{
  "abstract": "Background\n\nHypertension 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\n\nThe 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\n\nThis 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\n\nThis trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000557437).",
  "abstract_shown": true,
  "affiliations": [
    "Hypertension Research Laboratory, Victorian Heart Institute, Monash University, Clayton, Australia.",
    "Department of Pharmacology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, Australia.",
    "Nutrition & Health Innovation Research Institute, Edith Cowan University, Perth, Australia.",
    "Cardiometabolic Health and Exercise Physiology, Baker Diabetes and Heart Institute, Melbourne, Australia.",
    "Human Neurophysiology Lab, Department of Neuroscience, Monash University, Melbourne, Australia.",
    "School of Psychological Science, Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.",
    "Digital Nutrition Lab, Department of Nutrition, Dietetics and Food, Monash University, Melbourne, Australia.",
    "Victorian Heart Institute, Monash University, Clayton, Australia.",
    "Victorian Heart Hospital, Melbourne, Australia.",
    "Food Engineering and Nutrition Lab, Department of Chemical Engineering, Monash University, Melbourne, Australia.",
    "School of Health Science and Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.",
    "Baker Heart and Diabetes Institute, Melbourne, Australia.",
    "Hypertension Research Laboratory, Victorian Heart Institute, Monash University, Clayton, Australia. rikeish.muralitharan@monash.edu.",
    "Department of Pharmacology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, Australia. rikeish.muralitharan@monash.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
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        0,
        1
      ],
      "name": "Malindi Welathanthree"
    },
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        2
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      "name": "Matthew Snelson"
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      "name": "Donggyu Rim"
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        3
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      "name": "Brendan McCarthy"
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    {
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        3
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      "name": "Gianni Sesa-Ashton"
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      "name": "David G S Farmer"
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        1
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      "name": "Chaoran Yang"
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        1
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      "name": "Jianan Lu"
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      "name": "Phoebe T T Cheong"
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    {
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        5
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      "name": "Matthew P Pase"
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    {
      "affs": [
        6,
        7
      ],
      "name": "Tracy McCaffrey"
    },
    {
      "affs": [
        8
      ],
      "name": "Francis J Ha"
    },
    {
      "affs": [
        9
      ],
      "name": "Sushil Dhital"
    },
    {
      "affs": [
        8
      ],
      "name": "Esther Davis"
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    {
      "affs": [
        10
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      "name": "Elisabeth Lambert"
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    {
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        4
      ],
      "name": "Vaughan G Macefield"
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    {
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        1,
        11
      ],
      "name": "Francine Z Marques"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Rikeish R Muralitharan",
      "orcid": "0000-0002-7577-2123"
    }
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  "bibtex": "https://research.draconitic.com/paper/8fwzbfzv614v7.bib",
  "cited_by": 0,
  "doi": "10.1186/s13063-026-09911-0",
  "fulltext_url": "https://europepmc.org/articles/PMC13679180",
  "id": "8fwzbfzv614v7",
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  "landing_url": "https://europepmc.org/article/MED/42894232",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
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  "pdf_url": "https://europepmc.org/articles/PMC13679180?pdf=render",
  "pmcid": "PMC13679180",
  "pmid": "42894232",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/8fwzbfzv614v7.ris",
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    {
      "first_seen": "2026-10-30T12:19:42Z",
      "native_id": "MED:42894232",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Blood Pressure and Hypertension Studies",
      "subfield": "cardiovascular"
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  "title": "Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.",
  "title_text": "Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:24Z",
  "url": "https://research.draconitic.com/paper/8fwzbfzv614v7",
  "venue": "Trials",
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