Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

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

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.

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.

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)

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Change in urine metabolome profile after low fructose diet and an enriched fructose diet according to a crossover design

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

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

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

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 of body weight after low fructose diet and an enriched fructose diet according to a crossover design

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

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

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

Debray FG, Seyssel K, Fadeur M, Tappy L, Paquot N, Tran C. Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance. Clin Nutr. 2021 Jun;40(6):4246-4254. doi: 10.1016/j.clnu.2021.01.026. Epub 2021 Jan 27.