there is a reason why defensive timeouts are so widely criticized. there is a difference. it matters.
yes, an offense has game planned and knows the playbook. that's not the point of the issue, though. they're dictating the action of the game, not the defense. the defense reacts to what the offense puts out on the field, then reacts to what the offense does during the play. thus they shouldn't have an issue throwing personnel out there. there isn't any additional need, like the offense has. additionally, you need more points to win. yeah, it's obvious, but due to that simple fact, their role is more critical when it comes to timeouts.
if your offense is mixing up play calls at the D1 level, you've got more issues than time management. besides, that's not why you take a timeout, so i don't know why you brought up the playbook and mixing up of play calls. but if you did, then you'd get just as much scrutiny as a defensive timeout. probably more, in fact.
i mentioned cardio because they aren't in shape going into the game, not during the game.