Clinical trial NCT04545190: RibOSE - Glucose and Resistance Exercise Training
Official title: RibOSE - Effects of Glucose Ingestion During Resistance Exercise Training on Ribosomal Biogenesis in Skeletal Muscle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Strength/resistance training
Glucose supplementation
Skeletal muscle
Lead sponsor: Inland Norway University of Applied Sciences
Sponsor class: OTHER
First posted: 2020-09-10
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will be conducted as a 12-day placebo-controlled randomized clinical trial. Each day will consist of concomitant dietary intervention and resistance training. The dietary intervention consists of alternating days of ingesting glucose (GLU, 90 g) or placebo (PLAC) in connection with training. Likewise, training consists of alternating days of resistance training of the two legs (using identical training protocols), with Day 1 involving training of the first leg, Day 2 involving training of the second leg, Day 3 involving training of the first leg, etc. In this way, each of the two dietary interventions will be associated with training of one particular leg, allowing within-subject comparisons of the effects of GLU vs PLAC on muscle biology and recovery.
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to investigate the effects of ingesting glucose during five bouts of resistance exercise on muscle biological charateristics in m. vastus lateralis of moderately trained healthy individuals (20-45 years of age, n=20)

Detailed description: Muscular responses to resistance training vary extensively between humans, with many showing impaired growth. In such individuals, cellular plasticity is compromised, leading to reduced functional and health-beneficial outcomes of training. While this is likely due to a range of determinants, including epigenetic, genetic and physiological variables, recent studies suggest that it involves reduced ability to produce novel ribosomes in response to training. This eventually leads to less pronounced increases in protein synthesis, and thus decreased growth rates, and makes ribosomal content in muscle a potential proxy marker for training-associated muscle hypertrophy.

In a recent study, the investigators showed that increased resistance training volume was associated with more pronounced muscle growth, a trait that was associated with increased ribosomal biogenesis. Despite this, \~50 % of the participants did not exhibit true beneficial effects of increased training volume, which in turn coincided with reduced abilities to accumulate ribosomes. In such individuals, other means are likely necessary to circumvent the negative influence of genetic and epigenetic predispositions on muscle plasticity. Nutrient supplementation stand out as a potential therapy. However, at present, knowledge with regard to this perspective is limited to a selected few nutrients, with protein ingestion being the best studied potential adjuvant, for which adequate intake seems to be essential for achieving optimal muscle growth, potentially being interconnected with ribosomal synthesis. For other nutrients, such as glucose, little is know about their importance for muscle plasticity and ribosomal biogenesis.

In cell types such as cultivated kidney cells, exposure to high levels of glucose is an efficient mean to increase ribosomal biogenesis (and growth rates). This suggests that glucose is an important signaling molecule for increasing ribosomal production per se, perhaps acting as a ligand for signaling proteins or by acting to increase energy availability. In the human body (as opposed to cultured cells), glucose may also exert growth-stimulating effects by increasing insulin levels in blood. Overall, it thus seems plausible that glucose intake during resistance training may stimulate ribosomal biogenesis, in turn having beneficial effects for protein synthesis and muscle plasticity, perhaps acting in an additive manner to protein supplementation. At present, we do not know if this is the case, though studies have suggested that glucose ingestion during acute resistance training sessions may reduce training-induced muscle damage without affecting within-session work output (i.e. volume). This lack of knowledge is surprising given the long-standing appreciation of the beneficial effects of glucose intake for endurance performance, acting to delay muscular fatigue.

Eligibility criteria: Inclusion Criteria:

* Non-smoking
* Moderately trained (i.e. having performed 2-8 resistance training sessions per 14 days for the last six months)

Exclusion Criteria:

* Not able to understand Norwegian
* Unstable cardiovascular disease
* Illness or injury contradicting heavy strength training
* Disabling musculoskeletal disease
* Serious mental illness
* Allergy to local anaesthesia
* Impaired glucose tolerance

Primary outcomes:
measure: Total RNA in muscle tissue
timeFrame: Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
Secondary outcomes:
measure: Ribosomal RNA in skeletal muscle
timeFrame: Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
measure: Protein in skeletal muscle
timeFrame: Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
measure: Gene expression in skeletal muscle
timeFrame: Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
measure: Muscle fractional synthesis rate
timeFrame: Immediately after the intervention
measure: Glucose in blood, after glucose/placebo intake
timeFrame: Immediately before glucose/placebo intake and 30 min, 45 min, 60 min and 195 min after initial glucose/placebo intake
measure: Glucose in blood (after protein intake)
timeFrame: Immediately before protein intake and 45 min and 90 min after protein intake
measure: Hormone concentrations in blood (after glucose/placebo intake)
timeFrame: Immediately before glucose/placebo intake and 30 min and 60 min after the initial glucose/placebo intake
measure: Hormone concentrations in blood (after protein intake)
timeFrame: Immediately before protein intake and 90 min after protein intake
measure: Unilateral lower body isokinetic muscle strength (during the intervention)
timeFrame: Before the intervention and after the second, fourth and sixth training session
measure: Unilateral lower body isokinetic muscle strength (last days of the intervention)
timeFrame: Before the last training session and 30 min, 120 min and 24 hours after the last training session
measure: Unilateral lower body isometric muscle strength (during the intervention)
timeFrame: Before the intervention and after the second, fourth and sixth training session
measure: Unilateral lower body isometric muscle strength (last days of the intervention)
timeFrame: Before the last training session and 30 min, 120 min and 24 hours after the last training session
measure: Perceived muscle soreness (during the intervention)
timeFrame: Before the intervention and 24 hours after each training session
measure: Perceived feeling of the legs (during the intervention)
timeFrame: 30 min after each training session
Other outcomes:
measure: Training diary
timeFrame: During each training session of the intervention
measure: Body mass composition
timeFrame: Prior to the intervention
measure: Dietary registration
timeFrame: During each day of the intervention
measure: Unilateral lower body maximal strength
timeFrame: Before the intervention
measure: Blind test glucose vs placebo comparators
timeFrame: Immediately after the intervention
measure: Deuterium in spit
timeFrame: On each day of the intervention
measure: Fasting blood glucose
timeFrame: Before the intervention and immediately after the intervention
Locations:
city: Lillehammer
country: Norway
facility: Inland Norway University of Applied Sciences
Study officials:
affiliation: Inland Norway University of Applied Sciences
name: Stian Ellefsen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hammarstrom D, Ofsteng S, Koll L, Hanestadhaugen M, Hollan I, Apro W, Whist JE, Blomstrand E, Ronnestad BR, Ellefsen S. Benefits of higher resistance-training volume are related to ribosome biogenesis. J Physiol. 2020 Feb;598(3):543-565. doi: 10.1113/JP278455. Epub 2020 Jan 15.