The change in rear end gearing will reduce the towing capacity of the truck and may increase wear and tear on the engine and transmission but it is not going to do anything for your fuel economy.
Reducing the speed at which you drive by 10 MPH will help your fuel economy. Reducing the weight of the truck by 1000 lbs. will help your fuel economy. Not towing a trailer will definitely help your fuel economy.
Even with 4-speed transmissions and 4.10 gearing on my SUV's and trucks I got the same MPG as newer vehicles with 5 and 6 speed transmissions. The 5th and 6th speeds are both overdrive gears and more than compensate for the 4.88 gears. When towing the taller 4.10 gears in the F-450 are more likely to hurt fuel economy as the engine will spend more time outside its peak power band.
