Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Lausanne
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Metabolite concentration
Study Overview
Brief Summary
This study aimed to examine metabolic response to a short-term fructose enriched diet in carriers for hereditary fructose intolerance compared to controls. Effects of fructose coffees will be assessed in 7 healthy volunteers and 7 subjects with heterozygous mutation for ALDOB gene in a randomized, controlled, crossover trial.
Detailed Description
A high fructose intake also increases blood lactate and uric acid concentrations. It has been proposed that uric acid may contribute to insulin resistance by impairing endothelium-dependent vasodilation, promoting pro-inflammatory effects and dyslipidemia by activating de novo lipogenesis.
These consequences of fructose overconsumption may be even more marked in individuals with hereditary alterations in fructose metabolism. Indeed, individuals with hereditary fructose intolerance (HFI), due to biallelic mutations in the gene coding for aldolase B (ALDOB), may develop acute, life-threatening manifestations when exposed to fructose. Heterozygous carriers of ALDOB mutation are quite common in the general population, with a predicted frequency ranging between 1:55 and 1:120. Few studies have examined the effect of fructose ingestion in heterozygotes subject for HFI. Heterozygous carriers are generally considered to have normal fructose metabolism since a ~ 50% level of aldolase B activity is presumed to be sufficient for adequate function. However, heterozygous carriers were reported to have enhanced uric acid responses to large intravenous and/or oral fructose loads.
Investigators hypothesized that heterozygous carriers may also have mild defects of fructose metabolism and/or a larger increase in cardiometabolic risk factors than the normal population after ingestion of moderate amounts of fructose.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Case subjects: Heterozygous carriers for ALDOB mutation confirmed by molecular analysis
- •Control subjects: healthy individuals matched for weight and age to subjects
Exclusion Criteria
- •Fasting glucose > 7.0 mmol/L
- •Fasting triglycerides > 4.0 mmol/L
- •Chronic renal insufficiency (eGFR < 50 ml/min)
- •Women who are pregnant or breast feeding
- •For women: lack of safe contraception
- •Alcool consumption > 30g/d
- •Inability to discern
Arms & Interventions
Experimental diet Fru rich diet
Enriched fructose diet from day 1 to day 7.
Intervention: Experimental diet Fru rich diet (Other)
Experimental low Fru diet
Low fructose diet from day 1 to day 7.
Intervention: Experimental low Fru diet (Other)
Outcomes
Primary Outcomes
Metabolite concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
The primary endpoint is the change of metabolite concentration after ingestion of a test meal (oral glucose and fructose load) under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Secondary Outcomes
- Urine uric acid concentration(Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
- Plasma triglycerides concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma insulin concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma urea concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma amino acid concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Urine creatinine concentration(Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
- Urine urea concentration(Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
- Plasma fructose concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma creatinine concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma ammonia concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma aspartate transaminase (ASAT) concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Urine metabolome concentration(Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
- Plasma uric acid concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma lactate concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma phosphate concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma metabolome concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Blood pressure(Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
- Plasma glucose concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Plasma alanine transaminase (ALAT) concentration(Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal)
- Body weight(Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design)
Investigators
Christel Tran
Principal Investigator
University of Lausanne