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Reduced in vivo oxidative stress following 5‐methyltetrahydrofolate supplementation in patients with early‐onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype
Author(s) -
Coppola Antonio,
D'Angelo Armando,
Fermo Isabella,
Mazzola Giuseppina,
Minno Matteo Nicola Dario Di,
Cajani Alessia,
Sala Angelo,
Folco Giancarlo,
Tremoli Elena,
Minno Giovanni Di
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05732.x
Subject(s) - methylenetetrahydrofolate reductase , medicine , endocrinology , homocysteine , oxidative stress , creatinine , population , chemistry , genotype , biochemistry , environmental health , gene
Summary The protective role of folate in vascular disease has been related to antioxidant effects. In 45 patients with previous early‐onset (at age <50 years) thrombotic episodes and the 677TT methylenetetrahydrofolate reductase genotype, we evaluated the effects of a 28d‐course (15 mg/d) of 5‐methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8‐iso‐prostaglandin F 2 α (8‐iso‐PGF 2 α ), a reliable marker of oxidative stress. At baseline, patients’ fasting total homocysteine (tHcy) was 11·5 μ mol/l (geometric mean) and urinary excretion of 8‐iso‐PGF 2 α was 304 pg/mg creatinine, with the highest metabolite levels in the lowest quartile of plasma folate distribution ( P < 0·05). After 5‐MTHF supplementation, plasma folate levels increased approximately 13‐fold ( P < 0·0001 versus baseline); tHcy levels (6·7 μ mol/l, P < 0·0001) and urinary 8‐iso‐PGF 2 α (254 pg/mg creatinine, P < 0·001) were both significantly lowered, their reduction being proportional to baseline values ( r = 0·98 and r = 0·77, respectively) and maximal in patients with the lowest pre‐supplementation folate levels ( P < 0·05). The effects on folate ( P < 0·0001) and tHcy ( P = 0·0004) persisted for at least up to 2 months after withdrawing 5‐MTHF. In parallel with long‐lasting tHcy‐lowering effects, a short‐course 5‐MTHF supplementation reduces in vivo formation of 8‐iso‐PGF 2 α in this population, supporting the antioxidant protective effects of folate in vascular disease.