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Completed

NCT Number: NCT05574205

Dietary Protein Quality for Skeletal Muscle Anabolism in Older Adults

Dietary proteins potently augment muscle protein synthesis. Because of poorer anabolic sensitivity with ageing, studies and guidelines recommend higher dietary protein intake for older adults. Although higher doses would benefit skeletal muscle remodelling, large protein consumption is not feasible for many older adults. To circumvent, high-protein quality which possesses a high amino acid profile and digestibility appears to have an emergent role for supporting anabolism. Since currently the best line of defence against age related muscle loss is resistance exercise training and regular protein consumption, emphasising high-quality protein ingestion, such as whey protein, within meals may be feasible and efficacious in supporting musculoskeletal remodelling in older adults, without requirement for large protein doses.

The investigators propose that at low doses, high quality protein will have additive benefit to muscle protein synthesis compared to low-quality protein. Further, combining high-quality protein diets with resistance exercise training will have more profound benefits for muscle protein synthesis and muscle remodelling more so than low-quality protein diets.

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Key information

Age range

50 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Birmingham, School of Sport, Exercise and Rehabilitation Sciences

Edgbaston, West Midlands, B15 2TT, United Kingdom

About this study

Participants will be randomly assigned to a 10-day dietary intervention consuming primarily animal proteins (high-quality condition) or primarily plant proteins (low-quality condition). In both conditions, participants will undertake supervised single-leg resistance exercise training every other day, amassing five days resistance exercise sessions during the study. The groups will aim to be matched and counterbalanced for gender. Equally for unilateral exercise randomisation for leg dominance will aim to be counterbalanced within both groups.

Preliminary assessments:

5 days preceding the start of the dietary intervention, participants will report to the University of Birmingham, Sport, Exercise and Rehabilitation Science for the following:

  • Health questionnaire
  • Written informed consent
  • Anthropometrics (Height and Weight)
  • Body fat (bioelectrical impedance)
  • Start measuring habitual activity (provided with an activity monitor and pedometer)
  • Start measuring habitual diet (provided with diet diary)

2 days preceding the start of the dietary intervention, participants will report to the University of Birmingham, Sport, Exercise and Rehabilitation Science for the following:

  • Saliva sample (participant gives own saliva sample in a tube)
  • 10ml of blood taken for baseline measures (venepuncture by trained phlebotomist)
  • Loading dose of D2O (stable isotope of water ingested in 8 small 50ml doses taken 1 hour apart throughout the day)
  • Find 1 repetition maximum (1RM) during unilateral knee extension.

Dietary intervention each day throughout 10-day intervention participants will provide a saliva sample and then consume a top up dose of D2O, continue wearing an activity tracker and keep a diet diary to record eating times of provided meals.

Meals will be individualised to body weight for each individual to achieve a moderate protein intake of which will then consist of primarily higher quality or lower quality proteins.

Day 0 (first day of diet), participants will report to the University of Birmingham, Sport, Exercise and Rehabilitation Science at 0800h after fasting >10 hours the night prior for the following:

  • Resting metabolic rate (Laying down for 30 minutes to assess gaseous exchange while wearing a mask)
  • Muscle architecture (using non-invasive ultrasonography)
  • Whole-body composition assessment (DXA scan)
  • Bilateral muscle biopsies (small amount of muscle will be taken from the muscle in the thigh (vastus lateralis) by a trained person from the left and right leg, under local anaesthetic)
  • Maximal muscle strength (isometric dynamometry) and neural activation (interpolated twitch) during maximal muscle contraction on both legs in series.
  • Serial blood samples will be taken with a single cannulisation and 8 10ml blood draws taken throughout the visit (before and after consuming a breakfast which is either higher or lower in protein quality, according to the randomised condition).
  • Perceived appetite will be assessed during the visit, before and after breakfast, using visual analogue scales
  • Urine collection tub will be provided to collect urine over the next 24-hours.

After consuming specified breakfast on this visit, participants will continue to eat meals given to them according to their random allocation of either higher or lower quality protein diets.

Day 1, 3, 5, 7, 9

Participants will report to the University of Birmingham, Sport, Exercise and Rehabilitation Science to undergo single-leg resistance exercise on a knee extension machine. Eight sets will be completed on the machine at each visit at 75% of 1RM (determined during preliminary visits and will be supervised).

On day 9, the participant will be given a urine collection tub to collect urine over the next 24-hours.

Day 10 (Diet finishing during this visit), participants will report to the University of Birmingham, Sport, Exercise and Rehabilitation Science at 0800h after fasting >10 hours the night prior for the following assessments:

  • Resting metabolic rate (Laying down for 30 minutes to assess gaseous exchange while wearing a mask)
  • Whole-body composition assessment (DXA scan)
  • Muscle Architecture (using non-invasive ultrasonography)
  • Maximal muscle strength (Isometric Dynamometry) and neural activation during maximal muscle contraction (Interpolated twitch)
  • Bilateral muscle biopsies (small amount of muscle will be taken from the muscle in the thigh (vastus lateralis) from the left and right leg under local anaesthetic
  • Serial blood samples will be taken with a single cannulisation and 8 10ml blood draws taken throughout the visit (before and after consuming the final meal of the diet which is the breakfast which is either higher or lower in protein quality, according to the randomised condition)
  • Perceived appetite will be assessed during the visit, before and after breakfast, using visual analogue scales.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Males and Females aged between 50-70 years
  • Accustomed to normal physical activity levels (averaging at least 7000 steps a day)
  • Healthy body mass (i.e., BMI 18-25 kg/m2)
  • General good health indicated by health questionnaire
  • Free from COVID-19 (SARS-CoV-2) symptoms.

Exclusion criteria

  • Habitually high consumers of protein (>1.6g/kg/day) assessed by habitual diet diary
  • Food allergies
  • Lidocaine allergy
  • Smoker
  • Bleeding Disorders
  • Chronic/systemic illnesses (i.e., renal failure, rheumatoid arthritis, diabetes, poor lung function, heart disease, cancer, uncontrolled hypertension)
  • Regular consumption of any analgesic or anti-inflammatory drugs. Taking medications mknown to affect muscle metabolis (e.g. beta-blockers, corticosteroids).

Treatment and study plan

Resistance Exercise

Other

Supervised single-leg (unilateral) exercise will be undertaken every other day throughout the dietary intervention

Other names: Single-leg resistance exercise

Protein supplementation

Dietary Supplement

Participants will consume a protein supplement alongside a provided diet to control protein amount and quality.

Primary outcomes

  1. Muscle protein synthesis using muscle biopsies and deuterated water enrichment.

    Time frame: 0-10 days

    Muscle protein synthesis will be assessed during the high-quality and low-quality intervention and compared between exercised and controlled leg.

  2. Leg Strength using dynamometry

    Time frame: 0-10 days

    Evaluating change in leg strength, of trained leg, pre- and post-intervention with high-quality and low-quality protein condition

  3. Neural activation using interpolated twitch

    Time frame: 0-10 days

    Assessing change in neural activation via non-invasive interpolated twitch technique of between exercised legs pre-and post intervention in both protein quality conditions

  4. Muscle architecture using ultrasound

    Time frame: 0-10 days

    Using non-invasive ultrasound to determine change of muscle structure with training between protein quality conditions.

Secondary outcomes

  1. Appetite regulation using questionnaires

    Time frame: 0-10 days (3 hours postprandial)

    Assessing perceived hunger using a validated, 8 question, 100mm visual analogue scales.

  2. Appetite regulation, blood

    Time frame: 0-10 days (3 hours postprandial)

    Assessing the secretion of hunger and appetite hormones within the blood after meals which contain high-quality versus low-quality protein.

  3. Metabolic rate, metabolic cart

    Time frame: 0-10 days

    Evaluating alterations in energy expenditure before and after high-quality or low-quality protein containing meal using a metabolic cart.

  4. Nitrogen balance from urine and dietary protein intake

    Time frame: 0-10 days (24-hour urine collection)

    Evaluating change in nitrogen balance between adhering to high-quality or low-quality protein diets over a 10-day period

  5. Body composition using Duel- energy x-ray absorptiometry (DXA) scan.

    Time frame: 0-10 days

    Change in body composition (muscle mass, fat mass, bone mineral density) will be evaluated using a DXA scanner before and after adhering to single leg resistance exercise paired with either high-quality or low-quality protein diet.

  6. Muscle fibre specific analysis using immunofluorescence microscopy.

    Time frame: 0-10 days

    Evaluate changes in fibre specific differences in the distribution and localisation of key anabolic markers between trained and untrained legs for both protein quality conditions.

  7. Intramuscular signalling using western blotting

    Time frame: 0-10 days

    Evaluate changes in protein content and phosphorylation from the start to the end of the intervention.

  8. Physical activity levels using accelerometery and pedometer

    Time frame: -5-10 days

    Monitoring of habitual and habitual physical activity to evaluate if intensity and duration of activity is similar between habitual and intervention.

Sponsors and collaborators

Lead sponsor

University of Birmingham

Other

Collaborators

  • Maastricht University

Registry information

Official study title

The Importance of Dietary Protein Quality for Skeletal Muscle Anabolism in Older Adults

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Oct 10, 2022
Registry last updated
Aug 1, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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