Talk:Melatonin

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Conflict in the "immune system" section

There seems to be a conflict in the Immune System section.

"The body of research is overwhelmingly supportive of the claim that melatonin interacts with the immune system.[19] Melatonin may help fight disease,[20] but its true role in disease treatment is unknown. There have been very few trials designed to judge the effectiveness of melatonin in disease treatment. Most existing data are based on very small, incomplete, clinical trials."

Anyone want to rewrite that for NPOV? -- R'nway [ T C ]

I smell some bias here! =

"Because it does not have to be prescribed, and since it is in the public domain, few doctors care to publicize its advantages"

...sounds like someone has an axe to grind

I went through the Ambien roller-coaster while combatting chronic insomnia last year. I asked three different doctors about melatonin, and they all recommended me not taking it, but sticking with them on the Ambien train. A fourth doctor actually recommended melatonin, showed me a couple of websites which cited most of the research and results, and when I began taking it, it was like night and day. After less than three days, my chronic insomnia was under control. It still took me a couple months to recover from the effects of chronic insomnia (memory loss, attention problems, etc.), but I'm still taking just .3 milligrams (300 micrograms) and am doing fine. Mugaliens 14:30, 22 July 2006 (UTC)

Scroll down to the bottom comments, there's a number of scientific studies done that show teste shrinkage in animals, as well as a decreased sex drive.Urbanriot 02:41, 22 January 2007 (UTC)

2nd link is now bad

http://www.cris.com/~nubrain/melatonin.html is 404

• It has apparently been removed.

barrier

I once read that oral intake of Melatonin doesn't work, as Melatonin doesn't go past the blood brain barrier. Isn't that true? Thanks, --Abdull 02:10, 31 May 2005 (UTC)

Oral administration of melatonin in mouse will result in higher levels of both circulating melatonin and brain melatonin, producing up to a fourfold increase, depending on animal age: Lahiri DK, Chen D, Ge YW, Bondy SC, Sharman EH. Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortex. J Pineal Res. 2004 May;36(4):224-31.

Dogface 15:52, 15 July 2005 (UTC)

The bioavailability of orally-administered melatonin is approximately 50%, and yes, melatonin does cross the blood-brain barrier. Most tests of melatonin that support its claimed effects were done with orally-administered doses. Mugaliens 14:31, 22 July 2006 (UTC)

The bioavailability of orally-administered melatonin is significantly less than 50% judging by the review of evidence by Tan et al. 2007. The authors calculate a mean bioavailability of 18.9%, 17.7 folds of difference, by concatenating the results of four studies in humans. [1] Mnc4t 16:33, 13 February 2007 (UTC)

Nobody knows what dosages to take

Melatonin

Claims, Benefits: Promotes sleep, counters jet lag, improves sex life, slows aging, etc.

Bottom Line: This human hormone may help promote sleep, but the evidence is still not definite. The other claims are unproven. No serious side effects have been reported, but long-term effects are unknown. Hormones are powerful substances and can produce unexpected results, so we don't recommend melatonin.

Full Article, Wellness Letter, May 2000:

Melatonin: Questions, Facts, Mysteries

Look on any website selling supplements or in any health-food catalogue, and you'll find melatonin recommended for insomnia, jet lag, arthritis, stress, alcoholism, migraine, and the signs and symptoms of aging and menopause—along with assertions that it staves off heart disease and cancer. Some people recommend "melatonin replacement therapy" for all postmenopausal women. But now that scientific research is catching up with melatonin mania, you may want to proceed with caution.

Melatonin is a human hormone produced deep in the brain by the pineal gland, dubbed "the seat of the soul" by philosophers in ages past. Discovered about 40 years ago, melatonin has been called the "darkness" hormone. Production rises at night, falls by day, and affects our internal body clock and sleep cycles. Melatonin has been assumed, logically enough, to have some use as a sleeping pill. Here are some questions, facts, and mysteries.

Does melatonin production decline with age?

The answer, until recently, was thought to be yes. But a new study at the Harvard Medical School of healthy people taking no medications or drugs found no differences in melatonin levels between the young and old. In earlier studies medications such as aspirin taken by older people may have suppressed melatonin levels. Melatonin levels may vary naturally in different groups; age does not seem to be the factor. Different people have different levels, and levels vary according to time of day.

(Although the Harvard Medical School trial may have been accurate, in that melatonin doesn't change with age. That the medications older adults take decrease melatonin, and therfore effected the older studies. It should be noted that most people over a certain age in developed countries take those medications, and therefore have reduced melatonin as they get older, so the study was accurate for industrilized society on an average.) 68.210.132.212 02:45, 25 April 2006 (UTC)

Bottom line: If your body already produces enough melatonin, taking additional doses may not be advisable. No one knows what the long-term effect might be. And it's difficult to determine what "enough" is.

Is melatonin an effective sleeping pill?

Most scientists agree that melatonin helps people fall asleep faster, but it may not help them stay asleep. Like benzodiazepines (such as Valium or Halcion), often prescribed as sleeping pills, melatonin can produce a "hangover" and drowsiness the next day. Long-term safety is still a question. It's true, as one researcher puts it, that "no catastrophes have been related to its use" (such as the outbreak of severe illness caused by a similar "natural" substance, tryptophan, once sold as a sleeping pill). Melatonin is being heavily marketed as a sleeping pill, particularly for older people, but nobody knows if the dosages listed on labels are accurate or if the products are pure. Good clinical trials have never been done on melatonin treatment for insomnia.

Bottom line: If you need a sleeping pill, talk to your doctor. No known sleeping pill has proven safe and effective for more than short-term use.

Does melatonin alleviate jet lag?

Thousands take it for this purpose, but the benefits have never been clear. Various dosages of melatonin have been used in studies, making comparisons difficult. "Jet lag" itself is hard to measure. As reported recently in the American Journal of Psychiatry, a team of researchers devised a scale for measuring symptoms, and a group of Norwegian physicians flying between Oslo and New York were recruited as subjects. Melatonin showed no benefit against jet lag. If you're flying east, exposing yourself to sunlight the next morning is a pretty good treatment—most purveyors of melatonin suggest this, in addition to the pills. It's possible, though, that light is more effective than melatonin. You might be just as well off without the pills. Or maybe light works with the pills. Nobody knows.

Bottom line: The jury is still out on melatonin and jet lag.

Is melatonin replacement therapy justifiable for all postmenopausal women?

No. Some researchers think low melatonin levels cause menopausal symptoms, but they may be wrong. HRT (hormone replacement therapy) has been studied much more extensively than melatonin, but no one recommends it for all postmenopausal women.

Bottom line: Hormones are powerful substances that, even in small doses, can produce unexpected and unwanted results.

Is melatonin an antioxidant, and thus a protector against aging and chronic diseases?

A recent review of studies by researchers at Louisiana State University confirms that it is indeed a powerful antioxidant. But nobody knows what this means. Until we learn more, "the full potential benefits of melatonin must remain something of a mystery," these researchers concluded.

Last words: If you are taking, or thinking of taking, melatonin, talk to a physician—and one who's not selling melatonin. Having your levels measured won't tell you anything, since levels vary from person to person and from hour to hour. Chronic use of melatonin supplements may suppress the body's own production of the hormone. Nobody knows what might happen if you have high natural levels and take a supplement on top of that. Melatonin can interact with other hormones, which is why, in part, pregnant women and children should never take it. Such drugs as aspirin, beta blockers, and tranquilizers can affect melatonin levels. Finally, nobody knows what dosages to take. Products are not standardized. Thus, you really don't know what you're swallowing.

As a general rule, when people self medicate, they will keep uping the dose until they feel something, and if it feels good, they will keep going until it doesn't feel good. Several studies have said there is little or no toxic effect, even from doses as high as 6 grams, (600 times the natural amount) In hope that melatonin may be good for people who suffer from certain disorders (such as chronic insomnia) I fear that taking the high levels that are occuring in society will cause an undesired side effect of which the blame will reside on the hormone, instead of the level dosage. "The future is uncertain..." 68.210.132.212 02:59, 25 April 2006 (UTC)

6 grams an extraordinary amount of melatonin to be given - actually tens of thousands times natural daily production of melatonin according to the data I have seen. However one might expect levels to fall by a factor of more than 10000 in 14 half-lives which is about 8 hours (although I suspect the half life might be somewhat increased for very high doses). With regard to a point made by the previous poster, the empirical evidence is that melatonin supplementation does not suppress production of melatonin by the pineal, contrary to what some people guessed. Also, supplementary levels are generally much higher than natural levels (for a short time), so the addition of the two is of very little significance. The safety record of melatonin is virtually unblemished, by contrast with many drugs that are widely used. Elroch 20:33, 25 April 2006 (UTC)

Several studies have shown that the benefits for the most commonly-cited effects are achieved at dosages between .1 and .5 milligrams (100 to 500 micrograms), and that increasing this beyond that level has little, if any, measured effect. Furthermore, several other studies have shown that dosages higher than 3 milligrams lead to significant increases in the reported side effects. In response, one company markets 300 microgram (.3 milligram) tablets, which I use myself. Although I'm a 210-lb man, this "tiny" dosage works very well. Mugaliens 14:25, 22 July 2006 (UTC)

"...does not have to be prescribed"

Actually in most Commonwealth countries Melatonin must be prescribed by a doctor. Article should be edited to reflect a global viewpoint.

in Poland it is possible to buy melatonine without prescription, it costs about €5 for 30 tbl. 5 mg. Anyone can buy it by internet too: http://vena-vita.pl/produkty,nazwa,melatonina - see ?! - and because Poland is an EU member so i conclude that similar regulations is in many other EU-countries also. pwjbbb 01:09, 13 June 2007 (UTC)

"Melatonin taken in combination with MAOIs can lead to overdose..."

"Melatonin taken in combination with monoamine oxidase inhibitors (MAOIs) can lead to overdose because MAOIs inhibit the breakdown of melatonin by the body." Overdose of what? Too much sleepy-sleepy, or too much MAOI? Melatonin products bear consult physician counter-indications for those taking MAOIs, without explanation. -SM 13:48, 7 December 2005 (UTC)

This is overdose of melatonin (since melatonin will not be broken down and removed from the body). Melatonin overdose isn't really dangerous; it won't cause the hypertensive crisis typical of MAOI drug interactions; nor is it very likely to occur (the LD₅₀ is measured in grams per kilogram body mass, while melatonin tablets are sold at less than 10 milligrams each); but it's worth keeping in mind. ‣ᓛᖁ♀ᑐ 14:30, 7 December 2005 (UTC)

Since melatonin is a key ingredient in the production of serotonin, and SSRI (selective serotonin reuptake inhibitors) do not mix with MAOs as it will lead to excessively high levels of serotonin in the brain, I believe, if I'm not mistaken, than MAOs and melatonin is a bad combination because it, too, will lead to excessively high levels of serotonin. It may also be true that MAOs block melatonin metabolism. Mugaliens 14:21, 22 July 2006 (UTC)

Melatonin is not a key ingredient in the production of serotonin and melatonin is not contraindicated by SSRIs.

Do we have a source for this interaction? NIH doesn't seem to say anything about it. I'm not disputing it (don't know the biochemistry involved and it seems plausible enough) but a reference would be nice for the sake of completeness (and verifiability etc). I'd find one myself, but I'm too tired (appropriately enough!) BertieB 02:53, 15 December 2006 (UTC)

It is easy to verify with a literature search that serotonin is a precursor to melatonin, but the reverse conversion does not occur in the species studied (including humans). Therefore even large amounts of melatonin would not be expected to lead to high serotonin levels. 82.21.244.172 01:15, 29 January 2007 (UTC)

Basic chemistry thinking: if serotonin is a precursor to melatonin and you add melatonin from outside, then less serotonin is used up to produce melatonin and thus the serotonin level must go up. In other words serotonin is expected to go up, not because outside melatonin converts to serotonin - it doesn't - but because less serotonin is used up in making melatonin Drirpeter 19:55, 1 August 2007 (UTC)

Questionable reliability of reference

A reference has recently been added to an article "Harms from a pseudo-cure-all" by the late Dr. Victor Herbert. The sensational statements in his article set off alarm bells, and a search immediately uncovered material like this response by the author of a article relating to a study on Vitamin C from which Dr. Herbert was stated to have made to be a large number of false inferences. This alone makes me feel very uncomfortable relying on Dr. Herbert as a secondary source. It seems essential that Dr. Herbert's statements be replaced by ones referring to primary or balanced sources.

I am not sure how much can be inferred for humans from the effects of injecting large doses of melatonin into minah birds. As I understand it, the many studies relating to mammals whose genetic makeup is much closer to that of humans are generally considered to carry more weight as evidence for what might happen in humans. Also the current last sentence does not make sense: it is unquestionable that melatonin has several biochemical roles.Elroch 23:35, 17 February 2006 (UTC)

Elroch would do well to cite a better rebuttal to the Herbert's citation (if there is any scientific debate about the reliablity of Herbert's citation) than to cite an instance in which James E. Enstrom a PhD whose research funded by the tobacco industry was widely discreditedrebutted Victor Herbert MD JD on an unrelated matter pertaining to Vitamin C and not to melatonin. [2][3]Sinclarian 03:21, 4 March 2006 (UTC)

Interesting links, though perhaps moving from vitamin C to tobacco (which I detest) is drifting further off the point. I see that Enstrom is now working for the Jonsson Comprehensive Cancer Center at UCLA, which has an impressive record.

Despite Victor Herbert's long and prolific career, there is always a risk of throwing out the baby with the bath water when witch-hunting (please excuse the mixed metaphor). Herbert's article relating to melatonin gives an imbalanced view of research on melatonin and makes unwarranted generalisations.

1.Herbert refers to a "maximum demonstrable benefit" from melatonin which is unscientific without specifying the type of benefit desired (improved night's sleep or reduction of free radical damage to mitochondrial DNA, for example).

2.Herbert makes an unwarranted generalisation that "Doses above physiologic levels of almost every supplement prove more harmful than helpful in the long run". It is not scientific to generalise from one substance to another, and there is increasing laboratory and epidemiological evidence that for several supplements relatively high levels are beneficial. The statement is also, of course, not relevant to low dose supplementation.

3.There is a prediction at the end of Herbert's article, referring to the L-tryptophan affair - "One can reasonably predict that sooner or later similar problems will occur with melatonin supplements". This seems to be an inference along the lines that Plane A crashed. B is a plane. Therefore B will crash. Is this a scientific statement or doom-mongering?

Role of melatonin in the endocrine system

There seems little doubt that melatonin has an influence on different components of the endocrine system, but the literature provides viewpoints that are difficult to reconcile, and difficult to summarise in a short article. The edit replacing one long-standing unsourced statement that melatonin was the "master hormone" with another that it was not was an interesting anonymous viewpoint, but more information on the facts are needed, since melatonin is known to influence HGH, FSH, LH, the thymus gland etc. Elroch 01:30, 5 May 2006 (UTC)

This article is a big advert.

This article reads like literature on melatonin I have been given by drugs companies. It biased and therefor unreliable as an objective description of the substance. It could do with being reverted back to an earlier version, with less biased and extraneous information. (added by 84.64.155.79 on 7 August 2006

Please state specific examples of why you believe the article to be "biased and unreliable". The majority of the article states facts taken from peer-reviewed articles in scientific journals. 82.17.206.121 01:56, 10 October 2006 (UTC)

How about arguments that long term usage is completely untested and not recommended as per bottle labels and doctors? Or how about the suggestion that melatonin can reduce the size of testes of animals, as well as their sex drive? (http://www.usc.edu/health/usccare/services/health_tips/melatonin.html). Or how about this PDF detailing that melatonin in hamsters also caused teste shrinkage? http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3210136&dopt=Abstract . There's some serious bias in this article and it can be very misleading.Urbanriot 02:38, 22 January 2007 (UTC)

What is Urbanriot's concern? The article gives a simple account of the way that seasonal breeders are affected by melatonin, and actually gives a good reference for the example of hamsters. Clearly this will be useful information to anyone thinking of giving melatonin to their hamster :-). On Urbanriot's first (purely speculative) point, my own opinion, based on thousands of sources, is that a lack of melatonin may be dangerous for the health as endogenous levels decline. There is growing evidence for the dangers of low melatonin levels in diseases which are common in old age. 82.21.244.172 00:51, 29 January 2007 (UTC)

Crazy Dreams

I was a little surprised the word 'dream' didn't show up in the article. Everyone I know that's tried Melatonin (myself included) loved it at first, but if you take it every night, you'll soon start having extremely intense and bizarre dreams, often nightmares. Everyone I know that tried Melatonin stopped taking it for this reason. Perhaps it's OK in moderation and in smaller doses (like half a pill perhaps).

I agree, it does intensify the dreams, but I wouldn't say it gives you nightmares. I would assume that if you are getting nightmares while sleeping off of melatonin pills, they are probably related to the cause of your insomnia. What I mean is, something scary is happening in your life that is keeping you up, and that same something is probably causing your melatonin nightmares. When I tried a melatonin pill, even though I knew I would get to sleep just fine anyway, I had more intense dreams, but they were rather boring.--Moeburn 15:04, 22 November 2006 (UTC)

Combine melatonin usage with 5-HTP and you'll have some seriously lucid dreams. I discovered this accidentally and am able to reproduce it.Urbanriot 02:42, 22 January 2007 (UTC)

I agree that you can get nightmares with melatonin - I had that happen to me as well. It definitely intensifies dreams, but for people who already have sleeping problems to begin with, it will cause nightmares. —The preceding unsigned comment was added by 207.6.229.178 (talk) 16:25, 17 February 2007 (UTC).

I've created "Role in dreaming" section. You are welcome to expand, adding proper citations. --BorgQueen 04:16, 27 February 2007 (UTC)

CJD Transmission vector

I have a couple of CJD references that could be added:

• FDA Important alert: http://www.fda.gov/ora/fiars/ora_import_ia1704.html
• Transcript: http://www.fda.gov/ohrms/dockets/AC/01/transcripts/3681t2.rtf

I have not found any documented cases of this actually happening. Fri666 00:33, 3 April 2007 (UTC)

Legallity in australia

is it OTC in australia? —The preceding unsigned comment was added by 202.161.6.175 (talk) 08:42, 15 May 2007 (UTC).

Structure innacuracy?

I believe the three dimensional structural image on this page is innacurate. The 2 and 3 carbons are double bonded and thus should be sp2 hybridized. They are shown here as being sp3 hybridized, having extra hydrogen atoms. I'm confident in this and feel it should be corrected. Ccroberts 03:07, 23 May 2007 (UTC)

Yes, the whole indole ring would best be displayed as aromatic. I'll let the image creator know. Fvasconcellos (t·c) 11:16, 23 May 2007 (UTC)

Never mind, I see you've done so already; let's give him a couple of days to act on it, meanwhile I've removed the image. Fvasconcellos (t·c) 11:18, 23 May 2007 (UTC)

It's fixed now. Thanks for letting me know. I'm going back and checking all my indolines now... Sbrools ^{(talk . contribs)} 16:27, 26 May 2007 (UTC)

Redox recycling

"Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation."

Vitamin C first acts as an anti-oxidant before acting as a pro-oxidant.

I suggest that ", counterintuitively promoting free radical formation" be deleted.

Michael H 34 01:05, 22 June 2007 (UTC) Michael H 34

Here's my suggested edit:

The oxidized form of other anti-oxidants (such as vitamin C) may act as pro-oxidants through redox cycling. For example, although free radicals are reduced when vitamin C is oxidized, free radicals may be formed again when the oxidized form of vitamin C is reduced through redox recycling.

(If there exists a mechanism for redox recycling of vitamin C by enzymes, this should be mentioned.)

Michael H 34 21:23, 22 June 2007 (UTC) Michael H 34

Confusing Sentence

Melatonin, being two endogenous hallucinogenic indoles like N,N-dimethyltryptamine (DMT), is likely to be research priorities in this reemerging field of psychiatry.

What's that meant to mean? — 63.249.110.32 06:47, 23 August 2007 (UTC)