RibOSE - Glucose and Resistance Exercise Training (RibOSE)

RibOSE - Effects of Glucose Ingestion During Resistance Exercise Training on Ribosomal Biogenesis in Skeletal Muscle

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)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Glucose

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Lillehammer, Norway
    • Inland Norway University of Applied Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucose; Glucose will be ingested at three time points during resistance training (RT): 30 min prior to RT (30 g glucose mixed with 300 ml sugar-free Fun light lemonade), immediately prior to RT (30 g, 300 ml), and immediately after completion of training (30 g, 300 ml). Protein supplement will be ingested at two time points: 2 hours prior to RT (e.g. at 0700 hrs, 25 g) and immediately after completion of training (25 g). Placebo will be ingested during the afternoon (i.e. not during training; between 1800 hrs and 1900 hrs): 3 x 100 mg Stevia powder mixed with 3 x 300 ml sugar-free Fun light lemonade. (The dietary intervention spans from 2200 hrs on the evening prior to RT sessions to ~2.5 hrs after completion of RT. During this time frame, participants will ingest glucose and protein supplements only)	Dietary supplement: Glucose; To investigate the effects of glucose intake during resistance training on muscle biological adaptations
Placebo Comparator: Placebo; Placebo will be ingested at three time points during resistance training (RT): 30 min prior to RT (100 mg Stevia powder mixed with 300 ml sugar-free Fun light lemonade), immediately prior to RT (100 mg, 300 ml), and immediately after completion of training (100 mg, 300 ml). Protein supplement will be ingested at two time points: 2 hours prior to RT (e.g. at 0700 hrs, 25 g) and immediately after completion of training (25 g). Glucose will be ingested during the afternoon (i.e. not during training; between 1800 hrs and 1900 hrs): 3 x 30 g glucose mixed with 3 x 300 ml sugar-free Fun light lemonade. (The dietary intervention spans from 2200 hrs on the evening prior to RT sessions to ~2.5 hrs after completion of RT. I.e.: during this period, participants will ingest placebo and protein supplements only)	Dietary supplement: Glucose; To investigate the effects of glucose intake during resistance training on muscle biological adaptations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total RNA in muscle tissue	Total RNA content in m. vastus lateralis (ug per mg tissue)	Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ribosomal RNA in skeletal muscle	Abundances of ribosomal RNA species in m. vastus lateralis measured using qPCR	Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
Protein in skeletal muscle	Abundances of protein species in m. vastus lateralis measured using Western blotting (e.g. ECM proteins)	Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
Gene expression in skeletal muscle	Abundances of mRNA species in m. vastus lateralis measured using qPCR	Before the intervention and immediately after the intervention (i.e. after 5 training sessions of each leg)
Muscle fractional synthesis rate	Protein synthesis rate measured using heavy water (deuterium) and chromatography/spectrometry	Immediately after the intervention
Glucose in blood, after glucose/placebo intake	Glucose concentrations in blood (area under the curve), measured before and after intake of glucose/placebo on the two final days of the intervention (one day = glucose; one day = placebo)	Immediately before glucose/placebo intake and 30 min, 45 min, 60 min and 195 min after initial glucose/placebo intake
Glucose in blood (after protein intake)	Glucose concentrations in blood (area under the curve), measured before and after intake of protein on the two final days of the intervention	Immediately before protein intake and 45 min and 90 min after protein intake
Hormone concentrations in blood (after glucose/placebo intake)	Abundances of insulin, c-peptide, testosterone, growth hormone, cortisol and inflammatory markers in blood (area under the curve), measured before and after intake of glucose/placebo on the two final days of the intervention (one day = glucose; one day = placebo)	Immediately before glucose/placebo intake and 30 min and 60 min after the initial glucose/placebo intake
Hormone concentrations in blood (after protein intake)	Abundances of insulin, c-peptide, testosterone, growth hormone, cortisol and inflammatory markers in blood, measured after intake of protein on the two final days of the intervention	Immediately before protein intake and 90 min after protein intake
Unilateral lower body isokinetic muscle strength (during the intervention)	The ability of the knee extensors to exert maximal force during isokinetic movements (recovery/strength), measured before the intervention and at three time points during the intervention (~24 hours after training sessions)	Before the intervention and after the second, fourth and sixth training session
Unilateral lower body isokinetic muscle strength (last days of the intervention)	The ability of the knee extensors to exert maximal force during isokinetic movements (recovery/strength), measured before and at three time points after the last two training sessions (one day = glucose; one day = placebo)	Before the last training session and 30 min, 120 min and 24 hours after the last training session
Unilateral lower body isometric muscle strength (during the intervention)	The ability of the knee extensors to exert maximal force during isometric actions (recovery/strength), measured before the intervention and at three time points during the intervention (~24 hours after training sessions)	Before the intervention and after the second, fourth and sixth training session
Unilateral lower body isometric muscle strength (last days of the intervention)	The ability of the knee extensors to exert maximal force during isometric actions (recovery/strength), measured before and at three time points after the last two training sessions (one day = glucose; one day = placebo)	Before the last training session and 30 min, 120 min and 24 hours after the last training session
Perceived muscle soreness (during the intervention)	Muscular soreness measured before the intervention and at three time points during the intervention (~24 hours after training sessions) using a VAS-scale from 0 to 10 (0 = no soreness; 10 = maximal soreness)	Before the intervention and 24 hours after each training session
Perceived feeling of the legs (during the intervention)	Feeling of the legs measured immediately after each training session using a 9-point scale (1 = very very good, 9 = very very heavy)	30 min after each training session

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Training diary	Training volume (total kg lifted) during each day of the intervention	During each training session of the intervention
Body mass composition	Body mass composition measured using DXA	Prior to the intervention
Dietary registration	Nutritional intake during each day of the intervention, tracked using MyFitnessPal	During each day of the intervention
Unilateral lower body maximal strength	The ability of muscles of the lower body to exert maximal force during dynamic movements	Before the intervention
Blind test glucose vs placebo comparators	The ability to discriminate between glucose and placebo beverages, tested after the training intervention using a blinded randomized design: each participant will ingest six beverages (3 x glucose and 3 x placebo) and will be asked to identify theam as either glucose or placebo. The "ability to discriminate" will be determined based on analyses of the full study population	Immediately after the intervention
Deuterium in spit	Deuterium levels in spit on each day during the intervention measured using chromatography/spectrometry (sampled prior to each training session)	On each day of the intervention
Fasting blood glucose	Fasting blood glucose measured in serum, measured before the intervention and prior to training on the last two days of the intervention	Before the intervention and immediately after the intervention

Collaborators and Investigators

• Sponsor: Inland Norway University of Applied Sciences
• Investigators: Principal Investigator: Stian Ellefsen, PhD, Inland Norway University of Applied Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): December 20, 2020
• Study Completion (Actual): December 20, 2020

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: September 7, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Skeletal muscle; Strength/resistance training; Glucose supplementation
• Other Study ID Numbers: Trainome#024_2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No