We stopped the melatonin on Monday 3/22/21. My wife had 4 explosive liquid events between 7:30 and 11:30 AM on Tues and Wed, one event Thurs at 7:30 AM, followed by a soft but formed stool at 1:00 PM, and a small liquid event at 7:30 AM today, with no follow-up so far (2:30 PM).
Trying to understand why some people ( 0.1% of the population?) might experience diarrhea as an “adverse event” (AE) from melatonin supplementation, I read about
80 abstracts and 27 entire published papers dating from 1998 through 2021.
- Serotonin is a melatonin precursor. LabCorp gives a Lab Ref Range (LRR) of 21 – 321 ng/ml for males and 0 – 420 ng/ml for females. Other sources give narrower ranges (50-200, 100-280, <330) w/o the gender distinction. (My wife’s average level over several years is 3x my level and in the upper 3SD range of the LabCorp ref range).
- Folate and Vit B6 promote serotonin production. Many multivitamins and B-Complex supplements contain levels of these 2 vitamins that are up to 2x the recommended daily allowance for folate and 60x for Vit B6.
- Serotonin is found in the stomach and intestines. It helps control bowel movements and digestive function.
- Conversion of serotonin to melatonin is subject to very wide variation due to genetic SNPs.
- Endogenous melatonin production in subjects w/o supplementation varies from 2 – 84 pg/ml, - 40:1!
- There are large inter-individual variations in bioavailability of exogenous melatonin (1% to 37%) – median level 3x as high in females as in males.
- For sleep a dose of 0.3 mg/day is better than 0.1 mg or 3.0 mg.
- Peak concentration of melatonin after supplementation is proportional to dosage and subject to very wide inter-individual variations: 0.1 mg dose peak median is 5x baseline, - range of 2x-7x
- 0.3 mg dose “ “ is 10x “ “ of 5x – 15x
- 0.5 mg dose “ “ is 25x “ “ of 20x – 30x
- 3.0 mg dose “ “ is 600 “ “ of 300x – 1000x
- A 5 mg dose for 30 days raises the mean baseline level by 2.5x.
- 37 Randomized Controlled Trials (RCTs) with doses from 0.5 mg to 12 mg and followed for up to 29 weeks had levels of adverse events less than 2%, none of which were diarrhea, and none of which were clinically serious.
- High levels of serotonin can lead to “serotonin syndrome” which can be fatal, and has numerous symptoms including diarrhea.
It seems likely that a very small %age of people that are at the high end of peak concentration response to dosage, probably due to genetic variants, and/or that have elevated levels of serotonin, elevated levels of B vitamin supplementation, high levels of endogenous melatonin, and are female may have a particular sensitivity to supplemental melatonin that leads to diarrhea. It seems that the %age is low enough to have escaped detection in scientific trials. Some of them might get the benefits of melatonin supplementation at very low dosage - =< 0.3 mg.
Medical science is clearly unaware of this issue, and has not even seen all of the dots, let alone connecting them.
Post Edited (murrayv) : 4/2/2021 1:11:29 PM (GMT-6)