A new tune and new higher flow injectors that can support E85 would be required as well. To be honest, it's not really worth doing to your motor.
E85 has a much higher octane rating than premium gasoline. As such, you can run more advance and if you were boosted (turbo or s/c) you could turn up the boost to inject more air. E85 is also cheaper than gasoline.
Trade offs include the fact that E85 has less energy content than the same gallon of gasoline. That's why you get worse mpg on it because you're using more of it, all other things being equal with gasoline. Plus, it has more water in it and as others have said, your fuel tank and lines have to be able to support it.