This study evaluates the effect of vitamin D supplementation on outcomes of 10 weeks progressive strength training in 100 ageing subjects (\>45 years of age). Participants will be recruited into two similarly sized strata; one containing COPD patients and one containing healthy subjects of similar age. In each stratum, half the participants will receive vitamin D supplementation and half the participants will receive placebo
Physical activity is a potent way of relieving some of the adverse morbidities associated with COPD, such as muscle atrophy and reduced muscle quality. It is thus problematic that 20-30% of patients fail to elicit positive adaptations to training. This oddity has been ascribed inherent muscular properties, with potential links to comorbidities such as vitamin D and testosterone deficiency and the nature of the training program. In the present project, a double-blinded RCT will be performed to disclose the functional and biological efficacy of vitamin D supplementation (with concomitant ingestion of 1000 mg Ca2+) on the outcomes of 10 wks strength training in 100 aging individuals with or without COPD. The strength training intervention will be preceded by 3 weeks of progressive introduction to training protocols. 50 COPD patients and 50 healthy subjects will be allocated into two strata and separately randomized into two equally sized supplementation groups; (1) vitamin D3 and (2) placebo. The planned 50:50 ratio between COPD patients and healthy individuals may change, depending on the access to COPD patients. All subjects will perform lower-limb strength-training protocols in a contralateral manner: (leg 1) high-resistance (10 RM) and (leg 2) low-resistance (30 RM). Such a one-limb-at-a-time protocol ensures training that is unconfined by the cardiorespiratory limitations inherent to these patients, and allow comparison of the two training modalities in a manner unconfined by individual variation in exercise adaptability. A pilot study investigating the possible central pulmonary capacity limitation to two-legged strength training exercise in COPD patients will be performed. In this pilot study, we will compare exercise performance involving large and small muscle mass. In addition, all subjects will perform a selection of bilateral upper body exercises (10 RM), ensuring adequate hormonal responses and compliance to the study. The study is likely to revitalize guidelines for rehabilitation of COPD patients, and to provide vital information regarding the role of vitamin D in adaptations to strength training. For outcome measures specific to COPD pasients, final analyses will be performed on data from the COPD population only. For other outcome measures, final analyses will be performed on data merged from COPD patients and healthy subjects. An important rationale behind implementing healthy control subjects is to increase the statistical power of outcome measures unrelated to COPD epidemiology, which are of general relevance to physiological adaptation to strength training. In a related set of analyses, we will perform between-groups comparisons, including multivariate analyses. We will also compare the efficacy of high- and low-resistance strength training in COPD patients and healthy control subjects. The two training modalities are expected to result in similar muscular adaptations. In general, baseline vitamin D levels in blood, measured as 25(OH)D, is anticipated to be a determinant of the efficacy of the strength training intervention. In response to vitamin D3 supplementation, individuals with low baseline levels of 25(OH)D are expected to display more pronounced changes in biological active vitamin D, leading to more pronounced changes in functional and biological outcome measures in response to strength training. In contrast, supplementation may not lead to further elevation of blood 25(OH)D levels in individuals with high baseline levels, essentially meaning that vitamin D3 ingestion will be leveled out by or exceeded by the elimination of vitamin D derivatives. In these individuals, vitamin D3 ingestion will not have an additive effect on functional and biological outcome measures in response to strength training. To assess individual variation in vitamin D responses, data on functional and biological variables will be divided into quartiles based on baseline 25(OH)D-levels, whereupon comparisons will be made between low-end and high-end quartiles. Individual variation in responses to vitamin D supplementation and strength training will also be assessed using a mixed model approach.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
97
Vitamin D3 dissolved in olive oil, encapsuled
Olive oil, encapsuled
Inland Norway University of Applied Sciences
Lillehammer, Norway
Muscle size
Muscle cell cross-sectional area measured in biopsies from m. vastus lateralis using immunohistochemistry
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Muscle phenotype
Muscle fiber type composition measured in biopsies from m. vastus lateralis using immunohistochemistry
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Lung function
Lung function measured using spirometry
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
One-legged cycling
Performance indicies measured during an incremental one-legged cycling test
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Hormones in blood
Levels of hormones in blood
Time frame: Changes over the course of the intervention (week 0 to 28)
Cytokines in blood
Levels of cytokines in blood
Time frame: Changes over the course of the intervention (week 0 to 28)
Steroids in skeletal muscle
Levels of steroids in m. vastus lateralis
Time frame: Changes over the course of the intervention (week 0 to 28)
Androgen-converting enzymes in skeletal muscle
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Levels of androgen-converting enzymes in m. vastus lateralis
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Gene expression in skeletal muscle
RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Gene expression in skeletal muscle
RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome
Time frame: Changes from before to after familiarization to strength training (week 15 to week 17)
Protein abundances in skeletal muscle
Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Protein abundances in skeletal muscle
Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome
Time frame: Changes from before to after familiarization to strength training (week 15 to week 17)
Vitamin D in blood
Levels of vitamin D in blood
Time frame: Changes over the course of the intervention (week 0 to 28)
Step test
Performance and performance indicies measured during a 6 minutes step test
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Pasient-reported outcome measures, generic
Pasient-related outcome measures assessed using the generic survey SF-36
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Pasient-reported outcome measures, COPD-specific
COPD-specific pasient-reported outcome assessed using COPD assessment test
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Body mass composition
Body mass composition measured using Dual-energy X-ray absorptiometry (DXA)
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Bilateral upper body maximal strength
The ability of muscles of the upper body to exert maximal force during dynamic movements
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Grip strength
Isometric hand grip strength
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Sit-to-stand test
Performance and performance indicies measured during a sit-to-stand test
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Unilateral lower body maximal muscle strength
The ability of muscles of the lower body to exert maximal force during dynamic movements
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Unilateral lower body muscle endurance
The ability of muscles of the lower body to perform repeated dynamic contractions at a specified submaximal load to exhaustion
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Bilateral upper body muscle endurance
The ability of muscles of the upper body to perform repeated dynamic contractions at a specified submaximal load to exhaustion
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Unilateral lower body isokinetic muscle strength
The ability of muscles of the lower body to exert maximal force during isokinetic movements
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Daily life activity level
Daily life activity level measured using accelerometer
Time frame: Changes from before to after the intervention (week 0 to week 28)
Muscle cell biological traits
Muscle cell biological traits, including numbers of myonuclei, satelitte cells and capillaries, measured in biopsies from m. vastus lateralis using immunohistochemistry
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Muscle mitochondrial quantities
Mitochondrial quantities measured in biopsies from m. vastus lateralis
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)
Muscle mitochondrial functions
Mitochondrial functions measured in biopsies from m. vastus lateralis
Time frame: Changes from before to after the strength training intervention (week 19 to week 28)