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Mast Cells and Melatonin

Updated: Feb 17

Melatonin is your sleep hormone. Beyond sleep, melatonin also supports your blood pressure regulation, blood glucose, mitochondrial DNA, temperature regulation, eye health, gut health, and brain health. Increasing evidence suggests that melatonin and mast cells are connected. Let’s get into the connection between mast cells and melatonin.

What Are Mast Cells

Your mast cells are a type of white blood cells in your connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. They play an essential role in your immune system by storing various inflammatory mast cell mediators, such as histamine.

If you encounter a substance that triggers an allergic reaction, your mast cells will get activated and release histamine and other chemicals as part of your body’s natural immune response to protect you from harm. Your mast cells are programmed to react to other kinds of threats as well, including chemical exposures, and to physical stimuli, such as heat or cold. Your mast cells are essential for health. However, overactive mast cells lead to mast cell disorders, such as mast cell activation syndrome (MCAS), which may result in a variety of symptoms and health issues (1, 2, 3, 4). My academic presentation in 2021 about mast cell instability I developed to educate about mast cell involvement in a variety of health conditions, even without MCAS as the diagnosis. These include irritable bowel syndrome, fibromyalgia, skin problems, mental health diagnoses and numerous neurologic conditions.

What Is Melatonin

Melatonin is a hormone created by your body naturally. It is mainly produced by the pineal gland in your brain. It is also found in other areas of your body, including your gut, bone marrow, eyes, and mast cells (5, 6).

Melatonin is also known as your sleep hormone. Your body makes melatonin in response to darkness to help you fall asleep. Exposure to light blocks the production of melatonin. Melatonin supports your circadian rhythm, which is your body’s natural sleep-wake cycle or your internal clock. It helps you to feel relaxed and fall asleep. It’s not surprising that melatonin supplements are commonly used for insomnia, jet lag, shift work disorder, and other sleep issues (7).

Besides sleep, melatonin has many other functions. It is a powerful antioxidant that supports your mitochondrial DNA. It may help with blood pressure regulation, blood glucose, temperature regulation, eye health, acid reflux, migraines, and tinnitus (8, 9, 10, 11, 12).

Melatonin and Mast Cells

Melatonin is primarily produced by your pineal gland. However, melatonin may also be synthesized and released by your mast cells. This suggests an important relationship between melatonin and mast cells. The mast cell membrane has many receptors for chemicals in the body that can regulate or activate it. One of these is estrogen, which can activate mast cells. Another is melatonin, which has been shown to downregulate mast cells. When this happens, less histamine and other mediators are released. (13)

Sleep, Melatonin, and Mast Cells

A 2021 study published in the Journal of Pineal Research has found a link between mast cells, pineal glands, and circadian rhythms (13). Researchers discovered that your mast cells not only play a role in protecting your body from pathogens and inflammation but have a crucial role in your sleep cycle. Histamine and melatonin both play a role in sleep. The study suggests targeting both histamine and melatonin to restore circadian rhythms and reduce mast cell-related diseases.

Inflammation, Melatonin, and Mast Cells

A 2010 animal study published by Pharmacological Research has found that mast cells show the presence of MT1 and MT2 melatonin membrane receptors. Results indicate that mast cell activation may result in melatonin synthesis and secretion. This may suggest that melatonin may help to regulate inflammatory reactions caused by your mast cells (14).

Research suggests that melatonin may reduce mast cell activation, histamine release, and inflammation. A 2017 review published in the International Journal of Endocrinology has found that melatonin receptors in your mast cells may help to regulate inflammatory pathways and melatonin may help to reduce inflammation (15).

Chronic Disease, Melatonin, and Mast Cells

Poor melatonin levels have been linked to many diseases, including neurodegenerative conditions and cancer (16, 17, 18). It’s important to note that mast cell activation has been linked to several of these diseases as well.(19, 20, 21). It will be interesting to follow the research to determine if the mast cell-melatonin relationship is a core component of these diseases, which include multiple sclerosis, Alzheimers and malignancies.

Allergic and Skin Reactions, Melatonin, and Mast Cells

Melatonin may also help to reduce allergic reactions linked to eczema, dermatitis, asthma, and other allergic conditions. According to a 2013 study published in the Journal of Neuroimmunology, melatonin helps to protect your mast cells from chemical stimuli and related inflammation (22). A 2020 study published in the Journal of Basic and Clinical Health Sciences showed that melatonin may help to reduce allergic inflammatory reactions in allergic rhinitis (23).

Stress, Melatonin, and Mast Cells

Stress may also trigger your mast cells and histamine release and lead to symptoms. It seems that melatonin may be able to reduce stress-related reactions, such as skin issues. A 2005 animal study published in Acta Histochemica has found that melatonin treatment may help to decrease stress-induced mast cell degranulation in the dermis (24).


By far the most important recommendation I can make for protecting your melatonin levels is avoidance of artificial light and blue screens well into the night. It is important to shut off electronic devices one hour before your designated sleep time. The old adage “down when the sun goes down, up when the sun comes up” carries some truth, albeit not practical in the strictest sense for modern living. Still though, the fact that light pollution can dramatically interfere with melatonin production is important to consider.

To improve your melatonin levels, you may want to add some melatonin-rich foods to your diet, including tart cherries, goji berries, eggs, fresh fatty fish (eg. salmon), pistachios, grapes, and mushrooms. Please be mindful of your food sensitivities when introducing or increasing these foods, especially if histamine intolerant.

You may benefit from supplementing with melatonin. For the best results and safety, I recommend using high-quality pharmaceutical-grade melatonin. To improve your circadian rhythms and sleep, I recommend 3 mg of melatonin taken 2 hours before bedtime. Sensitive individuals may wish to “start low and go slow”, beginning with 1 mg and titrating upward.

You may also benefit from supplementing with 5-HTP. Serotonin is a precursor to melatonin (25), meaning it gets converted to melatonin, and 5-HTP is the precursor to serotonin . If you have low serotonin levels, you may benefit from supplementing with 5-HTP first before supplementing with melatonin directly. Gut issues are common in those with mast cell activation syndrome and histamine intolerance, and gut problems may lead to low serotonin levels (26, 27, 28). If you are taking any SSRI or SNRI medications, it’s important that you consult your doctor before taking 5-HTP.

Healthy conversion of serotonin into melatonin is necessary for increasing your melatonin levels, supporting sleep, and improving your health. The conversion relies on key nutrients as cofactors. They are zinc, magnesium, B12 and folate. You do not want to be deficient in these, and micronutrient testing can help determine levels.

If you are dealing with sleep issues, some other supplements that may help to improve your sleep include magnesium, L-theanine, GABA, chamomile, valerian, passionflower, and CBD oil (29, 30, 31, 32, 33, 34). Consult your healthcare provider, ideally a functional medicine doctor, before taking any supplements.

Next Steps

1. Working with a healthcare practitioner knowledgeable in MCAS and histamine intolerance is the best way to get to the root cause of your symptoms and to create an individualized treatment plan. I welcome you to start a personalized functional medicine consultation. You may book your consultation here.

2. Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.


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