We can do indirect calorimetry. One liter of oxygen consumed equals 5 kcal (how that was determined, I don’t know). So we can do experiments to measure how many calories are used, such as having someone walk on a treadmill using a mask connected to a metabolic cart that measures how much oxygen they are using, then convert that to calories.
This process is used often in measuring efficiency and economy (for, say, a new type of athletic shoe or bike handlebar system).
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