title: Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial.
abstract: BACKGROUND
  Evidence from clinical studies has suggested that cocoa may increase high-density lipoprotein (HDL)-cholesterol concentrations. However, it is unclear whether this effect is attributable to flavonoids or theobromine, both of which are major cocoa components.
  
  
  OBJECTIVE
  We investigated whether pure theobromine increases serum HDL cholesterol and whether there is an interaction effect between theobromine and cocoa.
  
  
  METHODS
  The study had a 2-center, double-blind, randomized, placebo-controlled, full factorial parallel design. After a 2-wk run-in period, 152 healthy men and women (aged 40-70 y) were randomly allocated to consume one 200-mL drink/d for 4 wk that contained 1) cocoa, which naturally provided 150 mg theobromine and 325 mg flavonoids [cocoa intervention (CC)], 2) 850 mg pure theobromine [theobromine intervention (TB)], 3) cocoa and added theobromine, which provided 1000 mg theobromine and 325 mg flavonoids [theobromine and cocoa intervention (TB+CC)], or 4) neither cocoa nor theobromine (placebo). Blood lipids and apolipoproteins were measured at the start and end of interventions.
  
  
  RESULTS
  In a 2-factor analysis, there was a significant main effect of the TB (P < 0.0001) but not CC (P = 0.1288) on HDL cholesterol but no significant interaction (P = 0.3735). The TB increased HDL-cholesterol concentrations by 0.16 mmol/L (P < 0.0001). Furthermore, there was a significant main effect of the TB on increasing apolipoprotein A-I (P < 0.0001) and decreasing apolipoprotein B and LDL-cholesterol concentrations (P < 0.02).
  
  
  CONCLUSIONS
  Theobromine independently increased serum HDL-cholesterol concentrations by 0.16 mmol/L. The lack of significant cocoa and interaction effects suggested that theobromine may be the main ingredient responsible for the HDL cholesterol-raising effect. This trial was registered at clinicaltrials.gov as NCT01481389.
authors.affiliation: Nutrition and Health Department, Unilever Research & Development Vlaardingen, Vlaardingen, Netherlands. nicole.neufingerl@unilever.com
authors.forename: Nicole
authors.initials: N
authors.lastname: Neufingerl
authors.forename: Yvonne E M P
authors.initials: YE
authors.lastname: Zebregs
authors.forename: Ewoud A H
authors.initials: EA
authors.lastname: Schuring
authors.forename: Elke A
authors.initials: EA
authors.lastname: Trautwein
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002099:Cacao / Q000737:chemistry*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013805:Theobromine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005419:Flavonoids; D013805:Theobromine