Heterogeneous Effects of Fructose on Blood Lipids in Individuals With Type 2 Diabetes
Systematic review and meta-analysis of experimental trials in humans
- John L. Sievenpiper, MD, PHD1,2,
- Amanda J. Carleton, BSC1,2,
- Sheena Chatha, MD1,
- Henry Y. Jiang, BSC3,
- Russell J. de Souza, MSC, RD4,
- Joseph Beyene, PHD5,
- Cyril W.C. Kendall, PHD1,2,6 and
- David J.A. Jenkins, MD, PHD, DSC1,2,7
- 1Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada;
- 2Departments of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada;
- 3Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada;
- 4Harvard School of Public Health, Department of Nutrition, Boston, Massachusetts;
- 5Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada, and Population Health Sciences, Research Institute Hospital for Sick Children, Toronto, Ontario, Canada;
- 6College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;
- 7Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Corresponding author: David J.A. Jenkins, cyril.kendall{at}utoronto.ca.
Abstract
OBJECTIVE Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes.
RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of ≥7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by χ2 tests and quantified by I2. Meta-regression models identified dose threshold and independent predictors of effects.
RESULTS Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05–0.44]), dose was >60 g/day (0.18 [0.00–0.37]), or follow-up was ≤4 weeks (0.18 [0.00–0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R2 = 0.13)/10% energy (R2 = 0.36). A total cholesterol–lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (−0.19 [−0.34 to −0.05]), dietary fat >30% energy (−0.33 [−0.52 to −0.15]), or crystalline fructose (−0.28 [−0.47 to −0.09]). Multivariate meta-regression analyses were largely in agreement.
CONCLUSIONS Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol–lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received March 31, 2009.
- Accepted July 6, 2009.
- © 2009 by the American Diabetes Association.
