Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease.
BACKGROUND
Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function.


OBJECTIVE
We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function.


METHODS
This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y.


RESULTS
The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4).


CONCLUSIONS
Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.
Stott
David J
DJ
Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom. d.j.stott@clinmed.gla.ac.uk
MacIntosh
Graham
G
Lowe
Gordon D O
GD
Rumley
Ann
A
McMahon
Alex D
AD
Langhorne
Peter
P
Tait
R Campbell
RC
O'Reilly
Denis St J
DS
Spilg
Edward G
EG
MacDonald
Jonathan B
JB
MacFarlane
Peter W
PW
Westendorp
Rudi G J
RG
D000368:Aged; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D012256:Riboflavin / Q000627:therapeutic use; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000097:blood / Q000188:drug therapy*; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D006710:Homocysteine; D014803:Vitamin B Complex; D025101:Vitamin B 6; D005340:Fibrinogen; D005492:Folic Acid; D014805:Vitamin B 12; D012256:Riboflavin