Anti-sarcopenic effects of active vitamin D through modulation of anabolic and catabolic signaling pathways in human skeletal muscle: A randomized controlled trial

IF 11.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Metabolism: clinical and experimental Pub Date : 2025-07-01 Epub Date: 2025-03-28 DOI:10.1016/j.metabol.2025.156240
Tetsuya Kawahara , Tetsuya Inazu , Shoichi Mizuno , Naoki Tominaga , Mikio Toda , Nagahiro Toyama , Chie Kawahara , Gen Suzuki , the DPVD Research Group
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Abstract

Background

The muscle-building and strengthening effects of the active form of vitamin D in humans remain unclear.

Methods

In this ancillary study of the Diabetes Prevention with active Vitamin D trial, we examined clinical and experimental aspects to investigate the effects and mechanisms of eldecalcitol, an active form of vitamin D, in preventing sarcopenia. We examined changes in molecules involved in muscle synthesis and degradation pathways in muscle samples from 32 participants before and after 1 year of eldecalcitol or placebo treatment. The protein levels of molecules involved in muscle synthesis and degradation pathways were examined using western blotting. Additionally, the skeletal muscle and body fat volumes were measured using bioelectrical impedance analysis with a body composition analyzer.

Results

We found that eldecalcitol treatment for 1 year resulted in higher phosphorylation levels of mTOR and FOXO1 signaling pathways, which are associated with increased muscle mass and strength than those with placebo treatment. Body composition measurements at 1 year showed that the eldecalcitol group had significantly higher skeletal muscle mass (1.9 % vs. −3.4 %, p = 3.26E−9) and muscle strength (4.1 % vs. −0.7 %, p = 2.57E−17), and lower fat mass (−3.2 % vs. 1.8 %, p = 1.73E−12) than those in the placebo group.

Conclusion

This study suggested that the active form of vitamin D regulates the protein synthesis and degradation pathways in human skeletal muscle and may help prevent sarcopenia. This study was registered at UMIN clinical trials registry, UMIN 000005394.

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活性维生素D通过调节人体骨骼肌合成代谢和分解代谢信号通路的抗肌肉减少作用:一项随机对照试验
背景:活性维生素D对人体肌肉的增强作用尚不清楚。方法:在这项用活性维生素D预防糖尿病试验的辅助研究中,我们从临床和实验的角度来研究钙骨糖醇(一种活性维生素D)在预防肌肉减少症中的作用和机制。我们检查了32名参与者在接受艾尔地骨糖醇或安慰剂治疗前后1年肌肉样本中涉及肌肉合成和降解途径的分子的变化。采用western blotting检测参与肌肉合成和降解途径的分子蛋白水平。此外,骨骼肌和体脂肪体积测量使用生物电阻抗分析与身体成分分析仪。结果:我们发现,与安慰剂治疗组相比,eldecalcitol治疗1年导致mTOR和fox01信号通路的磷酸化水平升高,这与肌肉质量和力量的增加有关。1年后的身体成分测量显示,与安慰剂组相比,骨骼肌量(1.9% vs. - 3.4%, p = 3.26E−9)和肌肉力量(4.1% vs. - 0.7%, p = 2.57E−17)显著增加,脂肪量(- 3.2% vs. 1.8%, p = 1.73E−12)显著降低。结论维生素D的活性形式调节骨骼肌蛋白质合成和降解途径,可能有助于预防骨骼肌减少症。本研究已在UMIN临床试验注册中心注册,UMIN 000005394。
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来源期刊
Metabolism: clinical and experimental
Metabolism: clinical and experimental 医学-内分泌学与代谢
CiteScore
18.90
自引率
3.10%
发文量
310
审稿时长
16 days
期刊介绍: Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism. Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential. The journal addresses a range of topics, including: - Energy Expenditure and Obesity - Metabolic Syndrome, Prediabetes, and Diabetes - Nutrition, Exercise, and the Environment - Genetics and Genomics, Proteomics, and Metabolomics - Carbohydrate, Lipid, and Protein Metabolism - Endocrinology and Hypertension - Mineral and Bone Metabolism - Cardiovascular Diseases and Malignancies - Inflammation in metabolism and immunometabolism
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