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The Effect of Replacing Refined Grains with Whole Grains on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Clinical Recommendation

Published:September 12, 2020DOI:https://doi.org/10.1016/j.jand.2020.06.021

      Abstract

      Background

      Observational data have established a link between the consumption of whole grains and reduced risk of cardiovascular disease (CVD); however, there is a need to review interventional research.

      Objective

      Our aim was to determine whether interventions providing whole grain or whole pseudo-grain for dietary consumption improved CVD-related outcomes compared with refined grain or placebo in adults with or without chronic disease and/or associated risk factors.

      Methods

      A systematic review and meta-analysis of randomized controlled trials that compared whole-grain vs refined-grain or placebo consumption by human adults was conducted. PubMed, CINAHL, Embase, Web of Science, and Cochrane CENTRAL were searched for studies of 12 weeks (or 2 weeks for inflammatory outcomes) duration until 21 February 2020. Data were extracted for 14 types of CVD risk factors (40 outcomes in total). Risk of bias was assessed using the Cochrane Risk-of-Bias tool. Meta-analysis was performed using Comprehensive Meta-Analysis software. The Grading of Recommendations Assessment, Development and Evaluation method was used to determine confidence in the pooled effects and to inform a clinical recommendation.

      Results

      Twenty-five randomized controlled trials were included and 22 were meta-analyzed. Interventions ranged from 2 to 16 weeks; most samples were healthy (n = 13 studies) and used mixed whole grains (n = 11 studies). Meta-analysis found that whole-grain oats improved total cholesterol (standardized mean difference [SMD] = –0.54, 95% CI –0.95 to –0.12) and low-density lipoprotein cholesterol (SMD = –0.57, 95% CI –0.84 to –0.31), whole-grain rice improved triglycerides (SMD = 0.22, 95% CI –0.44 to –0.01), and whole grains (all types) improved hemoglobin A1c (SMD = –0.33, 95% CI –0.61 to –0.04) and C-reactive protein (SMD = –0.22, 95% CI –0.44 to –0.00).

      Conclusions

      For adults with or without CVD risk factors, consuming whole grains as opposed to refined grains can improve total cholesterol, low-density lipoprotein cholesterol, hemoglobin A1c, and C-reactive protein. There is insufficient evidence to recommend the whole grains as opposed to refined grains for the prevention and treatment of CVD. Further interventional research is needed to better understand the preventive and treatment potential of whole-grain and whole pseudo-grain dietary intake for cardiovascular disease, particularly among those with existing CVD risk factors.

      Keywords

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      References

      1. Australian Dietary Guidelines. National Health and Medical Research Council, Australian Government, Canberra2013
        • McRae M.P.
        Health benefits of dietary whole grains: An umbrella review of meta-analyses.
        J Chiropr Med. 2017; 16: 10-18
        • Reynolds A.
        • Mann J.
        • Cummings J.
        • Winter N.
        • Mete E.
        • Te Morenga L.
        Carbohydrate quality and human health: A series of systematic reviews and meta-analyses.
        Lancet. 2019; 393: 434-445
        • Van Der Kamp J.W.
        • Poutanen K.
        • Seal C.J.
        • Richardson D.P.
        The HEALTHGRAIN definition of “whole grain.”.
        Food Nutr Res. 2014; 58: 22100
        • Arterburn D.
        • Flum D.
        • Westbrook E.
        • et al.
        A population-based, shared decision-making approach to recruit for a randomized trial of bariatric surgery versus lifestyle for type 2 diabetes.
        Surg Obes Relat Dis. 2013; 9: 837-844
        • 2015 Intergenerational Report
        Commonwealth of Australia.
        (Published March 2015. Accessed July 8, 2020)
      2. The Eatwell Guide. Public Health England.
        (Published 2016. Accessed July 8, 2020)
        • Australian Food Composition Database
        Food Standards Australia New Zealand.
        • Liu R.H.
        Whole grain phytochemicals and health.
        J Cereal Sci. 2007; 46: 207-219
      3. Mendis S. Puska P. Norrving B. Global Atlas on Cardiovascular Disease Prevention and Control. World Health Organization, Geneva2011
        • Aune D.
        • Keum N.
        • Giovannucci E.
        • et al.
        Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: Systematic review and dose-response meta-analysis of prospective studies.
        BMJ. 2016; 353: i2716
        • Zhang B.
        • Zhao Q.
        • Guo W.
        • Bao W.
        • Wang X.
        Association of whole grain intake with all-cause, cardiovascular, and cancer mortality: A systematic review and dose–response meta-analysis from prospective cohort studies.
        Eur J Clin Nutr. 2018; 72: 57
        • Wei H.
        • Gao Z.
        • Liang R.
        • Li Z.
        • Hao H.
        • Liu X.
        Whole-grain consumption and the risk of all-cause, CVD and cancer mortality: A meta-analysis of prospective cohort studies.
        Br J Nutr. 2016; 116: 514-525
        • Chen G.C.
        • Tong X.
        • Xu J.Y.
        • et al.
        Whole-grain intake and total, cardiovascular, and cancer mortality: A systematic review and meta-analysis of prospective studies.
        Am J Clin Nutr. 2016; 104: 164-172
        • Kelly S.A.
        • Hartley L.
        • Loveman E.
        • et al.
        Whole grain cereals for the primary or secondary prevention of cardiovascular disease.
        Cochrane Database Syst Rev. 2017; 8: CD005051
        • Baretta D.
        • Nardino M.
        • Carvalho I.R.
        • et al.
        Estimates of genetic parameters and genotypic values prediction in maize landrace populations by REML/BLUP procedure.
        Genet Mol Res. 2017; 16
      4. Covidence Systematic Review Software [computer program]. Melbourne, Australia: Veritas Health Innovation. Accessed 2019.

      5. Marshall S, Poetocz P, Duve E, et al. Systematic review data of whole grains versus placebo or refined grains on cardiovascular disease risk factors. Dryad. 2000. https://doi.org/10.5061/dryad.n2z34tmth

        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
      6. Handbook for Grading the Quality of Evidence and the Strength of Recommendations Using the GRADE approach. Updated October 2013.
        (Accessed January 15, 2019.)
      7. GRADEpro GDT: GRADEpro Guideline Development Tool [computer program]. McMaster University, Hamilton, ON, Canada2015
        • Borenstein M.
        • Hedges V.L.
        • Higgins J.P.T.
        • et al.
        Comprehensive Meta-Analysis [computer program]. Version 2.
        Biostat, Englewood, NJ2006
      8. Study summaries using more than one patient-reported outcome. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. Updated March 2011. Accessed July 8, 2020. www.cochrane-handbook.org

      9. Re-expressing SMD using a familiar instrument. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. Updated March 2011. Accessed July 8, 2020. www.cochrane-handbook.org

      10. metafor: A Meta-Analysis Package for R [computer program]. Version 2.1-0. R Foundation for Statistical Computing, Vienna, Austria2019
      11. Bootstrap Functions [computer program]. Version 1.3-23. R Foundation for Statistical Computing, Vienna, Austria2019
      12. R: A Language and Environment for Statistical Computing [computer program]. Version 3.6.1. R Foundation for Statistical Computing, Vienna, Austria2019 (Accessed July 1, 2020.)
        • Viechtbauer W.
        Bootstrapping with meta-analytic models.
        (Accessed January 20, 2019)
        • Van Den Noortgate W.
        • Onghena P.
        Parametric and nonparametric bootstrap methods for meta-analysis.
        Behav Res Methods. 2005; 37: 11-22
        • Giacco R.
        • Costabile G.
        • Della Pepa G.
        • et al.
        A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome.
        Nutr Metab Cardiovasc Dis. 2014; 24: 837-844
        • Giacco R.
        • Lappi J.
        • Costabile G.
        • et al.
        Effects of rye and whole wheat versus refined cereal foods on metabolic risk factors: A randomised controlled two-centre intervention study.
        Clin Nutr. 2013; 32: 941-949
        • Vetrani C.
        • Costabile G.
        • Luongo D.
        • et al.
        Effects of whole-grain cereal foods on plasma short chain fatty acid concentrations in individuals with the metabolic syndrome.
        Nutrition. 2016; 32: 217-221
        • Kirwan J.P.
        • Malin S.K.
        • Scelsi A.R.
        • et al.
        A whole-grain diet reduces cardiovascular risk factors in overweight and obese adults: A randomized controlled trial.
        J Nutr. 2016; 146: 2244-2251
        • Malin S.K.
        • Kullman E.L.
        • Scelsi A.R.
        • et al.
        A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
        Metabolism. 2018; 82: 111-117
        • Malin S.K.
        • Kullman E.L.
        • Scelsi A.R.
        • Godin J.P.
        • Ross A.B.
        • Kirwan J.P.
        A whole-grain diet increases glucose-stimulated insulin secretion independent of gut hormones in adults at risk for type 2 diabetes.
        Mol Nutr Food Res. 2019; 63: 1800967
        • Ampatzoglou A.
        • Williams C.
        • Atwal K.
        • et al.
        Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers.
        Eur J Nutr. 2016; 55: 183-195
        • Enright L.
        • Slavin J.
        No effect of 14 day consumption of whole grain diet compared to refined grain diet on antioxidant measures in healthy, young subjects: A pilot study.
        Nutr J. 2010; 9: 12
        • Giacco R.
        • Clemente G.
        • Cipriano D.
        • et al.
        Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people.
        Nutr Metab Cardiovasc Dis. 2010; 20: 186-194
        • Harris Jackson K.
        • West S.G.
        • Vanden Heuvel J.P.
        • et al.
        Effects of whole and refined grains in a weight-loss diet on markers of metabolic syndrome in individuals with increased waist circumference: A randomized controlled-feeding trial.
        Am J Clin Nutr. 2014; 100: 577-586
        • Kazemzadeh M.
        • Safavi S.M.
        • Nematollahi S.
        • Nourieh Z.
        Effect of brown rice consumption on inflammatory marker and cardiovascular risk factors among overweight and obese non-menopausal female adults.
        Int J Prev Med. 2014; 5: 478-488
        • Kikuchi Y.
        • Nozaki S.
        • Makita M.
        • et al.
        Effects of whole grain wheat bread on visceral fat obesity in Japanese subjects: A randomized double-blind study.
        Plant Foods Hum Nutr. 2018; 73: 161-165
        • Kondo K.
        • Morino K.
        • Nishio Y.
        • et al.
        Fiber-rich diet with brown rice improves endothelial function in type 2 diabetes mellitus: A randomized controlled trial.
        PLoS One. 2017; 12: 16
        • Nieman D.C.
        • Cayea E.J.
        • Austin M.D.
        • Henson D.A.
        • McAnulty S.R.
        • Jin F.
        Chia seed does not promote weight loss or alter disease risk factors in overweight adults.
        Nutr Res. 2009; 29: 414-418
        • Roager H.M.
        • Vogt J.K.
        • Kristensen M.
        • et al.
        Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial.
        Gut. 2019; 68: 83-93
        • Schutte S.
        • Esser D.
        • Hoevenaars F.P.M.
        • et al.
        A 12-wk whole-grain wheat intervention protects against hepatic fat: The Graandioos study, a randomized trial in overweight subjects.
        Am J Clin Nutr. 2018; 108: 1264-1274
        • Vanegas S.M.
        • Meydani M.
        • Barnett J.B.
        • et al.
        Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults.
        Am J Clin Nutr. 2017; 105: 635-650
        • Vitaglione P.
        • Mennella I.
        • Ferracane R.
        • et al.
        Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: Role of polyphenols bound to cereal dietary fiber.
        Am J Clin Nutr. 2015; 101: 251-261
        • Zhang G.
        • Pan A.
        • Zong G.
        • et al.
        Substituting white rice with brown rice for 16 weeks does not substantially affect metabolic risk factors in middle-aged chinese men and women with diabetes or a high risk for diabetes.
        J Nutr. 2011; 141: 1685-1690
        • Araki R.
        • Ushio R.
        • Fujie K.
        • et al.
        Effect of partially-abraded brown rice consumption on body weight and the indicators of glucose and lipid metabolism in pre-diabetic adults: A randomized controlled trial.
        Clin Nutr. 2017; 19: 9-15
        • Kristensen M.
        • Pelletier X.
        • Ross A.B.
        • Thielecke F.
        A high rate of non-compliance confounds the study of whole grains and weight maintenance in a randomised intervention trial—The case for greater use of dietary biomarkers in nutrition intervention studies.
        Nutrients. 2017; 9: 55
        • Maki K.C.
        • Beiseigel J.M.
        • Jonnalagadda S.S.
        • et al.
        Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods.
        J Acad Nutr Diet. 2010; 110: 205-214
        • Nakayama T.
        • Nagai Y.
        • Uehara Y.
        • et al.
        Eating glutinous brown rice twice a day for 8 weeks improves glycemic control in Japanese patients with diabetes mellitus.
        Nutr Diabetes. 2017; 7: e273
        • Shimabukuro M.
        • Higa M.
        • Kinjo R.
        • et al.
        Effects of the brown rice diet on visceral obesity and endothelial function: The BRAVO study.
        Br J Nutr. 2014; 111: 310-320
        • Andersson A.
        • Tengblad S.
        • Karlstrom B.
        • et al.
        Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects.
        J Nutr. 2007; 137: 1401-1407
        • Kristensen M.
        • Toubro S.
        • Jensen M.G.
        • et al.
        Whole grain compared with refined wheat decreases the percentage of body fat following a 12-week, energy-restricted dietary intervention in postmenopausal women.
        J Nutr. 2012; 142: 710-716
        • Kim J.Y.
        • Kim J.H.
        • Lee D.H.
        • Kim S.H.
        • Lee S.S.
        Meal replacement with mixed rice is more effective than white rice in weight control, while improving antioxidant enzyme activity in obese women.
        Nutr Res. 2008; 28: 66-71
        • Pick M.E.
        • Hawrysh Z.J.
        • Gee M.I.
        • Toth E.
        Barley bread products improve glycemic control of type 2 subjects.
        Int J Food Sci Nutr. 1998; 49: 71-78
        • Pins J.J.
        • Geleva D.
        • Keenan J.M.
        • Frazel C.
        • O'Connor P.J.
        • Cherney L.M.
        Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control?.
        J Fam Pract. 2002; 51: 353-359
        • Tighe P.
        • Duthie G.
        • Brittenden J.
        • et al.
        Effects of wheat and oat-based whole grain foods on serum lipoprotein size and distribution in overweight middle aged people: A randomised controlled trial.
        PLoS One. 2013; 8e70436
        • Tighe P.
        • Duthie G.
        • Vaughan N.
        • et al.
        Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: A randomized controlled trial.
        Am J Clin Nutr. 2010; 92: 733-740
        • Ho H.V.
        • Sievenpiper J.L.
        • Zurbau A.
        • et al.
        The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: A systematic review and meta-analysis of randomised-controlled trials.
        Br J Nutr. 2016; 116: 1369-1382
        • Zhou L.
        • Li C.
        • Gao L.
        • Wang A.
        High-density lipoprotein synthesis and metabolism.
        Mol Med Rep. 2015; 12: 4015-4021
        • Hollænder P.L.
        • Ross A.B.
        • Kristensen M.
        Whole-grain and blood lipid changes in apparently healthy adults: A systematic review and meta-analysis of randomized controlled studies.
        Am J Clin Nutr. 2015; 102: 556-572
        • Ross A.B.
        • Kristensen M.
        • Seal C.J.
        • Jacques P.
        • McKeown N.M.
        Recommendations for reporting whole-grain intake in observational and intervention studies.
        Am J Clin Nutr. 2015; 101: 903-907
        • McEvoy C.T.
        • Temple N.
        • Woodside J.V.
        Vegetarian diets, low-meat diets and health: A review.
        Public Health Nutr. 2012; 15: 2287-2294
        • Rahkovsky I.
        • Gregory C.A.
        Food prices and blood cholesterol.
        Econ Hum Biol. 2013; 11: 95-107
        • World Health Organization
        Top 10 causes of death.
        (Published May 24, 2018. Accessed July 9, 2020)
        • Ryan M.
        • Farrelly M.
        Living with an unfixable heart: A qualitative study exploring the experience of living with advanced heart failure.
        Eur J Cardiovasc Nurs. 2009; 8: 223-231
        • Davidson P.M.
        • Daly J.
        • Leung D.
        • et al.
        Health-seeking beliefs of cardiovascular patients: a qualitative study.
        Int J Nurs Stud. 2011; 48: 1367-1375
        • Mancino L.
        • Kuchler F.
        • Leibtag E.
        Getting consumers to eat more whole-grains: The role of policy, information, and food manufacturers.
        Food Policy. 2008; 33: 489-496
        • Jetter K.M.
        • Cassady D.L.
        The availability and cost of healthier food alternatives.
        Am J Prev Med. 2006; 30: 38-44
        • Barton P.
        • Andronis L.
        • Briggs A.
        • McPherson K.
        • Capewell S.
        Effectiveness and cost effectiveness of cardiovascular disease prevention in whole populations: modelling study. Version 2.
        BMJ. 2011; 343: d4044
        • Brunner E.
        • Cohen D.
        • Toon L.
        Cost effectiveness of cardiovascular disease prevention strategies: a perspective on EU food based dietary guidelines.
        Public Health Nutr. 2001; 4: 711-715
        • World Health Organization
        Global Health Observatory (GHO) data. NCD mortality and morbidity.
        • World Health Organization
        Global Status Report on Noncommunicable Diseases.
        World Health Organization, Geneva2014
        • Martínez-González M.Á.
        • Corella D.
        • Salas-Salvadó J.
        • et al.
        Cohort profile: Design and methods of the PREDIMED study.
        Int J Epidemiol. 2010; 41: 377-385

      Biography

      S. Marshall is an accredited practicing dietitian and scientific and education director, Nutrition Research Australia, Sydney, New South Wales, Australia, and a senior postdoctoral research fellow, Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia.

      Biography

      P. Petocz is a statistician, Nutrition Research Australia, Sydney, New South Wales, Australia.

      Biography

      E. Duve is a research nutritionist, Nutrition Research Australia, Sydney, New South Wales, Australia.

      Biography

      T. Cassettari is a project director, Nutrition Research Australia, Sydney, New South Wales, Australia.

      Biography

      M. Blumfield is a research dietitian, Nutrition Research Australia, Sydney, New South Wales, Australia.

      Biography

      F. Fayet-Moore is chief executive officer, Nutrition Research Australia, Sydney, New South Wales, Australia.

      Biography

      K. Abbott is research dietitian, Nutrition Research Australia, Sydney, New South Wales, Australia, and research dietitian, Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.