Talk:Melatonin/Archive 1

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, and 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 testis shrinkage in animals, as well as a decreased sex drive.Urbanriot 02:41, 22 January 2007 (UTC)

Very true and a good thing it is, too. Neither the species nor the individuals have anything to gain having young in a season when they're likely to starve or freeze to death by the age of 2 days. Humans or our ancestors were undoubtedly more seasonal animals in the past than we are now. Hordaland 18:50, 9 November 2007 (UTC)

It's North American bias also, melatonin is prescribed as an unlicensed medication to treat sleep disorders in the UK Waydee (talk) 18:07, 8 October 2008 (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.

Throwing in a comment in between, here. That study about the group of doctors flying Oslo - New York - Oslo has been criticized and essentially debunked. They were only in the USA for a few days and thus weren't entirely acclimatized before their return home. It wasn't a fair test of "flying east". --Hordaland (talk) 00:27, 13 October 2008 (UTC)

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)

So, bottom line: numerous studies have shown no toxicity, and no conclusive research supports anecdotal claims of improved sleep or other benefits. Sounds like something people ought to be able to try for themselves, no? If it helps them sleep or handle jet lag, good for them. The key point would seem to be the evidence that the hormone isn't toxic except perhaps when taken at very high dosages, or continually for a very long time. But from the tone of this section, that doesn't seem to be the point the author is trying to make.74.192.15.25 (talk) 05:07, 17 May 2008 (UTC)

"From the tone of this section..." Which section are you referring to: the article, the Safety section of the article, or this section of the Discussion page? Which "the author"?

In any case, I've just added some material to the article's Safety section which might address some of your concerns.

And, in any case, I agree that almost anyone who likes, probably can experiment. The timing is way more important than the amount, so playing around with a half a mg/day or so should be fine. I wouldn't, however, recommend it to anyone trying real hard to get pregnant, nor for kids, without involving a competent doctor. I've taken melatonin daily for over 4 years and (look at me!) I'm still healthy and sane, I think. --Hordaland (talk) 11:04, 17 May 2008 (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)

In Norway, which is not an EU country, melatonin is available only on the 2nd most restrictive type of prescription. (The most restrictive requires the patient to meet at the doctor's office or the pharmacy to get the day's dose.) To get melatonin, one has to have a specialist fill out an application, annually, with the patient's name and diagnosis on it. It takes a few days for the application to go through and for the pharmacy to order the melatonin. Over-the-counter it is NOT. Hordaland 14:09, 2 November 2007 (UTC)

Melatonin is OTC in Estonia too. One can choose between 2mg (30 pills for 5 euros) and 3mg (60 pills for 12 euros) pills. Kristjan.

That's interesting. It's strange that the rules vary so widely from country to country. I don't suppose anyone has the complete list. The stuff is a hormone, so I'd think there should be some controll....

--Hordaland (talk) 15:53, 16 December 2007 (UTC)

I live in Australia and I work in two health food stores and I can pick it off of the shelves and sell it to someone, Its not agaisnt the law in Aus to buy it without a Doc's note -Wolviechickie 2/2/08 —Preceding unsigned comment added by 202.81.69.153 (talk) 22:46, 1 February 2008 (UTC)

Thanks for explaining your edit! The purists would call this Original Research, but it's effective sometimes. --Hordaland (talk) 02:16, 2 February 2008 (UTC)

It would be interesting to know which state of Australia the above poster lives in. I'm from New Zealand and melatonin is prescription-only here. When I visited the state of Victoria (Australia) in January 2008 I was told by a health-food store that melatonin is also prescription-only there - in Victoria at any rate. I know what you may find on the shelves in New Zealand and Victoria is "homeopathic" melatonin rather than the "real" stuff.(203.109.212.84 (talk) 11:41, 21 February 2008 (UTC)) Citizen Kiwi, 22 February 2008

One would think that someone, an association of melatonin producing labs, for instance, would have a definitive list of where melatonin is:

1. OTC,
2. by regular prescription,
3. by restrictive prescription.

A friend on the east coast of Australia called a couple of chemists for me, just out of curiosity. One said it's OTC, the other said it's totally unavailable. So I gave up.

You've probably hit on (part of) the explanation. If "homeopathic" melatonin is 99.99% water, the authorities may not bother about it. --Hordaland (talk) 13:58, 21 February 2008 (UTC)

I work in Pharmacy at a hospital here in the UK, Melatonin is "unlicensed" so is legal to possess without a prescription but cannot be sold/given away OTC without one. I believe it is the unlicensed status that allows for its sale online, or perhaps it is sent from an EU country that allows its OTC sale - I am unsure. It's unlicensed status does not restrict us in any way from supplying or obtaining it and many doctors prescribe it. There is a single extended release formulation that is officially licensed but doesn't seem to be very popular, we do not stock it. Waydee (talk) 18:11, 8 October 2008 (UTC)

Thanks for interesting input. That can be added to the article if there's official info to that effect (preferably online). Over the years my Norwegian (not EU) pharmacy has acquired five different brands for me, from as many US states; 'twouldn't surprise me if your suppliers are American, too? They said what brand they got depended on what their supplier chose to import. Finally there was one brand I preferred to all the others and after my sleep specialist wrote a prescription for exactly that, that's what I get. (It's Natrol 60 ml from Chatsworth California. Though relatively expensive, it works and is convenient to use, not time release, not sublingual. Sounds like I'm writing an ad here.)--Hordaland (talk) 07:21, 9 October 2008 (UTC)

I'll certainly look for the relevant information online, I'm sure it won't be too hard to find. The Melatonin we currently dispense on prescription is the "Life Extension" brand in 1mg, 3mg and 10mg/60 capsules per bottle, I believe this is manufactured in the US, I'll have a closer look at the packaging when I can. I do not believe however that the NHS has a preferred supplier, they probably just buy it based on purity/value guarantee. I'm assuming it is of the "pharmaceutical" grade in that it is produced synthetically and not obtained from animal tissue. We cannot offer patients a specific brand. I will have to check this tomorrow but I believe the cost to the NHS is in the region of £3 for a bottle of 3mg capsules.

As an aside, we have found very few community pharmacies are willing to supply it - a lot of our patients are referred to our hospital pharmacy by their GPs to obtain it or have us mail their prescriptions to them because they are unable to get it locally. This is likely a result of it's unlicensed status, community pharmacies are probably under no obligation to supply it. Do you encounter a similar issue in Norway? or does the drug have official licensed status there? 81.79.191.187 (talk) 21:33, 12 October 2008 (UTC)

Hello, again. (Assuming you are Waydee and just not logged in.) I'm not sure of the terminology: "unlicensed" etc. A prescription for Melatonin in Norway is på registreringsfritak, directly translated: "on exception from registration". As I mentioned above, the prescription takes the form of an application (in triplicate!) to the authorities and it contains the patient's name, ID, address and diagnosis. Getting Melatonin used to be more time-consuming, as the annual application had to be cleared by the authorities before the pharmacy could obtain and release the medication. Now the pharmacy (my pharmacy, at least, which until recently was Alliance and now is 50px ) fills the prescription first and sends in the application afterwards.

Does that sound like what's meant by "unlicensed"?

I've heard before, from a patient in Scotland, that Melatonin can "only" be had from a hospital pharmacy.

Another patient, this one in Australia, uses a liquid melatonin and wrote recently: "I have to get it specially made up for me at a compounding pharmacy as it is not available pre-packaged from a normal pharmacy." --Hordaland (talk) 01:01, 13 October 2008 (UTC)

Nobody's mentioned Asia, so I'll make a small piece of input here on the situation in South Korea. (I'm a Westerner who's currently living there.) My local doctor claimed it's not available in Korea at all, for whatever reason. It wasn't listed on his pharmaceutical database, and in fact he appeared completely unfamiliar with it. Muzilon (talk) 08:52, 13 October 2008 (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. ‣ᓛᖁᑐ 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)

Good thinking but no. Melatonin production takes up a small portion of serotonin removal, MAO is the main remover of serotonin and exogenous melatonin does not affect endegenous production. —Preceding unsigned comment added by 202.161.1.185 (talk) 11:18, 4 November 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 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)

It's similar to psychedelic tryptamines, maybe peple just sleep though the psychedelic effects as dreams. is there a melatonin recptor antagonist? take them toghether and see —Preceding unsigned comment added by The Right Honourable (talk • contribs) 09:23, 18 October 2007 (UTC)

I read that the average 20 year old produces 75 micrograms of melatonin per day. Because I am 50 and don't sleep well, I try to take only 100 micrograms -- or possibly 200 if I really want to sleep a long time. I don't get nightmares with this amount. I can't imagine why anyone would be taking 1 or 3 miligrams, which is the amount in many popular supplements. This is way, way too much. Obviously, that's going to cause nightmares. —Preceding unsigned comment added by 71.190.204.90 (talk) 21:33, 31 December 2007 (UTC)

I realise that I'm responding to an old argument here, but I've been taking 3 milligrams of melatonin for about a year now, prescribed by my doctor. I definitely haven't seen a difference in my dreaming patterns, rather, I'm having less dreams at all. To say that it causes intenser dreams, especially in such high doses, seems a big assumption. (Then again, I am actually taking it to counter an autism-related deficiency.) arienh4^(Talk) 23:21, 16 January 2010 (UTC)

This page is for discussing the article, not personal experiences. (Nothing personal Arienh4! I've used melatonin daily for 5+ years, and it has little or no effect on my dreaming.) I'm archiving and am putting this section in the archive, even though the last comment is dated yesterday. - Hordaland (talk) 14:58, 17 January 2010 (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)

That sentence has been bugging me, too. Since no one has answered the question nor improved the sentence, I've shortened it. Don't know if it's correct, but it reads OK now. Hordaland 19:19, 9 November 2007 (UTC)

Uh, don't do that, guessing's a sure way to get from incomprehensible to incorrect in half of the cases. Anyways, if there's no source given and it cannot be verified to be correct from reliable sources (and the wishy-washy phrasing in this case suggests it is someone made up anyways), the sentence should just go altogether. Removing any made-up stuff doesn't hurt the article, it improves it. 129.105.14.148 (talk) 04:32, 12 March 2008 (UTC)

Alpha methyl melatonin

would this bind to the melatonin receptor, and would it be long lasting? —Preceding unsigned comment added by The Right Honourable (talk • contribs) 04:47, August 26, 2007 (UTC)

melatonin edit that i made

I currently made an edit, warning people about using melatonin too freely, and how it can cause hormonal fluctuations, i forgot to mention my source which was directly from melatonin.com.

Blc341 06:13, 27 August 2007 (UTC)

I see no reason to consider melatonin.com a reliable source! On the contrary, WorldWide Labs is very commercial. (That is not to say that there is anything wrong, or right, with your edit.) Hordaland 19:08, 8 November 2007 (UTC)

Dangerous side effects

I've removed this section to the talk as it has some serious problems that are best discussed before such information is included in the article. Let me be clear that I'm no apologist for the drug/supplement industry. Here's the removed text:

Dangerous Side Effects

Asthma

A study indicates that patients with nocturnal asthma may experience adverse effects from melatonin supplements. According to the study “Immunomodulatory Effects of Melatonin in Asthma”, even small amounts of supplemental melatonin worsen the symptoms of the inflammatory disease asthma by causing the body to release chemicals which provoke inflammation. The inflammatory chemicals include increased production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha.[E. Rand Sutherland, Richard J. Martin, Misoo C. Ellison and Monica Kraft (2002). "Immunomodulatory Effects of Melatonin in Asthma". American Journal of Respiratory and Critical Care Medicine. 166: 1055–1061. PMID 12379548.{{cite journal}}: CS1 maint: multiple names: authors list (link)]

Arthritis

An animal study indicates that there may be an association between melatonin and increased severity of arthritis in certain individuals. The scientific article titled "The pineal hormone melatonin exaggerates development of collagen-induced arthritis in mice." showed that mice who were injected with melatonin at day 1-10 developed more severe arthritis while those injected at onset did not differ significantly from corresponding controls. The study's results support the hypothesis that the pineal gland can exaggerate the development of CIA via a high release of melatonin, probably via enhancement of T-cell priming.[Hansson I, Holmdahl R, Mattsson R. (1992). "The pineal hormone melatonin exaggerates development of collagen-induced arthritis in mice". Journal of Neuroimmunology. 39(1-2): 23–30. PMID 1619037.{{cite journal}}: CS1 maint: multiple names: authors list (link)]

Testis Size

An animal study indicates that there is an association between melatonin and reduced testis size in hamsters. The scientific article is titled "Effects of melatonin and 6-methoxybenzoxazolinone on photoperiodic control of testis size in adult male golden hamsters." In this study, testis widths were determined at 2-3 week intervals, and after 66-73 days testes were removed and weighed. The study found that melatonin significantly influenced testis size in each experiment.[Anderson KD, Nachman RJ, Turek FW. (1988). "Effects of melatonin and 6-methoxybenzoxazolinone on photoperiodic control of testis size in adult male golden hamsters". Journal of Pineal Research. 5(4): 351–65. PMID 3210136.{{cite journal}}: CS1 maint: multiple names: authors list (link)]

Looking at each in turn: The asthma paragraph cites a primary source. Wikipedia prefers secondary sources, for good reason. One needs an independent author to assess the clinical relevance of such findings, place the study in context (has it generated criticism), compare it to other studies, etc. This study measured the levels of chemicals in the blood of 23 subjects. This isn't a large-scale study and so one should not extrapolate the result to the population at large. It did not find that melatonin "worsen the symptoms" as the symptoms were not measured - only chemicals in the blood that are associated with an inflammatory response. The study concludes with:

The clinical relevance of these observations requires formal evaluation. Our results indicate that melatonin causes increased PBMC production of selected cytokines in vitro, a finding that may have clinical relevance in patients who use over-the-counter pharmaceutical preparations containing melatonin. Data about the number of people using melatonin are scarce, but millions of Americans are reported to use melatonin (32), and a proportion of these individuals presumably suffer from asthma. For these patients, avoidance of melatonin may be appropriate until further information about the clinical effect of melatonin in asthma becomes available.

The authors accept that "formal evaluation" is required before we can be sure of any clinical relevance. In other words, this study may have no "clinical relevance". If that is the only research to-date, then it is too early for an encyclopaedia (or indeed, a medical textbook) to claim melatonin may make asthma worse. The final sentence contains the study-author's tentative personal advice. Such a suggestion is written for the benefit of medically trained people who can weigh it against other factors and decide if they agree. This is why WP needs a secondary source. If, for example, some significant medical body (e.g. a national Asthma charity's medical board) now advises people with asthma to avoid melatonin supplements, then we can cite them.

The arthritis paragraph cites a study in "DBA/1 mice", a strain bred to be susceptible to collagen-induced arthritis and to low-grade spontaneous inflammatory arthritis. The study's aim was to investigate the role of pineal gland and its (natural) hormone melatonin. The mice were subjected to altered daylight/darkness as well as being injected with the hormone. I'm unable to read beyond the abstract, but can't imagine the article contains anything that might suggest an "association between melatonin and increased severity of arthritis in certain individuals". This is low-level basic research. Extrapolating the effects of a natural hormone on mutant mice kept in very artificial conditions to effects in normal humans, is not allowed.

The testis paragraph cites a study in golden hamsters. It is unclear from the abstract if testes size is reduced (only "influenced"). Another study (PMID 1179207) indicates that small amounts of melatonin "prevented testicular regression" (during v. short days) but atrophy occurred with large amounts. Both studies are interested in the effects of melatonin during daylight-altered conditions. I'm guessing this is all to do with animals turning randy during appropriate breeding seasons. Not something that is relevant to humans.

All these studies show the danger of reading basic research and reporting on it in an encyclopaedia. I don't belive any of these studies have clinical relevance and as such don't merit inclusion. I'm sure that melatonin supplementation can have adverse effects. It may be a natural hormone but, so is insulin and that can kill people! We need to base any "Adverse effects" section on reliable secondary sources. Colin°^Talk 08:52, 28 September 2007 (UTC)

I have very serious concerns about removing the dangerous side affects from this article. I am sure that you know that the public looks on the internet (especially Google) for information on pharmaceuticals and supplements. This article appears as #2 when searching the term "melatonin" on Google; this article is probably the primary source of information for anyone considering or already taking this supplement.

I have been seriously ill for over a year due to taking this supplement with severe chest congestion & exhaustion, especially at night. After numerous medical tests, I went on a personal quest to eliminate variables within my environment that I thought might be contributing to illness. My initial source of information was the Wikipedia article - but all it contained was gushy information that sounded like it came directly from the supplement industry. Several additional months of suffering and heart/lung stress ensued until I went back to Google and performed a more complex search for any ill affects caused by melatonin.

What I found was peer reviewed scientific articles (one of which I cited) that described my situation exactly. I immediately stopped taking the supplement, and my symptoms completely disappeared.

Why any administrator of this site should want to suppress potentially life threatening, scientifically validated and peer reviewed information from the public makes me seriously question that person's ethics, credentials, and prerogative. I don't know anything about the administrators, so I assume that they are blindly following the administrative rules for this site, but this is a serious health issue and Wikipedia should be consulting with medical ethicists to come up with a serious policy which ensures communication of research which may be indicative of harmful or dangerous side effects before they get their ass sued. Wikipedia's policy should be similar to the legal requirement to include potential dangerous side affects with prescription drugs.

IMHO, God G. —Preceding unsigned comment added by GodGnipael (talk • contribs) 20:39, 29 September 2007 (UTC)

GodGnipael, please read the Wikipedia:Medical disclaimer. It could not be clearer: "WIKIPEDIA DOES NOT GIVE MEDICAL ADVICE". I appreciate that Wikipedia articles are widely read and that we should ensure the article is balanced and not full of "gushy information" from the "supplement industry". But two wrongs don't make a right. There is a clear conflict of interest and an element of original research involved in your desire to tell the world about potential lung problems with melatonin. Wikipedia is not a soap box, no matter how well meaning you may be. The sources you have found, and the text based on them, simply do not contain enough evidence on which to claim a significant danger to health among human beings. If you find more compelling sources, please discuss them here.

I do not wish to start an edit war with you, so I won't be the next person to revert your restoration of this text. I shall seek further input from other editors. There are various ways we can resolve this dispute, simply restoring the text is not the best solution at this point. Colin°^Talk 21:50, 29 September 2007 (UTC)

POV pushing again removed from article. At very least totally inappropriate location to place it (ie in midst of discussing its natural physiological role and before medical artificial supplementation even been mentioned). The section, even if it were to be kept elsewhere in the article would need be termed "Side effects" as per standard term used in drug articles, or "Adverse effects" as per WP:MEDMOS#Drugs. Studies on levels of circulating chemicals is not proof of worsening of asthma, to do so would be synthesis of published material (see WP:NOR). Likewise experiment in an animal model is not proof it would cause arthritis in humans. Any genuine evidence (or reliable sources for possible concerns) already have a place in Melatonin#Safety section - no need create a new section at all.

PS repeated reverting against consensus is disruptive. GodGnipael, note WP:3RR is not a license to revert 3 times a day without consequences, even one revert may result in action. GodGnipael you have revert twice now today, and given comments on your talk page pointing out other relevant policies, you will be blocked if you revert again without obtaining consensus first here on talk page.David Ruben ^Talk 00:40, 30 September 2007 (UTC)

Obviously I can not and will not fight this. As I said, I think this is a gushy article which may endanger the public health by omitting important scientific studies.

I guess you can keep your SAFETY section which starts out with the sentence "Melatonin is practically nontoxic and exhibits almost no short-term side effects." In my opinion, as wonderful as Wikipedia is, its policy on supplements is a little scary and should be examined - even if its a general disclaimer.

What if the DANGEROUS SIDE EFFECTS section was retitled? I personally think its contents should be included somewhere in the article. As I write this, I am looking at the slip of paper which is included with a prescription. The slip I am looking at includes information such as Impairment of Fertility, Pregnancy, Nursing Mothers, Pediatric Use, Adverse Reactions, Overdosage. Maybe supplements such as melatonin should use a similar format?

Anyway, sorry for the reversions.

God G. —Preceding unsigned comment added by GodGnipael (talk • contribs) 02:09, 30 September 2007 (UTC)

"Obviously I can not and will not fight this"—don't worry, God G.; we appear to be on the same page here, but there's a certain way we should go about things. Ideally, we should rewrite and expand the Safety section with information from more reliable sources. These appear to be the best available published reviews of melatonin efficacy and safety. They are both freely available, and neither is cited in this article—there is an over-reliance on animal studies. Perhaps we could use these sources to make the page more comprehensive and neutral? Fvasconcellos (t·c) 15:10, 30 September 2007 (UTC)

Irony: On a bottle of melatonin capsules I read, "Caution: If you have asthma or an autoimmune disease, do not take melatonin." This isn't an FDA caution and I suspect the manufacturer is just covering his back. I note the above reviews only have data on the safety of short-term use and warn that the product is not available in the consistent form that might be expected if it was a high-quality pharmaceutical. I've nominated this as a candidate Wikipedia:WikiProject Pharmacology/Collaboration of the Week. Colin°^Talk 14:25, 1 October 2007 (UTC)

Yes, I couldn't find anything on long-term safety. This European PI (linked to in the article) can probably be used to write up the usual interactions/adverse effects as a start; we should find more literature. RxCOTW seems like a nice idea, if it makes the "cut" :) Fvasconcellos (t·c) 14:34, 1 October 2007 (UTC)

"Melatonin is practically nontoxic and exhibits almost no short-term side effects." I came across that too reading through the article. The rest of the information in those paragraphs and the segment looks alright, but the openers of the first two paragraphs read like unsubstantiated sunshine-and-lollipops claims to promote the drug. I'll probably never come across it again but it might be more objective if the above quote, and "Even though it is seen as a relatively safe, benign drug," were removed. 124.177.178.52 (talk) 15:48, 19 November 2007 (UTC)

(Moving out to the margin again - just because.) In my not-so-humble opinion a hormone should never have been released (by whom? by FDA? I've seen somewhere that it was released) as a dietary supplement. Myself, I'm diagnosed with delayed sleep phase syndrome which is one of a couple of conditions for which exogenous melatonin really is indicated. Started out 4 years ago at 3 mg, down to 1 mg, now 1/4 mg -- and they all work and work just as well. The timing is much, much more important than the dosage. My point? Just that the FDA should take responsibility! Hordaland 13:56, 2 November 2007 (UTC)

Based primarily on primary research

This articles needs to be extensively rewritten to be based on review articles.Doc James (talk · contribs · email) 14:23, 19 March 2011 (UTC)

If there are no relevant review articles available, we can't use them. Studies on certain subjects are sufficiently infrequent that reports of experimental outcomes, when reported in peer-reviewed publications, are as good as it gets. Articles can be written on the basis of review studies only for heavily researched topics for which literature reviews are meaningful - e.g. Global warming, etc. The primary/secondary source distinction here is less important than:

1. Insisting on reliable sources. An article accepted for publication in a journal of good repute by peer reviewers is reliable. A page on some professor's website is not.
2. Don't make any claims that aren't (semantically) present in the source. While it's often necessary to rewrite to avoid copyright violations, the meaning should be left intact, insofar as possible. No conclusions should be drawn that the references don't.

Unless you have some citations of review studies you'd like to see included, I see no reason to presume that they exist. I'm removing the tag. Chester Markel (talk) 06:36, 4 June 2011 (UTC)

in many aspects of a subject like this, where results about therapeutic use are very variable, reliance upon unselected primary papers is not a proper use of sources. This is the logic behind the preference of review articles--it is only in this way that one can demonstrate the actual scientific consensus. Given enough primary papers on a subject in human biology, one can find a source for essentially anything, however eccentric. The result of relying upon individual scientific papers is a very low quality article like this, that says many things several times over, with contradictory statements about effectiveness. DGG ( talk ) 04:30, 6 August 2011 (UTC)

It is essential that this entire page be rewritten. It is possible that many people will decide to use the drug because it is OTC and because this website shows some support for the benefits of melatonin-when we do not really know what its effects can be. At least some disclaimer needs to be made over the safety of melatonin and that its use without physician discussion should be limited. — Preceding unsigned comment added by 173.80.245.161 (talk) 07:18, 29 May 2013 (UTC)

I suggest that you become familiar with WP:RD/G/M, WP:OR, WP:NPOV, and WP:!. Your opinion that it should not be used without physician discussion is not a valid source, and any disclaimer must be semantically present in any source to which you refer. I left in the reference in your most recent edit, but even this inclusion is on shaky ground considering that Ms. Ratzburg's article (see: http://www.vanderbilt.edu/AnS/psychology/health_psychology/melatonin.htm) does not explicitly contain any admonitions on safety per se, claiming instead that "Melatonin is one of the least toxic substances known." Again, any article content you wish to add must actually be present in the referenced source and be written by you in a neutral point of view, not in the form of advice or admonishment. Blacksun1942 (talk) 11:25, 29 May 2013 (UTC)

DELETE flag. I propose the flag now be deleted. The article does not "rely" on primary sources. The arguments rehearsed above seem at best to be tangential to the issue. LookingGlass (talk) 10:59, 28 November 2013 (UTC)

Outdated reference

The link about not taking melatonin when trying to concieve is outdated. http://sleepdisorders.about.com/cs/melatonin/a/melatonin_4.htm PizzaMan (talk) 18:02, 23 February 2012 (UTC)

Update: im deleting the remark as i found the reference, but its far from peer-reviewed. http://altmedicine.about.com/od/melatonin/a/melatonin_2.htm And as melatonin is a normal hormone everyone makes, id like to see a more convincing reference that its dangerous when conceiving. PizzaMan (talk) 18:11, 23 February 2012 (UTC)

IIRC, melatonin was once considered for use in a contraceptive. I know of no other "danger". --Hordaland (talk) 21:05, 1 March 2012 (UTC)

Sourcing problems

The article makes extensive use of primary studies to support claims. This violates the consensus in WP:MEDRS which requires recent, quality, secondary sources. A quick look on Google Scholar and PubMed for "melatonin review" seems to turn up plenty of possibilities, so I see no reason to use outdated primaries. It may be that this article needs re-writing from scratch if the recent secondaries don't match up with the current content. --RexxS (talk) 00:10, 3 March 2012 (UTC)

Incorrect citation?

Sale of melatonin over the counter with other supplements probably predates the mid-1990s. The citation (7) supporting that statement makes no mention of over the counter availability. CopyCustodian (talk) 00:54, 12 July 2012 (UTC)

Biosynthesis section needed

It is proper that an article on such a substance should brief us on how it gets formed in the body and what cofactors are used, under an appropriate heading. — Preceding unsigned comment added by 78.144.153.166 (talk) 21:52, 14 December 2012 (UTC)

Adverse effects

The article says "Unwanted effects in some people especially at high doses (~3 mg/day or more)" and then proceeds to list some side effects and gives a reference. If you follow the reference it doesn't say that at all. It does give possible side effects, but no dosage specific to those side effects. In fact it explains that: "circadian rhythm sleep disorders are often treated with 0.5 milligrams of melatonin a day, while doses of 3 to 5 milligrams a day might be used to treat jet lag or reduce the time it takes to fall asleep." I don't see how a recommended dosage could be correlated specifically with the side effects given and also called a "high dose." Now, I think it's entirely possible that 5mg is on the high end of what a person should take, seeing as most pills and liquids appear to top out at 3-5mg. The given reference is pretty weak in support of that though. 184.167.224.119 (talk) 01:10, 20 January 2013 (UTC)

I just added information on melatonin possibly worsening symptoms of asthma patients by promoting inflammation. Can someone please check the validity of this claim? 213.7.176.33 (talk) 14:22, 26 July 2014 (UTC)

Yes, I saw that you added that, and I see that it has been reverted. Since the admittedly small scale trial was done more than 10 years ago, there would be later papers & one or more reviews about this if anyone were taking it seriously. IMO. --Hordaland (talk) 21:32, 26 July 2014 (UTC)

Thanks! I've just sent a message to the person that reverted the changes. I disagree with removing this completely. Asthmatics should at least be cautioned to talk to their doctor, start with lower dosage etc. Is there a wikipedia rule that completely forbids citing primary sources if the text makes it clear that it is a primary source and that more research is necessary? — Preceding unsigned comment added by 81.4.144.74 (talk) 08:56, 27 July 2014 (UTC)

The "rules" are here: Wikipedia:Identifying reliable sources (medicine) --Hordaland (talk) 20:55, 28 July 2014 (UTC)

Results of my literature search

I just did a search on this, and am presenting the results here in case anyone finds some of them useful for improving the article:

"CONCLUSION: In these doses and clinical conditions, melatonin did not contribute to sedation of children." http://www.ncbi.nlm.nih.gov/pubmed/16782974?dopt=Abstract (2006)

"Melatonin [has] value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder [and has] been found to be useful for treating insomnia symptoms in elderly and depressive patients." http://www.ncbi.nlm.nih.gov/pubmed/16817850?dopt=Abstract (2006)

"Exogenous melatonin administration possesses circadian-phase-dependent hypnotic properties, allowing for improved consolidation of sleep..." http://www.ncbi.nlm.nih.gov/pubmed/16774150?dopt=Abstract (2006)

"A new study by MIT scientists and colleagues confirms that melatonin is an effective sleep aid for older insomniacs and others. Misuse of the hormone had led some to question its efficacy [...] only a small dose of melatonin (about 0.3 milligrams) is necessary for a restful effect. Taken in that quantity, it not only helps people fall asleep, but also makes it easier for them to return to sleep after waking up during the night--a problem for many older adults. The researchers also found, however, that commercially available melatonin pills contain 10 times the effective amount. And at that dose, 'after a few days it stops working,' said Wurtman, director of MIT's Clinical Research Center and the Cecil H. Green Distinguished Professor. When the melatonin receptors in the brain are exposed to too much of the hormone, they become unresponsive. As a result of these inadvertent overdoses, 'many people don't think melatonin works at all,' said Wurtman, who is also affiliated with the Department of Brain and Cognitive Sciences. This belief, coupled with potentially serious side effects related to high doses such as hypothermia, has earned the hormone a bad reputation in some quarters--'and something that could be very useful to a lot of people isn't,'" http://web.mit.edu/newsoffice/2005/melatonin.html http://web.mit.edu/newsoffice/2005/techtalk49-20.pdf

"In one large well-designed study, melatonin supplements did not relieve symptoms of jet lag, and only a few small studies suggest that these supplements can treat insomnia. [...] Adverse effects: Hangover drowsiness, headache, and transient depression may occur. Melatonin may worsen depression. Theoretically, prion infection caused by products derived from neurologic tissues of animals is a risk." http://www.merckmanuals.com/professional/special_subjects/dietary_supplements/melatonin.html?qt=melatonin&sc=&alt=sh (Last full review/revision May 2009 - Content last modified August 2013)

"Authors' conclusions: Melatonin is remarkably effective in preventing or reducing jet lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be." http://summaries.cochrane.org/CD001520/melatonin-for-the-prevention-and-treatment-of-jet-lag (2009)

"Melatonin decreased sleep onset latency in normal sleepers [by] 3.9 minutes. [...] The magnitude of this effect appears to be clinically insignificant. There was evidence of possible publication bias in the selection of studies that were analyzed [...] Evidence suggests that melatonin is not effective in treating most primary sleep disorders with short-term use, although there is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. Evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use. No evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shiftwork disorder. Evidence suggests that melatonin is safe with short-term use." http://archive.ahrq.gov/clinic/epcsums/melatsum.htm (2004. Also available as PDF, approx. 150 pages, http://archive.ahrq.gov/downloads/pub/evidence/pdf/melatonin/melatonin.pdf )

"The problem with melatonin is absorption. Pills get destroyed in your gut and you never get the full effect. The best way to take melatonin is in spray form. And watch the dose. Many folks take too much, killing its effectiveness. Make sure you only take 500 mcg to 1 mg of melatonin." http://www.alsearsmd.com/2009/06/26/natural-sleep-aids/

"Although more research is still needed, studies suggest that melatonin can help elderly people with insomnia fall asleep faster, and may also be beneficial for other people with insomnia; however, effects are generally small, with larger effects observed in patients whose sleep problems are caused by a circadian rhythm abnormality (disruption of the body's internal "clock"). Studies indicate that melatonin also appears to be safe at recommended doses for short-term use." http://nccih.nih.gov/health/sleep/ataglance.htm (Date Created: July 2009. Last Updated: April 2014.)

"Evidence suggests that melatonin is not effective in treating most primary sleep disorders with short-term use, although there is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. Evidence suggests that melatonin is not effective in treating most secondary sleep disorders with short-term use. No evidence suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag and shift-work disorder. Evidence suggests that melatonin is safe with short-term use." http://www.ncbi.nlm.nih.gov/books/NBK37431/ (2004)

"The effectiveness ratings for MELATONIN are as follows: [too long to quote here]" http://www.nlm.nih.gov/medlineplus/druginfo/natural/940.html (Last reviewed - 10/22/2014.)

"National Institutes of Health panel seeks to curb use. [...] A group of sleep research experts is warning against the growing use of the hormone melatonin as a sleep promoter..." http://trove.nla.gov.au/work/43052903?q&versionId=55935433 (1996)http://www.newsrx.com/newsletters/Cancer-Weekly/1996-08-26/0826961127695141CW.html

--Guy Macon (talk) 05:27, 28 April 2013 (UTC)

• Note that these 2 links (above) contain (at least partly) identical text:

http://archive.ahrq.gov/clinic/epcsums/melatsum.htm

http://www.ncbi.nlm.nih.gov/books/NBK37431/

I have today added some info to Guy Macon's comment above: Added dates (years) for each URL above (where the year isn't included in the URL) & in 1 instance added URL to the PDF. None of the links is a deadlink as of today. --Hordaland (talk) 16:44, 29 March 2015 (UTC)

Some additional changes made

I addressed 3 things: misleading statements about regulatory status in the introduction, and inflated claims made (or implied) around this dietary supplement as an antioxidant and in respect of cancer. It is not just that large sections of this article are a biased selection of primary sources claiming benefit: they're often animal studies or pure conjecture, not even necessarily primary studies. A lot of this could really just be pruned, and the article would be immeasurably better as a source of information for it. Hildabast (talk) 01:32, 6 June 2013 (UTC)

Could you explain this a little more? Melatonin is an antioxidant; that is not an "inflated claim," that is a chemical classification. "Inflated claims" would include the persistent pop-culture idea that supplementing the diet in excess of requirement for redox balance is necessarily a "good" thing (gout and psoriasis associated with elevated uric acid, a powerful antioxidant), let alone the plainly false claim that all orally administered antioxidants are equally capable of crossing the blood-CSF barrier (which renders the applicability of effects on isolated neural tissue culture essentially vacuous and inapplicable). None of that changes the fact, however, that (like uric acid), melatonin's endogenous production is essential for health in part *specifically because* it is an antioxidant, and reduced levels are associated with elevated risk of cancer (see Carcinogen#Circadian disruption). I see nothing whatsoever that's objectionable or dubious in this article regarding melatonin's function as an antioxidant. As in a section above, I must again politely insist that editors not alter technical content merely because they are personally incredulous; special care should be exercised with articles on scientific topics (such as endogenous hormones). Blacksun1942 (talk) 11:34, 6 June 2013 (UTC)

This mystifies me a little - I didn't remove the information about it being an antioxidant - clearly it is an antioxidant. I removed speculative non-neutral statements that implied a wide range of health benefits based generally on animal studies of supplementation, and that going from that to using words like "possibly increase longevity", even if hedged, in the context of an article that is for the most part very uncritical is a problem. You'd get the impression this was a miracle substance and the fountain of youth to boot, and that antioxidant supplementation can only be a good thing. As you point out, there is a pop-culture idea about this, even though it's also possible that antioxidant supplementation can have the reverse effect to the one intended. I agree that people shouldn't remove information with which they disagree, but these were partly unreferenced, references were sometimes quite old and selective towards only benefit - not a peep about the possible harm of antioxidant supplementation. I'm not sure why you would think I've operated with a bias against melatonin: the inaccurate statements I corrected that implied that most regulatory agencies around the world had rejected it should suggest that I'm not. (Indeed, when I saw the concerns from the help desk about this article, I went to look because I take it myself - for jetlag.) I thought that the implications around increasing longevity and the cancer issue were the most critical issues (other than correcting the regulatory issue). Also the help desk enquiry had stated there was an FDA warning, and I checked up on in detail what has been been happening at the FDA on this (saw no need for any change in relation to that, so I did nothing in regard to that). I agree with you in principle, but don't agree that it applies in this case. Hildabast (talk) 12:07, 6 June 2013 (UTC)

Well...? --Seduisant (talk) 02:08, 6 June 2013 (UTC)

...the proverbial "someone" should do it! ;) Hildabast (talk) 02:12, 6 June 2013 (UTC)

ref name="pmid8102180"

This ref was removed and replaced by one which looks similar, also 1993. But the replacement doesn't have a 'ref name'. I'm confused about whether the original one should still be there. Therefore I'm parking it here just in case.

A Few Suggestions

• Under the sub section "Light dependence" a line reads "Wearing glasses that block blue light in the hours before bedtime may decrease melatonin loss." 1. This line should be cited 2. Depending on what the data says, this statement doesn't make intuitive sense as, by bedtime, melatonin concentrations would be at their lowest due to light exposure throughout the day.
• Under the sub section "Antioxidant" it may be useful to readers if there were hyperlinks to the terms lipophilic and amphiphilic.
• Under the sub section "Immune system" the end of the line that reads "...and by doing this counteract acquired immunodeficiences." should be back checked for accuracy. While increased cytokine production does stimulate a heightened immune response, this may not necessarily counteract immunodeficiencies and could give readers a misconception of the effects of melatonin.
• The sub headings "Antioxidant" and "Protection from radiation" are very similar and it could be argued that they could be conglomerated.
• The page may benefit if the history heading/section was at the forefront of the page ahead of the Plants section.

Hhrdlick (talk) 02:41, 5 March 2014 (UTC)

Re your 1st point, you've misunderstood (which may indicate that some things are not well enough explained for the casual reader). Melatonin levels at bedtime are definitely not at their lowest, or, at least, they definitely should not be. They've been increasing for about two hours by then, initiating sleepiness and lowering body temperature in preparation for sleep. "Wearing glasses that block blue light in the hours before bedtime may decrease melatonin loss." I'll look for a citation for that. --Hordaland (talk) 14:21, 5 March 2014 (UTC)

Very good, thank you. Hhrdlick (talk) 16:29, 5 March 2014 (UTC)

Melatonin and Psychedelics

Article quote
It has been suggested that nonpolar (lipid-soluble) indolic hallucinogenic drugs emulate melatonin activity in the awakened state and that both act on the same areas of the brain.

Is there anything to this? I haven't heard of any melatonergic effect of psychedelics, and I don't think there is one. It just seems like an oversimplification by an author that assumed that psychedelic hallucinations are just waking dreams. Any objections before I remove it? Exercisephys (talk) 15:09, 5 May 2014 (UTC)

References

3D Structure Incorrect?

Why is there a hydrogen bonded to the oxygen atom in the acetyl group of the 3D structure? The oxygen is double-bonded to the carbon, so it shouldn't be able to bond to another hydrogen. — Preceding unsigned comment added by 69.121.252.60 (talk) 06:44, 7 July 2014 (UTC)

Major revision

Grotesque. The article indicates as if humans are the sole owner. In fact melatonin system is basically similar in all vertebrates, slightly different in invertebrates, more so in plants and microorganisms—take that for evolution. Undue info also in given for the medical applications, while the actual biology is incomplete at best. I'll fix some. Chhandama (talk) 03:33, 2 November 2014 (UTC)

Moving new comment to bottom of page

No one would have seen this comment up there in between comments from 2013:

I just read the article and it said basically that melatonin was the strongest antioxidant by saying it was twice stronger than vitamin E which is considered the most effective antioxidant (all that was stated). Later it also says it's more effective against ionizing radiation than the commonly used treatments, and that this is due to fighting free radicals. Also there is absolutely nothing at all linked with Melatonin in this article that would read as other than a positive effect. So... Maybe it was more perfect before, but right now the claims sound inflated to me. Dlamblin (talk) 05:19, 21 July 2015 (UTC)

--Hordaland (talk) 17:18, 21 July 2015 (UTC)