Melatonin Produced in the Gut Plays a Key Role Deuterium Homeostasis and is Also Linked to Long COVID
Nikhil Prasad Fact checked by:Thailand Medical News Team May 22, 2026 54 minutes ago
Medical News: A growing body of research is revealing that melatonin is far more than just a sleep hormone. Scientists are now uncovering evidence that melatonin produced in the gut may play a critical role in regulating mitochondrial health, controlling inflammation, supporting the gut microbiome, and possibly protecting against long COVID and neurodegenerative diseases.
Scientists uncover how gut-produced melatonin may influence mitochondrial health, inflammation, long COVID,
and brain protection
The new scientific review was conducted by researchers from the Massachusetts Institute of Technology (MIT) Computer Science and Artificial Intelligence Laboratory in the United States, Greg Nigh LLC in Rhode Island, the University of Patras in Greece, and the Nasco AD Biotechnology Laboratory in Piraeus, Greece.
While melatonin is commonly associated with the pineal gland in the brain and sleep regulation, the researchers emphasized that the gastrointestinal tract actually produces vastly larger quantities of melatonin. Some estimates suggest that the gut may generate up to 400 times more melatonin than the pineal gland.
Scientists Discover a Hidden Gut-Melatonin System
The review explains that specialized cells in the intestines known as enterochromaffin cells manufacture melatonin from serotonin, which itself is produced from the amino acid tryptophan. Scientists believe this locally produced melatonin serves many important functions in the digestive tract and throughout the body.
According to the researchers, gut-derived melatonin helps regulate inflammation, protects the intestinal lining, supports healthy mitochondrial energy production, and acts as a powerful antioxidant capable of neutralizing dangerous free radicals.
The paper also highlights that melatonin production is closely connected to the health of the gut microbiome. Beneficial gut bacteria produce compounds known as short-chain fatty acids, especially butyrate, that stimulate serotonin and melatonin synthesis in the intestines.
Why Butyrate Is So Important
Butyrate is increasingly being viewed as one of the most beneficial compounds generated by healthy gut microbes. The study notes that butyrate supports the integrity of the gut wall, lowers inflammation, improves metabolism, supports colon health, and may even possess anticancer properties.
Researchers explained that butyrate-producing bacteria are often depleted in individuals suffering from obesity, diabetes, inflammatory bowel disease, depression, and long COVID.
Animal studies reviewed in the paper showed that when gut microbes are absent, mitochondrial function becomes severely impaired. Colon cells lose their normal energy production capacity and show signs of metabolic stress. Scientists believe much of this damage results from a lack of butyrate.
The review also discussed how butyrate stimulates serotonin production in the colon, which indirectly boosts melatonin synthesis. This suggests that disruptions in the microbiome could directly reduce the body’s natural melatonin levels.
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The Strange Role of Deuterium
One of the most fascinating parts of the study centers on deuterium, a naturally occurring heavy form of hydrogen found in water and biological tissues. Although deuterium is harmless in small amounts, the researchers argue that excessive deuterium inside cells may interfere with mitochondrial energy production.
Mitochondria rely on extremely fast proton movement to generate ATP, the molecule that powers cells. Because deuterium is heavier than ordinary hydrogen, scientists believe it may slow down this process and damage delicate mitochondrial machinery over time.
The researchers proposed that melatonin metabolism inside the gut may help create “deuterium-depleted water,” which could protect mitochondria from stress and improve cellular energy production.
According to the paper, gut microbes generate hydrogen-containing molecules that are naturally lower in deuterium. These molecules eventually contribute to the production of methionine and melatonin. During repeated melatonin recycling processes in intestinal cells, enzymes may generate water molecules with lower deuterium levels, helping preserve mitochondrial stability.
This
Medical News report notes that although the theory remains controversial and requires additional clinical investigation, it offers a completely new way of thinking about metabolism, aging, and chronic disease.
Melatonin’s Ancient Evolutionary Role
The scientists also explored melatonin’s evolutionary origins. According to the review, melatonin first appeared billions of years ago in primitive bacteria as a protective antioxidant molecule.
The researchers believe melatonin evolved to help living organisms survive oxidative stress generated by oxygen metabolism. Even today, mitochondria themselves still manufacture melatonin locally inside cells.
This ancient connection may explain why melatonin appears to influence such a wide range of biological systems, including immunity, inflammation, energy metabolism, and brain function.
Long COVID and Neurological Damage
A major focus of the review involved the relationship between melatonin and long COVID.
The researchers described how SARS-CoV-2 infection can severely disrupt the gut microbiome, reducing beneficial bacteria while promoting harmful microbial populations. This imbalance may interfere with butyrate production and ultimately suppress melatonin synthesis in the intestines.
Scientists also discussed studies showing that melatonin may reduce viral entry into cells, lower inflammation in blood vessels and brain tissue, and suppress dangerous inflammatory pathways such as NF-kB that are associated with severe COVID-19 complications.
The review further highlighted evidence that melatonin may help calm the cytokine storms seen in severe COVID-19 by regulating immune responses and lowering inflammatory signaling molecules including IL-6 and TNF-alpha.
Importantly, the paper linked reduced melatonin levels to neurological symptoms commonly seen in long COVID, including brain fog, fatigue, memory impairment, and cognitive dysfunction. The researchers believe microbiome disruptions and declining butyrate-producing bacteria may contribute significantly to these problems.
Potential Protection Against Neurodegeneration
The study also examined melatonin’s ability to protect the brain from oxidative damage and chronic inflammation.
Melatonin appears to stimulate antioxidant systems involving glutathione, thioredoxin, catalase, and superoxide dismutase. These protective pathways help neutralize free radicals and reduce cellular injury.
Researchers noted that melatonin may help shift immune cells in the brain from inflammatory states into healing states, potentially reducing damage associated with Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions.
Questions About Melatonin Supplements
Although melatonin supplementation has become extremely popular worldwide, the researchers warned that most commercial melatonin is chemically synthesized and may contain manufacturing impurities or toxic byproducts.
They suggested that naturally produced melatonin generated within the body through gut microbial interactions may possess unique biological advantages that synthetic products cannot fully replicate.
The researchers also revisited tryptophan supplementation, explaining that increased dietary tryptophan intake may naturally boost serotonin and melatonin production within the gut.
Conclusion
The new review presents an ambitious and highly detailed hypothesis connecting gut microbes, melatonin metabolism, mitochondrial energy production, inflammation, long COVID, and neurological disease. While many aspects of the theory still require extensive clinical validation, the findings add to growing scientific evidence that the gut microbiome plays a central role in regulating overall human health. The research also strongly challenges the traditional view of melatonin as merely a sleep hormone, instead portraying it as a fundamental regulator of immunity, cellular energy, antioxidant defense, and brain protection. If future studies confirm these mechanisms, gut-focused approaches aimed at improving melatonin production and restoring microbiome balance could eventually become important strategies for treating chronic inflammatory and neurodegenerative diseases.
The study findings were published in the peer reviewed journal: Current Medicinal Chemistry.
https://www.eurekaselect.com/article/155753
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Read Also:
https://www.thailandmedical.news/articles/long-covid
https://www.thailandmedical.news/articles/supplements
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