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 alpha (8-iso-PGF(2 alpha)), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 mu mol/1 (geometric mean) and urinary excretion of 8-iso-PGF(2 alpha) 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 mu mol/1, P < 0.0001) and urinary 8-iso-PGF(2 alpha) (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 alpha) in this population, supporting the antioxidant protective effects of folate in vascular disease.

Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype / A. Coppola, A. D'Angelo, I. Fermo, G. Mazzola, M.N.D. Di Minno, A. Cajani, A. Sala, G. Folco, E. Tremoli, G. Di Minno. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 0007-1048. - 131:1(2005), pp. 100-108.

Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype

A. Sala;G. Folco;E. Tremoli
Penultimo
;
2005

Abstract

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 alpha (8-iso-PGF(2 alpha)), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 mu mol/1 (geometric mean) and urinary excretion of 8-iso-PGF(2 alpha) 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 mu mol/1, P < 0.0001) and urinary 8-iso-PGF(2 alpha) (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 alpha) in this population, supporting the antioxidant protective effects of folate in vascular disease.
oxidative stress; thrombosis; homocysteine; 5-methyltetrahydrofolate; 5, 10-methylenetetrahydrofolate reductase; 8-iso-PGF(2 alpha)
Settore BIO/14 - Farmacologia
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/9183
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