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Clearly, running fast is harder than running slow. If I run a 5k in 30 minutes, I will be panting harder and feel more uncomfortable by the end of it than if I jog it in 45 minutes.

Why is this? How can we quantify the difference? An obvious thing to try is to count calories - what is the energy cost of running a certain distance at a certain speed? However, it seems to be fairly well accepted that calories per kilometer is constant, independently of your speed. See e.g. Margaria et al. 1963, Energy cost of running. The claim is also stated very clearly in Carrier et al. 1984, which cites the first paper:

...the cost of transport for a running human does not depend on speed. Consequently, a man running a marathon will consume the same amount of energy for transport whether he runs at a slow jog or at a world-class pace.

If not calories, what is an appropriate way to measure "perceived effort" of running a given distance at a given speed?

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