If you don’t already have enough to worry about, have you ever thought about how stress is really bad for you?
We usually think of stress as a mental thing, but the feeling of being stressed is only the self-aware tip of a giant biological iceberg.
At the heart of this iceberg lies the hypothalamic-pituitary-adrenal (HPA) axis, a network made up of three small nodes – an almond-sized piece of the brain called the hypothalamus, the chickpea-sized pituitary gland just below it, and the walnut-sized adrenal glands above the kidneys.
While they wouldn’t be enough for a satisfying salad, these three tiny structures pack a huge punch hormonally.
Together they’re responsible for the release of cortisol – the infamous hormone responsible for both powering up and powering down the stress response.
Cortisol’s double life
Cortisol is like chocolate – having no chocolate is terrible, but so is your house being swept away in a freak chocolate flood. What’s best is having just the right amount to perk you up when you need it.
Cortisol has a bad reputation, but like all hormones, it’s just a messenger – a friendly internal postie who helpfully delivers instructions from one part of the body to another.
Cortisol delivers all sorts of messages during the day, but the dramatic ones happen when your body senses a threat and decides you need to feel stressed about it.
The stress response happens in seconds, even before you’re consciously aware that anything’s wrong. Alerted by the emotion-processing part of the brain, the hypothalamus puts two of its best on the job: the sympathetic nervous system and the HPA axis.
The modern electric nervous system works at lightning speed to tell the adrenal glands to release adrenaline. This immediately raises your heart rate, opens your airways, increases your blood pressure and blood sugar level, and sharpens your senses.
The HPA axis, working through the slower hormonal postal service, prompts the release of cortisol from the adrenal glands a few minutes later, with cortisol reaching its peak after around half an hour.
Cortisol picks up where the first burst of adrenaline leaves off, making further tweaks to systems and organs to keep tensions running high. However, once cortisol peaks, it also triggers a feedback loop that calms those same systems down and helps to repair tissue and reduce inflammation – this is why corticosteroids are prescribed for inflammatory conditions like arthritis.
Because cortisol does so many things in the body and fluctuates so much during the day, this complicates both its reputation as ‘the stress hormone’ and also the methods we currently have of measuring it.
No homeo
One of the reasons stress has been so hard to understand is that humans don’t just receive bad news and then drop dead from cortisol overload immediately – instead, the relationship of stress and disease is an incredibly complicated interplay of individual genetics, hormones, and how the body has learnt to respond to events in the past.
For most of the 20th century, scientists assumed that bodies were constantly working to maintain an ideal state of perfect balance, through a process called homeostasis.
But in the 80s researchers noticed something odd. People who grew up in peaceful times with stable jobs generally lived longer and stayed healthier than people who had more stressful lives. This threw a spanner in the works because everyone assumed that people who lived longer would accumulate more diseases over time. Instead, it seemed like the number of years wasn’t the sole determinant of health, but what happened during those years mattered a lot too.
This led to a new theory called allostasis, which suggested that bodies aren’t always yearning for a perfect balance but will do whatever it takes to get the job done, constantly adjusting to whatever fresh chaos comes their way. Genetics, life stage, environment, social situation (for social animals), and past experiences all influence how a body copes in the moment. It’s not about staying steady; it’s just about staying afloat.
But all that adapting takes effort – and some adaptations are better for long-term health than others. Researchers have a name for the wear and tear your body accumulates from constantly adjusting: allostatic load. If the load gets too heavy, it can tip into allostatic overload, and this leads to chronic health problems.
Here’s where cortisol, the stress hormone everyone loves to hate, comes back into the picture.
Cortisol and effect
Like your most dramatic friend, cortisol is good in short bursts. But too much time spent together can lead to other friends becoming distant – buddies like testosterone, insulin, your mental health, and your svelte waistline.
This is because cortisol is a catabolic hormone – it’s good at turning things into other things without being changed itself. It turns muscle protein into amino acids, stored fat into free-floating fat, and stored sugar into free-floating sugar – all fuel to power whatever heroic feats your body assumes you need to perform in the face of a threat.
If cortisol keeps hanging around and isn’t told to calm its farm, it’ll just keep this up forever – and if you don’t end up performing any energetic heroic feats you’ll just end up filled with a surplus of sweet, buttery human fuel.
Like filling a car up the ceiling with petrol, this puts a strain on all your systems, leading to fat redistribution, hormonal weirdness, a suppressed immune system, high cholesterol, and bad sleep, among many other things. It’s like your friend keeps giving you energy drinks to keep partying when it was past your bedtime two days ago – and hypes your other body parts to join in, even though no one’s having a good time any more.
Endocrinologists think that how cortisol works during a time of allostatic load might explain a lot about how chronic conditions like depression and heart disease develop – and how we might be able to treat them in the future. One particularly promising lead comes in the form of a sticky blob with a complicated name.
Corticosteroid-binding globulin
While cortisol is the star of the stress show, it’s actually got a secret little globulin helper. Traditionally, corticosteriod-binding globulin (CBG) was just seen as cortisol’s ride, passively transporting it through the bloodstream.
However, research led by Professor David Torpy and his team in Adelaide has shown that CBG is more like cortisol’s handler, holding the hormone back until it finds the perfect time and place to unleash it.
If something changes the level of CBG, it has flow-on effects to cortisol and the messages it’s supposed to deliver.
If there’s heaps of CBG around, it closely guards cortisol like a jealous chaperone, which means cortisol can’t get its message across properly. This can be disruptive to things like the circadian rhythm, digestive system and liver, who depend on cortisol to kick them into gear. But if there’s a lack of CBG, cortisol just runs wild, panicking everyone. This is particularly bad for the brain and heart, which are sensitive to hormones.
All of this means that individual differences in the CBG level can actually affect a person’s risk of developing long-term health conditions from their exposure to cortisol and stress. It also might mean that some people are especially vulnerable to stress and stress-related diseases based on how their genes encode CBG.
Can’t stress this enough
If you have a chronic illness, don’t feel like it’s your fault for not being a Zen master. There are so many individual variations that make someone more or less susceptible to stress.
If we’ve learnt anything from TikTok this past year, it’s that cortisol is evil and should be illegal.
However, cortisol is just a hormone doing its best with the information it has – the real enemy is a world that makes people constantly stressed.
Cortisol is more complicated than up = bad; down = good – how and when your cortisol might reach a damaging level involves an interconnected network of many different parts and the sum of your genetics and life history.
What’s important is doing your best to live a peaceful life (and seeing your doctor for regular checkups) – just don’t stress too much about it.