Health Matters

Melatonin – possibly the most understudied nutrient in ulcerative colitis treatment!


Melatonin is a neurotransmitter-like hormone (Lee et al, 2019) released into the blood stream by the brain’s pineal gland (Zhao et al, 2021) in response to darkness (Masters et al, 2014).

Melatonin has many functions. It controls our internal circadian rhythms, sleep and immune system functions (Zhao et al, 2021). It’s a powerful antioxidant, anti-inflammatory (Acuña-Castroviejo et al, 2014), and influences the functions of many genes toward better health (Carlberg, 2000).

In the gastrointestinal tract melatonin is produced and secreted by:

  1. enterochromaffin cells
  2. certain immune cells
  3. intestinal microbes

The gut produces 10-400 times the melatonin found in the blood (Acuña-Castroviejo et al, 2014) and production is controlled by diet, not by light (Zhao et al, 2021). Much of this melatonin is secreted into the intestinal lumen (Anderson & Georgios, 2019) where it mixes with your food and has health promoting effects intestinal lining cells and gut bacteria.

Supplemental melatonin helps improve the composition of gut microbiota (Park et al, 2020).

Studies of experimental colitis in mice and rats, show melatonin significantly reduces virtually all signs and symptoms of experimental colitis, including diarrhoea (Cuzzocrea et al, 2001 in Zhao et al, 2021).

One of the ways melatonin achieves these benefits is by altering composition of the gut microbiota, increasing the abundance of healthy bacteria and reducing harmful bacteria (Zhao et al, 2021).

Human ulcerative colitis (UC) patients have significantly lower melatonin in the descending sigmoid colon (the area most often affected in UC) and these levels decrease steadily as UC disease severity increases. Further, concentration of melatonin production enzymes is drastically reduced in colon cells of UC patients (Zhao et al, 2021).

Melatonin acts to specifically increase the number of butyrate producing bacteria in the colon, including:

  1. Firmicutes bacteria such as:
    1. Lactobacilli,
    2. Faecalibacterium,
    3. Eubacteria,
    4. Roseburia,
    5. Anaerostipes,


  1. Bacteroides bacteria such as:
    1. Bacteriodes thetaiotaomicron &
    2. Bacteriodies vulgatus (Zhao et al, 2021).

You may remember from my previous articles that UC patients have abnormally low levels of “butyrate” in their stool (Kumari et al., 2013) and that increasing colonic butyrate levels correlates with improved UC signs and symptoms (Kanauchi et al., 2002)

Despite all this evidence, only two studies have examined melatonin as a treatment for UC.

The first study gave UC patients standard care, plus melatonin (3 mg/d) or placebo. After 3 months researchers found melatonin significantly improved patient:

  1. symptom scores,
  2. faecal calprotectin levels,
  • energy and general health,

relative to placebo. The authors found melatonin safe and effective as an adjunctive treatment for mild to moderate UC (Shahrokh et al, 2021).

Note: Faecal calprotectin increases with worsening intestinal inflammation (Stříž & Trebichavský, 2004) and is used to help diagnose UC, or determine treatment success (Vaos et al, 2013).

The second study gave 60 UC patients mesalazine 2 x 1.0 g/day, plus melatonin 5 mg daily or placebo. After 12 months (when compared to patients on placebo), patients on melatonin:

  1. all remained in remission,
  2. had normal CRP levels (inflammation marker),

The authors concluded melatonin supplementation helps maintain UC remission (Chojnacki et al, 2011).

UC patients may like to discuss the viability of adding melatonin to their treatment plan, with their primary care physician or specialist.


Article Written + Submitted by:

Andreas Klein Nutritionist + Remedial Therapist from Beautiful Health + Wellness
P: 0418 166 269

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