Four examples in the lesson. In the last three ,you could translate con lo que as "despite"but that would not make sense in the first example and seems not to fit the pattern.
Yes, maybe as a more simple sentence "despite" would be used as a more direct translation. As we said in the lesson, there isn't one unique way to translate "con lo que" in English -depending on the actual sentence it will have a specific translation. This is why we didn't use "despite" in that first sentence in the lesson, and we used a more natural (although less literal) "with all the running you do...".
I tried to delete this question.
"Despite" would seem to fit more comfortably in a simple statment: "You are not exhausted despite all the running you do"
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