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Effect of homocysteine‐lowering treatment with folic acid plus vitamin B 6 on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo‐controlled, randomized trial
Author(s) -
Vermeulen E. G. J.,
Stehouwer C. D. A.,
Valk J.,
Van Der Knaap M.,
Van Den Berg M.,
Twisk J. W. R.,
Prevoo W.,
Rauwerda J. A.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01332.x
Subject(s) - placebo , homocysteine , medicine , gastroenterology , magnetic resonance imaging , b vitamins , magnetic resonance angiography , vitamin , surgery , pathology , radiology , alternative medicine
Background A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine‐lowering treatment with folic acid plus vitamin B 6 on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. Materials and Methods Using 158 healthy siblings (mean age 46·0 ± 7·6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo‐controlled trial using 5 mg of folic acid plus 250 mg of vitamin B 6 daily ( n = 78) or placebo medication ( n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). Results Seventeen (10·8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61·8%) and 48 (65·8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty‐four participants (15·2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13‐fold vs. placebo; P < 0·001) and vitamin B 6 (8·8‐fold; P < 0·001). Fasting and postmethionine total homocysteine concentrations decreased 38·7% (95% CI, 27·4–50·0) and 29·1% (95% CI, 19·2–39·0) vs. placebo (all P < 0·001). During follow up six individuals in the vitamin‐treated and 11 in the placebo‐treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0·48; 95% CI 0·17–1·41; P = 0·18 and 0·48; CI 0·14–1·60; P = 0·23, respectively). Conclusions These results could indicate a possible favourable effect of homocysteine‐lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.