A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49•58°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) versus achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95% lower CI) serum 25(OH)D (nmol/l) = 9•2 (8•5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35µg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0•044 × (total vitamin D) + 33•035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95% lower CI curvilinear and linear models predicted a serum 25(OH)D of 54•4 and 55•2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95% range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake–status relationship needs to be considered carefully when setting new reference intake values in Europe

Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers

Stimulant and non-stimulant drugs can reduce symptoms of attention deficit/hyperactivity disorder (ADHD). The stimulant drug methylphenidate (MPH) and the non-stimulant drug atomoxetine (ATX) are both widely used for ADHD treatment, but their differential effects on human brain function remain unclear. We combined event-related fMRI with multivariate pattern recognition to characterize the effects of MPH and ATX in healthy volunteers performing a rewarded working memory (WM) task. The effects of MPH and ATX on WM were strongly dependent on their behavioral context. During non-rewarded trials, only MPH could be discriminated from placebo (PLC), with MPH producing a similar activation pattern to reward. During rewarded trials both drugs produced the opposite effect to reward, that is, attenuating WM networks and enhancing task-related deactivations (TRDs) in regions consistent with the default mode network (DMN). The drugs could be directly discriminated during the delay component of rewarded trials: MPH produced greater activity in WM networks and ATX produced greater activity in the DMN. Our data provide evidence that: (1) MPH and ATX have prominent effects during rewarded WM in task-activated and -deactivated networks; (2) during the delay component of rewarded trials, MPH and ATX have opposing effects on activated and deactivated networks: MPH enhances TRDs more than ATX, whereas ATX attenuates WM networks more than MPH; and (3) MPH mimics reward during encoding. Thus, interactions between drug effects and motivational state are crucial in defining the effects of MPH and ATX

Are We Under-Estimating the Association Between Autism Symptoms?: The Importance of Considering Simultaneous Selection When Using Samples of Individuals Who Meet Diagnostic Criteria for an Autism Spectrum Disorder

The magnitude of symptom inter-correlations in diagnosed individuals has contributed to the evidence that autism spectrum disorders (ASD) is a fractionable disorder. Such correlations may substantially under-estimate the population correlations among symptoms due to simultaneous selection on the areas of deficit required for diagnosis. Using statistical simulations of this selection mechanism, we provide estimates of the extent of this bias, given different levels of population correlation between symptoms. We then use real data to compare domain inter-correlations in the Autism Spectrum Quotient, in those with ASD versus a combined ASD and non-ASD sample. Results from both studies indicate that samples restricted to individuals with a diagnosis of ASD potentially substantially under-estimate the magnitude of association between features of ASD

Estimation of the dietary requirement for vitamin D in healthy adults

Background: Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D.Objective: We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet.Design: A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20&ndash;40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 &micro;g/d) of vitamin D3 throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007).Results: There were clear dose-related increments (P &lt; 0.0001) in serum 25(OH)D with increasing supplemental vitamin D3. The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol&middot;L&ndash;1&middot;&micro;g&ndash;1 intake. The vitamin D intake that maintained serum 25(OH)D concentrations of &gt;25 nmol/L in 97.5% of the sample was 8.7 &micro;g/d. This intake ranged from 7.2 &micro;g/d in those who enjoyed sunshine exposure, 8.8 &micro;g/d in those who sometimes had sun exposure, and 12.3 &micro;g/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of &gt;37.5, &gt;50, and &gt;80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 &micro;g/d, respectively.Conclusion: The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (&gt;97.5%) of 20&ndash;40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 &micro;g/d.<br /

An updated systematic review and meta-analysis of the efficacy of vitamin D food fortification

Food fortification is a potentially effective public health strategy to increase vitamin D intakes and circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We updated a previous systematic review to evaluate current evidence from randomized controlled intervention studies in community-dwelling adults of the effect of fortified foods on 25(OH)D concentrations. Ovid MEDLINE, PubMed, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled intervention studies with vitamin D-fortified foods in free-living adults and data on circulating 25(OH)D. Two reviewers independently screened 441 papers for eligibility and extracted the relevant data. A meta-analysis of the absolute mean change in circulating 25(OH)D concentrations was conducted using a random effects model. Sixteen studies from 15 publications were included, of which 14 showed a significant effect of fortified foods on 25(OH)D concentrations. Heterogeneity was high (P = &lt; 0.0001, I 2 = 89%) and was partly explained by dose, latitude (range, 3-608), and baseline 25(OH) D (range, 24.0-83.6 nmol/L). When combined in a random effects analysis (n = 1513; 767 treated, 746 controls), a mean individual intake of ~11 µg/d (440 IU/d) from fortified foods (range, 3-25 µg/d) increased 25(OH)D by 19.4 nmol/L (95% CI: 13.9, 24.9), corresponding to a 1.2 nmol/L (95% CI: 0.72, 1.68) increase in 25(OH)D for each 1 µg ingested. Vitamin D food fortification increases circulating 25(OH)D concentrations in community-dwelling adults. Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health. © 2012 American Society for Nutrition