Age-Related Melatonin Decline: Age-Related Melatonin Decline: Is It Preventable With Phytomelatonin?

They would put melatonin in the drinking water of the animals, and they would age less. They would age somewhere on the order of like 20% less.

But let me just give you the six functions of melatonin. Chronobiotic effect. Very potent antioxidant. It's an anti-inflammatory agent. It's a neuroprotective agent. It regulates the mitochondria. It plays a role in detoxification.

Just the other day, I was talking with a friend who is a practitioner, and she's in her mid-70s, and she looks amazing. And she says, "Oh, I've been taking melatonin for decades. I think that's actually what has kept me young, you know, protocol."

So, there was a lot of popularity in the states to have melatonin gummies. It can be susceptible to oxidation. So when people have like jars of melatonin supplements or gummies, by the time you start to get to the bottom, chances are you're not going to have much active in that.

And that would Diana, welcome to the show. Great to be here with you, Inca. So, hi everyone. Today, we're here with Dr. Diana Minnik, who is a globally recognized nutrition scientist, lecturer, educator, and author with over 20 years of experience in academia and the food and dietary supplement industries. Dr. Minnik is currently the chief science officer at Symfony Natural Health. She's been active as a functional medicine clinician in clinical trials and in her own practice. She's the author of seven consumer books on wellness topics, four book chapters, and over 50 scientific publications. Through her talks, workshops, groups, and in-person retreats, she helps people to transform their lives practically and artfully through nutrition and lifestyle. Did that sound about right, or would you like to add something?

No, I think you covered everything just fine.

Awesome. So today, I would like to discuss melatonin and its importance to our health and its various roles in our biology, not just as a sleep hormone, but also as an antioxidant and as a brain uh cleaning hormone. And also how our bodies actually produce melatonin and how it reacts to melatonin supplements. So, melatonin supplements are of interest to many people at the moment, but there is great confusion around them. How to use them? What are the differences? So, we can discuss those details and get sort of like a clarity into that picture. And then hopefully, we also have time to discuss detox, especially nutritional detox, and its significance to health and longevity.

So, let's start with melatonin. So, um, we mentioned earlier that melatonin as a sleep hormone is an oversimplification, because it does so many other roles in the human body. Uh, so it's a major, major antioxidant, mitochondrial support, etc. So, could you tell us, what is melatonin? How do we produce it daily? And how do we produce it in different organs and cells, also those that are outside of our brain?

Yes, this is one of my favorite topics to talk about. Um, melatonin is a multitasking molecule, and it's actually quite ancient. It's been around and has evolved with us since we became these organisms that go through, um, aerobic respiration, since we developed our mitochondria. So, it's everywhere, essentially. It's in plants, it's in animals, it's throughout the human body. In fact, it's, it's so widespread in so many of our different body parts. It's in, in the brain. It's in the eyes. It's in the skin. It's, it's in the liver, in the thyroid. I mean, basically every part of our bodies contains melatonin. The only parts that wouldn't contain it would be like hair and nails, but our living, mitochondrial, I would say, um, infused organs would for the most part contain melatonin.

So, what is melatonin from a structural perspective? It is five, it, well, it's actually, if you look at the, the chemical structure, it's an acetyl-5-methoxyamine. So, it's kind of a mouthful. So, the way that melatonin was discovered was by a dermatologist back in the late 1950s, and he coined this compound, this molecule, as as melatonin because he was thinking that it had something to do with skin lightening. So, mela for the melanin, and tonin because the structure was related to serotonin.

So, if we look at, um, melatonin and the variety of different formats that are produced in the body, we have the pineal gland, which generates melatonin in response to dim light and darkness. But then we also have the extrapineal melatonin, which is the melatonin that's made throughout the body. It's found in the gut, in the skin, all of those other sources of melatonin that are not necessarily in response to darkness. And if we look at some of the functions, you had already listed some of the functions of melatonin. Often, we we hear that it just gets pigeonholed into sleep, which is not entirely accurate. It's actually more about being a chronobiotic agent. So, it keeps us connected to nature's rhythms through setting that that signal every night. So, it's a chronobiotic. It sets our circadian rhythm. And by way of doing that, it's helping us with sleep.

But let me just give you the six functions of melatonin as I see it. So, first and foremost, the chronobiotic effects, the circadian rhythm effects, and as part of that, we have sleep. Secondly, I think about it as a very potent antioxidant. So, one molecule of melatonin can quench up to 10 free radicals, which is, is actually quite unique because if you look at other antioxidants, they don't tend to have that same capacity, nor the same functionality in lipid and in water tissues. The third function of melatonin is that it's an anti-inflammatory agent. The fourth one is that it is a neuroprotective agent, and it helps with brain detoxification at night. The fifth is that it regulates the mitochondria. And I would say the sixth is that it plays a role in detoxification. Not just brain detoxification, but we can see that by way of seeing the increase of toxins in the body, what we can do is offset some of the effects of those toxins through melatonin's effects on reducing oxidative stress and also reducing inflammation. So, there are some studies looking at things like arsenic toxicity and how things like melatonin could be of value for that and to offset some of those effects.

So, melatonin again is multitasking. It's not just one molecule, one function. It has been with us, uh, for a very long time. And so, we are taking in melatonin in the diet. We produce it in the skin, in the gut. We're constantly producing melatonin. But as we get older, we start to produce less from the pineal gland. And this can be associated with different conditions that would be associated with things like neurodegeneration, brain impairment, or cognitive issues. So, perhaps we can dive into that a little bit more. But for most people, they experience what Dr. Dickin Weatherbe has referred to as melatonopause. So, we know about menopause, we know about andropause. There are all these different pauses. Melatonin has its own downward slope as we move through middle age and into our 50s and 60s, which some people think is associated with the rising rates of a lot of these different neurodegenerative issues and conditions.

I love that. Thank you so much. So, I just, just quickly review. So, you said chronobiotic. Yeah. Antioxidant, anti-inflammatory, neuroprotective, mitochondrial support, and important for detoxification. Um, okay, let's discuss about that age-related decline in melatonin. Many people do like know about, for example, collagen decline. Now, the mantra is that collagen starts degrading when you're 25, you need to start supplementing with collagen, and that's a natural process, you cannot prevent it. Do you think this age-related decline in melatonin, is it a, is it a natural adaptive process, or is it a sign of a dysfunction that contributes to aging and something that we can maybe prevent or slow down?

I think for everybody, it's a little bit different. I think that just normally, we have these changes in our endocrine system that happen over time. So, there's just a natural decline in the function and the intercommunication of a lot of the endocrine glands, right? I mean, I don't think that we can be 100% in our function until we die, like if we're in our 80s and 90s. I mean, we can help to blunt and buffer some of that, but I think just as a part of aging, we normally go down. But I think that some people are depleting their melatonin sooner than they need to be. And that might be because they have exposure to artificial light at night. So, they're not actually priming their pineal gland to secrete melatonin. So, that process is blocked by the artificial light at night. People might be a little bit more stressed, and so they're shunting their tryptophan into different pathways, like the kynurenine pathway, rather than making melatonin. There can be other things that are happening in the body. We have different gene variants. If we are in a state of inflammation, this just costs us more melatonin and more in the way of helping our body to accommodate from that inflammation and oxidative stress. Because if we look at why do we age, there's that whole aspect of inflammaging, right? Kind of like the low-level chronic aging that occurs with inflammation. And I think that for some of us, we're turning up the, um, the fire a little bit higher earlier in life. So, I do think that we can start to patch the gap of that lower melatonin level to perhaps help to come back and to be much more resilient.

You know, it was funny, Inca, because just the other day, I was talking with a friend who is a practitioner, and she's in her mid-70s, and she looks amazing. Now, she does do yoga and she does certain things, but I was talking with her about melatonin, and she says, "Oh, I've been taking melatonin for decades." She said, "I think that's actually what has kept me young." Like, we don't know for sure because, you know, protocol, but when I look at her, I'm always thinking, this woman doesn't age. Every time, she's still working. She's still working with clients, and she's still coaching them and helping them to good health. You know, I've also talked with other people in the melatonin field, like Dr. Russell Reiter, who, you know, is kind of like the, the father of melatonin. He's written about it. He's dedicated his life to doing research on it. And if you read his book, "Melatonin," which is an easy-to-read book for consumers, so it's not very sciency, but he takes the science and he distills it down in that book. Basically, he talks about a number of different animal studies where they would put melatonin in the drinking water of the animals, and they would age less. They would age somewhere on the order of like 20% less than the other animals that were not given melatonin.

So, this is almost like a supplemental melatonin then?

Yes. That would be supplemental. Yes. And it was given over time, right, throughout the animals' lifespan. So, yeah, you know, you could say, well, melatonin is pretty cost-effective. It doesn't cost a whole lot. It's rather safe, especially if we aim towards physiologic levels of melatonin. If we just patch the gap that happens with aging, where it's kind of like, if we think of our road of life, we want a smooth road, right? And sometimes we get kind of these pits in the road because of the inflammation, the oxidative stress, the nutrient-poor diet. You know, we're just not taking in the nutrients we need to offset a lot of these things that are happening to us. So, bringing in melatonin can help to patch the gap and smooth that road, if you will. So, I do think it's, it's something to bring in. And, but it's not the only thing. I don't want to perceive it as like the miracle molecule and it's the only thing we need. It's part of the web of our systems biology of what could help us to be much more resilient in our body systems.

For sure. Um, I love that approach, like we always need to look at things in context. I definitely want to cover about the melatonin supplements later. Before that, I'd like to go back to discussing a little bit more about the function of melatonin for different, uh, processes that decline during aging. For example, mitochondrial dysfunction is one hallmark of aging. And it seems to be that most people or a lot of people are living in some sort of mitochondrial depleted state. Maybe because we are surrounded by toxins, and there was COVID, and everything. So, melatonin is one of the few antioxidants that can actually enter into mitochondria directly, and mitochondria can also make their own supply. So, what's melatonin's role inside the mitochondria?

Well, if you think of the mitochondria, they're hubs for metabolism. They're like these little powerhouses of just churning out lots of ATP. And that's great because we need that golden currency of energy in order to do things, right? More mitochondria equals more metabolic fitness. So, this is metabolic flexibility, right? Where we can kind of, um, look at the mitochondria, look at its health, and then say, like, okay, these mitochondria are actually helping us to metabolize fuel properly. But as part of that metabolic churn, what we get is a lot of this, uh, spray of free radicals. And so, if we're taking in a lot of food, and we can, and this is why intermittent fasting and different fasting approaches are seen as being beneficial because of the autophagy, or the cell cleaning up effects, at least within the mitochondria, right? So, we kind of get all that garbage together, we clean up the cellular debris. So, meta, the, the melatonin that is in the mitochondria, we think is responsible for that cleanup process. So, while the mitochondria is doing its thing and giving us energy, there's a cost to that, and that cost is just letting out all of these free radicals. So, melatonin, because it is such a potent amphipathic antioxidant, can come in and rescue us from a lot of that free radical damage that can occur because that free radical damage can be implicated in the DNA, the DNA damage, damage to the cell, damage to tissues. So, with melatonin being strategically located in the mitochondria, it's helping to quell a lot of that oxidative stress that would normally occur.

The other thing I want to mention too, by way of that, is if you think of at night, when we are sleeping, this is a very restorative, rejuvenative process because what ends up happening is between 2 and 4 a.m., we peak in our level of pineal melatonin. And not only do we peak in melatonin, but we also peak in other antioxidant defense enzymes. So, things like superoxide dismutase, catalase, glutathione reductase, and even glutathione. There was one study in which they looked at different time points and they measured these enzymes. And they found that 2:00 a.m. was when all of them were highest relative to the other time points during the day or even later at night. So, what this tells us is that the body is undergoing repair and rejuvenation at the cellular level, and a lot of these different enzymes are important as part of the antioxidant defense system inside the cell. In fact, when we even think about detoxification, some of the most powerful ways to ensure that we are detoxifying properly is to prime those enzymes because we actually want an enzymatic, we want an endogenous way to protect ourselves from a lot of the, the damage that free radicals can do. So, melatonin is right there with this whole army of different, I would say, protective antioxidant defense systems that are working at night.

So, back to your question about mitochondria, that's essentially what it's doing. It's, it's helping us to repair, and it is helping to just kind of squeeze up and clean up a lot of those free radicals that the mitochondria produces.

I love that you mentioned the, the nighttime melatonin peak. One of your expertise areas is also the glymphatic system, and melatonin's role in that one, and that's pretty new, and almost no one knows about it yet. Um, it's hugely important, um, because when we talk about detox, almost no one never mentions the glymphatic system. Also, it's pretty new. I think it was discovered like 2012 or something. So, very recently, we realized, like, oh yeah, our brains are detoxing too, you know, just neck down, go figure. Can you discuss more about the melatonin and the glymphatic system, and why is it important? Why is it beneficial?

Yeah, this is one of my favorite areas that I don't think there's enough discussion about, and it's so interesting because for many years, even if you look at Greek philosophers, there was always this discussion, why do we sleep? Why do we dream? Is it something like we're processing something psychologically? And we can say all of those things. We can say it's memory consolidation, we're, you know, just allowing the brain rest time. But we can also say that there could be a very, I, I would say, directed focus into a clearing and cleansing of the brain at night when it is less active in our daily processes. So, this is referred to in many different ways in the scientific literature. It's referred to as brain washing, but in a good way, or it is a purification system of the brain. So, just like you said, there is this, um, this research that goes back to an animal study from 2012, and this was done in animals. They use tracers, and what they found was that there was a specialized waste clearance system from the central nervous system, and it kind of looked like the lymphatic system, and it was basically working together with the cerebrospinal fluid circulation, as well as the immune system and the vascular system. And what these researchers found was that it was most active during deep sleep. So, we, we do different things at different times of night, right? So, we have the non-REM sleep, we have the REM sleep, but essentially, the glymphatic system is active when we are sleeping. So, it's not active when we're talking like this, right? Or when we're active during the day. We need to be sleeping or under anesthesia in order to activate this glymphatic system.

There have also been studies looking at the timing, and it has been found that the dawn hours are greater in the glymphatic fluid flux than other times, whether it's like early morning or evening or daytime. And if you look at this glymphatic system and when it's active, it seems to sync up with exactly what we just talked about, which is that rise in melatonin, the rise in glutathione, and the rise in a lot of these other antioxidant defense systems. And so, I think what is happening here is, over the day, you know, we, we do a lot of different things in the brain, and then at night, when we have these toxic metabolites that have built up, they need to be removed, right? So, we need to create that fluid movement out. And so, it seems as though melatonin may play a role in the movement out of those toxins from the brain. Now, there isn't a lot of data on it. There is more in the way of, I would say, animal studies, preclinical studies. But what is unique about melatonin is that it is considered to be chemically amphipathic. Amphipathic means that it is fat-soluble and water-soluble at the same time. It can flex, which makes sense because we see melatonin in so many different body compartments, in the liquid and also in the fat-soluble tissues. So, that unique chemical functionality of melatonin could theoretically allow for the transport out of the fatty lipid structure of the brain into the less lipid structure of the lymphatic fluid and then into the lymphatics. Right.

So, some, you know, we always look to science because science, many times, will tell us in advance of the clinical medicine aspects, like 15 to 17 years out. And what we're already seeing in the science is that we are seeing some indication here that melatonin might actually be the mediator between glymphatic fluid flux and even mitochondrial dysfunction, which is very exciting. Now, I don't want to give you the idea that it's just about melatonin for glymphatic fluid flux. A lot of different things have been shown to be important for glymphatic fluid regulation and function. Having proper omega-3 fatty acids, if we think of the brain again being very lipid-rich, we want to ensure that we have healthy cell membranes that things can flow in and flow out. So, having a healthy omega-3 index is also important. Having proper hydration, having enough magnesium, uh, even looking at just the effect, the neuroinflammatory effects of the standard, all over the planet, processed diet. This is, I would say, inhibiting us from having proper brain health, right? And many people just aren't sleeping enough. Maybe they're not sleeping enough because they can't, or they're just not able to because of their lifestyle. So, they're shortchanging their glymphatic flow. That glymphatic flow is also connected to, um, even how we hold ourselves at night when we're sleeping. Like, if we are sleeping on our back or on our stomach, we have less glymphatic flow than if we're sleeping on our sides. And in fact, the right lateral side is where there is potentially more glymphatic flow. That might just be because of gravity or the carotid artery or the placement of the vasculature. So, there can be a lot of things that influence lymphatic drainage. You know, um, being physically active. There is some initial work being done with, um, kind of applying photobiomodulation to the scalp and seeing, um, more flux that way. Meditation might also be important for that. Uh, looking at 40 hertz light and enriching the eyes with different lights. So, a lot of different things might play a role in that glymphatic flow. But I do think we need to be looking at that a little bit more. And I can imagine in the future that within the biohacking world, we are going to see that there are ways to assess our glymphatic flow. So, maybe if we wear an Oura ring or we're wearing some metric to look at our sleep, we might actually get an indicator, and I'm putting this out there in case people develop technology, but I'd love to know how my glymphatic fluid flow is going and wake up and say, "Oh, I'm at 65%." Or, "Oh, you know, maybe I need to sleep, you know, change my sleeping position. Maybe I need to take melatonin." You know, I, I think that there can be different things that can help us to modulate that better because essentially, if that is better, then our brain detoxification is better. Our brain will function better the next day because it will be clean. It will be washed of a lot of those toxic metabolites.

Yeah, that's so powerful. And if there is any biotech founder now listening, then there is an idea that you might, you might consider. Um, yeah, it's quite, it's quite interesting the nighttime dynamics of the brain, how the brain cells shrink and there is more fluid going around and flushes itself. And, I guess one good proxy for that, possibly for the glymphatic efficiency, could be just to monitor, to start with, monitoring your deep sleep and are you getting enough? So, that would be the step one, and probably the only thing that we have available at the moment.

Yeah, I, I think that's true. And also, you know, eventually, we need better markers of hydration so that we can, I don't feel, I feel like something as basic as water is not very well metricized, even within the biohacking community. I mean, it's pretty remarkable if you think about it. And that's just a basic of circulation and transport. It, it funnels right into our detoxification conversation. But I just want to go back to something that you just said, because the 60%, um, change. So, the interstitial volume starts to increase by 60%. 60 to 70% is what we see in these animal studies. So, yeah, it's almost like our brain cells have to make room for this increased volume of that increased tissue space to let things out, right? So, it's like the brain and the vasculature is truly changing a lot at night. You know, I read somewhere as well, Inca, that on average, we, we shift our sleeping position something like 11 times per night. So, that's kind of interesting, right? And how we're shifting, and probably that mobility is pretty good for moving things around as well. Obviously, we probably see diminishing returns if we're tossing and turning, but having again, a bit of that right lateral sleep for people who can sleep on that side. And when I think about our anatomy, what do we have on the right side? We've got the liver. We've got the liver that we're engorging with blood when we're sleeping on the right side, right? So, better, the way I see it from a detox perspective is brain-liver access is engaged. So, when we're releasing all of that into the glymphatics to then go into the lymphatics, eventually, we're going to need to get that out of the body. So, what do we do first thing in the morning? We go to the bathroom, right? That's why, um, really connecting to detoxification in that way and making sure that we have proper elimination to deal with a lot of that brain metabolism that happened over the night and move that out of the body is so important. That's why the liver needs to be engaged in that whole process, right?

Um, now that we understand the fundamentally crucial roles of melatonin to our health and wellness, that goes way beyond just inducing sleep or initiating sleep. Let's discuss the supplementation, because they have, they are studied, they are well evidence-based, they are pretty safe. I actually want to share how, how I got to know melatonin supplement. It's a very untraditional story. It was about 10 years ago, I would say. It could be more. So, many of my listeners know that I, I suffered from chronic migraines and cluster headaches when I was growing up. And, um, so my neurologist actually first prescribed melatonin to my chronic cluster flare-up. It was pretty bad. And she asked me, "Do you, do you use melatonin?" I said, "No." Then she's like, "Okay, I'm going to prescribe to you, prescribe melatonin." And I thought it was for sleep. And I heard like, people take like one gram or something. I think my mom was taking one, one gram or something. And so she prescribed me 10, sorry, milligrams, not grams, but mill. And she was, she was prescribing me 10 milligrams of melatonin. And I thought that was huge. But of course, according to studies, then I went to look into the research afterwards, that 3 milligrams immediate-release melatonin is the minimal effective dose for migraine. And for cluster headaches, the range can be between 10 milligrams and up to 30 milligrams. Mhm. So, I tried it. Um, I wasn't able to continue. For me, the side effects were just way, way too much. But of course, I was like curious about all of that and why it would work for migraine. And probably a lot of the reasons relate to what we just covered. But also, it was interesting to me to notice that the, the actual, the chemical structure of the melatonin is pretty similar to some analgesic, analgesics. Have you looked into the research of using melatonin supplements to some pain-related conditions?

Well, that isn't my area of specialty, but I've heard about that from other people. Of course, there are all of these other, I would say, if, if we think of the mechanism of melatonin, it starts to make sense why you would use melatonin for pain, why you would use it for fertility, why you would use it for cardiovascular issues. You know, there are so many other applications because it does address inflammation. And when we're talking about migraine, we're thinking about neuroinflammation. We might be thinking about just overall brain chemistry. So, it makes sense from that perspective. And I know that there is definitely work that has been published on melatonin and migraine. So, from a mechanism perspective, that completely makes sense.

Now, as far as the dose and what the proper dose would be, I think like you alluded to, I think that there is a need to find the best dose for the person. And I think that, you know, in functional medicine, we talk a lot about go low, go slow, personalize to the individual, and kind of work your way up to kind of find that sweet spot of what is therapeutic for you as an individual. So, .3 mg is one of those lower physiologic doses where we see clinical data supporting that amount because if we think of, you know, what did we produce physiologically through our lifespan? We produce about a milligram from the pineal gland. Right? So, then if we, we go through life, and then at midlife, we're at about a third of that, and then in our 50s, we're at about 10% of that. How do we now bring back what we have lost? And perhaps that would be therapeutic for something like neuroinflammation in an individual? So, trying out a lower dose and then kind of staging it from there. You know, I think most of the science, if I, you know, I've done a lot of, I've published a scientific review with my team members, and so that gave us the opportunity to look at a lot of the science of melatonin used in a lot of different areas, whether dermatology, gastroenterology, reproductive physiology. I mean, goodness, there's so much about using melatonin to help with egg quality, to help with, which makes sense, right? Because we're helping the mitochondria to be more fit and creating more energetic fitness in that way. So, I think starting with a physiologic dose and then staging that on up if needed in order to achieve efficacy for the condition.

I think with migraine too, you know, I would be thinking at least in functional medicine terms about a lot of other things, not just about melatonin, but there could be other things to be looking at from a hormone perspective. And we know that melatonin, one of its functions is more hormonal as it relates to the pineal gland being part of the endocrine system. So, as an example, and this is kind of an interesting tidbit, and I don't know if this tied into your migraine, but for people that I have known with migraine, there are certain triggers for them. Sometimes those triggers are dietary. Sometimes they're connected to the menstrual cycle. Sometimes it's just a connection to even environmental factors like humidity, heat, or certain times of the month. And what is really interesting, I'm just going to toss this in here for the discussion because I don't think many people realize this, but there is a very interesting study where they found that endogenous production of melatonin, so that would be the pineal melatonin, that it was reduced four days before and four days after a full moon. And this study was done in a sleep lab where people didn't have the interference of light coming in or, you know, they were in a controlled situation, but they did find that sleep was impacted. So, there were a number of different features that they were looking at, but just even if we think about melatonin, what they found was that melatonin was reduced. There was this, if you look through the month, it was just fine during certain other phases of the moon, but as the, the moon started to become more full, that pineal melatonin went down, dipped down, and then it came back up after four days. Wow. So, this is like when some people say that I can't sleep because it's full moon, and other people go like, no, that's woo-woo. You can just dig out this paper and say, like, here's the science. Yeah, this is real. The paper was, um, published in, um, a biology journal in 2013, and it was looking at the lunar cycle influencing sleep. So, it wasn't just on melatonin, it was also looking at sleep, and they found that deep sleep was decreased by 30%, the total time to fall asleep was increasing by five minutes, the total sleep duration was reduced, and just endogenously, again, melatonin levels had come down. So, there is something to be said, and perhaps this touches upon your interest in circadian health, that we as human beings are run by rhythms. We're run by circadian rhythm, the 24-hour rhythm. We have a seasonal rhythm. We have a menstrual rhythm. We have a lunar rhythm. We have other hormonal rhythms, and we even have a birth month rhythm. What does that mean? So, there have been, uh, some studies looking at hospital records of people born in certain months of the year and correlating those to diseases to see if certain people's birth dates would be correlated, just because of, if you think of in utero development, having access to things like melatonin or vitamin D or certain things that would stimulate fetal programming or fetal development. And indeed, there seems to be a connection there between even our birth month and potentially later in life, what we might have some risk for developing. Now, that doesn't mean that our disease risks are absolutely predetermined, because we do know that our environment is strongly impacting the outcome of our gene expression. Right? So, but I just, what I'm emphasizing here is the role of rhythms that play out through us. And one of the ones I just mentioned, and I'm mentioning it because you're mentioning migraine, and I think about a lot of the connection of migraines and how there seems to be some kind of flux or some kind of rhythm to them. You know, me being in nutrition science, one of the things that I saw clinically was that migraine sufferers typically had some connection to a food intolerance, food allergies. Certain things would perturb their migraines or make their migraines worse, things that they were eating. And you could say, well, is it the food, or is it the effect on something like the gut microbiome, the gut-brain axis, the gut-immune axis? There's no end to that kind of discussion, right? It's just like, you kind of have to dive in and start to work with certain modalities to address and get to the root as closely as you can.

Yeah, absolutely. And to that, I'm actually in a lucky place because my migraine is in remission. And indeed, what you said is, it's all true. It's all linked to food. It's linked to exercise. It's linked to your circadian rhythm. It's linked to environmental toxins, your detox, everything. And I think all that feeds into inflammation, and that kind of is the, is the key or the thing that unifies it all. But anyway, um, I think one thing that I wanted to ask about the melatonin supplements more. Oh, and I should say also about the supplement story of mine that you said, go from, go low and go slow. For me, it went backwards because I started with 10 milligrams, right? So, then I thought maybe 5 milligrams. Then I thought maybe 3 milligrams. All the time, I got like huge side effects, and then I ended up to that sweet spot, 0.3 milligrams, which I actually, it works great, and I've been using that for a long, long time. Sometimes I do it up a little bit, um, depending on the supplement that I have. So, I think this is important. Yeah. So, that people will understand because some supplements that are from prescription melatonin, you know, the levels, how much melatonin do they contain? Then we have something that you can buy from the stores, they can contain pretty much anything. And then we have the phyto melatonin, which I know you're obviously an expert in, because you're also the scientific advisor or the chief scientific officer of Herbatonin, which I currently use and it works great. So, um, could you explain the differences between melatonin supplements, how they are made in the first place, and what should we know when we are maybe thinking of buying one or using one, or when we are using one?

Yeah. So, let's just go back to Dr. Aaron Lerner, the dermatologist that identified melatonin back in the 1950s. At that time, there was more exploration into melatonin, what it was doing. There was more research on the pineal gland. What is that doing? And so, then eventually, we started to move into the, um, the removal of pineal glands from animals and a concentration of melatonin. But as you can imagine, that's not very feasible. It's not very ethical. There's, uh, you know, you think of the small amount of melatonin that is in a pineal gland and the number of pineal glands you would need in order to extract melatonin. So, that would be challenging. And then you also have other issues with animal-derived sources like prions, infections, or just any number of things, right? It just wasn't very practical. So, what ended up happening with melatonin supplements was that they were then synthetically derived. So, typically through different prochemicals and through a chemical process whereby many of these different processes, by the way, were patented. So, you can actually go in and look at the patents and you can see the process of the organic chemicals that are used and how it's tracking through a number of sequences and steps in order to get the final product. Now, that made melatonin very accessible. It made it very inexpensive. But again, there was also a cost to that. 99% of the melatonin supplements on the market are actually synthetically derived. And there are at least two publications that I know of that talk about the risk of contaminants in synthetically derived melatonin. And I don't think many people realize this. And if we're talking about detoxification and living a more clean life, we want to be taking, if we're paying for a supplement to help our health, we obviously don't want anything that would, um, not be healthful in that supplement. But there are certain contaminants that have been identified, you know, up to 13 different contaminants, whether tryptamine derivatives, um, different phthalimide derivatives, and also some supplements out there. And there has been a publication where they pulled some melatonin supplements from the market. They analyzed the melatonin content and found that the products were ranging quite a large range, like upwards of something like 20% to over 450% of label claim. So, there was a lot of variation in the amount of melatonin that was in that supplement.

Inca, the other thing I think about is when melatonin is mixed with other things. And let me give you a little bit of an explanation of what I mean by that. So, there was a lot of popularity in the states to have melatonin gummies, which I understand people have pill fatigue. If you don't, you know, you don't want to take another capsule or tablet if you don't have to. And gummies are pleasurable and nice to chew and they give you sugar, but you don't actually know how that matrix, that hygroscopic watery matrix can actually change the activity of melatonin, right? And you know, then you have to measure the stability of that. The other thing is that melatonin, because it's an antioxidant, it can be susceptible to oxidation, right? It can change its configuration when it is subject to air, light. So, when people have like jars of melatonin supplements or gummies and they're sloppy about tightening the lid, by the time you start to get to the bottom, chances are you're not going to have much active in that. And that would go for things like vitamin C, too. You know, my, my husband and I, I'm always like, you have to close these jars because you cannot let light slip in.

So, let's talk about, like, now moving, like, how do you know if you have a good melatonin supplement? As you mentioned, I'm the chief science officer at Symphony Natural Health. Symphony has a number of different plant products, and one of them is called Herbatonin, and Herbatonin is derived from the plant cell matrix. So, it's actually still embedded in the plant material. So, it has an amplified response in its activity because it's not just the melatonin, but it's melatonin plus lutein, zeaxanthin, essential fatty acids, a lot of the different things that are in that plant, the chlorophyll. So, you know, all small amounts, but again, what we know about nature is that plants work with this beautiful composite of different things that are in the plant to create amplified or synergistic activity. So, with Herbatonin, you get 0.3 milligrams within this plant cell matrix. And there's also a three milligram dose for things like jet lag or like you were saying, when, when sometimes you might need a little bit of a higher amount, or with travel, or, you know, any number of different things. But there was a study that was published, and not many people know about this study, but the researchers used Herbatonin versus synthetic melatonin and just compared them side by side. And by the way, this is all published in an open-access journal. It was published in 2021. You can find it in the Molecules journal. And what they showed was, they did a number of cell studies to look at function. And they found that when they looked at anti-inflammatory activity, that the Herbatonin was 646% greater in its anti-inflammatory effects. And this was looking at COX-2 cyclooxygenase-2, the enzyme, one of the main enzymes that is connected to inflammation. Then there was another cell assay looking at free radical scavenging. What we were saying before about the mitochondria, looking at scooping up a lot of those free radicals. And what these researchers found was that there was a 470% greater free radical scavenging with Herbatonin versus synthetic melatonin. And then there was even a human skin cell model where they looked at how much reactive oxygen species were in the skin cells and what was there a difference with Herbatonin versus synthetic melatonin. And what they found was that there was a 100% better reactive oxygen species level with the Herbatonin. So, that's pretty remarkable because if you were to take Herbatonin at 0.3 mg, it's almost like, even though it's 0.3 milligrams of melatonin, it has the efficacy of 6 to 8 times greater than if you were just to take that 0.3 milligrams as synthetic melatonin. And again, I chalk it up to potentially all of the different things that are in the plant. And the other thing I want to mention is that Herbatonin is in a blister pack. So, it looks like this, right? So, you, you're taking out one at a time, and so it's preserved from oxygen, and you're, you're not getting degradation, so that you can ensure that when you're taking that melatonin, when you're taking the Herbatonin, that it's actually that dose of melatonin. So, yeah, you know, I have had friends, colleagues, practitioners, and when I start telling them about Herbatonin, and then they change over, they say, "Oh my goodness, I used to not be able to take melatonin, and now it just feels so smooth. I, it feels so different. My sleeping, I, I can't tell you how many people have, um, had such a great benefit and just a, a very different effect. Some people talk about too, um, better, um, I would say, blood sugar. You know, they have all of these other effects that seem to be also very helpful. And the fact that the melatonin is in the plant cell matrix is almost like mimicking the body's natural release of melatonin rather than some of these formats where you take the melatonin and then it's just like into the body and quickly, you know, that's not how melatonin is normally produced, right? Like, we have a gradual incline with the dim light, and then in the pinnacle of darkness, we have the peak production, peak production and secretion, and then it comes down. So, yeah, I'm a big plant lover, and, uh, I just, I, I think that there's something to this formulation of melatonin that is quite different.

Yeah. So, um, I actually have to share the same experience that a lot of your friends and colleagues, as you said. So, one of the reasons I invited you to this podcast is that you were in Seam's podcast, uh, a while back, I think maybe you've been even twice there, and we had Herbatonin at home, and I've been using pharma melatonin for a long time, as I alluded earlier, and then I switched to Herbatonin, and I was like, 0.3, like, this is nothing. But then I tried it, and I'm like, wait, but the effect was better, and I have less side effects. So, I've been actually using phyto melatonin since, and I've been very intrigued by, um, the whole, like, complex of nutrients that it has, rather than just the, I, I would assume, like, on some level, the carotenoids as well, protect the melatonin itself from degradation in the, in the, um, in the supplement. But as you said, you are a big plant lover, and you have several times talked about detox in this podcast, and the importance, and you also said that melatonin can help us with detox, detoxification. So, let's discuss detoxification a little bit, because this, I feel like it's also a topic that many people now start to realize is a huge thing. How much there is accumulation of toxins from the environment into our bodies, and how much we don't know what we contain, like, what's inside us. So, um, what is detoxification biologically? I guess many people when they hear detoxification, they think like a juice fast or something, or going to a sauna. But what is biologically, mechanistically, detoxification, and how does it work in the human body?

Yeah. Well, detoxification is nothing new. I mean, anytime that we are metabolizing and eliminating, excreting things from the body, that's the process of detoxification. And I think that detox has had a bad reputation because people are trying all of these different shortcuts to trying to force toxins out of the body. And some of them are quite unnatural, and some of them can actually make you sick. So, and people might say, well, that's the healing crisis. But I don't think that people need to become ill in order to effectively remove toxins. In fact, I think that there's a happy balance of not having food and

allowing the body to repair and turn over and clean up cellular debris and also bringing in nutrients because we we actually need nutrition to move things out of the body just like we were talking about the lymphatic fluid.

So, let's just zoom out for a second. Like the body takes things in, the body has to let go of things. We used to say in nutrition that you are what you eat and you are what you um but you are not what you are not absorbing. So like you're excreting, right? So that that proper balance of taking things in and releasing.

And for some of us we that that by the way that's a very enzyatic process. It's driven by proteins in the body for the most part when it's done in a more metabolic way. And let me just say that there are so many different kinds of toxins. So, it kind of depends on what toxins we're talking about. But if I'm thinking of things like toxic metals or I'm thinking of solvents or I'm thinking of pesticides, herbicides, insecticides, persistent organic pollutants, airborne toxins like molds and micotoxins. Um, you know, there are a whole bunch of other toxins too like endotoxins. Stress can also fuel a lot of um production of cytoines. It's just kind of like how do we define a toxin? I think that there's even debate about that.

You know, in one of my books, it's all on detoxification. And I define toxins as anything that stands in the way of your health. So, that's a big a big way to define them, right? So, it could be a toxic emotion. Maybe you have a ruminating thought that keeps you inflamed. Well, you could say that that in some way is toxic, but let's just talk about a physical process for detoxification that would apply to lipopilic toxins from the environment. And I'm saying lipopilic or lipidloving fat soluble toxins because those are some of the toughest ones to get out of the body because you know certain ones that are water soluble like bisphenol A tends to be more water soluble. So we can better eliminate that through the urine and we if we stopped having canned foods and stopped our intake of bisphenol we would start to turn that over pretty quickly through the body and it would be excreted.

But some of the other kinds of toxins like the ones that are lipid soluble, they're greasy, they're reinous, um they persist. That's why we call them persistent organic pollutants. They stay in the body and then they go into the fat tissue and they go into fatty tissues like the brain or even the kidney, the liver and then they start to change the function of those organs. So a lot of different health conditions have been related to increased toxin load. But not everybody gets sick from toxins even though we live on the same planet. So why is that?

I do think Inca that there is if we look at the systems of elimination like if we're sweating, we're urinating, we're defecating, we have glimpmphatic fluid excretion, right? All of those things can be very variable depending on the individual and what we are doing by way of that elimination. So, we can also have different genes that would maybe make some of our detoxification pathways not so efficient or we may need certain nutrients a little bit more to drive through those reactions or to quell some of the metabolites that are created by way of that detoxification process.

So I just want to also mention that hormones hormones like estrogen also go through the same pathway. Hormones like estrogen are also fat soluble. So they need a a lot of the same process. So let's just imagine we are taking certain things in that are loaded with pesticides. The first thing would be make sure your gut microbiome is really robust because this is our first line of defense. If we can prevent the toxin from getting in the body, that prevents us from using our internal reserves to move it out of the body because it takes a lot of energy to move things out. And many of these toxins are mitochondrial poisons.

So, one of the first things that we see as a result of increased toxin load is fatigue. Unexplained fatigue. Not knowing why we've got this diffused pain syndrome. We can't move. We have lethargy. We get headaches. You know, there can be a whole number of things that happen and sometimes quite diverse where you would see toxin load play out differently in different people. So, just to make it simple, you know, could you ask me about the the process of detoxific? It's a long discussion really, but let's just make it simple.

You know, basically there are three phases. One is we take that fat soluble toxin and we make it more water soluble. So we have certain enzymes that will attach certain groups onto that like a hydroxal group or an oxygen or a hydrogen in order to make it more water soluble. And sometimes what happens as a result of that is it starts to make that toxin more reactive in the body. So we can see that that starts to act as a free radical, right? That's where melatonin would come in and other antioxidants.

And then it moves along into what is commonly referred to as phase 2 detoxification which employs a number of different enzymes. lots of different enzymes whether glutathione s transferase, methyl transferases, sulfot transansferases, glucuronicil transferase, a lot of these different enzymes which they will take a a some kind of conjugate like an amino acid, a sulfur group, and then they'll attach that to that reactive compound. That'll make it even more soluble and then allow for the phase three process which is to get it out in the bile which will then go out into the gut into the feces into the stool or it can make it go into the blood and eventually into urine or maybe we even sweat it out right so um that's why sauna is such a detoxifying practice so I'll stop there because there could be a lot of different questions and again this is a a big discussion obviously It is a huge discussion.

I think maybe we even need to do another podcast because we are a little bit of short on time with this one. I would maybe like as a last question if you can give like um um one let's say one nutrient one supplement that you think would be absolutely beneficial for anyone outside of melatonin to support this detox uh pathway or all of the I guess there are defense for phase one and phase two but um at least one that will help us to get rid of all of the things from our body that we don't want in it.

Yeah. Well, then I'm going to go with the heavy hitters of the cruciferous vegetables. So, the stinky sulfur containing crucifers. Um, many times they are heavy-hitting on phase one and phase 2. You know, we think about water crest, broccoli, cauliflower, Brussels sprouts, kale. A lot of these veggies, they can modulate our detoxification process. Broccoli sprouts are amazing in terms of giving us again the glucosinylates that we need. Sulforophane comes from this this vegetable or plant family. So the brassasica vegetables I would say if you say Deanna hey next to melatonin what would you say? I talk about the crucifer all the time.

And what I would say here let me just add in a different punch to it. Not just the crucifer but purple varieties of cruciferous vegetables. So what do I mean by that? Like purple broccoli, purple brussel sprouts. because you want the polyphenols which come in from the purple in the plant but then also have the goodness of the glucosinylates and a lot of the other activives within the vegetable as it is to help with detoxification. So purple varieties of the brassasica vegetables are even better. I don't know if you have those in Estonia. Do you do you have a lot of purple varieties of like where you do have like purple kale and purple varieties of these green vegetables for the most part? We have some of those. Some of them are imported. Okay. Well, so not locally. Yeah. But we have you get Yeah. Um but so we go from idio greens to eat your greens and purples.

Yeah. Well, since I can only get one thing, I want to stack it with as much as I can. And maybe in our second conversation, we also bring in polyphenols, which polyphenols are a whole class of phytochemicals that are chronobiotics, a little bit like melatonin, and they seem to play a role in multiple body functions and systems. And they can act as binders in the gut. Some people will even call that an anti-nutrient, like, oh, they're binding things. Um, but they can be protective. So that's why I'm mentioning the purple together with the cruciferous vegetables. So yeah, that's what I would say. So stay stay tuned for the next episode. Um, thank you Dr. Minik so much for this. Like I learned so much and I'm sure the listeners as well. Can you do the finally I I know you are very active in social media too. Could you provide us your links, your books, everything that you're excited about at the moment and you would like people to learn more about? So, uh, direct us to learn more through your channels.

Sure. Thank you for that. Uh, my website has everything damn.com and through that you can get my social media handles. I would also say check out symphony naturaturalhealth.com. You'll learn much more about herbatonin. We also have products for women's hormones and men's hormones through maca. And maybe we even talk about the colors of maca and how that connects to function as it relates to the hormone system in the body, the endocrine system. So symphonyaturalhealth.com, dnaminn.com, you can check out our social media from there. You can sign up for my newsletter. I love educating and informing and providing a lot of information as much as I can. So, it's been a pleasure, Inca. Thank you for having me on. Thank you so much. It was an honor.