrations below 25 nmol/L. Overall, females, neonates/ infants and adolescents had the higher prevalence of poor vitamin D status. As expected, there was considerable variability between studies. Specifically, mean 25(OH)D ranged from 6.0 (in Italian centenarians) to 158 nmol/L (in elderly Turkish men); the prevalence of serum 25(OH)D?<?50 nmol/L ranged from 6.8 to 97.9% (in Italian neonates).

Conclusions

Contrary to expectations, there was a high prevalence of low vitamin D status in the Southern Europe and the Eastern Mediterranean regions, despite abundant sunshine. These data further emphasize the need for strategies, such as fortification of foods with vitamin D and/or vitamin D supplementation, which will be tailored to the needs of specific population groups with higher risk of insufficiency or deficiency, to efficiently tackle the pandemic of hypovitaminosis D in Europe.

     

Vitamin D supplementation,body weight and human serum 25-hydroxyvitamin D response: a systematic review

Purpose

There is considerable variation in incremental circulating 25-hydroxyvitamin D (25OHD) levels on vitamin D supplements, even when similar age groups and identical vitamin D doses are compared. We therefore aimed to investigate the importance of body weight for the dose–response relation in circulating 25OHD.

Methods

We performed a systematic review of randomized placebo-controlled vitamin D supplementation trials in all age groups ≥10 years to clarify the influence of body weight and other parameters on incremental circulating 25OHD levels (difference between baseline and in-study values) in vitamin D-deficient and non-deficient individuals.

Results

We included 144 cohorts from 94 independent studies, published from 1990 to November 2012, in our systematic review. There was a logarithmic association between vitamin D dose per kg body weight per day and increment in circulating 25OHD. In multivariable regression analysis, vitamin D dose per kg body weight per day could explain 34.5 % of variation in circulating 25OHD. Additional significant predictors were type of supplement (vitamin D₂ or vitamin D₃), age, concomitant intake of calcium supplements and baseline 25OHD, explaining 9.8, 3.7, 2.4 and 1.9 %, respectively, of the variation in circulating 25OHD.

Conclusions

This systematic review demonstrates that body weight is an important predictor of variation in circulating 25OHD in cohorts on vitamin D supplements. Our model provides an estimate of the daily vitamin D dose that is necessary for achieving adequate circulating 25OHD levels in vitamin D-insufficient or vitamin D-deficient individuals/cohorts with different body weights and ages.     

Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: A systematic review and meta-analysis

Objective

To conduct a systematic review and meta-analysis of longitudinal studies on the association of 25(OH)D with total cancer incidence and mortality.

Method

Relevant longitudinal observational studies were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases. Due to the heterogeneity across studies in categorizing 25(OH)D concentration, all results were recalculated for an increase of 25(OH)D by 50 nmol/L.

Results

In meta-analyses with random effects models, the summary risk ratios and confidence intervals (RRs (95% CI)) for the association of an increase of 25(OH)D by 50 nmol/L with total cancer incidence (5 studies) and mortality (13 studies) were 0.89 (0.81, 0.97) and 0.83 (0.71, 0.96), respectively. In sex-specific analyses no significant association with total cancer incidence was observed among men or women. A clear inverse association with total cancer mortality was observed among women (0.76 (0.60, 0.98)) but not among men (0.92 (0.65, 1.32)). Large heterogeneity was observed for studies on total cancer mortality (P < 0.01) but not for studies on cancer incidence (P = 0.41). No publication bias was found.

Conclusion

The meta-analysis suggests a moderate inverse association of 25(OH)D concentration with total cancer incidence and mortality.     

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

Background  

Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk.     

The response of serum 25-hydroxyvitamin D concentrations to vitamin D intake and insolation in sheep

1. Vitamin D-depleted, housed sheep were given diets providing fixed intakes of cholecalciferol ranging from 0.0 to 0.8 microgram/kg body-wt per d for 220 d. Thereafter they were shorn, deprived of dietary cholecalciferol and turned out from 30 June to 30 November. The concentration of 25-hydroxyvitamin D (25-OHD) in serum was determined at frequent intervals. 2. The serum concentrations of 25-OHD took approximately 10 weeks to stabilize after which they reflected dietary intake over 0.1--0.4 microgram/kg body-wt per d. For intakes of 0.4 and 0.8 microgram/kg body-wt per d the mean maximum concentrations were similar, but the rates of increase differed. The latter was proportional to the logarithm of intake over the range studied. 3. Changes in serum 25-OHD due to insolation were similar in all sheep regardless of their starting values, and consequently in some animals reached levels considerably greater than from the dietary source. 4. Although the response of serum 25-OHD to the higher dietary intakes appeared to be limited there was no evidence of any such control over the response ot endogenously-synthesized vitamin.     

25-hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs--but the meat produced has a lower content of vitamin D

In food databases, the specific contents of vitamin D3 and 25-hydroxyvitamin D3 in food have been implemented in the last 10 years. No consensus has yet been established on the relative activity between the components. Therefore, the objective of the present study was to assess the relative activity of 25-hydroxyvitamin D3 compared to vitamin D3. The design was a parallel study in pigs (n 24), which from an age of 12 weeks until slaughter 11 weeks later were fed approximately 55 microg vitamin D/d, as vitamin D3, in a mixture of vitamin D3 and 25-hydroxyvitamin D3, or 25-hydroxyvitamin D3. The end-points measured were plasma 25-hydroxyvitamin D3, and in the liver and loin the content of vitamin D3 and 25-hydroxyvitamin D3. Vitamin D3 and 25-hydroxyvitamin D3 in the feed did not affect 25-hydroxyvitamin D3 in the plasma, liver or loin differently, while a significant effect was shown on vitamin D3 in the liver and loin (P < 0.001). 25-Hydroxyvitamin D3 in the plasma, liver and loin significantly correlates with the sum of vitamin D3 and 25-hydroxyvitamin D3 in the feed (P < 0.05). Therefore, 25-hydroxyvitamin D3 should be regarded as having the same activity as vitamin D3 in food databases. Sole use of 25-hydroxyvitamin D3 as a vitamin D source in pig feed will produce liver and meat with a negligible content of vitamin D3, while an increased content of vitamin D3 in the feed will produce liver and meat with increased content of both vitamin D3 and 25-hydroxyvitamin D3.     

25羟维生素D水平与心血管疾病关系的Meta分析

目的定量评价25羟维生素D水平与心血管疾病的关系。方法检索以中英文全文发表的,研究体内25羟维生素D水平与心血管疾病关系的定量研究;采用Meta分析方法,应用Stata 11.0软件进行数据处理,对入选的8篇文献进行综合定量分析,并按国家、样本量对研究冠心病的文献进行亚组分析。结果 Meta分析表明25羟维生素D水平与心血管疾病发病相关,冠心病患者血清25羟维生素D水平较普通人群低1.66 ng/ml,心衰病人体内25羟维生素D较普通人群低10.17 ng/ml。25羟维生素D水平与冠心病的亚组分析结果显示,同欧洲冠心病人群相比,北美洲冠心病患者血清25羟维生素D降低的程度更明显(北美:WMD=-2.15;欧洲:WMD=-0.96),且在样本量过千的研究中体现的更加明显(WMD=-2.15,95%CI:-3.32~-0.98)。结论心血管疾病患者体内25羟维生素D水平明显低于正常人,心衰患者降低程度更为明显,提示可通过补充维生素D降低心血管疾病的发病率。     

Association between plasma 25-hydroxyvitamin D and colorectal adenoma according to dietary calcium intake and vitamin D receptor polymorphism

The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.     

Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis

Injecting and non-injecting drug users are at increased risk of contracting HBV infection, and show lower antibody response to hepatitis B vaccination compared to the general population. This systematic review and meta-regression analysis aimed to estimate seroprotection rates and identify host or vaccine factors associated with varying immune response following hepatitis B vaccination in drug using populations. Original research articles were searched using online databases (Medline, PubMed, and Embase) and from reference lists of eligible articles. HBV vaccine intervention studies reporting seroprotection rates in drug users, published in English during or after 1989 were eligible. Of 978 citations reviewed, 11 studies were eligible and included for final analysis. The reported seroprotection rates ranged from 54.5% to 97.1%. The studies were significantly heterogeneous (Q = 180.850, p = 0.000). Measurement of anti-HBs antibody at 2 months after the third vaccine dose (RR = 2.62, 95%CI = 1.16–5.94, p = 0.026) was significantly associated with higher seroprotection rates compared to measurement at 1 month and 6 month following third vaccine dose. Age, gender, current drug use, vaccine dose and schedule, anti-HBc, anti-HCV and anti-HIV antibody seropositivity, and proportion of IDU study population did not show a significant association with seroprotection rates. Recommendations for future research include the definition of a standardized time point for the measurement of anti-HBs antibody levels, to enhance comparability of the immune response between different studies. Studies should strive to accurately report all potentially relevant factors affecting immune response to vaccine. Long-term follow up studies are needed to assess the seroprotection status in drug using populations receiving hepatitis B vaccine by standard or accelerated schedules.     

The routine chemiluminescence assay for plasma 25-hydroxyvitamin D analysis does not overestimate the prevalence of vitamin D deficiency in adolescents

Vitamin D deficiency (VDD) is a global public health problem. Inaccurate methods for measuring plasma 25-hydroxyvitamin D (25[OH]D) may have contributed to the reported high prevalence of VDD. We hypothesized that the most commonly used assay for vitamin D status, chemiluminescence immunoassay (CLIA), underestimates 25(OH)D levels and thus overestimates VDD. Using both liquid chromatography–tandem mass spectrometry and CLIA for plasma 25(OH)D, we evaluated the prevalence of VDD in adolescents (11-16 years-old; n = 410) by both methods in a cross-sectional study. Subjects were selected from public middle schools from all the 6 Governorates of Kuwait using stratified multistage cluster random sampling. Cohen κ agreement, linear regression, and Bland-Altman plots were used to evaluate the classification of VDD by the 2 methods. VDD (25[OH]D < 50 nmol/L) was 85.9% with CLIA and 81.2% with liquid chromatography–tandem mass spectrometry. There was a good agreement between the 2 methods in classifying the study subjects as deficient, insufficient, or sufficient (κ = 85.1%, P < .001). The between-assay bias was very small with a mean percentage difference < 1% from the mean value of the 25(OH)D as assessed by the 2 methods. These data did not support our hypothesis, and we conclude that the routine methods used for plasma 25(OH)D levels have no or little impact on evaluating VDD as a public health problem or in clinical management.     

Serum 25-hydoxyvitamin D concentrations in relation to Hashimoto’s thyroiditis: a systematic review,meta-analysis and meta-regression of observational studies

European Journal of Nutrition - Available evidence on the relation between vitamin D status and Hashimoto’s thyroiditis (HT) remains inconsistent. We conducted a meta-analysis of serum...