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Fructose vs. glucose and metabolism: do the metabolic differences matter?

Sievenpiper, John L.a,b; de Souza, Russell J.c; Cozma, Adrian I.a,d; Chiavaroli, Lauraa,d; Ha, Vanessaa,d; Mirrahimi, Arasha,e

doi: 10.1097/MOL.0000000000000042
NUTRITION AND METABOLISM: Edited by Frank M. Sacks and Lawrence J. Appel

Purpose of review: Fructose is seen as uniquely contributing to the pandemics of obesity and its cardiometabolic complications. Much of the evidence for this view derives from the unique biochemical, metabolic, and endocrine responses that differentiate fructose from glucose. To understand whether these proposed mechanisms result in clinically meaningful modification of cardiovascular risk in humans, we update a series of systematic reviews and meta-analyses of controlled feeding trials to assess the cardiometabolic effects of fructose in isocaloric replacement for glucose.

Recent findings: A total of 20 controlled feeding trials (n = 344) have investigated the effect of fructose in/on cardiometabolic endpoints. Pooled analyses show that although fructose may increase total cholesterol, uric acid, and postprandial triglycerides in isocaloric replacement for glucose, it does not appear to be any worse than glucose in its effects on other aspects of the lipid profile, insulin, or markers of nonalcoholic fatty liver disease. It may also have important advantages over glucose for body weight, glycemic control, and blood pressure.

Summary: Depending on the cardiometabolic endpoint in question, fructose has variable effects when replacing glucose. In the absence of clear evidence of net harm, there is no justification to replace fructose with glucose in the diet.

aToronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto

bDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University

cDepartment of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton

dDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto

eSchool of Medicine, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada

Correspondence to Dr John L. Sievenpiper, MD, PhD, Knowledge Synthesis Lead, Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, #6137-61 Queen Street East, Toronto, ON, M5C 2T2, Canada. Tel: +1 416 867 7475; fax: +1 416 867 7495; e-mail:

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