The association between 25-hydroxyvitamin D concentration, physical performance and frailty status in older adults.

PURPOSE: 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. METHODS: This cross-sectional study included 756 men and women, aged ≥ 65 years. Serum 25(OH)D concentration and frailty status (Fried criteria) were assessed in the total population. Screening for frailty status included functional tests of gait speed and hand grip strength. In a subgroup (n = 494), the Timed Up and Go test (TUG) and knee-extension strength were measured. Associations of serum 25(OH)D status with physical performance were examined by multiple linear regression. Prevalence ratios (PR) were used to quantify associations between serum 25(OH)D deficiency (< 50 nmol/L) and frailty. RESULTS: In total, 45% of the participants were vitamin D deficient. Participants with vitamin D status < 50 and 50-75 nmol/L had significantly lower scores on the TUG and gait speed test, compared to participants with vitamin D status > 75 nmol/L. No significant associations with serum 25(OH)D concentrations were observed for handgrip strength or knee-extension strength. Participants with serum 25(OH)D status < 50 nmol/L were about two times more likely to be frail compared to participants with serum 25(OH)D status ≥ 50 nmol/L. No significant associations were observed between the pre-frail state and serum 25(OH)D status. CONCLUSION: In this study, serum 25(OH)D concentrations were significantly associated with frailty status and measures of physical performance, including gait speed and TUG, but not with strength-related outcomes.

No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov as NCT02349282 on January 28, 2015.

Cholecalciferol or 25-Hydroxycholecalciferol Supplementation Does Not Affect Muscle Strength and Physical Performance in Prefrail and Frail 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.

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.

Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults.

BACKGROUND & AIMS: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. METHODS: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 µg calcifediol or 20 µg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. RESULTS: Supplementation with 20 µg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 µg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 µg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. CONCLUSIONS: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 µg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION NUMBER: NCT01868945.

Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study.

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 <50nmol/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±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit µg/day during winter/spring: 3.1±0.75nmol/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 (R2=0.29), vitamin D intake (R2=0.24), and genes (R2=0.28) explained 35% (R2=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, 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.