Sleep optimization requires understanding the circadian rhythm (the body's internal clock governed by light exposure through the suprachiasmatic nucleus), which regulates melatonin production from tryptophan via methylation-dependent pathways requiring micronutrients like B vitamins, iron, and zinc; additionally, sleep quality depends on the balance of neurochemical signals including orexin (wakefulness promoted by hunger), norepinephrine (triggered by hypoglycemia), adenosine (accumulates throughout the day and requires zinc for production), histamine (promoted by mast cells), and the GABA-glutamate balance (where magnesium acts as both a GABA agonist and NMDA receptor antagonist), all of which are interconnected and rarely function in isolation.
Optimizing Sleep - Answering your QuestionsAñadido:
Crap.
>> Mhm.
>> Mhm.
>> All right. Hello everyone.
Um about ready to get started here.
Um yeah, I'm just waiting for Ray to confirm.
>> [clears throat] >> Ray, you don't hear my voice?
Sorry, we're just trying to sort out the the issues here with the audio.
Um but yeah, for everyone joining us on YouTube should be able to hear us. Um and then I'm also trying to double stream this on uh on Twitter as well, but we'll see we'll see how well that goes. This is my first time trying one of these things, so we shall see.
Um so yeah, we're going to be talking about optimizing sleep today. Um so I am I was planning on uh well, I still am planning on uh releasing a Twitter thread to kind of guide the conversation here.
Um but uh that will be released uh a little bit later today. I actually did not get time to finish it properly cuz I'm uh I'm on the road, but I have I have the entire outline here.
And um yeah, we're going to we're going to go through it.
Um so I will be taking I'll be taking questions at the end if you want to uh register so you can ask a question that I will prioritize that is in the description of the video if you're on YouTube, and then also um if you're on Twitter, it is in the the pinned tweet there. So all right, I'm going to go ahead and get started.
Um hang on. I'm just trying to get confirmation that uh the rake and hear me on both Twitter and on YouTube.
So until I get that.
Yeah, so.
We're going to start off mainly by talking about. I'm not going to be able to show you guys my outline cuz it's private but uh.
Yeah, there's a lot of talk about sleep. You know, I've posted a lot of content about sleep over the years and. Um.
I think it's oh I got confirmation from someone that they can hear. All right, excellent.
Um.
So yeah, I've I've posted a lot about sleep.
Over the years and people sleep issues are extremely common.
They're one of the most common health issues that I see both at prism with our clients and.
Um.
Both at prism with our clients and just people asking me stuff on social media.
So the the main.
The main thing that I typically see with sleep is that it is typically not an isolated issue. So it's very rare that I have someone come in as a client and is like I literally only have sleep issues.
Um.
So.
I can I'm sorry. Can I get confirmation on over on YouTube if you can hear me?
Um if not then that seems to be a problem.
>> [gasps] >> I apologize guys. I'm really trying to.
To figure out something new here.
So, So, yeah. Um like I was saying, [clears throat] sleep issues are often um Oh, okay. So, I did get I I did get uh confirmation from someone on YouTube that they can hear. So, I'm just going to proceed as normal cuz Ray is apparently not able to get any signal out in the Bahamas. So, Anyway, like I was saying, sleep issues are almost never isolated, but there are a number of different things that we can do to ensure that our sleep is uh regulated properly.
So, um I'm going to go through the the main governors of sleep uh in this stream.
And like I said, I'll be answering questions at the end.
Um So, yeah. First of all, we should talk about the circadian rhythm. This is the absolute most important thing when it comes to sleep. And if you don't already know, your circadian rhythm is essentially your body's internal clock system. So, it's governed at the uh you know, biological, the molecular level. And the circadian rhythm essentially tells every single cell in your body what time of the day it is.
So, you know, if you if your body doesn't even know what time it is, how can you expect to be ready to fall asleep? You can't. You can't really. Um and this is where melatonin comes into play. So, melatonin is probably the most famous of the sleep mediators, I guess you could say.
It's probably the known as the the sleep hormone, even though it's really not a hormone.
Um but it is a central circadian uh regulating molecule.
And melatonin is mainly uh produced in the pineal gland of your brain, which actually sits outside the blood-brain barrier, which is why you can take melatonin and still get the effects um the sleep-inducing effects of it.
But uh melatonin is actually synthesized from an amino acid called tryptophan, which we get in the diet from eating protein.
And tryptophan, you know, people think of tryptophan as going to serotonin, which it does, but the conversion from sel- uh the conversion of serotonin into melatonin also requires some other cofactors.
So, this is something to be uh very aware of, and your body needs uh the following micronutrients in order to pull this off. So, you need iron, you need vitamin C, you need vitamin B5, vitamin B6, and you also need healthy methylation and good mitochondrial function. So, methylation could be like its own entire stream, so I'm not going to go through all of it here, but people are pretty familiar with genes, the MTHFR, um and some of the other relevant enzymes in the uh in the methylation pathway.
And you also are going to need vitamin B2, vitamin B9 or folate, and you're going to need good vitamin B6 for that, which is also directly needed in melatonin synthesis, and vitamin B12.
You also are going to want to support both choline and glycine uh by having healthy intakes of those in the diet as well.
So, the reason that methylation is important is because you need methyl groups uh biochemically in order to take serotonin and convert it into melatonin.
And then you need good mitochondrial function because melatonin is actually produced in the mitochondria of your pineal gland cells.
And one of the conversions from serotonin into melatonin is known as uh the acetylation step, and you actually take that acetyl group from your mitochondria. So, if you're not generating energy in your mitochondria properly, if you have any sort of impairments in your energy metabolism, that is ultimately also going to affect your melatonin synthesis.
So, that's the that's the kind of basics in terms of the actual synthesis of it.
And then, what is the is the main like environmental signal that allows your body to produce melatonin? Well, of course, it's light.
And I don't know if I should be saying of course because it seems like a lot of people may not know this, but um yeah, light governs your circadian rhythm at the most basic level of anything. So, essentially, you have what is called the suprachiasmatic nucleus within your brain, and that is a region in your hypothalamus that essentially sets the circadian clocks throughout the entire body.
And it's cool because the light will actually come into your eyes, and it will hit the back of your brain almost like a straight shot from your eyes into your brain. It's really crazy how that works.
So, when the light enters your eyes, it goes into the suprachiasmatic nucleus in your hypothalamus, and that anchors your circadian rhythm for all of the other cells in your body. It starts producing different molecular clock proteins um that ultimately are going to regulate gene transcription and regulate things like melatonin and cortisol. So, your cortisol is supposed to be highest in the morning, that's what helps you wake up in the morning.
And your melatonin is supposed to be super low, and then your they kind of go in opposite directions. Your cortisol should be getting lower throughout the day, and your melatonin should be getting higher, mainly at the end of the day.
But the the way that your body is able to regulate those things is through light.
So, we have studies showing that bright light a lack of bright light exposure or putting people in dim light all day both increases their cortisol throughout the day. So, you don't get it flatline towards the end of the day, and also will dampen the melatonin signaling because you need strong light exposure through your eyes in the morning so that your body knows to raise melatonin at the end of the day.
So, this is all to say that getting bright morning light, especially sunlight for reasons that I'll discuss a little bit later, this is the most important thing that you can probably do for your sleep in general, but definitely for your circadian rhythm and your melatonin synthesis.
If you don't have bright morning light, you know, it's going to be extremely difficult to regulate your circadian rhythm and thus your melatonin and cortisol secretion.
So, this is part of the reason why things like blue blocking glasses can be so helpful because and this is why there's a lot of talk about blue light and not being good.
It's not good for other reasons as well, but it's mainly not good because uh it can disrupt your circadian rhythm, especially at night. And obviously, it's very common nowadays, you know, I was literally watching I was literally watching the the Spurs and the Thunder last night, you know, I'm not wearing blue blockers during that. That's definitely affecting my circadian rhythm. So, then after the game, you know, I don't want to watch the game in all red. So, once the game's over, I'll put on the blue blocking glasses and that'll help block out any of that blue light. And the blue light is really what shuts off your melatonin secretion.
So, it's really good to to try to put those on, you know, ideally you put them on like a couple hours before bed, but I know it's not always realistic. So, I think if you can put them on as close to bed as possible, you know, people like to read on their phone or scroll on their phone or whatever at night, at least they're on some blue blockers that your body can synthesize its own melatonin.
And that kind of brings me to the topic of supplementing melatonin.
So, you know, should you supplement melatonin?
Um well, I think it really depends. I think it can definitely be beneficial in several circumstances. I think if you're someone who, you know, your circadian rhythm may be all over the place if you have to work erratic hours or if you're traveling, you know, melatonin supplementation can serve as a primary essentially a way to reset your circadian rhythm.
So, it can be very helpful then.
Um melatonin supplementation obviously has other benefits because melatonin has a ton of benefits for your mitochondrial function, for your antioxidant function, for your immune system, etc. The question is like is it optimal? And I think the obvious answer to that is no. Obviously taking a supplement of hormone is not better than your body producing it on its own. Of course it's not. It just can't be, right?
So, if you are going to supplement melatonin, first of all, just understand that that's not really like the solution that we're looking for. We're going to go into more detail below on the things that govern sleepiness and wakefulness other than melatonin.
But if you need to rely on melatonin to start, you like to start addressing your sleep issues, I don't see a problem with that. I mean, you need it's better to sleep than not to sleep, right?
So, the main things that are important to consider here are timing and dosage.
Because a lot of the Well, we can talk about timing first, but like I was saying before, uh melatonin is released, you know, it's not like you get a big blast of melatonin all at once at night.
Your body gradually increases melatonin synthesis throughout the night, and it peaks at around 2:00 or 4:00 uh 2:00 to 4:00 a.m. in the, you know, in the morning. So, that's like when you're, you know, knocked out, like, the peak of your of your rest, typically.
So, taking a supplement and getting a big blast of melatonin all at once, yes, it will definitely help you fall asleep, and it will, in turn, help regulate your circadian rhythm, which can then be a positive feedback loop.
It's not, on its own, you know, that's not an optimal secretion pattern. You want it to be on the gradual release rhythm that your body is used to.
So, there are timer uh time-release melatonin supplements that you can take, and that might be helpful um for some people.
I think that's definitely preferable to take a time-release melatonin as opposed to a single blast. Um and they're actually quite common nowadays. You can probably find them at like your CVS or whatever.
But again, even the time-release is not going to perfectly mimic your body's natural secretion of it.
And the other problem is that most of the melatonin supplements out there just have too much freaking melatonin. I mean, a lot of these supplements, they'll they have supplements of 5 or 10 mg of melatonin, and that is way too much.
Way too much. Your body produces anywhere from 0.1 to 0.3 mg per night.
And yes, you're not going to absorb all of that, but you're going to absorb anywhere from 10 to 50%.
And your body is also producing its own melatonin even if you're not sleeping.
So, you don't want to fully replace that, either.
You know, you want to take as little as possible to help you get the job done.
So, if you are going to supplement melatonin, my what I would do, I'll say, is to A, also address the root causes that we're about to get into, because taking melatonin supplement is not a root cause solution.
Also, consider taking time release formulas.
Consider definitely doing a much lower dose than most uh supplements are out there, ideally under 1/2 mg.
And yeah, try not to rely on it to the best of your ability, you know, focus more on the light and the other uh governors of circadian rhythm that I'm going to address here in a second.
So, we talked a little bit about how cortisol is highest in the morning.
It should be, and then it's lowest at night, and the melatonin is kind of the opposite. If your circadian rhythm is messed up, all those things get screwed up. You'll have high melatonin during the day, and you'll have high cortisol at night, and you just become a mess because that's when you you're you're basically tired all day, and then you can't fall asleep at night. And this is obviously something very common that I see all the time with our clients.
By the way, for anyone who's listening, if you are interested in working with me and my team, and you want to become a client, um if you're on Twitter, you can book a call with us using the link in the in our in my bio. And if you're on YouTube, you can use the link in the description. Just a quick aside.
Um but that's a pattern that is very common among people.
Right? So, other than the light, what can you do to help entrain your circadian rhythm?
Well, you have different um regulators of this. They're known as uh zeit I've actually never heard anyone say this word. I've only seen this word written, so I think it's pronounced zeit zeitgebers or zeitgiebers.
But essentially that means time givers.
These are things that help anchor your circadian rhythm.
And aside from light, the two biggest ones would be your meal timing and your exercise. So I hope everyone here exercises.
But um you want to be able to time your meals um at consistent times throughout the day, so that your circadian rhythm can kind of get used to all right, we have a feed time here and then we sleep at this time. You know, you these are the things that help and train the circadian rhythm.
Uh exercise, same thing. So like personally um oh, and then another one that, you know, maybe it's it's not popular and it's not like a so-called natural one, but caffeine is another one. So obviously if you drink caffeine at night, it's going to screw up your circadian rhythm. But if you drink caffeine during the morning, it can actually help um in terms of regulating this rhythm cuz your body gets used to all right, I I'm supposed to be awake in the morning cuz I'm used to getting this this anti-wakefulness or sorry, this pro-wakefulness signal um in the morning.
So for me personally, I'll get up and I'll have coffee. I'll try to get up before sunrise. I'll have my coffee in the morning. I'll go out for a walk.
I'll have a staring contest with the sun to get the light in my eyes and I I win every single time, obviously. Um that's a joke. Don't look directly into the sun.
>> [laughter] >> But you do want to get sunlight in your eyes. You want to get out uh ideally before sunrise and you can see the sun, you know, and then your your day is ready. And then getting in exercise immediately after or getting in a meal or if you want to switch switch the order, I like to do exercise first and then I'll eat after.
But, that's a consistent routine that I get into and that, more than anything, allows me to get to sleep.
Um, and that, you know, overall, trying to have more rhythm in your days, it it's amazing how many people that I work with uh do not tend to have consistent routines, at least when it comes to these basic things. And I understand like different lifestyles, um it kind of is what it is, so it's not always within your control.
Um, but if you can do these things to optimize that, that's going to be it's going to be huge for you.
So, moving moving aside from circadian and and melatonin signaling, um let's talk about what are the signals within your brain that actually allow it to relax properly, that allow you to get into a good sleep.
So, your cerebral cortex, which is the outermost layer of your brain, that's typically thought of as the higher thinking region within your brain, it receives input from several different brain regions. So, you have um the basal forebrain, you have the hypothalamus, the thalamus, and the brainstem.
These basically all will output neurochemical signals to the cerebral cortex to either signal wakefulness or sleepiness.
So, I'm going to go through the main regulators of both right here.
So, the first one I'm going to go through is a neuropeptide called orexin.
So, you can remember the name orexin if you guys are familiar obviously with anorexia, which is a condition where people don't eat.
Um, that was what literally means, it means not eating. Orexin is promoting appetite. Basically, if you're hungry, you're going to have a lot of orexin. It helps promote appetite.
But, it also promotes wakefulness.
And this, just from a basic level, obviously makes sense. If you are hungry, you obviously are not going to be able to sleep, and your body wants you to stay awake to find food, right? That makes just logical sense.
But if you actually look at these signaling within the brain, this is also true on every level.
So, obviously, orexin is stimulated by the hunger hormone ghrelin, and it's actually turned off by leptin.
And leptin is also often called the satiety hormone, which isn't necessarily accurate because it's not really a satiety hormone in the short term. Like, it's not like you eat a steak and you just have a surge of leptin. That's more mediated by things like cholecystokinin in your gut.
But leptin does have an appetite-suppressing effect to a degree.
But leptin is more of a long-term signal of energy status. So, leptin is produced by your fat cells in proportion to how big they are.
And leptin will get released from your fat cells. It will uh travel to your brain, to your hypothalamus, and then from there, it signals um both the suppression of appetite, and it has other effects to increase energy expenditure that and metabolism that I'm I'm not going to get into right now because it just is not really relevant.
But leptin turns off orexin. So, leptin will actually allow you to sleep better because it turns off that hunger, that orexin that is actively promoting wakefulness in your brain.
So, what do you need in order to optimize these systems? Well, you need to eat enough in total.
Right? So, this is going to obviously be different for everyone. So, if you're already very lean, you know, you don't want to be restricting calories more than you need to.
That might be unpopular. I know a lot of people think that caloric restriction is good for longevity, but I've written about that in other areas um as well. So, I'm not a big fan of long-term restricting your calories if you don't need to.
Um so, that's obviously going to be huge.
But then also just being at a healthy body composition, if you're too fat, you're going to have a lot of leptin in your blood, but you're not going to be able to perceive that signal in your hypothalamus properly because you're insulin resistant, you're leptin resistant as well.
So, you want to be at a healthy body composition having enough fat for good leptin signaling, but not being too fat to where you're leptin resistant.
And some other things that help optimize leptin production, I've done a whole thread about this um on Twitter.
But in terms of optimizing your leptin production, you are going to want to make sure to incorporate carbohydrates cuz that is one of the Well, that more so than any other macronutrient helps produce leptin.
And then you also again Cool how things fit together, but ultraviolet light in your eyes actually helps your body in the signaling cascade of leptin because when leptin goes into your brain, it it acts on neurons that produce alpha-MSH. These are alpha-MSH and MSH stands for melanocyte-stimulating hormone, which is related to melanin. So, just like the sun hits your skin and you produce melanin, you get a tan, the sun hits your eyes and it simulates the melanocortin the melanocortin signaling pathway, which is the same pathway that leptin works on.
So, this is all to say that ultraviolet light also helps in the signaling of leptin, which is another way that it will help you sleep.
Another important sign of wakefulness is going to be norepinephrine or noradrenaline.
And this is one of the primary like arousal it's typically thought of as an arousal molecule in the brain and arousal neurotransmitter not in like a sexual way, but just in like a like a exciting type of way.
Um although I guess it could also be in the sexual way. But that's not really how it's typically thought of.
And the um and the main enzymes that allow you to break it down to break down noradrenaline or norepinephrine so that you can have low levels and go to sleep are MAO or monoamine oxidase and COMT or catechol-O-methyltransferase.
That's another methylation-dependent enzyme.
Uh COMT is.
But the main promoter of noradrenaline or norepinephrine secretion is hypoglycemia.
So if you have low blood sugar or you struggle with low blood blood sugar especially throughout the night or at night that is one of the primary triggers for your brainstem or I guess it's not technically in your brainstem, but the region in your brain that produces norepinephrine it flips it on.
And why is why would it do that? Why would low blood sugar increase norepinephrine?
Well, because low blood sugar typically means low energy throughout the body.
You're not getting food. Obviously you just like orexin, you need to be awake to get more food. That's what your body thinks. If you don't have enough food, your body Your body doesn't know that you're trying to fast for autophagy.
Your body just knows it doesn't have enough food. So, we can't sleep. We need to be awake. We need to go get more food.
So, having sufficient amounts of carbohydrate, um you don't necessarily need to be on a very high carb diet to maintain your blood sugar.
But, the reason for that is that if you're not eating carbs, you will have surges and things like norepinephrine, like cortisol, like adrenaline, like glucagon, that act as counter-regulatory hormones.
And part of the One of the things that norepinephrine does is it signals to different brain regions and directly innervates your adrenal glands to help you start producing more glucose from non-glucose sources, from basically protein.
So, norepinephrine is there to wake you up and to correct your hypoglycemia. So, if you just do the work for your body and give it the carbohydrates, give it the glucose that it needs, then you're going to be able to limit norepinephrine properly.
Hang on 1 second. I got to plug in my computer here.
So, like I was talking about before, those enzymes, monoamine oxidase and COMT or catechol-O-methyltransferase, those are the enzymes that help you break down uh norepinephrine. So, monoamine oxidase is dependent on vitamin B2, which is riboflavin.
And COMT is, like I said before, a methylation-dependent enzyme, which, as I said before, dependent on B2, B6, folate, B12, uh getting enough dietary protein, especially glycine and choline.
You know, again, there's more to the story of methylation than just that, but that's the the basic rundown on methylation. So, you can already see this is why I said at the beginning that, you know, it's very rare that I will have someone that comes to me at Prism and says, "I literally just have sleep issues. I have nothing else." You know, we make people go through these extensive questionnaires and symptom tracking and diet tracking, all these all these things. And I've after 600 clients, I've never seen one person say, "Nope, I have no other symptoms. My everything is perfect, but I just can't sleep." That just It just doesn't happen.
And you can see, because all of these causes, they're nutrient deficiencies, they're circadian rhythm disruptions, blood sugar dysregulation, um all these things are going to affect your overall health, not just your sleep.
And by that same token, hypoglycemia, you know, it's the classic like you wake up at 3:00 in the morning and you're either hungry or you just wake up for no reason.
A lot of times that is from hypoglycemia, because cortisol is another one of these counter-regulatory hormones that keeps you awake and produces more glucose. So, if you don't have enough glucose in your blood at the time, your body will typically respond with higher cortisol secretion, and that, like it's supposed to wake you up in the morning, like it's supposed to, it can also do that during the night if you are not giving your body enough fuel.
And the main source of that fuel for throughout the night is going to be glycogen in the liver.
Glycogen is the storage form of carbohydrate and it's released as blood sugar throughout the night.
So, if you haven't eaten enough carbs or your liver function uh your liver function is poor, then it's going to be tough to get throughout the night without waking up and wanting to eat something because your blood sugar's going to be low.
And you know, so that gets into two separate rabbit holes of how do you optimize cortisol and how do you optimize your liver function?
Well, lucky for you guys, I have written threads on both of those things um that go into deep dives. So, um I will post the the full thread on optimizing sleep kind of going through what we've talked about here.
Um I will post that on Twitter later today and you guys will have the references for all this stuff.
But, one of uh one supplement that I know can definitely help with uh liver glycogen storage is taurine. There's actually some older research showing that if you take taurine, you can actually increase how much uh glycogen your liver can store. I'm not sure if I've seen that with any other compound.
I'm honestly not even sure really how it does that. I haven't looked into it recently.
But, that could be something to look into.
Um I want to talk about adenosine now.
So, adenosine is pretty famous for being the thing that caffeine basically blocks in your brain.
And that that's not the only thing that caffeine does. Caffeine does a lot of other cool stuff. Um another thing that I've written a entire thread about.
Um but, that's not the point of this.
So, basically, adenosine does signal sleepiness. Adenosine levels accumulate throughout the day. This is another one of these things that kind of is in the circadian rhythm.
And adenosine signals tiredness and it signals sleepiness.
And you need proper adenosine um you need proper adenosine production and signaling in order to fall asleep properly.
So, you need um adenosine is created from ATP, again produced in your mitochondria, your body's main energy currency.
So, you're seeing now in multiple different ways why mitochondrial function is super important for your sleep because you need it for melatonin production and you also need it for ATP, which then converts into adenosine. So, probably your two primary things in your body that make you go to sleep, adenosine and melatonin, are both highly dependent on your mitochondrial function.
But anyway, so your body takes ATP and it will convert it to AMP, which is adenosine monophosphate, and then from there it can get converted into adenosine.
And the enzymes that help you break down ATP into or sorry, AMP into adenosine are actually highly dependent on zinc.
So, there are some studies out there showing that higher intakes of zinc or zinc supplementation can help you with sleep and this is probably one of the main reasons why. So, eat your oysters, eat your eat your red meat, eat your dairy. That stuff is going to be is going to be very high on zinc and then, you know, you can obviously consider supplementation.
Um you know, if you can't get enough of those foods or you have a higher need for it.
Zinc also has some other sleep promoting properties that I'll get into a bit later. Um you know, independently of adenosine.
So, let's talk about histamine now.
Histamine is another one of these wakefulness promoters in your brain.
This is why taking antihistamines, taking Benadryl, is going to knock you out because histamine is one of these things that kind of kind of makes you scatterbrained almost. It can It can really be thought of as like a stress hormone.
And in that cortisol thread, I talk about a little bit about how histamine in the brain can actually promote cortisol uh secretion. Histamine really is a stress hormone. Uh a lot of people know about histamine because of mast cell uh you know, um mast cell overactivation or obviously allergies.
And yes, histamine is definitely a obviously major mediator both of those things.
I think it's important to understand when it comes to sleep, though, is that histamine does not typically cross the blood-brain barrier.
Um histamine is produced locally in your brain, though, but it's it's broken down differently in your brain than it is in other areas of your body. So, in your gut and it peripherally, you have an enzyme called diamine oxidase, which you can actually take as a supplement, by the way, which is super cool to to help you with histamine uh peripherally.
But in the brain, it's again very dependent on methylation, which I've talked about several times at this point.
Um and I know some people even use like SAM-e or S-adenosylmethionine, which is important for methylation.
Um I know some people take that for sleep.
And you know, this is probably just one of many reasons why it could help.
But histamine is produced locally within your brain.
And that's important because you need to um you need to understand what creates histamine within the brain. You actually have mast cells in your brain. A lot of people don't know this, but like or at least don't talk about it much.
But your brain has a lot of a lot of cells that are not just like conductive neurons that are putting out neurotransmitters. You have astrocytes.
You have microglia, which are the main immune cells. And you have mast cells, which produce histamine in your brain. That's kind of crazy. So they can produce histamine and that will directly signal like I said before, cortisol secretion, but also just directly can contribute to wakefulness. So if you have mast cell issues other areas in your body, there's no reason to believe that that would not also be an issue in your brain.
And kind of sound like a broken record here, but I've done an entire thread about histamine and mast cell activation and uh really in the context of allergies as well, so you guys can go check that out.
But uh just real quick, some tools for limiting histamine and uh kind of dampening mast cell activation, one that's not talked about enough is dietary calcium. There's some older studies showing that oral calcium supplementation can basically uh stabilize mast cells and can cause them to degranulate less or put out less histamine.
And the reason for that seems kind of paradoxical because when calcium flows into mast cells, calcium basically turns them on. It causes them to degranulate.
But eating more calcium in the diet tends to reduce the amount of calcium that flows into all of your cells, whether it's your neurons, or your mast cells, um having a higher dietary calcium level is good for that because higher dietary calcium down regulates a hormone called parathyroid hormone.
Parathyroid hormone then suppresses the influx of calcium into cells. And it also limits your um breakdown of your hard tissues like your bones that release calcium.
So, higher dietary higher dietary calcium can actually lower calcium levels in various different types of cells.
So, that's super important. And most people do not get enough calcium. You know, I like to see our clients get at least a gram a day. And if you don't tolerate milk very well, or you just don't want to drink milk, um I don't know why you wouldn't, but um you can do things like cottage cheese, Greek yogurt, uh other type cheeses.
Um not a huge fan of calcium supplementation, um but you know, you can do things like fish bones as well.
Those can all be good sources of calcium. Some other things for histamine and mast cell activation, vitamin C can calm down mast cell activation. Uh L-carnitine, which is a nutrient found in meat, can help.
Um talked to you all about about diamine oxidase. That's not relevant in the brain per se.
Um the probiotic L. plantarum has an anti-histamine effect. Again, I'm not sure how relevant that is in the brain.
Um progesterone, this is a big one.
Estrogen and progesterone are you know, kind of antagonize each other.
And estrogen is one of the uh most powerful mast cell activators and thus histamine promoters in your body. Progesterone does the opposite.
And you could probably guess by this point, but I also have an entire thread about mastering estrogen and I have another thread about progesterone. So, be sure to go check those things out um if you are at all interested.
So, let's talk a little bit about dreaming. So, dreaming is really uh really happens in the REM stage of your sleep, which is the lightest stage.
And REM itself is dominated by acetylcholine, which typically is a wakefulness signal on its own and for that reason I wouldn't recommend like taking cholinergics or trying to increase acetylcholine for sleep. That's very counterintuitive.
Um but it is important to note anyway.
And then dopamine is really what creates the dreams themselves. So, acetylcholine will put you into REM sleep and then dopamine is really what helps you uh create those vivid dreams.
So, if you're low on dopamine for whatever reason, um one of the common things that you will see is that you will stop dreaming.
And if you have high serotonin, which probably also means that you have low melatonin in your brain, you will also uh have potentially nightmares and you will also be less likely to dream typically.
Um so, one of the biggest things when it comes to sleep is the GABA versus glutamate balance. So, glutamate is your brain's primary excitatory signal. GABA is the opposite. It's your uh your brain's primary inhibitory signal.
So, and they're actually only separated by I think one or two enzymes biochemically. So, it's a very important push-pull.
Excess glutamate in your brain is bad for a lot of different reasons, but it's also uh it's definitely not good for your sleep because that's the excitatory signal. It kind of keeps you sort of scatterbrained. Um Um it's relevant even in things like ADHD and anxiety.
GABA, uh on the other hand, is the total opposite. It allows your brain to chill out.
Um it's what alcohol acts on, which is why people feel more relaxed and not as nervous when they drink.
But obviously, that is not advice. I'm not telling you to go drink so that you can fall asleep better because of GABA. That's not That's not the takeaway here.
>> [laughter] >> Um but some things that can help you with GABA glutamate balance, uh vitamin B6 is important for uh GABA synthesis, can have a GABA promoting effect.
Magnesium is huge because magnesium basically uh has a twofold um effect here. Magnesium acts as a GABA-A receptor agonist. So basically, it acts on the on the GABA signaling pathway directly.
And it also is an anti-glutamate agent in that the NMDA receptor, which is a glutamate receptor, is actually primarily blocked by magnesium.
So that receptor, it allows in calcium as an as an excitatory signal.
Um but it also uses magnesium as its blocker, as its antagonist.
We also have things like L-theanine, um oral GABA, which I know everyone says that GABA doesn't cross the blood-brain barrier, which is not really necessarily true. I mean, it doesn't in huge amounts, but we have studies showing that taking oral GABA lowers your cortisol and helps you sleep and helps you relax. So, that's really all that matters.
Um other things that are anti-NMDA, um something like agmatine sulfate is an anti-NMDA uh rece- is a NMDA receptor antagonist, I should say. And remember, NMDA receptors are glutamate receptors.
Um one last thing that I want to touch on here.
Um if you know anything about me, you know I'm huge on gut first approach.
That's the approach that we take with our clients.
Um you know, it's obviously super important for your overall health, um and your sleep is no different. So, essentially, the if your if your gut is not in a good place, if you have lots of gut inflammation, you have leaky gut, you're going to have leakage of endotoxin or LPS into your bloodstream, and that LPS can trigger inflammation within your brain.
That inflammation within your brain can both increase cortisol secretion directly. Cytokines will act within the hypothalamus to produce uh or sorry, to promote the HPA axis, which ends up producing cortisol. That's an obvious pathway.
But, um LPS or endotoxin actually directly increases norepinephrine production, which we were talking about earlier.
Uh it increases that in the brain.
And inflammation in general tends to increase the amount of glutamate in your synapse because your astrocytes, which are a different type of cell in your brain, respond to inflammatory cytokines.
And if you have a lot of inflammation, those astrocytes basically they normally act to as a regulator.
They can pull out excess glutamate to prevent uh too much excitation within the cells.
But, if there's lots of inflammation, they kind of downregulate that process.
And then, this is just an intuitive thing to think about. If your gut is bothering you at all, really if any of your bodily systems are bothering you, but I'm just using the gut here as a as a primary one that I'm very familiar with, but like if there's any physical stimulation or irritation of any any part of your body, you're obviously going to like have disrupted sleep from that.
It's like saying like, you know, imagine if I just came up to you with like a little needle and I just started like poking you while you were sleeping. Like yeah, you'd probably wake up or at least you wouldn't have as good a sleep as you want.
And that's exactly what happens, but imagine that, but it's like in your gut.
Obviously, it's not as bad as a as a needle, but you're literally having physical irritation.
So, if you're someone, you know, that struggles with gut issues and this actually used to be a major problem for me back when my my gut issues were like terrible. Yeah, I couldn't really tolerate any sort of insoluble fiber. It would just really it felt like nails like running down my gut.
And I would notice that like if I ate any sort of insoluble fiber anywhere close to bed, I would just be waking up like five or six times a night. It was just awful.
But then once I took that out, I was able to reduce that to like only one or two times a night. Um so, that was that was a huge deal for me back then. So, um there's going to be other stuff that I discuss in this thread.
Um again, that will come out later today.
Um I would love to talk about sleep apnea, but that probably needs to be its own entire thread. Uh needs to be its own entire live stream.
So, I will do that at some point. Um there's other mediators as well, but I think I got through the main ones here.
So, we talked about GABA, glutamate, histamine, norepinephrine, adenosine.
Talked about hypoglycemia, we talked about cortisol, we talked about melatonin, we talked about circadian rhythms, leptin, orexin.
Um so, that gives you a lot to chew on there. I don't think I need to throw any more at you guys for now.
So, with all that being said, I am going to go and now I'm going to do um the Q&A portion. So, as I said before, um if you want to have your question answered, I already have like a decent amount here.
Um if you want your question answered, go check out either the link in the pinned tweet or in the description if you're on YouTube.
Um and you can submit a question there.
Um so, first question is kind of a long one.
It's from Anshul. Hopefully, I'm pronouncing that correctly. He says, "I had a problem with my stomach last year, then 1 year after uh All right, so, the kind of English is not the primary language here.
Uh a year after the hair started to fall out, then um He says, "Reports are normal." So, I assume that means lab work is normal. "I tried allopathy, homeopathy, and uh other types of alternative medicine that doesn't work.
Um yeah, so, clearly this person's in a lot of distress. I I'm sorry, I can't really I don't really understand what is what the question really is. I understand that you have a problem with your stomach and your hair is falling out.
Those are probably related.
Um I mean, I I would direct you towards my master gut and hair loss threads that I've put out.
Um but I I can tell this person's in quite a bit of distress, so I I'm very sorry to hear that and I would I would love to help, um but the something like this is not really for a Q&A, unfortunately. I just can't really get into all the details about this. So, if you are interested in actually getting help from me and my team, like I said before, if you're on Twitter, the link will be in the bio. If you're on YouTube, the uh link will be in the description below.
Book a free call with us, um and then I can actually devote a lot of my time to helping you and actually getting to understand the case better.
Um Kiara asked for uh sleep apnea issues. So, like I said before, I'm actually going to get into an entire thread about this cuz just full transparency, I don't actually know a ton about it. I know that there's a type of sleep apnea that is considered obstructive, like structurally, there's something wrong with your airways. Um I need to look more into what actually causes that.
And then there's the other type, which uh has more to do with your uh biochemical breathing or respiration sort of regulators. And what I can tell you for sure is that one of the important ones there is carbon dioxide.
So, if you're not getting enough If you're not breathing out enough carbon dioxide, you're not producing enough carbon dioxide, um you will not have sufficient oxygen delivery to your cells. That can cause sort of hyperventilation and I believe it can cause sleep apnea.
So, things for carbon dioxide production are going to be um are going to be I mean, you can literally supplement carbon dioxide by uh doing things like breathing exercises or bag breathing. Um But ultimately, low CO2 production is a metabolic issue cuz you can't breathe in a bag throughout the entire night. So, you're You produce carbon dioxide um during mitochondrial metabolism of carbohydrates. So, you need to be able to work on that.
John asks, is it safe to take glycine and magnesium glycinate together before bed?
Yes, I don't see why it would not be safe with the caveat of course that everyone is going to have unique reactions to certain things.
You know, when I say something is safe, I mean that in general for the vast majority of people it's not going to cause issues, but you know, there's people out there that you know, that have intolerances to the sun.
There's people out there that can't eat carrots like that doesn't mean that those things aren't safe. It just means that people have individual problems, but the main thing you want to look out for with glycine is that it is an inhibitory neurotransmitter and it can help you with sleep.
But glycine can also act as an agonist.
So it activates those NMDA receptors.
It's actually a co-activator.
So while it tends to in most people help you with sleep, it can also for some people cause either gut irritation or it can actually do the opposite and cause wakefulness.
But overall safety, yeah. I mean if you're taking them in reasonable doses, you should be fine.
Ruth asks, hot flashes every 90 minutes 24 hours a day.
Answers please. Oh my goodness, that sounds sounds awful. So sorry to hear that Ruth.
But um yeah, the hot flashes, I mean I assume that this is a menopausal issue.
Um So looking into targeted proper HRT, making sure that you know, your estrogen is transdermal, you're getting progesterone alongside it.
Um you're getting bioidentical versions of both.
Um you know, if you're a woman going through menopause, one of our practitioners is extremely dialed in with doing that if you're if you're interested. but yeah, lots of uh a lot of HRT historically and probably even still to this day is not done properly, which is why a lot of women still struggle. Um you also need to be careful about the timing of it cuz if you do the HRT too early or too late, you can actually end up worsening um your risk for dementia and things like that.
But hot flashes are also, I believe, um highly uh influenced by histamine.
So, everything that we talked about earlier with histamine uh is going to be relevant, uh but especially more so peripherally. So, diamine oxidase, you need copper for that. You can also supplement that directly.
Other things to calm down your mast cells, the calcium, the L-carnitine, the vitamin C, those are all going to be of interest for you as well.
Um We have a question here from Imrana.
Uh hysterectomy um hysterectomy due to heavy bleeding, uh what can help? Well, this is pretty classically an excess of estrogen issue.
So, again, I've written extensively about estrogen, but you need to think about gut health and bile because a lot of estrogen is excreted through your bowels.
Um other things for estrogen, um obviously being uh being overweight or insulin resistance can increase your aromatase expression sort of globally, um and then things that can really help you taper down the estrogenic tone are going to be progesterone, vitamin E, uh vitamin A as well, even though people hate vitamin A.
Um it does have an anti-proliferative effect, especially in the uterus.
Um so, that would be something that I would I would look into there.
Um Why asks vitamin K2 MK4 versus MK7? So, MK7 has a much longer half-life in the blood, so it'll like last longer and that will allow you to take lower doses of it. So, typically you'll see MK7 doses at like 90 microgram micrograms.
Whereas MK4, you can take in much higher doses and it's pretty pretty normal to take in much higher doses. Um MK4 is the the form found in animal foods that you're probably used to getting through the diet. It's I believe it's the version that your body actually uses and then MK7 needs to be converted.
I don't I'm not sure if MK7 on its own has any direct K2 activity.
Um I'd need to double-check that, but yeah, in general, I don't really recommend using MK7. Um I just don't really see the point. I mean, we have plenty of studies showing that MK4 has a ton of benefits and it um and I'm just I I I have more experience with it overall.
And there's there's no reason not to not to take it as far as I know.
Uh Elias or Elias, I think is how you pronounce it, asks how gut motility can affect sleep.
So, we talked about this. He says, "Yeah, I have slow motility and that affects my sleep, probably from SIBO."
Yeah, as we talked about before, um any problem with your gut is definitely going to impair sleep.
Like I said before, any physical irritation of your gut is going to act like someone poking you throughout the night because it's just you don't want to have any physical irritation that is going to just wake you up. So, yeah.
If you have any sort of gut issue, trying to fix your sleep, not considering that is just just just awful. It's just a nightmare.
>> [laughter] >> So, I would definitely try to um to focus on that.
Muhammad asks, uh I've been struggling with severe anhedonia, uh loss of libido from an ashwagandha supplement I took 6 years ago. My goodness. Um So, and he says, "Love your content." Thank you. Well, I love you back, Muhammad. Thank you for the support. Um I would need to look more into this, but I do know that ashwagandha can promote serotonin.
Serotonin is definitely uh can definitely be a driver of anhedonia. Um Serotonin, you know, is something that I've talked about over the years.
Serotonin does have important roles in your brain. I'm not saying you want no serotonin, but you also don't necessarily want to be promoting it with things like ashwagandha or definitely not SSRIs.
Um because those things can promote loss of libido, anhedonia.
Um and that's because serotonin really antagonizes dopamine at every level in your brain. When your brain releases serotonin, it directly cuts off the brain regions that produce uh dopamine.
So, dopamine is your motivation, your anti hit uh anhedonia, or your head your hedonic um neurotransmitter.
So, yeah, ashwagandha able to promote that.
So, you're really going to want to focus on lowering serotonin, promoting dopamine.
Um things like tyrosine, vitamin B6, um are just the basic starting points.
Vitamin C, very important for that. But, overall, we would probably need to put together a plan centered around raising dopamine, um potentially addressing any other systemic issues like thyroid or gut.
Um and he also asked, "I'm interested in your coaching program. Let me know if this is possible to reverse."
It is possible. I definitely think we can help. Obviously, I cannot guarantee results to anyone. I would never do that. Uh and anyone that does do that is uh you know, I would highly question what they bring to the table. So, I'm not going to guarantee that we can reverse it, but I will say that I think I have as good a shot as anyone at at being able to help you.
Kate asks, "My dad is stage four gallbladder cancer. How can I incorporate baking soda into his diet?"
Um first of all, I'm sorry to hear that about your father. Um I hope he gets better.
Uh stage four means that it is metastatic. It is spreading. So, this is obviously the worst possible stage.
Incorporate baking soda into his diet. I don't I'm not sure if this is asking about like should he like salt his foods with baking soda? I would not do that.
You're going to ruin all the poor man's meals.
Um you definitely want to dissolve it in water. But, the main thing you want to look for here is that there's one study showing um I believe it's also stage four pancreatic cancer.
And they basically showed that the urinary pH uh is what really predicts here. So, urinary pH um more acidic than seven, so basically below seven, is when you should try to alkalize and that's what baking soda does. It it raises the pH. It it makes you more basic.
Um so, trying to keep the urinary pH between seven and about 7.4 seems to be optimal for pretty much everything, but definitely for limiting um you know, excessive uh and well, any type of cancer spread is excessive. So, yeah, limiting en- the angiogenesis, the immune system suppression, the uh you know, the changes in the extracellular matrix that are seen uh with higher acidity.
That would be that would be my main um research-backed takeaway, not advice, but All right, so Rubina asks uh anxiety and Hashimoto's. Um again, that's unfortunately not really a question. I would direct you to the uh cortisol and autoimmune threads that I've done on Twitter.
Um but a lot of the things that we've discussed today, uh the wakefulness-promoting molecules in your brain when in excess, like glutamate or orexin, uh can also produce anxiety and thus the things uh that I've discussed, the GABAergic like the vitamin B6 and the theanine and and oral GABA and things like that, those will help to dampen the excitatory signaling and can thus be helpful with anxiety. Magnesium especially.
Um Maria asks what to do uh about getting up to pee at night. Well, I've definitely written a thread about this before.
And um the main the main thing that's going on with getting up in the night to pee is that you're not getting enough of a hormone called antidiuretic hormone or vasopressin.
So a diuretic basically causes you to pee, antidiuretic makes you not pee throughout the night.
And producing enough of that hormone is dependent on vitamin C, it's dependent on zinc.
Um you also are going to need enough salt and potassium.
Uh potassium was shown to basically um mediate your brain's per uh signaling, I believe it was, of vasopressin. So So, enough potassium, you're not going to be getting that. And that's actually something that we've seen our clients quite a bit is that adding in extra potassium, either to the diet or as supplemental form, can definitely help people not get up in the night to pee.
Um we were talking before about it, urinary pH and acidity. Uh the acid if the you have a acidic urine, that actually causes your bladder to be irritated and that can cause you to pee more throughout the night. So, a lot of people report positive results of baking soda.
Um then there's other factors going on that would uh direct you to that uh thread about waking up at night to pee.
All right, Mike asks uh lactoferrin, how long does one stay on a high dose? What antimicrobial to pair with it and should I be taking a binder?
Well, it really depends what your goal is. If your goal is mainly just like preventative or just like optimizing overall gut health, then you don't need an antimicrobial and you definitely don't need a binder. I don't think I would A binder is really better for like you're trying to rid toxins. Um and I don't really see why that would be relevant for lactoferrin.
Lactoferrin is really good for reducing inflammation in the gut. It's really good for select like being a selective antimicrobial. So, yeah, if you are dealing with some sort of dysbiosis, like there's a lot of different antimicrobials that you can consider depending on whether you're talking about candida, which lactoferrin has activity against, or you're talking about bacterial overgrowths.
Um it can be it can be either one of those things, but some some off the dome anti-candida agents, niacinamide, which is a form of vitamin B3, flowers of sulfur, um pau d'arco is kind of a is one that we use with our clients often. It uh it has anti-fungal and antibacterial properties.
Um and then you have the classic stuff, beer oregano, the uh golden seal or berberine. Those are definitely a lot harsher, so I would not consider those unless the the issue is pretty bad.
Um but yeah, that's something to consider.
Um I believe Let me just refresh here. Um Yeah, so that is all the questions that I got uh on the registration, which is all that I'm going to be able to take at this time.
Um which means that we're going to end the live stream now.
Um So >> [laughter] >> I appreciate you guys all coming by.
Once again, if you want any help from me and my team, definitely book a free call using the uh using the link in the description if you're on YouTube or the link in the bio if you're on Twitter.
Um you have any other questions about sleep or whatever, you know, feel free to shoot me a DM um on Twitter or whatever else uh whatever the platform I might be active on. I'll I'll try to help you out, but hope everyone has a great Saturday, and the recording of this will be on YouTube if you guys want to check it out, go back and watch the uh watch the beginning portions of it.
So All right, take care everyone.
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