We present directions for future research into the pathophysiological mechanisms that underpin athlete susceptibility to long-term issues. Special consideration is given to youth, masters, and female athletes, all of whom may be more susceptible to certain long-term health issues. The purpose of this review is to present the current state of knowledge regarding the potential long-term health problems derived from UER, specifically potential maladaptation in key organ systems, including cardiovascular, respiratory, musculoskeletal, renal, immunological, gastrointestinal, neurological, and integumentary systems. Serious acute adverse events are rare, but there is mounting evidence that UER may lead to long-term health problems.

Ultra-endurance running (UER) is an extreme sport that is becoming increasingly popular, and comprises running races above marathon distance, exceeding 6 h, and/or running fixed distances on multiple days.

It is well established that physical activity reduces all-cause mortality and can prolong life.

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