title: Effects of folic acid supplementation on inflammatory and thrombogenic markers in chronic smokers. A randomised controlled trial.
abstract: BACKGROUND
  Cigarette smoking may induce pro-inflammatory and pro-thrombotic changes. It is not known whether these abnormalities are caused at least partly by increased homocysteine levels. We investigated whether lowering homocysteine by folic acid supplementation might reduce the plasma concentration of inflammatory and thrombogenic markers in chronic smokers.
  
  
  METHODS
  Twenty-four healthy cigarette smokers (age 37.8+/-2.5 years, mean+/-SEM) were randomly assigned to 4 weeks of folic acid 5 mg/day or placebo. The following parameters were measured before and after treatment: (1) markers of inflammation (C-reactive protein, CRP, and white cell count, WCC); (2) blood coagulation screen (Activated Partial Thromboplastin time Ratio, APTR, and International Normalized Ratio, INR); (3) pro-thrombotic markers (fibrinogen, factor VIII coagulant activity, VIII:C, von Willebrand factor, vWF, and D-dimer).
  
  
  RESULTS
  Folic acid induced a significant reduction in homocysteine (10.8+/-0.6 vs. 8.2+/-0.5 micromol/l, p<0.001), plasma fibrinogen (3.15+/-0.14 vs. 2.87+/-0.14 g/l, p<0.05), and D-dimer (102+/-44 vs. 80+/-26 microg/l, p<0.05) concentrations. By contrast, no significant changes were observed in CRP (2.2+/-0.7 vs. 1.7+/-0.7 mg/l), WCC (7.2+/-0.5 vs. 6.8+/-0.5 10(9) cells/l), APTR (0.91+/-0.02 vs. 0.93+/-0.02), INR (0.92+/-0.01 vs. 0.91+/-0.01), vWF (103+/-8 vs. 102+/-9 U/dl), and VIII:C (120+/-8 vs. 107+/-8 U/dl) levels. Changes in folic acid plasma concentrations were significantly and negatively correlated with changes in fibrinogen (r=-0.48, p=0.01) but not with changes in D-dimer (r=-0.15, p=0.5) levels. Changes in plasma homocysteine concentrations did not correlate with changes in either fibrinogen or D-dimer. No significant changes in homocysteine, inflammatory and thrombogenic markers were observed in the placebo group.
  
  
  CONCLUSIONS
  Short-term folic acid supplementation had no significant effects on inflammatory markers but induced a significant reduction in plasma fibrinogen and D-dimer concentrations in healthy chronic smokers. Thus, folic acid might have an anti-thrombotic effect in this high-risk group independent of the homocysteine lowering effect.
authors.affiliation: Department of Health Care of the Elderly, Guy's, King's, and St. Thomas' School of Medicine, King's College Hospital (Dulwich), East Dulwich Grove, London SE22 8PT, UK. arduino.mangoni@kcl.ac.uk
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
authors.forename: Roopen
authors.initials: R
authors.lastname: Arya
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ford
authors.forename: Belinda
authors.initials: B
authors.lastname: Asonganyi
authors.forename: Roy A
authors.initials: RA
authors.lastname: Sherwood
authors.forename: Emma
authors.initials: E
authors.lastname: Ouldred
authors.forename: Cameron G
authors.initials: CG
authors.lastname: Swift
authors.forename: Stephen H D
authors.initials: SH
authors.lastname: Jackson
mesh_terms: D000328:Adult; D015415:Biomarkers; D001798:Blood Proteins / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D006710:Homocysteine; D005340:Fibrinogen; D005492:Folic Acid