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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Aug 14, 2025
Date Accepted: Feb 20, 2026

The final, peer-reviewed published version of this preprint can be found here:

Effect of Branched-Chain Amino Acid Supplementation Alone or Combined With Tryptophan or Methionine on Appetite Control and Related Health Outcomes in Older Adults: Protocol for a Randomized Controlled Trial

Zhang S, Ribeiro R, Raubenheimer D, Caillaud C, Tan J, Solon-Biet S, Cistulli PA, Simpson SJ

Effect of Branched-Chain Amino Acid Supplementation Alone or Combined With Tryptophan or Methionine on Appetite Control and Related Health Outcomes in Older Adults: Protocol for a Randomized Controlled Trial

JMIR Res Protoc 2026;15:e82436

DOI: 10.2196/82436

PMID: 42166751

The effect on supplementation of branched-chain amino acids by itself or combined with tryptophan or methionine on appetite control and related health outcomes in individuals aged 65-80: a randomized controlled trial protocol

  • Shulin Zhang; 
  • Rosilene Ribeiro; 
  • David Raubenheimer; 
  • Corinne Caillaud; 
  • Jian Tan; 
  • Samantha Solon-Biet; 
  • Peter A Cistulli; 
  • Stephen J Simpson

ABSTRACT

Background:

Branched chain amino acids (BCAAs) are essential amino acids that play a significant role in protein metabolism. A previous study in mice demonstrated that high intake of BCAAs relative to other amino acids on a high carbohydrate background was associated with hyperphagia, obesity and reduced lifespan. These effects were not attributed to BCAAs alone, nor did they manifest through canonical MTOR/IGF-1 pathways, but rather resulted from indirect effects of other AAs, notably tryptophan (Trp), on appetite.

Objective:

We report the design of a clinical study to assess the effects of BCAAs per se and in combination with Trp on appetite and other health measures in a cohort of elderly subjects, according to the protocol described in this paper.

Methods:

This is a randomised controlled clinical trial where a total number of 110 people, aged 65 to 80 with a BMI between 20 and 35kg/m2 will be recruited. Participants will be randomly allocated to one of the following study groups: 1) none; 2) BCAAs; 3) BCAAs + Trp or 4) BCAAs + Methionine (Met). The duration of intervention will be 4 weeks. The primary outcome measure will be appetite, which will be reflected by self-reported appetite and plasma blood Fibroblast Growth Factor 21 (FGF-21) level (a marker of protein appetite). Secondary outcomes will include energy intake, body composition, cardiometabolic health, gut microbiota, blood biomarkers, sleep and physical performance.

Results:

N/A

Conclusions:

This study will help determine the effect of BCAAs, either alone or in combination with tryptophan or methionine, on appetite and other health-related outcomes in an older population. The findings may offer a new nutrition intervention approach to address appetite regulation and health challenges to support healthy aging. Clinical Trial: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000402842. Date registered: 12 April 2021


 Citation

Please cite as:

Zhang S, Ribeiro R, Raubenheimer D, Caillaud C, Tan J, Solon-Biet S, Cistulli PA, Simpson SJ

Effect of Branched-Chain Amino Acid Supplementation Alone or Combined With Tryptophan or Methionine on Appetite Control and Related Health Outcomes in Older Adults: Protocol for a Randomized Controlled Trial

JMIR Res Protoc 2026;15:e82436

DOI: 10.2196/82436

PMID: 42166751

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