Fructose Supplementation in Carriers for Hereditary Fructose Intolerance
Kulcsszavak
Absztrakt
Leírás
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.
Dátumok
| Utolsó ellenőrzés: | 03/31/2019 |
| Első benyújtás: | 05/06/2018 |
| Becsült beiratkozás benyújtva: | 05/21/2018 |
| Első közzététel: | 06/03/2018 |
| Utolsó frissítés beküldve: | 04/18/2019 |
| Utolsó frissítés közzétéve: | 04/21/2019 |
| A tanulmány tényleges kezdési dátuma: | 04/30/2018 |
| Becsült elsődleges befejezési dátum: | 11/30/2018 |
| A tanulmány becsült befejezési dátuma: | 03/31/2019 |
Állapot vagy betegség
Beavatkozás / kezelés
Other: Experimental diet Fru rich diet
Other: Experimental low Fru diet
Fázis
Karcsoportok
| Kar | Beavatkozás / kezelés |
|---|---|
| Other: Experimental diet Fru rich diet Enriched fructose diet from day 1 to day 7. | Other: Experimental 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) |
| Other: Experimental low Fru diet Low fructose diet from day 1 to day 7. | Other: Experimental 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) |
Jogosultsági kritériumok
| Tanulásra alkalmas korok | 18 Years Nak nek 18 Years |
| Tanulásra alkalmas nemek | All |
| Egészséges önkénteseket fogad | Igen |
| Kritériumok | 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 |
Eredmény
Elsődleges eredménymérők
1. Metabolite concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
Másodlagos eredménymérők
1. Plasma glucose concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
2. Plasma insulin concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
3. Plasma fructose concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
4. Plasma uric acid concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
5. Plasma lactate concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
6. Plasma urea concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
7. Plasma creatinine concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
8. Plasma phosphate concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
9. Plasma triglycerides concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
10. Plasma metabolome concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
11. Plasma ammonia concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
12. Plasma amino acid concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
13. Plasma alanine transaminase (ALAT) concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
14. Plasma aspartate transaminase (ASAT) concentration [Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal]
15. 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]
16. 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]
17. 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]
18. 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]
19. 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]
20. 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]
