title: Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.
abstract: BACKGROUND
  A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown.
  
  
  OBJECTIVE
  The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee.
  
  
  METHODS
  Forty-eight subjects aged 19-65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing approximately 870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules.
  
  
  RESULTS
  The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 +/- 3.1 micro mol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women.
  
  
  CONCLUSIONS
  Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.
authors.affiliation: Wageningen Centre for Food Sciences, Nutrition and Health Programme, Wageningen, Netherlands. petra.verhoef@wur.nl
authors.forename: Petra
authors.initials: P
authors.lastname: Verhoef
authors.forename: Wilrike J
authors.initials: WJ
authors.lastname: Pasman
authors.forename: Trinette
authors.initials: T
authors.lastname: Van Vliet
authors.forename: Rob
authors.initials: R
authors.lastname: Urgert
authors.forename: Martijn B
authors.initials: MB
authors.lastname: Katan
mesh_terms: D000328:Adult; D000368:Aged; D002110:Caffeine / Q000009:adverse effects* / Q000097:blood; D003069:Coffee / Q000009:adverse effects*; D018592:Cross-Over Studies; D005215:Fasting; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012727:Sex Characteristics; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
chemical_list: D003069:Coffee; D010919:Placebos; D006710:Homocysteine; D002110:Caffeine; D025101:Vitamin B 6; D014805:Vitamin B 12