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* '''Glutamine hypothesis'''<ref name="OTBiochemical"/><ref name="OTPhysioReview"/>. Endurance exercise deplete glutamine levels and glutamine is important for immune system functioning. However decreased levels of glutamine have not been observed in overtrained athletes<ref name=" OTBiochemical "/>, and glutamine would only explain the compromised immune system, not other symptoms of [[Overtraining Syndrome]].
* '''Hypothalamus<ref name="OTBiochemical "/>/Adrenal Fatigue Syndrome<ref name="OTAdrenal"/> hypothesis'''. This hypothesis is based around compromise of the hypothalamus, pituitary gland or adrenal gland, which are all responsible for hormone levels. This hypothesis may have some limited support from the success in treating [[Overtraining Syndrome]] with hormone replacement therapy.
* '''[[Muscle ]] damage hypothesis<ref name="OTBiochemical "/><ref name="OTTrauma"/>'''. Exercise induces damage to the muscle cells and this hypothesis suggests that this damage is the underlying root cause of [[Overtraining Syndrome]]. It is deemed unlikely that [[Overtraining Syndrome]] would be caused directly muscular damage, but rather this damage would precipitate other changes leading to [[Overtraining Syndrome]]<ref name="OTBiochemical"/>. It is been observed<ref name="OTSickAnimals"/> that wounded animals exhibit "recuperative behavior", where they become lethargic, less sociable, and exhibit reduced appetite and thirst. This behavior is believed to encourage recovery by reducing activity and exposure to predators. This "recuperative behavior" in some ways mimics [[Overtraining Syndrome]] and depression in human beings. Unfortunately this hypothesis has never been supported by objective measurement<ref name="OTBiochemical"/>.
* '''Brain receptor hypothesis'''<ref name="OTDepression"/>.''' '''Exposure to chronic stress may lead to altered neurotransmitter receptors within the brain. Changes in these neurotransmitter receptors can modify the fundamental mechanisms of the brain and are believed to play a role in both [[Overtraining Syndrome]] and major depression.
* '''Brain plasticity hypothesis'''<ref name="OTDepression"/>. The human brain retains the ability to update its 'neurological wiring', which is part of our ability to adapt and learn. This neural plasticity is one of the adaptations that occurs to long-term exercise. While mild levels of exercise in harms the creation of new neurons, severe exercise stress causes neurological degradation.
