Sakurai points it out whenever he gets a chance and sometimes just on his own. He likes to stress how stressful it is, but in reality there's little difference between the development of Smash and any other franchise. All game development can be stressful, but with such a beloved franchise like Smash surely the opportunity for being at the helm is more rewarding than it is stressful, otherwise why do it?
There are other people who could direct an equally, if not better version of a new Smash. I'm sorry but if working on Smash is the sole reason for causing him physical/emotional distress, then Sakurai should seriously consider another career or at the very least another franchise.