I say don't do it.
I also say don't run octane booster.
Your engine was designed to run on 87 (regular) octane, so running higher/booster is just wasting your money. It will do absolutely bupkis for you (other than make you think you are doing something and empty your wallet faster)
Ford is stupid with their trucks IMO. They LOVE to underpower their trucks and that causes poor fuel economy.
The 4.6 should only be in rangers and cars. The 5.4 should only be in the F150. And the V10/Diesels should be in F250+.
My moms 2000 2wd Yukon with the 5.3l vortec and automatic trans got the same fuel miles as my dads 05 Silverado 2wd single cab shortbed v6 5sp.
Why? Because the bigger vehicle had a big enough motor to pull it's weight. If the 05 had the 5.3l it would get even better fuel miles.
The other day my buddy found a F350 DRW 4x4 on the internet with the 5.4L. I've driven a 5.4L F250 2wd and it was one of the most gutless things I've ever driven so I cant imagine that big ass F350.
The only way for you to get more fuel miles is to either do a diesel swap or put power adders on your engine. More power (to a point) will equal more MPG.