Melatonin: Better Sleep, Plus Its Inflammation-Fighting Role As A Natural Antioxidant

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Melatonin is best known for its role in supporting healthy sleep, but its benefits go beyond helping you drift off at night. This naturally occurring hormone also acts as an antioxidant and helps calm inflammation, both of which can support overall health. In this article, we will explore how melatonin supplements not only improve sleep patterns but may also play a role in reducing oxidative stress and supporting the body’s natural balance.

What is Melatonin?

Melatonin is a hormone your body naturally produces to help regulate the sleep–wake cycle, also called the circadian rhythm. It is made mainly in the pineal gland, a small structure deep within the brain. Production begins with tryptophan, which is converted into serotonin in other parts of the brain. Some of this serotonin reaches the pineal gland, where, under the influence of darkness, it is turned into melatonin through the action of a key enzyme known as arylalkylamine N-acetyltransferase (AA-NAT). Light signals from the retina travel to the suprachiasmatic nucleus (SCN) of the hypothalamus, which acts as the body’s internal clock and controls the timing of melatonin release. As night falls, melatonin levels rise and help the body prepare for sleep. When daylight returns, levels drop and the body shifts back toward wakefulness.

Although melatonin is best known for promoting sleep through its MT1 and MT2 receptors, research shows that its influence is broader. It exerts antioxidant and anti-inflammatory effects, helps regulate lipid and glucose metabolism, supports cardiovascular function, and may protect nerve cells by activating mitochondrial survival pathways. Melatonin also interacts with hormone pathways, immune function, and even bone metabolism. Some studies suggest it has oncostatic (cancer-suppressing) activity by modulating tumor suppressor genes and hormone signaling.

People often turn to melatonin supplements to help with sleep problems such as insomnia or to adjust their body clock after jet lag or shift work. These over-the-counter products mimic the effects of the hormone produced naturally in the body. The American Academy of Family Physicians recognises melatonin as a first-line pharmacological therapy for insomnia, although studies show mixed results on its effectiveness.

Melatonin has also been studied for a range of other uses, including rapid eye movement (REM) sleep behavior disorder, circadian rhythm disorders, age-related insomnia, post-traumatic brain injury, migraine prevention, and conditions involving the gastrointestinal tract, metabolism, cardiovascular health, and reproductive function. It occurs naturally in some foods, but only in amounts far smaller than the body produces on its own. [NBK534823]

melatonin treatment trial using a 50 mg daily bedtime dose for 37 days to a blind subject resulted in no change in the endogenous melatonin profile. We conclude that circulating melatonin … does not alter … melatonin secretion.

The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans [PMID: 9062869]

What are the Benefits of Melatonin?

• Improves sleep: Melatonin can help regulate the sleep-wake cycle and is often used to treat sleep problems, such as insomnia. [PMID: 33417003]
• Supports eye health: Melatonin has antioxidant properties that may help protect the eyes from damage and maintain good vision by reducing inflammation [PMID: 31724508] and affecting pressure inside the eye. [PMID: 31560946]
• Boosts the immune system: Some research suggests that melatonin may help strengthen the immune system, supporting the body’s ability to fight off illnesses. [PMC3645767]
• Anti-Inflammatory Effects: Melatonin has shown promise in reducing inflammation in the body, which could be beneficial in various conditions, including TBI. [PMC7979486]
• Antioxidant Properties: Melatonin acts as an antioxidant, helping to combat free radicals in the body. This may support overall cellular health. [PMID: 27500468]
• Brain Health: Some studies suggest melatonin could improve brain function and possibly even offer some protection against neurodegenerative diseases like Alzheimer’s. [PMID: 33957167]
• Stress Reduction: Melatonin may help reduce symptoms of stress by lowering cortisol levels, the body’s main stress hormone. [PMC1395802]
• Digestive Health: Some research has shown that melatonin might help in the treatment of conditions like irritable bowel syndrome (IBS).
  • Inflammatory Bowel Disease: Researchers state, “Melatonin can enhance the intestinal mucosal barrier, alter the composition of intestinal bacteria in favor of bacteria with anti-inflammatory properties, regulate the immune response, alleviate inflammation and attenuate oxidative stress.” [PMID: 36535545]
• Blood Pressure: Early studies have indicated that melatonin might have a role in improving heart health by reducing blood pressure and cholesterol levels. [PMC1395802, PMID: 12019357]
• Pain Relief: There’s some evidence to suggest that melatonin could have pain-relieving effects, helping to reduce different types of pain. [PMC7291209]
• Migraine Prevention: Researchers reviewing studies on this topic stated that “Observational studies also support melatonin’s efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg… 3 months or more may be enough duration for migraine therapy.”[PMC6370052]
• Fertility: Melatonin can scavenge free radicals such as reactive oxygen species (ROS), a key factor in reproductive functions. It plays an important role in oocyte maturation, fertilization, and embryonic development as well. [PMID: 34624677]
• Reduces jet lag symptoms: Taking melatonin supplements can help adjust your sleep schedule when traveling to a different time zone, making it easier to adapt to the new schedule. [PMID: 26731279]
• Mitochondrial function: Melatonin’s antioxidant activity may reduce the oxidative stress that causes damage to the “powerhouses of the cell.” [PMID: 21244359]

Melatonin, MMP-9, and The Blood-Brain Barrier

Spoiler Alert: Melatonin can bind to MMP-9, the destroyer of the blood-brain barrier.

MMP-9 activity is linked to many pathological processes, including rheumatoid arthritis, atherosclerosis, gastric ulcer, tumor growth, and cancer metastasis.

Melatonin inhibits matrix metalloproteinase-9 activity [PMC6932927]

The blood-brain barrier (BBB) is a protective barrier between the bloodstream and the brain that regulates the passage of substances into and out of the brain. It is formed by specialized cells lining the blood vessels in the brain and prevents the entry of harmful substances while allowing the passage of essential nutrients and oxygen. The BBB acts as a shield, maintaining the brain’s stable environment and protecting it from potentially harmful agents. It plays a vital role in preserving brain function and preventing the entry of substances that could disrupt normal brain activity.

A leaky blood-brain barrier (BBB) can let in substances that cause brain fog, problems with concentration and memory, headaches, feeling tired, changes in mood and emotions, and increased sensitivity to light and sound. These symptoms can affect cognitive function, cause fatigue, and impact mood and behavior. The causes of a leaky blood-brain barrier (BBB) can include inflammation, trauma, infection, certain diseases, chemotherapy, and disruptions in the normal functioning of the cells that form the barrier.

MMP-9 is an enzyme that breaks down the BBB. MMP-9 stands for “matrix metalloproteinase-9”. This enzyme breaks down the extracellular matrix components that act like the glue between the cells of the BBB. Inflammation can cause the release of MMP-9 leading to increased BBB permeability.

A leaky BBB allows substances, such as immune cells and molecules, to enter the brain more easily, which can contribute to neurological disorders or inflammatory responses in the brain. Therefore, maintaining the integrity of the BBB is crucial for the proper functioning of the central nervous system.

Melatonin For Brain Concussion

Concussion is a type of traumatic brain injury (TBI). Traumatic brain injury can have long-lasting effects and increase the risk of conditions like Alzheimer’s. Research is looking into whether melatonin could help prevent such future issues. So far, studies on animals are promising, showing that melatonin can reduce inflammation and improve brain function after a TBI. We don’t have enough studies on people yet to say for sure if melatonin is effective. [PMC8494149] A deep dive into the recent research with a lot of technical detail is covered in this Youtube Video.

Are there Food Sources For Melatonin?

The answer to this question is yes and no. Foods do contain minute amounts of melatonin, but these sources are orders of magnitude smaller than the amount in supplements as shown in the table.

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To Sum It Up

Melatonin is a hormone naturally produced by the pineal gland in the body that helps regulate sleep-wake cycles. It is commonly used as a sleep aid to assist with occasional sleep difficulties or jet lag. Melatonin supplements are available over-the-counter and are generally considered safe for short-term use when taken at appropriate dosages. While mild side effects such as daytime drowsiness or headaches may occur, they are typically temporary. It is important to note that no known toxicity level has been established for melatonin. Consulting with a healthcare professional can provide personalized guidance on its usage.

This Article is Not a Substitute for Medical Advice

This information is provided for educational purposes only and is not a substitute for medical advice. Supplement Sciences does not provide medical care and cannot ensure the safety or effectiveness of any product for your personal use. Always consult your physician before starting any supplement, especially if you are pregnant, breastfeeding, or managing a serious health condition such as cancer, liver disease, or kidney disease. Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease.

* These statements have not been evaluated by the Food and Drug Administration.