six barrel

Really a 6 pack is just like a spreadbore 4bbl, except harder to tune. With the outboards closed, as in cruising, it is just a 2bbl so I don't see a problem, or even a challenge; mpgs as far as a given engine is concerned, is in the efficiency of the particular engine-combo, which is;
Effective cylinder pressure, rpm, and tuning.
Effective pressure depends on; Scr, Ica, sealing, and throttle opening.
Throttle opening depends on load, rpm, AFR, and ignition timing.
Tuning at this point, is pretty much just AFR
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At 800ft a stock 318LA is predicted to generate 134 psi cranking cylinder pressure at 8.0 Scr, which is enough for most of them with 2.76 gears to break into the 20s mpgUSg
Also at 800ft, a stock 340 is predicted to make 169psi at 10.5 Scr.
So pressure is not the issue.
Imagine (jus saying) what would happen if you increased the pressure in the otherwise stock 318LA, also to 169psi. That would take an Scr of 9.55.
Really, about the only thing handicapping the 340 in terms of mpgs, is the 340 cam, with it's 44 degrees of overlap, compared to the teeners 20;
and the meager 104degrees of extraction, versus 122 for the 318.
With any cam, you can trade compression degrees for extraction degrees, by changing the ICL/Installed Centerline; which sometimes also pukes the effective overlap, and moves or kills some power.
For instance, this 340 cam in at 110, has 116* compression +104* of extraction= 220 degrees to play with. If you advance the cam another 4* to in at 106 you will swap 4 degrees FROM extraction, giving it to compression; 116/104 to 120/100. If you retard the cam 4 degrees, to in at 114*, that will trade 4 degrees away from compression, giving it to extraction; 116/104 to 112/108. While you could certainly do the latter, because 169psi is borderline too high anyway; watch out for what happens to the EFFECTIVE overlap.
In this case, it goes from 40* to 40*, but trades away early opening intake giving it to a later closing exhaust; which IMO, for this combo is probably a good thing. So to recap,
in at 114*, the events are;
268/112/108/276/44overlap/114LSA/Ica of 68* which drops the predicted pressure, with a 10.5Scr, to a much safer 161psi. BadaBOOM! That's about as cheap a change for gas-mileage ,as can be made. But I'm surprised by the change in cranking compression that, in this case, comes to 8psi for a 4* change. I checked it twice, with same results so, it is what it is. 161psi is a good number for iron heads at WOT, and you could run less for cruising.
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Did I mention, that I once put an entire 1969 318LA topend and cam into a 340? Yeah that made it a hi-compression big-bore 318, and it went like snot. That was about 1975/76, and back then, I didn't keep track of anything much less the fuel-mileage, but Ima guessing it was waaaay better than the stock 1970 Swinger 340/4-speed, that I had just sold.
Oh and BTW, it had the sweetest thoop-thoop slow-idle you ever heard,lol. I still have that engine, now torn down, and in storage.