Melatonin May Support a Healthy Immune System

According to a new study out of the Cleveland Clinic, melatonin is associated with lower rates of infection with SARS-CoV-2, commonly known as coronavirus or COVID-19. Published in PLoS Biology, the study applies statistical techniques to large datasets in an effort to identify likely and promising therapies. The study belongs to the emerging discipline of bioinformatics. This is an emerging interdisciplinary field that sits at intersections of biology, computer science, and mathematics.

The Cleveland Clinic study compares datasets of the proteins implicated in various diseases, including COVID-19. This allows the researchers to create a network map showing COVID-19’s pathological similarity or “proximity” to other diseases. The network map helps the researchers explain co-morbidities and identify drugs that might be repurposed to treat COVID-19.

For instance, asthma is a major risk factor for COVID-19. Looking at their network map, the researchers see that asthma and COVID-19 target some of the same cells and increase expression of some of the same genes. COVID-19 also decreases levels of metabolites known to protect against asthma. These are thus the likely biological pathways of comorbidity between asthma and COVID-19.

Network analysis also shows a significant proximity between COVID-19 and inflammatory bowel disease. IBD is not a significant risk factor for COVID-19 diagnosis. But apparently the two diseases operate on some of the same intestinal proteins, which helps explain why diarrhea is a common symptom of COVID-19.

Medical researchers working on COVID-19 have sought to find drugs already approved by the FDA to treat other diseases that might be repurposed to fight COVID-19. The Cleveland Clinic researchers reason that we should focus on drugs designated for those diseases with the highest network proximity to COVID-19. These are drugs and diseases that affect the same pathways and proteins as COVID-19.

The researchers computationally analyzed 3,000 FDA-approved or investigational drugs. And they were able to identify 16 drug candidates and 3 drug combinations that should be given high priority as trial therapies for COVID-19.

Network Analysis of Melatonin and COVID-19

From a non-practitioner’s perspective, the most exciting part of the Cleveland Clinic study is its analysis of data on 26,779 individuals from a COVID-19 registry. The researchers find that melatonin usage in this population "is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2." The association is particularly large among African Americans, "with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2."

No conclusions can be drawn about melatonin as a treatment for any disease. But this correlation in a large-scale patient dataset is promising. And it suggests that "randomized controlled clinical trials are urgently needed to test meaningfully the effect of melatonin for COVID-19."

This is particularly urgent for older patients. The body produces melatonin naturally in the pineal gland and throughout the gastrointestinal tract. But melatonin levels decrease with age. And older patients are at particular risk from COVID-19.

Fortunately, several randomized controlled trials testing melatonin’s effect on COVID-19 are already under way. Hopefully, we'll soon have a better idea of whether increased melatonin use can help. And ideally, we'll learn more about the amount of melatonin and the method of administration that would be required.

Health Benefits of Melatonin Supplements

Although melatonin is not a treatment for any disease, research does point to a role for melatonin supplements in support of healthy immune system function. According to the Cleveland Clinic, studies showed that "melatonin suppresses NLRP3 inflammasome activation induced by cigarette smoking and attenuates pulmonary inflammation."

Another study observes that "melatonin enhances both innate and cellular immunity." As described in the study, melatonin acts on the immune system via white blood cells. When stimulated via their melatonin receptors, the cells increase production of cytokines. And cytokines, in turn, mediate various immune functions.

In addition, researchers suggest that melatonin supplements may provide a number of other health benefits. For instance, melatonin shows promise for anti-aging. And studies have shown that melatonin can influence circadian rhythm, thereby functioning as an aid for sleep or jet lag.