For best performance on the stock tune, or any of COBB's OTS maps, you should always run the highest octane E10 fuel available from a 'Top Tier' rated gas stations. Ethanol-free fuels, even if rated at 91/93 OCT (R+M/2) will always be more knock-prone and perform worse than conventional E10 91/93 OCT equivalents.
Ethanol blended fuels have a lot of misinformation spread about 'em. Due to the chemical structure of ethanol as a molecule vs. the hydrocarbon chains found in conventional ethanol-free gasoline, the stoichiometric air/fuel ratio is richer - a greater number of ethanol molecules need to be mixed with the air entering the engine in order to achieve a balanced combustion reaction between oxygen and fuel. Since you have to inject more fuel for a given volume of air, you could say that ethanol has a lower chemical potential energy by volume compared to conventional gasoline. BUT - this is not a bad thing for performance!
One of the greatest advantages of ethanol fuel is that it has a greater latent heat of vaporization than conventional gasoline. It will absorb a greater amount of heat energy from its surroundings when in the air/fuel charge when compared to gasoline. Combine this latent heat of vaporization with the greater volume of fuel being injected, you get significantly lower combustion chamber temperatures. This is a significant contributor to resistance to knock.
For more detail on fuel characteristics, this document has some very helpful information:
http://iqlearningsystems.com/ethanol/downloads/Racing Fuel Characteristics.pdf
Increasing the knock threshold allows for an engine to safely run more ignition timing. The Raptor engine - along with most road going vehicles - are significantly octane limited. By increasing the knock threshold with ethanol fuels, very large power gains are attainable via tuning. In short, ethanol is your friend!
The stock tune (and all COBB OTS maps) are designed to run on an E10 blend of fuel. Fuel lines, fuel pumps, and fuel injectors are all designed to safely run on ethanol. While you may eek out 0.5-1MPG improvements by running ethanol-free fuel, the performance capability of the fuel will be drastically lower.
Here is a great video from the folks at HP Academy covering an example tune for ethanol vs. conventional pump gas:
Before you get too excited and fill up with E85, please remember that significant changes in ethanol content must be tuned for - the ECU needs to be programmed to "expect" the significantly richer AFR, or you risk max-ing out fuel trims and/or outrunning the fuel delivery capacity of the stock fuel system. Any COBB Protuner can get you setup with an ethanol blend tune via the Accessport - Goosetuned is getting great numbers via E50 on these trucks. His thread in the engine performance sub-forum has a lot of great information covering fuel quality and ethanol.
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How the truck reacts on the stock tune to varying fuel quality is a completely different story. There is an octane learning system called Knock Octane Modifier (KOM) that will adjust engine operation based on inferred octane. KOM is a global modifier that ranges in potential output from +1 (highest fuel quality) to -1 (lowest fuel quality). KOM interacts with ignition timing and the boost control system to increase timing and maximum load (boost) when inferred fuel quality is high, and decreases timing and maximum load when inferred fuel quality is low. Changes to ignition timing will be active at all engine loads - from highway cruising to WOT. With higher octane fuel, most people will notice improved fuel efficiency as well as increased power, as the ECU is running more ignition timing in most operating conditions. This makes for a more efficient translation of the force of the combustion event into rotational movement of the crank.
KOM will increase or decrease based on the presence of engine knock - this is what we mean by "inferred" octane, as there is no such thing as an octane sensor. The ECU uses feedback from knock sensors to either increase or decrease KOM. If significant knock is detected and individual cylinder ignition timing corrections are significantly low, KOM will lower. If no knock is detected AND the ECU is able to add a significant amount of positive timing correction, then KOM will increase. Driving style will determine how quickly KOM learns back up after the truck sees low quality fuel. I can get KOM to learn up from 0 (default after an ECU reset on the stock tune) to +1 in about a mile with 93 OCT in the tank. You generally want to drive at mid-load (30-40ish % throttle), in the middle of the rev range (2500-4500RPM) for a sustained stretch while keeping gas pedal inputs steady and manually shifting. This helps the engine operate in a zone where it can easily run large positive ignition timing corrections without encountering knock. Two or three steady pulls like this and KOM is back up at +1. On the other hand, I've seen some folks that have a driving style that won't allow KOM to learn up for days.
Car and Driver did a cool test for a few vehicles demonstrating the importance of premium fuel, with an F150 as a tester. What wasn't covered in this article is whether or not the stock ECU is programmed to adjust for varying octane fuels. We know that the Ford octane learning system is very active, and as a result we see very significant differences in C&D's test. Other vehicles that see less of a difference likely do not have an octane learning system on their factory ECUs, or are at least much less reactive.
https://www.caranddriver.com/features/a28565486/honda-cr-v-vs-bmw-m5-ford-f-150-dodge-charger/
We maintain the use of KOM on all of our OTS maps. However, we do not recommend leaning on this feature as an "auto-octane" system because it requires engine knock to occur in order to adjust for lower octane fuels. Imagine that you are driving around on a 93 OCT map, KOM is +1, and you fill up at a gas station with 87 OCT. You hammer the throttle out of the gas station, and before the ECU can learn the lower inferred octane and adjust KOM to safely retard ignition timing and reduce load, you get a ton of (potentially catastrophic) knock! If you are running an Accessport, you can easily change over to one of the pre-loaded lower octane maps or even the stock tune within 30-60 seconds - way faster than it takes to fill a 33 gallon tank! In our opinion, this is a much more fail-safe way of adjusting for varying fuel quality.