I'm just wondering about the possibility that some of us have such weak adrenals that we are unable to kickstart methylation. As for myself, I know now that I have had adrenal issues since I was a child, but not with the typical fatigue issues. I had more energy from the time I was born to about my 50th birthday than anyone I know. I literally never wore out, did multitudes of activities, did well in school, excelled at work, slept like a baby, managed a family of 6 and full time job, blah blah blah. What I do remember as a child that makes me think that I had adrenal issues is that I had strange pains in my lower back, and that I would be physically ill if I stayed up late. I'm guessing that my lifetime of energy may have come from excitotoxicity from wheat products (probably the folic acid component rather than the gluten). Once I stopped eating wheat or any other processed product about 5 years ago, at the same time as going through some horrific life stresses, my adrenal and MTHFR issues started to surface. Now, I seem to be among the group of PWCs that never have typical reactions to supplements (even my alternative practitioners are puzzled by me), and am not making progress with the methylation protocol. Actually, I have gotten more fatigued than ever (perhaps the supplements tax my adrenals). So.........here is my question.............do you think that those of us who are intolerant of potassium (another sign of adrenal insufficiency), and fail to respond to supplements, need to fix up adrenals before the supplements will work?