Hi PeterPositive. The Deplin tests found that that "Deplin is well tolerated with side effects similar to placebo". They were just giving those people arbitrary doses. This practice is to titrate to effectiveness. The sooner the folate insufficiency symptoms go away the more comfortable and the more healing. The amounts of B1, B2 and B3 can increase the amount of Metafolin needed. If a person has exposure to folic acid they may accumulate enough to block Metafolin and it can block 10x the Metafolin. I played with all sets of timing to get around that. For some people folinic acid and veggie folates can do the same except that the folinic can block up to 20x as much Metafolin. I found that people without symptoms are quite happy with 800mcg. People with a startup response often need 4000mcg. People with some degree of folic acid problems 8mg and people with folinic acid problems 16mg. This was before finding that too much b1, b2 and b3 can worsen folate insufficiency. That is why a person needs to find out if they have these sensitivities. I took 20mg a day for some years. Now I take 4-8 mg daily and haven't had an episode of folate insufficiency in months.