FX Medicine

Home of integrative and complementary medicine

Melatonin: mechanisms of action and it’s amazing role beyond sleep with Dr. Adrian Lopresti and Dr. Deanna Minich

Adrian_Lopresti's picture

Melatonin mechanisms of action & it’s amazing role beyond sleep with Adrian Lopresti & Deanna Minich

Dr. Deanna Minich provides a comprehensive exploration of the diverse aspects of melatonin for a deeper understanding on the mechanisms and benefits of this sleep-associated neurotransmitter. The discussion, hosted by fx Ambassador Dr. Adrian Lopresti, covers the different types of melatonin in the body, shedding light on its production sites and presence throughout most body systems.

Furthermore, it delves into the connection between melatonin and the gut, melatonin's impact on mitochondria, and a detailed breakdown of the six pivotal roles that melatonin plays. They discuss the variety of health conditions melatonin can support, and outline natural methods to boost melatonin production - starting with optimising exposure to light, dietary recommendations and the power of plant sourced melatonin.

Listeners will gain insights into the amount of melatonin produced endogenously across various life stages and, most importantly, the podcast discusses safety, varying regulation, and offers crucial dosage recommendations supported by evidence.


(00:33) Welcoming Dr. Deanna Minich
(00:57) What is melatonin?
(04:27) The role of melatonin in the gut
(06:31) The role of melatonin in energy production
(08:27) Therapeutic benefits of melatonin
(10:22) Melatonin’s role in ageing
(11:43) Melatonin in inflammation
(13:56) How light affects the production of melatonin
(21:14) How diet affects the production of melatonin
(29:21) Plant melatonin
(31:39) Melatonin production reduction through ageing
(34:34) Melatonin and the circadian rhythm
(40:57) Melatonin - a molecule of consciousness
(44:12) The role of stress in melatonin production
(46:27) Melatonin supplementation
(51:59) Melatonin dosage
(55:48) Timing on supplementation for sleep
(58:58) Synergystic effects of melatonin and nutritionals
(01:00) Melatonin dosage in perimenopause
(01:03) Thanking Dr. Minich and closing remarks


  • Defined types of melatonin:
    - pineal melatonin - involved the endocrine system (response to darkness and CLOCK system)
    - autocrine and paracrine types distributed throughout the body. Melatonin is amphipathic - both water and fat loving. Found in most body systems and cells.

There is 400x melatonin in the gut than pineal gland! Although not fully understood, gut melatonin is linked to motility, secretions, and immune systems interactions.

  • 6 roles of melatonin:
    • mitochondrial antioxidant defence system
    • anti-inflammatory
    • nerve growth factor, role of “cleaning” the brain by regulating glymphatic fluid
    • phase separation in regulating abhorrent cellular processes circadian rhythm

Melatonin can support mood disorders, dementia, pain disorders, T2DM, BGL regulation, sleep disturbance, migraine, and neurodegenerative conditions

  • Amounts of endogenous production of melatonin across the lifespan
    • Birth - Infants - Minimal melatonin that increases
    • Childhood - endogenous production is highest
    • Puberty - incremental decreases mid 50’s and onward - greatly reduced melatonin compared to childhood
  • Natural ways to inhibit melatonin suppression:
    • Biggest bang for buck - adequate exposure to darkness at night (light pollution is a type of endocrine/melatonin disruptor).
    • 10 lux max. For 3 hours prior bedtime to best align with natural day/night cycles.
    • Aim for zero lux for bedrooms.
    • Other lighting tips are discussed.
    • Diet and eating to influence zeitgebers, especially proteins (tryptophan) and eating the rainbow. Lutein and zeaxanthin (red and yellow foods) protect from blue light exposure.

Plant melatonin - ensure a high quality form is sourced (synthetic production is linked to high toxin as a byproduct). Melatonin works synergistically with vitamin-C to quench free radicals.

  • Dosage recommendations
    • 0.3mg: Adult dosing for replenishing levels that match endogenous production
    • 1 - 10 mg: Consider higher amounts for conditions like dementia, immune and acute states (i.e. jet lag, migraine) for short periods
    • To aid with sleep take 40-60 minutes prior to bedtime. Grogginess may effect people who are slow metabolisers (SNP CYP1A2 - aligns with caffeine metabolism gene). Increase the time prior to bedtime to counter this side effect.

Resources discussed and further reading


Deanna's website
Connect with Deanna: Instagram | Facebook | YouTube
Certification Program
Whole Detox




Journal: The role of Melatonin in Pregnancy and the health benefits for the newborn


Research: Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties 
Article: Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements 


Dr. Russell Reiter's book


Adrian: Hi, and welcome to fx Medicine, where we bring you the latest in evidence-based, integrative, functional, and complementary medicine. fx Medicine acknowledges the traditional custodians of country throughout Australia, where we live and work, and their connections to land, sea, and community. We pay our respect to the elders past and present, and extend that respect to all Aboriginal and Torres Strait Islander people today.

Dr. Deanna Minich is a nutritional scientist, international lecturer, and certified functional medicine practitioner. She has a Master of Science degree in human nutrition and dietetics and has completed her doctorate in the nutritional field. Deanna is the author of six books, including The Rainbow Diet and Whole Detox, and has published more than 50 scientific publications and book chapters. Recently, Deanna published a comprehensive scientific review on melatonin, where she referred to melatonin deficiency as a darkness deficiency. And it is her expertise in melatonin that we'll be discussing today. Welcome to fx Medicine, Deanna, thanks for being with us today.

Deanna: It's my pleasure to be here with you, Adrian. Thanks for having me.

Adrian: Yeah. So, today I wanted to talk about melatonin, and provide an overview for our listeners about melatonin and its role and benefits, and talk about its supplementation. But firstly, can you tell us a little bit about melatonin, and what it does in the body?

Deanna: You bet. So, melatonin, if we just break apart the name, mela, which is connected to the pigment in the skin, and it was thought to be something that lightened the skin. And then tonin, it resembled the structure of serotonin. So it was named as melatonin in 1958 by the dermatologist that basically was working on it for skin.

But basically melatonin is an indolamine. it looks like a neurotransmitter with an amine group attached to it. And what's really unique about melatonin is that it's everywhere, absolutely everywhere. In nature, it's in animals, in our bodies. And actually, we make it through the pineal glands. So you were asking, where is it made? There are different types of melatonin in the body, and I think that this is where a bit of the nuance comes into it. So we have what is referred to as the pineal melatonin, and the pineal gland, which is in the brain, is more part of the endocrine system.

So when the pineal gland produces melatonin in response to darkness, that then is sent systemically to connect to different cells and to basically key into the clock system. So that's one form of melatonin. And I think that that's the type of melatonin that most people are keyed into. The other type of melatonin is the more autocrine and paracrine types of melatonin. So that's the melatonin everywhere else in the body that's just produced within the cell.

So, as an example, the mitochondria are huge producers of melatonin. So every cell type that has a mitochondria, or the mitochondrion itself, or more than one, the mitochondria, would be producing melatonin. So we're talking pretty much all body tissues. And the reason why it's also all body tissues is because melatonin is amphiphilic. So it likes fat, it likes water, it can live in the brain. So it can live in fatty areas of the body, and it can also live in water compartments of the body, like the blood. So you're going to find it in the eye, the skin, the liver, the kidney, the thyroid, the thymus, I mean, skeletal muscle, reproductive system. There's probably very few cell types where you would not be finding melatonin.

Adrian: And I read there's about 400 times more melatonin in the gut mucosa than the pineal gland. So, what's the role of melatonin in the gut?

Deanna: I don't think we fully understand it, but here's what I see in the science. You're right. There's about 400 times higher concentration than the pineal gland, and it's not released in accordance with darkness. So that's also the trigger to produce melatonin is different in the gut. It seems to be produced in response to a meal. So there's a postprandial effect. Now, we know that most neurotransmitters are produced in higher amounts in the gut anyway. So melatonin is actually no real exception. We see that with serotonin, we see it with a number of other neuroactive compounds. But what we think is happening there is that it may play a role in, I think it's very interesting as it relates to gastrointestinal motility.

There are some studies looking at the gut microbiome and whether or not it's modulating the gut microbiome, is it modulating secretions in the gastrointestinal tract? And of course, we know that aside from the GI tract, there's a role for melatonin in the immune system, and 70% of the immune system is actually housed in the gut. So there might actually be a role right there locally as it relates to the immune system.

Adrian: And is it the microbiota that's making the melatonin? Is that where it's coming from?

Deanna: From my understanding, it's more the enterochromaffin cells that are releasing serotonin and melatonin. So it's more the neuroendocrine cell types within the gut. So that's why you find it pretty much throughout the extent of the gastrointestinal tract. So I would say it's not limited to the gut microbiome, because you do find it in the esophagus all the way down to the rectum. So I think it's probably connected to the neuroendocrine fraction and perhaps as it connects to the smooth muscle.

Adrian: And so, you also mentioned it's produced by the mitochondria. So is that then having a role with ATP production and energy production?

Deanna: Yes. What we think is happening with the mitochondria is that it's modulating the mitochondria. So, what does the mitochondria get used for? Well, it's the main hub of metabolism. So, oxidative phosphorylation, there's a lot in the way of reactive oxygen species that get produced by way of that metabolic process. And so, melatonin, it's hard to say what it's actually doing there, but this is my theory. I think that from an evolutionary perspective, through prokaryotes into membrane-bound eukaryotes, what we see is that... And melatonin is ancient, it's been around for a really long time. And I think that it was part of the cellular organelle as part of an antioxidant defence system process, and it became a part of that. And that's where we most probably need melatonin, is within the mitochondria, because of the oxidative bursts, all of the reactive oxygen species. So I think that just through the fine-tuning of our physiology over time, it just came to be that way that it was a protective molecule. I think that there's more to unpack there. I don't think that that is solid science. I think so many people focus on melatonin and sleep.

Adrian: Yeah.

Deanna: So there hasn't been a preponderance of research in all of these other areas, even though we know melatonin is active throughout the body and has a variety of different functions.

Adrian: Yeah. That's the thing that really surprised me, was reading the arc, well, it's found in the gut. And certainly, when people think about melatonin, it's associated with sleep. But certainly, it sounds like there's a lot more for us to learn about melatonin and its potential role in the body.

Deanna: Absolutely. And one of the emerging areas is that of its role in the glymphatic fluid exchange. This is really piquing my interest. You know, I kind of think of melatonin in six ways. Number one is an antioxidant that can flex to, like water or fat. Number two, it's anti-inflammatory, so that's why it had a lot of, I would say, attention during the pandemic because it was seen as an agent to quell the cytokine storm. So that's number two. Number three, which I'll go through, is what I find exciting, which is more the neural growth factor effect and its role to mediate the exit of toxic metabolites from the brain into the glymphatic fluid, which is active at night. So that's kind of like a brain detoxification. Some cell biologists are really nerding out into its role in what's called phase separation. And this is not known widely in clinical medicine, but basically, in a cell, viruses, amyloid, just even healthy things, can start to build up in a cell on their own without a membrane.

So they kind of set up a factory, and it looks like melatonin may stop the setup of those factories by viruses or amyloids. So that's why it's being seen as an active in things like dementia. And then, of course the circadian rhythm, sleep-wake cycle, that's branded into all of our minds. And then finally, the mitochondrial regulation. So if you think like a scientist, you'll say, "Oh, those are all interesting mechanisms. So if it works as an antioxidant, anti-inflammatory, mitochondrial regulator, it must play a role in chronic diseases of various types." It's like if you think like that, you can start to see that melatonin goes beyond the reaches of sleep.

Adrian: Yeah. I've even seen some work or some literature recently talking about this kind of role, as anti-aging agents too. Do you think that it plays a role there too?

Deanna: Yeah, because of all those things that I mentioned, right?

Adrian: Mm-hmm.

Deanna: If we look at aging as inflammageing, that there's a connection to inflammation, there's a connectedness to one's toxic load, there's a connectedness to hormone levels, also antioxidant defence enzymes. People with high glutathione are going to fare better than somebody with low glutathione. There's even a relationship between melatonin and glutathione. Melatonin is actually five times more potent than glutathione, and it can also help regulate glutathione and seems to sync up with that.

So if we just think of, what is aging? It's a lot of free radicals. It's an overabundance of oxidative stress. It's inflammation. It's when we don't clean up cells very well and improper autophagy. So, yeah, melatonin can work on a lot of these different pathways, which is why I think a lot of biohackers, at least in the states that I'm aware of, are really into melatonin. Not for the sleep, but for the anti-aging, or healthy aging as I like to say, properties.

Adrian: So you've got then, obviously, melatonin having anti-inflammatory and antioxidant effects. So, does the reverse also apply? Like if somebody is experiencing increased inflammation or increased oxidative stress, would that lower their melatonin concentrations?

Deanna: It should. Theoretically, it should.

Adrian: Mm-hmm.

Deanna: It's hard to say what's the chicken, what's the egg? Because in so many conditions, where you see low melatonin, already you know that there is inflammation issues with oxidative stress. So, in theory, yes, that would seem to be the case.

Some of the conditions that we know clinically, and I know that your podcast audience is more clinical, right? So we think of mood disorders, dementia, pain disorders, certain types of cancer, even type 2 diabetes might have a connection into melatonin. We see that melatonin plays a role in blood sugar. Things like migraine, of course, sleep disturbance, and many of the neurodegenerative conditions like Parkinson's and any kind of mitochondrial dysregulating conditions. So in theory, there's never just going to be one thing, right?

You know, when we think in functional medicine about root causes, many times there's multiple things going on. And what sets it off as a trigger can sometimes be a number of different things like toxic load, poor diet, sedentary lifestyle. So I think it's all kind of jumbled up in there. And melatonin is, I don't see it as the panacea, or it's not like you're just going to take a supplement and smooth over and reverse aging and be free of chronic diseases. But I think it's part of the larger picture of overall hormone balance and endocrine health.

Adrian: Yeah. I wish it was just as simple as just taking a supplement and all our problems would disappear. But unfortunately, that is certainly not the case.

Deanna: It's definitely not the case. It's a bigger context. It's so many different things to look at physically, emotionally, mentally, and spiritually.

Adrian: Absolutely. So, you've mentioned some, obviously, inflammation and antioxidants. So just for our listeners, tell us a bit about, if you can just review for us, what actually affects melatonin. How do we naturally increase our melatonin?

Deanna: Yeah. Well, let's first start, I kind of think of it as a pyramid or a triangle. What's at the base? Where can you get the biggest impact from just diet and lifestyle? And I would say the bottom, the base, the foundation is adequate darkness at night. We got to get our light right, we have to get our darkness right. So the problem in our everyday lives is that we live by electricity, which is really great for productivity, but it's really bad for melatonin production. And if we look at things like artificial light pollution, this is one of those, I call it an endocrine disruptor that is societally and globally accepted. I'm assuming in Australia, it's bright in Sydney, Melbourne, and Perth. And you have that same density of light that is distorting our ability just to naturally make melatonin, right?

Because it is truly the darkness hormone if we're talking about pineal-generated melatonin. So I think of children, they're on their phones at night, they're scrolling, maybe people are on Kindle reading their books late at night. They're at gyms with artificial lighting or fluorescent lighting. They're at shopping malls, or they're in brightly lit places when, really, if you look again at how nature runs us, it's by the sun, it's by the moon, it's by darkness. And we defy that.

We are in environments during the day that are probably a thousand or more times less bright than outside, and then at night, we reverse that and we make our nighttime environments much more bright than it is outside. So the name of the game is to go along with nature's rhythm of light and dark. And that means bright light during the early morning hours. And even that can help to prime nightly melatonin. So bright light, first thing in the morning. Being out in, even if it's a cloudy day, you're still getting full spectrum light. And then when it starts to get dim, and I know you're in winter and I'm in summer, so we're at opposite ends here, but essentially as it's getting dim, you need to somehow modify your inner environment. And there are different apps for this. I use an app to measure my indoor light, because there are certain measures of light, which would be almost like a safeguard. You need to know how your light measures up in your environment. So I use an app, and it's just free, you can download it. And it'll give you the number of lux. Lux is a measure of light. So 1 lux is equal to a candle flame, a metre away.

So, essentially, there are different light exposure recommendations. But essentially if you want to run with the sun and then go into the dark, you need to, for 3 hours before bedtime have up to 10 lux maximum. Now, that may sound like it's not a lot, I think it's actually quite bright, but in the bedroom or wherever one is sleeping, it should be no more than 1 lux. It should actually be zero lux. And that is possible to get. And that's again, if you don't measure the light in your environment, then you simply don't know what's too bright.

Some people are just used to overly bright blue, enriched light, and they don't even know it. The other thing that can help is to wear blue light-blocking glasses at night. There is some science to suggest that that can be very helpful. And believe it or not, eye colour can change your sensitivity to that artificial blue light. So I have light eyes, I have green eyes. People with green, blue, and light brown eyes will be more sensitive to the effects of that artificial blue light at night. So they're going to be more impacted and their melatonin suppression will be greater upon exposure to that artificial blue light versus somebody with dark brown eyes.

Now, that doesn't mean that they shouldn't be attentive to it as well, but it's a really big deal that we have to get our light right and get our darkness right too. I think most people have what we called in the article, darkness deficiency. When we think about vitamin D, and so much has been said about vitamin D over the pandemic, like, "Oh, my goodness, we have a sunlight deficiency. Everybody get out in the sun. This is antiviral, this is good for our immune system." So then people started to get that as a wake-up call and they started to realise, "Yeah, we have a sunlight deficiency. We have a vitamin D deficiency."

Well, I can say the same thing on the other side about darkness deficiency and melatonin. And melatonin and vitamin D, truly in my view are like brother and sister. They're like yin and yang. They work together, they're interrelated. Vitamin D is also considered a hormone. So, yeah, when you ask, well, what can we do to help with melatonin? That's the first thing.

Adrian: So, what's the app that you are referring to?

Deanna: Well, the one I have on my phone is called LightMeter.

Adrian: Yep.

Deanna: It's just all one word, basically. LightMeter, and the M is capitalised. And it's very easy to use. You have to point the camera of your phone as if your eyes were viewing in that direction.
It's amazing because I work in front of a window and my lux in front of the window can be up to 5,000. But if I was not working in front of a window and I was working in front of a wall, my lux would be 200.

Adrian: Wow.

Deanna: Which is not so good if I'm working during the day on a computer, and I have such low light exposure. Another thing, we just are coming off of a full moon. And there was a very interesting study and it was interesting because they did it in a sleep lab with no windows. And the subjects that were in the study did not know that the moon was being factored into the researcher's study here. But what they found was that melatonin production was lowest, plus or minus four days within a full moon. So there's something to perhaps a seasonal rhythm. You're in winter, I'm in summer.

There could be a lunar rhythm. Again, there's so many rhythms within nature, and nature is being responsive to that and essentially altering our physiology, whether we like it or not.

Adrian: Absolutely. I mean, it's interesting that you mentioned the light. I mean, last, not last night, the previous night, we had a significant storm here. And so, the electricity went out at about 8:30 p.m., and so we had no electricity, pure darkness, no streetlights, none of that. And that went out, and I think it came on again about 1:00 a.m. But I must admit that yesterday I just felt really good. I had nothing else to do, so I went to bed and slept and, I just felt much more refreshed. Now, that's an experiment of N equals 1, but it's really interesting that there was no light, and that's something that we really need to consider. And just how dark it really is when you have no electricity. So, it's amazing.

Deanna: Absolutely. And here's an idea for people too, because some people I would call them morning larks or evening owls. There's a chronotype, and everybody's a little different. And so, I'm a morning person. It's like I rise with the sun and I get tired, 6:00 p.m. I'm going down. It just continues. Other people are going up at 6:00 p.m. Like my husband, he likes to play music at night. So it's very difficult for somebody like that. So for an evening chronotype, what would be an option is just to dim the lights, and also, to use more red hues. So, as an example, we have one of those pink salt lamps, which is kind of nice.

Deanna: So things like candlelight, fireplaces, things that are red and not blue. It's like that white-blue enriched light on the computer, that is what deters the production of melatonin by the pineal gland. So, red light is okay. And again, if you can't get to that red light, wearing those blue light blocking glasses, which are actually red, it's kind of interesting. Because sometimes I'll take an evening flight, and I don't know why airlines do this, but they have this blue light on the plane when you're flying those evenings because they think it probably relaxes you.

Deanna: Well, I just wear the, the red light...well, they're blue light blocking glasses but they're red on the lenses, right? So those would be helpful to have.

Adrian: Now, seeing those glasses, they can vary quite a lot in price. Does it matter, in terms of price wise, can you get cheap $15, $20...

Deanna: Yes.

Adrian: ...glasses and they're okay?

Deanna: I think you can. I think you can.

Adrian: Okay.

Deanna: They have all different kinds too. Like one of the ones that I wear during the day just to prevent too much blue light on my retinas. Because the eyes are part of the brain. And the eyes are what are signaling to the brain in order to produce melatonin. So I will wear a pair that has kind of this iridescent look to it, so it's not red. It stops some of that blue light. And then there are other kinds of glasses where they have gradations of colour, like orange as it gets dim and then red for when it is later at night, like 9:00 p.m.ish when it's really dark. So, some people say that you should wear them like goggles so that you get no light even on the sides. So, some people are sticklers and they'll wear the kind with shields. They do look like goggles, right? It's blocking the light all around the eyes. I don't have those. I think that there's a huge range of prices there, and they don't need to be so expensive. I think that for the average person, you can buy a pair of $20-type glasses and be doing yourself good.

Adrian: Terrific.

Deanna: Unless you get them as prescription. Unless you get them as prescription. There are some where you can actually get prescription blue light blocking glasses. So, of course, that would not be a $20 purchase.

Adrian: Yeah, exactly. Okay. So, apart from light, what else affects melatonin?

Deanna: The second thing I think about is just taking care of the diet. I mean, you would expect me to say this because I am a nutrition scientist, and looking at, are we eating an antioxidant, anti-inflammatory, nutrient-dense, colourful rainbow way of eating? If I think of, how is melatonin made in the body? Well, we need protein. If we just back up biochemically, melatonin is made from serotonin. Serotonin is made from tryptophan. Tryptophan is an essential amino acid, and it's a unique one. It's got a certain structure to it, which makes it interesting from a variety of different cell biology perspectives.

But basically in the body, the way that the pineal gland is making that melatonin is by having tryptophan. So if you don't have enough protein in the diet, that's problematic on multiple fronts. From a detoxification front, skeletal muscle, so many things require protein. So that is important for melatonin. And I think just keeping a healthy metabolism. And also there are these, so I talked about light, there are other zeitgebers. Zeitgebers are time givers, and they help to punctuate our day and give us a sense of rhythm.

So when we eat breakfast in the morning, that's like punctuating our day. Our endocrine system is being informed that, okay, this is breakfast. So eating is a zeitgeber, and if we're eating late into the night, it kind of disrupts our rhythm, right? So we hear so much, it's very intuitive not to be eating something on the order of two to three hours before bedtime. Some people do what's called time-restricted feeding, where they just have an eight-hour window of the day, like from 9:00 to 5:00 that they eat, and then they don't eat after that.

Some people shift that a little bit forward and do like a 12:00 to 6:00 or 12:00 to 8:00 depending on their bedtime. But you have to note, not just what you're eating, but when you're eating, because that does inform circadian rhythm, and that does inform hormones in the entire endocrine circuit, namely insulin and glucagon, but they're tethered into the web of hormones, right? So that would be relevant to be considering.

So, number one, get your light right. Number two, make sure that you are eating adequate quality protein, adequate plants. Getting the rainbow of different types of foods so that you have copious amounts of antioxidants of all types that would go to different body systems and be protective. And then I think, oh, one more thing I want to say about that with the plants, lutein and zeaxanthin, which are two xanthophyll carotenoids found in plant foods, typically the yellow-green kind, that actually embeds into the macula of the eye and can help to protect against that artificial blue light exposure.

So that's really good because I think that more and more eye diseases are cropping up. I don't know if you've noticed this in, I don't know if you see clients or, but if you just talk with people, it's just people are complaining about their eyes. They've just been on technology way too much. And how can we protect the eye? Well, the eye is so aqueous, but yet it also has some fats. So these xanthophylls are perfectly primed to help get into the macula and work as molecular blinds to protect the eye from overexposure to light. So, I do think having plants in the diet can help us to ensure that we're getting some of those things.

Deanna: And then I think the tippy top of the triangle, if you will, okay, if you've done everything else, then to bring in a plant melatonin. And I specifically say a plant melatonin versus a synthetic one, back in the day, melatonin supplements were derived from animal pineal glands. And as you can imagine, that was a very inefficient process, because think of how small the pineal gland is, think of how small the production of melatonin is, and then trying to isolate that and put that into supplements for people at different doses.

Number one, it's unsustainable, it's unwieldy, it's inhumane, and it also would generate lots of issues with prions and viral concerns. So people stopped doing that and quickly pivoted over to something less expensive, like creating synthetic melatonin, which is much less expensive but has other issues. And this is in the scientific literature. This is not even just me saying it. There are even articles talking about the factories, the manufacturing of these types of synthetic melatonins where you get potentially up to 13 different contaminants, thalidomides and different kinds of compounds that can be formed. You can also get the pollution from these factories. There are a lot of patents. Everybody wants to really get melatonin. And since the publication of this article, I actually had a few groups reach out to me. One of them was a group of researchers working on a different source of melatonin from microbes which was interesting.

Adrian: Wow.

Deanna: So they wanted to pick my brain a bit about... I think people are trying to find other sustainable sources. Well, my vote is always going to be with plants. Plants, I feel, have an intelligence, and especially if the plant is connected into the matrix of the plant, right, where you have other things in there from the plant, not just the melatonin. But melatonin in a plant is the same melatonin that's in our bodies, so they can be used across the board.

Deanna: So I think, there you go, that would be the top of, if somebody has controlled for everything. And let's just imagine too, because Dr. Dicken Weatherby had interviewed me for his podcast, and by way of talking about all of this, he basically coined the term melatonipause, which I thought was kind of cool. Because, we were talking about perimenopause, post-menopause, andropause, adrenopause.

It's kind of like we just go downhill as we get older. From the 40s on out, our hormones are tanking. And the same thing happens with melatonin.

Endogenous production, by the time we're in our mid-50s, is a fraction of what it was compared to when we were children. Kids have the highest levels of me melatonin that are produced endogenously by the pineal gland. Before puberty, before they go into being a teenager, their levels are high. And then from puberty on, they start to incrementally go down. By the time we're in our 50s, we are bottoming out. So some people have questioned and postulated, all these hormones coming down, is this all connected into increased risk for chronic diseases?

Whether it's dementia, neurodegenerative conditions, and just like people are doing repletion with things like bioidentical hormones or phytoestrogens or testosterone replacement therapy, people are thinking like that.

Adrian: Yup.

Deanna: And so, thinking along the same line of, hey, do I need to fill the gap, the potholes where my body is lacking melatonin so that I can have this antioxidant, anti-inflammatory mitochondrial regulation effect? So, I'm just a little person in this whole melatonin space. There are giants who have made this their lifelong work, and I would recommend to everybody listening to follow the work of Dr. Russel Reiter, who is a researcher. I think he's in his 80s now, but he's dedicated much of his life to researching melatonin. In fact, he even has a book called Melatonin.

It was put out there some years ago, but it was so prescient. It was incredible, all of the things that he was talking about as it related to melatonin. So it's kind of like the people who love estrogen, progesterone, and testosterone and swear by it and do hormone replacement therapy. There's kind of like this undercurrent of a lot of people in longevity, anti-aging medicine, who would be strong proponents of doing the same thing with supplemental melatonin.

And saying, "Yeah, we need to fill the gap because otherwise, we're more prone to certain conditions."

Adrian: Saying that though, obviously, the levels are higher in children. Why do you think that's the case? What role is it serving with younger children as opposed to adults? Obviously, there's that natural progression. Why do you think that's the case?

Deanna: I think it's probably immune system and it's part of that whole entrainment of the circadian rhythm and the sleep-wake cycle. So for the first three months that a child is born, they have negligible melatonin. So they're not born, per se, with a lot of melatonin. It's starting to increase as they make their way up to like one year of age. In fact, I just found an article not too long ago, I think it was in May, just this year, 2023, talking about how the mother, if she takes melatonin, it's shaping the gut microbiome of the fetus or of the child. So that work is emerging. So, I don't know. There could be a role for maturation of the gut. We know that the brain is developing within that first year of life. Maybe it's connected to that.

But I do think that it is connected into that hormone web. So as a child goes through now puberty and they get older, now melatonin starts to quiet down and estrogen, progesterone testosterone start to come up. And then they kind of form this relay race and then they move into adulthood. But I don't know.

Honestly, I don't know why kids have the highest amount. But what's also interesting, Adrian, is that kids are more prone to the effects of artificial blue light. So they have greater amounts of suppression than something like adults do. Even though, just for adults, the amount of suppression can be great. Just within minutes of artificial blue light exposure at night, there can be between like 50% to 80% suppression of melatonin synthesis, which is huge. Now, of course, that's going to depend on many factors, how long you were exposed to the light, what colour are your eyes, those kinds of things. But children are actually, even though they have higher melatonin, they're also more susceptible to, yeah, the effects of artificial blue light. It's interesting.

Adrian: Yeah. Because I suppose then if somebody's then waking up in the middle of the night, turning the light on to go to the toilet. Is it that rapid in terms of effects on melatonin?

Deanna: Yeah. Yeah. It is. It is just within minutes that you can impede your melatonin production. Probably like a couple of minutes. So I was talking with Dr. Terry Wahls. You probably know who she is.

Adrian: Yes.

Deanna: She's all into multiple sclerosis. And we were talking and she said, "Yeah, but Deanna, people with MS, they don't have stability. So if they have to wake up in the middle of the night to go to their restroom, you need some kind of light." And so something like a nightlight should be okay.

And the reason I say that is just get the LightMeter app out and test it. I have tested it for myself and I'm surprised what is zero lux. Again, 1 lux is a candle flame 1 metre away. So a nightlight that's kind of dim, but on the floor and not at eye level, it may not be as pressing. Again, if you use the LightMeter app and you just figure out, what is the lux in my bedroom? What is the lux if I went to the bathroom at night and was exposed here? Obviously, you've got to go to the bathroom. You can't prevent yourself from doing that, but if you can just minimise the light a bit more, I think that... And maybe you put a pair of blue light blocking glasses on as you go to the restroom. That's also an option to just shield the eyes, but you can still see out of them, obviously.

Adrian: Yeah. You can get those sensor lights too that you just said, and then they emit a little bit of light and they don't emit too much light too.

Deanna: Yeah. Right.

Adrian: Now, I suppose something that the people need to be wary of is if they're using the LightMeter on their phone, they don't then after go, oh, let me just check my emails and, oh, Facebook.

Deanna: Oh, no. But what I mean is that they should already check out different scenarios using their LightMeter app.

Adrian: Yeah.

Deanna: So I have done this just even in my own bedroom. So, I have checked out, okay, if I put this little nightlight there, if I turn on the light next to my bed, how much lux am I getting? You don't do it in the moment, so you don't even have to pick up your phone. I don't know if you follow Bryan Johnson, but Bryan Johnson is, he's the most measured man. And he is doing all this to help his longevity. I think he talks a lot about his process on Instagram. In his bedroom, there is no light, it's total darkness, no windows, no nothing. Just a bed.

Adrian: Wow.

Deanna: Nothing. And truly, for healthy sleep hygiene, that is really healthy. Because I get interviewed on sleep podcasts and they're like, "Deanna, what's in your bedroom? What's your sleep routine?" It's like, I don't read, in my bed at night. I try to keep everything really bare bones, making sure that the shades, the blinds are drawn. Yeah, I've just gotten smarter just getting into melatonin, and understanding how to hack the light and dark in my environment. So I think if people just figure out and use that LightMeter app or some app that measures lux, they can figure out, okay, what is my tolerable zero lux? To what level can I go in my room and place lights as needed? And worst case scenario, if your room is too bright because maybe you live in an urban area and you just get the natural light from outside, wear an eye mask. That would be the next best thing. Because, again, it has to come in through the eyes.

Adrian: It'd be interesting for those people who have televisions in their bedroom, which I certainly advise against.

Deanna: No, no.

Adrian: But, yeah.

Deanna: That would be the worst. Sorry to say this.

Adrian: Yeah, exactly.

Deanna: No, I'm not. I think that would be absolutely the worst. Or, you know what I also think of people who fall asleep in front of the television? Here you've got that light, and we're not even getting into things like the electromagnetic fields and the effect on the pineal gland and changes in calcification over the years. The pineal gland is kind of special relative to some of the other endocrine glands. The thyroid gland is also kind of that sentinel gland. It's very responsive and it's subject to a lot of toxicity and influences in the environment. Pineal gland is so small and embedded in the brain, but yet it is very subject to things like calcification that can impact its function. And I don't think we fully understand why that happens. Some people talk about fluoride and just different things, but it's a very interesting gland.

And one of my favourite topics as well is consciousness, meaning more of the spiritual aspects and the more... In fact, I was telling my husband yesterday, the more I start reading about melatonin, the more I feel like, oh, my goodness, this is a molecule of consciousness. Because if you look at the literature, even on meditators, people who meditate or who are long-term meditators have higher serum serotonin and melatonin compared to people who don't meditate. I just find that that's really intriguing. And I also was reading last night, do you know what Dimethyltryptamine is? DMT?

Adrian: Mm-hmm.

Deanna: And it's an endogenously produced psychoactive. So there is this association of DMT with the pineal gland that melatonin and DMT are kind of chemical cousins, if you will. They're kind of related in structure. So then, so many people talk about DMT and whether their near-death experiences or these psychoactive effects. And it's kind of interesting because sometimes I listen to people tell me about their experience with melatonin and supplementing, and how sometimes it can have very, very vivid dreams.

Adrian: Yeah.

Deanna: And I've often thought, well, that's so interesting. We know that melatonin is metabolised through cytochrome 1A2. So there are different kinetics of how people can experience melatonin and the metabolites of melatonin. But I just think it's so interesting to look at... René Descartes back in the day talked about the pineal gland as the seat of the soul, which is just interesting as I start to read the literature process with a scientific mind, but also with an openness to consciousness, literature, and meditation. So when you ask me hey, Deanna, how else can people raise their melatonin? I would also say being in that meditative space can be a really good thing, right? At least from that one study, that was really interesting to see.

Deanna: And I think just also looking at stress, because 95% of the tryptophan in our body goes through what's called the kynurenine pathway, and only 5% is left over for things like serotonin and melatonin. So the more that we shunt tryptophan over to this kynurenine pathway to not give us enough melatonin, that becomes problematic. So that pathway can be hijacked during stress. So there are lots of things here. So many things. We're talking nutrition, we're talking lifestyle, we're talking lifestyle practices. I just think that it's really a rich area to explore, for sure.

Adrian: We really just keep repeating the same themes. When it comes to anything, it's really, eat well and take time out and care for yourself, and all those things. And we know that it just normalises, obviously, we're talking about melatonin today, but, it normalises and optimises a whole range of different hormones. So it's that same theme, exercise well and don't exercise too much, and get the timing right, and all those different things.

Deanna: It is. There's no magical hack here. I think that the only thing that melatonin brings to light is an appreciation for darkness. I think that that's the newer... Obviously nutrition and physical activity and all of those things, but I think the one thing that melatonin is unique with is that it tells us that we need to really be in sync with darkness. And we're not.

Adrian: Yup.

Deanna: We think it's cool to be awake so late at night. Working late, playing late. It's just, I think what these hormones are trying to do for us, Adrian, is to call us back to nature.

Adrian: Yeah. Yeah.

Deanna: It's like, we're out of alignment, we're out of coherence.

Adrian: And it's darkness at the right time, isn't it? It's not just, obviously, you've got teenagers who are spending during the day, they're in a room that's dark. So it's getting that timing right.

Adrian: Now, I just want to ask about, you've mentioned phytomelatonin, I suppose your plant-based melatonin. And in Australia, you can't buy melatonin over the counter. It is prescription-based, although you can now go into your pharmacy and the pharmacist can give it to you. So it's not as widely available as it is in the States, I understand so. What's your suggestion around melatonin supplementation? A lot of the research when it comes to melatonin in terms of supplementation has been done with the synthetic. What's your cautions against it? Who should use it? Who shouldn't use it? You got any suggestions around that?

Deanna: Well, there was a study published in Molecules in 2021, and it was actually looking at whether phytomelatonin was better than synthetic melatonin. And it was a head-to-head study looking at a variety of different cell assays. They were looking at things like COX-2 or Cyclooxygenase-2 as a marker of inflammatory activity. They were looking at reactive oxygen species in a skin cell line. They were looking at DPPH, which is often used for free radical scavenging and ORAC. And they found far and away that the plant melatonin was outperforming that of synthetic melatonin. And not by a little, but by a lot.

Greater than six times the amount of anti-inflammatory activity, more than double that of the cellular health activity in the respect of the skin cell line. And almost five times greater in anti-radical scavenging. And 10 times greater ORAC. So there's a big difference here between phytomelatonin and synthetic melatonin. One thing I want to mention is that, this term gets flipped around a lot, plant-based. Plant-based, what is plant-based? Even when it comes to food products. So plant-based to me just means, well, maybe the starter compound or something in there is from a plant, but it's not truly all plant. It could be a starter compound from corn that is then chemically processed, or it could be from soy and then chemically processed. But what I'm talking about is truly a plant melatonin. Not plant-based, but a plant melatonin. So as far as, I do think that there is superiority compared to synthetic melatonin. The question about dose always comes up, and as far as, who should take it, I'm a bit more modest here in terms of the amount.

I think people, in the States, we're like the Wild West here, right? So I think people are taking super physiological amounts of melatonin that I don't think are necessary for just replenishment. If you just look at the amount that the pineal gland makes, we're basically looking at, in middle age, it's about 0.3 milligrams. If we just want to get into replenishment, I think sticking with that and then building upon that depending on condition. For certain conditions like dementia or immune conditions, there might be reason to go higher. And there are definitely reasons to go higher for acute states like jet lag.

With jet lag, that's a whole different sleep protocol, right? That's like, okay, get your circadian rhythm intact before you travel, and use melatonin supplementally as a chronobiotic, meaning you're going to try to reset the circadian rhythm. You're not going to use it in a large dose as a hypnotic, you're going to use it as a chronobiotic. And then when you get to your location, especially if you're going east, you're going to take a higher dose in order to get to sleep at night. And that'll have more of the soporific, that sleepy kind of hypnotic effect, right? But that comes with that higher dose. But the 0.3 milligrams is more like, let's just fill the gap of, this person's in middle age, losing levels, just trying to fill the holes, so to speak.

Deanna: So I think that more is not always better. I think some people just get, some people tell me on podcasts and such, "Oh, yeah, I'm taking," and they'll say double digits of melatonin. And I'm like, why? There's not a lot of science to... And I don't think that more is always better, especially when it comes to something like an antioxidant. An antioxidant works within the whole framework of other antioxidants.

We see that there's a potentiation with things like vitamin C. Vitamin C and melatonin work really well together. They're actually, in some studies I've been looking into, there's synergy there.

You want that sweet spot. It's like the Goldilocks principle, not too little, not too much, just right. And sometimes that just right will vary a little bit for the individual, depending on, of course, their needs state, their age, even gender. Women seem to have better bioavailability of melatonin than men do from my recollection there, like how light are your eyes?

Deanna: So I think that it's good to start at a physiologic dose. And in fact, if I think back to some of the research of Dr. Richard Wurtman who was at MIT and who did a lot of this early research on melatonin, they tested different doses, and that 0.3 milligrams was the sweet spot. So, different opinion leader organisations are out there talking about, what would be safe levels for older adults, just as like a steady-eddy kind of a dose? And most of them, from what I can see, talk about between 0.1 milligram to 1 milligram, and most of them are talking about 0.3 milligram to 0.5 milligram. Now, for some people, their jaws dropped. They're like, "That's so low." But if we just look at physiologically, that should be sufficient unless we have something that warrants an additional dose. Like all the work on COVID and long haul there have been higher doses used, but for shorter durations. And even looking at certain chronic conditions, or not chronic per se, chronic diseases or looking at things like diabetes, hypertension, sometimes a bit higher doses have been used, anywhere between 1 milligram and 10 milligrams. But again, for defined periods.

Deanna: The safety of melatonin supplementation has been evaluated for up to two years, between six months to two years. So, again, I think your audience is a clinician audience, I do think it's good to have some clinical oversight of a person's use of melatonin. In the United States, there are melatonin formats that are very desirable for kids to eat. So we have a lot of things like chewables and gummies. Do you have gummies there? Is that a big thing?

Adrian: We do. Yeah.

Deanna: Yeah. So people are just crazy about all these gummies. And I think that when I see all these kids having melatonin gummies, I don't consider it a... I think there has to be caution. And I have been in the supplement industry and I don't favour that kind of gummy format in general for anything. I don't like it because I don't like the additional sugar. It's also a hygroscopic matrix, so it's watery. It's more prone to microbial overgrowth and also interactions. How do we know what happens to that melatonin when you put it into that matrix? Have companies tested that? Is there any interaction or breakdown, or what is the stability in that versus in something like a capsule? Because we do know that melatonin breaks down in light and oxygen. So that's why having it in a blister pack is preferred versus just a jar where you open it, cap. And I don't know about in your home, but I know that at least my husband doesn't always tighten that lid and then you just get oxidation, and by the time you're at the bottom, it's like, who knows what you have in that jar?

Adrian: Exactly.

Deanna: So, I think that there are a lot of things to consider here. It's very interesting to me how melatonin is regulated differently in different countries because of, just scientifically just knowing that there are many different uses of it. It's just that perhaps the dose needs to be better. I think better communication and education needs to be out there, and also the population that uses it. Again, I don't think that children need to be taking melatonin supplements unless...

Deanna: There is some scant literature on this, looking at the role for its use in autism, and also ADHD in children. But I would be pivoting to other things for those conditions more than something like melatonin. That would not be, in my mind, the first line of a therapeutic approach with a child. That just doesn't seem right. So I think its use has to be properly gauged for the individual and everything about that individual. Just like anything else, it has to be personalised.

Adrian: I've read some of the literature with regards to things like its use in migraine, and as a clinical psychologist, I've also been interested in reading some of the literature with bipolar and maybe for different phases of people experiencing the manic phase. Maybe there's a role there with higher doses for a short period of time. And like you said you've really got to kind of consider those circumstances too.

Adrian: Now, just a question if people were to take the phytomelatonin, when would they take it? What time would they take it?

Deanna: Forty to 60 minutes before bedtime, like any melatonin.

Adrian: Okay. Yep. Yep.

Deanna: So if we think of the half-life of melatonin, if it's breaking down over the night, it's best taken at that 0.3 milligram dose, 40 to 60 minutes before. Now, let me just give some disclaimers to that, because for some people they're really slow metabolisers, and then they get groggy in the morning. They get groggy. And I hear this from certain people and it's like, well, how much did you take? What form did you take? What else was in there? And what time did you take it? So for the people that, it's like you kind of have to find your sweet spot of what works for you. And for some people, if they are the person that gets groggy, they need to take it even earlier than that 40 to 60 minutes, right? So then that's telling me that their breakdown is delayed. You can kind of make some general estimation, since this, again, is a practitioner audience, people will know what I'm talking about here, but you can make some estimation based on if you know anything about a person's gene variability in cytochrome 1A2. So if somebody is a fast metaboliser of caffeine, that means that they're most likely going to be a fast metaboliser of melatonin. Meaning that they could take it at that 40 to 60 minutes before bedtime. But for people who are slow metabolisers of caffeine, they are the people that get the heart palpitations, they get the revved-up energy and it just lasts a long time. They can't drink coffee past 12 noon. Those are the people that probably need to take it a bit earlier so that the kinetics will land nicely to have them waking in the morning feeling more alert rather than groggy.

Deanna: And you know what, and I'll just mention this too, just some personal hacks, nothing science-based here. But I have some colleagues and we all like experimenting with taking the phytomelatonin and doing different things with it. So personally, I have been taking it with a little bit of vitamin C just to see if I experience anything different there. Because, again, the literature is telling me that vitamin C and melatonin work really well together. If you look at melatonin as an antioxidant, 1 molecule of melatonin can quench up to 10 free radicals. And what's really interesting, there's one article, I think it was by Dr. Tan who works with Dr. Reiter. They co-publish a lot. And basically, he was showing how the metabolites of melatonin can even act as antioxidants.

It's like Dr. Carrie Jones would say, the Russian doll approach to quenching free radicals. The mother molecule then brings out the next doll, and then there's more quenching of those radicals and then on and on and on. Vitamin C can quench between one and two free radicals. So that's just to give you a sense. But there's some kind of connection there between them. A friend of mine, because, again, we know that melatonin is fat-soluble and water-soluble, he takes it with a fish oil. So just one soft gel of an omega-3, he takes that together with melatonin and he feels like that hits the sweet spot for him. So that might help with bioavailability in certain people.

Adrian: Wow.

Deanna: Yeah. And he also takes magnesium at night. So everybody has to find that concoction that works best.

Deanna: Adrian, just to mention too, I'm just thinking, for perimenopausal women who have vasomotor symptoms at night to the point that it wakes them up. So I'm talking about hot flashes, night sweats, they wake up, they can't get back to sleep. There's something about that 2:00 a.m. to 4:00 a.m. window. I'm one of those women, and what I have found in my use of melatonin, that I needed to go higher. Because it's kind of like all those pauses hitting simultaneously. It's like, whoa there goes estrogen, whoa, there goes progesterone, and my melatonin is low. So, what I didn't mention already is that melatonin is also a hypothermic agent, meaning that it cools the core body temperature, which is kind of the nice process that initiates sleep, right? So melatonin is important for sleep, reducing sleep latency. It gets us to bed and gets us to sleep faster. And I think in part that's because of its ability to lower the core body temperature. So for those perimenopausal women who are having this change in the range of their hypothalamus and there are changes there from a thermal regulatory point of view, it might behove them... You don't see a lot of discussion about this, but I just personally have been trying that out for myself. And if we know that it's an anti-inflammatory, it helps with sleep-wake, it is an antioxidant, it helps with core body temperature, it might help some of the perimenopausal women out there that are suffering from night sweats and hot flashes. So it's just something to consider.

Adrian: It definitely makes theoretical sense, doesn't it?

Deanna: Yeah. I'm surprised that there are no papers, I can't find anything about it. I think I need to actually put together a nice little study of women who all want to try this because it's such an opportunity. And perhaps in those women, so many changes with the brain due to the withdrawal of estrogen. So, possibly some changes in glymphatic fluid flux, and who knows? There could be many different mechanism type of approaches to take with that.

Adrian: Well, thank you very much for... You're getting me thinking, and my head's spinning at the moment going through all these different possibilities. And I really thank you for the work that you've done, not only in melatonin, but I've read lots, follow a lot of your work over the years and the information that you talk about with, we could have another podcast about nutrients in general and colours of foods, and their potential benefits. But I thank you very much for joining us today, and really opening up people's ideas and thoughts about melatonin and providing some good sound education around melatonin. I really appreciate you having a conversation with us today.

Deanna: My pleasure. Thank you so much for having me. And I hope that it makes sense for everybody and gets those wheels turning. And if anybody has any questions, feel free to reach out.

Adrian: So, thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Dr. Adrian Lopresti, and thanks for joining us today. We'll see you next time.


The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.

Share this post: