Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

Laura Chiavaroli; Russell J de Souza; Vanessa Ha; Adrian I Cozma; Arash Mirrahimi; David D Wang; Matthew Yu; Amanda J Carleton; Marco Di Buono; Alexandra L Jenkins; Lawrence A Leiter; Thomas M S Wolever; Joseph Beyene; Cyril W C Kendall; David J A Jenkins; John L Sievenpiper

doi:10.1161/JAHA.114.001700

Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

J Am Heart Assoc. 2015 Sep 10;4(9):e001700. doi: 10.1161/JAHA.114.001700.

Authors

Laura Chiavaroli¹, Russell J de Souza², Vanessa Ha², Adrian I Cozma¹, Arash Mirrahimi³, David D Wang⁴, Matthew Yu⁵, Amanda J Carleton⁶, Marco Di Buono⁷, Alexandra L Jenkins⁸, Lawrence A Leiter⁹, Thomas M S Wolever¹⁰, Joseph Beyene¹¹, Cyril W C Kendall¹², David J A Jenkins⁹, John L Sievenpiper¹³

Affiliations

¹ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
² Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (R.J.S., V.H., J.B.).
³ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada (A.M.).
⁴ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
⁵ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) School of Dentistry, University of Minnesota, Minneapolis, MN (M.Y.).
⁶ Department of Undergraduate Medical Education (MD Program), Faculty of Medicine, University of Toronto, ON, Canada (A.J.C.).
⁷ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Heart and Stroke Foundation of Ontario, Toronto, ON, Canada (M.D.B.) American Heart Association, Dallas, TX (M.D.B.).
⁸ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
⁹ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada (L.A.L., T.S.W., D.A.J.).
¹⁰ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada (L.A.L., T.S.W., D.A.J.).
¹¹ Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (R.J.S., V.H., J.B.).
¹² Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada (C.C.K.).
¹³ Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (J.L.S.).

Abstract

Background: Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials.

Methods and results: MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials.

Conclusions: Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required.

Clinical trials registration: URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.

Keywords: lipids; meta‐analysis; nutrition.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Apolipoprotein B-100 / blood
Biomarkers / blood
Cardiovascular Diseases / blood
Cardiovascular Diseases / epidemiology
Chi-Square Distribution
Cholesterol, HDL / blood
Cholesterol, LDL / blood
Controlled Clinical Trials as Topic
Dietary Carbohydrates / administration & dosage*
Dietary Carbohydrates / adverse effects
Dyslipidemias / blood*
Dyslipidemias / diagnosis
Dyslipidemias / epidemiology
Energy Intake
Fructose / administration & dosage*
Fructose / adverse effects
Humans
Lipids / blood*
Metabolic Syndrome / blood
Metabolic Syndrome / epidemiology
Risk Factors
Time Factors
Triglycerides / blood

Substances

APOB protein, human
Apolipoprotein B-100
Biomarkers
Cholesterol, HDL
Cholesterol, LDL
Dietary Carbohydrates
Lipids
Triglycerides
Fructose

Associated data

ClinicalTrials.gov/NCT01363791

Grants and funding

102078/Canadian Institutes of Health Research/Canada