#154 - Sleep and Cortisol

0:02Hi there, and welcome back to the podcast. It's Matt here. Today, I want you to imagine a little plastic tube about four inches long, and inside the tube is a swab, and the directions for using it are pretty specific. When you first wake up, stick it in your mouth, let it soak, put it back in, and write down the time. 30 minutes later, do another sample, then a third sample at 45 minutes. It has to be exact because if not, you've broken the protocol. These tubes are given to thousands of research subjects across the globe because a vial of saliva upon waking up is a common way for us to measure our levels of stress hormones.

0:47And currently, this hormone is the villain on social media for many things, from weight gain to a puffy face, late-night awakenings, and more. And now you can buy cortisol detox products, cortisol face videos, cortisol lowering supplements, etc. So maybe the most straightforward question to ask is, is cortisol bad for you? Well, the answer is more complicated than the internet suggests. And if the allegations against this chemical are to be believed, they deserve to be addressed. So let's investigate the benefits and the drawbacks of cortisol. We'll hear the case for and against and after we'll issue a verdict Not a split decision either because the truth is actually fairly clear on the matter And it's not what the internet would lead you to believe The first point to consider is something that rarely comes up online You need cortisol to survive When the body cannot make enough of it, the result is a condition known as adrenal insufficiency or when the adrenal glands themselves are the thing that has failed Addison's disease.

1:58It is life-threatening, and the endocrinology literature is consistent on the point that early recognition and treatment are what prevent serious harm and death. And how does a person treat Addisons? By providing them with the missing hormone. The Endocrine Society has published an entire set of guidelines on how to replace cortisol in patients suffering from the disease. Cortisol's usual functions, as it happens, have surprisingly little to do with panic. In normal background amounts, it acts permissively. It helps keep metabolism, blood pressure regulation, and immunity running smoothly, maintaining a supply of glucose and general readiness to act.

2:45So what about the release schedule? Imagine a small office with two telephones feeding in and one secretary taking both calls. On a regular daily basis, regardless of whether there is any news, the first phone rings. The second phone only rings whenever something actually happens. The secretary answers both and relays the same message either way. That office is the HPA axis or hypothalamic pituitary adrenal axis, which is the main system your body uses to react to stress. And much of this trial depends on it having precisely those two inputs. One line is a clock, the biological rhythm that causes the daily cycle of cortisol release, regardless of whether anything stressful ever happens.

3:34The other line is an alarm, stress response, calling upon the system to secrete more cortisol on demand. The message is always the same. Mobilize resources to meet the need, whether the need is real or anticipated. One final opening point for the defense. Cortisol receptors exist in numerous organs and tissues throughout the body. and via them, the hormone alters the functioning of many systems in the interest of keeping the internal environment stable. In effect, it acts as a master signal for the whole body. Incidentally, this is the prosecution's strongest piece of evidence. A signal that so many things respond to is exactly the type of molecule whose lack and whose permanent overproduction would both cause problems everywhere at once.

4:29And here is the defense's star witness, the shape of your day. If you plot cortisol levels during the course of a day, you get one of the most robust rhythms in human biology. Low levels in the evening and the first part of the night, rising through the latter half of the night, peaking around the time you normally wake, with a last push in the half hour after you get up. This daily pattern was mapped in fine detail more than 50 years ago when researchers took blood samples every 20 minutes round the clock and saw the same regular rhythm playing out again and again. Healthy men were equipped with a sampler that reads cortisol continuously.

5:16The data showed the cortisol trough aligns with sleep onset and the cortisol peak aligns with waking in everyone. Put the wearable version on 214 volunteers and you see the same pattern again, only sampled in the tissues of the body. And this isn't something that sleep generates en route. Mistime a person's sleep experimentally and the plasma cortisol rhythm largely stays where it was, running to the clock rather than to the sleep. During the first 30 to 45 minutes after waking, cortisol rises steeply again, and that rise is distinct enough that it's got its own name, the cortisol awakening response, and its own guidelines for measurement, which is why there are the three timed spit tubes.

6:07Most of the day's cortisol in healthy people is secreted in the hours either side of morning awakening. Take a minute to digest that. If this is damage, your body is doing a good deal of it to itself over breakfast. The more plausible explanation is that the rise is preparatory. Consider a thermostat-controlled heating system. It starts firing up before any of the people in the house are awake, not because the house is cold, but because it will need to be warm very soon. The boiler is responding to a forecast. follow a couple of hundred adults over workdays and weekends, and the awakening rise was higher on the workdays, and highest still among those who reported the heaviest workloads and the most chronic worry.

6:57The prevailing view is that it's anticipating the day's demands and mobilizing resources to meet them. So what about stress and learning? Why can you remember some stressful events so accurately? Well, it turns out that the timing of stress can help or get in the way of memory consolidation. Across 113 studies and more than 6 ,000 people, stress arriving shortly after learning enhanced what was remembered. Whereas stress at the moment of retrieval impaired it, stress before or during learning generally impaired it too. The one exception being a very short delay with material directly related to the stressor.

7:43So the helpful window is narrow and it sits after the event rather than before it.

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9:12And now the closing argument for the defense. The ignition for cortisol, so to speak, has a dial on it. Waking into bright light instead of darkness increased cortisol levels by around a third over the following hour. The same light in the late evening did nothing. A subsequent study confirmed this morning effect and also found that blue and green light were more effective in boosting the cortisol response after awakening than red light. We gave morning light its own episode, the daylight mistake. What matters here is that the boost is not fixed and that early light turns it up. Now, here is where the trial pivots.

9:58We will next discuss the hinge or what turns the thing we need into the thing that is damaging us. In the short term, the defense makes the stronger case. Cortisol is necessary for adaptation and survival. and the model outlined so far explains a mechanism that does more good than harm. The current reviews agree with this interpretation. Cortisol is part of a stress response designed to keep you balanced during a crisis, embedded within the same circadian system that produces the daily rhythm. A good way to picture this argument is to imagine a smoke alarm. A smoke alarm is unequivocally a good thing to have.

10:44An alarm that fires continuously day and night inside a building from which there is no escape is something different. Chronic activation of the stress response results in cumulative damage, and it has its own name, allostatic load. There are four types or patterns. First, repeated hits from many different stresses, one after another. Second, the failure to adapt to a stressor that has been experienced before. Third, activation of the response followed by its non-shutdown. And lastly, an inadequate response requiring other systems to overcompensate. Allostatic load has been measured using neuroendocrine, immune, metabolic, and cardiovascular biomarkers.

11:31and a systematic review of the literature shows that higher allostatic load correlates with poorer health status. We are talking about observational research here and causation remains hard to establish. But this is the pivot upon which the entire case rests. Dosage, duration and timing determine whether a given compound operates as medicine or as poison. The compound itself doesn't change. The timing does. And that's precisely where the popular internet tale about cortisol goes wrong. The explanation is that a cortisol surge wakes you at 3 a.m. Yet the actual physiology at 3 a.m. shows cortisol either at its lowest for the entire day or in the usual pre-dawn rise towards its morning peak.

12:24Both the daily sampling and the continuous ambulatory data reveal the same. For the theory to be true, the story requires a mountain at the precise point where every measured curve draws a valley. During the night, short periods of arousal are a natural feature of sleep, part of the self-regulation of the night. REM sleep, a stage you are woken from more easily than from deep sleep, peaks in the early morning hours before you wake up. To surface briefly before dawn is simply to act according to the normal functioning of the system. But if you're experiencing distressing awakenings and or having daytime impairments, then this is a cause worth investigating.

13:11And now for the prosecution. This is the case for cortisol as culprit. It has a number of strong points, and on some charges, it should prevail. First up is chronic insomnia. Measure the HPA axis around the clock in patients with clinically diagnosed chronic insomnia, and the axis runs high. In the original 24-hour study, and it was a small one, 11 patients against 13 controls, the pituitary hormone that stimulates cortisol secretion was significantly higher than in the controls. Cortisol itself was higher too, though it fell just short of statistical significance. In both, the greatest elevations came in the evening and the first half of the night, exactly the time when they should be lowest.

14:03The sturdier evidence is the meta-analysis. 20 case control studies, some 800 people in total, finding moderately elevated cortisol in insomnia. There's an important caveat inside that word, moderately. The effect was real, but the individual studies varied, which fits cortisol being one symptom of the hyperarousal that drives chronic insomnia rather than a specific cause of it. We covered hyperarousal in an earlier episode, Tired But Wired. What's relevant here is that the stressed brain leaves biochemical traces. It can also work the other way, though the direction is genuinely contested. The insomnia work above concluded that sleep loss on its own usually leaves cortisol unchanged or lower.

14:57In the deprivation experiments though, cutting sleep does lift it. Restrict healthy subjects to four hours in bed and their cortisol runs 37 % higher the following evening. Take the whole night away and it goes up by 45 % with the usual evening decline delayed by at least an hour. Restrict young men to four hours a night for six nights and evening cortisol climbs alongside poorer glucose handling. So degraded sleep quality more than ordinary differences in duration changes how sharply this axis reacts to stress. Short sleep pushes evening cortisol up and elevated evening cortisol is what an unhealthy curve looks like.

15:47And chronic excess cortisol has a name, Cushing's syndrome. It creates progressive facial rounding and fullness, central obesity, muscle weakness, multi-system damage, and higher mortality rates. In the classic European population studies, the naturally occurring form of Cushing's syndrome turns up at two to three new cases per million people each year. Some newer smaller counts come in higher at four or five per million. This brings us to the question this entire trial can no longer put off. How does one even accurately measure cortisol? All of the numbers introduced in this case were produced by an instrument.

16:34Before they can be judged, they are subjected to cross-examination. Cortisol can be measured in urine, blood, and even hair, and different samples capture different lengths of time. A drop of blood or a spit into a tube freeze frame a moment. A 24-hour urine sample is more like tallying up your spending for the day. Hair grows at approximately a centimeter a month, so it is a running ledger month after month without the time of day issue at all. Even the Stolwitz serum test is more complicated than it appears and gives different results depending on the assay used. When used by clinicians appropriately, they are valuable tools.

17:21However, what they cannot do is support the wellness industry's pitch of using an ad hoc sample to assess one's level of chronic stress. The real problem is more fundamental. Cortisol isn't secreted evenly. It's secreted in short bursts on top of the normal rhythm. If you were trying to measure the ocean, there is the tide, which takes hours and is entirely predictable. There are the waves, which take seconds and aren't. You walk to the end of the peer, put the ruler in once, and you've got a number that doesn't tell you much of anything about either. This is what a cortisol measurement taken without regard to timing represents.

18:04A number at a random point along two overlapping oscillatory curves. The early studies that measured cortisol around the clock counted the waves, around nine secretary episodes per day, with the adrenal glands in active secretion for about a quarter of the day. Nine pulses per day. It's not sloppiness. Pulsatile hormone exposure is a key feature of how the HPA axis and the brain structures that regulate it maintain responsiveness, which is why clinical endocrinology is done the way it is, timed, repeated, and dynamic, and why the vials at the top of this episode ship in threes. So could a brain scan give us more insight here?

18:54Perhaps an EEG or the sleep stage graph your smartwatch generates? The answer is no. No brain scan directly measures cortisol. EEG is measuring the electrical activity of the cerebral cortex. Cortisol is measured in fluids and hair, But the two are connected and an EEG can be used to track the effects of cortisol in the body.

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20:43When researchers gave volunteers hourly injections of cortisol from early evening through to dawn, their sleep architecture changed measurably. Time spent in REM sleep dropped from about 20 % to about 12%, and time in deep slow-wave sleep increased by about 50%. And don't let anyone try to sell you slow-wave sleep supplements yet, because that was cortisol injected into a vein every hour from tea time through to dawn. Now, when the brain and cortisol hormone are recorded simultaneously, they run in opposite directions, so regularly in phase opposition that the researchers describe them as two independent generators kept in step.

21:30Delta activity is high during deep sleep while cortisol secretion is low, with cortisol rising as the night turns into morning. Time spent awake during the night goes together with increases in cortisol. This is important to note because it complicates the three o 'clock story yet again. When researchers deliberately woke sleepers, cortisol rose after the arousal, not before it. For spontaneous awakenings, the order is harder to pin down. The hormone and the arousal travel together, and which one leads the other is not fully settled. The thing that nobody disputes is the surge itself. The fact that the surge peaks around waking for every man in the continuous sampling study, that the surge is modulated by light and by expectation of future needs.

22:25A real-time scientific disagreement about the cause of something so clearly measurable is a sign that you have something worth paying attention to, especially next to a video claiming that cortisol science is settled and scary. A verdict should accurately represent what the evidence shows, and the evidence doesn't implicate the hormone itself. It's the shape of the curve again and again in the literature. Take 179 associations from 80 studies and find that flatter diurnal curves where cortisol levels change very little between morning and evening. Travel with poorer health for 10 of 12 types of outcome, most notably for immune and inflammatory ones.

23:13Track 4 ,047 British civil servants for an average of six years, and every standard deviation of flatness in the curve is associated with 30 % higher risk of dying of any cause, and almost twice the risk of dying of cardiovascular disease. Associated, not causally linked, these are observational cohorts and correlation doesn't equal causation because poor health itself may be the cause of the flattening. However, note what this evidence consistently points to, not the height of the peak. In the civil servant cohort, neither the mourning level nor the awakening response predicted who died. What did was a curve that stayed high into the night.

24:06Which leads us to our final point, exercise. Exercise elevates cortisol temporarily and proportionate to the challenge. In one small trial of 12 trained men, 30 minutes of moderate exercise increased it by approximately 40 % and strenuous exercise by approximately 80, while low intensity activity kept it practically unchanged compared to the declining rest level. This implies that there is a threshold and not just a huge overall increase. Long-term training doesn't cause the type of excessive cortisol seen with disease. Regular resistance training and interval training tend to lower resting cortisol.

24:50Regular endurance training nudges it up mildly and most clearly in highly trained endurance runners. And in intervention studies, physical activity lowered cortisol overall. 10 studies, a moderate effect, rated moderate certainty evidence. Hold that one a little loosely though. Most of those trials were in patients with breast cancer with few men and no older adults. Thus, the idea exercise increases cortisol, so don't do it, is defeated by the study itself. A spike that stops is good functioning. It is a spike that never stops that the study condemns. Overall, the verdict is this. The substance is innocent, but the timing can be guilty.

25:39That leads to five actions to consider, and none of which come in a capsule. First, let light in before letting content in. Bright light boosted the early rise by about a third in the original study, and in those experiments, the boost appeared in the morning and not in the evening. Second, protect sleep to protect stress. One night of less sleep raised the next evening's cortisol by a third or more, and six nights of less sleep left it higher, along with signs of altered metabolism. It's evening when a normal curve falls, and sleep helps keep it there. Third, don't fear the exercise spike. It's driven by demand and transient.

26:27The physiology is functioning normally. Across studies, regular physical activity lowers cortisol generally. Fourth, read rhythm, not results. One cortisol value is at some point along two superimposed rhythms. That's why clinical assays are timed, sequential, or dynamic. A single result, regardless of presentation is a dipstick taken once out of a flowing river. Fifth, ignore the 3 a.m. waking. In the middle of the night, your cortisol curve will be at or near its lowest, or simply in the pre-dawn climb. Small and short awakenings are part of normal sleep, and in studies of actual sleep patterns, the slight cortisol increase travels with the arousal rather than arriving as a 3am surge.

27:19If the waking is accompanied by genuine anxiety or daytime impairment, it needs investigation. So then, what about the saliva in the tube? The advice persists that cortisol is something you measure as a number and try to reduce. But consider what the researchers holding the tube actually do. They don't rely on one sample. The guidelines ask for at least three, because the individual value means so little. The data is in the rise between samples, and in the extent to which the peak associated with getting up has died away by nightfall. So the little plastic container of morning spit isn't so much a measurement of stress.

28:02It's more like taking the time. And overall, the hormone itself wasn't necessarily the problem the timing was. Thank you very much for listening. I am so grateful that you've shared your time and your attention. Spend your waking moments well with the right amount of cortisol and sleep a deep sleep tonight. Until next time, bye for now.