Heterogeneous effects of fructose on blood lipids in people with type 2 diabetes: Systematic review and meta-analyses of experimental trials in humans.
- John L Sievenpiper, MD, PhD,
- Amanda J Carleton, BSc,
- Sheena Chatha, MD,
- Henry Y Jiang, BSc,
- Russell J de Souza, MSc, RD,
- Joseph Beyene, PhD,
- Cyril WC Kendall, PhD (cyril.kendall{at}utoronto.ca) and
- David JA Jenkins, MD, PhD, DSc
- Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, CANADA (JLS, AJC, SC, CWCK, DJAJ); Departments of Nutritional Sciences (JLS, AJC, CWCK, DJAJ) and Medicine (DJAJ) and the Dalla Lana School of Public Health (JB), Faculty of Medicine, University of Toronto, Toronto, ON, CANADA; Michael G. DeGroote School of Medicine (HYJ) and Department of Clinical Epidemiology & Biostatistics (JB), McMaster University, Hamilton, ON, CANADA; Harvard School of Public Health, Department of Nutrition, Boston, MA, USA (RJD); Population Health Sciences, Research Institute Hospital for Sick Children, Toronto, ON, CANADA (JB), College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CANADA (CWCK)
Abstract
Background: Because of blood lipid concerns, Diabetes Associations discourage fructose at high intakes. To quantify the effect of fructose 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.
Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of ≥7d. Data were pooled by the generic inverse variance method and expressed as standardized mean differences (SMD) with 95% CI. Heterogeneity was assessed by Chi2 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 where the reference carbohydrate was starch [0.24 (0.05,0.44)], dose was >60g/d [0.18 (0.00,0.37)], or follow-up was ≤4wk [0.18 (0.00,0.35)]. Piecewise meta-regression confirmed a dose threshold of 60g/d (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,−0.05)], dietary fat >30% energy [−0.33 (−(0.52,−0.15)], or crystalline fructose [−0.28 (−0.47,−0.09]]. Multivariate meta-regression analyses were largely in agreement.
Conclusion: 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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- Received March 31, 2009.
- Accepted July 6, 2009.
- Copyright © American Diabetes Association
