Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Abstract

Background Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta-analysis of prospective cohort studies. Methods and Results MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane-Q and I2) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty-one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89-0.96]; 0.91 [0.88-0.95]; and 0.94 [0.90-0.97], respectively), coronary heart disease (0.88 [0.83-0.92]; 0.88 [0.84-0.92]; and 0.92 [0.87-0.96], respectively), and stroke (0.82 [0.77-0.88], 0.82 [0.79-0.85]; and 0.88 [0.83-0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85-0.93]; 0.88 [0.86-0.91]; and 0.87 [0.85-0.90], respectively), coronary heart disease (0.81 [0.72-0.92]; 0.86 [0.82-0.90]; and 0.86 [0.83-0.89], respectively), and stroke (0.73 [0.65-0.81]; 0.87 [0.84-0.91]; and 0.94 [0.90-0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was "very low" to "moderate," with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables. Conclusions Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03394339.

Keywords: cardiovascular outcomes; cohort; fruit; nutrition; vegetables.

Conflict of interest statement

Zurbau is a part‐time employee at INQUIS Clinical Research Ltd., a contract research organization. Khan reports he has received research support from the Canadian Institutes of Health Research (CIHR), the International Life Science Institute (ILSI), and National Honey Board. He has been an invited speaker at the Calorie Control Council Annual meeting for which he has received an honorarium. Vuksan has a Canadian (2410556) and American (7326.404) patent on the medical use of viscous fiber blend for reducing blood glucose for treatment of diabetes mellitus, increasing insulin sensitivity, and reduction in systolic blood pressure and blood lipids issued. Kendall has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri‐Foods Canada, Almond Board of California, American Peanut Council, Barilla, CIHR, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands Ltd, Pulse Canada, and Unilever. He 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, and White Wave Foods/Danone. He has received travel support and/or honoraria from the American Peanut Council, 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, Sun‐Maid, Tate & Lyle, Unilever, and White Wave Foods. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, McCormick Science Institute, and Oldways Preservation Trust. He 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 (EASD), is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD, and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. Jenkins 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, International Nut & Dried Fruit (INC), 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, Soy Nutrition 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 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 Limited, Kellogg Canada, and White Wave Foods. 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, 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, 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 Fundamentals 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 White Wave 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, 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, the American Society of Nutrition, Arizona State University, Paolo Sorbini Foundation, and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the US 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 Canadian Diabetes Association. He is a member of the International Carbohydrate Quality Consortium. His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the low glycemic index plant foods advocated here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978‐0‐12‐810510‐8) and 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. Sievenpiper has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), American Society for Nutrition (ASN), INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, National Honey Board, International Life Sciences Institute (ILSI), 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 an inaugural donation from the Calorie Control Council). He has received in‐kind food donations to support a randomized controlled trial from the Almond Board of California, California Walnut Commission, American Peanut Council, Barilla, Unilever, Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods, and Nutrartis. He has received travel support, speaker fees and/or honoraria from Diabetes Canada, Dairy Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Pulse Canada, Canadian Society for Endocrinology and Metabolism (CSEM), GI Foundation, Abbott, Biofortis, ASN, Northern Ontario School of Medicine, INC Nutrition Research & Education Foundation, European Food Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), and Physicians Committee for Responsible Medicine. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Wirtschaftliche Vereinigung Zucker e.V., and Inquis Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada. He serves or has served as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of ILSI North America. 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. His wife is an employee of AB InBev. The remaining authors have no disclosures to report.

Figures

Figure 1. Summary of evidence search and selection.

CV indicates cardiovascular.

Figure 2. Relation between intake of fruits and vegetables and total incident cardiovascular disease (CVD) (highest vs lowest level of intake).

Pooled risk estimates are represented by the black diamond, with principal exposures highlighted in bold. Principal exposures (fruits and vegetables, fruits, and vegetables) represent the pooled data of the risk estimates reported for these exposures and were not tabulated by pooling fruit and vegetable varieties. Values of I2≥50% indicate substantial heterogeneity, with significance at P>0.10. The mean important difference of 5% change in relative risk, indicating a clinically relevant association with lower or higher risk, is indicated by the dashed gray lines. CHD indicates coronary heart disease; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; and RR, risk ratio.

Figure 3. Relation between intake of fruits and vegetables and cardiovascular mortality (highest vs lowest level of intake).

Pooled risk estimates are represented by the black diamond, with principal exposures highlighted in bold. Principal exposures (fruits and vegetables, fruits, and vegetables) represent the pooled data of the risk estimates reported for these exposures and were not tabulated by pooling fruit and vegetable varieties. Values of I2≥50% indicate substantial heterogeneity, with significance at P>0.10. The mean important difference of 5% change in relative risk, indicating a clinically relevant association with lower or higher risk, is indicated by the dashed gray lines. CHD indicates coronary heart disease; CVD, cardiovascular disease; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; and RR, risk ratio.