Does the gut convert fructose into glucose to protect the liver?

Fructose Metabolism Effects on the Liver: Unraveling the Role of Defective Intestinal GNG in Individuals With Obesity

We will test whether the small intestine can turn normal amounts of fructose into glucose to protect the liver, and whether this process is weaker in people with obesity.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 20 Years to 55 Years
• Sex: All
• Sponsor: Touro University, California (Academic / other)
• Locations: 1 site (Vallejo, California)
• Trial ID: NCT07209202 on ClinicalTrials.gov

What this trial studies

This crossover study will enroll lean and obese but otherwise healthy adults to compare how the small intestine handles fructose. After a baseline sugar tolerance test, participants will complete four outpatient tracer/feeding visits approximately three weeks apart, consuming liquid meals that differ only in fructose content while receiving oral or intravenous 13C-labeled fructose. During each six-hour fed tracer protocol, blood and urine samples will be collected frequently and vital signs and anthropometrics will be measured. Comparing high- and low-fructose meals and oral versus IV tracers will allow quantification of intestinal gluconeogenesis and whether that protective mechanism is impaired in obesity.

Who should consider this trial

Good fit: Adults who are otherwise healthy and either lean (BMI 19–25 kg/m2) or obese (BMI 30–38 kg/m2) without diabetes, significant liver disease, recent major weight change, or disqualifying medical conditions or medications.

Not a fit: People with diabetes, known liver disease, very high triglycerides or cholesterol, recent weight-loss surgery, pregnancy or recent lactation, active infections like HIV/hepatitis, or use of anti-diabetic or lipid-lowering drugs are excluded and unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, the findings could clarify a gut-based protective mechanism and inform dietary guidance or new strategies to prevent fructose-related liver damage.

How similar studies have performed: Animal studies and some human tracer work support intestinal gluconeogenesis and its metabolic role, but human crossover tracer studies specifically linking intestinal glucose production to liver protection in obesity are limited.

Eligibility criteria

Inclusion Criteria:

* BMI 30 to 38 kg/m2 (obese group) or BMI 19 to 25 kg/m2 (lean group)

Exclusion Criteria:

* Pregnancy or lactation within the past six months;
* Type 1 or 2 diabetes mellitus (including fasting glucose ≥126 mg/dL, HgbA1c ≥6.5%);
* History of liver disease or AST and ALT 2x above the upper limit of normal;
* Fasting triglyceride \> 300 mg/dl; total cholesterol levels above the 95th percentile for age and sex;
* Hemoglobin (Hgb) \<12.5g/d or hematocrit\<3x Hgb value;
* Report of HIV or hepatitis B or C infection;
* History of cancer, other than basal cell or squamous cell carcinoma or kidney disease stage 3 or higher or patients currently on dialysis;
* Use of any anti-diabetic medications or hypolipidemic agents in the past six months;
* History of surgical procedure for obesity;
* Change in body weight \>5% in the past six months (by self-report);
* History of other conditions known to affect insulin sensitivity and lipid metabolism (e.g., polycystic ovary syndrome), history of galactosemia, hereditary fructose intolerance, or who test positive for fructose malabsorption at screening;
* Known intolerance to acetaminophen.

Where this trial is running

Vallejo, California

• Touro University California — Vallejo, California, United States (Recruiting)

Study contacts

• Principal investigator: Jean-Marc Schwarz, PhD — Touro University, California
• Study coordinator: Sally Chiu, PhD

Conditions Healthy Participants; Obese But Otherwise Healthy Participants; Fructose; Sugar