I'm not a fish expert, as my time in the hobby has been more focused on the plants, though I do keep 40 or so in my 46g. I'm currently running with an SMS controller and a glass-sintered (sp?) stone which produces a mist in front of my vertical spray bar. When I first when to the diffuser, I left off the controller. Within an hour of switching to this method (as opposed to an external reactor), I noticed fish losing color, labored breathing (excessive gill movement) and reduced movement. I slowed down the bubble count, swished my hand in the tank water for a minute or so and within 15 minutes, they were acting normal (in my eyes). I ran that way for a couple weeks, and (again) due to a flaky CO2 regulator setup, I eventually put the controller back in place.
Though I still don't see the wonderful 'pearling' that most see when running the diffuser method, I do see little bubbles swirling around my tank when the CO2 is 'misting' into the water column. To my untrained eye, the fish continue to behave as they did prior to the change.
FWIW, my fish consist of Cardinal and Rummynose tetras, Harlequin rasboras, Bushy-nosed plec, assorted corys and loaches, and Otos. Sorry, I don't know the latin names on any of these fellas.
One data point,