Has anyone experienced diarrhea with Melatonin use?

WOW! Am I glad to have found this website. My wife is 81 and I am 86 yrs old. For some unknown reason we have been a bit far from the front of the queue to get out Covid19 vaccine. I have been following Covid 19 research since early April 2020 and found out about the Ivermectin use last June. It looked like a winner by late July, but was not supported in the USA for lack of rigorous placebo controlled double blinded studies. My doctor agreed to use it on us if we contracted the disease, but would not consider prophylactic use. Then in Dec 2020 I found the FLCCC group and in Jan found their I-MASK+ protocol. Finally, at the beginning of March I found an on-line doctor that would prescribe Ivermectin for me, and, for lack of a vaccination I started the protocol for me and my wife . The protocol calls for 6 mg of melotonin daily before bed. I did a ton of research on melotonin and found many papers (50+) all written in the last 3 years, and all very positive about its numerous benefits , 11 benefits outside of sleep or circadian rhythm control, most importantly (in the context of Covid 19) suppression of inflammation, immunomodulation and anti-oxidant defense. Started melatonin 3/1/2021, 5 mg 45 minutes before bed, 5 days on, 1 day off.
On 3/12/21 my wife had one bout of very loose stool, but she had had a big helping of ice cream w/o taking an enzyme the day before, so that is where I put the blame. Then diarrhea on 3/14, 3/17, 3/20, 3/21, and today, 3/22. Each day was just before lunch, and the episodes became progressively worse – liquid, explosive diarrhea today. She has not had cramps, gas, nausea or multiple daily events.
I spent this AM thinking of any diet/supplement changes we have made that could have been a cause, and luckily thought to google “melotonin/diarrhea” and found y’all. Fantastic. My wife is off of melotonin, starting right now. We will continue with the rest of the MASK+ protocol until we have completed the vaccinations.
Curiously, I have had no problem, but I guess I will stop the melatonin too, in spite of its numerous possible benefits.

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.
Findings:
- 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)

I too had a visit from the diarrhea monster after taking 10mg of gummy melatonin. A few weeks ago I had a bad case of diarrhea. I had been taking melatonin for a couple of weeks initially with no bad side affects. Suddenly wam I was hit hard with diarrhea that lasted a week before I had remembered a cure for chronic diarrhea issues. I was told 20 years ago by a doctor to give my bowels a “rest” for 3 days by having just clear liquids. This cured my diarrhea. I had also stopped taking the melatonin at the same time. Well I did this again recently not knowing I could have just stopped taking the melatonin. The good thing about the 3 day fast is you’re cured faster then if you just stop taking the melatonin which others in this chat say takes 3 weeks on average to stop the diarrhea. So anyone out there having diarrhea after taking melatonin FIRST STOP TAKING MELATONIN and then I recommend the 3 day fast rather then suffering 3 weeks. Then take probiotics to put the good guys back in your system. Good luck, I feel for anyone going through this.