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.
Melatonin’s anti-inflammatory, antioxidant powers
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, anti-oxidant 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 anti-oxidant, neutralizing free radical cells and limiting oxidative stress and damage, which contribute inflammation.
Pro-inflammatory cytokines serve an important purpose, in marshalling the inflammatory response that fights off virus, 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.
How to use melatonin safely during the Covid-19 pandemic
Always consult your doctor before you begin taking a supplement or make any changes to your existing medication and supplement routine. This is not medical advice, but it is information you can use as a conversation-starter with your physician.
This emerging hypothesis around melatonin and Covid-19, and the research that supports it, looks promising.
So, does this mean we should all run out and start taking giant doses of melatonin? NO. Melatonin is a powerful hormone with broad effects on circadian rhythms and a wide range of other physiological functions. There are risks and side effects that come with taking too much melatonin, including:
- Disruption to circadian rhythms and sleep-wake cycles
- Low blood pressure
- Nausea, cramping, stomach irritation
- Pain in joints
- Depression, anxiety, irritability
Many adults taking melatonin supplements are dosing at higher levels than they need, or is beneficial—often without being aware of it. A general guideline for long-term daily dosing is between 0.2 and 0.5 mg per day. That daily low dose can effectively supplement a natural melatonin deficiency, which can occur increasingly with age, and as a result of lifestyle and environmental disruptions to melatonin production, such as irregular sleep routines and nighttime exposure to artificial light.
Within the 0.2-0.5 mg dosing range, younger adults and those without health conditions can probably stick to the lower end of the range, while older adults and people with underlying health issues will likely want to move to the higher end of the range.
These doses are for adults, not for children. In fact, some scientists theorize that a possible reason for the overwhelmingly mild presence of Covid-19 in children may have to do with children’s naturally high levels of melatonin.
For people interested in the potential protection melatonin may offer against the most serious complications of Covid-19, a daily dose in this range will be safe for most adults. I say, “potential protection,” because we don’t yet have definitive evidence that this protection exists.
The best time to take a melatonin supplement is about 30 minutes to 1 hour before bedtime.
The half-life of melatonin is between 20-50 minutes. Half-life refers to the amount of time it takes for a supplement or medication to reduce its concentration by 50 percent once in the body.
People with the following conditions should always consult with a physician before beginning to use a melatonin supplement:
- Pregnancy, and women who are breast feeding (It is recommended that women who are pregnant or breast feeding not use melatonin.)
- Bleeding disorders
- High blood pressure
- Seizure disorders
- Transplant recipients
What about your chronotype?
The best time to take melatonin will differ from chronotype to chronotype. Lions will tend to take melatonin earlier in the evenings than other chronotypes, while Wolves and Dolphins will need to take melatonin later than Lions and Bears.
And remember these OTHER important habits that help boost the body’s melatonin production:
- Keeping a consistent sleep schedule, with regular sleep and wake times that reinforce circadian rhythms.
- Avoiding nighttime exposure to artificial light. A low light environment allows the body to make more melatonin. Blue light blocking glasses can help you avoid the melatonin suppression that comes from nighttime light exposure—without having to sit in darkness, or forgo a little Netflix at the end of a long day.
Information on how to consider—in consultation with your physician– using melatonin if infected with Covid-19
The general dosing guidelines above are widely used for regular melatonin supplementation, and may provide some protection from the inflammatory effects of the coronavirus for people who have not yet been infected.
If you think you have contracted Covid-19, follow the instructions of your local public health officials about whom to contact and how, and be in touch with your personal physician. Follow these health professionals’ instructions about self-care at home, and when to seek medical attention at a hospital or treatment facility. Again, what follows is not medical advice. It is information to share with your doctor and other health care providers as they guide your treatment.
One of the most thorough research-based articles I’ve encountered on the topic of melatonin and Covid-19 was published in this Italian web journal. In that article are included dosing recommendations for melatonin and Vitamin C for people infected with Covid-19. You can read the full article here, and I’ll share with you those infection dosing recommendations here, for informational purposes only. Here’s what those recommendations say:
“Melatonin COVID-19 Infection Dosage: 5 milligrams to 50 milligrams
The lower range is for people with mild or no symptoms. The higher range is for older people or those with more severe symptoms.
IF you are taking ACE inhibitors, have cardiac conditions, hypertension, you need to consult your physician before taking high doses of melatonin. Melatonin may lower blood pressure and cause hypotension at higher dosages.
The Infection dose should ideally be divided into DAYTIME and NIGHTTIME doses.
DAYTIME – 40% of total daily dose, divided into small equal portions to be taken every TWO HOURS.
NIGHTTIME – 60% of total daily dose, divided into two portions taken 2-3 hours after dinner. The final dose at night should be completed by 10 pm (latest).
IF you are diabetic, or have insulin resistance, DO NOT TAKE MELATONIN before 3 pm. Melatonin is able to suppress insulin.”
Note the warning for people taking ACE inhibitors. High doses of melatonin may interfere with the safe function of these medications, and pose particular complications and risks for people with high blood pressure and other forms of cardiovascular disease. Under all circumstances, consult your physician before taking any new supplement, at any dosing level. This is critical for people with cardiovascular conditions who may consider taking high doses of melatonin.
Regarding the combination of melatonin and Vitamin C: There is evidence that Vitamin C, or ascorbic acid, suppresses NLRP3 inflammasomes, through several different mechanisms. Research also indicates that when used together, melatonin and vitamin C, two antioxidants, have synergistic effects. Using melatonin and Vitamin C together may be an effective means to reduce the risk of serious, uncontrolled inflammation in Covid-19 infections. From the Italian web journal article:
“Supplementation of high dose melatonin MUST BE SUPPORTED by ascorbic acid. You may not experience full benefits of melatonin in the absence of ascorbic acid.
Ascorbic Acid COVID-19 Infection Dosage: 1 gram every 15 to 30 minutes, depending on severity of symptoms. Increase to 2 grams every 15 to 30 minutes if symptoms are not reversed within 12-24 hours.”
Important information for selecting a melatonin supplement:
Scientific investigations have found that the actual melatonin content found in many supplements on the market may vary significantly from what product labels claim. Scientists at Ontario’s University of Guelph found that in more than 71 percent of melatonin supplements, the amount of melatonin was more than 10 percent different from what the product label indicated. Some products contained as much as 83 percent less melatonin, while other products contained as much as 478 percent more melatonin. That means a great many consumers aren’t taking what they think they are, when they use a melatonin supplement. Before you begin using melatonin, be sure to do your research and get your melatonin from a trusted source.
I expect that with the speed at which scientists are racing to learn more about Covid-19 and how to treat it, we’ll soon have more information about a possible role for melatonin in that treatment. I will keep you updated with the latest information as it comes in.
Michael J. Breus, PhD, DABSM
The Sleep Doctor
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