What I do is to take the big (5mg) methylfolate dosage early in the morning and the big (5mg) methylcobalamin dosage at noon. But I also take a multivitamin with normal quantities of both methylcobalamin and methylfolate in the morning and at noon. Appears to work for me. Another option, would be to take the big methylfolate dosage at nigh, after dinner, but I haven't tried that yet. I suspect/guess that in this latter case would lead to higher levels of serotonin.