Physiological exposure to low oxygen levels (hypoxia) occurs at high altitude. Hypoxia leads to reduced eating and body weight loss which depend mainly on the duration of exposure and level of hypoxia. Various mechanisms have been proposed to explain these phenomena (e.g. altered leptin release from fat tissue), but there is no general concensus on the underlying causes. Based on the hypothesis that eating in hypoxia is reduced because of increased release of gastrointestinal (GI) hormones that inhibit eating and a local inflammatory response in the GI tract, we performed in-vitro and in-vivo studies in rats and a field study in mountaineers at 500m and 4550m; tests were done on day 2 and 4 at 4550m. We replicated previous findings of reduced eating in hypoxia but this appeared to be unrelated to altered GI hormone release (e.g., CCK, amylin, glucagon) or local GI inflammation. Gastric emptying was rather accelerated in hypoxia. In the field study, some mountaineers required dexamethasone (dex) treatment due to symptoms of acute mountain sickness (AMS). Reduced energy intake in hypoxia appeared to be associated with the severity of AMS. Surprisingly, retrospective analysis of these individuals' data revealed that mountaineers that required dex had reduced insulin sensitivity and lower erythropoietin levels already under baseline conditions. In conclusion, reduced eating at high altitude was not associated with changes in the release of anorectic GI hormones or local GI inflammation. Further, individuals with lower insulin sensitivity may be at higher susceptibility to develop AMS.