Clinical Detoxification Update: Obesogens & the Liver, Gut, & Microbiome Connection | Deanna Minich

Wow. So, yes, I mean, I've been doing detox for a long time and thanks to Dr. Bland's work, working in the clinic and putting into motion a lot of the things that he's brought to light over the years. In fact, he and I even formulated a detox product together. So we've done a lot of things. So for me to squeeze decades of all of that research into 45 minutes will be challenging, but I'm going to try to slice the information in a little bit of a novel way. We're going to talk about the liver, the gut and adipose tissue as it relates to detoxification. And I would imagine that if Carrie Jones and Tom Gwilliams had put together a presentation, this might be the one. Because I'm going to talk a lot about hormones and a lot about phytochemicals, namely the polyphenols that Dr. Williams is going to be talking about tomorrow. So lots of different toxins. Many times when I'm talking with clients and groups of people, I try to dispel the fear factor as it relates to the number of toxins that are accumulating in our environment because it's profound. 85,000. About 1,000 new ones introduced every year. And about 1,000 of those meet the criteria of being an endocrine disrupting chemical. If we look at some of the newer conditions and some of the newer mechanisms that are arising by way of looking at those conditions, we can see that these endocrine disrupting chemicals may be at play. In fact, these EDCs are now being called metabolism disrupting chemicals or MDCs. So things like obesity, type 2 diabetes, fatty liver, fatty muscle are all playing into this aspect of mdcs. And so if we think of the functional medicine timeline, many times we're thinking of the in utero effects, we're looking at transgenerational effects. And we do see that these obesogens can be playing a role. Now you take those obesogens and you compound them together, you've got the cocktail effect. Even small amounts of some of these obesogens can have large effects. And you bring that as an overlay onto things like gene variance, the environment and you start to change the metabolism of the infant, just even at a very young age. So hopefully I'll be giving you some ideas because again, I don't want to depress the mood. We need to find solutions for this because I don't think that toxicants are going away. So from a mechanistic point of view, how are these EDCs or MDCs, whatever we want to call them. Now, how are they mechanistically having action on the cell? Well, if you look at the mesenchymal stem cell, you can see that it can go through a number of different pathways. And those pathways can be determined by the milieu, which makes sense. So there can be a milieu where there can be these EDCs that start to change up the size of the fat cells, the number of the fat cells, and then that can ultimately lead to changes in adipokines and can lead to changes in inflammatory potential. So so much of our metabolic potential. And I'm going to get into adipose tissue because I do think that many of these lipid soluble obesogens are going to the adipose tissue and they're changing up the adipocytes. So again, I think by way of our conversation today, we need to talk about that particular depot within the body. Now, for those of you who are in clinical practice and you're thinking of, well, what are some of these obesogens you just Talked about, the 1000 or so that are out there? There are a number of them. You know, I think that when we know something, we're going to do something about it. You can't unknow what you know. So informing and giving a lot of information to your patients, to your clients would be helpful. And, you know, I can remember years ago there was no discussion about endocrine disrupting compounds. And so, you know, looking at things like multiple chemical sensitivity or fibromyalgia, these were just states of, you know, oh, these are just diffuse pain disorders or just, you know, somebody's being more sensitive in their environment. And now we have a mechanism. Now we have a mechanism. So if you need patient tools, I would direct you to the National Institute of Environmental Health Sciences. A lot of great information on that site. You can see the link at the bottom. You can again give handouts and educate your patients as much as possible. Now, one of the things that I see in the literature and also through that website that I just mentioned is that oftentimes phytoestrogens are talked about as obesogens. They're talked about as endocrine disruptors. And I was scratching my head a little bit as I was reading that on the site, because I'm thinking, but if I think of the phytoestrogens, let's just take soy or flax. I mean, these are superfoods in so many ways. And a lot of the countries that consume a lot of these foods are not necessarily Obese. Now, what about the quality of those particular foods or what is the amount? Because there is a lot of processed soy that we're seeing come into the processed food market, right, as better alternatives. So I do want to call attention to this, of phytoestrogens as obesogens. I think that if you read this article like I did, what is happening with the genistein that is in soy is that it's about the amount. And much of how we take these soy isoflavones and metabolize them will determine their effects in our body. So if we have dysbiosis and we bring in a lot of genistein, we may not get the impact, or we could have a distorted impact. So I always take this with a grain of salt whenever I see that in the literature, endocrine disruptor compound activity, the way that it is working, is very similar to a hormone. And so some of the concern with things like genistein from soy or even bisphenol A is that they can bind much like a hormone could, to the receptor in the cell membrane or in the nuclear membrane. And as a result of that, they can change up cellular function. You can start to get different proteins, you can start to modify the DNA in certain ways, you can start to upregulate certain pathways within the cell. So I think from that perspective, being that these endocrine disrupting chemicals do work as almost like a hormone mimetic, we need to be concerned about all pathways that involve hormones. So this is just to show you some of the chemical overlay between these bisphenol A and estradiol. They kind of look alike. And I want you to remember this structure. I know that Dr. Bland has an organic chemistry background, and it was like one of my least favorite courses in college. I always thought, I'm never going to use this again. And then I soon came to realize that, wow, much of nutrition is organic chemistry. It's all about that composition of compounds and how these things are keying into the cell. So I want you to remember these structures more or less as we start to talk about polyphenols. So clinically, what do we do in order to modify the obesogenic potential of one's daily routine? And of course, even through functional medicine, we talk a lot about avoiding. That's the ultimate empowerment. Remove those things from the environment, block them, and then optimize the body systems so nutrient deficiencies, imbalances, toxicities. Looking at the diet, there's one study showing that a higher protein intake helped with Metabolic detoxification compared to a low protein intake. Why would that be? Because we need a lot of those amino acids as co factors for phase two detoxification. And then I think that we also have to look at the milieu, the emotional, mental, spiritual milieu of a person. In fact, I didn't really come into talking about emotional toxins and mental toxins until I started to do this work clinically. And I soon came to realize that as I worked with a person on their nutrition, they had this ripple effect that was happening through their lives. They started quitting their jobs, they, they left their partner, they moved to a different state, or even I had a woman who moved to a different country. So when you start to clear the noise from within, it's like the mind becomes clearer, the purpose becomes clearer. And we talk about detoxification within the functional medicine framework, but quite honestly, there's nothing new about detoxification. We've been trying to get clear and cleanse for as long as humans have been around. This is an ancient practice that is seen in so many different spiritual traditions. So I think that we need to see detoxification in a very holistic way to support a patient as they move through the nutritional aspects in the emotional, mental, and I would even say the spiritual, which is the purpose and meaning as we talk about through the functional medicine matrix, intestinal dysbiosis, and of course, genetic variants. It always amazes me whenever I ask audiences how many of you have done your gene panel? And like three people raised their hand out of 300. And I do think that this is the way, as Dr. Bland was speaking this morning to precision medicine, is to know somebody's genetics. When I look at all the different facets of medicine and how we can get at systems biology, this is really the portal into personalization and especially as it relates to metabolic detoxification. So normally the way that I approach detoxification is in a very classical sense, through nutrition. Romilly Hodges and I published this article back in 2015, and I got to say, it's almost 10 years now and there's so much growth happening in this area, looking at the different nutrients that are priming these pathways. So the way that we broke it out was looking at phase one, phase two, looking at NRF2, looking at metallothionine, and looking at the different nutrients that would upregulate or change those different enzymes or different systems within the cell. The other aspect that I always get queried about is, well, Deanna, I always see a lot about fasting and can fasting help detoxification? And my initial response is usually, well, wait a minute. Metabolic detoxification is a very nutrient requiring process. So fasting in the wrong individual at the wrong time may not be beneficial. However, there is this study that was published that I thought was very interesting. This is showing a heat map of the results. So these are urinary levels of different heavy metals and glyphosate. And as the color becomes more intense, whether red or blue, you can see the urinary concentration. So this is before and after a 10 day fasting program. If you look at the description of the fasting program, there still was some food, it was about 600 calories and it brought in a lot of liquids and everything was organic. There was light physical activity. So again, I think this speaks to personalization and, and how you might even want to have a nutritional detoxification program followed by depending on the health of the person and how they did, bringing in some aspect of food withdrawal and facilitating elimination and removal. All right, so that's kind of laying the groundwork now. I want to get into the juicy stuff as it relates to the newer emerging research. And I really do think we need to collapse that 17 year window between science and clinical application. And that's why all of you come to these meetings, because you know that, you know, you pick up maybe a pearl or two that you otherwise wouldn't have seen just in clinical practice. So I want to talk a little bit about adipose tissue. And I feel like fat gets maligned. You know, I did my doctoral work on fatty acids actually, so I really got into the trenches on all things fat for four years, researching fatty acids, their absorption, their metabolism. And I think that the tune around adipose tissue is changing. Fortunately, what we're seeing is that fat is much more complex. It's actually connective tissue. It's more than just a storage depot or just a reservoir of energy. It's doing a lot of different things. And one of the articles that really tickled me here, and this is again, I would say the newer work, is that there are different colors of fat. So each of those colors determines their different secretory molecules and agents and even placement within the body. So most of us, when we think of fat, we probably think of white or yellow fat, which is the storage fat, but there's also pink fat. There is this trajectory, this spectrum along that to yellow and beige, and ultimately to brown fat. And even though we think of babies mostly having a higher concentration of brown fat, we still do have brown fat as adults, and we can increase the amount of brown fat that we do have. So I'm going to talk about how we would do that Dr. Bland brought up some years ago when he and I were working together on the extracellular matrix. Now, this is something that, for the most part, I would say body workers, chiropractic physicians, people that do work that involves touch or that they have an acknowledgement of the tissues and fibrosis and kind of moving things along, because many times in detoxification, we talk about the elimination of products from the cell, and that has to happen through the extracellular matrix. So the ability of us to detoxify from the cellular level will be determined by some extent by the health of our extracellular matrix. So the fluid, the materials that we bathe ourselves in, and it's not inert, there are glycoproteins, there are all kinds of signaling agents. Now, with adipose tissue and with the exposure to obesogens, what can happen is with that hypertrophy and hyperplasia of adipocytes, we can start to change the function of the extracellular matrix. Things become tighter. We start to create cross links. We have adhesion proteins. And that prevents, ultimately, as you can already think ahead, into less, I would say, adequate detoxification. So what's really neat is that there are nutritional agents that can modify some of the matrix metalloproteinases that are active within that ecm. So when you think of adipose tissue, think of this as one of the, I would say, the primary tissues involved in detoxification and its relationship to extracellular matrix, which is why a bit of bodywork, a bit of sauna, sweating, movement during a detoxification is actually going to be very helpful and propel a lot of these things out. So how do we create functional fat? How do we move our white adipose tissue into a colorful array of options, whether we're moving from beige into brown? And I would say that there's a lot of different information out there as far as the different modalities. And we're seeing some work on cold therapies, hot therapies, any number of different, I would call them hormetic stressors, in order to kind of prime the body, prime the mitochondria, because that brown fat is actually very mitochondrial rich. That's the kind of fat that works for us. That's the kind of fat that keeps us warm, that gives us energy. And why do most people do a detoxification? What I have found in my experience is because they're low in energy, they're fatigued, and they can't figure out why. So how do we help them to create a more functional brown fat? And it's just beautiful because if I think back to even when I was in grad school in the 90s, thinking of the brain was stuck or the fat was static, we didn't have all this knowledge about how the body is always transforming. And I really love this idea that I think we need to love our fat. So much of our imprint around the adipose tissue is negative. It's about lowering body fat. And what I would say as a talking point for you with your patients would be, how do we transform that fat into something that's going to work for us? You can actually lose weight through certain types of fat, Right? So if you think about it like that, fat is truly our friend and not our foe. So what I find most exciting is that this can be done through the diet. If you look at some of the research that's been out there, and I'm just going to cite two studies, there are many different ones. We look at whether it's soy, again, the isoflavones, a lot of the herbs and spices. I just recently did a spice podcast. So, you know, spices and herbal teas. Keep these in your clinical toolkit as it relates to clinical detoxification. They're accessible to most people. They taste good. They're very easy to incorporate in everyday eating. So bringing in those spices, even on the podcast, I talk about seven spices. I talk about the rainbow of spices, make it three, you know, whatever it takes in order to get more nutrient density. And this is a very inexpensive way to do that. This is just another study also showing some similarities between the catechins, the resveratrol, the chili peppers. And I also want to bring into our discussion here that nothing works in a vacuum. So many of these different agents and even the adipose tissue and how it's responding to these different food compounds is working through the gut microbiota. So we can set the stage for obesity in a lot of these metabolic conditions by the nature, by the composition of our gut microbiome. And so we need to be thinking about how we can get the gut microbiome to actually work in our favor. And that's why many times before starting a clinical detoxification program, which might span from one to three months, some clinicians will focus on a gut restoration program, where for about, you know, maybe two months or so, just making sure that the gut is working well, elimination is happening prebiotics probiotics, polyphenols. That's my 3P approach to the gut. So enter in polyphenols. You know, I was just even talking with Medea at the break and she's like, you know about all these foods and how we eat all these wonderful, colorful foods and how they have polyphenols. Even her 16 year old knows what polyphenols are, right? So, I mean, they're becoming more and more widely discussed, which is great. Polyphenols are the largest cancer category of phytochemicals. So there are about 8,000 different structures that we even know about. And that does not include the secondary metabolites. And what's really unique about polyphenols is the structure. If you look at the structure, again, back to organic chemistry, we have that benzene ring like structure when it has a hydroxyl group. Now we have a phenol. When we have many of those rings, we have a polyphenol. And then it kind of starts to look like, what? Hormones, right? You know, it's very. Whenever I go traveling and I'm staying in hotels, I have a friend who will always say, deanna, what do the carpets look like? Because, you know, hotels have very strange carpets. Sometimes I don't know if it's to mask the stains or the spills or what it is. So as I was walking in today, I'm like, oh my goodness, we are surrounded with polyphenols and hormones in this room. Look at the carpet, right? We're surrounded with ring like structures. That must be a sign. So polyphenols do a lot of different things in the gut. They sensitize bacteria to xenobiotics. So for our discussion around detoxification, that's especially what we know about them. They can also help to block the endocrine disrupting compounds. In fact, much of the activity of polyphenols happens in the gut. And as you can see here, some of them are quite simple, like catechins, resveratrol. If you had a cup of coffee today, maybe you had chlorogenic acid, caffeic acid. If you chose for green tea, you probably had epigallocatechin gallate. If you chose to have some pomegranate or walnut, you're gonna get some big, bulky polyphenols, right? And what we're learning very interestingly is that because of these ring like structures, they have the potential to block things. 90 to 95% of them actually do not get absorbed in the gut. They get metabolized by the Colonic bacteria. So these. And in fact, there's some additional work to suggest that they may even help with food allergies. So keep that in your clinical toolkit. That higher polyphenols, because of their ability to block, which I think is a little bit different than a blockage of like dietary fiber, which is a long chain. But I do think that there's something about the polyphenols blocking that's very specific to the obesogens. So if you look at the literature, there is a preponderance of evidence to suggest that there's a role of these dietary polyphenols in metabolic diseases. On the left here, you see a lot of the different pathways as reported in in vivo models. So increasing uncoupling proteins. So it's active in the adipose tissue, it's active in the brain and in hormones, they're active in the mitochondria, they stimulate mitophagy. On the other side of things, if we look at more the enzymes, the enzymes approach, we can see that they may change up how we break things down just by the nature of these, again, the polyphenol compounds and perhaps getting in the way of certain of these enzymes. So that could change up metabolism, it can change up even the energy harnessing that we get from food. So I summarized a lot of those activities there. What I am going to talk about in a little bit is what I think is perhaps one of the more intriguing aspects, which is perhaps the chronobiotic effects of polyphenols. The chronobiotic effects. This is actually very breakthrough to think that a plant molecule can enable our bodies to tell time better, be in sync, better with the circadian rhythm. Why would we need to eat seasonally to get the proper chronobiotic polyphenols to align us better with nature's intelligence. So you might be thinking, well, Deanna, are there actually clinical trials that support what you're saying? This particular review went into different food products. And indeed, what you see is that when polyphenols of different types were given, you see improved insulin sensitivity, you see some changes in body weight and waist circumference. And you see this in populations even that are drinking a lot of green tea or having a lot of different spices. Now, some of the more well studied polyphenols would be the short list because I'm thinking like you so clinically, what are the ones that you actually emphasize with patients? Right? And who doesn't like these, you know, green tea, cocoa, coffee, berry, citrus, Fruits and ginger. All of these have a lot of good data based on their phytochemicals about their anti obesity effects. Now you have to perhaps modulate the intake of some of these in certain of your patients who may not do well with coffee or with green tea. So you just have to purchase, personalize that. I would say one of the studies that stands out in my mind the most is this one. We know that the Mediterranean diet is the most well studied diet on the planet. And this particular study had 294 people that were randomized to one of the following groups. One of the groups was Healthy Dietary Guidelines, so kind of generic guidelines. One of them was on the Mediterranean diet, and then the third group was on the Mediterranean diet plus polyphenols. So the polyphenol group, they had green tea. They also had this green plant called duckweed. I wish they used something more mainstream so that everybody could access it. But the takeaway for you is that basically it was a souped up polyphenol group in conjunction with the Mediterranean diet. What the researchers did was they were looking at weight loss, waist circumference. They also used MRI to look at abdominal fat. Now this is really remarkable because what they found was that weight loss, waist circumference loss, all of that was about the same among the Mediterranean diet and the Mediterranean diet and the polyphenols. But what was different was that the polyphenol group doubled their visceral adipose tissue weight loss. So it's very targeted to the type of adipose tissue that is lost. How many people, how many of your patients are complaining about belly fat? Oh, I wish I could get rid of that stubborn belly fat. That to me, when I hear that is a signal for more polyphenols. Right. And when I think of the structure of cortisol, which we know primes visceral adipose tissue, I do think that these polyphenols, based on their structure in some of the other literature, would suggest that it's competing and helping to negate the effects of cortisol. So isn't that promising? So, so again, one of your tips in your clinical toolkit would be in order to help with visceral adipose tissue with that stubborn belly fat, be thinking of polyphenols. And they only used 800 milligrams. All right, so let me just. Ooh. All right, so phytonuroendocrine system. This is a term that I recently just coined after I went to Dr. Bland's PLMI last year. And what I want to talk about in this section is take the polyphenols a little bit further and then talk about two other categories of plants as it relates to modulating the endocrine system. Because I do think that we need plants, smarty plants, right? Plants are very smart. They are stationary. They need to survive. And so I think that the more that we can align to different phytochemicals, that we can very astutely and smartly prime our inner physiology. So on that note, you know, much of obesity and obesogens, if we look at that whole milieu and that whole, I would say an epidemic that has been forming is that many times we see that there's a. A clock derangement, so a circadian rhythm issue. And we see that in shift workers, right? You see that outright. So what we're learning is that polyphenols may be that essential dietary component to keep the circadian system fit, to really stay in alignment with those circadian clock genes. So this is why eating seasonally would help our bodies to get the signal at the right time of year to sync us up better. What I think is also interesting is that polyphenols are very bitter. They're bitter and astringent. And we know a lot about the benefits of bitter. Bitter tends to be better. And so with polyphenols, they seem to have that ability, that have that capacity. And what we see is that taste, the chemosensory aspect of taste, also seems to have a rhythmic fluctuation with daily cycles, circadian rhythm, even menstrual cycles and seasonal cycles. So why is it that the traditional medicine systems talk about all the many flavors of food? And I think that what happens with people over time is they get into these food ruts. They're used to certain flavors, they're used to certain taste signatures. So how do we help them to expand beyond that? Because indeed, bitter is going to be better for a number of these different metabolic parameters because that is the signaler of the polyphenols. You know, it really makes me think about my colleague, Dr. Michael Stone. So I was part of a clinical trial with him, and we tasted bitter. Well, we use bitter tasting strips for people in the clinical trial. And it was so interesting to see who was the super bitter taster and who was not. And you can do that very easily with PTC strips. You have people put it on their tongue and they'll tell you right away if they taste it. That can help you to gauge their polyphenol intake. And what might be happening, you can actually change that dynamic a bit. I'm sure that some of you have seen that clinically, even with the elimination diet, if you do that for about seven days, the taste buds start to change. Right. So I just want to give you a couple of other, I would say, hacks as it relates to polyphenols. One of the things that helps even more to potentiate these polyphenols is to cut plant foods up, cut them up in the kitchen. So not to just bite into an apple, just bite by bite, but if you can actually slice it and cut it, you're going to increase the number of phenolics. In fact, the more that you cut something, you know, this is seen by the plant in some way if we personify the plant as some kind of stress that it needs to react to. So if you look at some of these, I mean, this is fascinating. So you can see the cutting style that's listed for the individual fruit and vegetable and the increase in the phenolic content. So just by shredding carrots, you increase it by 5.2 times versus slicing 1.67. Shredding carrots potentiates phenolic acids. So that's another tip that you can be giving patients. If we look at the liver, the liver responds really well to bitters. We know that from traditional medicine as well, can stimulate a number of the secretions in the gut. And as I was mentioning before, I think we can modify that somewhat. There are certain gene variants, certain genes that are connected to bitter taste. But what we're seeing is that there's a connection with obesity, there's a connection with body mass index. So now we're going to segue from polyphenols into another phytochemical class called the glucosinolates. I think you all know these. The glucosinolates are no stranger to detoxification. They help to upregulate hormone metabolism. They're heavy hitters. They work on phase one, they work on phase two. They're stinky, they're sulfurous, they upregulate glutathione, and I would say, most importantly, they increase sulforaphane. So in this particular study, this was done with broccoli, they gave people in the study 200 grams of cooked broccoli plus 20 grams of raw daikon radish for 18 days. And in so doing, they were able to favorably modulate the gut microbiome to be less obesogenic than when they didn't have those foods. And of Course, as we already know, the broccoli intake increased the pathways involved in the endocrine system and the transport and catabolism as well as energy metabolism. We all love broccoli, right? And by cutting broccoli and exposing that myrosinase enzyme, we know, again, what. What do we get? We get more in the way of a number of the different secondary actives. Now, what broccoli does in sulforaphane, notably, is that it upregulates our cellular antioxidant defense system through the NRF2 pathway. So that's pretty powerful, because one of the things I think we want to do is ensure endogenous defenses when. When it comes to detoxification, actually tickle the different genes that are going to be producing things like glutathione or catalase or superoxide dismutase. And that's what sulforaphane does. It helps to upregulate NRF2 and also helps to reduce inflammation. Now, as Nate was saying to me before I got on stage, he said, deanna, I see that you're a big fan of maca. And I would say I went to Peru this past December, and I've been taking maca for some time, and it's so interesting to see different places of the world and the foods that they have and why. And one of the things that I had learned is that broccoli and maca, well, actually, all of the cruciferous vegetables and maca, they're kind of like botanical cousins, and maca contains glucosinolates. So if we look at the different types of maca, we might want to ask the question, and I'll tell you why this would be. Could they have an effect on obesogenic potential? These are two of my favorite photos from my trip. I just think, yes, I know this is from a market. So there are 17 different kinds of maca. They're different colors. And I think by the picture on the package, you can get what this one would be for that vitality, the vigor. And then the one on the left is just so incredible, like how plants are planted and how that has been done over time in Peru. It's very sacred. It's, you know, it just really put me into a different resonance with plants. Plants and people as they connect to plants. I would say if you ever get to go to Peru, let yourself enjoy that, because I learned so much just through observation. So as you can see from the photograph, there are many different colors of maca. They're beautiful. You know, Whether red, purple, yellow, beige, black, all the different kinds. And in fact, I just recently published an article entitled not all maca is created equal. You know, all these different colors, they have different nutrients. And as we started to put together this paper, what I soon came to realize is that, wow, another one of my loves, detoxification, is coming through the maca literature. So we also see that this is a shared property with the cruciferous vegetables, right? And it led me to think, well, maybe it's because of the glucosinolates. So this is another teaching point for you with your patients, because many people will go into a grocery store, just buy a big bag of maca and then just start to take it in without any discernment. Or maybe they have a negative effect of it. They start to get acne or hair loss. I think it's because we really need to identify the phenotype. We need to know what type of maca is that. Is it an androgenic maca or is it a type of maca that helps to regulate the endocrine system overall? So this just tickled me to see all of these different phenotypes, these colors in the literature and how they've been described, and then to actually see this in motion in person. So you can see the article, I won't go through it, but there are some color signatures of each of the different types of maca and what they do. And I just have to give you this fun fact because, you know, it's fascinating that the seed of maca, the plant. So if you just take a seed and you plant it somewhere, it can express different colors depending on the environment that it's grown in. So in Peru, with incredible altitude, we're talking like 15,000ft, lots of winds, it's cold, it's dry. There are different microbiota in the soil. So the color actually comes through the environment and not the actual progenitor seed. Isn't it kind of beautiful if you just reflect on that? So what we're taking in, when we're taking in plants, this is some of their environmental express expression. So what I want to call forth here from the detoxification conversation that we're having is the glucosinolates in how the glucosinolates in maca are distinct from those in the cruciferous vegetable family. In fact, some of these glucosinolates have also found to be acetylcholinesterase inhibitors. So they may have broader application to things like memory, the mind, when most people think of maca, they think of the adaptogen effects, but again, there is this hormone regulation and production. A lot of good literature on that. You're going to have the slides here, so I'm not going to tour you through all of the aspects, but keying into the cannabinoid receptor, keying into the 5ht, kind of looking at the gut signaling. A lot of this is being borne out in some of the recent literature. And in the article, we talk about the different colors of MACA tickling and rippling through the entirety of the endocrine circuit. So different types, different combinations will come through in order to change up that endocrine circuit. So one of the things we have to ask is, are these endocrine disrupting chemicals actually causing premature ovarian decline and early perimenopause? So this article would suggest that these EDCs indeed are having a role in that. So there are a variety of different MACA preparations which have been codified and identified. And from a clinical perspective, four different clinical trials looking at the role of modulating the hypothalamus, pituitary, thyroid, adrenal and ovarian access in peri and in postmenopausal women to recalibrate and to help to optimize hormonal production. So again, MACA has a lot of power, like a lot of these different phytochemicals. These are some of the case reports on those MACA phenotypes. And I know that I'm just about at time, so I'm going to end with the last plant compound, which won't be as long. But essentially looking at how can we overturn what has happened with artificial light? All of this endocrine disruption that is occurring not because of the foods that we're eating, but because of the light that we are bathing our eyes in. So I would even say that this is an obesogen. In fact, I think it's one of the most societally accepted endocrine disruptors on the planet. We all know plastics are bad, we know heavy metals are bad. We often don't think of artificial blue light as being bad, but it is. It's disrupting our endocrine physiology. So we even have a new term now called the circadian syndrome, which really speaks to that whole disruption of our internal wiring as it interfaces with the external world. So we're changing up the entire endocrine system with artificial light at night. And NASA and other types of, I would say, companies, institutes, you know, this is something from a global perspective. We need to be looking at is our exposure to this light. In fact, I would say that we, it's not that we have sunlight deficiency anymore. I think people are really keyed into that and perhaps there's room for improvement. But I think what we're lacking is darkness. We're lacking the yin, we're lacking the utter. You know, most of us don't live by candlelight or a fireplace anymore. So we are again bathed in this endocrine disrupting, obesogenic, artificial blue light. And what do we produce in darkness? What's the darkness hormone Melatonin. Right. So there is a lot here as it relates to detoxification, the times of the day. I'm married to an acupuncturist, so, you know, I've learned a lot about traditional Chinese medicine and the different organ times, the chronotherapy that happens throughout that 24 hour window. And what I would say is that the liver is one of the organ systems with the highest number of oscillating genes to these clock rhythm signals. So just to let that sit for a second, that the liver is very key as it relates to taking on those signals from the circadian clock. So if we disrupt that, we're disrupting hepatic function, which means that detoxification is thrown off. So I have given a new name to vitamin D and melatonin. Vitamin D, what is it? Is it a hormone? Is it a vitamin? Some of these things, we put them into tight buckets and they're not really that they flex. Melatonin. Is it only a hormone? No, it's a lot of different things. It helps the mitochondria. It is a strong antioxidant, its primary chronobiotic rhythm. To me, these two are like brother and sister. They are circadian nutrients. And I think that what happens with people with a lot of endocrine disruption, they have issues with those too. So I'll just close the talk in saying that a lot of our detoxification actually happens at night. It happens when we're sleeping. We start to increase that glymphatic fluid, fluid exchange that only happens during sleep. And it seems that melatonin is at least in part responsible for some of the flux of the amyloid peptides from the brain out into the glymphatic fluid and then into the lymphatics. And if you don't believe me, I just want to show you here. This was also done looking at kind of that stage stimulation of the detoxification response in the early Morning hours, like between 2 and 4am is the time that your brain and antioxidant defense system is actually peaking. This is when you're going to see a potentiation of all of those different defense systems. And when do most people wake up? 2 and 4am Right. So think in your mind, is there a detoxification issue here? If this patient is constantly telling me that they're waking up at 3am Go in your mind to what I just showed you about the brain detoxification. Melatonin, be thinking about the liver. Because if we were to overlay the liver time, which is 1 to 3am we see that there's a connection. All right, I know that in my final words here. Just want to say, you know what's interesting? If we just bring this all forward. Circle. Melatonin in plants increases glucosinolates, and it's even sprayed on crops to potentiate the photosynthetic potential of plants. So what does that tell you, right? All of these things kind of bringing it all together. So just to summarize, because I know I took you in a lot of different places in kind of blandesque style of like looking at all of the crosstalk, right? So looking at the liver, the gut, the adipose tissue, the endocrine system. And instead of taking you through each of the different pathways, what I hope to do is to bring out some of the more emerging literature and to help to romance and connect to plants in a much deeper way that would apply to detoxification. Right. So looking at those polyphenols, which you're going to hear more about from Dr. Williams tomorrow. Tomorrow, the glucosinolates, which are not only in the brassicae family, from broccoli and other cruciferous vegetables, but also from maca. And then of course, my recent love of melatonin, I've also put together some patient materials. So putting together endocrine nutrition, looking at the different pathways, looking at the different endocrine glands and the foods that would feed those respective glands, thank you very much.