Melatonin is an indoleamine whose main function is the regulation of the neuroimmunoendocrine system which is found in all microorganisms. Melatonin is often used to support sleep or for its antioxidant properties in cancer; however, it has also been used successfully with cardiovascular disease, gastroesophageal reflux disease (GERD), and respiratory and viral infections.

After childhood and specifically in the elderly, melatonin secretion decreases. This decline may be related to chronic diseases, so increasing dietary intake or supplementation may be important for these individuals.

In a new review published two weeks ago in Life Sciences, researchers investigated melatonin as a potential immunity enhancement adjuvant.

Previous research has demonstrated benefits of melatonin in helping to mitigate acute respiratory distress caused by bacteria and viruses. Melatonin has indirect anti-viral activity due to its immune-enhancing, antioxidant, and anti-inflammatory properties. 

Animal studies have shown a reduced viral load from melatonin, and in respiratory syncytial virus models, melatonin down regulates acute lung oxidative injury, immune cell response, and inflammatory cytokines, including IL-6, IL-10, and TNF-α. Melatonin demonstrates anti-inflammatory effects through numerous pathways. It down regulates nuclear factor kappa-B (NF-kB) activation in T cells and lung tissue as well as has anti-inflammatory effects via the sirtuin-1 (SIRT1) pathway. All infection models demonstrate that melatonin provides a protective action. In addition, viral infections generate oxidative stress; therefore, the down regulating effect of melatonin’s pro-oxidative enzymes may be beneficial during acute viral infections. Melatonin also has immune-modulating effects by enhancing the production and maturation of natural killer cells, granulocytes, monocytes, and T and B lymphocytes. 

The NOD-like receptor 3 (NLRP3) inflammasome is part of the immune response in lung infection. This is the inflammasome that is activated during lung infections and has been associated with the cytokine storm. The efficacy of melatonin has been demonstrated in acute lung injury models to inhibit the NLRP3 inflammasome as well as reduce the attack of macrophages and neutrophils into the lung in acute lung injury.

Melatonin has showed encouraging results in other inflammatory conditions by reducing circulating cytokine levels. For example, one 8-week randomized controlled trial demonstrated a significant reduction in IL-6, TNF-α and hs-CRP levels in patients with diabetes mellitus and periodontitis with a dose of 6 mg per day of melatonin. In another study involving severe multiple sclerosis patients, 25 mg per day of melatonin for 6 months showed a significant reduction in TNF-α, IL-6, IL-1β and lipoperoxides. Also in acute inflammation situations such as surgical stress, brain reperfusion, and coronary artery reperfusion, melatonin supplementation at doses of 5 mg, 6 mg, or 10 mg per day showed a reduced level of pro-inflammatory cytokines. Furthermore, a recent meta-analysis of 22 randomized controlled trials demonstrated that melatonin supplementation significantly reduces TNF-α and IL-6 levels.

During this stressful time restful sleep could not be more important. Restful sleep has been associated with lower daytime secretion of interleukin-6 (IL-6), whereas sleep disturbance has been correlated with increased daytime IL-6 levels. 

Melatonin should not only be considered to help improve sleep but also for its potent anti-inflammatory, antioxidant, and immune-modulating effects. Other nutritional supplements that may be beneficial to help with inflammation and oxidative stress include tocotrienols, geranylgeraniol, resveratrol, quercetin, and specialized pro-resolving mediators.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Zhang R, Wang X, et al. COVID-19: Melatonin as a Potential Adjuvant Treatment. Life Sci. 2020 Mar 23: 117583.