Transcription
[music] Ask me about that.
So, recently I've been obsessed with mass cells. Um, I don't know if people know what they are or not. You will by the time you leave here. So, if you're interested, great. If not, you can leave now. But this was my personal obsession. So, when Neil said, "Hey, can you come give a talk?" I'm like, "Absolutely." So, you get to follow me along on my obsessive journey here.
So the title of this is a little bit misleading because we have not mastered the mass cell per se. We've identified it as a problem and there are ways that we can sort of fight it. It's a hopeful title. We're working on mastering it, but we have not done so yet.
Okay. What is a mass cell? Well, these were identified in the 1880s by someone named Van Recklinghouse. And I know I've heard a few physicians out there. They're physicians, right? I heard doctor so and so. Anyway, Van Recklinghouse will be recognized because there's something called Van Recklinghouse disease and it's actually neurofibromatosis. And what was interesting about that particular disease is these lesions are filled with mass cells. But it wasn't until a med student a bunch of years later, Paul Ehrlich, looked at them under a microscope and called them mast cells. And apparently in that German, it means well-fed because if you look at them, they look really stuffed. And I'm going to show you a picture of that in a second.
But what mass cells really are is they're first responders. We need to think of them as our EMS team of the immune system. And depending on what tissue they are in, they're very different. So here's our electron microscopy picture of a mass cell. And you see how the guy thought that they were well-fed. They're filled with a lot of granules, right? And if you look at it, depending on the cell, somewhere between 50 to 100 secretory granules, and they just sit there ready to release them. Okay?
Interesting thing about mass cells is they can be very long-lived. Most immune cells live for a couple days, a couple weeks. Mass cells can live for up to three years in humans. These things are sitting there and they're ready to go. And they also can undergo many rounds of degranulating. You'd think they would go, send out all of their their secret, their secrets home, and then die. But they don't. They keep making it over and over and over again. So, this is kind of going to be an enemy that we got to fight for a while.
Um, depending on where these cells are, they tend to have different types of granules. So just as an example, the mucosal mass cells, they have more tryptase in them and connective tissues have tryptase and chymase. So it's just an idea that they're variable depending on where you find them.
The life of a mass cell, this is only important in that it's different than other immune cells. Most cells are sort of what they are what they are. Mass cells are different. They they come, they're hematopoietic stem cells. They come from the progenitors and they travel around undifferentiated. They land in a peripheral tissue and then they decide what they're going to do. It's really interesting. And they always get drawn to areas that are exposed to the environment. So in for us that would be an airway, right? Because we breathe in air. Our gut, we're exposed to bacteria and our skin. So this is where they go. So for the most part, you find them in your gut, your skin, uh, and in your airway.
All right, just an example. So, they're floating around as progenitors. They go through your bloodstream. They end up in your skin. And then they decide to associate with different types of like uh things. Bad word, right? Blood. Sorry, caffeine's not kicking in yet. Um, so they they they go associated with blood vessels or nerves or fat or whatever it is. And what's really interesting is, you know, when you get that that tingle in your skin when something freaks you out, that's mass cell release. It's kind of really cool. And when you look at your skin, they live when you are young in your papillary dermis for any dermatologists out there. Rarely in the epidermis, rarely in the deep dermis until you start aging and then they become sort of more heterogeneous. So they change where they go.
Okay, I am going to demonize mass cells in just a little bit. But we all do need to appreciate that they're actually beneficial, right? Not all things are bad despite what I'm going to say about them in a little bit. Kind of like your best friend, right? Until they're not.
Okay. What do they do? They regulate your vascular system. They cause things to have an increased blood flow. So, they're going to vasodilate and you're going to get angiogenesis, which is useful if your skin's hypoxic. Not so useful if you've got a tumor sitting there, right? Uh, as I briefly mentioned before, it's an interacts with your immune cells. So, all the dendritic cells, macrophages, etc. triggers them to become what they need to be. Um, because we talked about how it interacts with the environment, responds to bacterial and parasitic infections. So if you look at someone's labs, you can sort of tell if they have a parasitic infection if you've got some elevated markers of mass cells as an example. I love this. They're important for venom detoxification. So if anybody out there's a snake handler, this is really important for you. Um, tissue repair, right? They need to uh they destroy tissue that's been destroyed uh so that they can clear it out and like make new tissue and then it's important for bone uh mineralization. So that's the essential list of like good things that they do.
How do they do this? They do this by releasing mediators. And there's three basic types. There's the granules that they've already made and they're sitting there ready to go. And the biggest example of this is going to be histamine or serotonin. Then there's mediators that you make on demand coming from the lipid membrane. And these going to be your leukotrienes and your prostaglandins. And then there's ones that you make sort of as you need it inside the cell in a normal fashion. So you get three sort of speeds as to what you can release.
Turns out everyone when you think about a mass cell thinks about histamine. Turns out there's hundreds, hundreds of different things that a mass cell can actually release. This is a truncated list and I'm sure you're all memorizing this right now, right? The point being is that some of them are pro-inflammatory, some of them are anti-inflammatory, some build tissue, some break tissue down. It's a huge set of things, but we're going to focus on the ones, however, that cause us the most damage. And these are the proteases. And this is why I think that this is particularly important.
What's a protease? A protease is something that dissolves protein. We are made of proteins. These will dissolve you, right? That's kind of disgusting, but it's what it is, right? We talk about proteases based on the amino acid that gets attacked. So there's two main categories. There's serine and then the serine are the most important. So there the trypticases and the chymases.
What's a trypticase? And I'm sorry, it used to line up a little bit better. Got moved. So try I'm always kidding around like trypticases trip over each other because they're just so compacted in there, right? It is the most prominent enzyme in a mass cell, the trypticases, and they create MMPs, specifically MMP9, and that dissolves collagen, specifically collagen one and collagen three. And those are the most prominent collagens in your skin and in your bone. So when you have too much tryptase, your skin falls apart as does your bone. That is not good. Weakens the dermal epidermal junction. If you look at skin and you get older, that dermal junction fails. Your skin slides and that's when people get that old sort of like skin that doesn't look quite right look. And that's a bad, bad. Should have had a picture of that. Next time I will.
Okay. Uh, chymases. Chymases are interesting. They also cause you to dissolve your skin by increasing MMP9. But they also take angiotensin one and convert it to angiotensin 2. What does that mean? It actually means that your high your blood pressure is going to go up because angiotensin 2 increases your blood pressure. And it turns out this enzyme also decreases an enzyme that gets rid of AGEs. So by going down a pathway of enzymes, you actually get increases in AGEs from chymases. Does that make sense? Yes. No. Sort of.
>> What's an AGE?
>> What's an AGE?
>> Really?
>> Uh, that is probably very untrue. So an AGE is an advanced glycation end product. And this is when glucose or a piece of glucose sticks to a protein and destroys it. Okay, there are 20-some subtypes, one of which is called methylglyoxal and the enzyme to dissolve that is inhibited by this. That makes more sense. Thank you. No, this is good. Chime in. I appreciate that.
>> The impact.
>> Why? No, the impact is more important. You get more damage from AGEs because of this problem. Correct. The idea is that it's negative. But thank you.
Okay, the other proteases, the serine class proteases are sort of less important. U I only mentioned it. Mass cell carboxypeptidase uh was sort of prevalent for a while. We don't have an answer for it yet, but it's on the list to be inclusive. Cathepsin C is really the more interesting one in this category. And the reason it's more interesting is it is an upstream uh activator of the chymases and the trypticases. So if you can turn this off, you save a lot of tissue destruction. And some very smart person has figured out to do this. There's a drug called brincotib. Practice saying that because it doesn't sound weird. Brincotib unfortunately is $88,000 a year. So if we can find someone in [clears throat] this crowd to help pay for all of us, that would be a great drug for us to take. I'm not picking out anyone in particular, but it would be nice.
>> [clears throat]
Okay, now we have to get to histamine because histamine has been demonized by everyone and a lot of people in the longevity world think we need to block histamine and to a certain degree that's true but not entirely. So let's talk about histamine for a little bit. It is a bioactive amine, right? Comes from histidine mostly from mast cells but also from basophils and it does a lot of things around the body. It is uh important for a lot of physiologic things, a lot of immune things. It's actually a neurotransmitter, right? It's kind of interesting that people don't really know. Stimulates keratinocytes to make more MMP9 which means you're dissolving more tissue. It also encourages angiogenesis like the uh the other molecules and it and it also stimulates gastric secretion. And we asked ourselves how does one molecule that's very small do all of these things? And it does it because you have histamine receptors.
A very long time ago when I was in med school, we had two histamine receptors. We had H1 and H2. Now we have four and probably years from now we'll have many more. H1 is the classical. So when a histamine receptor one is activated, you get the whole uh allergic reaction cascade. So you get bronchoconstriction. You get vasodilation. Everything that you think of when someone's in front of you having an allergy attack. Histamine or receptor 2 is mostly in the stomach and you get an increased acid. Interestingly enough, the cardiac tissue also has H2 receptors. So sometimes in in an operating room, we will give an H2 blocker to help with a cardiac issue. Uh, H3 is mostly uh in the brain. It's pre-synaptic. We'll see later that we can use some of these drugs to actually help neurologic diseases. Uh, H4 we don't know too much about. We know it's part of the immune system. And I can guarantee you some very smart person right now is coming up with medications to treat H4.
Okay, but that's histamine. Now, we're going to talk about mast cells, right? Because there's just one thing that came out of a mast cell. Let's talk about mast cells. Mass cells trigger via a gazillion different mechanisms. Okay? We usually think of it as just being immunologic, IgE, IgG, but it turns out that there's so many things that trigger mast cells. This is what makes them so toxic to us. So, they are so toxic because there are a zillion receptors. The standard receptor immunologic, this is a great name, immunoglobulin E Fc epsilon R1, okay, that is your immune receptor and everyone thinks about that at least in doctor world. The other one, Mas-related G protein-coupled receptor X2, is one that causes us a lot of problems that we don't think about. There are a zillion other ones, but the ones that I have separated are histamine type one and two. And the reason the histamine receptors on a mast cell are important is because you get a paracrine effect, meaning one mast cell puts out histamine, goes to its neighbor, the histamine goes to the histamine receptor and it activates another mast cell. So it is a horrible chain reaction. Okay, it's a paracrine effect much like a senolytic cell might be. Um, it also has cannabinoid receptors and that's going to be important because we will see how we can uh do that or change that with medications. Uh, anyway, a lot of different receptors and we'll get to them in a second.
So this is the one that uh is the most famous, right? And the way this works uh is IgE comes from a different cell. They attach themselves to the receptor and when an antigen comes along, it takes the two receptors, sort of puts them together, they homodimerize and it releases a whole allergic response. And in this response, we mostly get a lot of histamine and serotonin. And this is why mast cells essentially get demonized in popular culture.
When the Mas-related G protein-coupled receptor X2 does this, it doesn't it has nothing to do with IgE or IgG. Many things can trigger this. Many things: substance P, PAMPs, statins, oxytocin, a whole lot of things. And what's interesting is the trigger causes different things to be released. So instead of serotonin and histamine being released, you get more tryptase. And tryptase dissolves tissue as we just learned. So this is extremely devastating uh to the body.
Other things can activate mast cells and these are important things to know. Systemic hypoxia can activate mast cells. So if you are having some sort of ischemic event, not only are you is your heart in trouble from lack of oxygen, you're about to have a huge, huge release of all of these factors coming from mast cells. So it's going to take one problem and exacerbate it. Okay. Another thing to know, oxidized LDL. If you have any dyslipidemia at all and you're not on astaxanthin, you probably have a surplus of oxidized LDL. And that is going to create a baseline of mass cell release all the time. Who here's on astaxanthin? You guys are a bit disappointing. Neil, [clears throat] shouldn't you have fixed this by now? Okay. Radiation. Being out in the sun, that causes mast cells to degranulate. Being cold, I don't know why people go into those icy cold baths. Cold causes mast cells to degranulate. Uh, as does like firm pressure and again, snake venom. Snake venom is terrible for you.
>> Okay.
>> It's natural.
>> It is natural. So is botulism.
>> Botulism. It's true. [snorts] It's true.
>> Stress.
>> Stress can also activate mast cells. You can be physically allergic to stress. I used to think this was garbage, but it's absolutely true. Stress, corticotropin-releasing hormone is released when you are stressed. It comes from the hypothalamus. And it turns out you have receptors for that on your mast cells. So when you are stressed, this hormone gets released, causes your h your mast cells to trigger, and you can have a full anaphylactic reaction. Kind of. So keep your stress levels down. Interesting. Again, there are very smart people out there. There's a drug for that. It's called antalarmin and it's 5 to 600 bucks a month. So, if you're stressed out, it's not a bad deal. And I think the name is spectacular. Anti-alarmin. Like, don't be alarmed. That's fantastic. You guys don't you find I don't know if you guys find me funny or not. I find me funny.
Okay, this is where I'm going to demonize mass cells. Having a normal level of active mast cells, obviously we all need, right? But when they become overactive, they cause a plethora of very bad diseases. At the top, standard stuff. And then the list got a little skewed, so I apologize. Allergy, asthma, anaphylaxis, inflammatory bowel disease, a lot of cardiovascular disease, skin falls apart, you get eczema, you get osteoporosis. All sorts of things go wrong when you have too many mast cells and they degranulate. And my favorite, of course, is at the bottom, accelerated aging. And I have a funny feeling that no one here wants that, right?
All right, just a few cool examples. Migraine headaches. So it turns out you've got mast cells in your leptomeninges and this is the covering on your brain. You also have mast cells in your choroid plexus, your hypothalamus and a variety of places, but these are the important ones and when they degranulate, they cause uh neurogenic inflammation, causes your blood vessels to contract and you get a migraine. So theoretically, you can cure migraines by being on a mast cell stabilizer.
More importantly, cardiovascular disease. When you are healthy, you tend not to have mast cells in your heart or in your blood vessels. When you are not healthy, when you start having cardiovascular disease, they start accumulating. Okay. What's interesting is mast cells in your cardiac tissue when they degranulate will send you into cardiac arrhythmias. Uh, A-fib, uh, V-tach. People go, "Oh my god, I was fine and now I'm not." Well, maybe you weren't, but now it's worse. So a lot of people go into A-fib as they get older and I think this is one of the big causes of cardiovascular disease. As we get older, a lot of us get plaques in our blood vessels either in our coronary arteries or you know any arteries essentially and plaques accumulate mast cells. When the mast cells degranulate within these plaques, it causes these plaques to rupture. And at that point, if it's in your heart, you just had a cardiac arrest. I mean, you had an MI. If you had it anywhere else and it threw a clot to your head, you just had a stroke. So managing your mast cells is extremely important.
And here's my favorite because this is just so obnoxiously like in your face. You got to do something about it. Abdominal aortic aneurysms called AAAs. I don't know if you do you guys know what this is.
>> Yeah, the doctor in the corner does clearly. [snorts]
>> All right.
>> So >> it it's the letter depends on where exactly it is, right? Aortic can >> and you die.
>> So, so what he's explaining to you is in this picture, right? The normal aorta on the left, the aorta is the blood vessel going straight up and down and then it bifurcates and your kidneys are on the side. An aneurysm when people say I had an aneurysm, an aneurysm is a dilation of a blood vessel. Like if you had a big balloon and you were blowing it up, it got kind of big in the center. That is an aneurysm. All right? So mass cells accumulate in blood vessels as you get older and as you get sicker and when mass cells degranulate in your aorta, several things happen. So your collagen, as we talked about, starts dissolving. So the integrity of the blood vessel starts to go away, right? So that's bad number one. Number two, the smooth muscles become apoptotic. So another layer of protection goes away, right? And then it activates your renin-angiotensin system. And we talked about that earlier. Your blood pressure goes up, right? And your ability to make more collagen goes down. So now you've got this expanding balloon with more pressure about it. And you know what it's going to do? And it turns out if you rupture an AAA, there's over a 90% mortality. Even if you are in a hospital or an operating room, when this ruptures, there's over 90% mortality. So, this is, I think, the biggest reason that this is incredibly important.
Okay, as I've alluded to, mass cells increase as we get older. Uh, someone dissected a rat, looked at every organ, and the liver was the only one where mass cells did not increase. Um, in humans, we've not dissected everyone completely, but we do know there's significant evidence in skin, fat, and brain that mass cells increase. Just as two examples, found two great studies looking at skin. The first one was calf biopsies. They compared young people to old people, and they found twice as many mass cells in older people. And they found in that particular study that there were more frequent and severe anaphylactic reactions. And we know this. We see that grandma when she like, you know, has a peanut allergy, she's not going to do well. Second study compared 30-year-olds to 70-year-olds, 40% increase in mass cells. So we know this is a huge problem.
Interestingly enough, it's hard to dissect someone's brain and count mass cells. So very, very smart people looked at CSF, the cerebrospinal fluid. It's a fluid that sort of goes around your brain. And they looked at metabolites of histamine. And it turns out that if you were older, there's significantly, if not double, the amount of metabolites in an older person than a younger person. So, it's a big problem.
All right. So, what's our take-home message? Mass cells are pro, and this is a quote, so I'm going to read it. "Mass cells are probably a main factor that potentially can be involved in tissue damage and aging changes in skin." Obviously, I took this from an article that was skin. "Mass cells should be regarded as an important target for anti-aging therapy." And I would say it's not just skin, it's everywhere. And that's why we're talking about this.
So what do we do? So the first thing we're going to do is we're talk about histamine. And then the second thing we're going to do is talk about mast cells in general in terms of therapies. So histamine, we can reduce the amount of histamine we make. We can block the receptors to which they attack and then we can metabolize it more quickly. How do we do that?
So histamine is made with an enzyme called histidine decarboxylase. It takes histidine, decarboxylates it to make histamine. It's a very simple reaction and it turns out that uh this enzyme is in mast cells mostly but also in basophils and we can block it very easily with over-the-counter agents. So the list is here. It's gallic acid, proanthocyanidins. Turns out green tea is exceptional at this. So I think a lot of people probably already on green tea, right?
>> Yes.
>> Thank you. Thank you. Thank you. You failed astaxanthin, but at least you got the green tea. That was good. No.
>> Oh.
>> Oh, extra points. Extra points. Uh, propolis, naringenin. That's one of my favorites because it's also an osteoplastic activator. But there's easy things to reduce your histamine load.
Now, we get to the fun drugs. H1 blockers. There's first generation and second generation, and these are the things you buy over the counter for colds. Uh, first generation, uh, the first one was in 1933. Um, I'm blanking on the guy's name that invented this, but he won a Nobel Prize in 1957. So blocking this was extremely important uh because it was the first time that we could actually block anaphylactic death. Um, everyone knows that Benadryl as well as the other ones are still very available on the market, but because they are non-selective, because they're first generation, they get to the blood-brain barrier. So they're very sedating, right? So everyone's taken Benadryl because they want to go to sleep. Uh, and there are a variety of other options. Second generations, again, tons of them on the market. They're going to say non-drowsy. Why? Because they don't pass the blood-brain barrier, so they don't cause that sedation effect. They're very, very effective. There's tons of them on the market. They are, however, more likely to cause cardiac arrhythmias. Sorry. Everything has pros and cons. If you elect to block your histamine receptors, the [snorts] only thing you have to keep in mind is that because it's affecting a receptor, there is a feedback loop, right? So if you take a drug that blocks a receptor, your body goes, "Oh gosh, I need to make more receptors." So you make more receptors and then you need to take more drug and so on and so forth. So if you are going to use this particular strategy, which does work, you have to either rotate the drug or go on and off over a period of time to maintain the efficacy.
Okay. All right. H2 blockers. These are the blockers that reduce gastric acid secretion in the stomach. Um, incredibly popular medications. Uh, Tagamet was the first blockbuster drug in the 1970s. Was taken off the market from bad side effects. Zantac then was extremely popular. I think my mom lived on Zantac, but it turns out there are some additives in it that were carcinogenic. So that's off the market. Right now, we're living with Pepcid and Axid. We use Pepcid in hospitals if that's any indication. Um, problem is, long-term use of this has caused a lot of problems. So I don't recommend it. Um, pneumonia, peritonitis, uh, neck, C. diff, basically by I'm sorry, osteoporosis, absolutely. So, this is not a great strategy, but it's up there just so that you know that you can think about it, but I wouldn't do it all the time.
All right, H3 blockers are pretty much there's only one uh and it's I can never remember like how to pronounce it. Pitolisant or something like that. Anyway, it's it's used for narcolepsy, schizophrenia, has nothing to do with longevity, but it's in there for completeness sake. And we don't have any H4 blockers yet. I actually think that's going to be a huge industry in about five years.
Okay, last thing in this category is we can increase the metabolism of of histamine. And it turns out histamine is metabolized by two enzymes. There's diamine oxidase and histamine methyltransferase. And vitamin C is a cofactor for diamine oxidase. Right? So it turns out if you load with vitamin C, there's decent evidence that you can metabolize histamine faster. Not all studies have demonstrated this, but a lot of them have. And in a nod to you guys as a just picture, I went with life extension because I thought that was funny. Maybe no one else did. Okay, never mind.
Okay, let's talk about mast cells now. And we're all getting to the end. I know you guys are getting kind of like, what? Where in the hell is this lecture going? Okay, mast cells. We want to inhibit degranulation of mast cells. And there are some things that are endogenous, some things that are natural, and then there's some medications. So, we're going to start with the things that are endogenous. These are things that in your body naturally. Um, so heparin is incredibly effective. Unfortunately, if you take extra heparin, you will bleed out. So, that's not a good idea. Ones that are a good idea, chondroitin sulfate is incredibly good. People think that it helps with joints and I think it helps with joints because it's a mast cell stabilizer. Um, DHEA, very effective. Certain sex activators including fucoidan, very effective. Of course, NAD precursors seem to fix pretty much everything. Other than that, there's a bunch of steroids that do it. Pick and choose. Um, personally, I went with uh the the last three mast cell stabilizers in terms of things you can take. Everyone here knows about quercetin, right? So, I thought we're not going to go into that. Everyone knows that the only interesting thing about quercetin is that is a huge difference in men versus women. Men respond incredibly well to quercetin. Women do not. So I've never seen a study on it, but I have a big clinic and this is what I have found. So women do better with luteolin. So if you're going to pick one of the two, go with male female separation.
I googled on Google Scholar anything uh that you could take to block or to block degranulation and this was the list. I have absolutely no idea what's stronger than what other than the top ones. So take them for what it's worth because there's no comparative studies. However, one of my new favorites is PEA. It's listed at the bottom. So PEA, this is really cool. It's an endocannabinoid compound. So it's like an end, it's like a cannabinoid, but it's an endocannabinoid. And it turns out it blocks the receptors on mast cells. So this is incredibly effective as a mast cell stabilizer. Additionally, it's a PARP alpha agonist. Additionally, it's an AMPK activator. Additionally, your body upregulates it under stress. So, it's a self-help thing that you can even add more to. The only caveat to this is the bioavailability is terrible. So, the only one of the few times I've actually said you actually have to buy the micronized version. I've read many, many studies. So, unless you get micronized, it doesn't work. But I think that everyone should be on this at some point.
Okay, we're almost done. These are the drugs. Mast cell stabilizing drugs. Cromolyn is the most famous. Uh, it is an inhaled agent. We've been using it in kids mostly for asthma for a million years. Um, it works by binding to a calcium binding protein. So you can't degranulate. Problems are the bioavailability, as I said, is terrible. So you can't take it as a drug orally. You have to inhale it. The half-life is very short. So you have to use it at least four to six times a day and you have to be on it for two to six weeks to have any lasting effect. So, it's really not very helpful for our purposes.
I love the idea of this one. Pemirolast. I tried to order it from Japan after extensive research and it got trumped. You know what trumped means?
>> Yeah.
>> Means temporary suspension of acceptance of mail to the United States due to changes in US customs and regulations. I don't know what else to call it. You can't get it at the moment. We got trumped. However, you can get uh I keep calling it ketotifen, but apparently that's not how you actually pronounce it. It's ketotifen, but that just makes no sense to me. It looks like it should be ketotifen, so I'm going to say it and that's what it is. This is my new favorite drug. You can go to the grocery store and get this in in oral or eye drops or you can order it online and get the actual medication. Perfectly easy to get. Interestingly enough, it is an H1 blocker and it is a mast cell stabilizer. We use it for allergies all over the globe. It is more potent than cromolyn. In skin studies, it's six times more potent. Um, uh, in airway stuff, bronchitis, that sort of thing. It's it's 50 times more potent than cromolyn. It's also a leukotriene antagonist, so it's going to block a lot of inflammation. It's a phosphodiesterase inhibitor. It's going to increase blood flow. It's an iron chelator, so that we're not all iron overloaded. Bunch of studies. It's great for fibrosis. It's great for avoiding wrinkles. It's amazing. The only problem is that it's a little bit sedating. And how do I know this? Because I tried it. So when you take this, it's supposed to be for uh mast cell syndrome and the dose is 1 milligram twice a day. And I thought that's ridiculous. I don't have mast cell syndrome. I'm going to take 1 milligram once a day. And I was zonked for days. So I will tell you if you're going to try this, start very low. Uh, a half a milligram at night will help you sleep and it will help your mast cells. Uh, the other thing it is it does say drowsy, weight gain, irritability. I was a little irritable, so I, you know, take it with a grain of salt. Uh, and it does take a little while for the effects to come into place. So it took it's going to take about six to eight weeks. Mast cell stabilization stays, the side effects sort of go away. So I think this is going to be a winner.
Lastly, interestingly enough, I don't know if anyone here is on a statin, fluvastatin turns out to be an amazing mast cell stabilizer. Um, it binds to the mast cell LDL receptor. The problem with fluvastatin, it is the worst statin for dyslipidemia. It's terrible, but it's the best thing for this. So, if you like statins, you know, it's a thought. Uh, had to throw that in there to be complete.
And okay, so back to our sort of summation, our challenges. Mass cells cause inflammation and they dissolve tissue. We need to get rid of them. Some of them, not all of them, right? Overactivation with age leads to pathology, morbidity, and mortality. And we've got to figure this out. So what do we do? We're going to negative or we're going to uh negative, God, my brain. Sorry. We're going to minimize the negative effects of histamine. And we're going to try to reduce mast cell granulation. Be by either the things that I talked about or whatever we find coming up in the future because we have not mastered mass cells, but again, it's a work in progress.