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

J Acad Nutr Diet. 2020 Nov;120(11):1859-1883.e31. doi: 10.1016/j.jand.2020.06.021. Epub 2020 Sep 12.


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: Cardiovascular disease; Meta-analysis; Systematic review; Whole grains; Wholemeal.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Diet, Healthy / methods*
  • Edible Grain*
  • Female
  • Glycated Hemoglobin / analysis
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Triglycerides / blood
  • Whole Grains*


  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Triglycerides
  • hemoglobin A1c protein, human
  • C-Reactive Protein
  • Cholesterol