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Melatonin, it’s not just for bedtimeMelatonin, it’s not just for bedtime

The “sleep hormone” could have benefits around the clock

Lisa Polito

September 1, 2015

5 Min Read
Melatonin, it’s not just for bedtime

With the public health spotlight focused on nighttime exposure to blue light, sleep is taking center stage as a health concern, but that attention may also bring awareness of melatonin out of the shadows.

The ingredient, it turns out, has more to offer than a good night’s sleep.

 Often referred to as a “sleep hormone,” due to its association with human circadian rhythm and nighttime sleep, melatonin does not necessarily induce sleep—just ask someone with a sleep disorder. Indeed, nighttime darkness triggers a rise of melatonin in all animals, regardless of diurnal, nocturnal or crepuscular wake-sleep patterns, which hints at a more complex and far-reaching biological role than melatonin’s humble drowse-inducing reputation implies. Areas of melatonin research range broadly—from cancer, neurodegenerative disease, metabolic syndrome, and even acute sepsis to depression and addiction—but that research is clearly promising. A patent review in the Journal Expert Opinions on Therapeutic Patents (January 2015) noted that melatonin co-administered with other drugs, including tamoxifen, was a major trend in recent patent applications, with much of the ingredient’s efficacy derived from its potent antioxidant activity. 

According to researcher Russell Reiter, professor in the cellular and structural biology department, University of Texas Health Science Center, and editor-in-chief of the Journal of Pineal Research, melatonin is a superior antioxidant.  “When you think of antioxidants—vitamin C and E and others,” he says of melatonin, “There really is no comparison.”  Emphatically pointing to experiments that document melatonin’s effects in reducing the progression of diseases associated with free-radical damage, such as cancer, neurodegenerative, and type 2 diabetes, he posits that an age-related decline of melatonin contributes—not causes, he stresses— to those diseases.


Beyond the bed

Because most of those experiments involved animals or cell cultures, the effects of melatonin could be isolated from sleep. Longtime circadian melatonin cancer biology researcher, Dr. David Blask, professor and head of the Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, offers the example of rats, which are nocturnal, exposed in the laboratory to very dim light at night that only suppresses melatonin production but does not disrupt circadian systems and sleep patterns.  Though “normal in every other way,” he explains, “They’ll still develop cancer, their cancer progresses, and they’ll even develop metabolic syndrome due specifically to melatonin suppression.”  Reiter likewise notes animal experiments in which melatonin effects are distinct from sleep; when overweight rodents are administered small amounts of supplemental melatonin at night, they lose weight without a change in diet. 

In humans, however, melatonin is so deeply entwined with sleep that distinguishing the healthful attributes of one from the other can prove challenging.  People with higher disease risk due to melatonin-suppressing light exposure at night, such as shift workers, are probably also undergoing sleep deprivation, Blask points out.  “How much of their disease risk is due to sleep deprivation versus melatonin suppression?” he says, “It’s very difficult to do experiments on humans and separate those out.”

In some instances, however, melatonin’s effects can be distinguished from sleep. Reiter, whose pineal gland and melatonin research spans 50 years, refers to documented positive outcomes from treating infant sepsis with melatonin and notes current clinical trials of melatonin in adult sepsis ongoing in the UK.  Melatonin turns out to be a versatile player, not just a so-called sleep hormone or anti-oxidant, but also an anti-inflammatory, among other possible roles.  The reactions of melatonin with a receptor cell are what Reiter refers to as “context based” or dependent upon the cell receiving melatonin, offering the example of melatonin inhibiting blood supply to in tumors even as it enhances blood flow and growth in healthy tissue. Based on the anti-inflammatory effects of melatonin, Reiter has also suggested its use in the treatment of ebola, a highly inflammatory disease for which there is no treatment.  “It would not have done any harm,” he says. “And it may have done good.” 


Safe solutions

While his claim of doing good in the treatment of ebola remains extremely theoretical, the claim of no harm is widely accepted.  Melatonin is non-toxic and has a short half-life, or as Reiter puts it, “Melatonin is safer than water: you can drown in water.” Although melatonin supplementation can extend the body’s perception of night, or biological night, the main concerns associated with melatonin supplementation appear to involve interactions with pharmaceutical drugs.  Whether or not regular high-dose supplementation causes down-regulation, or a desensitizing of receptor cells, also remains “a hot topic of debate and consternation among melatonin researchers,” according to Blask.  Theoretically, down-regulation would be predicted with the long-term use of high dosage supplementation; however, Blask explains, “When you look at data and when you talk to people, anecdotally, who have taken melatonin for a long time in high doses, they seem to keep responding to melatonin supplements as if their receptors are not down regulated.  And so that gets to be a puzzling issue.”

Despite ongoing debate over possible down-regulating effects and a dearth of human clinical trials, both Reiter and Blask say they take daily melatonin supplements:  Reiter as a prophylactic against diseases with a free-radical basis and Blask not only for sleep but also for cancer protection and anti-inflammatory properties.  Neither researcher recommends melatonin supplementation to anyone; for each, taking the supplement is a personal decision.  As Blask puts it, the effects he sees in his pre-clinical animal research are so strong that he chooses not to wait. “I know melatonin is safe,” he says, “so I don’t have any reluctance taking it before any big clinical trials proving that this is of use in humans.” 

As exciting as the research may be, in the supplement industry, claims associated with such diseases run the risk of drawing FDA action.  Even general anti-inflammatory claims may run that risk, according to attorney Justin Prochnow, Greenberg Traurig, since the FDA considers unqualified anti-inflammatory claims as disease claims. That risk must seem worthwhile to companies such as, Life Extension, which hosts the article “Beyond Sleep: 7 Ways Melatonin Attacks Aging Factors,” replete with more than 100 references, in the magazine section of its website.  As to the risks associated with a claim that a supplement could replace the melatonin suppressed by blue light—or depleted by aging—the jury is still out.

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