Effect of lowering of homocysteine levels on inflammatory markers: a randomized controlled trial.
BACKGROUND
Elevated concentrations of homocysteine and low concentrations of folate may lead to a proinflammatory state that could explain their relation to vascular disease risk. We investigated the effect of lowering homocysteine concentrations by means of folic acid supplementation on markers of inflammation.


METHODS
In a double-blind, randomized, placebo-controlled trial among 530 men and postmenopausal women with homocysteine concentrations of 1.8 mg/L or higher (>/=13 micromol/L) at screening, we investigated the effect of folic acid supplementation (0.8 mg/d) vs placebo for 1 year on serum concentrations of C-reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density lipoprotein, and autoantibodies against oxidized low-density lipoprotein.


RESULTS
After 1 year of supplementation, concentrations of serum folate increased by 400% (95% confidence interval [CI], 362%-436%), and those of homocysteine decreased by 28% (95% CI, 24%-36%) in the folic acid group compared with the placebo group. However, no changes in plasma concentrations of the inflammatory markers were observed.


CONCLUSIONS
Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by means of 1-year folic acid supplementation does not influence inflammatory responses involving C-reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density lipoprotein, and autoantibodies against oxidized low-density lipoprotein.
Durga
Jane
J
Division of Human Nutrition, Wageningen University, and Wageningen Centre for Food Sciences, Wageningen, the Netherlands. jane.durga@wur.nl
van Tits
L J H
LJ
Schouten
Evert G
EG
Kok
Frans J
FJ
Verhoef
Petra
P
D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects*; D002097:C-Reactive Protein / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D006397:Hematinics; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D005492:Folic Acid