Unlock Your Brain with Better Glymphatic Clearance

In this episode of the Health Optimization Medicine Podcast, Dr. Scott Sherr, Dr. Allen Bookatz, and Jodi Duval explore:

• Why can getting eight hours of sleep still leave someone waking up with brain fog, neurofatigue, and the feeling that their sleep was not restorative?
• How does the glymphatic system move cerebrospinal fluid through the brain to help clear metabolic waste, and what role do aquaporin-4 channels play in this process?
• Why can elevated nighttime sympathetic activity and norepinephrine interfere with the interstitial expansion and fluid movement needed for effective glymphatic clearance?
• What role do circadian light exposure, evening temperature, autonomic regulation, sleep position, and sleep hygiene play in creating the conditions for healthy overnight brain clearance?
• How can gut barrier integrity, LPS, inflammation, and microglial activation potentially affect the biological environment surrounding glymphatic function?
• Why can wearable-induced orthosomnia and anxiety about sleep scores become counterproductive, and how does the HOMeHOPe approach use measurable circadian and metabolic markers instead of simply telling people to “get more sleep”?
• What does the HOMe glymphatic optimization protocol actually involve, and can creating the right chronobiological, bioenergetic, and environmental conditions improve the brain’s natural overnight clearance?

What We Discuss:

00:00 – Your Brain Cleans Itself While You Sleep
00:48 – Can You Force the Glymphatic System to Clear Brain Waste?
01:19 – Why Eight Hours of Sleep May Not Equal Eight Hours of Clearance
02:13 – How Sympathetic Tone Can Disrupt Glymphatic Flow
03:37 – Aquaporin-4 and CSF-ISF Fluid Exchange
04:36 – Health Optimization Medicine vs. Conventional Prevention
05:15 – Gut Barrier Integrity, LPS and Microglial Activation
05:52 – Brain Health, Healthspan and Nighttime Clearance  
07:09 – The HOMe Glymphatic Optimization Protocol
11:31 – Do This Now and Forever: Keep It Dark, Cold, Quiet & Lateral
12:34 – The Skeptical Case: How Much Can Lifestyle Change Glymphatic Function?
13:33 – Precision Metabolic Guidance vs. Generic Sleep Advice

Full Transcript:

[00:00:00] Dr. Allen Bookatz: Every night your brain shrinks its astroglial cells by 60% and pressure washes itself clean, but only if your autonomic nervous system decides it's safe enough to let that happen. So if you're waking up foggy after eight hours in bed, your brain didn't forget how to clean itself. It did exactly what a nervous system running elevated norepinephrine all night told it to do, and that's, uh, actually an input we can change.

[00:00:30] Dr. Scott Sherr: Welcome to the Health Optimization Medicine podcast. I'm Dr. Scott Sherr, board certified internist and health optimization medicine doctor. Joining me today on our clinical panel, our showrunner Jodi Duval, naturopathic doctor and home practitioner, and our home expert, Dr. Allen Bookatz, chief of emergency medicine and home doctor.

[00:00:48] Jodi Duval: Thanks, Scott, and today we are tackling a critical bioenergetic and chronobiological dilemma. Can you force your glymphatic system to wash away neural waste [00:01:00] while you sleep? So we're unpacking the perivascular CSF ISF fluid exchange, the aquaporin-4 water channels, the most abundant water transporting protein channel in the central nervous system, and why wearable-induced orthosomnia is crushing our brain clearance.

[00:01:19] Dr. Allen Bookatz: That's the framing, Jodi, and it takes us into our first comparative reframe here, functional medicine versus HOMeHOPe salutogenesis. So functional medicine comes at neuroinflammation or brain fog through pathogenesis. They ask what disease is present, what toxin is present, and what supplement suppresses it?

[00:01:40] Dr. Allen Bookatz: Now, that isn't necessarily the wrong question here and, you know, I ask it too. But in HOMeHOPe we shift that paradigm entirely to salutogenesis, asking what physiological conditions create and sustain cellular health and natural glymphatic flow at the network level? 

[00:01:58] Jodi Duval: Brilliant. So that brings [00:02:00] us to the $64,000 clinical question of the day.

[00:02:04] Jodi Duval: So why do patients or clients who get eight hours of tracker-measured sleep still wake up with severe brain fog and neurofatigue? 

[00:02:13] Dr. Scott Sherr: I'm sure some of you are thinking about what this means by just getting eight hours, right? Because eight hours in bed does not mean it equals eight hours in glymphatic clearance.

[00:02:22] Dr. Scott Sherr: If nocturnal HPA axis or hypothalamic pituitary adrenal axis activation keeps sympathetic tone high, norepinephrine stays elevated, and norepinephrine actually prevents the 60% interstitial expansion needed for cerebrospinal fluid to wash the brain cortex. 

[00:02:38] Dr. Allen Bookatz: And Dr. Scott's right about this. Like, and that's the, that's the patient we're talking about.

[00:02:43] Dr. Allen Bookatz: It's like they're eight hours logged, they're still exhausted, they're foggy, and what they're not thinking about is that their glymphatic clearance here is depending on this perivascular fluid movement that's driven by the arterial pulsations and these aquaporin-4 channels on [00:03:00] the astroglial end-feet. I didn't know that astroglial had feet, let alone end-feet here.

[00:03:05] Dr. Allen Bookatz: But when the but when that sympathetic tone stays high, the aquaporin channels, they depolarize away from those vascular end-feet and the interstitial flushing stops. 

[00:03:17] Jodi Duval: Excellent. Yeah. No, I didn't know they had feet either. I must look, I must look at their diagram. 

[00:03:21] Dr. Allen Bookatz: Yeah, I kinda, I kinda think of the, um- It's their baby feet

[00:03:23] Dr. Allen Bookatz: the vascular end-feet as like, uh, sphincters, you know? Yeah, 

[00:03:27] Jodi Duval: yeah. 

[00:03:27] Dr. Allen Bookatz: And so, you know, when your sympathetic tone or sphincter tone is high, then it would make sense that, you know, any type of flushing out stops. 

[00:03:37] Jodi Duval: Yeah. Yeah, absolutely. So now let's dive into the mechanism then, Allen. So walk us through the aquaporin-4 water channels or channel dynamics and the CSF-ISF fluid exchange.

[00:03:49] Dr. Allen Bookatz: Okay, so the clearance runs like an overnight crew here, and they only sort of get in when the building empties and the workers are all gone. So the, [00:04:00] the day workers are all gone. So in a healthy chronobiological state, the cerebrospinal fluid or CSF, it enters the brain parenchyma through these periarterial spaces that are driven by cardiac pulsation.

[00:04:11] Dr. Allen Bookatz: So every time your heart pumps, it squeezes through these little, these little channels here, and it exchanges with this interstitial fluid collecting metabolic waste. And so things like beta amyloid, tau, tau proteins, and cellular metabolites, those exit then those perivenous channels into the lymphatics in the dural system.

[00:04:30] Dr. Allen Bookatz: And so the aquaporin-4 channels at those astrocyte end-feet, they make the flux fast enough to even matter. 

[00:04:36] Dr. Scott Sherr: Is there a flux capacitor involved here- ... or would there need to be? Okay, I'm, I'm making, I'm making an old reference to Back to the Future, everybody. So but this actually brings us to our second mandatory comparative reframe, conventional preventative medicine versus health optimization medicine.

[00:04:51] Dr. Scott Sherr: So conventional preventative medicine focuses on disease prevention, trying to prevent Alzheimer's or dementia 20 years down the road by monitoring cognitive decline scores, for [00:05:00] example. So HOMeHOPe instead, or in contrast, focuses on health optimization today, measuring real-time metabolomic markers, circadian light alignment, and autonomic tone, the balance between your sympathetic and parasympathetic nervous system, to ensure optimal cellular clearance right now, right, Jodi?

[00:05:15] Jodi Duval: Absolutely, and that's the important part is that we're looking at this now so we can change it now, and this is the, uh, the, the hope I think for a lot of people, the HOMeHOPe that you can be doing things now. So from that naturopathic perspective, gut mucosal barrier permeability also heavily impacts this mechanism.

[00:05:31] Jodi Duval: So when the lipopolysaccharides or the little pieces of shit, I'm all across this today, aren't I? Um, cross the leaky gut, then they trigger this systemic inflammatory cell danger responses or the CDR1, and the microglia in the brain detect these circulating endotoxins, and then they release the pro-inflammatory cytokines that impair the aquaporin channel polarization.

[00:05:52] Dr. Allen Bookatz: I'm glad, really glad you took us, uh, to the microglia, Jodi, because it lands us on our third mandatory comparative reframe here. [00:06:00] So anti-aging medicine versus HOMeHOPe, HOMeHOPe peak healthspan. So anti-aging medicine, we know it focuses on lifespan extension, so stretching those chronological years to the very, very end of what's possible for a human, so regardless of what cell quality or tissue quality we're talking about.

[00:06:21] Dr. Allen Bookatz: So that's not wrong, it just, it's not necessarily complete here, right? We don't care about just extending the, uh, the actual lifespan. What we care about in HOMeHOPe is the peak health span and the biological quality of life here, and we do that by maintaining the mitochondrial bioenergetics and everything we just talked about, that clearing that neural waste every night through those aquaporin channels.

[00:06:44] Dr. Scott Sherr: The Health Optimization Medicine Conference is happening. Two days of events, October 2nd and 3rd, Chicago, Illinois, at the Drake Hotel. CMEs available to practitioners who need them. Just 150 people with amazing speakers on the cutting edge of health and wellness. This is a [00:07:00] community. It's not your average conference.

[00:07:02] Dr. Scott Sherr: If you're interested, go to homehope.org and save 25% on your ticket by using conference25 at checkout. I hope to see you there. 

[00:07:09] Jodi Duval: All right, so we all love takeaways. Mm. So let's deliver the actionable one-cent solution, Scott. What is the exact step-by-step protocol to optimize your glymphatic clearance? 

[00:07:20] Dr. Scott Sherr: Well, exact is kind of an exact word, Jodi.

[00:07:23] Dr. Scott Sherr: We're gonna give some generalizations- ... and be as exact as we can- There you go ... um, because this is really important though. And we're gonna talk about what we- we're gonna call, and for this podcast, the home glymphatic optimization protocol. So the first one here is called s- number one is circadian light anchoring.

[00:07:41] Dr. Scott Sherr: This is your morning, so 10 to 15 minutes of outdoor sunlight within 30 minutes of waking up to anchor what's called the suprachiasmatic nucleus, the SCN, it's up in your hyp- hypothalamus, and suppress daytime melatonin. Who does this on the call? Who does this? I've, I've been trying these days. Yeah. It's not easy.

[00:07:55] Dr. Scott Sherr: Absolutely. We do... Yeah. Absolutely. If you can't, the other thing you could do if you don't have light [00:08:00] is you also can get a lamp as well. Mm. If you don't have light outside or if it's dark when you wake up, you can get a, a lamp or a light box or something like that. I think those is... I have one in my closet if it's not, you know, light outside yet.

[00:08:11] Dr. Allen Bookatz: What about, Dr. Scott, if I put my phone up as, like, bright as it can and I have a picture of the sun on it, does that count? 

[00:08:17] Dr. Scott Sherr: Um, for you, Allen, I would say absolutely, but for nobody else. Because the, the problem with the, the, the, the light on the phone is that that's not the biggest issue. The biggest issue is that you're looking at your phone and it's the news, it's text messages, it's, it's like all this like stress, cortisol stuff that's kinda like burning in your brain right away, and you don't get that light.

[00:08:36] Dr. Scott Sherr: The light exposure's a much more natural way to s- to elevate your cortisol, which is what's supposed to happen in the morning. So all right, so that's number one. Number two is thermal drop signaling. This is in your evening. So drop b- bedroom ambient temperature to between 65 and 68 degrees Fahrenheit, about 18 degrees Celsius, two hours before sleep to facilitate core body temperature drop and aquaporin 4 channel polarization.

[00:08:58] Dr. Scott Sherr: You know where this is really hard to get done? [00:09:00] Europe in the summer. Not possible. They do not have- And Australia- ... really air conditioning there ... when it's 45 

[00:09:04] Jodi Duval: degrees Celsius outside. 

[00:09:06] Dr. Scott Sherr: No, at least you guys believe in AC. They don't believe in AC there. Um- True. They have, they have AC, but like it's in quotes, you know?

[00:09:12] Dr. Scott Sherr: That's what I would say. So all right, number three- 

[00:09:14] Dr. Allen Bookatz: The fan ... 

[00:09:14] Dr. Scott Sherr: is, and this is a big one, autonomic safety and evening cortisol suppression. So eliminate blue light about two hours before bed. This is the light coming from your screens for the most part, and lights like fluorescent bulbs and things like that.

[00:09:27] Dr. Scott Sherr: Discontinue wearable sleep score checking if it causes morning orthosomnia anxiety, right? So if you're getting anxiety about your ring... Oh, mine's off right now. Look at that. It's, you know, it's off. But usually I wear it, but if you worry about it all the time, you're gonna have anxiety about what your score is.

[00:09:42] Dr. Scott Sherr: And so in some of my patients, I just have them stop using it completely, and they sleep better, right? Because it's this orthosomnia that we've described here at HOMeHOPe that we see all the time in clinical practice. Okay, and then number four is position and fluid dynamics. I'm interested in your sleeping positions.

[00:09:59] Dr. Scott Sherr: I think I know [00:10:00] a couple. I think I have an idea of where you guys might sleep. I'm gonna guess after this. So f- so sleep in a lateral side-sleeping position, this is the most important, if you can, which clinical imaging shows maximizes perivascular CSF, ISF fluid flow compared to supine sleeping. I think actually it's the right, is the right side?

[00:10:16] Dr. Scott Sherr: The right side's better than the left side too because otherwise I think on the heart it's, uh, because you have less expansion, or is it the other way around? I, I'm trying to remember which way. But either way, I'm gonna p- I'm gonna choose. Okay. Jodi, you're going to be a side sleeper. 

[00:10:31] Jodi Duval: Absolutely. 

[00:10:32] Dr. Scott Sherr: Okay. Yeah, 

[00:10:32] Jodi Duval: through and through.

[00:10:33] Dr. Scott Sherr: All right, cool. Oh. Allen, you are going to be somebody who sleeps on his back just because you think it's fun. 

[00:10:42] Dr. Allen Bookatz: I'm just glad you didn't say the fetal position, so I'll tell you also face down. 

[00:10:47] Dr. Scott Sherr: Well, my wife sleeps on her belly too. So some people sleep on their belly- Yeah ... like, you know, it's, it's all these positions, right?

[00:10:51] Dr. Scott Sherr: But, but, but the, the one on the side, if you can do it, I actually have a side sleeping pillow if you guys can-- if you actually get one of these things, that helps you sl- sleep on the side. But okay, number [00:11:00] five. We're on number five here. Gut mucosal shield support. Now what does this mean, right? So support gut barrier integrity with targeted short-chain fatty acids like butyrate, for example, and mucosal nutrients to prevent LPS, little piece of shits, induced microglial activation.

[00:11:14] Dr. Scott Sherr: So this is kind of a big number five. There's a lot you can do here, to say the least. But in general, stop eating things that induce LPS. Is that, is that too broad too? But really you're trying to decrease inflammation. It's not too broad. Inflammation in your diet is the best way to think about that.

[00:11:31] Dr. Allen Bookatz: You know, Scott, you gave the whole protocol, and so we normally have our here's your do this on Monday, but this is our here, do this N- now and forever. And I'd stop. And it costs nothing Forget 

[00:11:43] Dr. Scott Sherr: about tomorrow 

[00:11:44] Dr. Allen Bookatz: So in fact, it might save you money here. So turning off all screen lights for two hours before bed, setting your thermostat to 67 degrees Fahrenheit and- That's 

[00:11:53] Dr. Scott Sherr: gonna cost you some money.

[00:11:53] Dr. Scott Sherr: Let's, let's be honest, right? Like doing that, you know, your AC bill's gonna go up. Let's, let's just be- Okay, 

[00:11:57] Dr. Allen Bookatz: fine. Maybe it's, maybe it's... Yeah, we're, we're [00:12:00] equalizing that 

[00:12:00] Dr. Scott Sherr: Maybe get a side sleeping pillow. So what are we talking about? Maybe a couple hundred dollars a month? I don't know. 

[00:12:03] Dr. Allen Bookatz: Yeah, there you go.

[00:12:04] Dr. Allen Bookatz: Sleeping on your side. So yeah, keep it dark, keep it cold, quiet, lateral. All right, and so those, those... Okay, and then going back, right, these are these thermal and these autonomic safety signals that, you know, we're trying to signal to our astroglial cells here to help them clear that neural waste or LPS overnight.

[00:12:23] Jodi Duval: Very well explained, both Dr. Scott and Dr. Allen. Well done. But now we need to counterargument with our- Ah, good times. Yes, the favorite part ... steel 

[00:12:33] Dr. Allen Bookatz: man. 

[00:12:34] Jodi Duval: Yes. So what is the strongest critique from conventional neurology? 

[00:12:39] Dr. Allen Bookatz: Okay, so I'm gonna put on my smarty pants hat here and step into the shoes of a sleep neurologist, not a sleepy neurologist.

[00:12:48] Dr. Allen Bookatz: Okay, so slow wave architecture and adenosine clearance are strictly hardwired. And really if we look at this, it's by our genetics and by our age. So [00:13:00] interstitial expansion is not necessarily something that we voluntarily can control, and we know that aging itself degrades these aquaporin channels and the density of them, regardless of whatever lifestyle intervention that we try to put in.

[00:13:12] Dr. Scott Sherr: Okay, okay. I mean, I think a lot of neurologists that I know are pretty sleepy. Let's be clear here. But uh, no, no offense to the neurologists listening. I think you guys are all great, and, and gals. But the critique I think is fair, Allen, for passive interventions, right? But it leads to our fourth mandatory comparative reframe: lifestyle medicine versus HOMeHOPe metabolic guidance.

[00:13:33] Dr. Scott Sherr: Standard lifestyle medicine gives broad unmeasured advice like get more sleep. HOMeHOPe uses precision clinical metabolomics and chronological testing, measuring organic acids, salivary cortisol slope, and circadian markers to guide specific bioenergetic and environmental unburdening. So from there, I wanna go to our take-homes, lady and gentlemen.

[00:13:53] Dr. Scott Sherr: These are the three ones that we want you to take away from this particular episode. And I know this is kinda chock-full of, of things to really do here, [00:14:00] but the first takeaway I would say is that time in bed does not equal brain detoxification. Glymphatic clearance requires a 60% interstitial expansion, which only occurs when nocturnal sympathetic tone drops.

[00:14:11] Dr. Scott Sherr: Jodi, what's number, number, number two here? 

[00:14:13] Jodi Duval: Yeah. You know, orthosomnia is real, and I see this in clients, you know, in my office all the time. Obsessing over these wearable sleep scores, it does spike a nervous system response and spikes cortisol, and then it shuts down the aquaporin for water channels. So it's not always ideal to, to be looking at your wearables.

[00:14:33] Jodi Duval: Just feel how you actually feel as well. 

[00:14:36] Dr. Scott Sherr: Number three, Dr. Bookatz. 

[00:14:37] Dr. Allen Bookatz: We've all heard that draining your lymph is good for you. Let's just extend that to draining your glymph is also and equally or more good for you. So glymphatic drainage or clearance in this case is salutogenic. So circadian-light alignment, things like a temperature drop and gut barrier integrity [00:15:00] measures, those restore the natural brainwashing that we're talking about here.

[00:15:03] Dr. Allen Bookatz: And so and none of those require a pharmaceutical. 

[00:15:06] Dr. Scott Sherr: Take us away, Allen. 

[00:15:07] Dr. Allen Bookatz: All right. So here's where we land. Your brain's glymphatic clearance is s- a cellular salutogenesis process in action. So remember, that's when we shift from a disease-centric thinking to network-level health optimization. We stop trying to force sleep with sedatives and start providing the exact chronobiological, the bioenergetic, and the environmental conditions that cells require for health coherency.

[00:15:35] Dr. Allen Bookatz: But if you're the person who keeps getting told that the sleep study looks fine while you're, you still wake up tired, then, you know, just know that your brain isn't failing at this. It's just answering the signals that it was handed all night and just before bedtime. And those inputs you can change.

[00:15:51] Dr. Scott Sherr: Thank you so much for listening to another episode of the Health Optimization Medicine podcast. To learn more, go to homehope.org, check out our modules on [00:16:00] chronobiology, metabolomics. We have lots of there to dig into. So join us next week for another deep dive into clinical health optimization. See you next time.

[00:16:10] Jodi Duval: See ya

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