Melatonin tends to be reduced to “sleep”, but that overlooks much of what makes it interesting physiologically.
Its best-known role is as a signal of darkness, helping coordinate the body’s circadian rhythm. But melatonin is also involved in mitochondrial protection, antioxidant defence, inflammatory and immune regulation, reproductive function, gut physiology and glucose metabolism.
For practitioners, this makes melatonin relevant well beyond clients who simply have difficulty sleeping.
Melatonin and Mitochondrial Function
One of the most interesting areas of melatonin research involves the mitochondria, where cells produce ATP for energy.
Energy production naturally generates reactive oxygen species. In normal amounts these have useful signalling functions, but excessive oxidative stress can damage mitochondrial membranes, proteins and DNA.
Melatonin has direct antioxidant activity and also supports the body’s antioxidant defence systems. Research suggests it has an important protective role within mitochondria, helping limit oxidative damage and support mitochondrial function.
Interestingly, research also indicates that mitochondria themselves can synthesise melatonin. This suggests melatonin has important functions within cells that are quite separate from its familiar role in regulating sleep.
Melatonin, Inflammation and the Immune System
Melatonin interacts with several pathways involved in inflammatory regulation, including NF-κB, which helps control the expression of inflammatory genes and production of cytokines.
It also influences immune cells, including macrophages and lymphocytes, as well as cytokine signalling.
Rather than simply “boosting” or suppressing immunity, melatonin is better described as an immunomodulator. Its effects vary according to the tissue and physiological circumstances.
This is an important distinction clinically. A healthy inflammatory response isn’t simply about initiating inflammation when necessary. The body also needs mechanisms to regulate and resolve that response appropriately.
Where Else Does Melatonin Matter?
Melatonin appears in several areas that at first seem unrelated to sleep.
In fertility, melatonin is present in follicular fluid surrounding the developing oocyte. Its antioxidant properties may help protect the oocyte from oxidative stress during maturation, and it has been studied in IVF research in relation to oocyte quality and embryo development.
The gastrointestinal tract also produces melatonin locally. Here it has been linked with gut motility, secretion, visceral sensitivity and protection of the gastrointestinal lining. Melatonin has consequently been investigated in conditions including IBS.
In the brain, its antioxidant, mitochondrial and anti-inflammatory actions have led to research into migraine and neurodegenerative conditions. This research is largely concerned with cellular protection rather than melatonin’s effect on sleep.
Melatonin and Glucose Regulation
Melatonin receptors are also present on pancreatic beta cells, linking circadian signalling with insulin secretion and glucose regulation.
This is particularly interesting because the metabolic response to food varies according to the time of day. Eating when melatonin levels are elevated can affect glucose handling differently from eating during the biological day.
Genetic variations in the melatonin receptor gene MTNR1B have also been associated with higher fasting glucose and increased susceptibility to type 2 diabetes.
It is another example of why circadian disruption can have consequences extending well beyond poor sleep.
Why Timing Matters
Melatonin is not simply something the body needs “more” or “less” of. Timing matters.
Under normal circumstances, melatonin begins to rise as darkness approaches, remains elevated during the night and falls towards morning. Evening light exposure, shift work, jet lag and irregular sleep patterns can interfere with this rhythm.
This means someone can have an adequate number of hours of sleep while still having disrupted circadian signalling.
Why Melatonin May Be Relevant in Practitioner Testing
Melatonin sits at the intersection of circadian regulation, mitochondrial protection, antioxidant defence, inflammatory and immune signalling, reproductive physiology, gastrointestinal function and metabolic regulation.
It is therefore worth considering as part of the broader physiological picture rather than viewing it solely as a sleep hormone.
The Melatonin Test Vial is included in the Antioxidant Test Kit, CCM Essential Nutrient Test Kit, Hormones & Gland Test Kit and Hormones & Biochemical Test Kit. These Test Kits are available in both Plastic Box and Flat Tray Box options.
References
Reiter, R.J., Mayo, J.C., Tan, D.X., Sainz, R.M., Alatorre-Jimenez, M. & Qin, L. (2016). Melatonin as an antioxidant: Under promises but over delivers. Journal of Pineal Research, 61(3), 253–278. https://doi.org/10.1111/jpi.12360
Reiter, R.J., Sharma, R., Rosales-Corral, S., de Campos Zuccari, D.A.P. & de Almeida Chuffa, L.G. (2022). Melatonin: A mitochondrial resident with a diverse skill set. Life Sciences, 301, 120612. https://doi.org/10.1016/j.lfs.2022.120612
Hardeland, R. (2018). Melatonin and inflammation: Story of a double-edged blade. Journal of Pineal Research, 65(4), e12525. https://doi.org/10.1111/jpi.12525
Carrillo-Vico, A., Lardone, P.J., Álvarez-Sánchez, N., Rodríguez-Rodríguez, A. & Guerrero, J.M. (2013). Melatonin: Buffering the immune system. International Journal of Molecular Sciences, 14(4), 8638–8683. https://doi.org/10.3390/ijms14048638
Söderquist, F., Hellström, P.M. & Cunningham, J.L. (2015). Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2. PLoS ONE, 10(3), e0120195. https://doi.org/10.1371/journal.pone.0120195
Karamitri, A. & Jockers, R. (2019). Melatonin in type 2 diabetes mellitus and obesity. Nature Reviews Endocrinology, 15(2), 105–125. https://doi.org/10.1038/s41574-018-0130-1