In this episode of The Thermo Diet Podcast Jayton Miller sits down and talks to Georgi Dinkov, a researcher and expert on the metabolic theory of health. They talk about what endotoxin is and how to get rid of it, how to down regulate serotonin, how to get rid of estrogen, and how to increase the protective hormones in the body. Check it out and let us know what you think!
Facebook Group and Fanpage -
Thermo Diet Community Group ( https://www.facebook.com/groups/16721... ) - Thermo Diet Fan Page ( https://www.facebook.com/thermodiet/ ) Youtube
Channels: - Christopher Walker ( https://www.youtube.com/channel/UCTA1... ) - UMZU Health ( https://www.youtube.com/channel/UC2IE... )
Instagram: -
@_christopherwalker ( https://www.instagram.com/_christophe... ) - @researchcowboy ( https://www.instagram.com/researchcow... )
Full Transcript
Jayton Miller:
Welcome back to the Thermo Diet podcast. I'm your host, Jayton Miller and I'm here with Mr. Georgi Dinkov, otherwise known as Haidut. If you've been following any of Ray Pete's work or Danny Roddy's work then you definitely know who this is. He is a man of much knowledge, so thanks for being on here, Georgi.
Georgi Dinkov:
Thanks for the nice words, let's find out if I'm a man of a lot of knowledge, hopefully your listeners think the same way.
Jayton Miller:
Definitely. So the first thing that I wanted to hop into was; what exactly is endotoxin, and what are some of the best ways that we can get rid of endotoxin from harming the system?
Georgi Dinkov:
So, endotoxin is a component that's part of the wall surrounding and protecting something called gram negative bacteria. So this bacteria, most people carry them in their gut their whole lives. They're typically much more difficult to treat with antibiotics, so you don't want an overgrow of gram negative bacteria, so whenever you take antibiotics and starts killing the bacteria, you may get this endotoxin reaction, like a die off, some people call it a die off reaction. I think it's called a [inaudible 00:01:16] reaction or something like that. So sometimes you may get fever, you get indigestion, a feeling of malaise, nausea, that kind of thing.
Georgi Dinkov:
So those are some of the symptoms people sometimes get when they get antibiotics at higher doses, because they start to kill of those gram negative bacteria in the gut, and when the bacteria dies and the cell wall ruptures, this endotoxin is released into the colon and some of it may absorb through the colonic wall into the bloodstream. The body views that endotoxin, which is also known as lipopolysaccharide or liposaccharide, it views it as a sign of the presence of bacteria in the body, so the body mounts an immune reaction. So this is a normal defense mechanism that the body mounts whenever it senses a significant number of endotoxin, significant amount in the bloodstream.
Georgi Dinkov:
Now, the problem is that the endotoxin is released from the bacteria, not only will the bacteria die, so basically you can get an endotoxin reaction any time the bacteria gets a significant amount of food that basically allows the bacterial colony to grow. So every time there's a constant turn over of bacteria, some of them die, others divide, and ever time there's a division, a bacteria dies or a general growth, the bacteria may shed some of this endotoxin, not may, it does share some of this endotoxin into the colon.
Georgi Dinkov:
Now, in most cases for people with well functioning gut barrier, this should not be much of a problem because not much of this endotoxin gets absorbed. It stays in the colon, but even if it stays only in the colon, over time if the colonic wall is constantly exposed to it, it can trigger a chronic inflammatory reaction and now some people are saying that inflammatory bowel disease such as Crohn's disease, ulcerative colitis, and all kinds of other inflammatory disease of the gastrointestinal tract that are on the same spectrum, now there is more and more recognition that a bacteria or pathogen of some kind is involved.
Georgi Dinkov:
Actually in fact, in some cases, in some countries in Western Europe, they now have an alternative protocol for treating Crohn's disease and it doesn't involve immune suppression, it actually is a three way combination of antibiotics, which you take at high doses for several months. They're claiming a pretty good curative rate, and that's unheard of. Crohn's disease, officially is an autoimmune disease, most medical systems around the world will tell you, it can't be cured, the only hope is suppressing the immune system and keeping it suppressed, yet more and more evidence is accumulating that all of these inflammatory, autoimmune conditions are actually some sort of a chronic inflammatory reaction which is [inaudible 00:04:14] called inflammatory bowel diseases.
Georgi Dinkov:
Endotoxin is really a very potent pro-inflammatory mediator, even if it stays only in the colon. Now, it becomes much more dangerous if the gut barrier is somehow compromised, and then a significant amount of this endotoxin ends up in the bloodstream. The first thing that it does is from the portal vein system which lines the gastrointestinal tract, this endotoxin will get carried to the liver. So the liver is overburdened every time it gets a dose of endotoxin, because you aid some kind of, let's say, resistant starch food which are very popular these days, to keep your blood sugar low.
Georgi Dinkov:
Every time you get some kind of undigested food through the colon, or to any place in your gastrointestinal tract where this gram negative bacteria resides, you're asking for trouble because it's going to start releasing endotoxin. Now, in a healthy person, not much will get into the bloodstream but it may still, over time, trigger inflammatory reaction in the colon. But if you drink alcohol, if you're exposed to stress which, who isn't these days, right? If your diet isn't optimal, if you haven't slept well, if you're angry, any time you have a decline in metabolic function, this gut barrier is not like the great Chinese wall that's built out of bricks, it actually depends on proper energetic function, proper function of the metabolism because this wall is entirely functional, it depends on the proper functioning of the epithelial cells that line the colon.
Georgi Dinkov:
So if those cells are not functioning well, then their permeability increases and they start accepting more and more of that endotoxin from the colon, and then they pass it into the bloodstream, the portal vein system and then it ends up in the liver. Now, if the liver is well functioning, well fed, you don't have fatty liver disease, steatohepatitis, also known NASH, if you don't have cirrhosis, now the liver should be able to get rid of most of that endotoxin, unfortunately if you look at the statistics, up to 40 to 50% of Americans currently, not just Americans, most people live on a west circle, western diet, they have a problem with their liver. They have some form of fatty liver disease, and the cases of cirrhosis, which is the end stage, the later stage is liver cancer, but really liver failure which is also known as cirrhosis, those rates are rapidly incasing.
Georgi Dinkov:
It looks like for a significant minority, if not even the majority of people, you don't want endotoxin to be reaching the liver because your liver is already in not very good shape. So any time you give it endotoxin, you're burdening it even more. Now, what's the problem with burdening the liver? Well, the liver is the main detox organ that we have together with the kidneys, and another major function of the liver, which we'll cover the topic separately, but it's related, is detoxifying estrogen. So, look, there's a limited capacity the liver has for detoxification and excretion of endotoxin, estrogens, xenobiotics, endocrine disruptors, you name it. so every time you give an endotoxin, it has less capacity to detox all of these other problematic substances, including the estrogens which we're going to talk about later.
Georgi Dinkov:
Not only that, but the liver expresses the receptor known as TLR4, toll-like receptor four which is the main receptor to reach the endotoxin triggers, the inflammatory reaction in the body. So the liver actually itself becomes inflamed every time you give it a dose of endotoxin. It is low grade inflammation, but over time this adds up and in fact, the low grade inflammatory process in the body are now known to be the major cause, if not the cause, of any kind of fibrosis. And cirrhosis, which is the end stage liver disease, is a type of fibrosis. So over the years, even though you think your gut barrier is functioning well, your liver is functioning well, every time you give your liver a dose of endotoxin, you're increasing inflammation and you're getting closer and closer to the fibrotic stage.
Georgi Dinkov:
Now, the liver if it can't actually cope with the endotoxin load, will release some of this endotoxin into the systemic circulation, and that's when you're really asking for trouble, because in an immunocompromised person or a very sick person, very weak person, with very few energetic resources, this can actually trigger something called septic shock and they can die out of multi-organ failure. In fact, septic shock is the major cause of death for hospitalized people. Closely followed by doctor's errors, but still, sepsis is the number one cause for death in in-patient hospitalizations.
Georgi Dinkov:
So, once it reaches the systemic circulation, even a little bit of endotoxin can cause a lot of damage because it's allowed, essentially, access to all of these organs and many of them express that TLR4 receptor. So any organ that expresses the TLR4 receptor will get into a state of low grade inflammation, depending on how much endotoxin actually gets to the systemic circulation. If a person has a really poor functioning liver, then when the majority of the endotoxin will get to the systemic circulation, and I think those are the people that are dying of septic shock. In healthier people, you'll get this feeling of malaise, you may get fever, you may get a rash on your skin, unexplained rash.
Georgi Dinkov:
So in general, it's not a pleasant situation and if it continues chronically, it can lead to the same fibrotic reactions in any organ that gets exposed to endotoxin, for a significantly longer time.
Jayton Miller:
Now, do you know if the endotoxin is in a reductive state, similar to a lot of those stress hormones?
Georgi Dinkov:
Yeah, actually the detoxification of endotoxin requires consumes a lot of NAD. So this means that if NAD gets consumed, the end product will be NADH. So just having endotoxin in the system shifts rapidly the balance of the redux state towards reduction, instead of oxidation. So it is a form of redux, and even if it's not a direct reductant, it gets to that point because it needs to be processed and excreted.
Jayton Miller:
So, what are some of the ways that we can prevent the absorption of endotoxin and get it out of the system?
Georgi Dinkov:
Well, I think a step even before that would be keeping the overgrowth of the microbiome, keeping it in check. In other words, don't eat foods that get digested so slowly and so incompletely that they reach the colon mostly undigested. You don't want to be feeding your bacteria, the only thing that bacteria in your colon should be getting are things like insoluble fiber, because the insoluble fiber actually has an antibacterial effect, and actually physically scrubs some of the [inaudible 00:11:19] bacteria that has formed and is attached to the walls of the colon, this insoluble fiber can quite physically scrape it off and help you excrete it with the fecal mass.
Georgi Dinkov:
So the first thing is; eating a decent amount of insoluble fiber every day, I'm sure your listeners have already heard of the recommendation to eat carrot salad, right? Cook bamboo shoots, mushrooms are another great source. I personally prefer charcoal, because charcoal actually can absorb endotoxin directly, so when you're eating the food and you're getting some charcoal with it, when it gets to the colon, even if there is undigested food and the bacteria starts literally chewing on it and releasing endotoxin, the charcoal will absorb most, if not all of it. So it will prevent that endotoxin causing issues even within the colon.
Georgi Dinkov:
So there'll be very little, if any left to even get to the bloodstream, it will actually first get to the liver and then get to the bloodstream. More importantly, or just as importantly, charcoal itself is a potent antibacterial effect, especially if it is combined with short to medium chain ... actually, with medium chain saturated fatty acids often found in coconut oil. Lauric acid, caprylic acids, capric acid, [inaudible 00:12:37] acid, all of these are found in coconut oil and they're known to have an antibacterial effect.
Georgi Dinkov:
So in synergy with the charcoal, you can keep your colon fairly sterile, fairly clean so that even if undigested food gets to it, not much endotoxin will be produced. Once the endotoxin gets to your liver, the best things you can do for your liver is provide anti-inflammatory nutrients in the food that will also get to the liver, and prevent some of the damage that the endotoxin is doing. Glycerin, the amino acid glycerin, the amino acid taurine, the amino acid proline, so in other words, eating gelatin, eating sea food that are very rich in these amino acids helps mitigate to a great degree, the inflammatory reaction that endotoxin is going to cause in the liver.
Georgi Dinkov:
Aspirin, caffeine are also great anti-inflammatory substances, and also happen to be antifibrotic as well, so even if endotoxin has already caused some damage in the liver over time, even starting late to taking these anti-inflammatory substances, you're giving the liver a significant break, you're allowing the liver to recover because you don't block the TLR receptor completely or you negate some of the downstream inflammatory damage which comes from [inaudible 00:13:56] TLR4, which is the release of nitric oxide, the release of serotonin, the release of this inflammatory called [inaudible 00:14:06]. In fact, some of the most popular drugs for inflammatory bowel disease conditions right now are KNF alpha blockers, but they're just targeting one pathway, the things like gelatine, glycerin, taurine, aspirin, caffeine, KLR antagonist such as Benadryl, everybody knows that drug. It's marketed as a drug for allergies, but older studies in the 60s and 70s found that this drug can actually directly block the TLR4 receptor.
Georgi Dinkov:
So basically, the preferable thing is to start as early as possible in the cascade, which is what the charcoal and the soluble fiber, and the medium chain saturated fatty acids will do. Once it gets to the liver, then the goal should be controlling inflammation and supporting the liver as much as possible with nutrients which means sufficient glycogen, which means carbs are very important, right? Because the liver consumes a lot of glycogen in trying to get rid of this endotoxin. So the active [inaudible 00:15:04] making sure glycogen stores are high. Avoiding the polyunsaturative fats because they are actually precursors to the inflammatory mediators known as prostaglandins and leukotrienes.
Georgi Dinkov:
So if you're ingesting a lot of [inaudible 00:15:18] in your diet together with ingredients that feed the bacteria, so in other words, if both [inaudible 00:15:26] and endotoxin make it to your liver, then it's a really much worse situation because endotoxin activates the enzymes, cyclooxygenase and lipoxygenase, and those family of enzymes synthesize potent inflammatory mediators from the poofer. So you're giving yourself a double whammy of an inflammation attack by consuming poofer and foods that feed of this endotoxin reaction.
Georgi Dinkov:
So yeah, the drugs; Benadryl ... and the good thing about it is that they act not only on the liver, but systemically as well. Then anti-serotonin chemicals like [inaudible 00:16:02] are also very important, [inaudible 00:16:05] because it's a problem with the most potent anti-nitric oxide agent that we have that's over the counter. It both neutralizes already existing nitric oxide in the blood and also inhibits its synthesis by reducing the expression of the enzyme known as [inaudible 00:16:23]. In general, try to keep stress low, trying to keep the gastrointestinal system supplied with sufficient blood, because any times you get stressed out, the body shifts the bloodstream from less crucial organs such as your GI tract, to organs such as the heart and the brain in order to basically keep you alive.
Georgi Dinkov:
But guess what? Every time you have a reduction in the blood flow, a reduction in the supply of nutrients to the cells in the gastrointestinal tract, you're dramatically increasing the permeability of this gut barrier, and you're getting that much more endotoxin supplied inside of your bloodstream.
Jayton Miller:
So, whenever it comes to the activated charcoal, is there a specific frequency that you typically recommend? Because the kelating properties of it tend to attract some of the minerals, don't they?
Georgi Dinkov:
That's right. I wouldn't use it every day. If a person is having a very severe endotoxin reaction, has been going on for a while, I would consider using it daily on an empty stomach for a few days, just to get that reaction to stop. After that, I think two to three times a week is probably sufficient because it has such powerful both antibacterial and endotoxin absorbing properties so it should not be used every day, because just like you said, it will collect not just endotoxin, but just about anything else in its path.
Georgi Dinkov:
In terms of dosages, I think for a very severe endotoxin reaction, 10 to 12 grams which is one big tablespoon dissolved in maybe orange juice, and you chug it with your orange juice, or mixed with coconut oil and then chugging that mixture, as unpleasant tasting as it sounds, it's actually not that bad, I've tried it myself. But you do this for a few days, and after your things are under control then you go back to a more regular schedule of maybe twice a week. I found that for me, twice a week actually works the best. Three times a week I started feeling symptoms of deficiencies such as; my skin gets dry which is really a sign of vitamin A deficiency, or a zinc deficiency.
Georgi Dinkov:
So for me, twice a week works best but for most people, the studies that have looked at animals, that have done animal [inaudible 00:18:38] on the charcoal consumption, usually two to three times a week works best. Anything more than that is only reserved for acute cases of food poisoning which is just another name usually for endotoxemia.
Jayton Miller:
So, you mentioned the relationship between endotoxin and serotonin, and by lowering endotoxin you can lower the amount of serotonin that's being produced. What are some of the other ways that you can lower the amount of serotonin in the system?
Georgi Dinkov:
Not many people know, actually, but more than 90% of the serotonin is produced in your gastrointestinal tract. So the serotonin is produced every time the gastrointestinal tract is somehow either physically damaged, and you don't have to ... by physical damage, I don't mean getting stabbed with a knife. Just running intensely or jumping up and down for a significant amount of ... let's say, more than 10 minutes, that stretching and the twisting and just in general the shaking that occurs in the gastrointestinal tract, that alone, that mechanical stimulation is enough to trigger the endochronophin cells in your GI tract to start producing significant amounts of serotonin.
Georgi Dinkov:
So make sure you leave your GI tract alone. Doing something crunches every once in a while is fine, but I found that crunches, if over done, are very, very, reliable way of actually triggering a serotonin reaction. Many of the listeners probably know of the expression ... part of the expression is called runner's diarrhea, because excessive serotonin leads to diarrhea, basically this immediately tells you that running for too long, which is known reliably to cause diarrhea, especially marathon runners, but you don't have to run 26 miles. Actually, it's been shown that anything more than four to five miles is already increasing serotonin levels enough to cause diarrhea.
Georgi Dinkov:
So basically, physically leaving your GI tract alone, and not stressing it is a great way to prevent this 90% of serotonin being produced. Other ways that you can limit the production of serotonin is by limiting the supply of the precursor to serotonin, which is the amino acid tryptophan, and it's been demonstrated that when you consume tryptophan ... first of all, you can select foods that have lower amounts of tryptophan, muscle meats are very high on tryptophan, a lot of the [inaudible 00:21:03] that people now tend to consume are also high on tryptophan and methionide which synergizes with tryptophan and serotonin in a bad way. Also, these [inaudible 00:21:12] tend to be the resistant starch types and you're also feeding off endotoxin.
Georgi Dinkov:
So, avoiding foods that are high in tryptophan is actually a good option. If you can't avoid those foods, then making sure you consume a significant amount, or sufficient amount of either glycerin, so gelatin, it actually tends to decrease the absorption of tryptophan from the food which is a great way to limit just how much serotonin your body can produce, because it doesn't have the raw materials, even if you're under stress it will not be able to produce the serotonin. So gelatin is known to inhibit the absorption of tryptophan from the gastrointestinal tract.
Georgi Dinkov:
The branching of amino acids which are find in many body building products, many fitness products, but also in protein rich foods such as milk, and especially cheeses, which is the casing portion of the milk, that's [inaudible 00:22:07] casing protein, first of all they have a lower amount of tryptophan per gram than meat, but also higher amounts of the branching amino acids that actually inhibit the absorption of tryptophan from the GI tract.
Georgi Dinkov:
Aspirin is another tool, it has also been found to inhibit the absorption of tryptophan from the gut and also polyphenols that are found in orange juice, such as apigenin naringenin, [inaudible 00:22:39], I think there's another one which is very similar, [inaudible 00:22:41], a lot of these flavonoids that are found in citrus juices are known to not only inhibit the absorption of tryptophan, but some of them are actually capable of even inhibiting the enzyme tryptophan hydroxylase which synthesizes serotonin from tryptophan. I should mention that enzyme, another great way to limit the production of serotonin is to inhibit that enzyme.
Georgi Dinkov:
There are drugs that do that, but they're not widely available, but things like caffeine, the steroids pregnenolone, progesterone, DHEA, testosterone, dihydrotestosterone, in fact, most androgens are known to be able to inhibit the enzyme tryptophan hydroxylase and is probably expressed to a great degree, the fact that they're potent antidepressant effects. Many people who abuse steroids, abuse them not so much for the physique, but effects on their physical composition, making them muscular, but because these steroids produce a very potent and rapid antidepressant effect. I think that a large portion of that effect is due to the fact that these steroids inhibit the sensors of serotonin from tryptophan.
Jayton Miller:
Now, is there a way to inhibit the amount of serotonin receptors that we have in the system? Or down regulate the amount of receptors that we have?
Georgi Dinkov:
So, you don't want to down regulate them because this will be a signal for the body, serotonin if you actually get an injection of serotonin chronically, will down regulate those receptors. So what happens is that if you withdraw the amount of serotonin, the body will, as a compensatory mechanism, increase the production of serotonin because the sensitivity of the receptors is low. You have less receptors and the body thinks that, "Oh, I need more serotonin in order to achieve the same effect."
Georgi Dinkov:
What you actually want to do is increase the expression of the serotonin receptors, because then when you remove ... and this is achieved by antagonists, so if you take the serotonin and that one such as [inaudible 00:24:45], you'll actually increase the expression of the serotonin receptors, you'll make them more sensitive to the effects of serotonin, so when you stop the [inaudible 00:24:52], over the next 24 to 48 hours, your endogenous production of serotonin will dramatically decline. The body thinks that it has plenty so it will down regulate actually the expression of the enzyme, tryptophan hydroxylase because it will basically think to itself, "Oh, I have plenty of serotonin, I don't need to produce more, so I'm actually not only going to limit the activity of the enzyme, I'm even going to reduce its production because tryptophan hydroxylase is just an enzyme like any other enzyme, and I gets produced by cells when needed.
Georgi Dinkov:
So, the body will down regulate the expression of that enzyme and you have higher sensitivity to serotonin, but low overall serotonin. It's the presence of serotonin really that has the amount of serotonin you have in your body, that is responsible for many of the chronic diseases. So you don't want the situation of higher serotonin sensitivity, but low overall amount of serotonin in the body.
Jayton Miller:
I see.
Georgi Dinkov:
But same thing happens ... I'll just interject. It has now been found that drugs that antagonize the glucocorticoid receptor, which is the receptor for cortisol, are potent antidepressants, and they work by increasing ... the role of cortisol in depression is at this point very well known. Now, many doctors will say, "Well, it's really controversial, yes, two thirds of depression patients have high cortisol," and they're so called non-suppressible because they have a special test called the dexamethasone suppression test.
Georgi Dinkov:
What this test does is they give you a pretty hefty dosage of a very powerful synthetic cortisol, an analog known as dexamethasone, now what happens is that if your body has sufficient number of cortisol receptors, when it gets this hefty dosage of a synthetic glucocorticoid, the body will say, "Oh my God, I'm overloaded with cortisol, I'm going to turn off my own production of the endogenous cortisol." So in depressed people, this reaction actually does not happen because their endogenous cortisol levels are high and they've been high for a long time, which means their cortisol receptors are down regulated. So when you give them this extra cortisol, the synthetic one on top, their body doesn't react the way it's supposed to be and says, "I don't feel any different."
Georgi Dinkov:
So the cortisol levels in depressed patients will stay high, when they actually are given the synthetic glucocorticoids. Two thirds of depressed patients with clinical depression are so called, "Non suppressible." Non responders of that test. Then they will follow up with a second dosage which is even higher, and if you don't respond to that, then usually this is actually a pretty solid indication of a condition such as Cushings syndrome, which is the over production of cortisol, due to a pituitary tumor or a tumor somewhere else in the body, usually the adrenal glands.
Georgi Dinkov:
But anyways, the role of cortisol in depression is very well established, and drugs that block these receptors that act as antagonists actually ... well, you take them for a few weeks and then when you stop, the body ... unless you have a tumor somewhere over producing cortisol, the body says, "Oh my God, I have all this cortisol floating around and now my receptors are basically so sensitive, there's such a high density of these receptors, I'm going to tone down the production of cortisol."
Georgi Dinkov:
The drug known as REO486 which is also used as an abortion pill, but is also a potent glucocorticoid antagonist, there are a number of studies showing rapid antidepressant effects within 24 to 48 hours after starting it, because its effects are increasing the sensitivity of the glucocorticoid system. The same thing happens when you take a serotonin antagonist, increases sensitivity of the serotonin system and basically you tone down the production of cortisol, serotonin which together are the major, if not the only causes of depression.
Jayton Miller:
So, do you think that serotonin is almost aligned with the amount of stimulus that the biological organism has to compensate with? So for instance, the psychedelics, our serotonin antagonists, and we can bring in more stimulus into the system. Do you think that there is a direct relationship there?
Georgi Dinkov:
Yeah, and I think the serotonin usually rises in response to stress. So the role of serotonin is a very ancient peptide, a very ancient neurotransmitter. By ancient, I mean it has been with us even when we're back in the stage of animus. If you look throughout the animal world, throughout the living world, even very primitive organisms produce serotonin. The major role of serotonin in the organs, actually two of them that I'm concerned with, one is; rapidly toning down metabolism. So in other words, when you're under stress, serotonin is the mechanism [inaudible 00:29:45], and the organism starts to conserve resources.
Georgi Dinkov:
If you're under stress, you don't want to be expending resources on, "luxury things," from a biological point of view such as reproduction, creativity, joy, good mood, running around, playing around, feeling good, all of these things are considered non-essential, and when you're under stress and there's some kind of a threat, it's the serotonin system which is really the key to actually making the organism go into a defense mode, and only keep its most vital functions. Serotonin is actually the primary regulator of the cortisol system, of the HPA access.
Georgi Dinkov:
To this day, when you go to medical school, in the classes of endocrinology, you'll learn that the HPA access consist of the hypothalamus, the pituitary and the adrenal gland. Actually, this knowledge has been around for a long time but recently it's come center stage. It turns out that serotonin is actually a much more potent activator of the adrenal system directly without even the involvement of the brain. It's a much more potent activator of the release of cortisol, than even the peptide produced by the brain known as CRH, which is what's thought to be the initial step in the cascade on the stress response. It's still there, we still use it, but it turns out serotonin is much more potent regulator, and now actually if you have Cushings syndrome, which is the disease of excessive cortisol production which can't be stopped, they found out that you can actually cure it by administering serotonin antagonists such as cyproheptadine.
Georgi Dinkov:
So basically, I think the role of serotonin is to tone down really the cautiousness and the vitality of the organism, when the organism is under threat. So if you're taking too many stimulants, I can totally see ... actually in fact, many of those stimulants have as a side effect, an increase of serotonin. The drug, ecstasy, it has a lot of potential for treating post-traumatic stress disorder, but it has to be used wisely and at not very high dosages, because in high dosages, it is a potent releaser of endogenous serotonin. I think the reason this serotonin is released is to act as a break on what the stimulant drug does to the brain.
Jayton Miller:
Now, do you think there's a compensatory mechanism with MAO?
Georgi Dinkov:
Yes, but basically for the MAO, there are two types. MAO A, and MAO B. Older studies demonstrated that drugs that predominantly inhibit MAO B are potent antidepressants, and actually can even treat Parkinson's disease, because MAO B preferentially degrades dopamine. MAO A degrades both dopamine and serotonin but preferentially degrades serotonin. So in other words, if you're inhibiting MAO A, you will increase your amount of serotonin in the system, and dopamine as well, but to a high degree [inaudible 00:32:54], because MAO A also degrades [inaudible 00:32:56] and serotonin. These two are stress mediators.
Georgi Dinkov:
Now, I haven't seen any evidence if serotonin itself has an effect on the MAO system, but I wouldn't be surprised because typically there are feedback mechanisms. So typically, if you have a high serotonin, initially it probably has a negative feedback mechanism, but being a stress mediator, stress mediators are known in extreme circumstances to flip that switch and make it a positive feedback mechanism. So I wouldn't be surprised if serotonin, if the levels are sufficiently high, if serotonin starts to inhibit MAO A because there are cases of so called, "Serotonin syndrome," which can be triggered by excessive stress, and since the MAO A, the system is still there and it's role is to degrade serotonin, in order for it to be overwhelmed without the person taking any MAO inhibitor drugs exogenously, if this can happen solely based on stress, this means that your organism is capable of producing something internally that acts as an MAO A inhibitor, and my suspicion that something is serotonin, when it reaches certain levels, when they become too high.
Jayton Miller:
Oh. Now, is there a relationship between serotonin and estrogen? And in the relationship, which one typically comes first?
Georgi Dinkov:
Actually, there is a very ... it's a bilateral relationship, both of them stimulate each other's synthesis. Now, I mentioned progesterone being an inhibitor of the enzyme tryptophan hydroxylase which synthesis serotonin, right? Well, logically you would expect something that acts the opposite way of progesterone which is estrogen in the body, you expect it to have an opposite effect, in other words, to activate tryptophan hydroxylase, and there are multiple studies published on the topic demonstrating that estrogen is one of the most potent endogenous inducers of the enzyme tryptophan hydroxylase.
Georgi Dinkov:
Conversely, serotonin is one of the most potent known inducers of the enzyme aromatase. So, if you have more serotonin, you will be producing more estrogen. If you have more estrogen, you'll be producing even more serotonin, so it forms a positive feedback loop, and that's why many people find it so hard to break out of this vicious cycle of chronic stress, because often it's many more than one of the stress mediators that is elevated, so some people will say, "Oh, I'm taking less aromatase inhibitor and my estrogen is now low, but I still don't feel well." Well, because the estrogen ramped up the production of serotonin, nitric oxide, growth hormone and a number of different mediators of stress. So, basically you have to address all of them at the same time.
Georgi Dinkov:
In my experience, taking a serotonin antagonist actually tends to calm down the entire system because it does seem like serotonin being a more ancient hormone, a more ancient neurotransmitter, it has a high role in the cascade of things in terms of controlling the overall health of the organism. If you have to choose which one of the two you need to address first, I will probably go with serotonin but they're both promoting each other's effects and synthesis.
Jayton Miller:
Now, saying that, we are taking steps in order to decrease a lot of those stress hormones and the stress mechanisms, how can we increase or enhance our ability to synthesize the protective hormones?
Georgi Dinkov:
So, we talked about keeping the levels serotonin low, I think you also had a topic to discuss keeping estrogen levels low, right? And they go hand in hand. So, in general you want to avoid eating foods that promote the synthesis of estrogen, or contain estrogenic mediators themselves. There are a number of different flavonoids, many of them found in soy, such as genistein, [inaudible 00:36:51], a number of different phenolic substances, the endocrine disruptors such as BPA, BPS, and many other found in plastics that are all known as potent estrogen antagonists, the [inaudible 00:37:05] and some of the other flavonoids are known as phytoestrogens, and some that are even more potent than the endogenous estrogen we produce, the very popular supplement lately is resveratrol, is itself a very potent phytoestrogen.
Georgi Dinkov:
So some people are taking it will say, "Look, I take this resveratrol, my estrogen levels go down." Of course they will, just like the test with the dexamethasone. If you give your body a potent estrogen agonist, the body will ramp down the endogenous production of its own estrogen, but it doesn't mean your estrogenic tone is declining, you are continuing to paint this exogenous estrogenic substance, resveratrol.
Georgi Dinkov:
So avoiding as much as possible the consumption of polyunsaturated fats, basically because of their polyunsaturated nature, multiple older studies have found that fats are not just used to heal, but they're also similar in substances. The more unsaturated a fat is, the more it acts like estrogen which is also a highly unsaturated steroid, and basically the more it acts like estrogen, and it can synergize with estrogen, and the combination of significant amount of [inaudible 00:38:14] with a very low amount of estrogen can give you an estrogenic response which is equivalent to the one of somebody taking a birth control pill which contains synthetic estrogens.
Georgi Dinkov:
So making sure basically that you avoid the polyunsaturated fats as much as possible, and that includes fish oils. Now if you look at the latest publications, [inaudible 00:38:36] medicine has wizened up to the fact that unsaturated fats are not good, but they're saying, "Oh, guess what? This only applies to the amino six fats." The amino three fats are good for us, so we want to load up on the amino three and not so much on the amino six. Well, they're all unsaturated and they've all been shown to have estrogenic and pro carcinogenic effects.
Georgi Dinkov:
Now, other things that can be done to limit the synthesis of estrogen is taking aromatase inhibitors, there are a number of different ones that are available over the counter, and some of them have been with us for centuries, if not millennia, some of the most potent ones include fat soluble vitamins. Vitamin E is a very potent estrogen receptor antagonist and aromatase inhibitor. Aspirin is capable of inhibiting the enzyme aromatase because that enzyme gets activated when there's chronic inflammation. Yet another reason to keep endotoxin low. If endotoxin is a very potent, and probably one of the primary mediators of inflammation in the body through the diet, we don't want endotoxin to be going high. Every time you activate an inflammatory system, our aromatase gets activated as well.
Georgi Dinkov:
The reason is that estrogen's role is basically a role of an acute state shock hormone which basically also dramatically ramps down metabolism in cells and allows the cells to survive with much less androgen than normal, but at the cost of dramatically reduced differentiation. So in other words, estrogen shifts your entire body which is just a collection of cells, it shifts the state of these cells from highly differentiated cells that make you, you. Some cells are your ears, some cells are your skull, some other cells are your organs and body, and the estrogen shifts that state from well differentiated thing that has a shape of a human, back to a very amorphous mass that is just an aggregation of cells and all these cells can do with the limited amount of androgen they have is divide and grow, which is the process of cancer.
Georgi Dinkov:
So, taking aromatase inhibitors and basically keeping stress low, because every time you're under stress, the protective hormones such as DHEA and testosterone that males produce, DHEA is produced by both males and females, testosterone is also produced in both sexes but mostly by males. These are protective hormones but they can convert it to estrogen quite easily. So with age, it's known that males go from a high testosterone state to a high estrogen stage, and for females from high progesterone to a high estrogen state.
Georgi Dinkov:
The reason is not only the increase of aromatization, but estrogen itself stops the reaction to reach the protective hormones are being synthesized and those protective hormones are progesterone, pregnenolone, DHEA and [inaudible 00:41:32] of progesterone such as allopregnanolone which mostly works in the brain, it's a very potent GABA agonist, but estrogen basically limits the activity of the enzymes that synthesize these steroids, so what happens is over time very little trickles down from cholesterol, down the [inaudible 00:41:50] pathway and because of estrogen and all of the stress and inflammatory mediators, the major pathway through which the [inaudible 00:41:57] continues to go, is through the estrogenic pathway.
Georgi Dinkov:
So whatever little hormones you produce with aging, tends to be mostly estrogen. Some of the reasons for that are both the accumulation of [inaudible 00:42:08] in the body, fat cells have a very high expression of the enzyme aromatase, and also the fact that [inaudible 00:42:14] itself is very estrogenic as well. It activates the enzyme aromatase, and it creates the state of chronic stress, and as we said, the role of estrogen is the role of a stress hormone, so every time you're under stress, all the stress mediators will increase in response, and if you're under constant stress, they will stay high.
Georgi Dinkov:
So, there will not be much chance of the body to produce the protective steroids, which necessitates in some people using these protective steroids exogenously as a supplement. Pregnenolone is probably one of the safest because it's so high up in the steroidogenic chain, there isn't much a chance, if any of it converting into estrogen, unless somebody has a true estrogen deficiency, in which case there may be some conversion into estrogen, but only as needed. In general, pregnenolone itself has an anti estrogenic effects, I'm sure you've seen some of the things I've posted.
Georgi Dinkov:
It is a mild aromatase inhibitor compared to some other steroids such as progesterone, and it happens to be relatively benign, regardless of the sex or age of the person taking it. It seems to only work if the person has a true deficiency or excess of a hormone somewhere in which case, pregnenolone tends to balance out the whole system. Progesterone is considered my medicine as a true hormone, because it actually attached to your receptor known as the progesterone receptor. In contrast, there is no such receptor known for pregnenolone, so pregnenolone is strictly as a precursor but there are receptors which pregnenolone attaches and works, but progesterone is considered a much more classic hormone because it has its own receptor. Progesterone is a potent aromatase inhibitor and a potent estrogen receptor antagonist.
Georgi Dinkov:
Even functionally, it tends to oppose many of the non-genomic effects, non-receptor effects that estrogen has, case in point. Estrogen increases the activity of the enzyme tryptophan hydroxylase. Progesterone decreases it. Estrogen activates the HPA access and increases the release of the hormone ACTH by the pituitary which triggers the production of cortisol by the adrenals. Progesterone reduces the synthesis of that steroid. Progesterone is also an antagonist of the glucocorticoid receptor, so it seems to be able to affect three systems just by one ... so it decreases the synthesis of serotonin, it's known that in high doses it can actually block the serotonin receptor three, which is mostly expressed in the gastrointestinal tract, 5HT3, but is also expressed in the brain and other organs.
Georgi Dinkov:
Antagonists of 5HT3 are now used normally as treatment for nausea, but now there's indication it may be able to treat mental health disorders, neurological diseases, Alzheimer's, Parkinson's, et cetera, long story short, progesterone seems to both decrease the serotonin, and oppose some of its effects, so it also is known to decrease a synthesis of estrogen and oppose direct effects through the receptors and also functionally.
Georgi Dinkov:
It's also known to, despite being a precursor to cortisol, progesterone is also known to decrease the levels of cortisol because it inhibits the enzyme that synthesizes cortisol and also simultaneously increases the enzyme that degrades cortisol. If that wasn't enough, progesterone is also a direct antagonist of the cortisol receptor. That's why some people, especially in a highly stressed, state of chronic stress or is acute state of very severe stress, they find that supplemented with the steroids propanolol, progesterone, and a little bit of DHEA to be highly beneficial.
Georgi Dinkov:
DHEA itself is a number of different good pro metabolic effects, however it needs to be used carefully because as I mentioned earlier, under stress it very easily can convert into estrogen.
Jayton Miller:
So, typically I see the DHEA and progesterone supplementation mixed together, is there a specific reason that those are together and could you also supplement that with pregnenolone to have that go down the more protective hormone pathway?
Georgi Dinkov:
Yes, so if you're supplementing with DHEA and progesterone together, you're getting most of the benefits because pregnenolone can only go down two pathways, progesterone or DHEA. So if you're taking already the top levels of these two pathways, the androgenic one and the progestogenic one, if you're taking progesterone and DHEA, you're already getting most of the benefits of pregnenolone, but pregnenolone lately has been found to have very interesting effects on its own that are not completely overlapping with progesterone and DHEA.
Georgi Dinkov:
One of these effects is potent blockade of the cannabinoid receptor, and activation of the cannabinoid receptor by smoking marijuana, which is responsible for giving people the high of smoking weed, but also that cannabinoid receptor has a darker side. It's known to be over expressed in cancer, and a number of different mental and neurological disorders. It's known that antagonists for that receptor are capable of not only blocking the high on marijuana, but also reverting the psychotic state which can come from abusing weed or smoking too much marijuana.
Georgi Dinkov:
Also now lately has been shown that antagonists of the cannabinoid receptor family may be capable of treating post-traumatic stress disorder, may be capable of treating chronic states of anxiety, may be capable of treating addiction disorders if you believe there is addiction, especially addiction to hard drugs. So, pregnenolone seems to have a very potent effect on the CB family of receptors, cannabinoid receptors, and pregnenolone have some of those, but according to the studies that I've seen it's not nearly as potent.
Georgi Dinkov:
So if you're taking progesterone and DHEA, in terms of steroid ureagenesis, and taking care of the pathways that are further down from these two steroids, I think you're covering all the bases. They'll convert into whatever is necessary, and having a ratio of progesterone to DHEA of at least three to one, it will protect DHEA from converting into estrogen because it is down on the pathway, right? So if the enzyme aromatase is inhibited, then DHEA can only convert, either stays DHEA or converts to testosterone, or dihydrotestosterone which are other very highly beneficial steroids, especially for males.
Georgi Dinkov:
So that's what the combination of DHEA and progesterone gives you. Then if you're prone to synthesizing more estrogen, if you have excess weight or you're an advanced age where you have some kind of chronic disease which absolutely guarantees you that the [inaudible 00:49:05] aromatase will be high and estrogen levels will be high, at least the tissues, that have a higher ratio of three to one maybe even desirable, maybe five to one, eight to one, up to 10 to one has been experimented with and the results seem pretty good.
Georgi Dinkov:
The combination of having a little bit of DHEA with progesterone prevents the anti-androgenic effects which progesterone tends to have in very high doses when given to men. For women, it's probably not that big of a deal, they can take very high doses of progesterone by itself and not experience much ill effects, but progesterone itself when used in too high doses in males, may have anti-libido and anti-androgenic effects which, you know, obviously males would not want that. Seems to, based on experiments, that adding just a little bit of DHEA seems to control for those effects if not completely prevent them.
Jayton Miller:
Oh. So, what other topics are you on fire about right now? Is there some specific that you're looking into or are interested in?
Georgi Dinkov:
Yeah, I'm not sure if you've seen, I mentioned on the forum that I basically ... the repeat forum that I now do my own studies, I work with two labs. One in Taiwan, and one in Bulgaria. I'm originally from Bulgaria but I live in the United States, I've been here half my life, so I guess I'm half and half at this point, as they say.
Georgi Dinkov:
But I still have contacts back in Bulgaria, classmates and other people who went into ... they have a career as scientists, so I reached out to them and said, "Hey, look, I want to do my own animal studies, both with our own products and new things that will synthesize," so I also got in contact with chemists, so now we're synthesizing some interesting new chemicals. Some of them based on steroids, some of them based on the idea of the fatty acid oxidation inhibitor. There is a drug known as mildronate, also known as meldonium, which is used to inhibit the oxidation of fatty acids, and that process is known to be highly protective.
Georgi Dinkov:
It was designed as treatment for cardiovascular disease, but at this point more and more studies are coming out and saying, "Look, if you inhibit the excessive oxidation of fats, you may actually be able to cure for good, disease such as cancer, Alzheimer's disease, Parkinson's and whatnot," because they all seem to be metabolic in origin and they all seem to have this excessive oxidation of fat in their base. What does oxidizing fat have to do with disease? It is the ultimate stress signal, and basically under stress, the cell switches from oxidizing glucose to oxidizing fat, under the command/influence of these stress mediators that we mentioned.
Georgi Dinkov:
Estrogen, serotonin, prolactin, growth hormone, cortisol, all of them have the effect of turning off glucose oxidation in favor of fat oxidation, because the fat oxidation, you actually have sufficient stores of fat and that's what happens when the organism is under threat and needs to survive. It switches from the fuel which is in short supply, which it tends to be glucose, right? Because you have to eat it from a diet, you cannot store more than a kilo of it, most of it in deliberate muscles, right? And then we do tend to have plenty of fat, so the stress mediators switch on the oxidation of fat, and that seems to be the signal for the development of virtually every chronic disease known to man.
Georgi Dinkov:
Very classically, diabetes, now more so it's started to become recognized in cardiovascular disease, and lately, very recently, a lot of [inaudible 00:52:41] have come out saying, "Wait a minute, we're seeing the dramatic increase of oxidation of fat and conversely, suppressed oxidation of glucose in infectious disease, in cancer, in Alzheimer's disease, in Parkinson's, in disease like [inaudible 00:52:56] sclerosis that are wasting diseases, very similar for cancer, and even in HIV. So, we're looking at synthesizing other molecules that can inhibit the fat oxidation much more effectively than mildronate can, and we're testing those in animal [inaudible 00:53:12]. So that's my work, that's most of my work outside of my day job which actually happens to be in IT.
Jayton Miller:
Okay, interesting. What does that look like?
Georgi Dinkov:
In the IT sector or? I'm basically in IT security sector, so I'm a hacker for hire, for the government, as a contractor. They just hire me to try to break into their computers and if I succeed, I write a report saying, "This is what you need to do to fix it so that other people, the politically correct black hats, they don't do the same without telling you."
Georgi Dinkov:
So I'm a white hat hacker, and they hire me before the black hat hackers come in and do their nefarious things.
Jayton Miller:
Awesome. Well, Georgi, I really appreciate your time, thank you for hopping on here. I think the listeners are going to love this, so I appreciate it.
Georgi Dinkov:
Thanks a lot, man. Thanks for inviting me, hopefully it's useful to your listeners.
Jayton Miller:
Definitely. If you haven't already, make sure to go check out Georgi's work, it's absolutely amazing, haidut.me, that's H-A-I-D-U-T dot me. Phenomenal website, amazing blogs, and then you're also under Haidut in the repeat forums, and you have a whole host of different podcasts and stuff that you're guest on. The Danny Roddy podcast on YouTube is also a really good one. So make sure-
Georgi Dinkov:
Simply search in Google for Haidut will usually come up mostly with results related to stuff that I've posted or said or done.
Jayton Miller:
Sounds good. Thank you.
Georgi Dinkov:
Thank you, I appreciate it.
Jayton Miller:
Definitely. Thanks for listening, and I'll talk to you next time.
