Ben Greenfield [00:00:00]: My name is Ben Greenfield, and on this episode of the Boundless Life podcast.

Deanna Minich [00:00:04]: The second function that I think about with respect to antioxidant function is the mitochondrial regulation, which is actually pretty exciting. Melatonin helps to create better efficiency of the mitochondria, so it can stabilize those mitochondrial membranes, it can reduce reactive oxygen species, and it just overall improves energy efficiency. So in part, I think that's why it's so pivotal in diseases of aging, metabolic disease, even neurodegeneration, any number of different neurologically based diseases which would be enriched with mitochondria. I think that that's what we're seeing as far as the cutting edge aspects of melatonin.

Ben Greenfield [00:00:48]: Welcome to the Boundless Life with me, your host, Ben Greenfield.

Ben Greenfield [00:00:52]: I'm a personal trainer, exercise physiologist, and nutritionist.

Ben Greenfield [00:00:55]: And I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

Ben Greenfield [00:01:09]: All right. As you guys know, I am a nerd. I like to read science. And there was a paper in Nature, and it was. I forget the exact name of the paper. My guest probably knows because she wrote it, but it was super interesting. It was about melatonin. Something like, is melatonin the next vitamin D? And it was such an interesting paper that I really want to get the author on to dive into all things melatonin, because I get so many questions about it.

Ben Greenfield [00:01:36]: And she knows way more about melatonin than I do. And I learned a ton from this paper, which I'll link to in the show notes. But her name is Deanna Minich. She is PhD. She's a certified functional medicine practitioner. She has a master's degree. She's a nutrition scientist. She lectures all over the place about this stuff for over 20 years in the food and dietary supplement industry.

Ben Greenfield [00:01:59]: If you want to check her out, it's DeannaMinich.com and I will link to all this stuff if you just go to BenGreenfieldLife.com/ Melatonin Myths. That's BenGreenfieldLife.com/ Melatonin Myths. Deanna, what's up?

Deanna Minich [00:02:15]: Hey, Ben. Good to see you. And it's so refreshing to see that you are in the melatonin camp. You know, I don't know why, but melatonin has been so polarizing. And when you and I spoke a few years, I think it was a few years ago at CHS, you were talking about microdosing melatonin. And I was thinking, okay, he's onto it. He knows the literature and the science.

Ben Greenfield [00:02:39]: So okay, well, I was going to save this for later, but, I mean, might as well start here. I've kind of gone beyond microdosing, so I'll tell you what I do. And I know there's a whole lot more we're going to talk about regarding melatonin. But I'll tell you what I do, because I know that some people who listen also do this after hearing me talk about what I do. But basically, I don't use melatonin much at all when I'm at home, and I don't use it that much when I travel, except when I cross more than about three time zones. Like I'm going to Australia on Monday, so I'll for sure do what I'm about to tell you. And then there's this company called Mitozen. I don't know if you've heard of them, but they have a product called Sandman.

Ben Greenfield [00:03:26]: And Sandman is basically what I call like a melatonin sledgehammer. It's got 300 milligrams of melatonin in it and there's an oral option and there's a suppository option. And I do this for the first two to three days when I get to my final destination, literally 300 milligrams, and I feel like I get over my jet lag way more quickly. I get accustomed to the new time zone more quickly. I'm a little groggy in the morning, but as soon as light hits my eyes, that goes away. And yes, it's a crapload of melatonin, but I didn't notice that much when I used to do 3, 5, 10 milligrams.

Ben Greenfield [00:04:07]: And then this guy, Dr. John Lieurance, who's got this company, Mitozen, he turned me onto the idea of high dose. And I swear by it, like, it works for me. But is that what's your take on the super high dose of melatonin?

Deanna Minich [00:04:21]: My take is we just don't know enough about it and the implications of high dose melatonin. Right. And there are different sleep protocols to help with jet lag, which would involve, like, trying to think about your sleep before you actually travel and then bringing in a different dose of melatonin once you're at your point of destination. But with high doses, what we don't know is, and I know we're going to unpack some of the functions of melatonin. And it sounds like you're just doing it for two days or so. Right. Just to kind of get you on.

Ben Greenfield [00:04:52]: Your way two to three days when I'm there and then usually when I get back for two to three days.

Deanna Minich [00:04:59]: Yeah. So you're using a pharmacological dose of melatonin short term, which again, we just don't know enough about. And it seems like, you know, there's so much buzz in some circles about melatonin that people think that if a little is good, more is probably better. And I'm going to, you know, we can kind of talk through this. But what I see in terms of the literature and the most pronounced effects are those that are physiologic and also repleting the levels that we lose with age. And that's why I think that within the biohacking movement there has been such an upswing on melatonin because it has so many other functions other than thinking about sleep or jet lag or, you know, just trying to get over that early morning wake up. And I think that's where the interesting piece is with melatonin.

Ben Greenfield [00:05:51]: Have you ever taken a whole bunch? Like 300?

Deanna Minich [00:05:53]: I've never taken a whole bunch in that way because, you know, I try to stick. You and I were talking about how we both live in Washington state and I do think that, you know, I'm, I'm into nature and I'm into plants. Not exclusively, it doesn't always have to be plants. But when we start getting up into those triple digit numbers of melatonin, we also just have to look at the quality of the melatonin, how it was synthesized. Because what ended up happening back in the 90s is that there were all these different methods, right? Proprietary patents on making melatonin and synthesizing deriving melatonin from petrochemicals. So yeah, I stick close to the amounts that we find in nature and just try to replete what we lose with age. But that's just my personal approach. And again, it's just based on the science and the different clinical work that's been done.

Deanna Minich [00:06:47]: And also I've talked to a lot of different experts like you, like Russel Reiter, who I call the grandfather of melatonin.

Ben Greenfield [00:06:54]: He's the guy John Lieurance, when I interviewed him. And John Lieurance is the guy who told me about high dose melatonin. He said he also learned a ton from this guy, Russel Reiter.

Deanna Minich [00:07:03]: I love Russel Reiter. Right. And I've actually sat with him, I had breakfast with him. He has published so much on melatonin. So I think as we kind of get into the science of melatonin, it'll become clearer all the Many ways that we can use it and perhaps what doses and what forms would be best. Because I think that there are some hacks in the way of how to take it, how it plays with other nutrients. I know we're going to talk about vitamin D, so I think as we start to scratch the surface, we're going to see that there's a lot more there and perhaps we have to tailor the dose to the application that we're looking to serve in the body.

Ben Greenfield [00:07:43]: Yeah, yeah. Like if you're using it for, I don't know, I suppose something like cancer management versus sleep. And I know that you call like the multitasking molecule, but what does it do beyond just like chronobiology and its effects on sleep? What else does it do?

Deanna Minich [00:08:01]: Yeah, so let's go through. There are six major functions of melatonin. And the first one is, I think one of the more intriguing ones is an antioxidant. And I know that that may sound very mundane like, oh, but vitamin C is an antioxidant, vitamin E is an antioxidant. So many plant compounds are antioxidants. But the difference with melatonin is that it is what is called an amphiphilic antioxidant, which means that it can flex to being water soluble and fat soluble. So. So it can traverse through many different body systems and quench free radicals in those different body compartments.

Deanna Minich [00:08:42]: In fact, Dr. Tan had published a study in which. No, not Barry, no. Dun Xuan Tan. He actually worked with Dr. Russel Reiter and what he found was that one molecule of melatonin has the ability to quench up to 10 free radicals. So even the metabolites of melatonin have antioxidant properties. Whereas with vitamin C as an example, vitamin C can quench only in the water compartment of the body about one to two reactive oxygen species. So not only is it scavenging to a great quantity, but also its metabolites can scavenge free radicals and it can upregulate antioxidant enzymes like glutathione peroxidase and superoxide dismutase.

Deanna Minich [00:09:34]: So when I hear people out there talking about, oh, glutathione, the master antioxidant, I often think about, well, what is actually one of the precursors even of glutathione. And melatonin can stimulate glutathione. So I think that's one of the big functions.

Ben Greenfield [00:09:53]: Yeah. And sometimes, you know, based on the oxidation inflammation that occurs with something like airline travel. I wonder at the back of my mind, like how much of the, how good I feel when I use melatonin when I'm traveling is derived from the sleep benefits versus it just helping to fight a lot of the oxidation I've experienced while I'm traveling.

Deanna Minich [00:10:11]: Yeah. And actually because you're getting more solar radiation and ultraviolet radiation with travel, and there are studies looking at melatonin's use for those types of radiation and helping to buffer against those sources. So that's true. I do think we have to think about all the many implications. The second function that I think about with respect to antioxidant function is the mitochondrial regulation, which is actually pretty exciting. We know that melatonin helps to create better efficiency of the mitochondria, so it can stabilize those mitochondrial membranes, it can reduce reactive oxygen species, and it just overall improves energy efficiency. So in part I think that's why it's so pivotal in diseases of aging, metabolic disease, even neurodegeneration. So I think that that's what we're seeing as far as the cutting edge aspects of melatonin is more in line with things like dementia, Parkinson's, any number of different neurologically based diseases which would be enriched with mitochondria.

Ben Greenfield [00:11:22]: Okay, all right, so we got mitochondria, we got antioxidant. Yeah, you said there's six.

Deanna Minich [00:11:27]: Yeah. Okay, so those are two. The second one is anti inflammatory. So usually antioxidants act as anti inflammatory agents. And we know that melatonin can help to down regulate pro inflammatory cytokines. So things like TNF Alpha, IL 6. So it's just a natural modulator of immune responses and very helpful for things, you know, even when people were looking into viruses and Covid, melatonin was part of the protocol to help with the cytokine storm.

Ben Greenfield [00:11:58]: Yeah, I remember that. Yeah, that was what all the kooks were using, Ivermectin and you know, the horse dewormer people, they were also on.

Deanna Minich [00:12:05]: The melatonin bandwagon and melatonin was there. In fact, that's kind of what piqued my interest because me and nutrition science, melatonin wasn't always part of my mental landscape. Right. It was kind of like, oh, but you know, it does all of these other things.

Ben Greenfield [00:12:20]: Okay. And then the fourth is neuroprotective.

Deanna Minich [00:12:23]: So what? Because melatonin is lipid soluble, it can cross the blood brain barrier, so it can protect the neuronal tissues. It can protect against things like excitotoxicity. In fact, I even just posted this morning on my Facebook page about how melatonin is now being looked at and utilized to help with glymphatic fluid exchange and flux. And I'm sure you know all about this, right? So it's brain detoxification at night. It's the way that the brain gets rid of toxic amyloid protein and tau proteins. And so it appears that melatonin acts as a shuttle, a helpful vehicle for the release of a lot of these metabolites, and also helps with the aquaporins that are responsible for that polarization and that shift in that movement in the brain at night.

Ben Greenfield [00:13:16]: I've been messing around with this ultra human ring and it has these things called power plugs on it where it'll do like cycle tracking, all sorts of different little add ons. But one of them they just added is glymphatic drainage efficiency at night based on some different sleep parameters that they've correlated with that they just turned it on like two days ago. So I haven't done this experiment yet, but it would be kind of cool to see if I take melatonin if the glymphatic drainage score on this goes up.

Deanna Minich [00:13:49]: Yes, you should try that. And I'm assuming that they're basing that on slow wave sleep because that's where we tend to see most of the glymphatic fluid blocks.

Ben Greenfield [00:14:00]: Exactly. They're approximating glymphatic drainage efficiency based on sleep architecture.

Deanna Minich [00:14:05]: Okay, got it. Interesting. Well, check into that because I feel like if you start to connect the dots again, back to Alzheimer's, back to neurodegenerative conditions, we see that there is this connection with detoxifying the brain at night, which again syncs up when melatonin is highest. So moving on from the neuroprotective effects, which again, that's probably my biggest interest personally. We also have the antiviral aspects. So what we see. And Doris Loh, you probably know who she is, she talks a lot about viral replication and how melatonin can help to modulate intracellular biology to prevent phase separation. So that could be helpful.

Deanna Minich [00:14:51]: I think we need a little bit more research there. In general, we know that melatonin is an integral part of the immune system. But I think in terms of looking at viruses, a lot of that work is still preclinical. So I think looking deeper into that will be good. And then the last function that I think about is one that you already mentioned, and I'm not going to say sleep, it's not actually sleep, it's that it's a chronobiotic agent. So usually when people. And this is the biggest myth. Well, one of them on melatonin, is that many people think that melatonin is for sleep, when really it's about opening the sleep gate by in training the circadian rhythm.

Deanna Minich [00:15:32]: It's helping us to synchronize to the circadian rhythm. And it does that through the element of darkness. And that's happening through our eyes. As we start to perceive less blue light and it starts to become darker, we have increasing levels of endogenous pineal melatonin. Then those levels peak between 2 and 4am and then we start to come down. So we have negligible pineal melatonin throughout the day. It's really happening in the period of the day that is dim or dark.

Ben Greenfield [00:16:07]: What if you took melatonin and then, like, during the day, like, if you're just like, out in the light under the sun, maybe under LED fluorescent lights, whatever, would you get sleepy or would it just not work at all if it's light outside?

Deanna Minich [00:16:19]: Mixed reviews on that. There's a very personalized response to melatonin. So if we are taking melatonin during the day, which actually, you know, Russ Reiter talks about how he takes it for its antioxidant function, and he doesn't get sleepy, so he doesn't get that soporific effect. Some people do get a little bit sleepy. And so if they're driving, operating machinery and they want to take it during the day, they just have to be a little bit wary and more alert about its effects. And part of that is because of how we metabolize melatonin. Some people are quick metabolizers of melatonin, and other people are slow metabolizers of melatonin. In fact, the same enzyme that metabolizes caffeine metabolizes melatonin.

Deanna Minich [00:17:07]: So in some way, you can deduce how you would respond to melatonin by how you respond to caffeine.

Ben Greenfield [00:17:14]: Interesting. Okay, well, I'm a super fast caffeine metabolizer. Like, if I had to, I'm the guy who could, you know, fit in Italy pretty well because I could do three shots of espresso before dinner and go to sleep just fine. So maybe that's why I feel better with more melatonin.

Deanna Minich [00:17:30]: Maybe. Maybe. Yeah. And also the only thing to note with, again, those high levels is that melatonin still works through receptors. And if you look at Dr. Richard Wurtman, his work at MIT and others, they talk about saturating the receptors. So saturating those receptor sites, you know, you can get to a point where you've over saturated. Then you just kind of hit a ceiling on that.

Ben Greenfield [00:17:55]: Right, that's possible. Although like I mentioned, I use a suppository which I know is gross for a lot of people, but it kind of like slowly comes in during the night, all night. So maybe it causes a little less receptor saturation. I don't know. What was that word you used earlier? Soporification.

Deanna Minich [00:18:13]: So perfect. It just means sleepy or hypnotic effect. Like some people can get that with certain things, like even L theanine, which has kind of like a restful alertness effect for most people. Like some people get kind of entranced or you know, they get that kind of hypnotic sleepy effect. So that's what I'm referring to with melatonin. Some people can get that.

Ben Greenfield [00:18:34]: Okay, interesting. So perfect. All right, so the. I mentioned cancer and obviously that's kind of like a controversial word. Some people don't like it because they think they're going to cancel. I don't mind talking about it, but the Alzheimer's piece makes sense. Based on what you said about neuromodulation. I could see it having effect on glucose regulation based on the antioxidant, anti inflammatory effects.

Ben Greenfield [00:19:01]: And you talk about those in your paper. But the cancer piece, talk to me about that.

Deanna Minich [00:19:06]: Yeah. And you know, the expert that is Dr. Paolo Lissoni, an Italian oncologist. So if you start to look at the literature on cancer, what you're going to find that in the 1990s is when he started to take cancer patients and give them higher dose melatonin. So we're talking double digits, not triple digits. So between 20 and 50 milligrams in combination with chemotherapy. And what he found was, was that the melatonin helped the healthy cells to stay healthy and to help the chemotherapy actually better target the cancer cells. So he has a number of publications on that actually.

Deanna Minich [00:19:49]: And it makes sense because if we're looking at cancer as an inflammatory process and we are working through the mitochondria, because again, if we look at things like even metabolic syndrome or insulin resistance in the connection with things like cancer, if we're getting at that metabol, metabolic machinery in the mitochondria with melatonin to protect it and to fortify it, what we can see is that ripple through effect of the cellular effects on cancer. So yeah, so just from a cell perspective, you know, just kind of looking at that point of view, melatonin can inhibit cancer cell growth, it can promote apoptosis, it can suppress blood vessel growth, that leads to greater tumor growth. So I think it's worthwhile to explore with a healthcare practitioner if somebody is interested in that piece.

Ben Greenfield [00:20:41]: Yeah, you hear about, for example, cancer hyperthermia treatments and heat increasing the cytotoxicity effect of chemotherapy. And you hear the same thing about oxygen, you know, like hyperbaric oxygen, ozone, things like that. It sounds like, I don't know if the mechanism of action is better, cytotoxicity of the chemo or something else. Like you mentioned the anti inflammatory effects. But it sounds like melatonin might fit into the lineup of kind of like a functional medicine approach to cancer.

Deanna Minich [00:21:09]: Yeah, yeah, definitely. I think too, if you look at some of the literature, that taking melatonin during chemotherapy treatment can also reduce side effects. So you know, with a lot of those different therapies, and I think we're, you know, if we just kind of bundle them all together and look at, well, mitochondrial resilience or helping with cellular health, you know, it just stands to reason that bringing in a lot of these different therapies could be impactful. But then where do you reach the threshold where you've pushed the cell to the, to that instability or that place of where it's not as resilient? Right. I think that there's a sweet spot, especially when it comes to the mitochondrion, that it's like not too little, not too much, just right for mitoresilience.

Ben Greenfield [00:21:57]: Are you talking about the idea that if you take too many antioxidants, you'd kind of suppress your body's own endogenous antioxidant capabilities?

Deanna Minich [00:22:05]: Yeah. In some cases, when people do high doses of certain antioxidants, they can actually get kind of this redox cycling where you can even see prooxidant effects. Right. But melatonin is unique in that it does not undergo that redox cycling. So it's one of the safe, I would say probably one of the safest antioxidants that somebody can take. It's not to say that the whole array of different kinds aren't good to get in the diet, but I think when people just do supraphysiologic doses of certain antioxidants, and I don't know if you remember beta carotene, when it was given to smokers, this was a study back in the 1990s, what they showed was that the smokers actually had greater lung cancer incidence when they took the beta carotene versus when they didn't, because those high levels in that toxic milieu led to kind of this propagation of like a pro oxidant effect. Whereas melatonin doesn't seem to have that propensity like some other antioxidants.

Ben Greenfield [00:23:12]: Yeah, it seems to kind of parallel the research they did in, for example, swimmers with high dose antioxidants like vitamin C and vitamin E and the suppression of the training effect when done in excess because again, the body didn't mount the natural inflammatory response that would result in a better training response. That's interesting though about the ability of melatonin to kind of act as almost like a selective antioxidant. I think you could say the same for another one that's become popular recently, molecular hydrogen. Like the hydrogen tablets that I don't know if you've experimented with that at all. Like the hydrogen tabs in the water or the hydrogen water bottles.

Deanna Minich [00:23:50]: Yeah, yeah. It's a very interesting idea and concept. And again, I think for me as a nerdy scientist, I always look at what is the point of origin for that molecule. Hydrogen has been around, it's a part of us. Melatonin is an ancestral molecule, it basically co evolved with us. So. Yeah, and the data on melatonin, you know, thousands upon thousands of articles. There are so many references.

Deanna Minich [00:24:20]: I mean every day I get PubMed alerts looking at the newer data on melatonin and it doesn't stop, it just continues to increase based on what we're finding.

Ben Greenfield [00:24:30]: Yeah. And the paper you say vitamin D, what's the name of the paper again and again, I'll link to it in the show notes.

Deanna Minich [00:24:36]: Yeah, it's melatonin, the next vitamin D and it was published in the Nutrients journal in September of 2020. Yeah, okay.

Ben Greenfield [00:24:44]: Nutrients. I think I said Nature. Okay, so when you use the word vitamin D, are you saying melatonin acts like vitamin D? Are you just saying it's similar in terms of it being kind of a pleiotropic like compound that one could take?

Deanna Minich [00:24:59]: Actually you said that really well. So with vitamin D, one of the things that we look at there is is it truly a vitamin or is it a hormone? Is it anti inflammatory, Is it a mitochondrial regulator? It's an antioxidant. It's a lot of different things and it seems to connect. I call it a circadian nutrient. So vitamin D connects to the sunlight. Right, we all know that. So I think again there was a lot of visibility and there has been a lot of visibility around taking vitamin D supplements or Being out in the sunlight and how important that is for the synthesis of vitamin D. We also know that we lose vitamin D as we age, whether it's reduced absorption or increased need.

Deanna Minich [00:25:42]: So then if you look at vitamin D as being kind of the yang, being connected to light, sunlight, when you put melatonin side by side with vitamin D, you start to see a lot of similarities. Melatonin has similar functions to vitamin D. I don't even think we can pigeonhole and say that melatonin is a hormone like some people say. It's not just a hormone, it's all of those six things that we talked about. The flip side of melatonin is that instead of sunlight, it needs darkness. We need darkness for its synthesis by the pineal gland.

Ben Greenfield [00:26:19]: Okay, so you're not saying you need darkness for it to act or bind to a receptor or something like that. You need darkness for the synthesis, for.

Deanna Minich [00:26:28]: The production and the secretion by the pineal gland? Yes, that's a good distinction to make.

Ben Greenfield [00:26:34]: Okay, yeah, because like we were saying earlier, like the guy, Russel Reiter, who takes it during the day for the anti inflammatory effects, the light wouldn't negate the anti inflammatory effects. But if you were looking for the natural synthesis, and this is why people like, you know, wear the blue light blocking glasses at night or give them the screens, you need to have some element of darkness or absence of particularly blue light.

Deanna Minich [00:26:56]: You do, you need to have absent blue light. You do need to have that connection to in some way. It could be a red light, but it just can't be the wavelength that corresponds to blue light.

Ben Greenfield [00:27:09]: I was going to ask you that. Like if you get in the, like if you're underneath some red light panel or in a red light bed at night, it's not that kind of light. It's the actual blue light spectrum.

Deanna Minich [00:27:19]: Correct. And in fact, I mean our eyes, our retina, I mean our eyes are an extension of the brain. Right. So when you think about your eyes and what you're looking at, it's very relevant for thinking about pineal melatonin. So if we are around technology like you said, or even if we're at a gym with fluorescent lighting, some people go to the grocery store, they go shopping late at night, all of that is going to have an impact.

Ben Greenfield [00:27:45]: Grocery stores and malls and airports are so bad. Like they're the worst.

Deanna Minich [00:27:50]: It is. And especially, I mean, you're about to fly to Australia. I mean, I fly a lot as well and it's so interesting to me because I choose to fly at night or early in the morning when solar radiation is lower. And what you find is that the airlines, many times they will put on blue lights to calm you at night.

Ben Greenfield [00:28:09]: Yeah, it should be red, shouldn't it?

Deanna Minich [00:28:11]: It's ridiculous. Well, there's one airline I was on not too long ago where they did use red. They were smart enough to do that. But we know that candlelight has negligible suppression on melatonin. In our house, what we have are the Philips hue bulbs. So we can just control them, we can dim them, we can change them to purple, to red to orange. But you know, Ben, I really do think that artificial light at night, this blue enriched electric light, it's like one of the most societally accepted endocrine disruptors. You know, it's not just disrupting the pineal gland through the eyes, it's disrupting thyroid.

Deanna Minich [00:28:50]: I mean the whole endocrine circuitry is all connected. So if you're changing up pineal, it's this ripple through effect.

Ben Greenfield [00:28:57]: Well, people say it's great for the GDP to be able to stay up later and work longer hours, but like, well, what about you screwing your sleepover so you gotta then like sleep in or have lower productivity during the day. I'd rather people like finish work earlier, have fewer shops open at night, people get to bed at a decent time, get great sleep and maybe work a little bit more earlier in the day.

Deanna Minich [00:29:18]: Absolutely, absolutely. Or if you have to work at night, wear the blue light blocking glasses, use a dimming filter on your technology. And the other thing is, I can't see what color eyes you have, but eye color does tie into your light sensitivity and your effects on. Yeah. So there was one study in which they looked at people with blue eyes, green eyes, light brown eyes and dark brown eyes. And they found that those with light colored eyes were even more susceptible to the suppressive effects of blue light. So it was something like 17% greater suppression compared to people with dark colored eyes. Now that doesn't mean just if you have dark colored eyes, you should just forget about the blue light at night.

Deanna Minich [00:30:07]: It's just that people with light eyes, like I have green eyes, so I am very sensitive and I make sure that I am wearing those blue light blocking glasses and that I'm off tech as much as possible possible.

Ben Greenfield [00:30:18]: Are there things that you could take at the same time as melatonin to help it work better? Because like with vitamin D, they say we'll take it with vitamin K2 and magnesium to enhance absorption. Is there something similar? Like some kind of rule to follow with melatonin?

Deanna Minich [00:30:34]: Well, a couple of things. Some people will talk about vitamin C potentiating some of melatonin's effects. In other cases, what I think about is also the absorption and being that melatonin is also fat soluble. And some people do this thing where they take sustained release or some kind of slowed release of melatonin. And that's not as ideal because many times in those formulations, which tend to be enteric coated, they have phthalates or parabens. And so again, we're bringing in endocrine disruptors. But one natural way to slow the release of melatonin is to have it as plant melatonin in its natural matrix, which, in full disclosure, I am chief science officer at Symphony Natural Health, which has that plant melatonin called HHerbatonin.

Ben Greenfield [00:31:25]: Oh, I've heard of that. Somebody gave me some of that stuff one time to try. I seem to recall it working pretty good. I don't think it's the one that, that, that I get from Lieurance. I don't think his is plant based. But either way, this is interesting. So. So you can get different kinds of melatonin?

Deanna Minich [00:31:41]: Yeah, you can. And the HHerbatonin one is from rice, alfalfa and chlorella. And it was measured head to head against synthetic melatonin, and it was six to nine times greater in collectively its antioxidant capacity, its anti inflammatory activity. They even tested it in a skin cell model and found it was 100% better at quenching a lot of those free radicals. So because it's still in the plant base, you still have things in it. You have that plant matter. And so it' amplifying the effects of melatonin. Whereas with the synthetic melatonin, it's just the melatonin.

Deanna Minich [00:32:19]: And sometimes you have to think about contaminants. There are at least two studies in which they talk about the risk of contaminants and synthetically produced melatonin. So things like thalamide derivatives or serotonin or tryptamine derivatives that, you know, when people say that they get a negative effect from taking a melatonin supplement, many times I ask them, you know, what is the quality of that supplement? What else is in there? And if you put other things in it that modify that enzyme that we were talking about that metabolizes caffeine, you can actually speed up the metabolism of melatonin even more.

Ben Greenfield [00:32:57]: Now, this is a dumb question, but do plants actually make melatonin like you said, you get it from alfalfa and chlorella. You're actually getting melatonin out of the plants.

Deanna Minich [00:33:06]: Yes. In fact, this is. I love this because I love plants. One of the first applications of using melatonin was as a growth factor in plants. So even this morning I was reading an article looking at how using just the right amount of melatonin and applying it agriculturally to crops would be helpful for growth. The only thing is that if you use too much melatonin in that application, you can actually stunt the plant's growth, which is why, again, I think about that seesaw, that happy balance of just having the right amount of melatonin. But, yeah, I mean, plants make it and they obviously don't have a pineal gland, but they are using it as a growth factor. So it stimulates things like phytochemicals, like glucosinolates, and helps the plant with the photosynthetic process.

Ben Greenfield [00:33:58]: Wow. Who knew? I don't remember that from high school biology.

Deanna Minich [00:34:01]: No, I didn't either, actually. Well, and that's why some people say, like, oh, just have a handful of tart cherries before you go to bed so you can get some melatonin.

Ben Greenfield [00:34:11]: Right, yeah, I've seen that. I didn't know it was because of the melatonin.

Deanna Minich [00:34:15]: Well, and actually, if we start to unpack that a little bit, I did some of the math to calculate what is the average amount of melatonin that occurs in cherries. And when you do the calculations, you arrive at, like, 2,700 cherries that you would need to eat. Why would we be eating all of this before we go right to bed? Whether it's pistachios or walnuts or cherries.

Ben Greenfield [00:34:37]: You wouldn't sleep anyways because it takes a really long time to eat 2,000 cherries when you'd be up to, like, four.

Deanna Minich [00:34:42]: Yeah, no, that's true. And also, I mean, I love all of those foods. So, I mean, I'm not going to say don't eat those foods, but don't eat them to get your physiologic dose of melatonin. Right. So if we look at the life cycle of what when people are producing melatonin, kids actually produce the most amount of endogenous melatonin. So when you were a child, you were at your peak level of melatonin. But then it's kind of like a roller coaster where, like, you peak, then you start to come down. So, like, by midlife.

Deanna Minich [00:35:14]: Well, what is midlife anymore? But by the age of about 35, you have about a third of what you had when you were a child. Right. So then, and then when you're in your 50s, you have about 10% of what you had as a child. And then as you move your way into the 60s, you're like bottoming out. So a lot of people ask me, they'll say, Deanna, but if I take melatonin, like HHerbatonin, aren't I suppressing or stopping my endogenous production? And first of all, there's no science to suggest that. Secondly, you already have such little melatonin to begin with at that time of life. What you're trying to do is smooth the gap and get better and trained with your circadian rhythm.

Ben Greenfield [00:35:58]: Yeah, yeah. It'd be like a six year old man with low testosterone saying, well, if I get on testosterone, aren't I going to suppress my own Sonny? And it's like, well, you aren't making that much. So yeah, that makes sense. But there. So you just said something important. So there is no that, you know, of like negative feedback loop for melatonin. Like if you take it, you're not going to suppress it?

Deanna Minich [00:36:18]: No, not that I can find. There were actually at least four prospective studies that set out to answer that question and they could not find that melatonin worked like other hormones with this negative and positive feedback loop, which all stands to kind of support what we were saying about how it's not really a classic hormone, it's a circadian nutrient. I also, by the way, did ask Russel Reiter that question and he just kind of smiled and shook his head and he's, he said, you know, there's no indication that taking melatonin is going to reduce your endogenous melatonin. We would have seen that in the literature, especially because melatonin has been so well studied. So we, you know, the only thing again just to bring back is potential downregulation of receptor sites and that would be high dose use of melatonin over time.

Ben Greenfield [00:37:10]: Is there like a test for that though? Could you test how much melatonin you're making or how many receptor sites you have or anything like that?

Deanna Minich [00:37:16]: That would be difficult because that changes. The best you can do in terms of determining how much melatonin you have is to do a urine test. Actually, there are two tests. One is the saliva test, which measures the curve of melatonin production. It is tracking your dim light melatonin onset. So you have to do multiple saliva samples when it is dark. But just keep in mind that any little exposure of light is now going to change your results. Right.

Deanna Minich [00:37:44]: So it's not very reliable. The other one is to look at urinary levels of a sulfur derived metabolite of melatonin in your first morning urine. But that's really only telling you how you're metabolizing it. It's not telling you what you produced. The other thing that is of interest, so I like genetics. I think it's just a nice constitutional. It's just good to have that information on your constitutional type. Right.

Deanna Minich [00:38:17]: And there are certain receptors. There are two of them. And some genetic companies are now assessing whether or not people have gene variants in that specific receptor. So I just checked mine recently because I wanted to see and I don't have that gene variant. So that means that my body would seem to have normal receptor activity with melatonin. It's not delayed. If you have a gene variant, it can lead to melatonin sticking on the receptor for longer, which could lead to circadian imbalance and also some changes in other hormones like insulin. So there might be a way in the future, but for right now we can only get indirect assessments as to whether or not somebody has healthy levels of pineal melatonin.

Ben Greenfield [00:39:06]: Which genetic test did you do?

Deanna Minich [00:39:09]: I've done a lot of them, but the one I did most recently and she heard me talking on melatonin and they actually changed their lab report to include this. They're called 3x4 Genetics.

Ben Greenfield [00:39:19]: Oh, I know them. Yeah, I've used, I think they, they are available on like the RUPA lab testing platform. I test with them pretty long time ago, so I doubt my results are on there.

Deanna Minich [00:39:31]: You know what, contact them again because they just updated the report after the melatonin masterclass that I did in November. So now they have it programmed and they reran my my results. So I was able to see. So if you contact them, you can ask and just say, hey, I talked with Deanna and I'm kind of curious about that melatonin receptor. Whether or not I have a snp. I would just like to look at that specifically.

Ben Greenfield [00:39:55]: Cool. Got you mentioned that some of the melatonin has like synthetic petroleum based derivatives in it, such as the stuff with the coating for slow release. What, what about the part, I'm sure you saw this. There was some study that tested a bunch of melatonin supplements and the actual amount in them widely varied.

Deanna Minich [00:40:17]: Yes, no, that's true. That was a Canadian study and they looked at 31 different dietary supplements. I just know this because it has come up so many times. And what they found was that there was a huge range of melatonin in the products. Something on the order of, like, between 17 to 478% of their label claim. Yeah, it was a huge variation.

Ben Greenfield [00:40:41]: Sorry, sorry. Canadian supplements, well, they took from a.

Deanna Minich [00:40:45]: Variety of different ones. They were just Canadian researchers. And what they also found was that I think it was 8 out of the 30 supplements or so contained serotonin. And so they were looking at contaminants.

Ben Greenfield [00:40:58]: As well, which would be a big deal if you were on, like, an SSRI, right?

Deanna Minich [00:41:01]: Yeah. And just to kind of back it up, because I think you're going to find this of interest. So if we back up the biochemistry of melatonin in the body, like, how does the pineal gland produce it and secrete it? Ultimately, it's coming from tryptophan. So when you say, hey, Deanna, are there any other nutrients in order to think about amplifying the effect of melatonin? As we talked about vitamin C, what we didn't get into, though, was even taking it with omega 3 fatty acids, like a fish oil, soft gel, or even liquid, to kind of naturally slow the release. I've actually heard anecdotally that some people have a better response, especially if they're a fast metabolizer like you and me, where we need something to kind of be slower. So having the plant matrix of Herbatonin and potentially even having fish oil with it, I think that would be of interest to look at for sure.

Ben Greenfield [00:41:55]: Okay, so the pineal gland, you said that that is responsible for making melatonin. But you hear a lot about these neurotransmitters, for example, that we often think are generated in the. In, like, the brain. Actually, they have some origin in the gut also. Is there anything like that going on with melatonin, or are there factors related to the gut that would influence melatonin?

Deanna Minich [00:42:18]: Okay, so this all remains a huge mystery, but the gut produces 100 to 400 times the level of melatonin that you find from the pineal glands. So that's why I specifically say pineal melatonin when I'm talking about the pineal gland.

Ben Greenfield [00:42:36]: 100 to 400.

Deanna Minich [00:42:38]: Yeah, it's a lot.

Ben Greenfield [00:42:39]: Oh, my God. I think everybody thought it was just all made in the brain.

Deanna Minich [00:42:43]: No. And it's not a response to darkness either. You know, so people are asking the question, well, why is the gut producing extra pineal melatonin? Right. So here's the thing with the pineal gland. This is a classic endocrine effect. So in response to the darkness, we get that secretion of melatonin from the pineal gland, and then it goes throughout the body. It synchronizes all of the peripheral clocks to circadian rhythm. It has, like, that one function, right, that's really important, or at least the primary function in the gastrointestinal tract.

Deanna Minich [00:43:18]: It's not an endocrine function, per se. It is an autocrine or paracrine effect, which means that it appears that the melatonin is working more locally. And we actually know that a lot of different neurotransmitters and hormones are produced in the GI tract. But what we see is that you produce it at every segment in the lumen, in the mucosa, in the muscle layer. And it seems that it may have some role in establishing a healthy gut microbiome. It may also play a role in the motility of the gut. So some people talk about how their bowel patterns change when they take melatonin. So that could also be.

Deanna Minich [00:43:58]: And in fact, that might even tie into jet lag, if you think about it. When our bowel movements do get messed up, if you think about it, 70% of the immune system is in the gut. And we know that melatonin is a modulator of the immune system, so it could also be having some immune effects there. So I think that's of interest. You know, short chain fatty acids, which are produced in the gut from prebiotics, also seem to be stimulating the release of serotonin, which can then lead to the production of melatonin. Again, I just want to go back to what I was saying, too. Like, tryptophan is the precursor to serotonin and then melatonin. So one way to naturally support the body's melatonin is also to ensure that you have enough tryptophan in the diet.

Deanna Minich [00:44:44]: The pineal gland makes it through that conversion of tryptophan, serotonin, melatonin, and you need B6 for that conversion. You actually have five different enzymes that go into the making of melatonin from the pineal gland. So if you have gene variance or something lacking in that whole process, then you're going to be low in the amount of melatonin that your pineal gland can actually produce. So I just want people to be aware of that.

Ben Greenfield [00:45:10]: Yeah. Okay, so micronutrients matter here. Also, interesting. Why does melatonin give some people nightmares? Like my wife says, oh, I don't want to take that. It gives me weird dreams.

Deanna Minich [00:45:21]: Yeah, well, it has been shown to subtly change some of the phases of sleep. It may also change. You know, there are different theories about this, of course, so. And the question is, is it a good thing that melatonin can enhance the dream state? Because maybe, you know, I have a theory. I believe that melatonin is a molecule of consciousness. I do think that it is connected to different states of awareness. So maybe things start to surface and bubble on up in that 2 to 4am window when people start to wake up. Because many people ask me, like, why am I waking up when melatonin should be actually be very high? And I think part of the reason for whether nightmares or wake up or whatever it is, we have to look at a variety of different things.

Deanna Minich [00:46:12]: It's not really just the melatonin. It could just be your sleep patterns, your sleep cycles are changing. We see this with women going through menopause. And by the way, estrogen also goes through one of those same enzymes that metabolizes melatonin, which also speaks to gender differences for men and women in their response to melatonin.

Ben Greenfield [00:46:34]: Which one does it work better in men or women?

Deanna Minich [00:46:36]: It depends. Well, it's not about better. It's just like if a woman has high estradiol in her body, so let's just say she's premenopausal, she's a cycling woman, she's going to be using more of that cytochrome 1A2 that metabolizes melatonin. So there's going to be more competition for that enzyme, just like caffeine. So for women, they might be a little bit more sensitive to the effects or they may have a change in their metabolism. But a menopausal woman, let's just say her estrogen levels are much lower. You know, she's not going to have that same competition with the enzyme. So in essence, like she might have a, you know, less metabolic effects related to that enzyme.

Deanna Minich [00:47:21]: So they, she could just have a more, I would say something similar to what men would experience in that respect.

Ben Greenfield [00:47:28]: Yeah. Yeah, that is kind of interesting. Postmenopausal women can. They can fast a little bit more like men and don't see as many hormonal issues with fasting. Sounds like they might be able to do melatonin a little bit more. Yeah, I mean, postmenopausal women are just men, is that what you're saying?

Deanna Minich [00:47:44]: No, no, but it just, we don't have the interference of estradiol getting in the way of metabolizing melatonin. So we can change some of those things. I just want to go back to what you're saying about dreams as well. Because what the dream state might suggest to us is that there can be a brain liver connection. So if we look at traditional Chinese medicine, chronotherapy, we see that liver time is between 1 and 3am 1 and 3. So when people are waking up at 2am, you know, often I start to think, do they have high toxic load, do they have detoxification issues that they need to tend to? So is the body kind of getting more metabolically active in order to start to move things out through the glymphatic fluid? Right, so it may, if there are heightened dreams or wake up during that time of night, it may actually call us to be looking at how just our liver health detoxification and addressing detoxification and just looking at whether or not we can change the sleep state and the dream state would be something to explore. There isn't a lot of science on that per se, but that's just more kind of connecting clinical dots and saying to me, that tips me off that there could be a metabolic detoxification thing to explore.

Ben Greenfield [00:49:11]: So knowing all this, like having written this paper and studying melatonin for so long, what does your personal protocol look like as far as how you use melatonin?

Deanna Minich [00:49:21]: So I'm 54 and I know that I don't have a SNP in the gene variant. So the way that I receive melatonin is normalized and I take the Herbatonin 0.3 milligrams. So I take it on a daily basis because again, if I'm in my 50s, my mid-50s, I'm looking at, you know, I have a fraction of what I had. I am also postmenopausal, so I know that just keeping all of my hormones in alignment, I feel like that's good practice for me from an antioxidant and anti inflammatory perspective. And I do up the dose. When I'm traveling, before I travel, I'm more attentive. I'm trying to, especially if I'm going over time zones, I'm trying to shift my sleep a little bit like by 15 minutes per night. That's in the ideal world, like three nights before.

Deanna Minich [00:50:10]: But then when I travel, when I'm on site, I do 3 milligrams, 3 to 6. If I'm in Europe, I'll do up to 6. But if I'm in the US just traveling over time zones from west to east coast, I'll do 3 milligrams. Yeah.

Ben Greenfield [00:50:24]: So you'll go like 10 to 20 times sometimes what you'd use at home.

Deanna Minich [00:50:27]: I do. And keep in mind, because Herbatonin is six to nine times the function of synthetic melatonin, you're actually getting greater amplification and functionality.

Ben Greenfield [00:50:37]: Oh, I didn't know that. Okay, that's a good point.

Deanna Minich [00:50:40]: Yeah. Because 0.3 milligrams, if you take even on the higher end of that from its antioxidant potential, we're looking at almost 3 grams functionality. So speaking.

Ben Greenfield [00:50:50]: Yeah. Okay. Is that like a tablet or a capsule or a pill?

Deanna Minich [00:50:55]: It's a capsule and it looks green because it again is from the plant matter. And it's very easy. I mean, because it's such a small amount, it's very easy to swallow, especially the 0.3 milligram one. So I keep it in my bathroom. I take it right before bedtime. Much like you. I know that I'm a fast metabolizer of caffeine now, even though I can drink an espresso before going to bed, I wouldn't want to do that with melatonin for me personally, because that could change my kinetics of melatonin. So what I usually do is I just, you know, I usually, I do two cups of coffee a day at most and usually by 2pm and then I'm done with that caffeine.

Deanna Minich [00:51:35]: But the 0.3 milligrams works for me. My husband's a little bit different, though. He is. His chronotype is he's more of a night owl, I'm more of a morning person. And for him, he's a slower metabolizer. So for him, he takes that 0.3 milligrams about three hours before bedtime. And that seems to be the sweet spot.

Ben Greenfield [00:51:55]: Slow metabolizer, take it farther before bed, fast metabolizer, closer to bed. If you don't know, but you've had a genetic test, maybe look at your coffee metabolizing and that's going to give you a pretty good clue.

Deanna Minich [00:52:08]: Yeah, I think those are some of the steps. And, you know, just if you're, look at your age, you know, if you are in your 40s, your 50s, you know, I just think preventatively, it's just smart to patch the gap with a physiologic dose. You know, there are more indications for the safety of a low dose of melatonin than there would be for the high dose of melatonin over time. Right. So again, I just kind of think of it like a road and like we get potholes and so melatonin to me just feels like it's filling the potholes of like just smoothing out any inflammatory response helping me to not get sick as often. Now one of the things I noticed not this is just anecdotally just me, but I don't get sick as often. Like I don't get like the annual cold or flu that many people get. I don't know if that's from melatonin.

Deanna Minich [00:52:58]: You know, I do a lot of different things, but I do think that bringing that in, I don't know, in some way I feel like it's made a difference.

Ben Greenfield [00:53:07]: Yeah. Well based on what you said about the antiviral and anti inflammatory antioxidant effects that make sense and also the gut immune axis, I can think of all sorts of reasons. Deanna, we're about out of time. But for those of you who want to put on your propeller hats and dive into Deanna's paper, I'll link to it in the show notes @bengreenfieldlife.com/ Melatonin Myths also link to Deanna's website. I'll hunt down a link to this Herbatonin stuff and you can check that out if you want to try a different variant of melatonin made from chlorella and alfalfa and all that good stuff. And Deanna, thank you so much for coming on the show.

Deanna Minich [00:53:45]: Hey, thanks for having me. Great to have a conversation and I loved your questions.

Ben Greenfield [00:53:49]: Thank you so much. All right folks, again, shownotes are at BenGreenfieldLife.com/ melatonin myths until next time, I'm Ben Greenfield along with Deanna Minich signing out from BenGreenfieldLife.com have an incredible week to.

Ben Greenfield [00:54:01]: Discover even more tips, tricks, hacks and content to become the most complete, boundless version of you, visit BenGreenfieldLife.com in compliance with the FTC guidelines, please assume the following about links and posts on this site. Most of the links going to products are often affiliate links, of which I receive a small commission from sales of certain items. But the price is the same for you and sometimes I even get to share a unique and somewhat significant discount with you. In some cases, I might also be an investor in a company I mention. I'm the founder, for example, of Kion LLC, the makers of Kion branded supplements and products, which I talk about quite a bit. Regardless of the relationship, if I post or talk about an affiliate link to a product, it is indeed something I personally use support and with full authenticity and transparency recommend in good conscience, I personally vet each and every product that I talk about. My first priority is providing valuable information and resources to you that help you positively optimize your mind, body and spirit. And I'll only ever link to products or resources, affiliate or otherwise, that fit within this purpose.

Ben Greenfield [00:55:17]: So there's your fancy legal disclaimer.