No effect of calcifediol supplementation on skeletal muscle transcriptome in vitamin D deficient frail older adults

Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults

Collection and analysis of published scientific information as preparatory work for the setting of Dietary Reference Values for Vitamin D : External Scientific Report

In recent years, there has been much attention for the global high prevalence of low blood concentrations of 25(OH)D, as an indicator of vitamin D status. These 25(OH)D concentrations primarily depend upon the level of sun exposure. However, also dietary vitamin D intake is of importance, especially at higher latitudes during winter. To get insight in the amount of oral vitamin D needed to achieve and maintain an adequate 25(OH)D blood concentration, the aim of this review was to systematically investigate the intake-status relationship for vitamin D under minimal endogenous vitamin D synthesis, as preparatory work for the setting of Dietary Reference Values for vitamin D. Searches were conducted in Medline, Embase and Cochrane. All published prospective cohort studies with the vitamin D intake-status relationship as the primary aim of investigation, as well as all trials, issued through 23-7-2014 and covering all ages, were included in this review, which resulted in 7,807 unique hits. Subsequently, 1,323 potentially relevant articles were identified by title and abstract screening. Hand searches led to the inclusion of 22 additional potentially relevant papers. Thus, in total, 1,345 full-text papers were screened. After full text screening, 56 articles met the predefined inclusion criteria, resulting in the inclusion of 65 studies, i.e. 57 trials and 8 prospective cohort studies, in infants, children or adults (one article corresponding to one to three studies). Two of the included studies were conducted in infants, eight in children or adolescents, and 55 in adults. The majority of the studies examined the impact of vitamin D3. Most trials studies showed a dose-response relation between vitamin D intake and status. However, as the impact of a similar dose of vitamin D on 25(OH)D concentration substantially differed across the studies, it is difficult to quantify this dose-response relationship. Therefore, the exact nature of the vitamin D dose-response relationship warrants further investigation, for instance by performing meta-regression analyses

Relative Validity and Reliability of Isometric Lower Extremity Strength Assessment in Older Adults by Using a Handheld Dynamometer

Background: Handheld dynamometry (HHD) is a practical alternative to traditional testing of lower extremity strength. However, its reliability and validity across different populations and settings are not clear. Hypothesis: We hypothesize that HHD is a valid and reliable device to assess lower extremity strength in a population of older adults. Study Design: Cross-sectional/cohort. Level of Evidence: Level 3. Methods: This study included 258 older adults (≥65 years). Isometric knee extension and flexion force were measured by 1 examiner, using an HHD (n = 222), including 3 repetitions to calculate within-day intrarater reliability. These measurements were repeated by the examiner in a subgroup (n = 23) to analyze intrarater reliability over a test-retest period of on average 8 weeks. In addition, HHD force measures were performed by a second examiner (n = 29) to analyze interrater reliability. In another subgroup (n = 77), isometric knee extension and flexion torque were measured by 1 examiner using both the HHD and Biodex System 4 to assess relative validity. Results: HHD and Biodex measurements were highly correlated and showed excellent concurrent validity. HHD systematically overestimated torque as compared with Biodex by 8 N·m on average. Same-day intrarater intraclass correlation coefficients (ICCs) ranged from 0.97 to 0.98. Interrater reliability ICCs ranged from 0.83 to 0.95. Conclusion: HHD represents a reliable and valid alternative to Biodex to rank individuals on leg strength, or to assess within-person changes in leg strength over time, because of the high validity and reliability. The HHD is less suited for absolute strength assessment because of significant systematic overestimations. Clinical Relevance: Clinicians are encouraged to use HHD to rank older adults on leg strength, or to assess within-person changes in leg strength over time, but not to compare readings with cut-offs or normative values

Food sources of vitamin D and their association with 25-hydroxyvitamin D status in Dutch older adults

Various populations are at increased risk of developing a low vitamin D status, in particular older adults. Whereas sun exposure is considered the main source of vitamin D, especially during summer, dietary contributions should not be underestimated. This study aims to identify food sources of vitamin D that associate most strongly with serum vitamin D concentration. Data of 595 Dutch adults, aged ≥65 years, were analysed. Vitamin D intake was assessed with a food frequency questionnaire and 25-hydroxyvitamin D (25(OH)D) was determined in serum. Associations of total vitamin D intake and vitamin D intake from specific food groups with serum 25(OH)D status were examined by P-for trend analyses over tertiles of vitamin D intake, prevalence ratios (PRs), and spline regression. The prevalence of vitamin D deficiency was high, with 36% of the participants having a 25(OH)D status <50 nmol/L. Participants with adequate 25(OH)D concentrations were more likely to be men and more likely to be younger than participants with vitamin D deficiency. Total median vitamin D intake was 4.3 μg/day, of which 4.0 μg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8 μg/day, followed by the intake of fish and shellfish with 0.56 μg/day. Participants with higher intakes of butter and margarine were 21% more likely to have a sufficient 25(OH)D status after adjustment for covariates (T1 vs. T3: PR 1.0 vs. 1.21 (95%CI: 1.03–1.42), P-for trend 0.02). None of the other food groups showed a significant association with the probability of having a sufficient 25(OH)D status. This study shows that vitamin D intake was positively associated with total serum 25(OH)D concentration, with butter and margarine being the most important contributors to total vitamin D intake