Warning: Scientists discover melatonin is a popular sleep supplement that can compromise gut health

One study indicated that the hormone, which is readily available for purchase in pharmacies and often used as a supplement, intensified the symptoms of Crohn’s disease and ulcerative colitis in laboratory mice. The effect, however, depended on the gut microbiota profile of the animals.

Often referred to as the sleep hormone, melatonin is used extensively as a dietary supplement (typically without doctor’s approval) by individuals suffering from sleep problems.

The Cardosos laboratory conducts research on inflammatory bowel disorders, including Crohn’s disease and ulcerative colitis. These disorders are immune-mediated, resulting from abnormal immune cell activity in overreacting to a pathogen, with destructive effects on the gut microbiome and severe clinical symptoms, such as abdominal pain, constant diarrhea, bleeding, and fatigue.

Treatment involves suppressing or inhibiting the immune response in order to reduce the excessive inflammation that damages the intestines. In addition to corticosteroids and immunosuppressants, treatment may involve immunobiologic drugs, which are most effective for moderate to severe cases but not affordable for most patients. In Brazil, they are only paid under certain circumstances by the SUS (Sistema nico de Sade, as the National Health Service is known) or by health plans in case of a court order.

Our lab works to gain a better understanding of these diseases and propose new, more cost-effective treatments, said Cardoso, who holds a dental degree from the Federal University of Uberlndia (Minas Gerais state) and a PhD. in basic and applied immunology from USP, with postdoctoral internship at the Forsyth Institute, an affiliate of the Harvard School of Dental Medicine (USA).

In addition to the cost-effectiveness issue, he added, many patients do not respond well to even the most advanced treatments and must undergo surgery to remove parts of their intestines. These invasive procedures have a highly negative effect on their quality of life. For this reason, we have been pursuing new therapeutic options in recent years, based mainly on the modulation or regulation of the immune response, he said.

Cardoso and his team have years of experience researching hormones and recently started focusing on melatonin. Look, I’m in no way saying that melatonin has no beneficial effects. On the contrary, in fact. There are few studies or reports that indicate any negative side effects, he said.

Indeed, melatonin can act as an antioxidant and improve various physiological or pathological conditions. We started this study with the assumption that we might be able to develop a new treatment for Crohn’s disease and ulcerative colitis, but to our surprise, we found just the opposite and patients should be aware of this danger, he said.

The study involved an experiment where colitis was induced in mice and they were treated with melatonin. Their conditions got worse instead of better. Importantly, no human patients were involved in the study. The animals’ intestinal inflammation got much, much worse, Cardoso said.

We then started trying to figure out why. We found that melatonin had a positive effect on disease if the effect on the gut microbiota was ignored and the mice were treated with broad-spectrum antibiotics to eliminate all bacteria.

The negative effect of melatonin therefore depends on the bacteria that live in the intestine and are also associated with inflammatory diseases of the region. Certain features of the gut microbiota increase inflammation and dysregulate the immune system in response to melatonin treatment, damaging the digestive system.

What is the meaning of all this? I would say that all that glitters is not gold. We should pay close attention to drugs, hormone supplements or hormones offered as dietary supplements. You buy a dietary supplement at the pharmacy and you think it’s not a drug, it won’t alter anything in your body, it’s just going to do you good because it’s sold as a dietary supplement after all, but that’s not really the case. It’s a hormone, and regulating the interaction between all hormones and the immune system is very delicate, Cardoso said.

Regulation

ANVISA, the Brazilian national health surveillance agency, has recently updated the information and rules on the sale of melatonin as a dietary supplement, but even so the control is more flexible than with drugs. It’s important to point this out because we talk about the need to take care, but people might think, Oh, but I’ll go to the pharmacy and buy some, it’s been approved by ANVISA. True, but only when labeled as a dietary supplement, and the question in the study is whether it’s really a simple dietary supplement. What are the risks? Cardoso said.

Reference: The microbiota-dependent pejorative effects of melatonin on intestinal inflammation by Jefferson Luiz da Silva, Lia Vezenfard Barbosa, Camila Figueiredo Pinzan, Viviani Nardini, Irislene Simes Brigo, Cssia Aparecida Sebastio, Jefferson Elias-Oliveira, Vnia Brazo, Jos Clvis do Prado Jnior, Daniela Carlos and Cristina Ribeiro de Barros Cardoso, February 11, 2023, Microorganisms.
DOI: 10.3390/microorganisms11020460

The study is one of the results of a project led by Cardoso and funded by FAPESP.