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
Top Institute Food and Nutrition, P.O. Box 557, 6700, AN, Wageningen, The Netherlands.
Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708, WE, Wageningen, The Netherlands.
BMC Geriatr. 2019 May 28;19(1):151. doi: 10.1186/s12877-019-1156-5.
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.
维生素D缺乏在老年人中很常见，且与肌肉无力有关。补充维生素D已被提议作为改善老年人肌肉功能的一种策略。本研究的目的是调查骨化二醇（25-羟基胆钙化醇）对维生素D缺乏的体弱老年人骨骼肌全基因组基因表达的影响。
对维生素D缺乏的体弱老年人（年龄在65岁以上）进行了一项双盲安慰剂对照试验，其特征为血液中25-羟基胆钙化醇浓度在20至50 nmol/L之间。受试者被随机分为安慰剂组和骨化二醇组（每天10μg）。在补充骨化二醇（n = 10）或安慰剂（n = 12）6个月前后获取肌肉活检样本，并使用Affymetrix HuGene 2.1ST阵列进行全基因组基因表达谱分析。
在人类骨骼肌活检样本中几乎检测不到维生素D受体基因的表达，其Ct值超过30。补充骨化二醇后血液中25-羟基胆钙化醇水平（87.3±20.6 nmol/L）显著高于安慰剂组（43.8±14.1 nmol/L）。在力量指标上未观察到治疗组之间的显著差异。骨化二醇和安慰剂对全转录组的影响非常微弱，这体现在使用错误发现率校正多重检验后，在任何合理的阈值下均未产生任何差异表达基因（所有q值约为1）。P值在所有基因中均匀分布，表明低P值很可能是假阳性。偏最小二乘判别分析和主成分分析无法区分治疗组。
补充骨化二醇对体弱老年人的骨骼肌转录组没有显著影响。我们的研究结果表明，补充维生素D对骨骼肌基因表达没有影响，这表明骨骼肌可能不是老年人中维生素D的直接作用靶点。
本研究于2015年1月28日在clinicaltrials.gov上注册，注册号为NCT02349282。
