Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Metabolite concentration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Case subjects: Heterozygous carriers for ALDOB mutation confirmed by molecular analysis
- •Control subjects: healthy individuals matched for weight and age to subjects
排除标准
- •Fasting glucose > 7.0 mmol/L
- •Fasting triglycerides > 4.0 mmol/L
- •Chronic renal insufficiency (eGFR < 50 ml/min)
- •Women who are pregnant or breast feeding
- •For women: lack of safe contraception
- •Alcool consumption > 30g/d
- •Inability to discern
研究组 & 干预措施
Experimental diet Fru rich diet
Enriched fructose diet from day 1 to day 7.
干预措施: Experimental diet Fru rich diet (Other)
Experimental low Fru diet
Low fructose diet from day 1 to day 7.
干预措施: Experimental low Fru diet (Other)
结局指标
主要结局
Metabolite concentration
时间窗: 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
次要结局
- Plasma triglycerides 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 urea 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)
- 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)
- Plasma fructose 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 ammonia 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)
- 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 phosphate 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)
- 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)
- Plasma glucose 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)
- 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)
研究者
Christel Tran
Principal Investigator
University of Lausanne