Melatonin

melatonin

Melatonin is a hormone found naturally in the body. Melatonin used as medicine is usually made synthetically in a laboratory. It is most commonly available in pill form, but melatonin is also available in forms that can be placed in the cheek or under the tongue. This allows the melatonin to be absorbed directly into the body.

People use melatonin to adjust the body’s internal clock. It is used for jet lag, for adjusting sleep-wake cycles in people whose daily work schedule changes (shift-work disorder), and for helping blind people establish a day and night cycle.

What is Melatonin?

Melatonin , chemically N-acetyl-5-methoxytryptamine, is a substance found in animals, plants, fungi and bacteria. In animals it is a hormone that anticipates the daily onset of darkness; however in other organisms it may have different functions. Likewise, the synthesis of melatonin in animals differs from that in other organisms.

Melatonin chemical structure
Melatonin chemical structure

In animals, melatonin is involved in the entrainment (synchronization) of the circadian rhythms of physiological functions including sleep timing, blood pressure regulation, seasonal reproduction and many others. Many of melatonin’s biological effects in animals are produced through activation of melatonin receptors while others are due to its role as a pervasive and powerful antioxidant, with a particular role in the protection of nuclear and mitochondrial DNA.

The hormone can be used as a sleep aid and in the treatment of some sleep disorders. It can be taken orally in liquid form as well as capsules or tablets in immediate- or prolonged-release form. It is also available in a form to be used sublingually, and as transdermal patches. Melatonin is sold over-the-counter in the U.S. and Canada. In other countries it may require a prescription or it may be unavailable.

In recent times, melatonin has become available as a drug and a dietary supplement. It appears to have some use against insomnia, jet lag, and circadian misalignment. Melatonin is a powerful antioxidant which can easily cross cell membranes including the blood-brain barrier. It has been studied for the treatment of cancer, immune disorders, cardiovascular diseases, depression, seasonal affective disorder, and sexual dysfunction; the results of most of these studies remain inconclusive. However, it has been shown to clearly ameliorate seasonal affective disorder and circadian misalignment, in studies by Alfred J. Lewy (OHSU) and other researchers.

Melatonin is referred to by some biochemists and human physiologists as the master hormone, because it regulates the production of most human hormones, both paracrine and endocrine. In addition, melatonin, taken alone, is an immunoregulator that enhances T cell production somewhat. However, when melatonin is taken in conjunction with calcium, it is a very potent immunostimulator of the T cell response. This is the reason it is used extensively as an adjuvant in many treatment protocols. Because it does not have to be prescribed, and since it is in the public domain, few doctors care to publicize its advantages. For the same reason, few clinical trials have been done to see its effectiveness in treating various diseases, such as cancer, obesity, h.i.v. infection, and others.

Melatonin Dosage

Light therapy may advance the phase about one to two-and-a-half hours and an oral dose of 0.3 or 3 mg of melatonin, timed correctly a few hours before bedtime, can add about 30 minutes to the ~2 hour advance achieved with light therapy. There is no difference in the average magnitude of phase shift induced by the two doses (0.3 or 3 mg)

Insecticides Increase Risk of Metabolic Disease by Mimicking Melatonin

New research out of the University of Buffalo has found that the synthetic chemicals that make up pesticides affect our biological clocks by binding to the receptors that govern them.  In these findings, it is noted that exposure to these chemicals has a negative impact on melatonin receptors, which put individuals at higher risk of metabolic diseases like diabetes.

Published in Chemical Research in Toxicology, the research combined standard laboratory experiments with big data that used computer modeling of several million chemicals.

Past research does prove that a disrupted circadian rhythm leads to higher risk of metabolic diseases; however, it is uncertain as to which mechanism is responsible.

Senior author of the study, Dr. Margarita L Dubocovich, PhD, SUNY Distinguished Professor at University of Buffalo’s Department of Pharmacology and Toxicology and a senior associate dean at the Jacobs School of Medicine and Biomedical Science, notes that this research clearly demonstrates a negative interaction between the common environmental chemicals found in almost every household and melatonin receptors.  There have been no other theories to suggest these compounds would affect the melatonin production.

For the sake of understanding the chemicals’ effects, this research focused on just two: carbaryl and carbofuran.  Carbaryl is the third most popular insecticide used in the United States, and carbofuran is the most toxic insecticide on the planet.  Carbofuran is banned from use on food crops meant for human consumption.  Unfortunately, other countries like Mexico still use it in trace amounts on plants and wildlife.

Marina Popeyska-Gorevski, co-author of the study and researcher in Dr. Dubocovich’s lab during her time as a graduate student, stated that the team found both insecticides to be similar in structure to melatonin.  Both seemed to bind quickly to the MT2 receptors, which likely affect glucose regulation and insulin production.  This leads to the conclusion that exposure to these two chemicals would likely put an individual at increased risk of diabetes and sleep disorders.

This research shows that further studies are needed to look at how environmental chemicals disrupt circadian activity, which is currently not considered by federal regulators.  The team of UB researchers are creating a bioassay to assess these chemicals more closely

Using computer simulation, researchers integrate the environment chemical screening with in vitro and in vivo techniques to determine the risk for a variety of diseases.

There are approximately 4 million toxic chemicals listed in the UB database.  Hundreds of thousands of compounds were pulled from these chemicals to be analyzed by the research team in order to understand the chemical structures.  Chemicals were grouped according to similarity, and several of the clusters were similar to melatonin.

In vitro experiments with melatonin receptor cells and predictive computations modeling showed that carbamates do interact with the melatonin receptors, and the interaction disrupts signaling and regulatory processes.

These findings lead the researchers to conclude that this direct interaction with the melatonin receptors means that chemicals like carbaryl can disrupt physiological processes and circadian rhythm, while also altering metabolic function.  This increases the risk of metabolic disorders like diabetes.

Dr. Dubocovich gives the example of the delicate balance between glucose in the pancreas and the release of insulin at regular times throughout the day; however, should that balance be disrupted frequently and over a long periods, the individual is at risk of diabetes.

Is Melatonin Safe?

Melatonin taken with MAOI drugs can also lead to overdose because MAOIs inhibit the breakdown of melatonin by the body.Fortunately, melatonin exhibits almost no toxic side effects, except for the occurrence of somnolence in most of the population at higher doses. There are as of yet no reports about melatonin toxicity, notwithstanding the dosage administered, nor the amount of time the medication has been taken, except for clinical changes as noted in various studies. Exogenous melatonin does not affect the endogenous melatonin profile in the short or medium-term.There have not been sufficient studies done on pregnant women concerning possible carcinogenic effects of melatonin.

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