Today you’ll learn about the development of a potential new Covid vaccine in the form of a nasal spray, how your circadian rhythm affects how intensely you feel pain, and how the old saying that you need 8 glasses of water a day could be a myth.
Today you’ll learn about the development of a potential new Covid vaccine in the form of a nasal spray, how your circadian rhythm affects how intensely you feel pain, and how the old saying that you need 8 glasses of water a day could be a myth.
Pain Worse at Night
Who Needs Water?
Covid Nasal Spray
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Find episode transcripts here: https://curiosity-daily-4e53644e.simplecast.com/episodes/pain-worse-at-night-who-needs-water-covid-nasal-spray
NATE: Hi! You’re about to get smarter in just a few minutes with Curiosity Daily from Discovery. Time flies when you’re learnin’ super cool stuff. I’m Nate.
CALLI: And I’m Calli. If you’re dropping in for the first time, welcome to Curiosity, where we aim to blow your mind by helping you to grow your mind. If you’re a loyal listener, welcome back!
NATE: Today you’ll learn about the development of a new potential Covid vaccine in the form of a nasal spray, how your circadian rhythm affects how intensely you feel pain, and how the old saying that you need 8 glasses of water a day could be a myth.
CALLI: Without further ado, let’s satisfy some curiosity!
[SFX: WHOOSH]
NATE: You ever notice how physical pain fluctuates throughout the day, but usually gets way more intense at night? For years, we thought this was just a coincidence, but recent research out of France suggests it’s not - as a matter of fact, our pain is more closely tied to our circadian clocks than we previously thought.
CALLI: Wait, seriously? Okay, so, this has been a mystery to me, about fluctuating pain. One minute, I’ll be recording a science podcast, but the next my back feels like I’ve been hit by a bus.
NATE: Exactly! So the good news is now we know why your pain fluctuates. Our bodies have something called circadian rhythms, which is basically our sleep cycles. During the night, our bodies are more relaxed and during the day, we’re more alert. And these rhythms can influence how intensely we feel pain based on the time of day we feel it.
CALLI: That doesn’t make sense though. Why does my back hurt more at 3am when I’m supposed to be more relaxed? Sometimes it will even wake me up.
NATE: Because the researchers discovered, for the first time, that any short burst of pain radiates as heat in the body and disrupts the rhythm. Think of it like your body’s balancing act. It’s trying to balance the scales between hyper-activity and sleep to create something more neutral. But then it’s like somebody comes up and screams BOO in your body’s ears and the balance is disrupted.
CALLI: This seems like a tricky thing to study. Wouldn’t the existence of a monitored study be an inspiration for the circadian rhythm to disrupt, too? It’s not a natural part of our relaxation.
NATE: It’s definitely tricky, which is why the participants are in something called “constant routine protocol.” This means everything stays constant for the duration of the study: same lighting, same temperature, consistent access to food, and most importantly, no sense of time. Then, the participants lie down in a dimly lit room for 24 hours and can’t leave, can’t sleep, or use the bathroom. Food is manually fed to the participants as a small snack, and although participants can talk to the researchers, the researchers are strictly forbidden to discuss the time.
CALLI: That… sounds like prison. That sounds worse than prison.
NATE: In a way, it is kinda like prison. Both literally and figuratively, since it throws off the body’s rhythm completely. Which is how it was identified that any natural rhythm in the body during this hellish event has to come from the circadian timing system.
CALLI: Oh man, and when you throw people in pain into this situation, it sounds kind of unbearable.
NATE: I bet it was. The version of this study that focused on pain had 12 healthy young men who did this for 34 hours straight. Every two hours, the researchers put a device on the subjects’ forearms that slowly increased in temperature by 1 degree Celsius until they reported pain. Nearly every participant stopped the device before it reached 46 degrees Celsius, or 115 degrees Fahrenheit.
CALLI: It freaking sounds to me like you’re describing war crimes to me!
NATE: Perhaps, but they’re CONSENSUAL war crimes. None of the men were lied to, and the tests were meant to identify pain tolerance, not actually hurt them. They DID get tested at 42, 44, and 46 degrees Celsius, though, and were asked to rate each with the level of pain they felt.
CALLI: Uh huh. And what did they find out with all of this?
NATE: I’m not done, there’s one more step they needed to take: they had to measure each person’s body clock. Basically: who’s a night owl? Who’s a morning person? Who’s in between, and so on.
CALLI: Who’s the permanently exhausted pigeon?
NATE: Sure. They figured this out by collecting saliva samples every hour to evaluate how melatonin rose, which is the hormone our bodies release two hours before normal bedtime. Once they figured out the clocks, they synchronized everybody’s rhythm onto one single 24 hour clock.
CALLI: Okay, so this is kinda like the phenomenon of when people’s periods sync up when you spend enough time with them, right? That’s kinda wild.
NATE: It is, and the results made themselves known immediately. Everybody’s pain synced up. Between 3 and 4 am, the pain reached its peak, before plummeting substantially by 3 or 4 pm.
CALLI: That’s so weird to think about. Okay, but I remember hearing once that middle of the night pain was related to sleep deprivation. Is that not true?
NATE: They tested for that, too, and the quick answer is: nope. The longer answer is that any pain sensitivity caused by sleep deprivation would build up in tandem with the pressure to sleep. So maybe you feel like something is more painful but it’s because you’re already stressed about sleeping. To be fair, the researchers admit that the study should be repeated specifically on those deprived of sleep… but 80 percent of their data is best explained by a circadian clock rather than deprivation.
CALLI: I think we spend just as much time on this show dispelling things I thought were true, as we do learning about things I never knew about. I guess I’m curious, though, does the same logic apply to women and other people who aren’t men?
NATE: No clue yet. We know that estrogen affects the circadian rhythm, so there might not be a similar pattern if the study is repeated with cisgender women or people assigned female at birth. That being said, the researchers don’t think the pain intensity is likely to change much.
CALLI: Got it. So what’s next for the study?
NATE: Looking into the circadian relationship to pain caused by health conditions—like cancer or shingles -- is the important next step, because researchers believe it might be better to give pain treatments based on the body's internal clock. They cited another study from 2019 that showed hospital prescriptions for pain medications surged in the morning and dwindled at night. In other words: the hospital had its own 24-hour rhythm—just one that didn’t accurately reflect the needs of its patients.
CALLI: This is fascinating. So the next time my back is flaring up at the end of the night, my best instinct is to scream at the sky “DANG YOU CIRCADIAN CLOCK”?
NATE: I think your best instinct should be to just see a doctor but sure, you can try that.
CALLI: Yeah, I’ll look into it.
[SFX: WHOOSH]
NATE: If you’ve ever told someone that drinking eight glasses of water a day is necessary to meet your nutritional needs then, turns out, you’ve been spreading misinformation.
CALLI: Why am I really concerned about this story already?
NATE: It’s because it’s about pee! That’s right. You’ve developed a sixth sense for that sort of thing and you’re right on.
CALLI: Great.
NATE: Okay, but, going back to the water. It turns out there’s a massive range in the amount of water healthy people consume all over the globe and it’s almost never eight glasses filled with eight ounces each of water, like common knowledge would dictate. They did a new study where they measured the water consumption of 5,600 people from 26 countries. And these ages ranged from 8 days to 96 years old. The average consumed was between 33 and 222 ounces of water per day. And several people were consuming a whopping 330 ounces per day.
CALLI: If you measure that, that’s like one of those huge Arrowhead water jugs with the taps you can buy at a grocery store. That’s close to 2.5 gallons?! That’s how much water people are drinking?! How did they measure - oh I don’t wanna know how they measured this.
NATE: That’s right, you know how they measured it. That’s where the topic comes in, they measured their pee. Or they used their pee to measure the water; we’ll get into that. So, previous studies of water consumption relied on volunteers self-reporting their water and food intake, which as we know is an unreliable way to conduct most studies. But for this, they changed it up. The study had the participants drink “labeled water.” And I don’t mean a brand of water bottle that comes with a label on it. They drank water containing trackable hydrogen and oxygen isotopes. Isotopes are atoms of a single element that have slightly different atomic weights, which makes them distinguishable from other atoms of the same element in a sample. When they expelled the water, the hydrogen isotope told the researchers how much water was actually being “turned over,” which is the term for the actual digestion and retention of water.
CALLI: Okay so what is the importance here of knowing how much water is being “turned over” or I guess that you’re not keeping in the body?
NATE: Body water turnover signifies how much water is lost in a given period of time. It helps us figure out how much a body ACTUALLY needs to consume in order to be healthy. If there ended up being any outliers in the study who turned over water too quickly, or not quickly enough, that could be a sign of an underlying health issue. So, the researchers collected and analysed data from the participants comparing it to environmental factors like temperature, humidity, and altitude of their hometowns to measure water turnover as well as energy expenditure, body mass, sex, age, and athletic status.
CALLI: This actually seems really complicated for just trying to disprove the “8 glasses a day” myth.
NATE: It might sound complicated, but it had a pretty simple outcome: water consumption differs for EVERYBODY based on their age, gender, athleticism, and a lot more. Water turnover volume peaked for men in the study during their 20s, and women plateaued from 20 to 55 years of age. And in total, men and women differed by about 16 ounces of water turnover.
CALLI: So you and I probably aren’t THAT different in body weight, I’m pretty tall for a girl so, what you’re saying is that even though we might be similar in body weight, our differences mean that we’re gonna have different water needs?
NATE: Exactly. For example, the study found that an average 20-year-old male non-athlete who weighs 154 pounds, lives at sea level in a well-developed country with an average climate, would take in and lose about 108 ounces of water every day. But a woman of the same age, activity level, and environment who weighed 132 pounds would go through 91 ounces. And as you use more energy, the need for water grows as well. So if you’re a hunter-gatherer or a farmer, you definitely need more water than someone who lives in a more industrialized economy.
CALLI: Okay, got it. So this is kind of like figuring out calories for your diet based on the Body Mass Index: your needs will vary depending on everything from your height to your current health to even the climate you live in.
NATE: Exactly! These new measurements will improve the ability to predict more specific and accurate water needs in the future, ESPECIALLY during emergencies. Plus, knowing how much water humans consume is more important every day because of the population growth and growing climate change. It’s always better to know how to figure out exactly what we need instead of relying on a measurement that basically boils down to someone saying, “Um, maybe it’s 8 glasses per day?”
CALLI: While this is a fascinating story, maybe our next story doesn’t need to involve the bathroom.
[SFX: WHOOSH]
CALLI: Okay, so, no one likes getting shots, even if they’re essential for helping us gain immunity for diseases like Covid, but what if there were a more effective way that didn’t hurt at all, and just involved breathing mist up your nose?
NATE: Ooh, not a huge fan of needles, even when they are necessary. So, if you’re telling me I can get better protection with less pain? Uh, yeah. I am very interested. Will my next Covid booster be up the nose?
CALLI: It actually might be! New research is showing that inhaled vaccines, called “mucosal” vaccines, might be even more effective at stopping Covid than the vaccines we use right now. Some of these inhaled Covid vaccines are already in use in China, and could help us achieve a more thorough Covid immunity.
NATE: Ok, now wait, real quick, can we go over again first how vaccines work?
CALLI: Oh yes, absolutely, sure. So vaccines are a little interesting, they work by prompting an immune response in your body. They show your body what a disease looks like, so it can have the right tools to fight it if the actual disease ever enters your body. Like a little blood cell power-point presentation. Right now we use a needle to put the vaccine directly into your muscle. In response, your body uses immune system T cells to destroy infected cells, and B cells, to make specialized, disease fighting antibodies. Those antibodies float in your bloodstream, ready for the next time the disease shows up!
NATE: But if they’re in the bloodstream, why do some vaccinated people still sometimes get sick, even if just mildly, with diseases they have antibodies for?
CALLI: Well since they are in the bloodstream, they have to circulate and get to the places where the infected cells are entering, like your nose and mouth. It takes them time to get there, and they’re not there in high enough levels to give you instant protection.
NATE: Is there a way to get more instant protection then?
CALLI: Yeah, actually! Researchers aim for what is called “sterilizing immunity,” immunity that blocks even those mild cases and keeps you from transmitting the disease to other people. It's really hard to get a vaccine to do this, but new nasal, mucosal vaccines could change the game, especially for Covid.
NATE: Well if we aren’t putting these vaccines in the muscle, do they just bop around your nose, mouth, and lungs?
CALLI: Like more standard vaccines, your whole body reacts to these vaccines and the antibodies will exist in the bloodstream, but they also help your body form specialized immune cells in your respiratory tract. They stay embedded in the tissue in the mucusy bits of your nose, mouth and lungs. These cells are ready and onsite exactly where Covid enters, and could potentially fight an entering virus before it has a chance to make you even a little bit sick!
NATE: Oh that sounds great! But it sounds almost too good to be true. Do we have to develop whole new vaccines to distribute like this?
CALLI: There are more than 1000 of these mucosal vaccines in development right now. For some of them, researchers created a different formula, but for others, the recipe for the vaccine that goes into your muscle seems to work in your nose too.
NATE: Well, do they work? Does the vaccine actually work like this?
CALLI: We aren’t sure. Researchers are testing it right now as a first dose for unvaccinated people, and as a booster for those who have had their shots. But there is an interesting wrinkle, it's hard to create a placebo group because it is so hard to find people who have never had Covid. Spoiler: I’m one of them.
NATE: Ok here is a simpler question, are we sure the tech works at all? Do we have other mucosal vaccines for other diseases that we know work?
CALLI: Oh yes! About 9 of them are in use right now for various diseases including Polio! They don’t work for all diseases though, as your body reacts differently and sometimes having a bit of a vaccine in your nose does not generate enough of an immune response to create antibodies effectively.
NATE: Ok, well if these tests go well, when will we see them next? Am I done getting Covid shots? Am I all the way on board for Covid sniffs?
CALLI: It’ll be about a year or two before we get data or results from large-scale human trials in the US and Europe. We need to see how well they fight the virus, if they’re better than standard vaccines, and see how close they get to sterilizing immunity.
NATE: Well, I hope they work well! I would love to stop getting shots, but still want the benefit of life saving medicine!
[SFX: WHOOSH]
NATE: Let’s recap what we learned today to wrap up.
CALLI: Your next Covid booster might not be a shot, it might be a sniff! Mucosal vaccines may offer easier, less painful, and potentially more effective vaccination than traditional shots.
NATE: Oh, the beauty of severe pain fluctuating throughout the day. Many once believed it was a psychological illusion. But new research out of France suggests that the reason we feel more in pain at certain times of the day is because the pain is throwing off our circadian rhythm. And what’s more - that pain can sync up with others experiencing similar pain!
CALLI: Eight glasses of water per day to stay hydrated? Turns out this “common knowledge” isn’t right after all! The average healthy person actually drinks anywhere between 33 and 330 ounces of water per day globally, and their needs vary from person to person, place to place, and by health status. Knowing the formula to how much water you need could actually help combat any emergencies of the present and future - such as climate change!