Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype.
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 28 d-course (15 mg/d) of 5-methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 micromol/l (geometric mean) and urinary excretion of 8-iso-PGF2alpha 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 micromol/l, P < 0.0001) and urinary 8-iso-PGF2alpha (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-PGF2alpha in this population, supporting the antioxidant protective effects of folate in vascular disease.
Coppola
Antonio
A
Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, 'Federico II' University, Naples, Italy. antocopp@unina.it
D'Angelo
Armando
A
Fermo
Isabella
I
Mazzola
Giuseppina
G
Di Minno
Matteo Nicola Dario
MN
Cajani
Alessia
A
Sala
Angelo
A
Folco
Giancarlo
G
Tremoli
Elena
E
Di Minno
Giovanni
G
D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D013763:Tetrahydrofolates / Q000627:therapeutic use*; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D013763:Tetrahydrofolates; D006710:Homocysteine; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate