Effects of Dietary Fructose on Glucose and Lipid Metabolism in Healthy Human Subjects
Summary
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. 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 4 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 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. In a subgroup of 10 subjects an euglycemic hyperinsulinemic clamp will be performed using [6,6- 2H2]glucose.
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.
Study Design
Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention
Conditions
Healthy
Intervention
Fructose
Location
University Hospital Zurich
Zurich
Switzerland
8091
Status
Active, not recruiting
Source
University of Zurich
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01021969
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-07-24T14:10:47-0400
Clinical Trials
Acute Effect of Fructose on Lipid Metabolism and Gender Differences
It has been widely documented that fructose overfeeding increases plasma triglycerides and hepatic de novo lipogenesis, and impairs insulin sensitivity in healthy male volunteers. The effe...
Pharmacokinetics and Pharmacodynamics of Fructose
The purpose of this study is to determine whether sucrose vs high fructose corn syrup from a soft drink results in differences in various metabolic byproducts such as fructose, glucose, se...
Effects of Fructose and Exercise on Hepatic Lipid Metabolism
8 healthy male volunteers will be studied each on 3 occasions, ie - after 4 days on a weight maintenance diet containing 5% simple sugars + low physical activity - after...
The Effect of Fructose on Blood Fats in Dialysis Patients and Healthy Volunteers
This study will evaluate how a common dietary sugar (fructose) raises blood fats (triglycerides). We will determine whether the production of fat from fructose is higher in dialysis patie...
Acute Metabolic and Endocrine Responses of Glucose and Fructose in Healthy Young Subjects
The purpose of this study is to investigate the metabolic and endocrine responses during 3 hour after taking 75g fructose or glucose in young Chinese.
PubMed Articles
Fructose feeding increases hepatic de novo lipogenesis (DNL) and is associated with non-alcoholic fatty liver disease. Little is known, however, about individual variation in susceptibility to fructos...
The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids.
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructos...
ChREBP deficiency leads to diarrhea-predominant irritable bowel syndrome.
Fructose malabsorption is a common digestive disorder in which absorption of fructose in the small intestine is impaired. An abnormality of the main intestinal fructose transporter proteins has been p...
Metabolism of fructose in B-cells: A C NMR spectroscopy based stable isotope tracer study.
Earlier studies on glucose metabolism in B-cells suggested an active TCA cycle in both naïve B cells and differentiated IgA plasma cells. Glycolysis was shown to be more active in IgA plasma cells th...
Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first...
Medical and Biotech [MESH] Definitions
Fructose Intolerance
An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1-phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet.
Fructose-bisphosphatase
An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC 3.1.3.11.
Fructose Metabolism, Inborn Errors
Inherited abnormalities of fructose metabolism, which include three known autosomal recessive types: hepatic fructokinase deficiency (essential fructosuria), hereditary fructose intolerance, and hereditary fructose-1,6-diphosphatase deficiency. Essential fructosuria is a benign asymptomatic metabolic disorder caused by deficiency in fructokinase, leading to decreased conversion of fructose to fructose-1-phosphate and alimentary hyperfructosemia, but with no clinical dysfunction; may produce a false-positive diabetes test.
Phosphofructokinase-2
An allosteric enzyme that regulates glycolysis and gluconeogenesis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-2,6-bisphosphate, an allosteric effector for the other 6-phosphofructokinase, PHOSPHOFRUCTOKINASE-1. Phosphofructokinase-2 is bifunctional: the dephosphorylated form is a kinase and the phosphorylated form is a phosphatase that breaks down fructose-2,6-bisphosphate to yield fructose-6-phosphate.
Phosphofructokinases
Allosteric enzymes that regulate glycolysis and gluconeogenesis. These enzymes catalyze phosphorylation of fructose-6-phosphate to either fructose-1,6-bisphosphate (PHOSPHOFRUCTOKINASE-1 reaction), or to fructose-2,6-bisphosphate (PHOSPHOFRUCTOKINASE-2 reaction).
