Effects of folic acid supplementation on inflammatory and thrombogenic markers in chronic smokers. A randomised controlled trial.
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.
Mangoni
Arduino A
AA
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
Arya
Roopen
R
Ford
Elizabeth
E
Asonganyi
Belinda
B
Sherwood
Roy A
RA
Ouldred
Emma
E
Swift
Cameron G
CG
Jackson
Stephen H D
SH
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
D015415:Biomarkers; D001798:Blood Proteins; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D006710:Homocysteine; D005340:Fibrinogen; D005492:Folic Acid