I see Ken has mentioned exhaust.....
Back in the early 70's, I took my 63 GMC with 305 V6 to Midas Muffler and had a dual exhaust setup installed. Don't know if your big 5000 has the same single exhaust like all the 305's did coming from the factory that way.
That being said, I went from a steady 11 mpg to over 13 with dual exhaust and nothing else- nothing crazy- just two inch pipe through some low back-pressure type "turbo" mufflers that do not make a bunch of noise like some do today, and I noticed a BIG difference in how the engine performed, and it absolutely was better on the hills. The engine just breathes so much better. It was the best $80 I ever spent (back then). In my own situation, I had the mufflers installed outside the frame rail and dumped the exhaust out the sides at a 45 degree angle in front of the rear wheels/tires. Sounded great too! With a 20 percent jump in fuel "economy", I was impressed with this change.
Something ELSE to consider......FWIW,
JimJ AZ