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A Systematic Review and Dose-Response SYSTEMATIC REVIEW AND META-ANALYSIS Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies Qi Liu, BSc; Sabrina Ayoub-Charette, BSc; Tauseef Ahmad Khan, MBBS, MSc, PhD; Fei Au-Yeung, MSc; Sonia Blanco Mejia, MD, MSc; Russell J. de Souza, MSc, ScD; Thomas M.S. Wolever, MD, PhD; Lawrence A. Leiter, MD, FRCPC, FACE, FAHA; Cyril W.C. Kendall, PhD; John L. Sievenpiper, MD, PhD, FRCPC Background-—Sugar-sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose-containing sugars with incident hypertension using a systematic review and meta-analysis of prospective cohort studies. Methods and Results-—We searched MEDLINE, EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log-transformed risk ratios (RRs) for incident hypertension were pooled using pair-wise meta-analysis and linear and nonlinear dose-response meta-analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar-sweetened beverages showed harmful (RRper-355-mL, 1.10 [95% CI, 1.08, 1.12]) whereas fruit (RRper-240-g, 0.94 [95% CI, 0.96, 0.99]) and yogurt showed protective associations (RRper-125-g, 0.95 [95% CI, 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses (RRat-100-mL, 0.97 [95% CI, 0.94, 0.99]). The pair-wise protective association of dairy desserts was not supported by linear dose- response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was “low” for sugar-sweetened beverages, 100% fruit juice, fruit, and yogurt and “very low” for fruit drinks, sweet snacks, and dairy desserts. Conclusions-—The harmful association between sugar-sweetened beverages and hypertension does not extend to other important food sources of fructose-containing sugars. Further research is needed to improve our estimates and better understand the dose- Downloaded from http://ahajournals.org by on December 16, 2019 response relationship between food sources of fructose-containing sugars and hypertension. Registration-—URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02702375. ( J Am Heart Assoc. 2019;8:e010977. DOI: 10.1161/JAHA.118.010977.) Key Words: dairy • fruit • fruit juice • hypertension • SSBs • yogurt ypertension is a major risk factor for developing certain individual behavioural risk factors, including unhealthy H cardiovascular disease (coronary heart disease and dietary choices.2 Fructose and fructose-containing sugars stroke).1 The global prevalence of hypertension has been have been implicated as a dietary contributor to the increasing in the past decades.2 The World Health Organiza- development of hypertension.3–5 The suggested mechanism tion attributes the increasing prevalence of hypertension to is thought to involve uric acid, whereby high intakes of From the Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre (Q.L., S.A.-C., T.A.K., F.A.-Y., S.B.M., R.J.d.S., T.M.S.W., L.A.L., C.W.C.K., J.L.S.), Division of Endocrinology and Metabolism (T.M.S.W.L.A.L., J.L.S.), and Li Ka Shing Knowledge Institute (T.M.S.W., L.A.L., J.L.S.), St. Michael’s Hospital, Toronto, Ontario, Canada; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (Q.L., S.A.-C., T.A.K., F.A.-Y., S.B.M., R.J.d.S., T.M.S.W., L.A.L., C.W.C.K., J.L.S.); Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada (R.J.d.S.); College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (C.W.C.K.); Population Health Research Institute, Hamilton, Ontario, Canada (R.J.d.S.). Accompanying Data S1, S2, Tables S1 through S6, and Figures S1 through S13 are available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.118. 010977 Correspondence to: John L. Sievenpiper, MD, PhD, FRCPC, St. Michael’s Hospital, 6137-61 Queen St E, Toronto, ON, Canada, M5C 2T2. E-mail: [email protected] Received September 19, 2018; accepted October 8, 2019. ª 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. DOI: 10.1161/JAHA.118.010977 Journal of the American Heart Association 1 Fructose-Containing Sugars and Hypertension Liu et al SYSTEMATIC REVIEW AND META-ANALYSIS data are available within the article and the online Supporting Clinical Perspective Information. What Is New? • Fructose intake is purported to elevate blood pressure. Design • Dietary guidelines and public health policy are moving from We followed the Cochrane Handbook for Systematic Reviews – nutrient- to food- and dietary pattern based recommenda- of Interventions14 for the conduct of our systematic review tions. and meta-analysis and reported our results according to the • We examined the relation of important food sources of MOOSE (Meta-Analysis of Observational Studies in Epidemi- fructose-containing sugars with incident hypertension. ology) and Preferred Reporting Items for Systematic Reviews 15,16 What Are the Clinical Implications? and Meta-Analyses (PRISMA) guidelines. • We identified the following associations of food intake with incident hypertension: harmful: sugar-sweetened beverages; Search Strategy protective: fruit, yogurt, and 100% fruit juice (moderate dose We conducted systematic searches in MEDLINE, EMBASE, only); and no association: dairy desserts, fruit drinks, and and Cochrane Library databases through December 13, 2018 sweet snacks. • Overall, this systematic review and meta-analysis of 26 with no language restriction (Table S1). Targeted manual reports, including 15 unique prospective cohorts, showed searches served to supplement database searches; these that only sugar-sweetened beverages as a food source of included finding related articles from references of review fructose-containing sugars have a harmful association with articles, perusing articles with data from major prospective incident hypertension. cohorts that usually report dietary data and speaking to experts in the field. Our search terms reflect the most- consumed food sources of fructose-containing sugars in the fructose raise uric acid, which, in turn, activates the renin- North American diet17,18 (eg, “fructose,”“sugar-sweetened angiotensin system and inhibits the nitric oxide system, beverage,”“fruit,”“yogurt,”“ice cream,” and “sweets”) as well 4–6 leading to hypertension. as our study design (eg, “prospective study”) and outcome of Sugar-sweetened beverages (SSBs) are a major source of interest (eg, “hypertension”). Downloaded from http://ahajournals.org by on December 16, 2019 fructose in the North American diet.7 Although systematic reviews and meta-analyses of prospective cohort studies have shown a consistent association between SSBs and incident Study Selection 8 hypertension, the same has not been shown for the fructose- We included all prospective cohort studies of ≥1 year duration containing sugars they contain independent of food form, that assessed the association of important food sources of both in prospective cohort studies and in controlled feeding fructose-containing sugars, including nonalcoholic beverages 9,10 trials. It is also unclear whether the association observed (eg, SSBs), grain and grain-based products, fruit and fruit- for SSBs holds for other important food sources of fructose- based products, dairy and dairy-based products, and sweets containing sugars, such as fruit and fruit-based products, and desserts with incident hypertension in participants free of grains and grain-based products, dairy and dairy-based hypertension at the start of the study. If several studies products, and sweets and desserts. As dietary guidelines provided results on the same outcome and used overlapping and public health policy move from nutrient-based recom- groups of individuals, we included the study with the longest – mendations toward food- and dietary pattern based recom- follow-up. Abstracts and unpublished studies were not 11–13 mendations, it is important to understand the included. contribution of these different food sources of sugars to the risk of hypertension. To address this gap, we conducted a systematic review and meta-analysis of prospective cohort Data Extraction studies of the relation of important food sources of fructose- Two independent reviewers (Q.L., S.A.C.) extracted relevant containing sugars and incident hypertension. data using a standardized proforma. The main outcome was incident hypertension expressed as risk ratios (RRs) with 95% CIs. Data on the amount of food source consumption, Methods distribution of cases and person-years, and RRs and 95% The authors declare that the methods have been made CIs were extracted. Translation of articles published in publicly available with the registered study protocol (Clini- languages other than English was done online or by calTrials.gov; identifier, NCT02702375), and that all supporting colleagues fluent
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