Melatonin, or N-acetyl-5-methoxytryptamine, as some scientists would say, is not just one out of several, it is the circadian hormone, per se. Being produced in the pineal gland, melatonin has been shown to reset, regulate and synchronize the internal clock of our bodies (Arendt. 1987).
In the late evening, when the sun sets and the production of melatonin is no longer suppressed by the light-induced negative feedback on the pineal gland, your natural melatonin production kicks in.
Unfortunately, next to artificial light, which is something you can easily avoid by wearing a blindfold in bed, aging (Karasek. 2004) and metabolic diseases incl. obesity (Reiter. 2012) will also inhibit the increase in serum melatonin in the hours before you go to bed.
Melatonin Supplements Are A Potential Fountain Of Youth
Studies have shown that the natural melatonin production starts to decline by the age of 30 – and that at a pace pretty rapid pace of approximately 2% per year (Sack. 1986). This decline in melatonin, which is still falsely considered to be a simple “sleep hormone” by many medical practitioners, goes hand in hand with a decline in antioxidant defenses. The same decline, of which researchers believe that it is at the heart of the anatomical and functional degeneration organs undergo during when we age. Accoringly, Reiter is spot on, when he points out in a 1994 paper in the peer-reviewed scientific journal Acta Neurobiologiae Experimentalis that the age-induced decline in melatonin production “may well play a significant role in aging processes,” and that its prevention (e.g. by supplementation) “could be prevented” or at least “[delay] the aging process” (Reiter. 1994).
The scientist from the University of Texas in San Antonio also believes that supplemental administration of melatonin may be beneficial in delaying age-related degenerative conditions, particularly in view of the fact that free radical damage has been implicated in a number of neurodegenerative disorders, which may be forestalled by chronic melatonin administration.
Melatonin and the prevention of neurodegenerative diseases
More recently, scientists from the Netherlands Institute for Brain Research supplied further evidence that Reiter’s 20-year old hypothesis may actually be true (Wu. 2005). In their paper in the Journal of Pineal Research, Ying-Hui Wu and Dick F. Swaab report that they were able to show that the disruption of melatonin production is a characteristic feature of Alzheimer’s that can be observed “as early as in the very first preclinical stages” (Wu. 2005) of this debilitating neurological disease. It is thus not surprising that early rodent data suggests that melatonin supplementation can reduce or even prevent both, the normal and pathological aging process of the brain and could thus help you to avoid a whole host of neurological problems we see in the elderly, today (Ramírez-Rodríguez. 2012; Peng. 2013). Many of these hypothetical benefits have already been confirmed for Alzheimer disease, Parkinson disease, Huntington’s disease and Amyotrophic Lateral Sclerosis (Polimeni. 2013).
Melatonin as a Zeitgeber and antioxidant
Whether the benefits are a mere result of the powerful antioxidant capacity of melatonin, of which scientists from the Atatürk University have shown that it they are 10x more pronounced than those of vitamin E (see Figure 1), is something researchers are still debating.
Figure 1: Percentage inhibition of lipid peroxidation by melatonin and
alpha-tocopherol in a linoleic acid emulsion as a marker of the potent
anti-oxidant activity of melatonin (Gulcin. 2002)
What stands out of questions, though, is the fact that at least part of the benefits of melatonin are mediated by its ability to synchronize and reset the central (brain) and peripheral (liver, muscle, fat, etc.) clocks of your body.
This is an important effect, since the loss of synchronicity of central and peripheral clocks has been associated with the whole spectrum of diseases of civilization ranging from “C” as in cancer to “O” as in obesity, almost all of the contemporarily increasing ailments is in one way or another related to the lack of synchronicity of the central and peripheral clocks in our brain and organs tissue.
No wonder, shift work, and even the chronic exposure to bright (specifically blue) light at night have been consistently linked to increased obesity and cancer risks in men and women (Hansen. 2002; Kubo. 2006; Viswanathan. 2007; Antunes. 2010).
The anti-obesity, pro-metabolic effects of melatonin supplements
Rodent studies show that the provision of melatonin supplements can realign the peripheral and central clock and prevent mammals from the negative side effects (Prunet-Marcassus. 2003). In their 2012 review of the literature, F. Nduhirabandi, E. F. du Toit and A. Lochner list 24 experimentally verified metabolic benefits of melatonin supplementation (see Figure 2 ).
Figure 2: Obesity related health parameters that may improve with melatonin treatment
In view of the fact that melatonin has also been implicated as a regulator and controller of brown, i.e. fat burning adipose tissue mass and activity, it is obvious that the pineal hormone is already touted as the most promising “naturally occurring substance with no reported toxicity” that “may serve as a novel approach for treatment of obesity” (Tan. 2011) by researchers all around the world (Bonnefont-Rousselot. 2014; Cipolla ‐ Neto. 2014).
Figure 3: Summary of metabolic and chronobiological actions of melatonin resulting in the regulation of energy metabolism, energy
balance, and ultimately body weight (left); and consequences of the absence or reduction in melatonin production (right; cf. Cipolla-Neto. 2004).
As Cipolla-Neto et al. explain in their review of the negative effects of a lack of melatonin, even the scope of the already known ill health effects is huge (see Figure 3 , right). The same can be said of the health benefits that may be achieved by its specific and well-timed supplementation:
While all of the previously listed benefits have been observed in rodent studies, the unwarranted fear that the use of melatonin supplements could have negative side effects, let alone shut down the natural melatonin production permanently is to blame that corresponding human trials are rare.
General antioxidant activity – Polish scientists found that the provision of 5mg of melatonin approximately 1h before bed for 30 days normalized the age-related decrease in erythrocyte anti-oxidant status and may thus “prolong the lifespan and improve the quality of life of elderly people.” (Kędziora ‐ Kornatowska. 2007). Similar beneficial anti-oxidant effects have been observed by the same researchers in hypertensive subjects and type II diabetics, as well (Kędziora ‐ Kornatowska. 2008; Kędziora ‐ Kornatowska. 2009).
Blood pressure control – In 1998, already, Cagnacci et al. reported significant improvements in artery blood flow, decreased blood pressure, and a reduces stress response in young, healthy women in response to the administration of 1 mg of melatonin. Similar effects have subsequently been reported by Arangio et al. (1999) in young men. More recently, scientists from the Netherlands Institute for Brain Research have been able to show similar benefits in response to chronic supplementation with 2.5mg of melatonin before bed. The supplementation regimen reduced the systolic and diastolic blood pressure in hypertensive men during sleep by 6 and 4 mm Hg, respectively (Scheer. 2004). Similar results have been reported by Ray et al. (2003) who observed that melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans.
Cancer prevention and treatment – Blask et al. observed a rise in markers of tumor suppression in a human volunteer in response to a commercial 3mg preparation of melatonin (Blask. 2005).
Metabolic syndrome – Koziróg et al. (2011) report that comparatively small doses of 5mg/day (rodent studies often use 10mg or more) melatonin improve blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome.
Along with other studies, the previously cited experimental evidence has long convinced our the AgeForce R&D team of the great health benefits of melatonin supplements, which may be significantly augmented by the time-released delivery of melatonin through the skin.
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