During a marathon, what is the main contributor to muscular fatigue over 2-3 hours of exercise?

The primary contributor to muscular fatigue during prolonged aerobic exercise, such as a marathon lasting 2-3 hours, is the exhaustion of carbohydrates, primarily during aerobic glycolysis. During extended periods of exertion, the body relies heavily on glycogen stores, which are the stored form of carbohydrates in muscles and the liver. As these glycogen reserves are depleted, the ability to sustain high-intensity efforts diminishes, leading to the onset of fatigue.

Aerobic glycolysis is the process through which carbohydrates are converted into energy in the presence of oxygen. This pathway is efficient for producing ATP, the energy currency of the cell, but it relies on adequate glycogen levels. When carbohydrates are exhausted, the body struggles to maintain performance, which can result in a reduced ability to contract muscles effectively, thus contributing to fatigue.

Without sufficient carbohydrates, the body is compelled to resort to fat oxidation, which is less efficient and cannot meet the high energy demands of intense exercise as quickly as glucose can. This inefficiency can further exacerbate feelings of fatigue as the energy supply for sustained physical activity becomes limited.