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Effects of dietary fructose on glucose and lipid metabolism in healthy human subjects

English title Effects of dietary fructose on glucose and lipid metabolism in healthy human subjects
Applicant Berneis Kaspar
Number 119706
Funding scheme Project funding
Research institution Klinik für Endokrinologie, Diabetologie und Klinische Ernährung Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Clinical Endocrinology
Start/End 01.06.2008 - 30.09.2011
Approved amount 279'000.00
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Keywords (4)

Fructose; lipids; LDL size; humans

Lay Summary (English)

Lay summary
Introduction: It is well known and highly debated that world wide and particularly in the USA sucrose and glucose are being replaced by fructose as a sweetener. The increasing intake of fructose has been associated with an increase in obesity among US children and adolescents, but its “dose dependent” effects on insulin sensitivity and lipid metabolism has not been studied in detail. However, fructose feeding in animal models has been shown to generate hypertension, dyslipidemia and obesity. In a recent study we found that in overweight children free dietary fructose originates more from sweets and drinks and less from fruits and vegetables when compared to normal weight children. In addition even small amounts of fructose were associated with a potentially atherogenic decrease in LDL particle size. Thus, fructose may also exert unfavourable effects on lipid metabolism in children when consumed in low amounts. Methods: 36 healthy male adult human subjects will be included in this study. They will be randomly allocated into a low, moderate or high fructose, a moderate or high glucose and a sucrose diet for 3 weeks. In randomized order and with four week wash out intervals each subject will receive all six different diets. Three day food records will be used to measure total fructose and glucose intake. During the low fructose diet subjects will be instructed to avoid nutrients containing fructose aiming at consumption of less than 1g fructose/d. During the moderate fructose diet subjects will receive 3x13.3g of fructose or glucose, respectively. High fructose diet subjects will receive either 3x26.7g/d of fructose, 3x 26.7g/d of glucose or 3x 26.7g/d of sucrose in the form of three daily soft drinks taken together with the three main meals. 75 g oral glucose tolerance testing will be performed and composite insulin sensitivity index will be calculated according to Matsuda and de Fronzo. Additional analyses include blood pressure and waist circumference. Plasma lipids, adiponectin and resistin will be measured by standard methods and LDL size will be measured by gradient gel electrophoresis. The presence of phosphorylated fructose metabolites in plasma will be measured by targeted LC-MS/MS. In addition, metabolite biomarkers in plasma will be screened by untargeted metabolite profiling using both LC-MS and GC-MS. Body composition will be measured by bioelectrical impedance analysis at baseline and after each visit. In a subgroup of 10 subjects a euglycemic hyperinsulinemic clamp instead of oral glucose testing will be performed using [6,6- 2H2]glucose to measure peripheral glucose uptake and hepatic glucose production.Hypothesis: It is hypothesized that low, normal and high fructose feeding will exert specific effects on lipid and glucose metabolism. Isoenergetic replacement of glucose with fructose allows direct comparisons of different metabolic effects of glucose vs. fructose in healthy human subjects. Based on our preliminary data in children it is hypothesized that fructose feeding even at moderate amount will have unfavourable effects on plasma lipids when compared to low or normal fructose diets or to isocaloric diets with glucose. In addition it is hypothesized that insulin sensitivity will be decreased in the moderate and high fructose diets when compared to normal or low fructose diets and when compared to the moderate and high glucose diets. High fructose diets may result in decreased peripheral glucose uptake and increased hepatic glucose production.RationaleThe described studies aim to assess the metabolic effect of different dosages of fructose using euglycemic clamp technique combined with a metabolomic approach. Thus, the lipogenic potential of fructose in humans will be compared with isocaloric amounts of glucose. Particularly, the question whether lipogenic effects are continuously dose dependent or whether there is a lipogenic shunting and if yes, at what level of ingested fructose will be addressed. Thus, these studies will help to understand better the pathophysiological properties of fructose.
Direct link to Lay Summary Last update: 21.02.2013

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