MELATONIN: A SCIENTIFIC REVIEW- SLEEP, STRESS, IMMUNITY & HEALTH
By Robert A. Schinetsky
Melatonin is a hormone most well-known for its role in regulating circadian rhythm and sleep.
Our bodies synthesize melatonin from the essential amino acid L-Tryptophan, and it is secreted by the pineal gland -- a small gland in the brain that’s often referred to as “the third eye.”
While melatonin is vital to sleep, that just begins to scratch the surface of this ever-important naturally occurring chemical.
Melatonin also affects[1,2]:
- Blood pressure regulation
- Immune function
- Ovarian physiology
- Core body temperature
- Antioxidant defense systems
Given melatonin’s bevy of activity in the body, it’s no wonder that the compound is a source of intensive research among the scientific community, even though it’s been studied hundreds of times.
Today, we recap some of the latest, most intriguing findings surrounding melatonin and the human body.
Latest Melatonin Research
It’s no secret that the health and proper functioning of the immune system is at the forefront these days.
As we mentioned above, melatonin not only plays a pivotal role in sleep, but also affects immune function.
Melatonin assists in immune system regulation, and it directly enhances the immune response by improving proliferation and maturation of natural killer (NK) cells, T and B lymphocytes, granulocytes and monocytes.
Like most other hormones in the body, melatonin production is high during the earlier phases of life, but declines with age. This may, in part, explain while older populations are more susceptible to more deleterious outcomes when they become infected.
As such, a number of studies have been published in recent months investigating the utility of melatonin as an adjuvant treatment for respiratory ailments, including COVID.[4,5,11]
Researchers note that while melatonin is not virucidal, it possesses indirect antiviral actions due to its anti-inflammation, anti-oxidation and immune supporting features.
These findings bolster previous research which found that melatonin had positive effects in alleviating respiratory distress induced by bacteria and virus.[7,8,9]
Specifically regarding infections, melatonin acts as a potent antioxidant and anti-inflammatory that helps mitigate oxidative stress and the excessive production of pro-inflammatory cytokines and chemokines in lung tissue.
In fact, melatonin intake of 10 mg/d (the same dose included in AML Calming Cocktail) was noted to help reduced levels of pro-inflammatory cytokines.
The reason this is noteworthy is that the cytokine storm intensifies the danger signal of the virus invasion and also leads to inflammation and host cell damage.
Additionally, a 2019 meta-analysis indicated that melatonin supplementation was associated with a significant reduction of inflammatory markers TNF-α and IL-6.
Melatonin has also been noted to decrease viral infections in obese and diabetic patients (two of the most at-risk populations of COVID).
Interestingly, research indicates that COVID-19 infection may attack the melatonin synthetic pathway leading to decreased melatonin levels at a time when melatonin is critical.
Perhaps most importantly, melatonin has a high safety profile. In fact, even when melatonin was given to humans at dose of 1 gram (1,000mg) per day for a month, there were no adverse effects observed with the treatment.
The utility of melatonin in supporting immune function and health may best be surmised by the following, which was published in a study entitled Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis:
“The collective data, in addition to its very high safety profile, indicate that melatonin would be effective as a treatment for COVID-19 and support the recommendation of the published reports that encourage its use for this purpose [, , , , ]. Melatonin is inexpensive, non-toxic over a very wide dose range, has a long shelf-life and can be self-administered which is a major advantage when large numbers of individuals are involved. Thus, the use of melatonin to mitigate the COVID-19 pandemic would be feasible and a socially-responsible measure to attempt.”
Improve Sleep & Stress
Sleep is vital to the body’s ability to recover and repair damage done through intense exercise. It also directly impacts hunger and satiety signaling, cognitive performance, and physical activity levels.
Perhaps most poignant to current times, sleep also impacts immune function and stress levels.
Poor sleep is known to increase cortisol (stress) levels in the body, and chronic stress is a very real concern these days, perhaps now more than ever.
This chronic state of stress can impair sleep and create a state of inflammation, further increasing the susceptibility to illness and infection. Sleep deprivation can also contribute to the development of cardiovascular disease, hypertension, and type 2 diabetes.
Melatonin is a powerful antioxidant and anti-inflammatory molecule that can help reduce sleep onset latency, delayed sleep phase syndrome, and regulate the sleep-wake patterns.
Moreover, melatonin is recognized as a safe and effective natural sleep aid that possesses no known withdrawal or safety issues related to the use or discontinuation of the compound. It’s extensively studied and known to be helpful at a wide range of doses from 0.3mg to 10mg.
Antioxidants reduce harmful inflammation and limit cellular and DNA damage from oxidative stress, which occurs as a result of free radical proliferation.
Chemicals that function as antioxidants can neutralize the damaging effects of free radicals, supporting the proper functioning of genes and cells as well as defending against illness and infection.
Seeing as melatonin is one of the most powerful antioxidants in the body, it stands to reason that it plays a key role in promoting health and wellness.
This is all the more noteworthy when you understand that oxidative stress can damage brain cells, which contributes to age-related cognitive decline and the development of neurodegenerative diseases, including Alzheimer’s disease.
Emerging research indicates that melatonin may be a powerful ally in the war against cognitive decline, primarily due to its potent antioxidant and anti-inflammatory qualities.[18,19]
The Best Melatonin Supplement
No doubt, melatonin is a powerful and vitally important hormone for health and wellness. Not only is it necessary for quality sleep, it also plays key roles in controlling stress, inflammation, and immune function.
Melatonin even helps the body burn fat by boosting energy expenditure via increasing brown adipose tissue (BAT) concentrations and activity.
AML Calming Cocktail supplies a robust, research-backed dose of 10mg melatonin per full serving.
AML Calming Cocktail is a comprehensive, nighttime relaxation aid engineered to help manage stress and anxiety while simultaneously encouraging relaxation and more restorative sleep. AML Calming Cocktail is a natural alternative to other agents typically used to “take the edge off” at night that doesn’t come with the habituation, tolerance, or unwanted side effects.
ThermoHeat Nighttime is a non-stimulant nighttime sleep and recovery aid formulated to help boost metabolism, manage stress and regulate appetite. It also promotes relaxation and sleep. In addition to melatonin, every serving of ThermoHeat Nighttime also includes stress-relieving, relaxation-promoting agents including: L-Theanine, 5-hydroxytryptophan (5-HTP) and gamma-aminobutyric acid (GABA).
- Savage RA, Zafar N, Yohannan S, et al. Melatonin. [Updated 2020 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534823/
- Kräuchi, K., Cajochen, C., Pache, M., Flammer, J., & Wirz‐Justice, A. (2006). Thermoregulatory effects of melatonin in relation to sleepiness. Chronobiology International, 23(1-2), 475-484. https://doi.org/10.1080/07420520500545854
- Lok R, van Koningsveld MJ, Gordijn MCM, Beersma DGM, Hut RA. Daytime melatonin and light independently affect human alertness and body temperature. J Pineal Res. 2019;67(1):e12583. doi:10.1111/jpi.12583
- Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. doi:10.1016/j.lfs.2020.117583
- El-Missiry MA, El-Missiry ZMA, Othman AI. Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19. Eur J Pharmacol. 2020;882:173329. doi:10.1016/j.ejphar.2020.173329
- Reiter R.J., Ma Q., Sharma R. Treatment of Ebola and other infectious diseases: melatonin “goes viral” Melatonin Res. 2020;3:43–57. doi: 10.32794/mr11250047.
- Yip, H.‐K., Chang, Y.‐C., Wallace, C.G., Chang, L.‐T., Tsai, T.‐H., Chen, Y.‐L., Chang, H.‐W., Leu, S., Zhen, Y.‐Y., Tsai, C.‐Y., Yeh, K.‐H., Sun, C.‐K. and Yen, C.‐H. (2013), Melatonin treatment improves adipose‐derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury. J Pineal Res, 54: 207-221. doi:10.1111/jpi.12020
- Huang, S.‐H., Cao, X.‐J., Liu, W., Shi, X.‐Y. and Wei, W. (2010), Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. Journal of Pineal Research, 48: 109-116. doi:10.1111/j.1600-079X.2009.00733.x
- Habtemariam S, Daglia M, Sureda A, Selamoglu Z, Gulhan MF, Nabavi SM. Melatonin and Respiratory Diseases: A Review. Curr Top Med Chem. 2017;17(4):467-488. doi:10.2174/1568026616666160824120338
- Nordlund J.J., Lerner A.B. The effects of oral melatonin on skin color and on the release of pituitary hormones. J. Clin. Endocrinol. Metab. 1977;45:768–774. doi: 10.1210/jcem-45-4-768.
- Alex Shneider, Aleksandr Kudriavtsev & Anna Vakhrusheva (2020) Can melatonin reduce the severity of COVID-19 pandemic?, International Reviews of Immunology, 39:4, 153-162, DOI: 10.1080/08830185.2020.1756284
- Zarezadeh M., Khorshidi M., Emami M., Janmohammadi P., Kord-Varkaneh H., Mousavi S.M., Mohammed S.H., Saedisomeolia A., Alizadeh S. Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials. Eur. J. Nutr. 2019 doi: 10.1007/s00394-019-02123-0.
- Miller S.C., Pandi-Perumal S.R., Esquifino A.I., Cardinali D.P., Maestroni G.J.M. The role of melatonin in immuno-enhancement: potential application in cancer. Int. J. Exp. Pathol. 2006;87:81–87. doi: 10.1111/j.0959-9673.2006.00474.x.
- Reiter RJ, Sharma R, Ma Q, Dominquez-Rodriguez A, Marik PE, Abreu-Gonzalez P. Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis. Med Drug Discov. 2020;6:100044. doi:10.1016/j.medidd.2020.100044
- Reiter, R. J., Abreu-Gonzalez, P., Marik, P. E., & Dominguez-Rodriguez, A. (2020). Therapeutic algorithm for use of melatonin in patients with COVID-19. Frontiers in Medicine, 7. https://doi.org/10.3389/fmed.2020.00226
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- Chitimus, D.M.; Popescu, M.R.; Voiculescu, S.E.; Panaitescu, A.M.; Pavel, B.; Zagrean, L.; Zagrean, A.-M. Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules 2020, 10, 1211.
- Shukla M, Govitrapong P, Boontem P, Reiter RJ, Satayavivad J. Mechanisms of Melatonin in Alleviating Alzheimer's Disease. Curr Neuropharmacol. 2017;15(7):1010-1031. doi:10.2174/1570159X15666170313123454
- Halpern, B., Mancini, M. C., Bueno, C., Barcelos, I. P., De Melo, M. E., Lima, M. S., Carneiro, C. G., Sapienza, M. T., Buchpiguel, C. A., Do Amaral, F. G., & Cipolla-Neto, J. (2019). Melatonin increases Brown adipose tissue volume and activity in patients with melatonin deficiency: A proof-of-Concept study. Diabetes, 68(5), 947-952. https://doi.org/10.2337/db18-0956