I might be able to shed some light on the problems you guys have with adenosylcobalamin (AdoCbl, AdB12, dibencozide). It's not good for me either - it exacerbates my fundamental CFS fatigue. Years ago my research involved the design and synthesis of adenosyl-/adenosine-containing drug mimics of natural products. That adenosyl functionality (component) lends the potential to interfere with (inhibit) many enzymes in the human body that use adenosine-containing substrates or cofactors.
So either AdB12 itself and/or a metabolite/reaction product (including adenosine) is likely simply inhibiting one or more of these enzymes. There are too many possibilities to know for certain which, but since we're talking about the Methionine (methylation) Cycle here, and just as an example only, a potential troublemaker in that pathway might be S-adenosylhomocysteine hydrolase (AdoHcy hydrolase). It converts AdoHyc to homocysteine + adenosine. It's inhibited by many adenosine analogues and derivatives. So, theoretically, taking large (non-physiological) amounts of AdB12 could inhibit the function of that enzyme in susceptible people (i.e., those with a particular SNP or combinations of SNP's) to the point they'd feel bad. Again, this is just a single possible example (it's probably hindering to some degree many pathways in large doses).
The bottom line is that by taking AdB12 you may be "shooting yourself in the foot" and blocking (if only temporarily) the very pathways you're hoping to increase activity in. Personally, since I'd already bought a bottle of the stuff a while back (Source Naturals, 10mg), I'm just taking a tablet once or twice a week - when I'm not planning on needing to be active - to (possibly) top off my stores of this form for the time being. Once I run out I won't use it anymore. There's no need for the vast majority of people - both hydroxycobalamin and methylcobalamin are normally converted to adenosylcobalamin to about the same degree. I only bought it in the first place because my succinate levels tested low and I wanted to see if attempting to increase the activity of methylmalonyl-CoA mutase, which uses AdB12 as a cofactor, might help. It didn't. (I'd actually first tried it several years ago and was just double-checking.)
If AdB12 makes a person feel bad, I'd just stick with hydroxycobalamin if you're an "overmethylator" (you're COMT+ and/or you react badly to SAMe and MeB12) or with MeB12 if you're an "undermethylator" (you're COMT- and/or you like SAMe or react badly to hydroxycobalamin). Or a combination of both if you're somewhere in between.
