Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.

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.

Vitamin D is proposed as an antihypertensive agent, but current evidence is inconclusive. Calcifediol is more potent in raising vitamin D status. It might, therefore, be more effective in lowering pulse pressure than cholecalciferol especially in patients with low vitamin D status and high levels of parathyroid hormone (PTH). This study investigated the efficacy of calcifediol on pulse pressure in older adults with vitamin D deficiency and elevated PTH levels. Supplementation with 15 μg calcifediol resulted in lower pulse pressure (Δ 35.4 mm Hg, 95%CI: 4.8, 66.1 mm Hg, P = 0.021) and PTH levels (Δ 1.83 pmol/l, 95%CI: −0.1, 3.7 pmol/l, P = 0.065) compared to 5 μg calcifediol. These effects were observed in a limited sample size of 16 older adults and therefore need confirmation in a larger trial.

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 and the calcifediol group (10 μg per day). Muscle biopsies were obtained before and after 6 months of calcifediol (n = 10) or placebo (n = 12) 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, with Ct values exceeding 30. Blood 25-hydroxycholecalciferol levels were significantly higher after calcifediol supplementation (87.3 ± 20.6 nmol/L) than after placebo (43.8 ± 14.1 nmol/L). No significant difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak, as indicated by the fact that correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any reasonable cut-offs (all q-values ~ 1). 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 significantly 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. This study was registered at clinicaltrials.gov as NCT02349282 on January 28, 2015.

Sufficient 25-hydroxyvitamin D (25(OH)D) concentrations might prevent a decline in physical performance, and are considered important for the prevention of frailty. This study investigates the association of serum 25(OH)D concentration with physical performance and frailty status in Dutch older adults.

Background Vitamin D supplementation is proposed as a potential treatment strategy to counteract functional decline in older adults. However, data from randomized trials are either limited or inconsistent. Objective This study investigated the effect of daily supplementation with 25-hydroxycholecalciferol [25(OH)D3] or cholecalciferol (vitamin D3) on muscle strength and physical performance in older adults. Methods This was a randomized, double-blind, placebo-controlled trial of 6 mo including 78 prefrail or frail (according to the Fried criteria), community-dwelling older adults (n = 43 men) aged ≥65 y, with a baseline 25-hydroxyvitamin D [25(OH)D] concentration between 20 and 50 nmol/L. Participants were supplemented daily with 10 µg 25(OH)D3, 20 µg vitamin D3, or a placebo capsule. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. The primary outcome was maximal isometric knee-extension strength (Biodex System 4); secondary outcomes included knee-flexion and hand grip strength, Short-Physical Performance Battery score, Timed Up and Go score, postural sway, muscle mass (dual-energy X-ray absorptiometry), and muscle fiber type and size. Results The mean baseline serum 25(OH)D concentration was 37.7 nmol/L (95% CI: 35.4, 39.9 nmol/L). After 6 mo of supplementation, concentrations increased to 98.7 nmol/L (95% CI: 93.1, 104.4 nmol/L) in the 25(OH)D3 group and to 72.0 nmol/L (95% CI: 66.1, 77.8 nmol/L) in the vitamin D3 group, compared with 47.5 nmol/L (95% CI: 41.8, 53.3 nmol/L) in the placebo group (P-interaction < 0.01). Knee-extension strength did not significantly change in the 25(OH)D3 group (5.9 Nm; 95% CI: -6.2, 18.0 Nm), in the vitamin D3 group (5.5 Nm; 95% CI: -6.8, 17.8 Nm), or in the placebo group (1.8 Nm; 95% CI: -10.7, 14.4 Nm) (P-interaction = 0.74). Furthermore, mean changes in physical performance tests, muscle mass, and muscle fiber type and size did not differ between the groups. Conclusion Increasing the serum 25(OH)D concentration over a period of 6 mo did not significantly change muscle strength and physical performance in prefrail and frail older adults. This trial was registered at www.clinicaltrials.gov as NCT02349282.

Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults.Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged >= 65 years. Sun exposure was assessed with a structured questionnaire (n = 1012), vitamin D intake using a Food Frequency Questionnaire (n = 596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n= 2530).Results: Serum 25(OH)D concentrations <50 nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66 +/- 25 nmol/L vs not being outside daily during summer: 58 +/- 27 nmol/L, P = 0.02) and vitamin D intake (per unit mu g/day during winter/spring: 3.1 +/- 0.75 nmol/L, P < 0.0001) were associated with higher 25 (OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R-2=0.29), vitamin D intake (R-2=0.24), and genes (R-2=0.28) explained 35% (R-2=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BM1, education, alcohol consumption, smoking, physical activity, and self-rated health status (n = 185).Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH) D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency. (C) 2015 Elsevier Ltd. All rights reserved.

EFSA Supporting PublicationsVolume 13, Issue 2 766E External scientific reportOpen Access Collection and analysis of published scientific information as preparatory work for the setting of Dietary Reference Values for Vitamin D Elske M. Brouwer-Brolsma, Elske M. Brouwer-Brolsma Wageningen University, Division of Human NutritionSearch for more papers by this authorAgnes A. M. Berendsen, Agnes A. M. Berendsen Wageningen University, Division of Human NutritionSearch for more papers by this authorAnouk M.M. Vaes, Anouk M.M. Vaes Wageningen University, Division of Human NutritionSearch for more papers by this authorCarla Dullemeijer, Carla Dullemeijer Wageningen University, Division of Human NutritionSearch for more papers by this authorLisette C.P.G.M. de Groot, Lisette C.P.G.M. de Groot Wageningen University, Division of Human NutritionSearch for more papers by this authorEdith J.M. Feskens, Edith J.M. Feskens Wageningen University, Division of Human NutritionSearch for more papers by this author Elske M. Brouwer-Brolsma, Elske M. Brouwer-Brolsma Wageningen University, Division of Human NutritionSearch for more papers by this authorAgnes A. M. Berendsen, Agnes A. M. Berendsen Wageningen University, Division of Human NutritionSearch for more papers by this authorAnouk M.M. Vaes, Anouk M.M. Vaes Wageningen University, Division of Human NutritionSearch for more papers by this authorCarla Dullemeijer, Carla Dullemeijer Wageningen University, Division of Human NutritionSearch for more papers by this authorLisette C.P.G.M. de Groot, Lisette C.P.G.M. de Groot Wageningen University, Division of Human NutritionSearch for more papers by this authorEdith J.M. Feskens, Edith J.M. Feskens Wageningen University, Division of Human NutritionSearch for more papers by this author First published: 21 February 2016 https://doi.org/10.2903/sp.efsa.2016.EN-766Citations: 10 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Published date: 21 February 2016 Question number: EFSA-Q-2014-00099 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume13, Issue2February 2016766E ReferencesRelatedInformation

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 <50nmol/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 4.3μg/day, of which 4.0μg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8μg/day, followed by the intake of fish and shellfish with 0.56μg/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.