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The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.
Nutrients. 2018 Nov 20; 10(11)N

Abstract

Objective:

Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (≤10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control.

Methods:

We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ≥1 week that investigated the effect of small doses (≤50 g/day or ≤10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence.

Results:

We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = -0.38% (95% CI: -0.64%, -0.13%); MD = -0.20% (95% CI: -0.34%, -0.06%)) and fasting glucose (MD = -0.13 mmol/L (95% CI: -0.24 mmol/L, -0.03 mmol/L)); MD = -0.30 mmol/L (95% CI: -0.57 mmol/L, -0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate.

Conclusions:

Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates.

Authors+Show Affiliations

Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. jarvis.noronha@mail.utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. jarvis.noronha@mail.utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. catherine.braunstein@mail.utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. catherine.braunstein@mail.utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. sonia.blancomejia@mail.utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. sonia.blancomejia@mail.utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. tauseef.khan@utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. tauseef.khan@utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. cyril.kendall@utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. cyril.kendall@utoronto.ca. College of Pharmacy and Nutrition, University of Saskatchewan, Saskatchewan, SK S7N 2Z4, Canada. cyril.kendall@utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. thomas.wolever@utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. thomas.wolever@utoronto.ca. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5B 1T8, Canada. thomas.wolever@utoronto.ca. Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. thomas.wolever@utoronto.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. leiterl@smh.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. leiterl@smh.ca. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5B 1T8, Canada. leiterl@smh.ca. Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. leiterl@smh.ca. Department of Medicine, University of Toronto, ON M5G 2C4, Canada. leiterl@smh.ca.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. john.sievenpiper@utoronto.ca. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. john.sievenpiper@utoronto.ca. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5B 1T8, Canada. john.sievenpiper@utoronto.ca. Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada. john.sievenpiper@utoronto.ca.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

30463314

Citation

Noronha, Jarvis C., et al. "The Effect of Small Doses of Fructose and Its Epimers On Glycemic Control: a Systematic Review and Meta-Analysis of Controlled Feeding Trials." Nutrients, vol. 10, no. 11, 2018.
Noronha JC, Braunstein CR, Blanco Mejia S, et al. The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. Nutrients. 2018;10(11).
Noronha, J. C., Braunstein, C. R., Blanco Mejia, S., Khan, T. A., Kendall, C. W. C., Wolever, T. M. S., Leiter, L. A., & Sievenpiper, J. L. (2018). The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. Nutrients, 10(11). https://doi.org/10.3390/nu10111805
Noronha JC, et al. The Effect of Small Doses of Fructose and Its Epimers On Glycemic Control: a Systematic Review and Meta-Analysis of Controlled Feeding Trials. Nutrients. 2018 Nov 20;10(11) PubMed PMID: 30463314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. AU - Noronha,Jarvis C, AU - Braunstein,Catherine R, AU - Blanco Mejia,Sonia, AU - Khan,Tauseef A, AU - Kendall,Cyril W C, AU - Wolever,Thomas M S, AU - Leiter,Lawrence A, AU - Sievenpiper,John L, Y1 - 2018/11/20/ PY - 2018/10/17/received PY - 2018/11/07/revised PY - 2018/11/14/accepted PY - 2018/11/23/entrez PY - 2018/11/23/pubmed PY - 2019/1/29/medline KW - HbA1c KW - allulose KW - catalytic dose KW - fructose KW - glucose KW - glycemia KW - insulin KW - meta-analysis KW - sorbose KW - tagatose JF - Nutrients JO - Nutrients VL - 10 IS - 11 N2 - Objective: Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (≤10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ≥1 week that investigated the effect of small doses (≤50 g/day or ≤10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence. Results: We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = -0.38% (95% CI: -0.64%, -0.13%); MD = -0.20% (95% CI: -0.34%, -0.06%)) and fasting glucose (MD = -0.13 mmol/L (95% CI: -0.24 mmol/L, -0.03 mmol/L)); MD = -0.30 mmol/L (95% CI: -0.57 mmol/L, -0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate. Conclusions: Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/30463314/The_Effect_of_Small_Doses_of_Fructose_and_Its_Epimers_on_Glycemic_Control:_A_Systematic_Review_and_Meta_Analysis_of_Controlled_Feeding_Trials_ L2 - https://www.mdpi.com/resolver?pii=nu10111805 DB - PRIME DP - Unbound Medicine ER -