Hereditary Fructose Intolerance
Conditions
Keywords
Fructose, Uric acid, Glucose homeostasis
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.
Interventions
OTHERExperimental diet Fru rich diet
7 days (day 1 to day 7) with fructose enriched drinks 3x/d. Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight)
OTHERExperimental low Fru diet
7 days (day 1 to day 7) with low-fructose diet (\<10g/d). Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight)
Sponsors
University of Liege
University of Lausanne
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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) * Drugs * Women who are pregnant or breast feeding * For women: lack of safe contraception * Alcool consumption \> 30g/d * Inability to discern
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolite concentration | 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
| Measure | Time frame | Description |
|---|---|---|
| Plasma insulin concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in insulin concentration after ingestion of a test meal under 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 | Change in fructose concentration after ingestion of a test meal under 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 | Change in uric acid concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma lactate concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in lactate concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma urea concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in urea concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma creatinine concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in creatinine concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma phosphate concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in phosphate concentration after ingestion of a test meal under 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 | Change in triglycerides concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma metabolome concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in metabolome concentration after ingestion of a test meal under 2 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 | Change in glucose concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma amino acid concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in amino acid concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma alanine transaminase (ALAT) concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in alanine transminase (ALAT) concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| Plasma aspartate transaminase (ASAT) concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in aspartate transaminase (ASAT) concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
| 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 | Change in urine metabolome profile after low fructose diet and an enriched fructose diet according to a crossover design |
| 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 | Change in urine creatinine profile after low fructose diet and an enriched 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 | Change in urine urea profile after low fructose diet and an enriched fructose diet according to a crossover design |
| 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 | Change in urine uric acid profile after low fructose diet and an enriched fructose diet according to a crossover design |
| 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 | Change of body weight after low fructose diet and an enriched fructose diet according to a crossover design |
| 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 | Change of systolic and diastolic pressure after low fructose diet and an enriched fructose diet according to a crossover design |
| Plasma ammonia concentration | Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal | Change in ammonia concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design |
Countries
Belgium
Outcome results
None listed