The Science of Sleep Optimization: Why Your "Healthy" Sleep Routine is Failing You

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Hey, welcome back to Cell to Systems. In this episode, we're going to cover sleep. We're going to go deep into every aspect that you can possibly think about because sleep is so important. So, without further ado, let's get going. So, there's a study that came out talking about sleep and sleeping too much. Do you guys know about this one where if you're sleeping beyond 9 hours it has some risk for cardiovascular or all-cause mortality?

I hadn't heard about it, but I do know that when I oversleep, it doesn't help. I feel really tired and sluggish, my mind doesn't really work, and I actually feel like I go to bed earlier that night, too. So, I'm not sure what the study said, but I could definitely feel it. It would be interesting to understand how it's related to cardiovascular disease, though. Well, focus and attention are tough, and staying on task is difficult. Especially focus, I would say, is where the hardest part is for me. There have been days when I've been sitting with patients in the room and I can feel myself like—it’s pretty unpleasant.

Dr. Ferree, is that undersleeping or is that oversleeping? Usually, it's undersleeping. You know, you can override sleep with adrenaline for a little while and then it starts to catch up to you. Yeah, you know, it's interesting. I once had a conversation with William Dement, the godfather of sleep medicine who wrote The Promise of Sleep, and he basically said that there were more deaths really attributed to lack of sleep than even drunk driving.

Not long after that, I actually saw an 18-wheeler in Chicago on the freeway where the guy had fallen asleep. It was crazy; we called 911. It was wild to see that someone actually fell asleep at the wheel. And I've had that happen to me where, traveling so much, I fell asleep at the wheel one time. Luckily, the person that was with me grabbed the wheel, but it's pretty scary actually to think about it. I don't know if that's ever happened to anyone here on the show, but yeah.

Definitely happened to me. I woke up in the middle of the grass on the highway when I was really young. I had been moving, packing up from college all day, and then had a long car ride home. I dozed off and luckily nothing happened—same situation, someone had to grab the steering wheel. That was really scary; I haven't actually thought about that in a long time. So that stat is probably surprising but does make a lot of sense.

Even when I used to work the overnight shift, which talk about being bad for your health—I worked the overnight shift, 8:00 p.m. to 8:00 a.m., for three years. I remember those drives home were kind of scary, trying to stay awake. And we have so many nurses and doctors working in hospitals all night long, so it makes sense. It's scary and not talked about a lot, though.

I remember those days. I did plenty of overnights too in the early portion of my career, and I just remember I had about a 30-minute drive home from the hospital. I remember those moments where I would close my eyes—knowingly close my eyes—and just sort of keep going down the road with my foot on the gas and hand on the steering wheel, knowing like, "Okay, you've got to open your eyes right now because if you go one or two more seconds, you really are going to fall asleep." Terrifying.

Working in the hospital, you know that the beeper is going to go off. So you have this sort of Pavlovian response to the beeper where your body just goes. I remember after residency—this is back in the days of beepers, which shows how old I am—I was a surgery resident and you get called for traumas in the middle of the night. After residency, if I was around a few people that had beepers and I'd hear that same sort of tone, I'd have an adrenaline surge because you get used to not sleeping and staying in this sort of hyper-vigilant state.

You hear it from patients now too. I have this one patient who is the mother of a son who's neurodivergent. As part of his neurodivergence, he has seizures that occur typically in the middle of the night. This mother has hyper-vigilance and it keeps her from sleeping; she’s got to keep one ear open and she's in this chronic sleep-deprived state where she's not getting any deep or REM sleep. We know a lot of diseases and medical problems come from that. She recently had a fairly significant cardiovascular event that has affected a lot of things in her life. So, it's pretty terrible.

It's pretty wild when you think about it. I have sleep apnea and I didn't know for years. My wife would say, "Well, you know, you snore," but then I finally had a sleep study and, sure enough, I stopped breathing 26 times a night, which was considered moderate. How often do you run into that when you see patients, Craig? Is that something you guys are looking at? Are you looking at sleep scores? Because these wearables drive people crazy, but how are we tracking it to really know if someone has sleep apnea?

Yeah, it's one of those questions that you just can't pass up. It's got to be addressed anytime there's a new patient intake. I'm always asking patients, "Do you snore? Are you waking up throughout the night at any point in time gasping for air? Do you feel like your heart's racing? When you wake up in the morning, do you feel as though you're well-rested and functioning on all cylinders from a cognitive standpoint?"

The risk associated with untreated sleep apnea is multifactorial. It ranges from driving up your blood pressure to pulmonary hypertension and the risk for atrial fibrillation and other cardiac arrhythmias. So it's one of those things that needs to be addressed always. What I'm surprised by is the amount of people who understand the downstream negative sequelae of untreated sleep apnea and just say, "No, I'm never going to wear a mask," or "I don't really want to go get the test in a sleep lab." You're dealing with a life-and-death situation. We know that bad sleep apnea is one of the most common causes of cardiac death at night when someone is trying to get rest.

So it's something that needs to be addressed and always inquired about. The people that do ultimately incorporate some component of positive pressure support do have substantial improvements in their quality of life. I'm curious, Dr. Pastana, there are a lot of sleep medications out there. Three come to mind right away. What are your thoughts on the long-term effects of those? I think at one point in time, Dr. Jed Black had said to me that they felt like long-term use of one of them was not a problem. But I wonder, do you guys think that's an issue for patients?

Well, it's really hard because we know how important sleep is. My recommendation was always to try as hard as you can to stay off of them, just because once you go down that route, in my experience, most people have to stay on it. The sleep they are getting even with medications is not even that great a sleep to begin with. So we try to delay any type of prescription sleep medication as long as we possibly can.

Now, there are other things like some more natural products. I've had good success with L-theanine, ashwagandha, and things like DHHB (dihydrohonokiol), but what I’ve found is that it's more about lifestyle modifications around sleep rather than what the right supplement or drug is. Usually, I find caffeine intake, being stimulated before bedtime, and the environment where they're sleeping are almost bigger levers to pull than actual medicine.

I also noticed that different people have different issues with sleep. One is falling asleep to begin with, and the other is staying asleep. People have different personalities; for those with a high-active brain type, things like L-theanine work really well. It’s not necessarily a sleep aid, but it just calms the brain down so they can get into sleep. So I think it's a very personalized approach, but it's one where I haven't seen great benefit—even as a pharmacist—when it comes to sleep medications. It's more about lifestyle modifications.

Yeah, the modern world rewards sympathetic dominance but then balks when people can't sleep. I just don't think you can supplement yourself out of a dysregulated nervous system. You have to realize that longevity is in these lifestyle things. We know that the mitochondria don't work as well when you're not sleeping well. With undersleeping, you're going to find things like an increase in reactive oxygen species and nitric oxide species; you're going to find impaired NRF2 and altered NF-kappaB. All of these things increase inflammatory processes in the body.

When you go to sleep, if you look at your HRV, it should look like a hammock. That lowest point in your HRV is when the glymphatic system opens up. The glymphatic system is this beautiful network of channels that allows for—I always tell patients this—trash collectors to come take the trash out of the brain. The brain can function for only so long with an accumulation of trash. Imagine in your office if you're accumulating trash; you can function for a while, but at some point, you have to remove it to continue doing what you do.

The biggest concern for me regarding longevity and sleep is that you have to be able to sleep; otherwise, we're talking about neurodegenerative states. Yeah, it's that deep sleep where the amyloid plaques are removed, right? That's where that's happening. Interesting. What was it we were talking earlier about—the person that had the propane therapy? And then there was the cold immersion. Can we talk about that again, please?

Sure. Most of my patients wear wearables, and we talk about what they're doing with their deep sleep. One of them came in a few weeks ago and was talking about his wearable. He was getting around one minute of deep sleep per night. As I treated him, we did about three therapeutic stellate infiltrations. They were weekly. At the end of the three weeks, his wife was sending me his Oura ring reports, and she was like, "Oh my gosh, he's got 45 minutes of deep sleep!" So that was really great.

The second client was another interesting one because she does cold plunging. She had been fighting against doing cold plunging for a long time, but she regularly monitors her sleep. She gets a decent amount of regular deep sleep, but not a massive amount—about 20 minutes on a regular basis. She has two young boys, so she's a little hyper-vigilant. She finally went and did a cold plunge with lots of resistance. She was fearful, but she went in and did about two minutes. As long as she keeps her hands out, she's fine. She got two hours of deep sleep the night that she did her cold plunge, and she's repeated that test a couple of times with the same results. It is fascinating to watch.

That is fascinating. Right before sleep? No, it was just the day of sleep. The day of. Okay, because I'd imagine that would really wake you up before you went to bed. Exactly. That's really interesting. There was talk about how taking a warm bath before going to bed actually helps somehow to get to sleep. For me, I never have a problem falling asleep; I always have a problem waking up in the middle of the night.

Recently I started doing something—I don't know if it's a good idea or not—but Christy suggested I take some ketones before going to bed because I always wake up hungry in the middle of the night. So I started taking some EAAs (Essential Amino Acids) and ketones before going to bed. I have to tell you, when I do that, I get a full night's sleep. It works really well for me. Does that make sense in any way, shape, or form to any of you?

Well, KetoneAid on their website has a direct link to the NIH study that shows a significant reduction in wakefulness after sleep onset with the use of exogenous ketones. So, yeah, I think the science is there. Leonard, you were going to say something? No, I've heard of people using small doses of ketone esters right before bed. I didn't know there was an NIH study, but it wasn't the first time I've heard of it. I wasn't sure what the mechanism was because it's also the same thing I drink before I go on a long run. So, it's interesting these things that give you energy can also impact how well you sleep at night.

Well, keep in mind everything is "Goldilocks," right? You have to have a certain amount of IL-6 and a certain amount of cortisol in order to be able to fall asleep. I'm always pretty happy when I wake up in the morning and realize I actually slept through the whole night as opposed to waking up a couple of times. Research also shows that sleep that is too fragmented is just as detrimental as building up chronic sleep debt. Someone can be hitting all the metrics of time in bed, but if it's fragmented, the quality isn't there.

I tell my patients that sleep really begins when you wake up in the morning. Building those habits—getting morning sunlight, activating dopamine, supporting that cortisol surge, and avoiding caffeine within the first 60 minutes—lets your body do the heavy lifting with wakefulness and alertness. Then, as you continue through the morning, that's when we should focus the majority of our exertional training.

Cutting out caffeine after maybe 1:00 p.m. is important because some people are slow metabolizers. Caffeine blocks adenosine receptors. Adenosine is the product residual from ATP and energy that becomes an overwhelming impulse allowing us to get to sleep. Some people have a caffeine half-life of 8 to 12 hours and don't even realize it. Looking at reducing blue light exposure, keeping the room cold, and maybe using heat exposure followed by rapid cooling—like a hot shower—helps induce drowsiness. Keeping in-home temps between 60 and 68 degrees seems really great.

You guys were talking about behavioral modifications rather than medicine. Leonard, you talked about L-theanine. That was part of a protocol someone was talking about: magnesium threonate, L-theanine, and apigenin. They were really big on that, but I think at some point, don't we all just get used to what we're taking and it becomes less effective?

Well, that's what I felt. L-theanine has to be a high dose, too—I was taking up to 600 milligrams. But yeah, I feel the same way. I might get a good night or two, but if you use it all week long, you just don't get the same effect. You feel like you found the perfect combination of magnesium and L-theanine, and then day three or four it doesn't work like it did.

Well, and we've started doing that Intellix DNA test on people too. One of the cool things about that test is they show us histamine intolerance. There are 8 or 10 histamine-elevating gene variants they test for. It's really interesting because histamine is an excitatory neurotransmitter. In the beginning of spring in Georgia, before I have sinus symptoms, I'll start to feel anxious and wakeful. I’ll ask why I'm so anxious, and then I realize, "Oh yeah, it's February."

If you have these genetic variants related to histamine removal (like DAO) or production, you need to remove as many histaminic things from your environment as you can—both diet and the world. In some cases, you might need an antihistamine because typically at bedtime, histamine is converted to histidine so you go to sleep, just like glutamine is converted to GABA. Those things sometimes don't happen because of genetic variance.

That is super interesting. The notion of histamine and diet—at one point, someone said leftovers can create a high amount of histamine, which I thought was interesting because so many people talk about meal prepping. Wouldn't that create a bunch of histamine? I tell my mom that she freezes everything. She freezes pizza from two months ago, and I'm like, "Mom, please just throw the two extra slices away or get a new pizza."

I'm going to use this as an excuse to eat my wife's leftovers. She'll say, "Craig, why did you eat that? I wanted to eat that." And I'll say, "Babe, I'm saving you from a histamine storm. I don't want you to feel anxious." Loving and thoughtful!

So, we've covered a lot of sleep hygiene: the cold, the dark room, all of that. Are there any other things? Obviously, the elephant in the room we haven't talked about is alcohol and how that affects sleep. There's been a lot of talk about that recently. Anyone want to take a stab at that one?

Just from personal experience, when I had my Oura ring, it was just awful. I know when we used to get together at the masterminds, you're excited to see friends and you have a couple more drinks than you typically would. Your mind is stimulated because you're learning so much. But for some patients, it's hard to convince them because they think they sleep better or fall asleep better when they drink. They feel like they sleep harder, but as Craig was saying, it's interrupted. Alcohol is the number one thing that is going to ruin your sleep.

Yeah, it's just keeping you out of that glymphatic system. You're never opening the trash shoots. That to me is the most important thing; there's so much damage happening to us on a daily basis, and that glymphatic system is where the waste removal and recovery happen. We've had a lot of discussions on exercise, and this is when recovery from exercise and injuries is really happening. When you drink, you're preventing that recovery. Athletes, especially professional athletes, take their sleep really seriously now because it determines how well they perform the next day.

For traveling teams, I think it's tough trying to get sleep on the road. I remember reading an article about sports betting. If a team was traveling cross-country, even to a neutral place, the people who set the lines would change the statistics by a couple of points just because of the team having to travel and change time zones.

It's definitely a real thing. But the next question is: okay, you got really bad sleep, there's nothing you can do about it now—what do you do in the morning? Does anybody have an "I didn't sleep but I have a lot of stuff to do" protocol for the morning? Ketones. Exogenous ketones and water. Yeah, the ketones for sure. And then there was that study that recently came out with 15 to 20 grams of creatine. Did you guys hear about that one? It was a sleep deprivation study where they found they could almost eliminate the cognitive side effects of sleep deprivation with 20 grams of creatine. You might get a lot of water retention—I'd be the Stay Puft Marshmallow—but they showed it erased the cognitive decline.

Then there's the genetically engineered ZBiotics that breaks down acetaldehyde. Oh, is that that ad I keep getting with the guy with the bottle? Yeah, he was on Shark Tank. Yep. That's fascinating.

Any other sleep hygiene things we should be thinking about? What about pets in the bed? Oh gosh, right. It’s so hard; I love my dog. I get mad at my dog when he leaves the bed; I’m like, "Where are you going? I thought we were getting comfortable."

When our dog was a puppy, he slept in the bed, but at some point, we had to let him move on. It was kind of tough and I felt bad for him, but I was really glad not to be disturbed by him moving around all night. I'm a light sleeper, so it was not really healthy for me. Also, I think there's an issue around pet dander and hair. If you imagine what they're bringing in from outside, it's like putting your shoes in your bed. Sometimes I leave my shoes around the house and Kristen gets mad at me, but she doesn't mind cuddling with the dog in the bed.

We also have to think about our partners in the bed. There's a reason why people used to sleep in separate twin beds; they slept better because they didn't have the disruption. There certainly are mattresses now that can be helpful for removing that disruption. Then there is the middle-of-the-night waking to urinate, restlessness, or snoring. I encourage some clients to wear sleep masks. Envy makes these beautiful silk masks that are copper-infused to prevent infections.

And earplugs—Leonard, you were telling us last time about that headphone thing Kristen got you, the BrainTap. Yeah, the BrainTap. Another thing I forgot we had—because we just moved and didn't bring it with us—was the Ooler. Those things change the temperature of your mattress. That really made a difference for me because we were able to get the mattress down to 60 degrees. We're in Florida, so the bed gets hot, but being freezing helps me.

I have a BedJet and it's my favorite toy in the whole world. It’s an air conditioning unit that goes into what they call a "cloud sheet." It has two layers, and you can turn it up to 109 degrees or down to 60. Mine is set to turn on at 109 degrees for five minutes while I get in the shower; I come back to a warm bed, it stays off until 1:00 a.m., and then it goes down to 60 degrees for the rest of the night.

There's nothing worse than being hot and trying to go to sleep. A couple of years ago, I was in Costa Rica and it was hot. I was rooming with people from the UK, and they were really reticent to turn up the AC to the level I would like. Those were miserable nights trying to get to sleep when it’s 92 degrees in the bedroom.

The other elephant in the room is the TV in the bedroom. I don't have a TV in my bedroom, and I think having one is a poor choice. I think it does poor things for relationships and for sleep. Even if you're wearing blue light blocking glasses, there's an awakefulness that happens. Sometimes you'll fall asleep watching TV, and there's the influence of that "drone of consciousness" on your subconscious as you're sleeping. We need to be aware of how that pulls us into the polarity happening around the country.

Some people feel they fall asleep better with the TV on. A sign of sleep deprivation is if you hit the pillow and you're out within a minute. I hit the pillow and I'm out. But what happens is, at 2:00 in the morning, if the TV is still on, my subconscious is listening to The Big Bang Theory or Friends, and I wake up so frustrated.

I'm a morning person and Kristen is a night person. If you think about the difference between deep sleep (physical recovery) and REM sleep (emotional restoration), having the TV on in the middle of the night can really disturb that "emotional cleanup" that happens during REM.

Let's not forget how sleep deprivation affects intestinal barrier dysfunction. Things that affect the intestinal barrier include sleep deprivation, colonoscopy prep, infections, and cortisol. We use an oral peptide that is a tight junction barrier restorer. I'm a huge fan; more than 50% of my patients respond well to it within two weeks. Restoring that tight junction can lower your histamine load. Improving sleep dysfunction is helpful because it’s a chicken-and-egg thing: if they're not sleeping, their intestinal barrier gets worse; if their intestinal barrier is worse, their sleep gets worse. You have to break the cycle somewhere.

The bottom line is that sleep is super important and a lot of things go into it. It seems like now more than ever people are aware, and there are solutions to make sure you're sleeping the right way. As we wrap up, any final thoughts?

It is one of those core elements at the foundation of any cellular or longevity medicine practice: sleep, stress management, nutrition, exercise, and strength training. It's indispensable. Those who don't do it well, unfortunately, suffer health consequences. It’s critically important for immune surveillance, cancer surveillance, and recovery.

I often ask patients, "Is there something you're not listening to yourself about?" Do you need to change a career, a relationship, or a way of living? Almost always, sleep deprivation is due to some sort of choice you're not willing to make or a decision you're putting off. That’s great advice. I've noticed that myself; I just can't out-supplement a tough decision or something I'm worried about. I'll complain about not being able to sleep, then the project I was working on for six months finishes, and I sleep with no problem until the next bright idea keeps me awake. It’s situational.

What about people who engage in transcendental meditation? I bet their sleep looks amazing. One thing I want to come back to—phone in the room. I am terrible about putting on YouTube and listening to something to fall asleep. If I wake up in the middle of the night, my premium subscription starts finding crazy things to play and I’m dreaming along with it. It’s the most bizarre thing.

There's interesting information on electromagnetic fields and exposure to the brain. The recommendation is that the phone is at least 6 feet away from your head. We have an old-school alarm clock that projects the time on the ceiling so you don't even have to turn your head. The phones go in the kitchen at night.

If I fall asleep and the phone falls on my head, that breaks the six-foot rule, right? Because that's how Kristen found me a couple of nights ago. It's tough; we are primed to be always accessible, and I think it's changing our brain. I remember when "death scrolling" right before bed would really affect my sleep, but now I can fall asleep with my phone on my face and sleep just fine. That tells me my brain changed.

It’s so interesting—20 years ago we didn't have these devices. The ability to watch something like that is wild. To think a brain could change that quickly around technology. MP3—that’s a term I haven't heard in a long time! We were talking about beepers before, so I think I win the "old" contest.

All right, guys. As always, this was a ton of fun. I hope everyone who watches this gets information that could change their life. Thanks for joining us on this episode of Cell to Systems. Please remember to like, share, and subscribe. We truly appreciate it and look forward to seeing your comments. Thanks for joining us.