One of the most frequently asked questions I get around sleep is, “If I use a supplement containing melatonin, will I become addicted?” or “Will I build tolerance and be unable to sleep without it?”
Let me clear the air on this topic since I recently wrote about many of the benefits melatonin provides in keeping your immune system in peak shape, especially during the cold and flu season.
I can confidently say that melatonin is one of the safest supplements you can take. Of course, when considering the use of melatonin (or any other supplement to treat COVID-19), the safety of each individual product it comes in is of utmost importance. Some products are certainly of higher quality than others.
As reviewed previously, short-term use of melatonin is incredibly safe, even when given in high doses, and the reported adverse effects are limited to occasional dizziness, headache, nausea, and sleepiness. Generally speaking, melatonin's safety profile in humans is very high (Andersen et al., 2016). In clinical trials, doses of 3 mg, 6 mg and 10 mg of melatonin oral intake by patients in ICU showed satisfactory safety when compared to placebo (Bourne et al., 2008; Mistraletti et al., 2010; 2015).
I typically never go beyond 3 mg in practice with my patients, but some studies have even gone as high as 1 gram per day for a month with no adverse effects reported (Nordlund & Lerner, 1977). Although there are no clinical trials to assess the use of melatonin in COVID-19 patients, in individuals with other inflammation-causing diseases, the use of melatonin has shown promising results with respect to boosting the immune system.
The safety of melatonin has been verified in many human studies. It is important to note that taking Melatonin 1.5 hours or earlier before bed improves its effectiveness and prevents one from experiencing any minor side effects.
Melatonin Effects in Cytokine Levels in Humans
In a randomized controlled 8-week trial (RCT), oral supplementation of 6 mg per day of melatonin caused a significant decrease in serum levels of the inflammation-producing cytokines IL-6, TNF-α, and the inflammatory cardiac marker hs-Creactive protein (hs-CRP) in patients with diabetes mellitus and teeth & gum disease (periodontitis) (Bazyar et al., 2019). When these powerful cytokines associated with causing tons of tissue damage subside, the immune system is able to work more favorably against overarching pathogens causing disease.
In another study with patients suffering with severe multiple sclerosis, 25 mg per day of melatonin for 6 months also led to a significant reduction in serum concentrations of the cytokines TNF-α, IL-6, IL-1β, and lipoperoxides (Sánchez-López et al., 2018). In acute phases of inflammation, such as during surgery, (Kücükakin et al., 2008), melatonin intake of 10 mg per day, 6 mg per day, and 5 mg per day for less than 5 days reduced the level of circulating pro-inflammatory cytokines. Lastly, in a meta-analysis of 22 RCTs, it was found that melatonin is associated with a significant reduction of TNF-α and IL-6 level (Zarezadeh et al., 2019).
All of this clinical evidence (in addition to the past 3 previous posts) suggests that the use of melatonin as a supplement may effectively reduce the inflammation and in turn, lessen the harm caused by many chronic disease and pathogens (i.e., COVID19). By boosting the immune system, melatonin can improve clinical outcomes.
Any risk of melatonin in COVID-19 is theoretical at this point. The potential beneficial effects of melatonin as adjuvant use in COVID-19 in anti-inflammation, anti-oxidation, and immune response regulation has been repeatedly demonstrated in respiratory disorder models induced by infections and associated complications. Melatonin’s safety profile is near excellent.
And despite the direct evidence of melatonin application in COVID-19 is unclear, both its use in experimental animal models and in humans has continuously documented its efficacy and safety and its use by COVID-19 patients predictably would be highly beneficial.
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