Isocaloric Navy-Bean Substitution in Adults With MASLD

Rationale: Diet acts on MASLD progression through the gut-liver axis, in which microbial composition, intestinal barrier integrity, and microbe-derived metabolites influence hepatic inflammation, steatosis, and fibrosis. Navy beans supply fermentable fiber, resistant starch, and polyphenols that nourish short-chain-fatty-acid-producing microbes, and prior human work (the BE GONE trial) demonstrated increased microbial diversity, enrichment of beneficial taxa, and favorable metabolomic and proteomic shifts following an 8-week navy-bean intervention. An isocaloric substitution approach isolates bean-specific biologic effects from weight change, addressing a major confounder in MASLD dietary trials.

Inclusion criteria

• Adults 18-75 years of age with capacity to provide informed consent
• Enrolled in the Mount Sinai Steatotic Liver Disease registry with a clinical diagnosis of MASLD, confirmed by imaging (MRI-PDFF or VCTE) or prior biopsy
• Intermediate-stage fibrosis (F2-F3) confirmed by one of the following (most recent qualifying result): VCTE (FibroScan) 8.0-14 kPa, MRE 3.0-4.6 kPa (2D EPI @ 60 Hz), or liver biopsy read as F2-F3
• Body mass index 25-45 kg/m²
• Stable medications for ≥12 weeks for diabetes, hypertension, dyslipidemia, or weight management
• Alcohol intake below MASLD thresholds (≤15 drinks/week for men, ≤10 drinks/week for women)
• Willing and able to consume study navy beans and complete dietary recalls (ASA-24/DSQ)
• Able to undergo MRI and MRE (no contraindications) and attend study visits
• Agrees to biospecimen collection (blood, stool, saliva) and patient-reported outcomes

Exclusion criteria

• Other chronic liver disease (hepatitis B, hepatitis C, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis)
• Decompensated liver disease (ascites, variceal bleeding, encephalopathy) or Child-Pugh B/C cirrhosis, or clinical portal hypertension/decompensation
• Heavy alcohol use above MASLD thresholds, or alcohol use disorder within 12 months
• Legume/bean allergy or intolerance
• Initiation or dose change of antidiabetic, lipid-lowering, antihypertensive, or weight-loss medications within the past 12 weeks, or anticipated changes during the trial
• Recent initiation of agents known to affect hepatic fat or fibrosis (e.g., GLP-1 receptor agonist, SGLT2 inhibitor, pioglitazone, resmetirom) within 12 weeks
• Use of hepatotoxic drugs likely to confound liver enzymes in the prior 12 weeks (per investigator judgment)
• New supplements targeting weight loss, liver health, or the microbiome within 8-12 weeks (e.g., berberine, high-dose omega-3, pre/probiotics)
• Antibiotics, probiotics, or colonoscopy preparation within 8 weeks
• Planned bariatric surgery or other major weight-loss intervention during the study
• Recent weight change >5% within 8-12 weeks prior to baseline
• Severe gastrointestinal disease (inflammatory bowel disease, celiac disease, short bowel syndrome) that may impair tolerance
• Uncontrolled diabetes (HbA1c >10%), severe renal dysfunction (eGFR <45), or unstable cardiovascular, thyroid, or psychiatric illness
• Pregnant or breastfeeding
• Contraindications to MRI (e.g., non-compatible implants, severe claustrophobia)
• Participation in another interventional study within the last 30 days