The mammalian gastro‐intestinal tract is a NOT a major extra‐pineal source of melatonin

Abstract

In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000–100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. 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‐one 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 0.05–0.19: 1 is likely. The gut is not a major extra‐pineal source of melatonin; indeed it may well not produce any.

Role of Melatonin in Viral, Bacterial and Parasitic Infections

“…In general, the concentration of extra-pineal MLT is reported to be several orders of magnitude higher than that of the circulating pool derived from the pineal gland. Nevertheless, it has recently been found that the gastrointestinal tract is not a major source of extra-pineal MLT, as was formerly believed [ 5 ]. It is, therefore, possible that some of the early studies in this field overestimated the MLT content because of methodological flaws.…”