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The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No\u2010one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05\u20130.19: 1 is likely. The gut is not a major extra\u2010pineal source of melatonin; indeed it may well not produce any.<\/jats:p>","DOI":"10.1111\/jpi.12906","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T07:41:28Z","timestamp":1693467688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The mammalian gastro\u2010intestinal tract is a NOT a major extra\u2010pineal source of melatonin"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-3514","authenticated-orcid":false,"given":"David J.","family":"Kennaway","sequence":"first","affiliation":[{"name":"Robinson Research Institute and Adelaide School of Medicine, University of Adelaide, Adelaide Health and Medical Science Building North Terrace  Adelaide South Australia 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