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You can use an adjustable fuel pressure regulator to lean the mixture out at wide open throttle to tune for power or fuel economy.  A richer a/f mixture such as 12.5:1 will consume more fuel for the same amount of air than a leaner a/f mixture.  So hey, why not just lean it out so you only swipe your gas card bill once a month?  Well, too lean a mixture will pretty much run on the scary side of an engine's Big Bang Theory: the mixture may not ignite and you'll get lean misfire. Not to mention your car would emit pollutants (nitrogen oxides and hydrocarbons) like a coal mine.

Gearing also plays a role in fuel consumption.  Lower gears have higher gear ratios and produce a higher output torque, which as you pointed out is helpful for accelerating quickly and can help the engine maintain speed under load such as a steep grade.  A first gear ratio of 2.3:1 means the crankshaft will turn 2.3 times for every revolution of the transmission.  A higher gear has a lower gear ratio, such as 0.8:1.

Imagine this is a perfect testing environment- one automotive journalists dream about- and for simplicity's sake suppose you maintain a set a/f ratio with either of two gears selected just cruising at light loads.  The engine would consume the equivalent quantity of fuel for each revolution of the engine.  When using a lower gear, the engine will turn more times and consume more fuel; a higher gear would result in fewer revolutions of the engine and consume less fuel. Basically, higher gears = better fuel economy; one more point for accelerating to your speed more slowly.

Just to show the effect of gearing using our previous example, I've backed into speed (mph) at specific fuel consumption units.  Again, assuming stoichiometric air/fuel ratio, you can see how you could be going faster in 4th gear than you could in 3rd gear for the same mass of fuel consumed.

 This graph reads left to right at specific fuel consumption units.  In this example, you'd consume about 31.4% more fuel at 50mph in 3rd gear than you would in 4th gear.

So let's stop making an ASS of U and ME.  Modern engines use more intelligent fuel metering to adjust the air/fuel ratio for all driving conditions.  The engines are in constantly variable load environments and in the real world, there really is no rpm/load that is most efficient (or at least can be constantly maintained) for fuel economy.  Acceleration causes the engine computer to adjust for a richer air/fuel ratio and consume more fuel than a lighter load cruising condition such as slowly getting up to speed.

Quick and easy answer: Generally, the best fuel economy is usually found in higher gears and lower rpm, but you can make a greater impact to fuel economy by stripping your car of excess weight, keeping the tires properly inflated, and maintaining your engine.  A clean air filter, spark plugs, cap and rotor, and ignition wires in good working order, and functioning O2 sensors (which will keep your a/f ratio where it should be for all conditions) can all make a huge difference in gas mileage.  Avoid stop and go traffic- brakes waste kinetic energy on non-hybrid cars.  Hybrid cars actually recover some kinetic energy during braking, energy which is usually dissipated as heat in the brakes.

If you want to monitor your fuel economy, you can use a vacuum gauge to monitor manifold pressure. When the throttle is closed such as at idle, the vacuum is high.  Engine vacuum is near zero at wide open throttle.  A greater manifold vacuum typically indicates the engine is consuming less fuel.  A vacuum gauge can also provide some insight into the condition of your engine.  At idle, if the needle is jumping around a lot, you may have worn or stuck valves or fouled spark plugs.  While accelerating, a jumpy needle could even indicate a blown head gasket.  An always low vacuum reading could show a vacuum leak or bad ignition timing, more causes of bad fuel economy.

So onto engine longevity, how low (rpm) can you go?  Hypermilers flaunt about never getting above 1500-2000 rpm in order to get huge mpg numbers.  While this driving style may provide the best gas mileage, it's not ideal for engine longevity.  You don't want to place a heavy load on an engine at low rpm.  If your engine is bucking, not only do you prescribe a fine dose of whiplash for you and your passengers, but at an unusually low rpm the oil forms a thinner film and won't provide adequate bearing oil coverage for high loads.  This is more apparent when you get below the engine's normal idle speed.  However, this isn't really a likely or comfortable driving scenario anyways!  A brief period of time at an uncomfortably low rpm won't damage your engine but it's not something you should attempt long term.

 The Stribeck Curve demonstates the friction (and consequently wear) between two surfaces as it relates to viscosity, speed, and load.  It mostly pertains to start ups but lugging higher gears in extreme cases illustrates the same correlation.

In boundary lubrication, two surfaces are mostly in contact. This occurs usually at start up.  Mixed lubrication occurs as speeds start to increase or the load decreases. This is when fluid film begins to form and when the friction coefficient drops off sharply.  In hydrodynamic lubrication, surfaces are separated by a vicsous film. You can also see friction increases slightly in the hydrodynamic region due to fluid drag.  Think of this as how much more effective your water aerobics exercise is when you try running through water versus just walking through it.

Got a difficult tech question? Email Sarah at asksarah@motoiq.com