Melatonin, which we typically associate with the regulation of circadian rhythms, has actually been shown to improve many markers of pulmonary inflammation and lung function. It is actually one of our most basic protective antioxidants. So in addition to regulating our sleep cycle, Melatonin has also been found to impact our metabolism, brain health, bone formation, physical growth, reproductive health, oral health and most importantly during these times our immune system function.
Melatonin has many receptors found in most every system of the body, much like other key signaling molecules and hormones. Although mostly produced in the pineal gland, research also suggests Melatonin is produced in the lymphocytes, thymus, and bone marrow as well as various cells in the gastrointestinal tract, all of which influence the immune system.
Many studies have established that as we age, our melatonin levels decline and our rhythms of melatonin become altered. Reduction in melatonin, as well as other important antioxidants like CoQ10 and Glutathione, lead to a decline in the function of our organs, cells and overall body systems which contribute to the onset of many diseases that occur during the aging process. Of all these antioxidants, Melatonin seems to be a critical factor when it comes to susceptibility and response to infections.
Melatonin is one of the hormones in the body that have a circadian variation. Cortisol and DHEA both cycle in a 24 hour period, which is the opposite of Melatonin.
Nearly all immunocytes (any cell of that has an immunologic function) and their related cytokines (substances like interferon, interleukin and growth factors, secreted by certain cells of the immune system and affecting other cells) have a circadian type variation which is influenced by sleep. Nighttime sleep is associated with the lowering of natural killer cells, lymphocytes and monocytes and then increase to levels seen during the daytime the following afternoon and evening. When normal nighttime sleep is missing, the drops and rise of these lymphocytes is missing. Prolonged disruptions of these normal sleep patterns seem to produce a pro-inflammatory state.
Melatonin affects the levels of inflammatory mediators and the circadian variation of the immune response. Oppositely, inflammatory cytokines like TNF (Tumor Necrosis Factor-a) influence nighttime melatonin production. In a severe illness like for example sepsis, melatonin release is impaired, while in other critical care settings, Melatonin release may be dysregulated. Circadian rhythms have been shown to be totally disrupted by certain viral infections which may increase viral replication. In animal studies Melatonin supplementation has been shown to reduce the proinflammatory effects caused by sleep deprivation as well as the inflammatory response to certain types of bacteria while also reducing immunocyte infiltration and tissue damage in the lungs.
Studies have shown that sleep and/or Melatonin supplementation improves interactions between anti-gen presenting cells and T helper cells which improve immunological memory. Melatonin has also been shown to increase natural killer cell activity and production as well as antibody-dependent cellular cytotoxity. Melatonin opposes the wakefulness actions of cortisol but also works against cortisol’s immunosuppressive effects.
Melatonin reduces the affects of inflammation by inhibiting the NLRP3 inflammasome (a protein complex that initiates an inflammatory form of cell death and triggers the release of proinflammatory cytokines). Activation of the NLRP3 inflammasome adds to the pathology in many conditions associated with chronic low-grade inflammation like Diabetes and Alzheimer’s disease. Melatonin has been shown to help protect against these conditions. Some level of NLRP3 activation is needed for a normal and protective response to microbial invaders as well as mediating excessive inflammation.
Animal studies show Melatonin has protective effects for conditions like Atherosclerosis, Osteoporosis, Diabetic Cardiomyopathy, as well as Radiation Injury due to its ability to inhibit NLRP3 inflammasome activation. Additional studies have shown Melatonin increases levels of interleukin (IL)-10 which provides anti-inflammatory benefits.
More than one human study has shown that Melatonin reduces C – reactive protein levels and/or various pro-inflammatory cytokins in conditions associated with chronic inflammation like Type 2 Diabetes, Multiple Sclerosis and Periodontitis. In surgical settings doses ranging from 3 mg to 20 mg have been shown to reduce inflammation markers. Results from a 2019 meta-analysis of randomized controlled trials showed Melatonin was a valid anti-inflammatory therapy. Supplementation with 3 mg – 25 mg of Melatonin for a period of 4 weeks or longer significantly decreased TNF-a and IL-6 levels.
Further studies on Melatonin are ongoing.
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