Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance

Sponsors

Lead Sponsor: University of Lausanne

Collaborator: University of Liege

Source University of Lausanne
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.

Overall Status Completed
Start Date 2018-05-01
Completion Date 2019-04-01
Primary Completion Date 2018-12-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Metabolite concentration Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary Outcome
Measure Time Frame
Plasma glucose 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 fructose concentration Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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 urea 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 phosphate concentration Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma triglycerides 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
Plasma ammonia 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
Plasma alanine transaminase (ALAT) 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
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
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
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
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
Enrollment 12
Condition
Intervention

Intervention Type: Other

Intervention Name: Experimental diet Fru rich diet

Description: 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)

Arm Group Label: Experimental diet Fru rich diet

Intervention Type: Other

Intervention Name: Experimental low Fru diet

Description: 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)

Arm Group Label: Experimental low Fru diet

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

65 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Location
Facility: Guillaume Debray
Location Countries

Belgium

Verification Date

2019-04-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Lausanne

Investigator Full Name: Christel Tran

Investigator Title: Principal Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Experimental diet Fru rich diet

Type: Other

Description: Enriched fructose diet from day 1 to day 7.

Label: Experimental low Fru diet

Type: Other

Description: Low fructose diet from day 1 to day 7.

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Prevention

Masking: None (Open Label)

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