No benefits of prolonged vitamin D3 supplementation for adaptations to resistance training in old adults

Background Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those chronically diseased (e.g. chronic obstructive pulmonary disease, COPD), and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods Ninety-five male and female participants (healthy, n=71; COPD, n=24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (in average, 3333 IU.day-1), followed by 13 weeks of combined supplementation (2000 IU.day-1) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n=7), endurance performance (n=6), and muscle mass (n=3, legs, primary), as well as muscle quality (legs), muscle biology ( m. vastus lateralis ; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%) and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, − 6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3%-points), myonuclei·fibre-1 (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. ∼336 differentially expressed genes). Vitamin D3 supplementation led to robust increases in [25(OH)D]serum (Δ49% vs placebo), but did not affect training-associated changes for any of the main outcome domains, with no interaction being evident with disease status or pre-RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue, strength gains in participants with high fat mass, and [cortisol]serum (Δ20%), all of which advocate further study. Conclusions Vitamin D3 supplementation did not affect muscular responses to resistance training in old adults with or without COPD. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02598830 ### Funding Statement The study was funded by Inland Norway University of Applied Sciences, Innlandet Hospital Trust (grant number 150339) and Regional Research Fund Inland Norway (grant number 298419). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Regional Committee for Medical and Health Research Ethics - South-East Norway (reference nr: 2013/1094) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data generated or analysed during this study are included in this published article (and its supplementary information files).