Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.
14 affiliations
- 1Hypertension Research Laboratory, Victorian Heart Institute, Monash University, Clayton, Australia.
- 2Department of Pharmacology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, Australia.
- 3Nutrition & Health Innovation Research Institute, Edith Cowan University, Perth, Australia.
- 4Cardiometabolic Health and Exercise Physiology, Baker Diabetes and Heart Institute, Melbourne, Australia.
- 5Human Neurophysiology Lab, Department of Neuroscience, Monash University, Melbourne, Australia.
- 6School of Psychological Science, Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.
- 7Digital Nutrition Lab, Department of Nutrition, Dietetics and Food, Monash University, Melbourne, Australia.
- 8Victorian Heart Institute, Monash University, Clayton, Australia.
- 9Victorian Heart Hospital, Melbourne, Australia.
- 10Food Engineering and Nutrition Lab, Department of Chemical Engineering, Monash University, Melbourne, Australia.
- 11School of Health Science and Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.
- 12Baker Heart and Diabetes Institute, Melbourne, Australia.
- 13Hypertension Research Laboratory, Victorian Heart Institute, Monash University, Clayton, Australia. [email protected].
- 14Department of Pharmacology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, Australia. [email protected].
Abstract
Background
Hypertension affects 1 in 3 Australian adults and is a major contributor to stroke and myocardial infarction. Despite the availability of various medications, over 50% of patients struggle to control their blood pressure (BP) due to nonadherence, difficulty finding the right treatment, or avoidance of medication. Diet plays a key role in cardiovascular health, with high-fiber intake shown to lower BP through the production of short-chain fatty acids (SCFAs), metabolites formed during fiber fermentation. A previous clinical trial found that incorporating a specific type of resistant starch - high amylose maize starch enriched with acetate and butyrate (HAMSA/B) - significantly reduced blood pressure in hypertensive patients. While the exact mechanism remains unclear, SCFAs may influence BP via the gut-brain axis by reducing muscle sympathetic nerve activity (MSNA), which has vasoconstrictor function and is elevated in hypertensive individuals.Methods
The GRAINS-BP clinical trial will recruit 29 adults with untreated hypertension (≥ 140/90 mmHg) for a double-blind, cross-over study using HAMSA/B administered as a shake delivered twice daily. The assessment period will span 48 days and include four visits at the Alfred Hospital, Melbourne, Australia. At visit 1, baseline measurement will be taken, including muscle sympathetic nerve activity (MSNA) and electrocardiogram (ECG). Participants will be randomised to the order in which they receive the placebo and HAMSA/B shake. Each intervention period will last 14 days, separated by a 20-day washout before participants cross over to the alternate treatment. At each visit, faecal, urine, and blood samples will be collected to investigate microbiome, cardiometabolic, renal, and immune profiles, respectively. Univariate and multivariate statistical analyses will be conducted to examine treatment effects and to identify correlations among microbiome, cardiometabolic, renal, and immune outcomes.Discussion
This project's primary outcome is change in autonomic nervous system activity. Secondary outcomes include 24-h BP, gut microbiome composition, SCFA levels, immune cell profiles gastrointestinal transit time, quality of life, anxiety and depression symptoms, cognitive function, gut barrier integrity, and circulating micro- and nanoplastics. Findings from this study will reveal whether SCFAs reduce blood pressure by their influence on the autonomic nervous system.Trial registration
This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000557437).
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BibTeX
@article{welathanthree2026regulated,
title = {{Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.}},
author = {Malindi Welathanthree and Matthew Snelson and Donggyu Rim and Brendan McCarthy and Gianni Sesa-Ashton and David G S Farmer and Chaoran Yang and Jianan Lu and Phoebe T T Cheong and Matthew P Pase and Tracy McCaffrey and Francis J Ha and Sushil Dhital and Esther Davis and Elisabeth Lambert and Vaughan G Macefield and Francine Z Marques and Rikeish R Muralitharan},
journal = {Trials},
year = {2026},
month = jul,
doi = {10.1186/s13063-026-09911-0},
url = {https://europepmc.org/article/MED/42894232},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.
AU - Malindi Welathanthree
AU - Matthew Snelson
AU - Donggyu Rim
AU - Brendan McCarthy
AU - Gianni Sesa-Ashton
AU - David G S Farmer
AU - Chaoran Yang
AU - Jianan Lu
AU - Phoebe T T Cheong
AU - Matthew P Pase
AU - Tracy McCaffrey
AU - Francis J Ha
AU - Sushil Dhital
AU - Esther Davis
AU - Elisabeth Lambert
AU - Vaughan G Macefield
AU - Francine Z Marques
AU - Rikeish R Muralitharan
PY - 2026
DA - 2026/07/01
JO - Trials
DO - 10.1186/s13063-026-09911-0
UR - https://europepmc.org/article/MED/42894232
AB - Background Hypertension affects 1 in 3 Australian adults and is a major contributor to stroke and myocardial infarction. Despite the availability of various medications, over 50% of patients struggle to control their blood pressure (BP) due to nonadherence, difficulty finding the right treatment, or avoidance of medication. Diet plays a key role in cardiovascular health, with high-fiber intake shown to lower BP through the production of short-chain fatty acids (SCFAs), metabolites formed during fiber fermentation. A previous clinical trial found that incorporating a specific type of resistant starch - high amylose maize starch enriched with acetate and butyrate (HAMSA/B) - significantly reduced blood pressure in hypertensive patients. While the exact mechanism remains unclear, SCFAs may influence BP via the gut-brain axis by reducing muscle sympathetic nerve activity (MSNA), which has vasoconstrictor function and is elevated in hypertensive individuals.Methods The GRAINS-BP clinical trial will recruit 29 adults with untreated hypertension (≥ 140/90 mmHg) for a double-blind, cross-over study using HAMSA/B administered as a shake delivered twice daily. The assessment period will span 48 days and include four visits at the Alfred Hospital, Melbourne, Australia. At visit 1, baseline measurement will be taken, including muscle sympathetic nerve activity (MSNA) and electrocardiogram (ECG). Participants will be randomised to the order in which they receive the placebo and HAMSA/B shake. Each intervention period will last 14 days, separated by a 20-day washout before participants cross over to the alternate treatment. At each visit, faecal, urine, and blood samples will be collected to investigate microbiome, cardiometabolic, renal, and immune profiles, respectively. Univariate and multivariate statistical analyses will be conducted to examine treatment effects and to identify correlations among microbiome, cardiometabolic, renal, and immune outcomes.Discussion This project's primary outcome is change in autonomic nervous system activity. Secondary outcomes include 24-h BP, gut microbiome composition, SCFA levels, immune cell profiles gastrointestinal transit time, quality of life, anxiety and depression symptoms, cognitive function, gut barrier integrity, and circulating micro- and nanoplastics. Findings from this study will reveal whether SCFAs reduce blood pressure by their influence on the autonomic nervous system.Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000557437).
SN - 1745-6215
ER -