The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14–16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data ...available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25‐hydroxyvitamin D 25(OH)D concentration i.e. the sum of 25(OH)D3 and 25(OH)D2 remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers e.g. 1α,25(OH)2D3, 3‐epi‐25(OH)D, 24,25(OH)2D3, vitamin D‐binding protein, free/bioavailable 25(OH)D and parathyroid hormone be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml–1 (30 nmol l–1) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml–1 and 50 ng ml–1 (50–125 nmol l–1) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed.
Abstract
Context
Vitamin D is classically recognized as a regulator of calcium and phosphorus metabolism. Recent advances in the measurement of vitamin D metabolites, diagnosis of vitamin D ...deficiency, and clinical observations have led to an appreciation that along with its role in skeletal metabolism, vitamin D may well have an important role in nonclassical settings. Measurement of the circulating form of vitamin D that best describes total body stores, namely 25-hydroxyvitamin D, can be unreliable despite many sophisticated methodologies that have been proposed and implemented. Likewise, evidence from clinical studies showing a beneficial role of vitamin D in different disease states has been controversial and at times speculative. Moreover, the target concentrations of 25-hydroxyvitamin D to address a number of putative links between vitamin D inadequacy and nonskeletal diseases are further areas of uncertainty.
Setting
To address these issues, an international conference on “Controversies in Vitamin D” was held in Pisa, Italy, in June 2017. Three main topics were addressed: (i) vitamin D assays and the definition of hypovitaminosis D; (ii) skeletal and extraskeletal effects of vitamin D; (iii) therapeutics of vitamin D.
Results
This report provides a summary of the deliberations of the expert panels of the conference.
Conclusions
Despite great advances in our appreciation of vitamin D metabolism, measurements, biological actions on classical and nonclassical tissues, and therapeutics, all of which this report summarizes, much more work remains to be done so that our knowledge base can become even more secure.
This summary statement reports the deliberations and conclusions of an international conference on “Controversies in Vitamin D.”
The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D 25(OH)D concentrations measured by standardized liquid chromatography-tandem mass spectrometry.
We ...describe patterns for total 25(OH)D and individual metabolites in persons aged ≥1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables.
We measured 25-hydroxycholecalciferol 25(OH)D3, 25-hydroxyergocalciferol 25(OH)D2, and C3-epimer of 25(OH)D3 C3-epi-25(OH)D3 in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES total 25(OH)D = 25(OH)D3 + 25(OH)D2.
Concentrations (median, detection rate) of 25(OH)D3 (63.6 nmol/L, 100%) and C3-epi-25(OH)D3 (3.40 nmol/L, 86%) were generally detectable; 25(OH)D2 was detectable in 19% of the population. Total 25(OH)D, 25(OH)D3, and C3-epi-25(OH)D3 displayed similar demographic patterns and were strongly correlated (Spearman's r > 0.70). Concentrations of 25(OH)D2 (90th percentile) were much higher in persons aged ≥60 y (17.3 nmol/L) than in younger age groups (≤4.88 nmol/L). We noted significant race-ethnicity differences in mean total 25(OH)D non-Hispanic blacks (NHBs), Hispanics, and non-Hispanic whites (NHWs): 46.6, 57.2, and 75.2 nmol/L, respectively and in the prevalence of total 25(OH)D <30 nmol/L overall (24% of NHBs, 6.4% of Hispanics, and 2.3% of NHWs) as well as stratified by season (winter months: 30% of NHBs, 7.5% of Hispanics, and 3.8% of NHWs; summer months: 17% of NHBs, 4.4% of Hispanics, and 1.6% of NHWs). Persons with higher vitamin D intakes (diet, supplements, or both) and those examined during May-October had significantly higher total 25(OH)D. Significant race-ethnicity interactions in a multiple linear regression model confirmed the necessity of providing race-ethnicity-specific estimates of total 25(OH)D.
Race-ethnicity differences in the prevalence of low total 25(OH)D remained strong even after adjustment for season to account for the NHANES design imbalance between season, latitude, and race-ethnicity. The strong correlation between C3-epi-25(OH)D3 and 25(OH)D3 may be because the epimer is a metabolite of 25(OH)D3. The presence of 25(OH)D2 mainly in older persons is likely a result of high-dose prescription vitamin D2.
Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D 25(OH)D measurements.
To accurately assess vitamin D status trends ...among those aged ≥12 y, we used data from the cross-sectional NHANESs.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446). Weighted arithmetic means and the prevalence of 25(OH)D above or below cutoff concentrations were calculated to evaluate long-term trends.
Overall, mean predicted 25(OH)D showed no time trend from 1988 to 2006, but during 2007-2010 the mean measured 25(OH)D was 5-6 nmol/L higher. Those groups who showed the largest 25(OH)D increases (7-11 nmol/L) were older, female, non-Hispanic white, and vitamin D supplement users. During 1988-2010, the proportions of persons with 25(OH)D <40 nmol/L were 14-18% (overall), 46-60% (non-Hispanic blacks), 21-28% (Mexican Americans), and 6-10% (non-Hispanic whites).
An accurate method for measuring 25(OH)D showed stable mean concentrations in the US population (1988-2006) and recent modest increases (2007-2010). Although it is unclear to what extent supplement usage compared with different laboratory methods explain the increases in 25(OH)D, the use of higher vitamin D supplement dosages coincided with the increase. Marked race-ethnic differences in 25(OH)D concentrations were apparent. These data provide the first standardized information about temporal trends in the vitamin D status of the US population.
Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a ...lesser role. Our objectives were to assess UVB availability (Jm(-2)) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51-54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe.
Our objective in this study was to estimate calcium intakes from food, water, dietary supplements, and antacids for U.S. citizens aged ≥1 y using NHANES 2003-2006 data and the Dietary Reference ...Intake panel age groupings. Similar estimates were calculated for vitamin D intake from food and dietary supplements using NHANES 2005-2006. Diet was assessed with 2 24-h recalls; dietary supplement and antacid use were determined by questionnaire. The National Cancer Institute method was used to estimate usual nutrient intake from dietary sources. The mean daily nutrient intake from supplemental sources was added to the adjusted dietary intake estimates to produce total usual nutrient intakes for calcium and vitamin D. A total of 53% of the U.S. population reported using any dietary supplement (2003-2006), 43% used calcium (2003-2006), and 37% used vitamin D (2005-2006). For users, dietary supplements provided the adequate intake (AI) recommendation for calcium intake for ~12% of those ≥71 y. Males and females aged 1-3 y had the highest prevalence of meeting the AI from dietary and total calcium intakes. For total vitamin D intake, males and females ≥71, and females 14-18 y had the lowest prevalence of meeting the AI. Dietary supplement use is associated with higher prevalence of groups meeting the AI for calcium and vitamin D. Monitoring usual total nutrient intake is necessary to adequately characterize and evaluate the population's nutritional status and adherence to recommendations for nutrient intake.
ABSTRACT
Aims As part of a larger study to estimate the global burden of disease attributable to alcohol:
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to quantify the relationships between average volume of alcohol consumption, patterns of ...drinking and disease and injury outcomes, and
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to combine exposure and risk estimates to determine regional and global alcohol‐attributable fractions (AAFs) for major disease and injury categories.
Design, methods, setting Systematic literature reviews were used to select diseases related to alcohol consumption. Meta‐analyses of the relationship between alcohol consumption and disease and multi‐level analyses of aggregate data to fill alcohol–disease relationships not currently covered by individual‐level data were used to determine the risk relationships between alcohol and disease. AAFs were estimated as a function of prevalence of exposure and relative risk, or from combining the aggregate multi‐level analyses with prevalence data.
Findings Average volume of alcohol consumption was found to increase risk for the following major chronic diseases: mouth and oropharyngeal cancer; oesophageal cancer; liver cancer; breast cancer; unipolar major depression; epilepsy; alcohol use disorders; hypertensive disease; hemorrhagic stroke; and cirrhosis of the liver. Coronary heart disease (CHD), unintentional and intentional injuries were found to depend on patterns of drinking in addition to average volume of alcohol consumption. Most effects of alcohol on disease were detrimental, but for certain patterns of drinking, a beneficial influence on CHD, stroke and diabetes mellitus was observed.
Conclusions Alcohol is related to many major disease outcomes, mainly in a detrimental fashion. While average volume of consumption was related to all disease and injury categories under consideration, pattern of drinking was found to be an additional influencing factor for CHD and injury. The influence of patterns of drinking may be underestimated because pattern measures have not been included in many epidemiologic studies. Generalizability of the results is limited by methodological problems of the underlying studies used in the present analyses. Future studies need to address these methodological issues in order to obtain more accurate risk estimates.
Vitamin D deficiency in Europe: pandemic? Cashman, Kevin D; Dowling, Kirsten G; Škrabáková, Zuzana ...
The American journal of clinical nutrition,
04/2016, Letnik:
103, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D 25(OH)D distribution data for the European Union are of very variable quality. The NIH-led international ...Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys.
This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe.
The VDSP protocols were applied in 14 population studies reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n= 55,844). Prevalence estimates of vitamin D deficiency using various serum 25(OH)D thresholds were generated on the basis of standardized 25(OH)D data.
An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations.
Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.
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