Leaving space in your animation frame canvas will indeed take up more space than if you trim the frames. In runtime it's going to be counted as the nearest power of 2 when it's placed in vram. I'm not sure how much of a difference there is between frames with content and completely transparent frames of the same size, though. However, as long as you're not doing anything insane, like a 989x750 canvas for a 125x80 sprite, the difference should be negligible.
But, here's the neat thing. You can work with the frames in any size you like. But when you're done, trim them. What's important is the origin point, and that information is kept when you do the trim. So there really is no need to have large spaces in your frames, but having them is not something that's going to have too much of an impact.