Could Melatonin Help Protect Against COVID-19?

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This question has been flooding my inbox and social media:

Dr. Breus, I’ve heard that melatonin can help me avoid COVID-19—is that true?

There’s a lot of information swirling around out there right now, about treatments and prophylactics, medications and supplements to protect against COVID-19, the disease caused by the coronavirus now circulating the U.S. and the globe.

We’ve only known of this virus for a handful of months, but scientists have been working furiously to understand better how it operates and to find ways to treat it—that’s all in addition to the race to develop a vaccine. I read this article just the other day, which shows how COVID-19 research has overtaken nearly all of scientific study at this time, and has transformed—at least for now—the way scientists around the world collaborate.

One of the treatments that is under investigation, and showing some early promise, is melatonin. In this article, I’ll talk about that COVID-19 melatonin research and what it is revealing, as well as the underlying reasons why melatonin might be a promising candidate for a COVID-19 therapy. We’ll take a grounded, careful look at the science that supports this theory.

To be clear: there is currently nothing definitive in the science showing that melatonin can protect against the most serious effects of COVID-19. But there are indications that melatonin may reduce the severity of the disease, and the overblown immune response and subsequent severe damage to the lungs that is present in the virus’ most critically ill patients.

How Melatonin Works

Melatonin is best known as a sleep facilitator. It is not a sedative; instead, melatonin regulates sleep through its influence over the body’s bio clock and sleep-wake cycles.

Melatonin is a hormone the body produces naturally. It is also available in supplement form. Scientific research shows that melatonin supplementation can strengthen and improve sleep-wake cycles.

Natural melatonin is produced primarily by the pineal gland in the brain. The brain receives light and dark cues through the retina of the eye, which are then communicated along the optic nerve to the brain’s master bio clock, the superchiasmatic nucleus, or SCN, which sends the signal to the pineal gland to increase its production of the hormone.

Like most hormones, melatonin follows a daily circadian rhythm. Melatonin production rises in response to darkness, and is suppressed by exposure to light. Melatonin levels begin to rise significantly around 9 p.m. and peak sometime during the overnight, falling to their lowest levels in the morning.

(The timing of individual melatonin cycles vary, and different chronotypes see their melatonin rise and fall at different times. A night-preferring Wolf experiences rising and peak melatonin later in the evening than an early-rising Lion.) Melatonin’s strong ties to the 24-hour cycle of light and dark are a key reason why nighttime light exposure can be so detrimental to sleep and to health.

We’ve learned a lot in recent years about the broad spectrum of functions that melatonin plays in the body, and its array of potential therapeutic uses. I wrote earlier this year about some of the new, emerging ways that melatonin may protect health and treat diseases ranging from diabetes and heart disease to cancer and neurodegenerative disorders.

Among melatonin’s important functions are its work as an antioxidant and anti-inflammatory agent, and its ability to modulate immune activity. It is melatonin’s capacity to hold inflammation in check, and to restrain immune activity, that has brought it into the spotlight as a possible treatment for COVID-19.

Melatonin’s Anti-Inflammatory, Antioxidant Powers

Melatonin, of course, is best known as a sleep regulator. But melatonin also plays an important role in regulating the immune system. One way it does so is by influencing the production of small proteins known as cytokines, which act as signalers from the immune system to cells around the body. Cytokines can be inflammation producing (pro-inflammatory cytokines) or inflammation restricting (anti-inflammatory cytokines). Melatonin has been shown to reduce the production of pro-inflammatory cytokines. Melatonin also is well known to be an antioxidant, neutralizing free radical cells and limiting oxidative stress and damage, which contribute inflammation.

Pro-inflammatory cytokines serve an important purpose, in marshaling the inflammatory response that fights off viruses, bacteria, and other pathogens. That’s the protective mechanism of inflammation at work. But for the pro-inflammatory cytokine response to be beneficial, it must be proportional to the threat. A too vigorous response of pro-inflammatory cytokines creates a dangerous amount of inflammation—and can actually serve to spread the viral infection, rather than tamping it down. It is this inflammatory overreaction and viral spread that appears to take place in the most serious cases of COVID-19.

The Inflammatory Dangers of COVID-19

COVID-19 is an acute respiratory disorder that in some cases launches an exceptionally aggressive attack on the lungs. While most cases of COVID-19 come with mild symptoms similar to cold and flu, this disease caused by the current coronavirus also can lead to pneumonia. In the most critical cases, COVID-19 leads to acute lung injury and acute respiratory distress syndrome, which render the lungs and respiratory system unable to take in enough oxygen and distribute it through the bloodstream. These patients require ventilators to breathe for them.

(Slowing the rate of infection of the coronavirus—what we’ve all come to know as “flattening the curve”—will help keep our health care systems from being overwhelmed by too many of these critical patients at once, without enough ventilators to meet their needs.)

Underlying the pneumonia and lung damage that are the signatures of COVID-19 is an exaggerated inflammatory response by the body’s own immune system. In people with serious and critical cases of COVID-19, the coronavirus has triggered their immune systems to a dangerous overreaction—and it’s this rush of inflammation that creates the lung and respiratory injury that is proving so dangerous.

In particular, the coronavirus that causes COVID-19 activates an agent of the immune system known as an inflammasome. Inflammasomes are immune sensors that scout for potential threats, and respond to those threats by triggering the production of inflammation to combat the threat it perceives.

This coronavirus activates particular inflammasomes, including one called NLRP3. This inflammasome has been shown in research to have a close connection to acute lung injury and acute respiratory distress syndrome. NLRP3 is a key trigger of the immune over-response that can lead to these disabling, life-threatening lung disorders. The coronavirus triggers NLRP3 inflammasomes, which launches a series of reactions that create a “cytokine storm,” flooding the lungs with inflammation.

Melatonin Inhibits NLRP3 Inflammasome—Can It Fight Off COVID-19?

The reason for the interest in melatonin as a potential treatment for COVID-19? Melatonin has been documented in scientific research to suppress the action of the inflammasome known as NLRP3—one of the primary inflammasomes involved in the exaggerated immune response seen in critical COVID-19 cases. Melatonin’s ability to suppress the activation of NLRP3 has been found to counteract severe inflammatory responses, lower production of proinflammatory cytokines, lower infiltration of immune cells into lungs, and reduce lung tissue injury.

• Studies in animals conducted over the past several years have shown that melatonin inhibits NLRP3 inflammasomes, and reduces inflammation from severe to mild in mice with inflammatory diseases.
• Other animal research has shown that regular low dosing of melatonin in older mice can stop the escalation of inflammation.
• And mice studies that looked specifically at the effects of melatonin on acute lung injury found that melatonin offered protection against the most severe lung injury, because of its ability to suppress NLRP3 inflammasomes.

This capacity of melatonin, to target this inflammasome that is so critical to the most serious and life-threatening complications of COVID-19, along with melatonin’s high degree of safety and benefits for sleep, is drawing attention from scientists as a therapy to de-escalate the immune response to coronavirus, potentially reducing the severity of COVID-19.