I have two mutations, MTHFR 1298AC and MTHFR 677CT, along with candida biofilm. I am an undermethylator with frequently elevated histamine. Health issues started with intestinal inflammation and food sensitivities, progressing to complete carbohydrate intolerance, fatigue, muscle weakness, and more. I have tried many methylation protocols, but each one just jams up my liver, including methyl B12 injections, 5MTHF, cal/mag/zinc, milk thistle, ALA, TMG, methionine, glutamine, and more. Coffee enemas and saunas give some relief, but I am not progressing in my body's ability to conduct Phase I or Phase II detoxification, nor the ability to eat a wider diet (strictly meat and veggies right now). I have not yet tried Simplified Protocol as listed by Rich, but I believe that it is my next step. I'm working with a very new DAN doctor whose son has the same genetic mutations as I do, but unlike his son, I have not responded. I would love guidance in trying the Simplified Protocol, especially since I have always reacted to even reduced dosages of supplements.