Benadryl is a first generation antihistamine which crosses Blood-brain barrier and makes you sleepy. Its mechanism of action is very different from melatonin and it has much more severe side effects (bad feeling after wake up) than melatonin.
I works great when you have this "thinking in your sleep and wake up even more tired" syndrome.
Melatonin related supplemements helps you relax quickly and really sleep deep.
I personally found that taking 1/3 of recommended dose works perfectly.
Taking full doze making me wake up in such a limb state - that it takes me literally one hour for muscles to get back into their ability to move the body.
Another thing is that I found that taking it for a week or two (no more) is optimal. Few cycles of deep, relaxed sleep are enough for body/mind to get into relatively better balance than before.
Adding regular physical exercise to the mix helps to reignite the whole system back.
I can confirm the 1/3 size dose (the strips are 3 mg and I take one third of that, 1 mg), I take it from time to time when I get insomnia and that seems to be the sweet spot.
Haven't read the article yet, but Melatonin does wonders for my sleep habits. Without it, it seems like my body really wants to function on a day that's 26 or so hours long. That tends to put me in a constant cycle of being not tired enough to go to sleep yet, falling asleep too late, not having enough sleep and being tired all day, then going to sleep the next night too early and starting over again the next day. Melatonin has made it much easier to get about the same amount of sleep every night.
Melatonin supplements have helped me numerous times to get to sleep after tossing and turning in my bed. It is something that I've taken as needed and as a nightly supplement. The biggest drawback to melatonin supplements is that you can sometimes wake up slightly groggy the next morning. The stuff is dirt cheap and commonly available. If you haven't tried it, this could be the sleeper supplement your missing.
I take it when I travel across time zones to reset my internal clock. Works great! If I take if for more than 3-4 nights in a row it seems to lose its effectiveness.
Why didn't you mention about the effects of a calcified pineal gland resulting from a Vitamin D and magnesium deficiency? Those are very common among the older folk, resulting in poor sleep quality, poor immune system, even increased chance of heart attacks.
Pineal gland calcification happens to almost everyone[1], whether you're vitamin D deficient or not. Not only is it completely normal, the health effects you mention have certainly not been shown to correlate with calcification.
Honestly, the only people that bring this up are people still steadfast against fluoridation of water and people looking for an overly simplistic cause for alzheimer's.
Your study focused on newborns to 20 yrs. It didn't consider the 30 to 70 crowd. Children and young adults usually don't have this problem since their bodies are rapidly growing and absorb large amounts of iron/calcium/etc to grow.
Not only that, but your study observed extreme cases: "The majority of patients included in the study had a history of seizures or minor head injury."
I never heard of calcification linked with fluoridation and Alzheimer's. So I wasn't suggesting that.
Apparantly you've never given magnesium citrate to older family members and watched them get the best sleep in a long time. Moreover, an American diet filled with calcium + little magnesium + Americans taking calcium supplements for osteo-porosis + plus deficiency of various nutrients is bound to lead to various problems. Then again, I'm not a doctor. In fact, I don't even have a college degree. So feel free to ignore anything I say.
If people want to be more concerned about vitamins/supplements rather than a diet rich in iron/HFCS + deadly FDA-approved drugs, so be it. I will take my chance with the vitamin fanatics like Linus Pauling (took mega doses of Vitamin C, died of cancer... at the age of 93).
I will grant your wish. I will stop talking about vitamins and supplements on HN. However, for any crackpot vitamin fanatics out there, head over to http://knowledgeofhealth.com That's one of the best sites I know and are very good at spotting mistakes in mediocre research proving that vitamins are deadly, cancer inducing toxins.
There are some problems with Melatonin (as supplied) - you don't really know how much (if any) you're getting. Investigators found that quality control was very poor and some brands contained very little melatonin. (I can't find it now, but it was something like Consumer Reports or similar?)
It's a prescription only med in some places (UK) so you might not be able to get it.
But it is "remarkably effective"[1] for jet lag.
You might want to consider sleep hygiene[2] as well as (or instead of) melatonin or other sleep meds. (I really like zopiclone.)
Wikipedia suggests prescription only in the UK. I think this is because it was banned as a food supplement in the 1990s, and only one medication got a licence, and that was a POM. Thus, any melatonin product is either an unlicensed medication (illegal) or prescription only.
The page you link to doesn't allow me to buy any product. Entering [melatonin] in their search box doesn't return any products containing melatonin.
That link shows some automated content brought in from healthnotes/aisle7 which is a Portland, Oregon based company. If you search Amazon UK for melatonin you'll find lots of supplement that are described as 'melatonin-like' but don't contain any active ingredients.
I buy it when I'm in the US which is fine for me as I take it for jet lag but I know GPs (family doctors) I talk to are often confused to learn they can prescribe melatonin and will often prescribe much more powerful and, in my opinion, dangerous hypnotics. I think that's probably because there's no patent on melatonin so not much marketing push to inform GPs of its uses - though I believe there's a patented slow release version of melatonin that might get a bit of marketing behind it.
Zopiclone can be habit forming and has an associated increase risk of road traffic accidents like most hypnotics - wikipedia is a good start for the risks.
I think melatonin is a better drug for correcting problems with sleep cycles which can include jet lag, changes in season and the like but there's plenty you can do help your sleep quality without drugs.
Here's a great article (about Huntington's disease but applies to everyone - it really helped me) based on a published paper in Experimental Neurology:
There was a study by Kripke showing that many sleeping pills, namely benzodiazepines, tripled your likelihood of death even if taken very infrequently.
Zopiclone is not a benzodiazepine but I don't know if it has been studied in a similar manner.
> (I can't find it now, but it was something like Consumer Reports or similar?)
Are you thinking of the Consumer Labs report? I quoted that in a footnote, but it does not show what you seem to think it showed:
> Can melatonin help you sleep? "Melatonin supplements may help some people get to sleep sooner, particularly those with chronic sleeping problems, but don't just buy any supplement - they vary [substantially] in strength, dosage, and cost," says ConsumerLab.com President, Tod Cooperman, M.D. ConsumerLab.com recently selected and tested nine different melatonin supplements. The testing showed that all contained their labeled amounts of melatonin, but the suggested daily dosage ranged from 1 mg to 50 mg [!]; and cost ranged from just 4 cents to $1.36 for an equivalent dose of melatonin. This means you may not be using the right dose for your needs and you could be paying as much as 33 times more than necessary. ConsumerLab.com also found that one supplement failed to properly disclose all of its ingredients.
That is, each contained all the melatonin it claimed to, but there were irresponsible doses being offered. Unfortunate, yes, but this is not a problem for anyone who did their homework and know what dose they want to try.
I use melatonin regularly to regulate my sleep cycle. It's a very effective part of a regimen (sleep hygiene, f.lux, etc) that allows me to manage a nearly-decade long problem of insomnia.
However, from a psychological standpoint, it's a very good thing melatonin is so safe. Every single person I've ever recommended melatonin to, I've directed to this article and discussed it with them. Every single such person then went ahead to promptly forget the discussion, NOT read the article, and take mildly retarded doses. For example, "one (5mg) pill didn't work, so I took 8 more at 4am." Another uses it almost recreationally - large doses to intensify his dreams; pretty much zero attempt to use it to improve his sleep. I don't talk to people about melatonin anymore.
This whole discussion is starting to make me feel reckless in a hilariously inconsequential way. I literally said to myself "I think people take melatonin when they have trouble sleeping...", went to the drug store, bought a bottle, and started taking the dose it recommended, at the time it recommended. Apparently I skipped out on a whole bunch of research I was supposed to have done.
what about feedback effect and pineal gland attrofiation?
every hormone that you have in excess of what the body expects, have compensation of the opposing message hormone, feedback effect. anyone has any idea which one is for this case?
another consequence is that the original producer of such hormone will get de prioritized by the body and atrophies after too much time. does this happen here?
I have terrible sleep habits and often find it difficult to fall asleep before 5am. I have been considering trying melatonin but my major concern is that I will become dependent on it. I don't want my body to stop producing whatever small amount it already does through its use as a supplement.
How dependent on it would you say you are? How well would you function if you were unable to get hold of it?
It's very unlikely that you will become dependent on Melatonin, it's simply not addictive. It isn't a sleeping pill either, it mainly supports an existing sleep disposition. If you don't want to sleep, you won't sleep.
Thanks. I use f.lux already and it's great (it makes my eyes feel a lot better) but hasn't really helped me fall asleep. I think I am going to try a no back-lit screens after 23:00 rule.
I don't feel any physiological dependence, as I go on and off it with no consequences that I can detect (other than becoming more prone to slip off my sleep schedule). Generally I only take melatonin daily when I'm adjusting to a new timezone/schedule or have lapsed by purposely staying up. Otherwise I use it maybe twice a week, and have gone months without any.
When I don't take it my sleeping time seems to be a function of sleep hygiene.. Your melatonin production cycles are probably most strongly controlled by zeitgeber factors, like the mentioned blue light wavelengths. My insomnia used to be as bad as yours and now it's fairly normal for me to fall asleep at 1am, even using the computer. Once you get in a pattern, it has some persistence to it.
It's not addictive. In fact I found myself not wanting to take it after a while because I had so much energy from getting good sleep, I wanted to stay up late doing stuff. (Even though I should, so I get to sleep at a decent hour.)
I recommended 1mg per 50lbs of body weight, and get the fast acting one, not the slow-dissolving one; those made me drowsy the next morning.
It is a little harder to snap to attention right after waking up, but I shake that off quickly; probably a sign I slept well.
It does affect everyone differently though. I haven't had any negative effects myself, other than with the slow-dissolving "long-lasting" pills (but some might need that to stay asleep).
Interesting. I'm not sure I've seen extended-release melatonin. IIRC melatonin does not help you stay asleep, so that would be fairly useless.
I recommend starting at the smallest dose you can find designed for sublingual (under-the-tongue dissolving) administration. 0.3mg to 1mg is a good range.
Use 500mcg pills. It only takes around 300mcg to get the full effects of melatonin. Once you reach around 1mg, your body will quickly adapt and it will lose effectiveness.
I used 300mcg for months and months, slept better, had vivid dreams, and the effect didn't change. I switched to 500mcg pills from Trader Joe's only because the 300mcg pills stopped being carried locally.
Source: an in-depth article I read years ago that I can never seem to find.
I don't have personal experience with it; but my sleep schedule is horrible (I tend to stay up to 5am on alternate nights), so I may give it a try to enforce a normal bedtime, and kick the procrastination monster down a bit (if I don't have the option of doing the unpleasant work at 2am, it's far easier to force myself to do it during normal hours).
Search MetaMed (a few screens down) for Eliezer Yudkowsky's experience with a sleep disorder (his normal day is 24.5 hours): after spending years trying a whole laundry list of solutions including melatonin, he finally paid MetaMed somewhere north of $5K for their analysis, and got a solution using melatonin that worked (but was not the normal approach to melatonin supplementation).
"their best suggestion, although it had little or no clinical backing, was that I should take my low-dose melatonin 5-7 hours before bedtime, instead of 1-2 hours, a recommendation which I’d never heard anywhere before.
And it worked.
I can’t #&$ing believe that #$%ing worked.
(EDIT in response to reader questions: ”Low-dose” melatonin is 200microgram (mcg) = 0.2 mg. Currently I’m taking 0.2mg 5.5hr in advance, and taking 1mg timed-release just before closing my eyes to sleep. However, I worked up to that over time – I started out just taking 0.3mg total, and I would recommend to anyone else that they start at 0.2mg.)"
This is how I do it as well. I use 300 microgram time released at sunset. Then a 1000 microgram instant release before bed. The 1000 microgram is not needed for me to get good sleep, but it puts my dosage at where body temp drops can be seen.
It's my understanding that taking Melatonin supplements will mess up your bodies natural ability to make it's own Melatonin (as will taking a lot of supplements). You are far better off trying to get your body to produce Melatonin on it's own.
As for Melatonin Adverse Events, it's my site that's linked to under 'Uses', (http://www.drugcite.com/?q=melatonin) It's important to sort the data by age and gender as the AE's can vary greatly. That data is FDA FAERS data that runs against many other datasets by the way.
As I've pointed out in the past to you, I'm not sure what use we're supposed to be making of your admittedly nice site, given that we don't know how many people are using melatonin, how reliable any of these cases are, or what.
The problem with a lack of FDA regulation is that there is no guarantee on what you are taking. The freshness of the product and the veracity of what's in the pills will always be suspect to me.
If I could trust where I get my melatonin from, I would gladly take it. But I've learned too much about how terrible this industry is.
I'd also strongly recommend the Trader Joe's brand. I've been using melatonin for a couple of years and haven't found anything that has been as consistently effective.
I agree that oversight is important. Incidentally, that's why bottled water is generally more dangerous than tap water. Public water supplies are held to stricter standards in terms of quality control and regular testing.
Thats a very good point, also it's important to look for off label side effects (Adverse Events) to the non prescription drugs. I own the site linked to in the 'Uses' section (http://www.drugcite.com/?q=melatonin), it's also to sort the data by date and gender to get more accurate information. This data is put together from numerous data sets including FDA FAERS.
The issue here is that it is a natural chemical and with that nobody can patent it. The cost for drug approval (in many countries) is high and this is the crux. No company is going to finance the approval process as they have no way to control there financial return upon that investment as they can not patent the drug they are getting approval upon. So everybody else can just ride there investment and that is the case now in that nobody has any incentive to put it thru the costly FDA approval. Same can be seen for Omega-3 and other naturaly occuring benificial products.
This also means that people with depression or sleep disorders can not be prescribed these products as they are not FDA approved and insurance will not pay for it either. This forces people into patented phara drugs that may or may not be better for them and in all cases have more side effects (upto including death being common disclaimer on the long list).
Same issue in the UK and more so in that melatonin is not allowed to be sold. Sure you can get it on the internet, but from some contries but as there are no standards it is hard to tell. Is it syntheticly made or the type extracetd from animal and with that the whole area of concern starts to rise.
If only some benificial billionair would fund FDA tests for approval for this and other unpatentable naturaly occuring medicines. Certainly be positive for everybody.
Companies can obtain market exclusivity without a patent. In the US, the FDA assigns 5 years of market exclusivity based on a NDA approval. If it's an orphan disease, it's 7 years. You can also bump up the exclusivity by 6 months if you get approved in a pediatric indication.
That said, there isn't much incentive for a company to do this. Let's say a company spend $200M getting FDA approval for melatonin. Considering the huge population that it would be used in, the FDA would require a very large trial to determine safety. Once launched, the drug company would need to recover that cost plus a profit, so suddenly melatonin goes from a few pennies per dose to several dollars. The push back from the public would probably kill any chance of making it a profitable venture.
What drug companies did do was create melatonin analogues. Rozerem by Takeda is a great example. It hasn't done that well.
As for omega-3s, GSK did get Lovaza approved by the FDA although they did have a patent on it (a specific form of omega-3s).
That is encouraging, sadly not aware of anything comparable in the UK, though was unaware of this avenue you mention and with that thank you.
Sad about the investment needed for the limited return window which would be enough time to promote the benifits intime for the market to mature just outside the window of opertunity.
Does make you wonder how many good useful medications are kept back due too fiscal investment to get the various approvals. Not aware of a universal World accepted standard of drug approval, certainly would make sense cost wise for the global return. But guess there is money in running trials as well.
There is an approved form of pharmaceutical melatonin in the UK (Circadin, 2mg modified release), but it's only licensed for use in adults aged over 55.
Any doctor can prescribe it off-label if they wish, although they might be hesitant in the non-insomniac population due to the relatively high cost (>50p per 2mg dose)
I used to deal with periodic weeks of insomnia. As a stifle I really could not afford to spend a whole week without sleeping more than 5 hours as I would be basically non functional after a couple days. I began supplementing a single 5mg dose of melatonin and it has almost completely erased my insomnia. I have found that it has improved the quality of my sleep as well. The only side affect I've noticed is increased dreaming while taking it, however I quite enjoy that.
I found melatonin to be very effective, especially on mountaineering trips, where I'm not guaranteed a decent sleeping environment but really need to get some sleep when given the opportunity.
My girlfriend however reported nightmares when she started supplementing with it, but it appears to have gotten better.
I've taken it and really does help me sleep better. It helps me fall asleep easier if I wake up in the middle of the night. I was taking about 1/3 of a 3mg tablet.
I did stop taking it though because I felt depressed after about 2 weeks of taking it every day.
I will probably take it again periodically if I am traveling.
Melatonin does work wonders, but you never know how your own body might react to it.
I have many issues with my sleep cycle and quality of sleep. Melatonin is one of the few things that alleviates my problems. However, for me, it's only good for one night. I can take melatonin for one night out of a month, and get a blissful, restful night of sleep. If I take it two nights in a row, evil side-effects start creeping up.
It begins with a headache. If I take melatonin two nights in a row, the next day I will wake up with a headache that's hard to shake. My dreams, while very vivid and pleasant the first night, become more gloomy and depressing the second night. By the third day, my dreams are full-on, vivid, terrifying nightmares. I feel depressed and angry all day, and the headache borders a migraine. After four days of melatonin, I'm a wreck. It no longer puts me to sleep, nor gives me restful sleep. It becomes nothing more than a pill full of nightmares, depression, anger, and a bad migraine.
The first time I started taking melatonin, I had no idea it was causing these side effects. It took a while to pin down, and I just assumed it was related to my ongoing battle with sleep. I do recommend it, just know that you may have adverse reactions to continued use.
I'm curious as to what dosage you're taking. Several sources I've seen suggest the dosage they recommend on the package is too high for many of the typical brands out there. Do you experience these symptoms when taking low-dose melatonin (<= 0.5 mg)?
I've tried both high and low dose, and many different brands. Effects are the same either way. I usually go with the high dose since I'll only be taking it for one night anyway.
Interesting. I work on call shifts. (Linux sysadmin, one week out of three is 24/7 on call -- which works much better than rotating one day out of three.) I've used Melatonin for years to 'regulate' my sleep cycle so that I can stop my tirelessly creative brain from thinking about that article I read a few hours ago on Hacker News.
My other 'hacks' to keep my sleep cycle regulated are f.lux where possible, using only dim incandescent lights in the evening around the house once I am ready for bed, and NOT using a laptop, iPad, or anything with white/blue LEDs in bed. Wake-up is accomplished with an alarm clock that activates a piece of "wall art" that slowly changes color spectrum to full daylight using LEDs and shines on the bed.
Having good control of my sleep cycle keeps jet lag, time changes, mid-night alerts, and other things that disrupt most people from disrupting me as much for as long.
Melatonin does NOT work as a remedy for jet lag. I don't find open access links to the relevant studies right now but http://www.nojetlag.com/melatonin.html might give you a first idea.
Anecdotally, melatonin works wonders for me when traveling.
I take 1mg of melatonin between 7 and 9pm in the target time zone's frame, usually starting the day I travel or sometimes the day before. This translates to taking a pill at noon or so in SF before flying to Europe. I follow that up with a pill on the first few evenings of a trip.
I've been doing this for a few years now, and the only remnant of jetlag on such trips is that I feel terrible around 3pm in Europe, which translates to 6am. So I'm guessing that my natural not-yet-shifted sleep cycle is rebelling at that point and trying to convince my body that I just stayed up all night.
Of course, I am an n=1 population size, and the routine has worked so well that I haven't dared to do a significant time zone shift without it. So it could just be me, or it could be the placebo effect. And I'm perfectly ok with that, as long as the jet lag stays at bay.
Wow, you linked a homeopathic reference. This doesn't really deserve a response but I'll give it anyways.
It's anecdotal, but for the first 3 days after a major timezone travel difference (6+ hours), I take 2 pills (I think 6mg?) for the first 3 days after I travel about an hour before sleeping, then drink a couple cups of coffee in the morning.
I guess it depends on how you define "remedy" but this helps me sleep all the way through the night, and the caffeine helps keep me awake during the day.
This combination takes my jetlag from debilitating to annoying.
I've taken meltonin for 19 years now. I've moved up my dosage in the last few months. I stayed on a very low dosage for a really long time, but am up to 10mgs now, and sleeping wonderfully.
The main side effect is being much more tired when you wake up, and that is cured by coffee. I love the stuff.
The main side effect is being much more tired when you wake up, and that is cured by coffee. I love the stuff.
I noticed this the very first time I tried it - I slept in on a weekend, about 13h total and then felt very fuzzy and hung over.
That only happened once, and now I take it nightly.
Other recommended sleep hack: Tempur-Pedic sleep mask.
Seriously, it costs a lot more than the cheap plastic ones (although still only $30) but it is worth its weight in gold. For shift workers, it's great - you can sleep like a baby in full sunlight.
Keep in mind that melatonin is a hormone. Exogenous hormones can downregulate your body's natural production. Like anything hormonal you should not take it continuously for long periods of time.
I've been using melatonin for years every night. As a person that has extreme obstructive sleep apnea, I credit melatonin with providing me a modicum of restful sleep for the years I didn't use a CPAP. Now that I have one, melatonin helps improve my "normal" sleep patterns.
Anecdotaly, I find melatonin usage helps my brain rewire itself every night. My belief is that increases the number of connections and associations that various concepts have, and it also elevates my mood. Not bad for something that costs mere pennies!
During the time I had almost no sleep, I would take quite a bit of melatonin in a desperate attempt to get some kind of rest. At times I would pop 25mg or more. I found there were no side effects, except perhaps being sleepy for the next couple of days.
I've also quit a number of times for various reasons. Just a few months ago I quit for three months due to surgery. I found quitting to be completely symptom-free, which kind of amazed me. I figured with years of usage, quitting would make it impossible to sleep. I based this opinion on numerous studies that show when you replace a naturally-occurring hormone with a supplement, your body stops producing it. Instead, I slept fine. Once I was out of the no-supplements period after surgery, I started back up with the melatonin. No side effects, and I almost immediately noticed an increase in creativity and mood.
I'm a supplement junkie. It's that irrational thing that I do, my black swan interest. Yes, I know, most of the market is just BS and marketing hype. But not all of it. Melatonin is one of the 2 or 3 supplements I use that I believe really make a huge and immediately perceivable difference. Can't recommend it highly enough.
Resveratrol is on my "maybe" list. I'm seeing some really interesting research, but the good stuff may end up being patented and sold as a drug, which sucks.
I'm still a Vitamin C fan, even though it's fallen out of favor. Seems to help when I've stressed out my system through alcohol or other chemical irritants.
Also on my "to-watch" list is delta tocotrienols, one of the components of vitamin E. Saw some interesting evidence that it might be good at actually helping to remove coronary artery blockage, but it's still WAY preliminary. And no, that's not a recommendation for vitamin E itself, which in larger doses can cause all sorts of problems. Just the delta series.
The B series of vitamins are interesting, as there seems to be a good-sized gap between the amount most people have in their bloodstream and the amount that they can carry easily. A little dose of B-12 seems to help me enormously with concentration. At least for a short period. YMMV.
Note this is all subjective, and based on half-assed research and gossip. That's one of the rules in this arena: there are no rules. :)
First, it's not a "limited number of hand-selected studies." The Brzezinski meta-study ( http://www.gwern.net/docs/melatonin/2005-brzezinski.pdf ) alone covered 17 studies and 284 participants. There's even a clear, well-documented causal mechanism, which can't be said for most of the supplement industry.
Even if it were a limited number of studies, gwern's not going for "absolute confidence". (Indeed, requiring "absolute confidence" before attempting a thing is irrational by the following sentence.) Irrational here means doing something with expected value less than zero. If you're a person living in an industrialized society with ready access to electrical lighting -- the possible gains are too large to be balanced out by the time wasted trying it. That's what gwern's saying.
And how do you claim to calculate expected value here? You are making the same error he is by ignoring the possible "black swan", which, with every drug, can have dramatic consequences.
> You are making the same error he is by ignoring the possible "black swan", which, with every drug, can have dramatic consequences.
The black swan is a pretty useless concept at this point, because people like you will drag it out against anything they dislike. You cannot give any rigorous formulation or evidence for it, and the best you can do is drag out some old example like thalidomide.
No rigorous formulation? The black swan has a very simple mathematical model: an unlikely event with an effect so great that it will affect the expected value. For example, a greater risk of dying after 20 or 30 years of use - which has not yet been studied. In your calculation of ROI you completely ignore unknown long term effects.
Yes it's hard and often impossible to quantify black swans. But keeping them in mind is a way to avoid overconfident articles like the one you wrote.
> The black swan has a very simple mathematical model: an unlikely event with an effect so great that it will affect the expected value. For example, a greater risk of dying after 20 or 30 years of use - which has not yet been studied. In your calculation of ROI you completely ignore unknown long term effects.
Alright, let me clarify it then: by the remotely meaningful version presented by Taleb, your argument doesn't work and Taleb's writings support taking melatonin, rather than not taking melatonin. Why? Because even in the event of a negative 'black swan' your losses are strictly limited: the worse that can happen is you die. In fact, if I may borrow Taleb's 2x2 table from _The Black Swan_ where he brings up positive 'black swans' as well, it's easier to make a case that taking melatonin is a positive 'black swan': the negative possibilities are strictly in Mediocristan, with limited losses, easy to measure over large populations, predictable, not varying over time; while the positive possibilities look like some of Taleb's examples of attempting to exploit positive 'black swans' in Absurdistan - improved productivity, healthy, and seizing opportunities, things with potentially unlimited payoffs - such as moving to cities and networking with people.
> For example, a greater risk of dying after 20 or 30 years of use - which has not yet been studied.
Yes you are right, the effect is limited: you die. That's true of every black swan - the worst that can happen is everybody dies. But I don't think that anybody would consider that a "mediocre" outcome. And at the end, you could/should quantify it in your model, or at least mention it as an unknown in your ROI.
You do not mention any studies of long term effects and you consider FUD raising the possibility that there could be adverse effects. When more and more studies show negative long term effect of substances that were considered innocuous (like vitamins), it's not FUD, it's being reasonably cautious.
> That's true of every black swan - the worst that can happen is everybody dies.
Not at all. Taleb like to use the example of selling insurance and shorts, where your downside is unlimited. Millions, billions, trillions... Think AIG or LTCM. Not everything has consequences solely for health.
> You do not mention any studies of long term effects and you consider FUD raising the possibility that there could be adverse effects.
In the absence of any evidence whatsoever for that, and plenty of positive correlations, short-term studies without any problem... Yes. It is FUD. Fear, uncertainty, and doubt.
> When more and more studies show negative long term effect of substances that were considered innocuous (like vitamins), it's not FUD, it's being reasonably cautious.
Only some vitamins show any mortality effects, the mortality effects while real are pretty small, the vitamins did not deliver the long-term health benefits promised (but never really demonstrated in experiments) which might offset the harm, and the vitamins were being consumed in huge doses. The first reduces the possibility of any such outcome, the second points out that you are exaggerating the harm, the third means that vitamins were a purely speculative play unlike melatonin, and the fourth reduces the concern that any such thing would happen with melatonin when one sticks to the suggested doses like 0.5mg rather than 5mg.
Using a meta-study that showed tiny changes (statistical significance is irrelevant here, virtually any intervention could have had that kind of impact) to bolster a handful of anecdotes is pretty silly.
I don't argue that this doesn't help a fraction of people, but the case is pretty weak and the long-term results of tampering with a critical hormone are unknown.
No offense to the author but I've read at least 3 of his articles posted here and they all follow a similar pattern.
In general, the pattern of regulation of "dietary supplements"[1] in United States law allows a lot of claims that go beyond the available evidence to be made without legal consequences. In an environment like this, I would do more than just listen to anecdotes from satisfied users.
[1] "Dietary supplement industry says 'no' to more information for consumers (again)" 3 October 2013
Do you have any references for that? I'm not pro or con either way (yet), I'm just gathering research. I'd love to know if there are any recorded cases of this and the doses involved.
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[ 4.5 ms ] story [ 261 ms ] threadMelatonin related supplemements helps you relax quickly and really sleep deep. I personally found that taking 1/3 of recommended dose works perfectly. Taking full doze making me wake up in such a limb state - that it takes me literally one hour for muscles to get back into their ability to move the body.
Another thing is that I found that taking it for a week or two (no more) is optimal. Few cycles of deep, relaxed sleep are enough for body/mind to get into relatively better balance than before.
Adding regular physical exercise to the mix helps to reignite the whole system back.
http://vibrantme.isagenix.com/ca/en/brainsleepsystem.html
1 week was enough for me.
It allows to relax and fall asleep quickly. Small doses will do and they will not diminish your ability to wake up and take care of kids.
Again - start with 1/3 of recommended dose and you should be fine.
Definitely recommend it if you travel internationally.
300 - 600 mg: magnesium citrate.
My favorite brand is "30 Minutes of Sunshine" http://www.lifespannutrition.com/lsn/products.asp?itemnumber... Bio-Tech Vitamin D3 is also very good: http://www.biotechpharmacal.com/
Honestly, the only people that bring this up are people still steadfast against fluoridation of water and people looking for an overly simplistic cause for alzheimer's.
[1] http://radiology.rsna.org/content/142/3/659.full.pdf
Not only that, but your study observed extreme cases: "The majority of patients included in the study had a history of seizures or minor head injury."
I never heard of calcification linked with fluoridation and Alzheimer's. So I wasn't suggesting that.
Apparantly you've never given magnesium citrate to older family members and watched them get the best sleep in a long time. Moreover, an American diet filled with calcium + little magnesium + Americans taking calcium supplements for osteo-porosis + plus deficiency of various nutrients is bound to lead to various problems. Then again, I'm not a doctor. In fact, I don't even have a college degree. So feel free to ignore anything I say.
If people want to be more concerned about vitamins/supplements rather than a diet rich in iron/HFCS + deadly FDA-approved drugs, so be it. I will take my chance with the vitamin fanatics like Linus Pauling (took mega doses of Vitamin C, died of cancer... at the age of 93).
I will grant your wish. I will stop talking about vitamins and supplements on HN. However, for any crackpot vitamin fanatics out there, head over to http://knowledgeofhealth.com That's one of the best sites I know and are very good at spotting mistakes in mediocre research proving that vitamins are deadly, cancer inducing toxins.
It's a prescription only med in some places (UK) so you might not be able to get it.
But it is "remarkably effective"[1] for jet lag.
You might want to consider sleep hygiene[2] as well as (or instead of) melatonin or other sleep meds. (I really like zopiclone.)
[1] (http://summaries.cochrane.org/CD001520/melatonin-for-the-pre...)
[2] (http://www.nhs.uk/Conditions/Insomnia/Pages/Treatment.aspx)
(http://www.nhs.uk/Conditions/Insomnia/Pages/MedicineOverview...)
Doesn't seem to be prescription-only unless I'm misunderstanding.
The page you link to doesn't allow me to buy any product. Entering [melatonin] in their search box doesn't return any products containing melatonin.
(http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofme...)
"You can't buy melatonin over the counter in the UK" (http://www.webmd.boots.com/sleep-disorders/insomnia-in-adult...)
MHRA does regulate melatonin sales and prescriptions. Here are two examples:
UK website has prescription only melatonin, being advertised for off-label use (jet lag) and is told to stop (http://www.mhra.gov.uk/Howweregulate/Medicines/Advertisingof...) (Even though Cochrane found it's excellent for jetlag)
Also, unlicenced product (http://www.mhra.gov.uk/Howweregulate/Medicines/Advertisingof...)
EDIT: also, a web search for [buy codeine uk] returns many hits for offshore pharmacies selling into the UK.
I buy it when I'm in the US which is fine for me as I take it for jet lag but I know GPs (family doctors) I talk to are often confused to learn they can prescribe melatonin and will often prescribe much more powerful and, in my opinion, dangerous hypnotics. I think that's probably because there's no patent on melatonin so not much marketing push to inform GPs of its uses - though I believe there's a patented slow release version of melatonin that might get a bit of marketing behind it.
I think melatonin is a better drug for correcting problems with sleep cycles which can include jet lag, changes in season and the like but there's plenty you can do help your sleep quality without drugs.
Here's a great article (about Huntington's disease but applies to everyone - it really helped me) based on a published paper in Experimental Neurology:
http://en.hdbuzz.net/120
Zopiclone is not a benzodiazepine but I don't know if it has been studied in a similar manner.
Are you thinking of the Consumer Labs report? I quoted that in a footnote, but it does not show what you seem to think it showed:
> Can melatonin help you sleep? "Melatonin supplements may help some people get to sleep sooner, particularly those with chronic sleeping problems, but don't just buy any supplement - they vary [substantially] in strength, dosage, and cost," says ConsumerLab.com President, Tod Cooperman, M.D. ConsumerLab.com recently selected and tested nine different melatonin supplements. The testing showed that all contained their labeled amounts of melatonin, but the suggested daily dosage ranged from 1 mg to 50 mg [!]; and cost ranged from just 4 cents to $1.36 for an equivalent dose of melatonin. This means you may not be using the right dose for your needs and you could be paying as much as 33 times more than necessary. ConsumerLab.com also found that one supplement failed to properly disclose all of its ingredients.
That is, each contained all the melatonin it claimed to, but there were irresponsible doses being offered. Unfortunate, yes, but this is not a problem for anyone who did their homework and know what dose they want to try.
However, from a psychological standpoint, it's a very good thing melatonin is so safe. Every single person I've ever recommended melatonin to, I've directed to this article and discussed it with them. Every single such person then went ahead to promptly forget the discussion, NOT read the article, and take mildly retarded doses. For example, "one (5mg) pill didn't work, so I took 8 more at 4am." Another uses it almost recreationally - large doses to intensify his dreams; pretty much zero attempt to use it to improve his sleep. I don't talk to people about melatonin anymore.
For a quicker idea of where melatonin sits vis-à-vis other sleep drugs (WARNING: Hilarious Ambien Walrus referenced): http://slatestarcodex.com/2013/09/28/sleep-now-by-prescripti...
every hormone that you have in excess of what the body expects, have compensation of the opposing message hormone, feedback effect. anyone has any idea which one is for this case?
another consequence is that the original producer of such hormone will get de prioritized by the body and atrophies after too much time. does this happen here?
How dependent on it would you say you are? How well would you function if you were unable to get hold of it?
You might consider installing blue-light reduction software like f.lux - it's drastically improved my ability to fall asleep late at night.
When I don't take it my sleeping time seems to be a function of sleep hygiene.. Your melatonin production cycles are probably most strongly controlled by zeitgeber factors, like the mentioned blue light wavelengths. My insomnia used to be as bad as yours and now it's fairly normal for me to fall asleep at 1am, even using the computer. Once you get in a pattern, it has some persistence to it.
I recommended 1mg per 50lbs of body weight, and get the fast acting one, not the slow-dissolving one; those made me drowsy the next morning.
It is a little harder to snap to attention right after waking up, but I shake that off quickly; probably a sign I slept well.
It does affect everyone differently though. I haven't had any negative effects myself, other than with the slow-dissolving "long-lasting" pills (but some might need that to stay asleep).
I recommend starting at the smallest dose you can find designed for sublingual (under-the-tongue dissolving) administration. 0.3mg to 1mg is a good range.
http://www.jamiesonvitamins.com/node/1418
This is the one I use that works great:
http://www.jamiesonvitamins.com/chocolate_mint_melatonin
I used 300mcg for months and months, slept better, had vivid dreams, and the effect didn't change. I switched to 500mcg pills from Trader Joe's only because the 300mcg pills stopped being carried locally.
Source: an in-depth article I read years ago that I can never seem to find.
But: see here, this is very relevant: http://hpmor.com/notes/98/
Search MetaMed (a few screens down) for Eliezer Yudkowsky's experience with a sleep disorder (his normal day is 24.5 hours): after spending years trying a whole laundry list of solutions including melatonin, he finally paid MetaMed somewhere north of $5K for their analysis, and got a solution using melatonin that worked (but was not the normal approach to melatonin supplementation).
"their best suggestion, although it had little or no clinical backing, was that I should take my low-dose melatonin 5-7 hours before bedtime, instead of 1-2 hours, a recommendation which I’d never heard anywhere before.
And it worked.
I can’t #&$ing believe that #$%ing worked.
(EDIT in response to reader questions: ”Low-dose” melatonin is 200microgram (mcg) = 0.2 mg. Currently I’m taking 0.2mg 5.5hr in advance, and taking 1mg timed-release just before closing my eyes to sleep. However, I worked up to that over time – I started out just taking 0.3mg total, and I would recommend to anyone else that they start at 0.2mg.)"
The article says:
> A 2010 trial tested a delayed-release melatonin over 6 months and found minimal adverse effects and no tolerance or "addiction"
If I could trust where I get my melatonin from, I would gladly take it. But I've learned too much about how terrible this industry is.
This also means that people with depression or sleep disorders can not be prescribed these products as they are not FDA approved and insurance will not pay for it either. This forces people into patented phara drugs that may or may not be better for them and in all cases have more side effects (upto including death being common disclaimer on the long list).
Same issue in the UK and more so in that melatonin is not allowed to be sold. Sure you can get it on the internet, but from some contries but as there are no standards it is hard to tell. Is it syntheticly made or the type extracetd from animal and with that the whole area of concern starts to rise.
If only some benificial billionair would fund FDA tests for approval for this and other unpatentable naturaly occuring medicines. Certainly be positive for everybody.
That said, there isn't much incentive for a company to do this. Let's say a company spend $200M getting FDA approval for melatonin. Considering the huge population that it would be used in, the FDA would require a very large trial to determine safety. Once launched, the drug company would need to recover that cost plus a profit, so suddenly melatonin goes from a few pennies per dose to several dollars. The push back from the public would probably kill any chance of making it a profitable venture.
What drug companies did do was create melatonin analogues. Rozerem by Takeda is a great example. It hasn't done that well.
As for omega-3s, GSK did get Lovaza approved by the FDA although they did have a patent on it (a specific form of omega-3s).
Sad about the investment needed for the limited return window which would be enough time to promote the benifits intime for the market to mature just outside the window of opertunity.
Does make you wonder how many good useful medications are kept back due too fiscal investment to get the various approvals. Not aware of a universal World accepted standard of drug approval, certainly would make sense cost wise for the global return. But guess there is money in running trials as well.
Any doctor can prescribe it off-label if they wish, although they might be hesitant in the non-insomniac population due to the relatively high cost (>50p per 2mg dose)
My girlfriend however reported nightmares when she started supplementing with it, but it appears to have gotten better.
I did stop taking it though because I felt depressed after about 2 weeks of taking it every day.
I will probably take it again periodically if I am traveling.
I have many issues with my sleep cycle and quality of sleep. Melatonin is one of the few things that alleviates my problems. However, for me, it's only good for one night. I can take melatonin for one night out of a month, and get a blissful, restful night of sleep. If I take it two nights in a row, evil side-effects start creeping up.
It begins with a headache. If I take melatonin two nights in a row, the next day I will wake up with a headache that's hard to shake. My dreams, while very vivid and pleasant the first night, become more gloomy and depressing the second night. By the third day, my dreams are full-on, vivid, terrifying nightmares. I feel depressed and angry all day, and the headache borders a migraine. After four days of melatonin, I'm a wreck. It no longer puts me to sleep, nor gives me restful sleep. It becomes nothing more than a pill full of nightmares, depression, anger, and a bad migraine.
The first time I started taking melatonin, I had no idea it was causing these side effects. It took a while to pin down, and I just assumed it was related to my ongoing battle with sleep. I do recommend it, just know that you may have adverse reactions to continued use.
I had to stop taking it.
My other 'hacks' to keep my sleep cycle regulated are f.lux where possible, using only dim incandescent lights in the evening around the house once I am ready for bed, and NOT using a laptop, iPad, or anything with white/blue LEDs in bed. Wake-up is accomplished with an alarm clock that activates a piece of "wall art" that slowly changes color spectrum to full daylight using LEDs and shines on the bed.
Having good control of my sleep cycle keeps jet lag, time changes, mid-night alerts, and other things that disrupt most people from disrupting me as much for as long.
I take 1mg of melatonin between 7 and 9pm in the target time zone's frame, usually starting the day I travel or sometimes the day before. This translates to taking a pill at noon or so in SF before flying to Europe. I follow that up with a pill on the first few evenings of a trip.
I've been doing this for a few years now, and the only remnant of jetlag on such trips is that I feel terrible around 3pm in Europe, which translates to 6am. So I'm guessing that my natural not-yet-shifted sleep cycle is rebelling at that point and trying to convince my body that I just stayed up all night.
Of course, I am an n=1 population size, and the routine has worked so well that I haven't dared to do a significant time zone shift without it. So it could just be me, or it could be the placebo effect. And I'm perfectly ok with that, as long as the jet lag stays at bay.
It's anecdotal, but for the first 3 days after a major timezone travel difference (6+ hours), I take 2 pills (I think 6mg?) for the first 3 days after I travel about an hour before sleeping, then drink a couple cups of coffee in the morning.
I guess it depends on how you define "remedy" but this helps me sleep all the way through the night, and the caffeine helps keep me awake during the day.
This combination takes my jetlag from debilitating to annoying.
On the 4th day I have 0 jetlag related issues.
The main side effect is being much more tired when you wake up, and that is cured by coffee. I love the stuff.
I noticed this the very first time I tried it - I slept in on a weekend, about 13h total and then felt very fuzzy and hung over.
That only happened once, and now I take it nightly.
Other recommended sleep hack: Tempur-Pedic sleep mask.
Seriously, it costs a lot more than the cheap plastic ones (although still only $30) but it is worth its weight in gold. For shift workers, it's great - you can sleep like a baby in full sunlight.
In practice, however, that didn't occur, at least for me.
I have no idea why. It would interesting to see if this is true for others. It's certainly true for other hormones besides melatonin.
Anecdotaly, I find melatonin usage helps my brain rewire itself every night. My belief is that increases the number of connections and associations that various concepts have, and it also elevates my mood. Not bad for something that costs mere pennies!
During the time I had almost no sleep, I would take quite a bit of melatonin in a desperate attempt to get some kind of rest. At times I would pop 25mg or more. I found there were no side effects, except perhaps being sleepy for the next couple of days.
I've also quit a number of times for various reasons. Just a few months ago I quit for three months due to surgery. I found quitting to be completely symptom-free, which kind of amazed me. I figured with years of usage, quitting would make it impossible to sleep. I based this opinion on numerous studies that show when you replace a naturally-occurring hormone with a supplement, your body stops producing it. Instead, I slept fine. Once I was out of the no-supplements period after surgery, I started back up with the melatonin. No side effects, and I almost immediately noticed an increase in creativity and mood.
I'm a supplement junkie. It's that irrational thing that I do, my black swan interest. Yes, I know, most of the market is just BS and marketing hype. But not all of it. Melatonin is one of the 2 or 3 supplements I use that I believe really make a huge and immediately perceivable difference. Can't recommend it highly enough.
What would the other 2 or 3 be? I've found Vitamin D (taken as a liquid) to be one.
Resveratrol is on my "maybe" list. I'm seeing some really interesting research, but the good stuff may end up being patented and sold as a drug, which sucks.
I'm still a Vitamin C fan, even though it's fallen out of favor. Seems to help when I've stressed out my system through alcohol or other chemical irritants.
Also on my "to-watch" list is delta tocotrienols, one of the components of vitamin E. Saw some interesting evidence that it might be good at actually helping to remove coronary artery blockage, but it's still WAY preliminary. And no, that's not a recommendation for vitamin E itself, which in larger doses can cause all sorts of problems. Just the delta series.
The B series of vitamins are interesting, as there seems to be a good-sized gap between the amount most people have in their bloodstream and the amount that they can carry easily. A little dose of B-12 seems to help me enormously with concentration. At least for a short period. YMMV.
Note this is all subjective, and based on half-assed research and gossip. That's one of the rules in this arena: there are no rules. :)
I consider it irrational for someone to believe that a limited number of hand-selected studies can give you absolute confidence.
Even if it were a limited number of studies, gwern's not going for "absolute confidence". (Indeed, requiring "absolute confidence" before attempting a thing is irrational by the following sentence.) Irrational here means doing something with expected value less than zero. If you're a person living in an industrialized society with ready access to electrical lighting -- the possible gains are too large to be balanced out by the time wasted trying it. That's what gwern's saying.
A positive but cautious conclusion like http://www.vanderbilt.edu/AnS/psychology/health_psychology/m... would have been much more appropriate.
The black swan is a pretty useless concept at this point, because people like you will drag it out against anything they dislike. You cannot give any rigorous formulation or evidence for it, and the best you can do is drag out some old example like thalidomide.
Yes it's hard and often impossible to quantify black swans. But keeping them in mind is a way to avoid overconfident articles like the one you wrote.
Alright, let me clarify it then: by the remotely meaningful version presented by Taleb, your argument doesn't work and Taleb's writings support taking melatonin, rather than not taking melatonin. Why? Because even in the event of a negative 'black swan' your losses are strictly limited: the worse that can happen is you die. In fact, if I may borrow Taleb's 2x2 table from _The Black Swan_ where he brings up positive 'black swans' as well, it's easier to make a case that taking melatonin is a positive 'black swan': the negative possibilities are strictly in Mediocristan, with limited losses, easy to measure over large populations, predictable, not varying over time; while the positive possibilities look like some of Taleb's examples of attempting to exploit positive 'black swans' in Absurdistan - improved productivity, healthy, and seizing opportunities, things with potentially unlimited payoffs - such as moving to cities and networking with people.
> For example, a greater risk of dying after 20 or 30 years of use - which has not yet been studied.
FUD.
You do not mention any studies of long term effects and you consider FUD raising the possibility that there could be adverse effects. When more and more studies show negative long term effect of substances that were considered innocuous (like vitamins), it's not FUD, it's being reasonably cautious.
Not at all. Taleb like to use the example of selling insurance and shorts, where your downside is unlimited. Millions, billions, trillions... Think AIG or LTCM. Not everything has consequences solely for health.
> You do not mention any studies of long term effects and you consider FUD raising the possibility that there could be adverse effects.
In the absence of any evidence whatsoever for that, and plenty of positive correlations, short-term studies without any problem... Yes. It is FUD. Fear, uncertainty, and doubt.
> When more and more studies show negative long term effect of substances that were considered innocuous (like vitamins), it's not FUD, it's being reasonably cautious.
Only some vitamins show any mortality effects, the mortality effects while real are pretty small, the vitamins did not deliver the long-term health benefits promised (but never really demonstrated in experiments) which might offset the harm, and the vitamins were being consumed in huge doses. The first reduces the possibility of any such outcome, the second points out that you are exaggerating the harm, the third means that vitamins were a purely speculative play unlike melatonin, and the fourth reduces the concern that any such thing would happen with melatonin when one sticks to the suggested doses like 0.5mg rather than 5mg.
I don't argue that this doesn't help a fraction of people, but the case is pretty weak and the long-term results of tampering with a critical hormone are unknown.
No offense to the author but I've read at least 3 of his articles posted here and they all follow a similar pattern.
That kind of numbers is a red flag to me. It indicates that these studies may have issues, which I suspect they do.
[1] "Dietary supplement industry says 'no' to more information for consumers (again)" 3 October 2013
http://www.sciencebasedmedicine.org/big-supp-resists-giving-...