Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

University of Lausanne (UNIL)

Status: Completed

Conditions: Hereditary Fructose Intolerance

Treatments: Other: Experimental diet Fru rich diet; Other: Experimental low Fru diet

Study type: Interventional

Funder types: Other

Identifiers

NCT03545581

2016-00289

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

12 participants in 2 patient groups

Experimental diet Fru rich diet

Other group

Description:

Enriched fructose diet from day 1 to day 7.

Treatment:

Other: Experimental diet Fru rich diet

Experimental low Fru diet

Other group

Description:

Low fructose diet from day 1 to day 7.

Treatment:

Other: Experimental low Fru diet