In regards to the article at the top of the page on 25 Sept: Assuming training is sufficient and the environmental conditions are neutral, the factor which will limit performance most on an ultra-distance (loop) course is muscle damage.
There is a muscle lengthening (eccentric) and a muscle shortening component (concentric) to each stride during running. Running on a flat course increases the amount and intensity of eccentric contractions compared to running on a course that changes slightly (or largely) over the distance.
Eccentric contractions are what produces muscle damage (primarily) in the quads during running. You have muscle damage when your muscles are sore and tender 24 to 48 hours after a run.