Methionine (Met) is the precursor of S-adenosylmethionine (SAM), donor of methyl groups in more than 50 metabolic reactions, among them synthesis of creatine and phosphatidylcholine and DNA methylation. In the transmethylation pathway (TM), after giving its methyl group, SAM is converted into S-adenosylhomocysteine (SAH) and then into homocysteine (Hcy). The latter can be catabolized into cysteine or remethylated into Met. The role of the remethylation cycle is to ensure a constant supply of SAM, even when Met supply is low. Remethylation of Met can be achieved using preformed labile methyl groups provided by choline and betaine or by methylneogenesis. For endogenous production of methyl groups, tetrahydrofolate (THF) accepts a 1-carbon unit, mostly provided by catabolism of serine, glycine or formate, to form 5,10-methylene-THF which can be irreversibly converted into 5-methyl-THF. The latter transfers its methyl group to the vitamin B₁₂ coenzyme which acts as an intermediary for the transfer of the methyl group to Hcy to regenerate Met and THF. In multiparous dairy cows, when Met supply is above 2.2% MP, a supplement of folic acid and vitamin B12 has no effect on TM but when Met supply is lower than 1.9% MP, the vitamin supplement increases TM. In the latter, the supplement of vitamins also increases AHCY (SAH hydrolase) supporting the previous observation that, when Met supply is low, methylneogenesis allows maintaining TM. The fate of Hcy flowing TM, however, varies according to plasma Met concentration. When plasma Met is low, plasma Hcy and Cys are decreased by the vitamin supplement; methylneogenesis reduces the need for Met by increasing the number of times that a molecule of Hcy is remethylated within hepatic cells before being catabolized. However, when plasma Met is high, this effect is reduced and plasma Hcy and Cys increased. Providing an adequate supply in folic acid and vitamin B12 allows for sufficient endogenous production of methyl groups to support TM, which is likely to be especially of critical importance when methionine supply is low.