Low Concentrations of Folate in Serum and Erythrocytes of Smokers: Methionine Loading Decreases Folate Concentrations in Serum of Smokers and Nonsmokers

Recent data suggest that hyperhomocysteinemia is associated with an increased risk for premature vascular disease. Total plasma homocysteine (tHcy) may be increased by impaired activity of enzymes or suboptimal availability of B vitamins (1). Homocysteine transsulfuration reactions are catalyzed by the enzymes cystathionine β-synthase and cystathionine lyase in the presence of coenzyme vitamin B6, and remethylation of homocysteine is performed by the enzymes methionine synthase and betaine-homocysteine methyltransferase with vitamin B12 as a coenzyme for the former enzyme. 5-Methyltetrahydrofolate (5-methylTHF) or betaine are methyl donors during remethylation. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) with coenzyme FADH2 synthesizes 5-methyl-THF from 5,10-methylenetetrahydrofolate (5,10-MTHF) (2). The postmethionine load (PML) abnormal tHcy increments may reflect suboptimal plasma vitamin B6 or deficiency of cystathionine β-synthase (3). The present report describes the effects of methionine loading on serum and erythrocyte folate, tHcy, and related thiols in smokers and nonsmokers. We recruited 63 apparently healthy smokers [ages 37.8 ± 0.8 years; body mass index (BMI), 25.4 ± 0.5; male/female, 39/24; cigarettes/day, 16.2 ± 0.8; smoking period (years), 19.7 ± 0.7], 44 nonsmokers (ages 37.8 ± 1.0 years; BMI, 24.5 ± 0.5; male/female, 26/18), and 23 former smokers who refrained from smoking for ≥3 months …