title: Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial.
abstract: BACKGROUND
  Evidence from dietary intervention studies shows that the intake of flavanols and procyanidins can be beneficial for cardiovascular health. Nevertheless, there is a clear need for advancing our understanding with regard to safe amounts of intake for these bioactives.
  
  
  OBJECTIVE
  The aim was to investigate in healthy adults the effects of cocoa flavanol (CF) intake amount and intake duration on blood pressure, platelet function, metabolic variables, and potential adverse events (AEs).
  
  
  METHODS
  This investigation consisted of 2 parts. Part 1 was an open-label, intake-amount escalation study, in which 34 healthy adults (aged 35-55 y) consumed escalating amounts of CFs, ranging from 1000 to 2000 mg/d over 6 wk. Primary outcomes were blood pressure and platelet function, select metabolic variables, and the occurrence and severity of AEs. Secondary outcomes included plasma concentrations of CF-derived metabolites and methylxanthines. On the basis of the outcomes of study part 1, and assessing the same outcome measures, part 2 of this investigation was a controlled, randomized, double-masked, 2-parallel-arm dietary intervention study in which healthy participants (aged 35-55 y) were asked to consume for 12 consecutive weeks up to 2000 mg CFs/d (n = 46) or a CF-free control (n = 28).
  
  
  RESULTS
  Daily intake of up to 2000 mg CFs/d for 12 wk was not associated with significant changes in blood pressure or platelet function compared with CF-free controls in normotensive, healthy individuals who exhibited a very low risk of cardiovascular disease. There were no clinically relevant changes in the metabolic variables assessed in either of the groups. AEs reported were classified as mild in severity and did not significantly differ between study arms.
  
  
  CONCLUSIONS
  The consumption of CFs in amounts up to 2000 mg/d for 12 wk was well tolerated in healthy men and women. This trial was registered at clinicaltrials.gov as NCT02447770 (part 1) and NCT02447783 (part 2).
authors.affiliation: Mars Inc., McLean, VA; and Departments of javier.ottaviani@mss.effem.com.
authors.forename: Javier I
authors.initials: JI
authors.lastname: Ottaviani
authors.affiliation: Mars Inc., McLean, VA; and Departments of.
authors.forename: Marion
authors.initials: M
authors.lastname: Balz
authors.affiliation: Nutrition and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kimball
authors.affiliation: Nutrition and.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Ensunsa
authors.affiliation: Nutrition and.
authors.forename: Reedmond
authors.initials: R
authors.lastname: Fong
authors.affiliation: Nutrition and.
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Momma
authors.affiliation: Mars Inc., McLean, VA; and Departments of.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kwik-Uribe
authors.affiliation: Mars Inc., McLean, VA; and Departments of.
authors.forename: Hagen
authors.initials: H
authors.lastname: Schroeter
authors.affiliation: Nutrition and Internal Medicine, University of California, Davis, Davis, CA.
authors.forename: Carl L
authors.initials: CL
authors.lastname: Keen
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002099:Cacao / Q000737:chemistry*; D002140:California / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D044948:Flavonols / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D057194:Intention to Treat Analysis; D059012:Lost to Follow-Up; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010974:Platelet Aggregation; D012307:Risk Factors; D012639:Seeds / Q000737:chemistry*; D014970:Xanthines / Q000097:blood / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D044948:Flavonols; D014970:Xanthines
keywords: cocoa; epicatechin; flavanol; procyanidin; safety