Since the COVID-19 pandemic in 2020, a condition called long COVID has emerged. Long COVID is a chronic, sometimes debilitating, condition that develops after an acute COVID infection or after getting a COVID vaccination.

And it's not rare.

In fact, it's estimated that a little over one in five adults with COVID-19 develop long COVID.¹ And as of 2024, approximately 3.8 million people in America are living with long COVID.²

But because of how new this condition is, patients with long COVID are often misdiagnosed and not properly treated by their primary doctors. This is typically the case for many of the patients I see. You can read more about long COVID in my last blog here.

Even though research surrounding the treatment of long COVID is in the early stages, we know that it’s primarily a result of immune dysregulation. Because of this, researchers have been able to identify already well-known medications and supplements that are safe and work remarkably well for the treatment of long COVID.

One of these supplements is melatonin. While melatonin supplementation is best known for its positive effects on sleep, it also improves inflammation and helps regulate the immune system - both of which are essential for overcoming long COVID.

What is Melatonin?

Melatonin is a hormone that's naturally made primarily by the pineal gland. The pineal gland is about the size of a pea, and it's located in the center of the brain. Melatonin is also made in other cells in the body like the bone marrow,³ the retinas (a part of the eye), the gastrointestinal tract (stomach and intestines), and certain parts of the immune system.⁴

When the sun goes down and it gets dark, our brain tells the pineal gland and other areas of the body to start making melatonin. This makes us feel tired and want to go to sleep.

Besides darkness, melatonin production is also affected by the seasons as well as lunar cycles. Melatonin production decreases with age, and the biggest decline is noted after 40 years of age.⁵

The most well-known function of melatonin is to help regulate our sleep-wake cycle - also known as our circadian rhythm.

But melatonin does much more than that.

What Does Melatonin Do In the Body?

The functions and benefits of melatonin go far beyond helping us get a good night's rest. Melatonin is important for several different processes and functions in the body.

A diagram of the functions of melatonin, including how it can help treat long COVID. — The different functions of melatonin.⁶

In addition to regulating sleep-wake cycles, melatonin has been shown to:⁷

Help keep bones strong
Prevent blood pressure from getting too high
Regulate cholesterol and blood sugar
Suppress the development of cancer
Help reduce pain
Support a healthy reproductive system

Melatonin also protects against a process called apoptosis, which is the death of cells. This is especially important when it comes to cells in the brain and nervous system. High rates of apoptosis have been linked to conditions such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease. So melatonin may be able to decrease the risk of getting these diseases.⁸

Additionally, melatonin has been found to help with mental health conditions such as anxiety and depression. A medication called agomelatine, which increases the amount of melatonin used by the body, is approved for treating depression in Europe.⁷

Melatonin plays a key role in controlling inflammation, regulating the immune system, and getting rid of damaging toxins. And it’s because of these characteristics that melatonin is used to help treat long COVID.⁹

How Melatonin Helps With Long COVID

The cause of long COVID is primarily a dysfunctional immune system. When the immune system can’t regulate itself properly, the result is often an over-functioning immune system. This dysfunction happens because of the initial COVID-19 virus as well as certain toxins in the body.

Inflammation is a defense mechanism our immune system uses to help fight off foreign invaders. So if the immune system is working more than it should, this is going to result in increased inflammation throughout the body.

Melatonin targets all three of these factors that contribute to long COVID, making it an excellent choice for treatment.

Melatonin is an Antioxidant

Melatonin helps the body get rid of toxins. Every day, our bodies produce and are exposed to toxins called free radicals. These free radicals can increase more when we're sick with a virus, such as COVID-19.¹⁰

And when the levels of free radicals increase too much in the body, they can cause inflammation, cell damage, cancer, and other chronic illnesses like long COVID.

To get rid of free radicals in the body, we need antioxidants. There are many different types of antioxidants, and melatonin is one of them.⁴ Melatonin is also able to encourage the body to release other types of antioxidants, which increases the body’s ability to get rid of the damaging free radicals.¹¹

Melatonin Decreases Inflammation

Another driving force behind long COVID is body-wide inflammation. So taking a supplement that helps to decrease inflammation is important for treatment.

There are different molecules throughout the body that work as messengers to communicate with the immune system. Cytokines are one of these messengers, and they control the inflammatory response of the immune system.

And with long COVID, cytokines signal too much - causing increased inflammation throughout the body. High amounts of cytokines are the main reason for many of the symptoms of long COVID. A study found that patients with long COVID have abnormal levels of inflammatory cytokines for at least eight months after the acute infection.¹²

Melatonin has been shown in numerous studies to decrease the production and activity of different cytokines.⁴⋅¹¹⋅¹³ Over time, this results in decreased inflammation and improved symptoms of long COVID.¹⁴

Melatonin Helps Support the Immune System

Lastly, melatonin helps to regulate and support the immune system.

Melatonin has been shown to regulate the production and activity of certain white blood cells. These white blood cells are what fight off foreign invaders in the body and help our body recover after an infection.¹⁴ So it's important to make sure they're not over-active or under-active.

Melatonin is also able to regulate the production of different antibodies.¹⁵ Antibodies are proteins that bind to white blood cells and give them directions on how to fight off a foreign invader. Our bodies get antibodies by coming into contact with a virus, bacteria, or other invader or by getting a vaccination.

Are There Any Risks or Side Effects to Using Melatonin for Long COVID?

Overall, melatonin is considered a safe supplement. Some mild side effects have been reported, but this is typically only with higher doses of melatonin.

Possible side effects of melatonin include:⁷

Drowsiness
Daytime sleepiness
Nausea
Headaches

Since melatonin can cause drowsiness, melatonin shouldn’t be taken with medications that have similar side effects. Doing so can cause severe drowsiness and sedation. These medications include opiates (used to treat pain) and benzodiazepines (used to treat anxiety).⁷

But as always, it's best to talk with your functional medicine provider or primary care provider before starting a new supplement. They can make sure that it's safe for you to take melatonin and advise you on the right dose for the condition you're taking it for.

How To Add Melatonin Into Your Routine for Long COVID Recovery

When it comes to treating long COVID, melatonin is often started at a lower dose and increased slowly as needed. I typically start my patients at a dose of 0.5 to 1mg daily, and often we increase the dose to 20 to 50mg daily.

Melatonin is typically continued for 30 to 60 days or until symptoms improve.

One tip I give my patients is to take the melatonin about 30 to 60 minutes before bedtime. This allows enough time for it to take effect. It can also be taken in the morning. Usually it makes people feel drowsy the first few days and then often this will subside.

Patients often ask if they'll become dependent on the melatonin supplement they're taking. But at this time, there's currently no evidence showing that you can develop a tolerance to melatonin.⁷

What Else Is Melatonin Used For?

Melatonin has been studied for its use in other medical conditions. While there are many, the ones I’d like to review are cancer and COVID-19 infection.

Melatonin to Treat and Prevent Cancer

The development of cancer is strongly linked to the immune system. When the immune system is functioning well, it’s able to recognize abnormal cancer cells and get rid of them. But if the immune system isn’t working properly, these cancer cells get missed and eventually grow to form a tumor.¹⁶

For this reason, melatonin has been studied for the treatment and prevention of cancer. By regulating the immune system, melatonin helps decrease tumor size in those with cancer. It’s been found to be especially helpful at ridding the body of cancer cells in places where they can’t be surgically removed (such as cancer cells deep in an organ).¹⁷

Melatonin also helps decrease the side effects from types of cancer therapy like chemotherapy and radiation.¹⁷

Melatonin Can Prevent COVID-19 Infection

Because of melatonin’s ability to decrease inflammation, regulate the immune system, and help get rid of free radicals, it’s also been shown to prevent COVID-19 infection.⁹

When we get sick with a virus like COVID-19, it’s largely due to our immune system not being able to fight off the virus before it causes infection. So by taking melatonin, the immune system is able to function well and effectively fight off viruses like COVID-19.

Treating an Acute COVID-19 Infection With Melatonin

Melatonin has started to be studied for the treatment of acute COVID-19 infection. At high doses, research has found that melatonin has anti-viral properties and is effective against the virus that causes COVID-19 (SARS-CoV-2).⁹⋅¹⁸

Additionally, melatonin has been found to decrease the severity of COVID-19 infection. A response called a cytokine storm can happen with COVID-19. This is essentially when cytokines in the body overreact to the virus and cause severe inflammation. This has been linked to worse outcomes as well as long COVID.

Melatonin has been shown to prevent this over-signaling of cytokines, which helps decrease the severity of COVID-19 infection.⁹

Are You Interested in Learning More About Treatments for Long COVID?

If you've recovered from an acute COVID-19 infection but you're struggling with lingering symptoms that affect your daily life, you may have long COVID.

While more research is needed to fully understand melatonin's role in long COVID, existing studies show that melatonin may help correct several of the underlying causes of long COVID. This makes melatonin an excellent addition to long COVID treatment.

By decreasing inflammation, regulating the immune system, and serving as an antioxidant, melatonin has helped many of my patients with long COVID.

If you have long COVID, I know how debilitating the symptoms can be. Schedule an appointment with me at the link below to see how melatonin and other supplements like vitamin C can help you recover from long COVID today.

Schedule an Appointment Today

References:

1. Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022 – (nih.gov)

2. Long COVID Disability Burden in US Adults: YLDs and NIH Funding Relative to Other Conditions – (nih.gov)

3. Melatonin and its relation to the immune system and inflammation – (nih.gov)

4. Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care – (nature.com)

5. Can melatonin reduce the severity of post-COVID-19 syndrome? – (nih.gov)

6. Melatonin: Avenues in cancer therapy and its nanotechnological advancements – (wiley.com)

7. Melatonin – (nih.gov)

8. Apoptosis and apoptotic body: disease message and therapeutic target potentials – (nih.gov)

9. Protective Effect of Melatonin Administration against SARS-CoV-2 Infection: A Systematic Review – (nih.gov)

10. Free Radical and Viral Infection: A Review from the Perspective of Ferroptosis – (nih.gov)