Does fructose worsen metabolism and liver inflammation in people with MASH?

Fructose is a Metabolic and Inflammatory Pathogenic Factor in Metabolic Dysfunction-associated Steatohepatitis (MASH)

This test looks at whether short-term dietary fructose changes metabolism and increases liver inflammation in people aged 45–65 with MASH, people with simple fatty liver (steatosis), and healthy controls.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 45 Years to 65 Years
• Sex: All
• Sponsor: Queen Mary University of London (other)
• Locations: 2 sites (London and 1 other locations)
• Trial ID: NCT07013916 on ClinicalTrials.gov

What this trial studies

This is a four-week, randomized, double-blind, parallel-arm food supplement intervention comparing the metabolic and inflammatory effects of fructose versus glucose in three groups: people with MASH (F2–F3 fibrosis), people with simple steatosis, and healthy controls. Participants aged 45–65 who are overweight or have stage I obesity will attend up to five visits including long baseline and post-intervention visits with standardized test meals and hourly blood sampling over about six hours. A subset of up to 24 participants will take part in an optional sub-study using a small stable isotope tracer to trace how fructose or glucose is metabolized after a meal. All primary visits are in-person and involve FibroScan or prior biopsy records to confirm liver status and frequent blood-based measurements of metabolic and inflammatory markers.

Who should consider this trial

Good fit: Ideal candidates are adults 45–65, overweight or with stage I obesity, without diabetes (HbA1c <48 mmol/mol), and with confirmed MASH (F2–F3 fibrosis by biopsy, FibroScan/AST criteria, or FAST score), or with simple steatosis, or healthy controls per FibroScan criteria.

Not a fit: People with diabetes, known fructose intolerance, pregnancy, ages outside 45–65, BMI outside the specified ranges, or advanced/other excluded liver disease are unlikely to be eligible or to benefit from the results.

Why it matters

Potential benefit: If successful, the results could clarify whether reducing dietary fructose lowers liver inflammation and metabolic stress in MASH and guide dietary advice to slow disease progression.

How similar studies have performed: Previous research has studied fructose effects in healthy volunteers, but using this randomized, controlled approach specifically in people with MASH is novel and not previously established.

Eligibility criteria

Inclusion Criteria:

* Able and willing to give written informed consent
* Age 45-65 at consent
* HbA1c \< 48 mmol/mol
* Overweight and stage I obesity using BMI thresholds adjusted for ethnicity:

  * 23.0kg/m2 - 32.4kg/m2 in South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean populations
  * 25kg/m2 - 34.9kg/m2 in White populations

MASH Patients:

Clinical diagnosis of MASH and F2 - F3 fibrosis:

Either:

Liver biopsy within 12 months of baseline

Or:

• History of histologically-diagnosed MASH with current evidence of fatty liver, AST\>20 and Fibroscan CAP≥248 dB/m and stiffness 9.5kPa -14kPa

Or:

• FAST score \>0.67

Patients with steatosis:

• defined by Fibroscan CAP≥248dB/m and stiffness \<7.9kPa.

Healthy controls:

• defined by Fibroscan CAP\<248dB/m and stiffness \<7.9kPa.

Exclusion Criteria:

* Unwilling or unable to give consent
* Age \<45 or \>65
* Any form of diabetes mellitus
* Currently pregnant
* Known fructose intolerance or food allergy
* Diagnosis of cirrhosis or Fibroscan stiffness \>14kPa
* Current Child-Pugh B/C or episode of decompensation in last year
* Non-MASLD liver disease known to participant (including viral hepatitis, auto-immune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, haemochromatosis, sarcoidosis, cystic fibrosis, sickle cell disease)
* Regular alcohol intake \> 14 units a week for females and \>21 units a week for males (participant-reported)
* Smoking, vaping or use of nicotine-containing products within the last month
* Taking prohibited medication:

  * Probiotic or antibiotic use within last 4 weeks (Note: participants will be considered eligible if they have undergone a 4-week washout from probiotics or 4-weeks after discontinuing antibiotic use)
  * any oral steroids within the last 6 weeks
  * current, or within 3 months, use of immunosuppressive medication
  * Amiodarone, nitrofurantoin, or anti-fungals within 3 months
  * Use of anti-obesity medication - orlistat or GLP-1 receptor agonist-containing treatments within 6 months
  * Use of vitamin E, pioglitazone or other medication for MASH including current or within 3 months enrolment in clinical trial unless documented to have been on placebo
* History of malignancy (except basal cell carcinoma), or medication for malignancy within the last 2 years
* Any major organ transplant (excluding corneal or hair)
* Clinical diagnosis of chronic kidney disease 3 or above, or of heart failure (NYHA 3 or 4)
* COPD requiring home oxygen
* Known eating disorder (e.g. anorexia nervosa) or severe mental illness (e.g. schizophrenia)
* Investigator opinion that study is unsuitable for patient

Where this trial is running

London and 1 other locations

• Royal London Hospital — London, United Kingdom (RECRUITING)
• Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: William Alazawi, MA(Cantab), MB, PhD

Conditions: MASH - Metabolic Dysfunction-Associated Steatohepatitis, MASH With Fibrosis, Steatosis of Liver, fructose, MASH, MASLD, liver, inflammation