Several years ago I told Rich that, if it were possible to start the methylation supplements with just ONE molecule, I would do it! Well, I didn't start then. But in late January, I decided to start FolaPro and methylcobalamin at miniscule doses. I should say that I have a very long history with extreme multiple chemical sensitivities and food intolerances (could only eat a handful of foods, and I was basically a prisoner in my home to avoid chemical exposures for a few years) so I have lots of experience getting HUGE reactions from tiny specks of medications and supplements scraped off of a tablet, or emptied from a capsule. The weakness and fatigue component of this illness started about 20 years ago. The most significant improvement I got was when I was treated with chemotherapy (Rich has pointed out that folinic acid is infused along with the meds). I have also been helped by doxycycline. So, in late January of this year, I opened a 1,000 mcg capsule of methylcobalamin, removed a speck, and broke off a very small fraction of a Folapro tablet. I emptied both of these into one cup of water. Then, I measured a quarter teaspoon and put it under my tongue. I could only hold it for a few seconds and I have had to stop this sublingual method because my bottom teeth would ache and ache. To give some perspective on just how small a dose this is, I have only used 4 FolaPro tablets since I began 3 months ago.and realize, that all but approximately 1/200th of that ended up down the drain! I know that this sounds odd and perhaps unbelievable. But I have a difference in energy. Im not sure where my boundaries are for weakness/fatigue. This in itself is very unusual since most days in the past 20 years I have been right at or even beyond that boundary. Its very exciting for me but I am resisting the impulse to increase the dose. The idea that some kind of switch has been flipped really resonates for me. I am cautiously increasing my exercise, without forcing it. Usually, when I have walked my dogs, I have been grateful for their constant stopping and sniffing. Now, I find that I am impatient with them, and try to walk without them so I can go faster(!!!). I have even experienced muscle soreness from walking faster and yet I have NOT experienced PEM. Wow. Rich, I want to thank you for all the information you have provided. I have been following your ideas for years now; I just wish I had acted sooner. The reason I am writing this is to encourage those who may be afraid to gamble with their current state of health. I have enjoyed a half life for several years and I didnt want to risk it on something that could potentially make me feel worse, even for a while. I believe that starting at a VERY small dose is a rational strategy for others like me.