Melatonin: Connection to Leaky gut and Rheumatoid Arthritis

This post explains the importance of melatonin in not only regulating your sleep cycle but also its ability to repair epithelial and luminal linings of the duodenum and intestines.

Melatonin is mostly produced in the pineal gland at a specific time at night to help your body go into a deep sleep so that the body can turn on ‘repair mode’. Sommansson A. et al. (2013) states that the gastrointestinal tract may be the largest extrapineal source of endogenous melatonin. This means that the intestinal tract produces the most melatonin in the body outside of the pineal gland! Many more studies explain how Melatonin promotes a Th1 response. When you get a melatonin spike in the middle of the night, you get a spike in Th1 immune cells which helps in intestinal mucosal restoration (repairs leaky gut) and it improves surveillance against microbes in the intestine. Melatonin promoting a Th1 response also helps diminish excessive mucosal permeability (aka leaky gut). This discovery about melatonin emphasizes the need for deep and effective sleep because individuals with insomnia or poor quality sleep can shift towards Th2 dominance which can lead to intestinal permeability and autoimmune diseases. Taking Melatonin, especially during an autoimmune flare, can be extremely beneficial to supporting the healing of the intestinal lining which can help to reduce inflammation. You can take up to 12 mg of melatonin depending on the severity of your sleep difficulties. There are certain cases where you do not want to supplement with melatonin (except under the guidance of a health care practitioner) such as in rheumatoid arthritis flares (see below).

Sjoblom M. & Flemstrom G. (2003) states that Luminal Melatonin (Melatonin in the duodenal lumen) is a potent stimulant of mucosal bicarbonate secretion. The production of bicarbonate is how the duodenum protects itself against acid from the stomach and transforms the bolus of food by reducing its acidity. A person who is less capable of producing melatonin in duodenal lumen may be more vulnerable to erosive effects of the mucosal lining in the duodenum (duodenal ulcers). Ensuring you’re getting consistent sleep and following your circadian rhythm will ensure you’re producing enough luminal melatonin to prevent ulcerations from forming.

Another confirmation Melatonin’s ability to increase Th1 immune cells is in patients with Rheumatoid Arthritis. While most autoimmune diseases tend to be Th2 dominant (humoral), Rheumatoid Arthritis is typically a Th1 dominant condition (cellular). Individuals with RA tend to be Th1 dominant rather than Th2 which means you don’t want to be stimulating Th1 immune cells further. It has been found in many studies that individuals with RA who are Th1 dominant have a flare up in the middle of the night as melatonin levels spike. Because melatonin triggers a Th1 response, if the individual is already Th1 dominant, triggering more Th1 cells to be produced can lead to a flare in their condition. In other words, as melatonin spikes, Th1 immune cells spike triggering more Th1 dominance in patients with Rheumatoid arthritis.

Cutolo M. et al. (2003) shows many graphs explaining how melatonin counteracts the effects of cortisol and how articular inflammation in patients with RA change consistently throughout the day. Their pain and joint stiffness are greater after waking up in the morning than in the afternoon or evening. This is because the melatonin spike in the middle of the night leads to more Th1 production which triggers the autoimmune process in these individuals (see image below).

They also state that A diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and are related to the immunomodulatory effects exerted by cortisol and melatonin, respectively. This article from Cutolo M. et al. (2003) is incredibly in depth in its explanation as to how melatonin affects our bodies inflammation levels.

The point of this article is to show the importance of good quality sleep. If we are not sleeping well, we are pushing our bodies towards a Th2 dominance which can leave us susceptible to chronic pathogenic imbalance and can trigger intestinal permeability which then leads to food sensitivities and chronic inflammation. If you wake up in the morning after a very bad sleep with itching skin or a flare up, it is because you did not get that melatonin spike to help calm your inflammation, repair tissues and clear pathogens from the body (your body relies on this every night to clean house). The job of our Th1 immune system is to scan the body for pathogens and repair mucosal tissues. This cannot happen if we are not getting proper melatonin secretion… aka good deep sleep every night. If you think you need to have bad sleep in order to keep rheumatoid arthritis in balance, you are wrong! While yes, melatonin supports Th1 immunity, you still want to get good quality sleep and instead, find other ways to build up and support your Th2 immune system so that you can achieve a balance between Th1 and Th2 immune responses if you have a Th1 dominant condition.


Circadian rhythms in RA. M Cutolo, B Seriolo, C Craviotto, C Pizzorni, A Sulli. Ann Rheum Dis. 2003 Jul; 62(7): 593–596.

Melatonin in the Duodenal Lumen Is a Potent Stimulant of Mucosal Bicarbonate Secretion. Sjoblom M. & Flemstrom G. J Pineal Res 2003 May;34(4):288-93.

Melatonin decreases duodenal epithelial paracellular permeability via a nicotinic receptor-dependent pathway in rats in vivo. Sommansson A., Nylander O., Sjoblom M: Journal of Pineal research 54(3) 2013.



2 Replies to “Melatonin: Connection to Leaky gut and Rheumatoid Arthritis”

  1. I always notice how my skin looks the most calm in the mornings during my flare ups. However, I tend to get itchier at night time, around 2ish. Is there any reason behind that as well?

    1. Itchier at night is coming from inflammation from foods youre sensitive to that you ate during the day. For example if you have a sensitivity to lemon and you ate some in the afternoon,it takes approx 5 hours for the reaction to start so by evening/night time you’d be itchier.

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