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Sleepdex - Resources for Better Sleep

Melatonin

Melatonin is a hormone produced by the pineal gland, a small gland in the brain, that plays a part in the body's sleep cycles. The brain makes this neurohormone from the amino acid tryptophan.

In humans and other diurnal animal species, melatonin secretion happens during normal sleep hours, in contrast to nocturnal animals which are at the peak of their activity while producing melatonin. Melatonin is sometimes called "the hormone of the night." The melatonin cycle is roughly the opposite of the body temperature cycle. (More on thermoregulation.) At 4 am, the temperature is at its lowest and the melatonin level is at its highest.

Very small amounts of melatonin are found in foods although how much diet contributes to melatonin levels in the body is not clear. How it actually causes sleepiness is unknown as are the details of its metabolism and excretion from the body.

Melatonin has been used to adjust the circadian system in people with jetlag, shiftwork, delayed sleep phase syndrome, and some sleep problems of the elderly. No long-term safety data exist, and the optimum dose and formulation for any application remains to be clarified.

An American Academy of Sleep Medicine task force issued a guideline in 2007 for doctors treating blind patients with sleep disorders, and recommended consideration of timed melatonin administration for people with is indicated for shift-work disorder, jet lag, delayed sleep phase disorder, and free-running disorder. This is because blind people do not respond to the zeitgebers of daylight that sighted people can see.

Even in sighted people melatonin has been used in treatment of jet lag, shift work sleep disorder, DSPS, ASPS, free-running sleep disorder, and ISWRD.

Melatonin was discovered as a neurohormone in 1958.  (It was known as a chemical decades earlier.) Melatonin is now sold in pill form (like vitamin supplements) in retail stores. As with viatimins, the manufacture and sales marketing of melatonin is not regulated by the FDA or by the regulatory agencies of the various states. Melatonin itself has few side effects, but you don't really know what else is in the pill. Further dosages may be different from what is printed on the label (a common problem with nutritional supplements) Most doctors do not prescribe or recommend melatonin supplements.

Incredible as this sounds, there is no consensus agreement on the half-life of melatonin in the body.  (Believe us, if you know anything about pharmacology, that is incredible.)  The government’s Agency for Healthcare Research and Quality quotes
(http://www.ahrq.gov/clinic/epcsums/melatsum.htm)  a half-life between 30 minutes and 2 hours and further says "the time required to reach peak values ranged from 0.25h to 13h".  This is an atonishingly wide range, based probably on the different forumations of the melatonin supplements.

This is another example of how the prescription drugs approval process generates useful data for everyone – data that can be used even after the developer loses patent protection.  It is difficult to gauge the quality and efficacy of melatonin on the market.

High melatonin levels (either natural or from taking melatonin tablets) are associated with the type of physiological activity seen before bedtime - sleepiness, lower core temperature, and loss of body heat. This suggests that melatonin pills can make people sleep better or longer. They are not as strong as prescription sleep aids, however, and the US Food and Drug Administration has never actually approved melatonin for circadian rhythm sleep disorders.

A 2005 meta-analysis (an analysis of other studies on melatonin) concluded that melatonin treatment reduces sleep onset latency, increased sleep efficiency, and increased total sleep duration. However, the average increase in sleep duration was only 13 minutes. The Agency for Healthcare Research and Quality conduced a meta-analysis and said there was a "substantial amount of heterogeneity across studies of melatonin." Substantial amount of heterogeneity meaning there are no clear answers.

Doubts about melatonin.

Another meta-analysis showed that only a small dose of melatonin (about 0.3 milligrams) is necessary for a restful effect. However, that commercially available melatonin pills contain 10 times the effective amount.

The government’s Medline - http://www.nlm.nih.gov/medlineplus/druginfo/natural/940.html - lists melatonin as “likely safe” although cautions are given that is possibly unsafe for pregnant women and children.  Medline also cautions against use by people with hypertension, diabetes, depression, and seizures.

Melatonin agonists - chemicals that more or less mimic melatonin in the body - are under development for treatment for insomnia. Melatonin has also been found to be connected to brown adipose tissue. It may elevate the metabolic activity of adipocytes, which is of interest to obesity researchers.

Some blind people use melatonin to help them sleep on the same cycle as sighted people (who have visual sunlight cues to adjust their cycles). It seems to work in about half of people who try it. Blind teens are advised to not use melatonin because of concerns that it might affect puberty. Large amounts of melatonin are known to inhibit ovulation.

There is some recent interest in use of melatonin for treatment of tinnitus.

Taking melatonin

Like prescription and antihistamine sleeping pills, melatonin is taken shortly before the person wants to go to sleep.  The user does not feel an onslaught of sleepiness; it’s a subtle change.  Taking the pill about an hour before bedtime seems to work.  For instance, if you have flown three time zones East and now want to go to sleep three hours earlier than your body is used to, take the melatonin supplement an hour before bed.

Where does the melatonin come from?

The packaging might say where it comes from, but probably not.  Some melatonin is derived from animal sources, and it can also be synthesized.

The chemical name for melatonin is N-acetyl-5-methoxytryptamine. (CAS 73-31-4) Here's the structure, for chemistry buffs:

chemical structure of melatonin

Sleeping with the lights on causes cancer!

No, but there was a headline a few years ago saying "Sleeping with lights on might trigger cancer through melatonin suppression." Sleeping with the lights on lowers the amount of melatonin in the bloodstream. Melatonin is an antioxidant and so might contribute to a lower risk of cancer. It also inhibits the growth of tumors. And there are overall health benefits to going through a full circadian cycle, which includes a period of darkness. So there might be some benefit to sleep without the lights on.

A bit of an exaggeration to say sleeping with the lights on "triggers" cancer. There has been concern that the shift work leads to higher rates of cancer. However an epidemiological study at Ohio State University found no link.

Dreams

There are user reports that melatonin causes vivid dreams. Actually, all sleep aids appear to some users to produce more vivid dreams. What is most likely happening is that the drug modifies the sleep cycle so the person emerges from REM sleep (when dreams are most vivid) to waking quickly – more quickly that when no drug is used. The user subjectively reports the drug as producing vivid dreams.

Melatonin and sleep in aging population.

Melatonin and Wine

Scientific Articles

Melatonin and its Agonists: An Update - British Journal of Psychiatry article from 2008

Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders

Melatonin and melatonergic drugs on sleep: possible mechanisms of action.

Read about valerian, an herb used to help people sleep.


It's interesting that he was a dermatologist and focued most of his research on pigment disorders. Melatonin is a pigment, of course, but it is mostly known for its role in the circadian cycle.

 

 

 

 

Antihistimines

Benzodiazepines

The Z-Drugs

 

Other Drugs

Melatonin Agonists

Orexin Antagonists

Most Prescribed Sleeping Pills

Barbituates

Related

Taking Sleeping Pills

Z-Drug Zombies

Multiple Sleep Latency Test

Prescription Drugs and Their Effect on Sleep

Non-Drug Approaches

 

"Sleep hath seized me wholly"

(William Shakespeare – Cymebline)

 

 sleeper with head in hand