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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

LanguageEnglish
Article number151
JournalBMC Geriatrics
Volume19
DOIs
Publication statusPublished - 28 May 2019

Fingerprint

Calcifediol
Frail Elderly
Transcriptome
Vitamin D
Skeletal Muscle
Placebos
Genome
Genes
Biopsy
Gene Expression
25-hydroxyvitamin D
Muscles
Placebo Effect
Calcitriol Receptors
Vitamin D Deficiency
Muscle Weakness
Gene Expression Profiling
Discriminant Analysis
Least-Squares Analysis
Double-Blind Method

Keywords

  • 25-hydroxyvitamin D
  • older adults
  • skeletal muscle
  • transcriptomics
  • Vitamin D

Cite this

@article{c8fda3a0892443d2acfb91a4016ef4bf,
title = "No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults",
abstract = "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.",
keywords = "25-hydroxyvitamin D, older adults, skeletal muscle, transcriptomics, Vitamin D",
author = "Hangelbroek, {Roland W.J.} and Vaes, {Anouk M.M.} and Boekschoten, {Mark V.} and Verdijk, {Lex B.} and Hooiveld, {Guido J.E.J.} and {van Loon}, {Luc J.C.} and {De Groot}, {Lisette C.P.G.M.} and Sander Kersten",
year = "2019",
month = "5",
day = "28",
doi = "10.1186/s12877-019-1156-5",
language = "English",
volume = "19",
journal = "BMC Geriatrics",
issn = "1471-2318",
publisher = "Springer Verlag",

}

No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults. / Hangelbroek, Roland W.J.; Vaes, Anouk M.M.; Boekschoten, Mark V.; Verdijk, Lex B.; Hooiveld, Guido J.E.J.; van Loon, Luc J.C.; De Groot, Lisette C.P.G.M.; Kersten, Sander.

In: BMC Geriatrics, Vol. 19, 151, 28.05.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults

AU - Hangelbroek, Roland W.J.

AU - Vaes, Anouk M.M.

AU - Boekschoten, Mark V.

AU - Verdijk, Lex B.

AU - Hooiveld, Guido J.E.J.

AU - van Loon, Luc J.C.

AU - De Groot, Lisette C.P.G.M.

AU - Kersten, Sander

PY - 2019/5/28

Y1 - 2019/5/28

N2 - 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.

AB - 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.

KW - 25-hydroxyvitamin D

KW - older adults

KW - skeletal muscle

KW - transcriptomics

KW - Vitamin D

U2 - 10.1186/s12877-019-1156-5

DO - 10.1186/s12877-019-1156-5

M3 - Article

VL - 19

JO - BMC Geriatrics

T2 - BMC Geriatrics

JF - BMC Geriatrics

SN - 1471-2318

M1 - 151

ER -