Q: What is melatonin and what is it used for? - Technical

A: The pea-sized, light-responsive pineal gland is buried in the middle of your brain 3 – 4" behind the center of your eyebrows. For most of the 20th century the pineal was believed to be left-over and of little interest, even though it is the first organ to develop in the fetus, being discernable about three weeks after conception. Ancient wizards called the pineal the “third eye”, and imbued it with great powers over mood, sexuality and consciousness. Recent science shows that the ancients were pretty close to the truth.

Melatonin
5-methoxy-N-acetyltryptamine
Empiric formula	C13H16N2O2
Molecular weight	232.28
Bioavailability	30 - 50%
Metabolism	Liver
Elimination half life	32 - 40 minutes
Excretion	Urine
Pregnancy category	?
Delivery	1mg, 2.5mg, 3mg, and 5mg capsules; 1mg/mL or 1mg/4mL liquid; .5mg and 3mg lozenges; 2.5mg sublingual tablets; 1mg, 2mg, and 3mg timed-release tablets
Indicated for: insomnia jet lag sleep disorders

Melatonin, or 5-methoxy-N-acetyltryptamine, is a hormone produced by pinealocytes in the pineal gland, located in the brain, but also in the retina and GI tract. It is a derivative of the amino acid tryptophan.

Melatonin produced in the pineal gland acts as an endocrine hormone since it is released into the blood. On the other hand, melatonin produced by the retina and the GI tract is considered a paracrine hormone.

Melatonin helps regulate sleep-wake or circadian rhythms. Normally, production of melatonin by the pineal gland is stimulated by darkness and inhibited by light. Melatonin can suppress libido by inhibiting secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary gland -- especially in mammals that have a breeding season when daylight hours are long, such as sheep. Nobel Prize laureate Julius Axelrod performed many of the seminal experiments elucidating the role of melatonin and the pineal gland in circadian rhythms. Beta blockers decrease nocturnal melatonin release.

Melatonin is synthesized by various plants such as rice and ingested melatonin was shown to be capable of reaching and binding to melatonin binding sites in the brain of mammals.

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.

To synthesize melatonin, serotonin is converted to N-acetylserotonin by the enzyme 5-HT N-acetyltransferase. N-acetylserotonin is then converted to melatonin by the enzyme 5-hydroxyindole-O-methyltransferase. See serotonin for details on how tryptophan is converted to serotonin.

Melatonin has been shown to increase the lifespan of mice by 20% in some studies 

Other studies have noted that wearing garments such as bras are linked to a decrease in melatonin production. 

In 1958, Aaron Lerner, a dermatologist at the Yale University, discovered that the pineal secretes a powerful hormone, which he named melatonin.  It took another 20 years to establish that melatonin is the circadian pacemaker of the human body, without which you would lose the temporal organization of the hormone cascade, with consequent progressive degenerative changes in the brain and other organ systems.

Though it cost Yale over 10 million dollars for Lerner to first isolate and then synthesize a few milligrams of melatonin, the ingredients for this hormone are so simple, it now costs only pennies to make. Because of its near zero toxicity, melatonin has become commonplace in public use, both as a sleep aid and to combat jet lag, for which purposes it works reasonably well.  Consequently, many folk think of this most powerful hormone merely as a trivial remedy. 

In animals that are seasonal breeders, including birds, melatonin controls their annual cycle, from the sprouting of antlers in deer, to animal and bird migrations, to sexuality and reproduction, to seasonal changes in fur and plumage, even birdsong.  In the low light of winter, melatonin rises to lower testosterone, and shrivel the gonads of male animals, and eliminate the menstrual cycle, and dry the mucous membranes of females. It also changes body odor and other sexual cues, thereby reducing sexual behavior to near zero.

Because we disrupt our circadian rhythms (and those of our domestic animals) with artificial light, modern humans (and their pets) can breed anytime, and scientists used to believe that human reproduction was no longer under melatonin�s influence.  No way!  Inuit women, who live in the traditional way, stop menstruating when the dark winter months of the North greatly raise their melatonin.  The return of daylight in spring lowers melatonin, allowing the menstrual cycle to re-start and return them to fertility.