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

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

Interventions

DIETARY_SUPPLEMENT

Protein Supplementation

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.

Sponsors & Collaborators

• University of Nottingham

  lead OTHER

Principal Investigators

• Philip J Atherton · University of Nottingham

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-03-14

Primary Completion

2029-02-01

Completion

2029-02-28

Countries

• United Kingdom

Study Locations