When supporting methylation pathways, it is important consider synergistic nutrients in addition to folate and vitamin B12. In some of the toughest cases, the patient will not get effective lowering of homocysteine until choline is supplemented. Choline converts to betaine with the help of riboflavin and aids methylation in this step of the pathway. In addition, TMG (trimethylglycine) provides extra methyl groups. The most common block in the homocysteine pathway is the conversion of cystathionine to cysteine, which requires vitamin B6 to activate the cystathionine beta-synthase enzyme. Serine is also needed along with B6 to help convert homocysteine into cystathionine.