#155 - Sleep & Nature's Call

0:02Hi there, it's Matt here and we're back for another episode of the podcast. Today, let's discuss a measuring jug, the sort you'd get in any kitchen, the one that holds one liter made of clear plastic and you probably don't trust it past the halfway mark. It has one function and one function alone to tell you how much of something there is. If you fill it to somewhere between 300 to 500 milliliters, you've got yourself a typical adult bladder capacity. The whole point of today's episode is how quickly does that capacity fill up and when is it supposed to normally fill up throughout the day? The problem commonly associated with this reservoir is the nocturnal visit to the toilet.

0:46It's often joked about or dismissed as the cost of getting older or perhaps a personal failing best kept quiet. It is in fact a medical condition which has a medical name, nocturia. Its clinical definition was determined by the world's continence experts in 2002 and has been discussed in research papers for many years. And I'd like to ask a slightly silly question. Is it really your bladder waking you at night? Quite a lot of the time, it very often isn't. Something else is to blame and the bladder is taking the fall. Sometimes it's the kidneys that haven't noticed it's nighttime. Sometimes it's the throat that closes up.

1:26Sometimes you're already awake and the bladder just provides somewhere to go. So keep hold of that measuring jug because by the end, you'll be looking at it very differently. Before 2002, no one knew how often was too often. Each study used a different method and the results from these studies weren't comparable. The International Continence Society resolved this issue in 2002, as science tends to do, by using a committee. From that moment on, it was formally established that nocturia is defined as having to get up at night to urinate, and the research community now had a standardized tool to compare data.

2:06In 2019, the definitions and the way the condition is measured were refined on the back of 16 years of research by the same group. In 2010, a different panel entirely made up of urologists, urogynecologists, nurses and behavioral therapists defined a normal adult bladder as one that empties about eight times a day and no more than once in the night. Give a couple of hundred women of normal lives two-day bladder diaries and barely one in eight ticks every box for normal bladder function. Then the number people actually report. Send a questionnaire to 6 ,000 randomly selected adults aged 18 to 79 from a national population registry and about 6 in 10 reply.

2:56At two or more trips per night, the age standardized prevalence works out at roughly one adult in eight and about the same for men and women. Scrutinize 43 community studies over nearly 20 years, and at two or more void trips, anywhere from 2 to 17 % of men aged 20 to 40 are affected, and 4 to 18 % of women of the same age. For both men and women over 70, it ranges roughly from around 30 to 60%. Reduce the requirement to one bathroom trip per night, and these older men go to about 70 to 90 % plus. and younger men go at a rate of just over 10 to 35%. The rates for older women for one trip were roughly 75%, whilst younger women went 20 to 44%.

3:48Overall, younger women suffer the nighttime void more than younger men, and the curve generally reverses with age. Then we get to the flip side of normal, since the trips must originate from somewhere. The adage of eight glasses of water a day is the only dietary recommendation nearly universally repeated by everyone, but entirely unsubstantiated by anyone. Search for the literature backing up this figure in healthy adults in temperate climates, and you will find none. The official numbers substituted for it, about 3.7 liters per day of total water intake for men and 2.7 for women, are survey medians.

4:32These numbers reflect what a random national sample of people happened to drink, include the water in food, about a fifth, and do not decline with age. These amounts were never prescriptions. And the amounts of fluid that our bodies process is not constant across the lifespan. We can follow water through 5 ,604 people from 8 days old to 96 in 23 countries, using a labeled isotope. Water turnover peaks around 30 in men, around 4.3 liters per day, and holds a plateau from 30 to the mid-50s in women, around 3.4, then drops to around 3 liters in men and just under 3 liters in women after 70. That includes water through the body from all sources, including food and metabolism.

5:23It is not a drinking target. The amount actually available for drinking is much lower than that. So the figure on the bladder side of normal is more of a committee room convention, and the figure on the drinking side of normal is based on a set of survey averages.

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8:17Most of our deep sleep happens early on in the first few hours of the night. When a trip to the bathroom lands in that window, this is where Nocturia trims sleep the most. We can see it most clearly in people who are otherwise healthy. Take 39 older women in a 2019 Pittsburgh study with no drug company involvement who underwent rigorous screening, no urgency or leakage symptoms, adequate fluid intake, normal daytime frequency, normal results on formal bladder function testing. And 21 of them, more than half, still wake at least once a night to urinate. In the majority of those 21, the kidneys were overproducing urine overnight.

9:02The 21 women who woke to void had approximately three hours of uninterrupted sleep before that first trip. The 18 who slept through had just over four. The ones with the shorter first stretch reported poorer quality sleep on a single restlessness question rather than a full sleep questionnaire. Three hours compared to four. It wasn't necessarily a shorter night, more so the night was sliced in a different place. This pattern persists in people with nocturia. In a group of more than 750 nocturia patients, measured before treatment in a drug trial, those whose first bathroom trip occurred within around 70 minutes of bedtime were nearly three times as likely to have a poor whole night sleep quality score than those who slept longer than two and a half hours.

9:52The key question isn't how much sleep is being lost, but in which phase of sleep are the awakenings happening in? The relationship is bi-directional. Following a little over 8 ,000 people in a Japanese community over five years, nocturia at baseline is associated with a higher likelihood of developing poor sleep at the end of the study period. However, poor sleep at baseline is also associated with a higher likelihood of developing nocturia at the end of the study period, though this association reached statistical significance only in women and people younger than 50. The link is stronger in one direction, but exists in both.

10:34A separate survey of 3 ,000 people adds a detail. Nocturia is tied tightly to waking in the middle of the night. A fair number of people drink tea or alcohol in the evening because they believe it will help them sleep, which worsens both problems at once. Some bladder wakes then are simply awakenings with a convenience void attached. You were up anyway, and the bladder was available. Now, a quick note before we move on. All of the outcomes I've listed so far are associations and do not prove causation. Next, we'll move on to discuss the production of urine and how nocturia arises because it is not one disease.

11:16There are at least four different problems that share the same symptom and they can often overlap. This taxonomy has been established for over a decade. Either the body produces too much urine over 24 hours or it produces too much at night alone. Third, the bladder capacity is too small or finally there is a sleep disorder causing the waking with the bladder being incidental. The diagnostic tool is a frequency volume chart. This is not any fancy imaging, but a simple measuring jug and a notebook to log urination frequency and volume for two or three days. Think of the kidney like a tap. By day, the tap is on.

11:58At night, the supervisor turns it down and any urine made comes out small and concentrated. The supervisor is a hormone, vasopressin, and in a healthy young person, it increases at night and does exactly that. But as humans get older, the hormone loses its nightly surge. The supervisor still turns up, just not as much, and the tap stays closer to daytime rates throughout the night. There are two cardiovascular ways of getting to the same tap. In salt-sensitive hypertension, the kidney doesn't get rid of enough salt during the day and has to make up for it at night. In heart failure, lying flat moves fluid into the chest, distends the heart, and sets off a hormone to excrete salt and water.

12:43Different paths to the same result of urine production at the wrong time of day. Now what about thirst level across the lifespan? In careful laboratory work, seven healthy men in their late 60s and early 70s and seven in their 20s went 24 hours without water. The older men showed stronger dehydration signals in their blood, and yet they were less thirsty, drank less when allowed, and concentrated their urine less well. The picture is not uniform though. A different research group raised blood saltiness with an infusion rather than withholding water. They found older adults' thirst intact, which suggests the blunting is specific to going without water rather than a general failure of the alarm.

13:30But at population level, the consequence is that many older adults quietly fail to stay hydrated, and dehydration in that group predicts longer hospital stays, readmission, and worse outcomes. Think of a smoke alarm whose battery is running down. The fire is exactly as real, but the alarm is simply quieter. The next instance involves a blameless bladder and a guilty airway. Aggregate 13 studies of patients with obstructive sleep apnea and they are about 40 % more likely to have nocturia than those without it, with the association being greatest in severe apnea and independent of how the condition was diagnosed.

14:13The effect is significant in men, but not thus far in women. A separate systematic review also confirmed that nocturia increases with severity of sleep apnea and stated bluntly that the mechanism underlying this link remains largely unexamined. The conventional wisdom is that it's a mechanical phenomenon. Picture a throat closed like a valve, a chest expanding and contracting like a bellows, and a heart acting as a pressure transducer situated between the two. The negative pressure within the chest becomes increasingly pronounced as breathing is blocked. The tug pulls the heart. The heart interprets the stretch as an excess of fluid aboard and dispatches a hormone ordering the kidneys to excrete salt and water in direct conflict with vasopressin.

15:07The bladder becomes full because the airway closed up. This is a good story, and the most current comprehensive review notes its weaknesses. It doesn't fully explain the underlying mechanisms. Apnea also disrupts the autonomic nervous system, increases oxidative stress, and damages blood vessel endothelium. We have good data on the association, but we don't fully yet know why. So let's next talk about the levers you can manipulate yourself, beginning with the jug. Fill it just slightly beyond the quarter mark, about 280 milliliters, and drink it right before going to bed. 55 middle-aged men did this, wired to a portable EEG recorder and monitored for a full night in a hotel room.

15:52The results showed they were more likely to wake and urinate on the night they drank it, compared to a night they had nothing to drink for the final hour before sleep. The time it took to fall asleep and the time spent awake after falling asleep were unaffected, though it took longer to reach REM sleep, and REM sleep tended to be shorter. The price to pay is the nighttime urinations, and looking at 19 separate studies, nocturia is associated with roughly three times the odds of self-reporting a bad night's sleep. Salt is the other fluid lever, which may seem odd. Take individuals consuming large amounts, give them instructions to reduce consumption and follow their intake through urinary testing.

16:38Out of 321 participants, 223 succeeded. And they went from an average of 2.3 nighttime voids per night to 1.4, while the fraction of their total daily urine volume passed at night also declined. The 98 who failed to cut their salt saw no improvement in any symptom. Now, this was not a randomized trial, and everyone began with a high level of salt intake, so we shouldn't expect the result to apply to someone already eating low levels of salt. So, what about alcohol? The common wisdom is that alcohol turns off your anti-diuretic hormone, so you pee. But controlled experiments show a biphasic night.

17:24The tide goes out, then comes back in. When researchers gave eight men a significant quantity of alcohol between six and nine in the evening, compared to fruit juice on another occasion, urine output increased for the first three hours. Then, from midnight to six in the morning, the body shifted into water retention mode, conserving nearly half of a water load given in the morning, compared with only about an eighth on the control night. But in the early diuresis that followed, blood vasopressin was not any different from the control session.

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19:34Another group looked at a stable marker of the same hormone in 10 men across four randomized sessions. After 90 minutes, the marker had dropped in every session, alcohol or not, with no difference between them, although the men produced more urine when alcohol was consumed. Those authors read this as the normal dip being prolonged by alcohol rather than switched off. By 12 hours, both the hormone and blood sodium had gone up again. So the abrupt switching off of vasopressin that we keep hearing about was not what either experiment saw in those early hours, and the hormone was actually higher during the late water-retaining phase.

20:18When a systematic review of the entire diet and bladder field, 111 papers, was performed, most were given the lowest rating for quality of evidence. Only a handful of randomized trials could really be considered direct evidence, which is why the final finding in this section is even more puzzling. When over 1 ,500 Finnish men aged 50, 60, and 70 were followed for five years, there was a clear increase in the incidence of nocturia with obesity. Obese men had about one and a half times the risk of developing mild nocturia and more than double the risk of developing moderate or severe nocturia compared with men of normal weight.

21:02There was no increase for coffee, no increase for smoking. But those men who drank modestly under about 150 grams of alcohol per week, about a drink or two a day, were less likely to develop moderate or severe nocturia than those who did not drink. The obesity finding was also replicated. In the United States National Health and Nutrition examination survey, there was a 40 % increase in the odds of nocturia for those whose body mass index was greater than 30, increasing further in a stepwise fashion with increasing weight. The alcohol finding was observational and only in men. Light drinkers are different from abstainers in many ways, but it is not a fluke.

21:45The same systematic review that rated the field so poorly also independently reported an association of modest alcohol intake with fewer urinary symptoms in men. So what actually works to help someone who suffers from regular nighttime bathroom trips? First, the drugs, bluntly. A synthetic version of vasopressin, the night shift manager, which is taken to replace the signal that the aging body can no longer produce at night. In summary, the evidence says modest benefit, clear risk. In terms of benefit, a Cochrane review of 14 trials involving almost 3 ,000 men found that short-term, up to three months, the drug may have had a similar effect on the number of nightly voids to placebo based on low-quality evidence.

22:34It might improve over 3 to 12 months, and its efficacy seemed comparable with that of standard drugs for the prostate. A previous systematic review estimated a net gain of an extra hour before the first void and around three quarters of a void fewer per night with no further improvement at higher doses and noted that four of the included studies were at high risk of bias. Then there's the trial that was never about the bladder in the first place. Take older adults with insomnia, randomize them to receive a short behavioral sleep intervention or to receive an information leaflet, then only consider the 30 of them who also complained of waking at night to urinate.

23:16The intervention never mentioned the bladder. It consisted of two things, spend less time in bed and maintain a fixed sleep-wake schedule. Counted over a fortnight of diary entries, before and after the intervention group's total number of nighttime voids dropped by around 6.5 and the control group's rows by around 1. Six and a half fewer nighttime voids across that fortnight amounts to half a void a night from an intervention focused entirely on sleep. It's a small trial of 14 people against 16 measured four weeks after the intervention and based on self-reported voids. But as a demonstration that the bladder isn't always the problem, it's about as good as it gets.

24:04Then there's the airway. If apnea is the cause, treating the airway treats the bladder. Pool 5 studies involving 307 patients with apnea and nocturia who were prescribed continuous positive airway pressure, and their nighttime voids decreased, their nighttime urine volume decreased, and their daytime sleepiness improved too. An independent group that followed almost 100 patients through polysomnography, then through one to three months of home treatment, found that their nighttime awakenings to void dropped from around two and a half a night to less than one. That's what you get when apnea is the cause.

24:46It's not a general treatment for nocturia. The current major review concludes that it helps in some patients and not all patients, and it recommends considering the whole patient rather than just the airway. So overall, the takeaway from the episode is this. The bladder is the recipient of the message. It is rarely the originator. What wakes a bladder up at 3am is more likely than a bladder full of water, a kidney that forgot it's 3am, a throat that has shut, or a brain that was awake anyway and went snooping around for an excuse. Nocturia is a clinical symptom. So this next part is a summary of the research.

25:29It may be something to discuss with a doctor and should not be treated as a prescription. Shift fluids to earlier in the day rather than drinking less overall. Fluids consumed immediately prior to bed will increase the number of times you wake up, but the evidence suggests shifting fluids earlier. Second, think of evening alcohol consumption as a bladder issue as well as a sleep issue. It flushes water early in the night and retains it late in the night, and in controlled trials, the hormone was not abruptly switched off during the early flushing. At most, its normal dip was prolonged, and it rose during the late retention.

26:13Third, if you eat a lot of salt and you suffer from multiple nighttime bathroom trips, Cutting back is definitely an option. People who ate a lot of salt and reduced their intake were able to go from about 2.3 to 1.4 times per night in a non-randomized trial that began with high levels of consumption. Fourth, take a two-day bladder diary before your doctor's visit with the measuring jug and learn the two signs that indicate a change in direction. The diary distinguishes between overproduction and storage issues, and it's step one in the medical literature. Two times per night is when bothersomeness and quality of life start to decline, so it's appropriate to bring it up at this point.

27:00And finally, if you snore or have witnessed breathing pauses during sleep, the bladder may be being blamed for airway problems, And in some cases, treatment for sleep apnea decreases the number of voids. And if you have trouble sleeping, in a small trial, treating insomnia also decreased nocturnal urination. This isn't the whole story or the final say. The criteria are arbitrary, the salt data is weak, and the drug data isn't as strong as its reputation suggests. But the science so far has provided us with some practical insights. Above all, the insight that the bladder is most often a messenger and rarely a source.

27:42Thank you so much for listening. I really appreciate you giving me your time and your attention. Please look after yourself. Make the most of your waking hours. And tonight, may you sleep a deep and undisturbed sleep with any luck. Bye for now.

28:07Thank you.