Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies

Abstract

Objective: To assess the effect of different food sources of fructose-containing sugars on glycaemic control at different levels of energy control.

Design: Systematic review and meta-analysis of controlled intervention studies.

Data sources: Medine, Embase, and the Cochrane Library up to 25 April 2018.

Eligibility criteria for selecting studies: Controlled intervention studies of at least seven days' duration and assessing the effect of different food sources of fructose-containing sugars on glycaemic control in people with and without diabetes were included. Four study designs were prespecified on the basis of energy control: substitution studies (sugars in energy matched comparisons with other macronutrients), addition studies (excess energy from sugars added to diets), subtraction studies (energy from sugars subtracted from diets), and ad libitum studies (sugars freely replaced by other macronutrients without control for energy). Outcomes were glycated haemoglobin (HbA1c), fasting blood glucose, and fasting blood glucose insulin.

Data extraction and synthesis: Four independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by random effects models and overall certainty of the evidence assessed by the GRADE approach (grading of recommendations assessment, development, and evaluation).

Results: 155 study comparisons (n=5086) were included. Total fructose-containing sugars had no harmful effect on any outcome in substitution or subtraction studies, with a decrease seen in HbA1c in substitution studies (mean difference -0.22% (95% confidence interval to -0.35% to -0.08%), -25.9 mmol/mol (-27.3 to -24.4)), but a harmful effect was seen on fasting insulin in addition studies (4.68 pmol/L (1.40 to 7.96)) and ad libitum studies (7.24 pmol/L (0.47 to 14.00)). There was interaction by food source, with specific food sources showing beneficial effects (fruit and fruit juice) or harmful effects (sweetened milk and mixed sources) in substitution studies and harmful effects (sugars-sweetened beverages and fruit juice) in addition studies on at least one outcome. Most of the evidence was low quality.

Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on glycaemic control. Although most food sources of these sugars (especially fruit) do not have a harmful effect in energy matched substitutions with other macronutrients, several food sources of fructose-containing sugars (especially sugars-sweetened beverages) adding excess energy to diets have harmful effects. However, certainty in these estimates is low, and more high quality randomised controlled trials are needed.

Study registration: Clinicaltrials.gov (NCT02716870).

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Diabetes Canada and the Diet, Digestive tract, and Disease Centre through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund for the submitted work. TMSW is a part owner and president of Glycemic Index Laboratories, Toronto, Canada, and has authored several diet books on the glycaemic index for which he has received royalties from Phillipa Sandall Publishing Services and CABI Publishers; and has received consultant fees, honorariums, travel funding, or research support from or served on the scientific advisory board for Canadian Institutes of Health Research, Canadian Diabetes Association, Dairy Farmers of Canada, McCain Foods, Temasek Polytechnic, Northwestern University, Royal Society of London, Glycemic Index Symbol programme, CreaNutrition AG, McMaster University, Canadian Society for Nutritional Sciences, National Sports and Conditioning Association, Faculty of Public Health and Nutrition—Autonomous University of Nuevo Leon, and Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes. VV has a Canadian (2 410 556) and American (7,326.404) patent on the medical use of viscous fibre blend for reducing blood glucose for treatment of diabetes, increasing insulin sensitivity, and reduction in systolic blood pressure and blood lipids issued. CWCK has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada, Almond Board of California, American Pistachio Growers, Barilla, Calorie Control Council, Canadian Institutes of Health Research, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands, Pulse Canada, Saskatchewan Pulse Growers and Unilever; has received in-kind research support from the Almond Board of California, American Peanut Council, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Quaker (PepsiCo), Primo, Unico, Unilever, WhiteWave Foods; has received travel support or honorariums from the American Peanut Council, American Pistachio Growers, Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, Peanut Institute, Pulse Canada, Sabra Dipping, Saskatchewan Pulse Growers, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods; has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, McCormick Science Institute, Oldways Preservation Trust, Paramount Farms and Pulse Canada; is a member of the International Carbohydrate Quality Consortium, executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the European Association for the Study of Diabetes; and is a director of the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. RJdS has received research support from the Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation; travel and consultant fees from the World Health Organization; consultant fees from Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes and Health Canada; and a speaker’s honorarium from McMaster Children’s Hospital. DJAJ has received research grants from Saskatchewan Pulse Growers, the Agricultural Bioproducts Innovation Programme through the Pulse Research Network, Advanced Foods and Material Network, Loblaw Companies, Unilever, Barilla, Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg’s Company (Canada), Quaker Oats (Canada), Procter and Gamble Technical Centre, Bayer Consumer Care (Springfield, NJ, USA), Pepsi/Quaker, International Nut and Dried Fruit, Soy Foods Association of North America, Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, Sanitarium Company, Orafti, International Tree Nut Council Nutrition Research and Education Foundation, Peanut Institute, Soy Nutrition Institute, Canola and Flax Councils of Canada, Calorie Control Council, Canadian Institutes of Health Research, Canada Foundation for Innovation, and Ontario Research Fund; has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, American Peanut Council, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (PepsiCo), Pristine Gourmet, Bunge, Kellogg Canada, and WhiteWave Foods; has been on the speaker’s panel, served on the scientific advisory board or received travel support or honorariums from the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies, Griffin Hospital (for the development of the NuVal scoring system), Coca-Cola Company, EPICURE, Danone, Diet Quality Photo Navigation, Better Therapeutics (FareWell), Verywell, True Health Initiative, Institute of Food Technologists, Soy Nutrition Institute, Herbalife Nutrition Institute, Saskatchewan Pulse Growers, Sanitarium Company, Orafti, Almond Board of California, American Peanut Council, International Tree Nut Council Nutrition Research and Education Foundation, Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter and Gamble, Abbott Laboratories, Dean Foods, California Strawberry Commission, Haine Celestial, PepsiCo, Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, Advanced Foods and Material Network, Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, Canadian Agri-Food Policy Institute, Pulse Canada, Saskatchewan Pulse Growers, Soy Foods Association of North America, Nutrition Foundation of Italy, Nutra-Source Diagnostics, McDougall Programme, Toronto Knowledge Translation Group (St Michael’s Hospital), Canadian College of Naturopathic Medicine, The Hospital for Sick Children, Canadian Nutrition Society, American Society of Nutrition, Arizona State University, Paolo Sorbini Foundation, and the Institute of Nutrition, Metabolism, and Diabetes; has received an honorarium from the US Department of Agriculture to present the 2013 W O Atwater Memorial Lecture and the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council; has received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian Diabetes Association; and is a member of the International Carbohydrate Quality Consortium. DJAJ’s wife, Alexandra L Jenkins, is a director and partner of Glycemic Index Laboratories, and his sister, Caroline Brydson, received funding through a grant from the St Michael’s Hospital Foundation to develop a cookbook for one of his studies. JLS has received research support from the Canadian Institutes of Health Research, Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre, American Society for Nutrition, INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), and the Nutrition Trialists Fund at the University of Toronto (a fund established by the Calorie Control Council); has received food donations to support randomised controlled trials from the Almond Board of California, California Walnut Commission, American Peanut Council, Barilla, Unilever, Unico/Primo, Loblaw Companies, Quaker (PepsiCo), Kellogg Canada, and WhiteWave Foods; has received speaker fees or honorariums from Diabetes Canada, Canadian Nutrition Society, Mott’s, Dairy Farmers of Canada, Alberta Milk, FoodMinds, Memac Ogilvy & Mather, PepsiCo, The Ginger Network, International Sweeteners Association, Nestlé, Pulse Canada, Canadian Society for Endocrinology and Metabolism, GI Foundation, Barilla Centre for Food and Nutrition, Abbott, Biofortis, California Walnut Commission, American Society for Nutrition, Loma Linda University, Dietitians of Canada, European Food Safety Authority, and Physicians Committee for Responsible Medicine; has ad hoc consulting arrangements with Winston and Strawn, Perkins Coie, and Tate and Lyle, and Wirtschaftliche Vereinigung Zucker eV; is a member of the European Fruit Juice Association’s scientific expert panel; is on the clinical practice guidelines expert committees of Diabetes Canada, European Association for the Study of Diabetes, Canadian Cardiovascular Society, and Obesity Canada; serves as an unpaid scientific adviser for the Food, Nutrition, and Safety Programme and the technical committee on carbohydrates of the International Life Science Institute North America; and is a member of the International Carbohydrate Quality Consortium, executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, and director of the Toronto 3D Knowledge Synthesis and Clinical Studies foundation. JLS’s wife is an employee of Unilever Canada. VLC, EV, SBM, AIC, TAK, VH, and LAL declare no competing interests. There are no products in development or marketed products to declare.

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Figures

Fig 1

Flow of literature for the effect of food sources of fructose-containing sugars on glycaemic control

Fig 2

Summary plot for the effect of food sources of fructose-containing sugars on glycated haemoglobin (HbA1c). Data are weighted mean differences (95% confidence intervals) for summary effects of individual food sources and total food sources on HbA1c. Analyses conducted by generic, inverse variance random effects models (at least five trials available) or fixed effects models (fewer than five trials available). Interstudy heterogeneity was tested by the Cochran’s Q statistic (χ2) at a significance level of P<0.10

Fig 3

Summary plot for the effect of food sources of fructose-containing sugars on fasting blood glucose. Data are weighted mean differences (95% confidence intervals) for summary effects of individual food sources and total food sources on fasting blood glucose. Analyses conducted by generic, inverse variance random effects models (at least five trials available) or fixed effects models (fewer than five trials available). Interstudy heterogeneity was tested by the Cochran’s Q statistic (χ2) at a significance level of P<0.10

Fig 4

Summary plot for the effect of food sources of fructose-containing sugars on fasting blood insulin. Data are weighted mean differences (95% confidence intervals) for summary effects of individual food sources and total food sources on fasting blood insulin. Analyses conducted by generic, inverse variance random effects models (at least five trials available) or fixed effects models (fewer than five trials available). Interstudy heterogeneity was tested by the Cochran Q statistic (χ2) at a significance level of P<0.10