Assessing the Impact of a Leucine Enriched Whey Protein vs Isonitrogenous Whey on Muscle Protein Synthetic Responses in the Rested and Acute Post Exercise States in Older Adults

NCT06971822 | Recruiting

• 1 other identifier: AFI3- FMHS 63-0125
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Occupying \~45-55% of body mass, skeletal muscle is the largest organ of the body and plays a pivotal role in locomotion, structural support and whole-body metabolic health. Additionally, skeletal muscle serves as the largest reservoir of amino acids (AA), which negatively adapts in states of disease and fasting to provide energy and AAs for vital organs, but also positively adapts to nutrition (i.e. protein consumption) and exercise (i.e. resistance exercise (RE)). With the current global ageing population, pressure on health and social care systems is continuing to mount due to increased frailty and other age-related co-morbidities. Sarcopenia, the loss of muscle mass (atrophy) and function with advancing age, predisposes an individual to an increased likelihood of physical disability, falls/fractures and mortality. Whilst sarcopenia is multifaceted and has no sole cause, reduced responses to environmental stimuli (namely nutrition (i.e. protein feeding) and exercise) termed "anabolic resistance", appears to be a governing role in the progression of age-related muscle atrophy. The maintenance of muscle mass is regulated by the dynamic relationship between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) with anabolic resistance, therefore, centering upon the blunting of increases in MPS and/or suppression of MPB. Aged muscle has consistently shown depressed MPS rates following feeding and also exercise when compared to young muscle. Additionally, older individuals need to consume a greater amount of protein compared to younger individuals to drive an MPS increase above baseline levels. This can often prove difficult due to older adults exhibiting increased satiety, likely contributing to the inadequate daily consumption of protein in such populations. Fortifying protein with leucine may, therefore, provide a nutraceutical avenue for combating anabolic resistance in ageing muscle. Leucine, both an essential amino acid (EAA) and branched chain amino acid (BCAA), is the key AA for stimulating MPS via activation of mechanistic target of rapamycin complex 1 (mTORC1), meaning protein rich in leucine may be advantageous to trigger MPS. Recent work has shown that a submaximal protein (10 g) drink enriched with leucine (4.5 g), compared to the non-essential amino acid (NEAA)- alanine (4.5 g), elevated MPS in older individuals, with anabolic signalling also being robustly triggered when administering \~6g BCAAs contain \~2.6 g leucine in older adults. However, research has also shown that in the absence of a full AA profile, leucine alone failed to stimulate MPS in postmenopausal women. It, therefore, remains inconclusive whether standalone or adjuvant supplementation of leucine is most effective to sufficiently stimulate MPS across aged populations and it remains to be investigated whether submaximal doses of complete protein enriched with leucine may lead to enhanced muscle anabolism in older adults. In this study, we aim to assess the impact of dietary supplementation with a "super-whey" (SW) protein (with \~40% enhanced leucine and \~20% enhanced EAAs) vs. isonitrogenous whey protein (WP) on muscle protein synthesis (MPS). We will examine these effects both in the rested state, as well as the 24 hour post-exercise period under tightly controlled activity and feeding conditions.

Conditions

Healthy Male Volunteers Over 65

Keywords

Leucine; Muscle Mass; Sarcopenia; Nutrition; Protein

Outcome Measures

Primary Outcomes (1)

• Muscle Protein Synthesis

  We measure myofibrillar fractional synthesis rates (FSR) based on the incorporation of deuterated hydrogen from heavy water (D2O) in the muscle. Participants will consume the heavy water the day before the onset of the study, and then muscle biopsies will be taken at various points over the next three days for rested and post-exercise muscle protein synthesis measures.

  From enrollment there is a three day lead in to the study with a controlled diet and limited physical activity, followed by two and a half days of study visits.

Study Arms (2)

Isonitrogenous Whey Protein Group

ACTIVE COMPARATOR

This group will receive a 20g supplement of isonitrogenous whey protein supplement with each of their controlled meals on the study visits.

Dietary Supplement: Protein Supplementation

BLG

EXPERIMENTAL

This group will receive a 20g supplement of BLG (leucine enriched protein) supplement with each of their controlled meals on the study visits.

Dietary Supplement: Protein Supplementation

Interventions

Protein Supplementation DIETARY_SUPPLEMENT

We are assessing the supplementation of a controlled diet with beta-lactoglobulin protein compared to regular isonitrogenous whey protein. We will make these comparisons over both the 24 hour rested and 24 hour post-exercise states. Beta-lactoglobulin has a higher leucine content than traditional whey protein, with this leucine amino acid thought to have a critical role as an anabolic stimulus to initiate muscle protein synthesis.

BLG; Isonitrogenous Whey Protein Group

Eligibility Criteria

• Age: 65 Years+
• Gender Eligibility Details: Male participants are eligible for this study.
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may not qualify if:

• A BMI \<18 or \>35 kg/m2
• Active cardiovascular, cerebrovascular or respiratory disease: e.g. uncontrolled hypertension (BP \> 160/100), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event, COPD, pulmonary hypertension or recent (6 mo) stroke
• Any metabolic disease
• Clotting dysfunction
• A history of, or current neurological or musculoskeletal conditions (e.g. epilepsy)
• Lactose intolerance
• Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

Royal Derby Hospital Medical School

Derby, Derbyshire, DE22 3NE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Sarcopenia

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Philip J Atherton

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jake Cox

CONTACT

07731 755075; mbyjc16@nottingham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Philip Atherton

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 14, 2025
• Study Start: March 14, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)