Background The prevalence of hyperuricemia and gout has increased in recent decades. The role of dietary fructose in the development of these conditions remains unclear.
Objective To conduct a systematic review and meta-analysis of prospective cohort studies investigating the association fructose consumption with incident gout and hyperuricemia.
Design MEDLINE, EMBASE and the Cochrane Library were searched (through September 2015). We included prospective cohort studies that assessed fructose consumption and incident gout or hyperuricemia. 2 independent reviewers extracted relevant data and assessed study quality using the Newcastle-Ottawa Scale. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Results 2 studies involving 125 299 participants and 1533 cases of incident gout assessed the association between fructose consumption and incident gout over an average of 17 years of follow-up. No eligible studies assessed incident hyperuricemia as an outcome. Fructose consumption was associated with an increase in the risk of gout (RR=1.62, 95% CI 1.28 to 2.03, p<0.0001) with no evidence of interstudy heterogeneity (I2=0%, p=0.33) when comparing the highest (>11.8% to >11.9% total energy) and lowest (<6.9% to <7.5% total energy) quantiles of consumption.
Limitations Despite a dose–response gradient, the overall quality of evidence as assessed by GRADE was low, due to indirectness. There were only two prospective cohort studies involving predominantly white health professionals that assessed incident gout, and none assessed hyperuricemia.
Conclusions Fructose consumption was associated with an increased risk of developing gout in predominantly white health professionals. More prospective studies are necessary to understand better the role of fructose and its food sources in the development of gout and hyperuricemia.
Protocol registration number NCT01608620.
- systematic review
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Contributors All authors had full access to all of the data (including statistical reports and tables) in this study and take full responsibility for the integrity of the data and the accuracy of the data analysis. RJdS, CWCK, DJAJ and JLS contributed to conception and design. JJ, SR, SBM, RJdS, TAK, LAL, TMSW, CWCK, DJAJ and JLS were involved in the analysis and interpretation of the data, contributed to critical revision of the article for important intellectual content and provided final approval of the article. JJ, SR and JLS were involved in the drafting of the article. RJdS provided statistical expertise. RJdS, CWCK, DJAJ and JLS obtained funding. SBM provided administrative, technical or logistic support. JJ, SR, SBM and RJdS were involved in collection and assembly of data. JLS is the guarantor.
Funding This work was funded by a Canadian Institutes of Health Research (CIHR) programmatic grant (funding reference number, 129920) through the Canada-wide Human Nutrition Trialists' Network (NTN) and an unrestricted grant from the Calorie Control Council. The Diet, Digestive tract, and Disease (3-D) Centre, funded through the Canada Foundation for Innovation (CFI) and the Ministry of Research and Innovation's Ontario Research Fund (ORF), provided the infrastructure for the conduct of this project. RJdS was funded by a CIHR Postdoctoral Fellowship Award. DJAJ was funded by the Government of Canada through the Canada Research Chair Endowment. JLS was funded by a PSI Graham Farquharson Knowledge Translation Fellowship, Canadian Diabetes Association (CDA) Clinician Scientist award, CIHR INMD/CNS New Investigator Partnership Prize and Banting & Best Diabetes Centre Sun Life Financial New Investigator Award.
Disclaimer None of the sponsors had a role in any aspect of the present study, including design and conduct of the study; collection, management, analysis and interpretation of the data and preparation, review, approval of the manuscript or decision to publish.
Competing interests RJdS has served as an external resource person to the World Health Organization (WHO) Nutrition Guidelines Advisory Group on trans fats and saturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012–2015 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has held a grant from the Canadian Foundation for Dietetic Research as a principal investigator, and is a co-investigator on several funded team grants from Canadian Institutes of Health Research. TMSW is a part owner and the President of Glycemic Index Laboratories, Toronto, Ontario, Canada and has authored several popular diet books on the glycemic index for which he has received royalties from Phillipa Sandall Publishing Services and CABI Publishers. He has received consultant fees, honoraria, travel funding or research support from or served on the scientific advisory board for CIHR, CDA Dairy Farmers of Canada, McCain Foods, Temasek Polytechnic, Northwestern University, Royal Society of London, Glycemic Index Symbol program, 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, Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes. CWCK has received research support from the Advanced Foods and Material Network, Agrifoods and Agriculture Canada, the Almond Board of California, the American Pistachio Growers, Barilla, the California Strawberry Commission, the Calorie Control Council, CIHR, the Canola Council of Canada, Hain Celestial, the International Tree Nut Council Nutrition Research and Education Foundation, Kellogg, Kraft, Loblaw Companies, Orafti, Pulse Canada, Saskatchewan Pulse Growers, Solae and Unilever. He has received travel funding, consultant fees and/or honoraria from Abbott Laboratories, the Almond Board of California, the American Peanut Council, the American Pistachio Growers, Barilla, Bayer, the Canola Council of Canada, the Coca-Cola Company, Danone, General Mills, the International Tree Nut Council Nutrition Research and Education Foundation, Kellogg, Loblaw Companies, the Nutrition Foundation of Italy, Oldways Preservation Trust, Orafti, Paramount Farms, the Peanut Institute, PepsiCo, Pulse Canada, Sabra Dipping, Saskatchewan Pulse Growers, Solae, Sun-Maid, Tate and Lyle and Unilever. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the European Association for the Study of Diabetes (EASD) and has served on the scientific advisory board for the Almond Board of California, INC International Nut and Dried Fruit Council, Oldways Preservation Trust, Paramount Farms and Pulse Canada He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. DJAJ has received research grants from Saskatchewan Pulse Growers, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg's Company, Canada, Quaker Oats, Canada, Procter & Gamble Technical Centre Ltd., Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, INC International Nut and Dried Fruit Council, Soy Foods Association of North America, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, the Canola and Flax Councils of Canada, the Calorie Control Council, the CIHR, the Canada Foundation for Innovation and the Ontario Research Fund. He has been on the speaker's panel, served on the scientific advisory board and/or received travel support and/or honoraria from the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system, the Coca-Cola Company, EPICURE, Danone, Saskatchewan Pulse Growers, Sanitarium Company, Orafti, the Almond Board of California, the American Peanut Council, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamental for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, the Coca-Cola Company, the Griffin Hospital, Abbott Laboratories, the Canola Council of Canada, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, the Nutritional Fundamentals for Health, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Saskatchewan Pulse Growers, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael's Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the United States Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the CDA. He is a member of the ICQC. His wife, ALJ, is a director and partner of Glycemic Index Laboratories, Inc., and his sister 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 CIHR, American Society of Nutrition (ASN), CDA, Banting & Best Diabetes Centre (BBDC), Calorie Control Council, The Coca-Cola Company (investigator initiated, unrestricted), Dr Pepper Snapple Group (investigator initiated, unrestricted), Pulse Canada INC International Nut and Dried Fruit Council, and The Tate and Lyle Nutritional Research Fund at the University of Toronto. He has received travel funding, speaker fees and/or honoraria from He has received speaker fees and/or honoraria from the CDA, CNS, University of Alabama at Birmingham, Abbott Laboratories, Canadian Sugar Institute, Dr. Pepper Snapple Group, The Coca-Cola Company, Dairy Farmers of Canada, NFI, C3 Collaborating for Health, WhiteWave Foods, Rippe Lifestyle, mdBriefcase, Alberta Milk, FoodMinds LLC, Memac Ogilvy & Mather LLC, PepsiCo, and Pulse Canada. He has ad hoc consulting arrangements with Winston & Strawn LLP, Perkins Coie LLP and Tate & Lyle. He is a member of the European Fruit Juice Association Scientific Expert Panel. He is on the Clinical Practice Guidelines Expert Committees of the CDA, EASD, and Canadian Cardiovascular Society (CCS), as well as an expert writing panel of the ASN. He serves as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of the International Life Science Institute (ILSI) North America. He is a member of the ICQC, Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of Unilever Canada. JJ, SR, SBM, and TK declare no competing interests related to this manuscript.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
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