Sustained homocysteine-lowering effect over time of folic acid-based multivitamin therapy in stroke patients despite increasing folate status in the population.
OBJECTIVE
It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy.


METHODS
We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined.


RESULTS
Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively; p < 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: -4.1, -4.1, -3.1 and -3.6 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.56).


CONCLUSIONS
The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.
Hankey
G J
GJ
Stroke Unit, Department of Neurology, Royal Perth Hospital, Perth, Australia. gjhankey@cyllene.uwa.edu.au
Eikelboom
J W
JW
Loh
K
K
Tang
M
M
Pizzi
J
J
Thom
J
J
Yi
Q
Q
D000368:Aged; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000494:pharmacology; D005500:Follow-Up Studies; D006397:Hematinics / Q000097:blood / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000097:blood* / Q000494:pharmacology; D020521:Stroke / Q000097:blood*; D013997:Time Factors; D014805:Vitamin B 12 / Q000097:blood* / Q000494:pharmacology
D006397:Hematinics; D006710:Homocysteine; D005492:Folic Acid; D011736:Pyridoxine; D014805:Vitamin B 12