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Probably, since years of evolution went into designing it.
But to push yourself 'til it hurts seems like a waste.
What is a substitute for saltine crackers??? Is there even a substitute it???
Both are correct, you can say substitute for or substitute with.
I used applesauce as a substitute for oil in the recipe to make it healthier.
There is not a substitute for treacle. This has to do with cooking.