Reply posted by @Anders to an entry on my blog. Needs to be here. Please tag @Anders on any replies or if a moderator can change the owner of this thread to Anders please. PLEASE HELP! Someone out there who understands methylation far better than we do, must be able to figure out the terrible problem we are having: Our son has suffered from depression for years, when it went from moderate to severe, it began with an entire year of Chronic Fatigue, after several back to back viruses. The chronic fatigue gradually got better, but the severe depression did not. Fast forward years down the road. After trying every antidepressant out there with no success, our so discovered he was homozygous for mthfr a1298c. Since then, he has tried various strengths of methylfolate to try to achieve remission. He can not tolerate the higher doses of methylfolate, and settled on 2 mg. He took a break from everything at one point, and then reintroduced methylfolate at 2mg, and this time he took it with methylcobalamin at 2.4mg. Within 3 days, he had an amazing (almost miraculous response), which we thought was the answer. His response lasted about a week and then fizzled out and he became depressed again. He continued to take the MTHF and the MTH-CBL for awhile but nothing. He went up on the MTHF and MTH-Cbl gradually but nothing. Then he decided to take a short break. After about 5 days, he reintroduced the original 2mg & and 2.4mg doses of mthf and mth-cbl, and again got the wonderful robust response which had him again feeling normal for the second time in years, only to fizzle out 5 or 6 days later. He has been able to replicate this response several more times, but each time it lasts about a week and then fizzles. How can we help him achieve a sustained response? Has anyone seen or heard of this kind of thing before? There has to be a methylation solution. Please help us!!! Does he need way more MB12? Does he need a different kind of B12? Maybe he needs less B12 or no B12? Is he taking too much mthf? Is there something else going on with his methylation? Is this a methyl-trap?