I don't have ME, but this forum is the most helpful resource ever, so I hope it is okay to post here. My blood test showed that I'm homozygous for the MTHFR mutation - I am 24 years old. This was a huge relief to learn, as my health has been quickly deteriorating over the past few years, and nobody could figure out why. The same thing has happened to both of my brothers, so they are getting tested as well. My symptoms are: Extreme internal anxiety (even though everyone thinks I'm "so calm" on the outside) Shortness of breath Insomnia (waking up frequently and early) Constant tightness / dread in chest Extreme irritability at trivial things, especially noises Headaches out of nowhere (especially in the middle of the night) Me and my entire family also have a history of drug / alcohol abuse, although I have completely stopped out of concern for my health. We also have a history of stroke, heart disease, and joint pain. My doctor prescribed Klonopin to help with the shortness of breath, but it didn't help at all. I remained irritable and anxious, in addition to just feeling exhausted. After reading as much as I could, I found that Sam-E is a methyl donor and can provide immediate relief to undermethylators. It definitely did. I hadn't responded to any other supplement, but Sam-E made me feel a million times better. Three weeks later, the effects have worn off and all of my symptoms have returned. I decided to try and address the root of the problem by taking two 1000mcg Solgar Methyl-Folate last night. I woke up at 2am feeling like someone was squeezing my heart in their fist. My shortness of breath was terrible, I couldn't take a single full-feeling breath. My anxiety and dread were horrible, terrified that I was never going to feel happy again. It's 3pm now and I feel mostly back to "normal" (regular intensity of my usual symptoms). Can someone please help me understand what in the world just happened? I've read that folate is a serotonin re-uptake promoter. Should I just avoid it? And if so, then how can I get to the root of my methylation issues? I want to help my siblings too. We used to be so fun-loving, social, successful, competitive, happy, and energetic in high school. Now we're all just miserable. Thank you!