Episode 140

Quick — tell us everything you know about the pineal gland.

It’s probably not much, right?  That’s ok, because until surprisingly recently, scientists didn’t know much either.

But we now know quite a lot, including the pineal gland’s essential function producing melatonin.  Dr. Richard Wurtman, Cecil H.Green Distinguished Professor emeritus at the Massachusetts Institute of Technology, talks to us about his work studying the pineal gland and melatonin.

The Third Eye

Your pineal gland is a small endocrine gland in the brain.  It was first studied in relation to amphibians (turns out it lightens frog skin) where it’s linked to the parietal eye (also known as the “Third Eye”), which regulates the circadian rhythm based on levels of light in the environment.

But scientists didn’t think it had any function in mammals — considering it an atrophied, vestigial photoreceptor — and certainly nothing to do with melatonin (which was only discovered in the late 1950s).

Eventually, however, Dr. Wurtman and colleagues discovered that if you put animals in constant, bright light, their pineal glands would shrink, and melatonin production would be severely curtailed.

So, it turns out, the pineal gland is still like a third eye, although it’s no longer a photoreceptor, which is why light is first detected by your retina, before that information is passed on to the pineal gland.

High At Night and Low In the Daytime

Once the connection between light and the pineal gland was discovered, it was easy to piece together the role of melatonin.

Environmental levels of lightness and darkness entrain your circadian rhythm, so you sleep when it’s dark and are awake when it’s light.  This, in turn, affects melatonin production, so that melatonin is actively produced at night, with very little produced in the day time.

Since levels are high at night, Dr. Wurtman began wondering if melatonin had something to do with sleep onset.  Spoiler alert:  It did.

Melatonin promotes sleep onset and maintenance, i.e. falling and staying asleep.

Your Aging Pineal Gland

Among other indignities that occur as you age, your pineal gland is calcifying, meaning it’s producing less melatonin at night.  This is why older adults have a hard time staying asleep — they produce enough melatonin to fall asleep, but not enough to stay asleep throughout the night.

It’s a pretty easy condition to fix:  just supplement with melatonin.

But wait, it’s not that easy.  Why?  Because the correct dose of melatonin is fairly small (0.3mg) but your body very quickly metabolizes melatonin.

So, if you take 0.3 mg of melatonin before bed, you’ll easily fall asleep, but it won’t be enough to keep you asleep throughout the night.

So just take a much higher dose, right?  Nope.

Melatonin Desensitization

Older adults do need to take melatonin every night, but they’re taking doses that are much too high.

Melatonin is often sold in pills of 3 mg (and even higher), which is 10x the recommended dose (here’s a time-release melatonin pill in the correct dose).  The good news is that melatonin is extremely non-toxic, so you’ll never overdose.

But you will blow out your melatonin receptors, so that melatonin supplements stop being effective.  When you have so much extra melatonin in your system, your melatonin receptors become desensitized and stop reacting to all that extra melatonin.

Companies are able to sell such high dosage melatonin because the FDA decided to classify melatonin as a dietary supplement, resulting in little oversight.

Dr. Wurtman points out what a mistake this is, since melatonin is clearly a hormone, not a dietary supplement, and no food has ever been found to raise melatonin levels.

Bottom line

The correct dose of melatonin is 0.3 mg.  Taking the lowest effective dose will avoid desensitizing your receptors.

Tune into the episode for more on melatonin, plus how different light wavelengths and meal times affect your sleep.

Episode Highlights

0:42Melatonin with Dr. Richard Wurtman
1:46This Week in Neuroscience: Frigatebirds sleep in mid-flight
6:20News and audience interaction
8:43What is a neuromodulator?
10:24Discovery of the pineal gland’s function and how melatonin works
20:43Differences in melatonin levels as we age, sleep efficiency, and desensitization
25:05What doses should people be taking?
28:35How does excess melatonin get cleaned out of our systems?
29:30Melatonin and light sensitivity
33:29The relationship between melatonin and insulin production
34:14Is melatonin an antioxidant? (Not really…)
36:19Ruthless Listener-Retention Gimmick: Setting free the words trapped in our heads

PS:  Don’t stay in the dark — sign up for our weekly Brain Breakfast!

Episode Transcript hideshow

Dr. Richard Wurtman: Well, if you look at a textbook of medicine or physiology that was published even up until the 1960s, you look up “pineal,” you would see it described as a vestige, an organ that had some function much earlier in evolutionary history but has lost that function with evolution.  They were wrong of course, but the reasons people believed this was that, first of all, in lower animals, in amphibians for instance, the pineal is, in effect, a third eye, it’s a photoreceptor, and with mammals, that’s completely lost.  So it had a function and then it lost its function.  Then another thing, in you and I, the gland itself that makes it starts to become calcified, and you can visualize that with X-rays in someone who’s eight or ten-years-old, and it gets worse and worse, and worse and worse.  And usually calcification is what happens after a tissue dies.  The lungs used to be full of calcium in the case of tuberculosis.  People thought that, “Well, the pineal, it’s not important.  It doesn’t do anything it used to, and it just sits there as a lump of calcium.” No function was known, and that’s the way thing stood, at least in the textbooks, until the 1960s. 

But actually there had been some work done before the ‘60s that suggested where things were going to go.  1924, some studies were done at Johns Hopkins by a couple of endocrinologists, McCord and Allen, and this was kind of the heydey of finding new hormones.  What people would do is they would set up a bioassay something that responded if you had a biologically-active compound you threw in.  Then they would take a gland, like the thyroid for instance, and mash it up and put it in the medium where tadpoles were swimming.  And the thyroid gland contains something, thyroxin, which when you expose tadpoles to it, it accelerated their maturation, they became frogs faster.  Okay, so once you knew that there was some biologically-active compound, you could purify it and see what else it does.  Well at the same time, in 1924, these same people, they took their tadpoles, they took pineal glands from cattle and they mashed them up, and they threw them into the mix, the bouillabaisse if you will, and it turned out that the tadpoles became very light colored.  Now, tadpoles and amphibians treat pigment differently from you and I.  We make pigment in cells that are called melanocytes in the skin, and they make the pigment and then the melanocyte cells turn over, that’s why you lose your sun tan three or four weeks after the end of the summer.  But in amphibians, the pigment is retained in cells called melanophores, and what they do, they stay there, they don’t turn over; what they do is they have pigment granules inside the cell, and when the cell is stimulated by something called a melanocyte-stimulating hormone, the pigment granules spread out, and so the animal appears black.  And then when you expose the animals, it turned out to melatonin, the pigment granules coalesced around a nucleus, so the animal looked white.  So anyhow, in the 1920s it was shown the pineal contained something that caused the animal to appear white because it caused the pigment granules to kind of coalesce.  That was one fact which turned out to be very important.

Another fact had to do with the gonads.  Boys especially will sometimes rarely develop precocious sexual maturation, precocious puberty, and it was thought that the precocious puberty was caused by a tumor of the pineal, so the pineal had something to do with the gonads.  This has not held up over the years, but it was believed and it turned out to be important in that generated some key research.  And the third thing, again, is related to the third-eye business.  Even though the pineal of a human or a rat is no longer a third eye, people wondered whether light had something to do with the pineal anyhow.  And so a woman at Wellesley College, Virginia Fisk, she got to do one piece of research every seven years, they gave her time off for it.  She took a bunch of rats and she put them under constant light or constant darkness, and she took out their pineal glands—this was already in the 1950s—and she weighted the pineals, and she discovered that light suppressed the rat, the mammalian pineal.  Okay, so by the end of the 1950s, what was known as the pineal gained an active compound that did something to pigment cells, the pineal might have something to do with the gonads, and the pineal was responsive to light.

So then I kind of came on to the scene, I became a medical student at Harvard.  Around this time, the government was trying to encourage the doctors to go into research.  Believe it or not, they sent people around saying, “Won’t you please take our money and dedicate part of your career to doing research?” So there was the dean at Harvard whose job it was to try to seduce medical students into spending part of their time on research.  I wanted to do that anyhow; I’d come to medical school, I wanted to do work in what used to be called the mind-body problem, and that would’ve involved research.  So anyhow, I agreed to do research and they paired me up with a professor, a guy named Mark Altschule, and Altschule had what turned out to be a totally wrong theory, and the theory was that the pineal gland has something to do with schizophrenia.  And so, he wanted me to set up assays for schizophrenia.  I won’t bore you with all the details, but anyhow it introduced me to the pineal gland, and I looked into it and found that very, very little was known but it was kind of interesting.  So I started doing some research in medical school in which I took out the pineals of animals and, guess what, their gonads matured more rapidly, or I got some bovine pineals, ground them up, and gave extracts, that maybe the gonads delayed maturation.  Then I found that if you took animals and put them in light the way Dr. Fisk had done, the pineals would shrink and they would get the accelerated maturation; giving them pineal extracts would block the effect.  So anyhow, I came away from that with the notion that, hey, the pineal makes something which is probably a hormone and which probably has something to do with sexual maturation, at least in rats, and something to do with light.

Okay, 1959.  In New Haven, a dermatologist, a guy named Aaron Lerner, reads the old literature and decides he would like to know what is the compound in pineal extracts that cause those tadpoles to lighten.  And the reason he’d wanted to do this work was there’s a disease called vitiligo.  Perhaps you see people—people get deep pigmented spots… He was a dermatologist and he thought he could treat these people by giving them something that would cause pigment to go away everywhere so that spots wouldn’t be so noticeable.  So he got something like a quarter of a million pineal glands from Armour & Company, the livestock company in Chicago.  And he did very good chemistry, and purified a compound, and found the compound that was very, very potent at making the tadpoles turn white, and he wanted to name it “yalin” as he did the work at Yale, but people encouraged him not to do that, so instead he named it melatonin.  So by the end of the 1950s, there’s a compound in the mammalian pineal that is biologically active.

Now, parenthetically it turns out that it has no real effect on pigment in people and there still is no evidence that amphibians even actually make the compound.  But we knew, hey, here’s a compound that does something, so people could start looking to see whether or not it did things that were interesting and important.  And again, I’d meanwhile shown that it had something to do with gonadal maturation, something to do with light effects, and the pineal had something to do with it.  So we could ask the question, is the active principle in the mammalian pineal that does these other things, by the way the same compound as the compound that lightens amphibians? And I’d moved to the National Institutes of Health after finishing some residency training, and started working with a wonderful man named Julius Axelrod, and Julie was fascinating in himself.  He didn’t get his PhD until he was 47 or 48-years-old, he couldn’t afford to go to school.  But he worked as a technician in a lab at the NIH and made great discoveries, and by the time he was 47-48, he’d published a hundred papers even though he didn’t have a PhD.  And he decided to go get a PhD, he went to George Washington University, took the language test, that was all that was needed then.  Got his PhD and he started taking post-docs and I was his second post-doc, and he won the Nobel Prize about five or six years later.  He was the guy that discovered uptake, which is how drugs like Prozac work, they block Prozac.

So when I got to work with Julie, told him what I had been doing prior to coming down, he got very interested, because melatonin chemically contained a methyl group, and Julie had been discovering the enzymes that put methyl groups on things.  And so, we decided to see whether or not melatonin, besides making tadpoles light, was also a pineal hormone.  And we did studies and it turned out that they were very active, and we wrote the first paper in 1962-1963 saying melatonin is a hormone.  So then we went back and tried to see whether or not the other things that had been attributed to the pineal could also be attributed to melatonin.  For instance, we knew that light, exposure to light made pineals small.  Well, what did light do to melatonin production? So we did some studies and showed that, hey, if you put animals under continuous light, not only did their pineals shrink, but they pretty much stopped making melatonin, they reduced melatonin production by 80% to 90%.  And we figured out what’s the pathway by which information goes from the eyes through the pineal is no longer a photoreceptor, so you need a pathway that will do that.

So by the mid 1960s then, it was known that, well, there’s this compound, melatonin, which is biologically active and which is controlled by light exposure and which has various biological effects.  Well then I moved on to MIT and set up a laboratory and the lab worked on a lot of different things, there are about 40 people in it, but one of the things always was melatonin, let’s see if we can figure out what melatonin does.  Well, we knew that melatonin production was suppressed in light and stimulated in darkness.  What happens in people? So we set up ways of measuring blood melatonin levels in people, and in 1975 I think it was, we discovered that in people, yes, blood melatonin levels are high at night time and low in the day time.  And it’s not that light and dark cause these changes, rather light and dark entrain the circadian rhythm.  So there’s normally a circadian rhythm, as I said, and during the nocturnal period melatonin production goes on actively, and during the day time there’s very little melatonin.  We published this and, okay, now we know that melatonin is up at night time, it happens at night time, most people sleep at night time.  So I began wondering whether perhaps melatonin might have something to do with initiating sleep onset and maintaining sleep and what have you.  But then I realized that, okay, you’re sleeping in the middle of the night, but rats aren’t, they’re running around.  So it can’t be related to sleep, right? So I put the project aside for about ten years.

But then I had a really great post-doctoral fellow, Andy Dollins, he said, “Why don’t we look and see what happens with melatonin and sleep anyhow, because maybe rats are different from people.” So in the mid 1990s, giving very small amounts of melatonin, we found that melatonin does, in fact, promote sleep onset and also sleep maintenance.  Did those studies in normal people, gave them melatonin in the middle of the day around noon, allowed them to lie down, and many of them fell asleep.  So then we decided to look at a particular population that I thought might really benefit from having melatonin…

Jesse: Let me interrupt with a question real quick: how does melatonin interact with adenosine, another one of the brain’s chemical modulators for when we get sleepy?

Dr. Richard Wurtman: There’s no evidence that it does.  I think there are redundant mechanisms that had to do with sleep.  Melatonin, again, is a hormone and it gets into the brain and it combines with so-called melatonin receptors on brain neurons, and through this action on the receptors it promotes sleep onset and sleep maintenance.  I’m not exactly sure how adenosine works.  So we had shown—and other people had also found—that as you get older, because your pineal gland is calcifying, it puts out less and less and less melatonin at night time.  So whereas in a normal young person blood levels are let’s say 10 in the day time, there’s very little being secreted, but they rise to 150 pg/mL at night time—big daily rhythm.  An older person like me, they’re still 10 in the day time, there’s very little being secreted anyhow, but instead of rising to 150, they only rise to about 30 or 40.  So what happens is you have enough melatonin to help you fall asleep but not enough to keep you asleep throughout the night, and the reason that lots of older people tend to awaken at two or three in the morning and lie awake in bed for half an hour or longer, unable to fall back asleep, we thought might be because they were deficient in melatonin during the night.

So by the year 2000, we started doing some studies on older people who complained about this kind of insomnia and who, in fact, we could show had low blood melatonin levels during the night.  And we found that, yes, if we gave them supplemental melatonin before they went to sleep or before they awaken, we could help them to sleep through the night.  It’s something called sleep efficiency.  Sleep efficiency is really what percent of the time that you’re lying there are you actually asleep.  In normal younger people, it’s like 92% to 93%.  Everybody awakens, but you’re not even aware of it.  You may awaken and go pee or something and then go back to sleep.  But older people, the sleep efficiency may only be like 60% or 70% during the middle of the night, and that’s really not very pleasant.

So we did studies and we found that, yeah, giving melatonin to these people would very much promote the maintenance of sleep throughout the night.  But the dose that you had to give was very, very low.  You only wanted to give enough to get them back up from 10 to 150, but people started taking immense doses of melatonin, partly I guess because in America we always think bigger is better.  They would take doses of, let’s say, 3 mg or 5mg, which are like 10 to 15 times more than they should take.  And if they took it just for one night while they were flying to Europe or something, that would be okay because you can’t do too much damage.  But if they tried to take it every night the way older people really need to do, what happens is the ability of the melatonin to stimulate its receptors in the brain diminished; the receptors became less sensitive to melatonin.  So you have people who say, “Oh doctor, it was great, I responded beautifully for a week or so and then it stopped working.” Well, that’s why it stops working: you desensitize the receptors.

The problem is you want to give enough melatonin to people if they’re taking it at bedtime so that levels are still high in the middle of the night.  But the turnover time is pretty fast, so if you give people 0.3 at bedtime, then the odds are that by two o’clock or three o’clock in the morning, there really isn’t going to be very much left in the circulation.  So, why not give them ten times as much when they go to sleep so you’ll have it when you need it in the middle of the night? Well then your levels get to be far too high, and that’s what causes the desensitisation, etc.  So what companies have been doing is playing around with long-acting preparations, and one that really intrigues me, it’s a capsule, and there’s a capsule within a capsule inside it.  So inside the outer capsule there’s a solution that contains a starter dose, 0.3 of melatonin, and then the inner capsule contains another dose of melatonin, 0.6.  So you take the outer capsule and you get the solution right away, but then over a period of time you break down the inner capsule and get basically the second dose in the middle of the night, and apparently it’s highly effective.  But I think that this sort of thing, a preparation that presents it so that blood levels are high enough when you need it but not terribly high when you don’t need it, I think that really will be a big advance.

Jesse: Yeah, I’m kind of surprised they haven’t been doing that already because it seems like—I think it’s called buffering pills that have that time release mechanism as a fairly solved problem.

Dr. Richard Wurtman: Well here’s the thing: if you go into a health food store, you’ll find a bunch of things on the shelf that claim they have a delayed action component which releases it.  But then you look and you ask, well, have they ever actually done a study to give these pills to people and take some blood and measure the melatonin? And then they glare at you and they walk away.  But you can claim anything you want.  In any case, we’ve not only found that melatonin would help people to stay asleep, but also we found that, perhaps paradoxically, the lower the dose, the better, and the dose that people should take is 1 mg or less.  Most older people do well with 0.3 mg if they can find it for sale at a store, or else they buy 1 mg pills and kind of cut them in half.  Anyhow, we published this in 2001 and then, unfortunately for a lot of reasons, it appeared on 9/13/2001.  Well, what happened two days earlier? 9/11.  So MIT had prepared major press releases about this to go everywhere because they really thought it was important.  No newspaper was interested in publishing anything about melatonin and sleep two days after 9/11, and for that reason it took a long time for it to catch on.

The other thing that happened, when MIT decided to go ahead and patent the discovery—I don’t have any patents, but MIT has a bunch of patents of things that I’ve discovered, and okay, that’s the condition of employment.  They decided to go ahead and patent it, but they made a mistake.  Instead of patenting any dose of melatonin, they figured that, no, let’s just patent it up to 1 mg because the FDA is going to regulate this.  After all, we’re using it as a drug, right? And if the FDA regulates it, they’re not going to let companies sell 10, 15, 20 times more than what’s needed.  Good idea, but the FDA decided not to regulate it.  They decided to call this hormone a dietary supplement.  Dietary supplements are not regulated by the FDA so as a way of getting it out of their hair.  The thing is, it’s not a dietary supplement.  No food has ever been shown to raise blood melatonin levels.  There are a lot of compounds in foods, like serotonin, which have some chemical properties similar to melatonin, but if you do the kind of rigorous testing you have to do, no one has ever demonstrated melatonin in food and no one has ever demonstrated any food raises blood levels of melatonin.  So, calling it a dietary supplement is just plain wrong.

What this meant though is that if companies sold more than 1 mg of melatonin, they didn’t have to pay MIT its royalty of a hundredth of a penny per pill.  So, that’s the reason if you go into a dietary supplement store right now, you’ll see loads of bottles of 10mg pills, 5 mg pills, of 3 mg pills, you’ll see some of 1 mg but rarely will you see the correct dose, which is 0.3 mg.  So the companies, they really ought to give people what the correct dose is, but I guess they have the wrong business reasons for not doing so.  If someone is just taking melatonin because they have a trip coming up and they need some assistance in falling asleep on the jet for one night or two nights, it doesn’t really matter much what dose they take.  On the other hand, if they’re going to need it continuously, then they really should take the lowest fully effective dose because anything more than that is going to desensitize their brain and make them less and less responsive to melatonin. 

So, that’s kind of where things are right now.  Loads of people take it.  I’ve received some information from the branch of the NIH that deals with dietary supplements.  One and a half to two million people in America presumably bought and used melatonin last February, that was the month that they kind of assessed this.  And people are using it, and the main use for it, again, is not in people who are going to Europe, it’s in older people who can’t make enough and who need it to kind of stay asleep.  And I’m really delighted that so many people are using this thing that I kind of found, because you cannot commit suicide with melatonin, it’s utterly non-toxic, and that’s another reason I think why the FDA was willing not to label it a drug or label it a hormone.  They just wanted to get it out of their hair.  They were dealing with this at the same time they were deciding to try to get nicotine less available, and I guess they figured they had enough fish to fry at that time.

Jesse: How does melatonin sort of clear the system when the sun is up and we don’t need it, the higher levels within our body? Is it something that is actively cleaned out of the blood?

Dr. Richard Wurtman: Yes, in the liver.  Melatonin chemically is very lipid-soluble.  Melatonin is simply serotonin in which the two ends in serotonin that are electrically charged, they’re blocked.  As a consequence, melatonin is very, very soluble in lipids.  It’s also soluble in water, but more so in lipids.  So, it’s secreted into the circulation, and of course the brain is lipid, and it goes everywhere but it really concentrates in the brain, which is where it’s supposed to work.  But then when it goes through the liver, it’s further changed enzymatically to water-soluble metabolites, which are excreted in the urine.  And so if you stop secreting it for a couple of hours, its levels fall pretty rapidly.  That’s why the blood melatonin levels really look like a square wave.  It’s low, and then wham, it gets to be high around 10-11 at night, stays up until 5 or 6 in the morning, and wham, comes back down again until the next night.

Jesse: As far as how the body knows when it’s light and dark, is there any particular wavelength of light? Is this light coming through the eyes? Does the skin have anything to do with it? Some of those questions I guess would be interesting to talk about.

Dr. Richard Wurtman: Sure.  The way the body knows for melatonin really is through the eye.  Every now and then you’ll hear a paper… There was a paper a couple of years ago, I was just laughing about it, in which someone said if you shine light in the back of the knee, that controls melatonin.  Let us just say that has not been confirmed, okay? But it got a lot of publicity because I think reporters want to get a lot of publicity, right? No, it comes in by the eye and the information about light goes to the brain, but the portion of that information that will control hormone secretion, melatonin, goes to a different part of the brain.  Then eventually it goes through this pathway that I discovered in animals, down the spinal cord and out sympathetic nerves.  And sympathetic nerves usually run to blood vessels, but in this case sympathetic nerves run right back up into the head and communicate with the pineal cells that control the production of melatonin.  So in darkness, you have sympathetic nerves firing and the nerves go to the pineal, and so it makes more melatonin.  And in light, the sympathetic nerves paradoxically stop firing and they stop making the melatonin.

Now in terms of wavelength, virtually any visible wavelength will suppress melatonin production.  The most potent visible wavelength is yellow/green, that’s the strongest suppressor.  But they all will do it.  Now, some people believe that they benefit by spending the early evening in blue light.  I find it awfully hard to read by blue light, but blue light only minimally suppresses melatonin production.  But there too, it depends on the intensity of the light.  If you provide enough light to have some practical benefit, like being able to read, then it really doesn’t make much difference whether the light is blue, or even red, or green, or what have you.  There was a lot of interest 30-40 years ago in using light, per se, as a treatment for diseases.  This came about because, actually the Russians showed this, if you have newborn kids that had jaundice, as a lot of kids do, and you took their bed out of the nursery and put it under the direct sunlight, then you cured the jaundice.  And there it was shown that, in fact, it was the blue light and sunlight that got rid of the bilirubin in the blood, and some companies began manufacturing blood light-emitting devices for the treatment of kids, particularly premature kids, with a lot of jaundice.  And they work beautifully, but that really does work via the skin, not via the pineal gland.

Jesse: It seems like there’s been a lot of buzz in the past couple of years about different wavelengths of light and how this has different effects on us, waking us up in the morning or keeping us up late at night, that the wavelength itself can be a big circadian trigger.  It sounds like from what you’re saying that’s a little bit overblown?

Dr. Richard Wurtman: I think that’s true.  I think what’s more important is the intensity of the light.  Instead of going sharp on, sharp off, if you modulate it, you go from no lights gradually over a period of some minutes up to full light and then back down again, I think that probably is effective, at least for some people.

Jesse: And what about people who are fully blind and aren’t getting any information at all through their eyes? Do they exist in a constant melatonin state naturally?

Dr. Richard Wurtman: Well, they’re all over the map.  Some blind people will continue to have a circadian rhythm that’s pretty close to 12 hours, some of them will have a circadian rhythm that can be 10 or even 14 hours, and some of them will have irregularity from day-to-day in what their rhythms are.  The question is how do these people respond to the lighting environment if they don’t perceive light? The answer is they’re not really responding to the lighting environment, they’re responding to other behaviors that are coupled to the lighting environment.  I mean if you live in a world in which at a certain period of the 24-hour cycle people are talking to you, there’s noise, people are working, etc., that’s called day time, right?

Jesse: Right, you hope.

Dr. Richard Wurtman: Yeah, you hope, that’s right.  So people can get some control over circadian rhythms by using other cyclic environmental cues above and beyond light.  Eating, for instance.  Eating can be a major cue controlling metabolic function of the body.  If you eat a food that contains a fair amount of protein, this turns on production of a lot of proteins, like albumin for instance in the liver, and it also turns on serotonin production in the brain if you’re eating mostly carbohydrates.  So you can respond to those cues, which are spread out through the 24-hour cycle, and get some benefit that way.  However, it’s not as good as having sight.

Jesse: Speaking of food actually, there’s a relationship, as I understand it, between melatonin and insulin production, and this might sort of inform when we might want to time our meals with our sleeping.  Can you talk about that a little?

Dr. Richard Wurtman: This is something that has been written about by a couple of people.  It’s by no means ready to go into the standard melatonin literature.  Here’s what I mean by that: There’s an internet textbook called UpToDate that a very large number of doctors subscribe to, and I write the section on melatonin in that.  So every year I have to ask myself, well is the evidence solid enough so that I can canonize it by putting it in? I have not yet put melatonin and insulin in yet.  I’m following it; it will be very interesting if there is a relationship.  All I can say is I will continue to follow it.  I don’t think at this point enough is known to warrant changes in lifestyle to deal with it.

Jesse: You mentioned in an email that I might come across information on melatonin as an antioxidant, that that was a spurious claim, something to watch out for.  Do you want to officially debunk that one?

Dr. Richard Wurtman: Yeah, if you give melatonin to raise blood levels to 1 to 10,000 times higher than they normally are, that has some antioxidant activity, and that’s what’s been shown.  People have measured antioxidant activity in a test tube; they’ve put in concentrations of melatonin that are utterly unrealistic, concentrations that which if you put in a hundredth as much vitamin C, you’d get an equivalent amount of antioxidant activity, or vitamin E for instance.  I suspect—now this sounds conspiratorial—that the people who are selling these mega-doses of 10mg of melatonin, maybe they know in their heart of hearts they shouldn’t be doing it for sleep.  And they say, “Well, it’ll be good for your oxidation capacity.” I don’t know.  It’s way off the charts in terms of the concentrations that are needed.

Jesse: The pineal body, other than producing melatonin and slowly calcifying, is there anything else that it seems to be doing? Any other functions?

Dr. Richard Wurtman: Every now and then somebody will write a paper exclaiming that he has found some peptide in the pineal, but then they don’t get confirmed and so they kind of fall by the wayside.  I’m afraid I would have to say no to your question right now, with the disclaimer that it wouldn’t utterly shock me that next month an article appears that’s a good article claiming that something else has been found.  Nevertheless, word has not been spoken on these things, and it’s important, if you’re interested, to follow.  But no, I’m afraid at this point there’s nothing else that I know of that one can claim the pineal does of biological importance besides make melatonin.  Stay tuned. 

Written by Hannah Sabih
Hannah believes there's nothing 8 hours of sleep and some kale can't cure (yes, she's from California). She's an avid runner, reader, and traveler, who brings you the latest and greatest in neuroscience via our social media channels.
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