Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

Source at https://doi.org/10.3390/nu11010074.The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Source at http://doi.org/10.1371/journal.pone.0170791Background:Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.Methods:In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.Findings:We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and Interpretation:In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths

Rapid increases in obesity in Jamaica, compared to Nigeria and the United States

<p>Abstract</p> <p>Background</p> <p>Weight gain in adulthood is now common in many populations, ranging from modest gains in developing countries to a substantial percentage of body weight in some Western societies. To examine the rate of change across the spectrum of low to high-income countries we compared rates of weight change in samples drawn from three countries, Nigeria, Jamaica and the United States.</p> <p>Methods</p> <p>Population samples from Nigeria (n = 1,242), Jamaica (n = 1,409), and the US (n = 809) were selected during the period 1995–1999 in adults over the age of 19; participation rates in the original survey were 96%, 60%, and 60%, respectively. Weight in (kg) was measured on 3 different occasions, ending in 2005. Multi-level regression models were used to estimate weight change over time and pattern-mixture models were applied to assess the potential effect of missing data on estimates of the model parameters.</p> <p>Results</p> <p>The unadjusted weight gain rate (standard error) was 0.34(0.06), 1.26(0.12), 0.34(0.19) kg/year among men and 0.43(0.06), 1.28(0.10), 0.40(0.15) kg/year among women in Nigeria, Jamaica, US, respectively. Regression-adjusted weight change rates were significantly different across country, sex, and baseline BMI. Adjusted weight gain in Nigeria, Jamaica and US was 0.31(0.05), 1.37(.04), and 0.52(0.05) kg/year respectively. Women in Nigeria and the US had higher weight gains than men, with the converse observed among Jamaicans. The obese experienced weight loss across all three samples, whereas the normal weight (BMI < 25) had significant weight gains. Missing data patterns had an effect on the rates of weight change.</p> <p>Conclusion</p> <p>Weight change in sample cohorts from a middle-income country was greater than in cohorts from either of the low- or high-income countries. The steep trajectory of weight gain in Jamaica, relative to Nigeria and the US, is most likely attributable to the accelerating effects of the cultural and behavioral shifts which have come to bear on transitional societies.</p

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary123456

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA

Biomarkers of folate status in NHANES: a roundtable summary123456

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999–2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991–1994 and NHANES 1999–2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007–2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography–tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA

Differences in gut microbiota and fecal bile acids between Caucasian and Hispanic children and young adults with ulcerative colitis

Abstract Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) that has been associated with gut dysbiosis. Changes in the gut microbiome lead to changes in bile acids (BA) metabolism, which changes the BA profiles in patients with UC. We conducted this study to investigate the differences in bile acids and gut microbiota between Hispanic and Caucasian children and young adults with UC. Twenty‐seven Caucasian and 20 Hispanic children and young adults with UC were enrolled in the study. BAs were extracted from the subjects' stool samples and analyzed by liquid chromatography–mass spectrometry. Microbial DNA was also extracted from the stool samples to perform 16s rRNA amplicon sequencing. The median levels of cholic acid and taurolithocholic acid were found to be significantly higher in Hispanic children and young adults with UC compared to their Caucasian counterparts. The abundance of the gut microbiota that metabolizes BAs such as Proteobacteria, Pseudomonadaceae, Pseudomonas, Ruminococcus gnavus, and Escherichia coli were also all significantly higher in Hispanic children and young adults as well. The distinct BA profile that we found in Hispanic children and young adults with UC, in addition to the unique composition of their gut microbiome, provide them with a protective gut environment against inflammation, which is contrary to the common believe that Hispanics have worse IBD

Towards harmonization of directly measured free 25-hydroxyvitamin D using an enzyme-linked immunosorbent assay.

The majority of circulating 25-hydroxyvitamin D (25(OH)D) is protein bound and perhaps less available than the free fraction of 25(OH)D; therefore, researchers have proposed that the measurement of free 25(OH)D in human serum may be a better indicator of vitamin D health status than total 25(OH)D. The availability of a new enzyme-linked immunosorbent assay (ELISA) for the determination of free 25(OH)D provides a method for direct measurement of the low levels of non-protein bound 25(OH)D. As an initial step towards harmonization of measurements of free 25(OH)D, the ELISA was used to measure free 25(OH)D in three existing Standard Reference Materials (SRMs): SRM 972a Vitamin D Metabolites in Frozen Human Serum, SRM 2973 Vitamin D Metabolites in Frozen Human Serum (High Level), and SRM 1949 Frozen Prenatal Human Serum. Target values for free 25(OH)D in the nine SRM serum pools, obtained by combining the results from two laboratories, ranged from 3.76 ± 0.36 to 10.0 ± 0.58 pg/mL. Of particular significance is the assignment of free 25(OH)D target values to SRM 1949, which consists of four serum pools from non-pregnant female donors of reproductive age and pregnant women in each of the three trimesters and which also has values assigned for vitamin D binding protein, which increases during pregnancy. The availability of target values for free 25(OH)D in these SRMs will allow researchers to validate new analytical methods and to compare their results with other researchers as an initial step towards harmonization of measurements among different studies and laboratories

Implications of standardization of serum 25-hydroxyvitamin D data for the evaluation of vitamin D status in Germany, including a temporal analysis

Abstract Background Comparability of 25-hydroxyvitamin D (25(OH)D) measurements is hampered by method-related differences in measurement values. International standardization of laboratory assays has been suggested to solve this problem. Methods As part of the European Commission–funded project ‘Food-based solutions for optimal vitamin D nutrition and health through the life cycle’ (ODIN), original measurements of serum 25(OH)D of three German national health surveys conducted between 1998 and 2011 have been standardized retrospectively. In these representative population-based samples including persons aged between 1 and 79 years, the original 25(OH)D values were compared with those after standardization. Mean values and prevalences of vitamin D deficiency, insufficiency, and sufficiency (25(OH)D levels  =50 nmol/l, respectively) were calculated by sex and age groups based on original and standardized 25(OH)D data. Results In comparison to the original 25(OH)D levels, the standardized levels showed higher means overall and in age- and sex-specific analyses. After standardization, the prevalence of vitamin D deficiency was lower in all surveys while the prevalence of vitamin D sufficiency was higher. Nevertheless, even after standardization ~ 15% of adults and 12.5% of children had serum 25(OH)D levels < 30 nmol/l. Thus, the proportion of deficient vitamin D levels in the German population is still considerable. Conclusions The use of standardization of 25(OH)D levels has a substantial impact on estimates of the vitamin D status in Germany. Since clinical diagnostic, therapeutic and public health decision-making require valid and comparable data, standardization and calibration of commercial, clinical and research laboratory assays for 25(OH)D measurement should become common practice. Until then, researchers, health practitioners and policy makers should be aware of the peculiarities of the measurement methods when comparing and interpreting 25(OH)D levels

Rapid increases in obesity in Jamaica, compared to Nigeria and the United States-2

by time between measurements) by country, Nigeria, Jamaica, and the US for each of three BMI categories (BMI < 25, 25 = 30). Data were collected from 1995 to 1999 from Nigeria, Jamaica and the United States (US). Only participants with at least two weight determinations are depicted in this figure.<p><b>Copyright information:</b></p><p>Taken from "Rapid increases in obesity in Jamaica, compared to Nigeria and the United States"</p><p>http://www.biomedcentral.com/1471-2458/8/133</p><p>BMC Public Health 2008;8():133-133.</p><p>Published online 23 Apr 2008</p><p>PMCID:PMC2390537.</p><p></p