title: Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials.
abstract: BACKGROUND
  The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established.
  
  
  OBJECTIVE
  We examined the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides], lipoproteins [apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100], blood pressure, and inflammation (C-reactive protein) in adults aged ≥18 y without prevalent CVD.
  
  
  METHODS
  We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta-regression. Publication bias was evaluated by using funnel plots and Egger's and Begg's tests.
  
  
  RESULTS
  Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (-4.7 mg/dL; 95% CI: -5.3, -4.0 mg/dL), LDL cholesterol (-4.8 mg/dL; 95% CI: -5.5, -4.2 mg/dL), ApoB (-3.7 mg/dL; 95% CI: -5.2, -2.3 mg/dL), and triglycerides (-2.2 mg/dL; 95% CI: -3.8, -0.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity < 0.001 each); stronger effects were observed for ≥60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (-11.5 mg/dL; 95% CI: -16.2, -6.8 mg/dL) than in healthy populations (-2.5 mg/dL; 95% CI: -4.7, -0.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found.
  
  
  CONCLUSIONS
  Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations.
authors.affiliation: Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and delgobbo@stanford.edu.
authors.forename: Liana C
authors.initials: LC
authors.lastname: Del Gobbo
authors.affiliation: Life Sciences Research Organization, Bethesda, MD.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Falk
authors.affiliation: Life Sciences Research Organization, Bethesda, MD.
authors.forename: Robin
authors.initials: R
authors.lastname: Feldman
authors.affiliation: Life Sciences Research Organization, Bethesda, MD.
authors.forename: Kara
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
mesh_terms: D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D018849:Controlled Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood / Q000178:diet therapy / Q000517:prevention & control; D015536:Down-Regulation; D019317:Evidence-Based Medicine; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000178:diet therapy / Q000517:prevention & control*; D006973:Hypertension / Q000097:blood / Q000178:diet therapy / Q000517:prevention & control; D009754:Nuts; D014197:Trees
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D002784:Cholesterol
keywords: apolipoprotein; cardiovascular; cholesterol; lipids; nuts