For 18 months using 500mg Idebenone changed my life. I increased my activity, had little fatigue(still had severe venous pooling meaning I have to lie down several times a day), and got to the point where I could walk around the block without set back. I was doing light resistance work on my back daily, and was able to type without bicep fatigue. The difference between using Idebenone and day to day life prior was huge. 5 weeks ago all that changed. First of all I jogged on a treadmill for the first time in 14 years(about 5 mins). I pushed to do this. I started with walking and got up my pace. Now bear in mind I was bed ridden a decade ago, and 2 years prior only walked a couple of hundred meters at a time. After this I had some breathing trouble but not severe PEM. 1 week later I added B12 and mixed B Vitamin oils. I immediately used high dose. 3 days later severe crash. Adrenaline dump, weakness in arms, tingling, jelly like limbs and severe breathing problems. Now Idebenone does not work at all. Just typing fatigues my muscles. It is like the exercise, then B vitamins have changed my biochemistry, now Idebenone gives me heartburn within minutes after transdermal application. It also causes some heart racing and breathing problems. What the hell is going on? In the last 18 months I was barely on any forum, because I was progressing and had hope. I did not need any doctor input. Now I am scrabbling for help. So frustrating.