Negative consequences of HPA axis reactivation and caffeine as its regulator


Theabbreviation HPA comes from its English name: hypothalamic-pituitary-adrenal axis or hypothalamus-pituitary-adrenal axis. It is one of the main neuroendocrine autoregulatory systems of the body. As its name implies, the HPA axis represents certain links between the hypothalamus, pituitary and adrenal glands.


Thefirst mentioned, i.e. the hypothalamus, is a small part of the mesenchyme. However, it has an important role. Itregulates virtually every important activity of our body. Its neuronal networks contain information about our internal environment, which it compares with real values. Its purpose isto maintain homeostasis. The balance of our body system.

The moment it detects differences in the monitored values it reacts. Using the HPA axis system or through the autonomic nervous system (ANS) it initiates changes in the internal functions of our body. The ANS controls the function of internal organs and smooth muscles. It uses the enteric, parasympathetic and sympathetic nervous systems to do this. At the same time, the hypothalamus not only controlsthese organs and muscles , but also receives feedback from them through the ANS about their current state.


When the HPA axis is activated, the hypothalamus synthesizes the hormones vasopressin and CRH (corticotropin-releasing hormone or corticotropin-releasing hormone). These two hormones then influence the production of the hormone corticotropin (ACTH - adrenocorticotropic hormone) in the anterior lobe of the pituitary gland, which is sent to convey the message to the adrenal glands to make and release glucocorticoids into the body. These are steroid hormones the most important of which is cortisol.

The hormone cortisol is well known to us, especially nowadays when it is talked about a lot. In fact, it is associated with the most common problem of modern times - stress. For this reason, cortisol is also nicknamed the stress hormone. Cortisol is found in the body quite naturally and is responsible for many vital functions. It regulates the metabolism of certain organs such as the liver, kidneys and brain.


Our body normally regulates cortisol levels according to circadian rhythms. That is, according to our biological perception of time. The commands to produce and secrete cortisol reach the adrenal glands in pulses during the day. We have the most cortisol in the body in the morning. It helps us get up and start the day.

It also plays an important role in terms of immunity. In the case of an overactive immune system, for example in allergies or inflammation, it suppresses its activity. Reduced cortisol production results in weakness, low blood pressure or hypoglycaemia.


Our body ideally self-monitors the level of cortisol in the body. TheHPA axis not only gives orders to produce cortisol, but by feedback from the receptors to which cortisol binds, it receives information about the current state. Accordingly, the "control centre" of the HPA axis (hypothalamus) can adjust its commands to the pituitary gland, which influences the adrenal glands.

This sophisticated circuit prevents cortisol from becoming dangerous to the body due to its high concentration in the body. The problem on the HPA axis occurs when feedback about the level of cortisol in the body is not received.


The effects of cortisol on the body are used by the body as a natural stress response. Themoment a certain stressor is acting on us, it is the job of the HPA axis to balance this deflecting influence. To dothis, it sends cortisol into the body. The hypothalamus, as we described it above, takes care of balancing our bodily functions. Stress means imbalance for our body, so our HPA axis tries to break it down and activates.

Every problem, i.e. that stressor, must be resolved. Only then can our body be in harmony again and our organism function properly again. The function of the HPA axis and its reaction to stress stems from the original problems of humanity. The most basic ones, which basically had only two solutions. "Fight or flight." We can't really imagine that today. To literally live to survive. So that nothing eats us, but so that we can eat.


When prehistoric man, let's call him Alf, was foraging for food, it was quite common to encounter a predator. A hungry lion, for example. That's when the lion became a problem - a stressor. In an instant, Alf's mind decided what to do and what was the best chance for survival. Usually there are only two options. Either Alf is strong enough to kill the lion or he must quickly flee to safety. At that point, Alf's life is on the line and he has to give ithis all. Whether to run or to fight.

Alf getsthe necessary strength from the energy of his body. To survive, he must use all the energy in his body. That's what cortisol does. An active HPA axis will cause the cortisol levels in the body to rise. There are a number of receptors in our body that pick up cortisol. The receptor picks up the cortisol and it further adjusts the body's functions to allow attack or escape. It corrects the energy in the body so that it is not consumed in other activities, because now the body is all about life.


When our Alf wins a fight with a lion or escapes, the problem is solved. Alf's body no longer has reason to stress and the HPA axis adjusts cortisol production. Everything is back to normal. The body can once again distribute energy into all sorts of processes and functions. For example, it can resume digestion or production of various hormones, which was suspended due to dealing with stress, the lion, cortisol.

It's great that the body can take care of itself in this way as part of self-preservation. But how does this relate to our reality today? We don't live in the wilderness and most people have never been attacked by a lion in their entire lives. Times have changed, living standards have changed, environments have changed, and stressors have changed. Today we don't have a problem with a wild animal, but with thepressures of society, with particular people or with ourselves. Generally we call these problems civilisational stress. Well, what about cortisol? It still works and in the same way.


The moment we encounter our stressor, we should fight or flight. However, for various reasons, we cannot do so. We basically forbid ourselves to do so. A typical example is psychological abuse from a boss or a colleague at work. We know that we cannot afford to physically assault such a person and at the same time we do not want to leave the workplace.

If we don't find a constructive solution to this problem in the short term, we will encounter our stressor on a daily basis and the HPA axis will continually respond by producing cortisol. Prolonged elevated levels of cortisol in the body essentially blunt the receptors that cortisol latches onto. They just get tired of picking it up when there's still a lot of it. At that point, the feedback loop of the HPA axis is disrupted.


Cortisol receivers - receptors - are also transmitters that send information about the amount of cortisol. When the feedback loop is disrupted, the hypothalamus does not know that there is enough cortisol in the body. But the stressor is still there, so the HPA axis is still making and producing cortisol. Eventually, the body is essentially poisoned by the cortisol it made. The result is high blood pressure, diabetes, reduced immune system function, and therefore a greater likelihood of disease.

A list of the most serious problems associated with too much cortisol in our bodies include shortening ofconnections between neurons, shrinking of certain areas of the brain and cell atrophy. The negative effect of too much cortisol on the human brain leads topsychological problems and also Alzheimer's disease.


In this context, a study has been conducted to confirm theories that caffeine can reverse some of the negative effects of elevated cortisol in the body. Specifically, it involves the re-establishment of HPA axis feedback. The results of this study give hope that caffeine could be instrumental in this way to alleviate the course of Alzheimer's disease or even prevent it.

The study is based on the definition of adenosine receptors as master regulators of glucocorticoid function. The main glucocorticoid, as mentioned above, is cortisol. Adenosine receptors therefore influence cortisol function. Since caffeine is compositionally matched to these receptors, it can be captured by them. By its action at adenosine receptors, it has a chance of reversing the effects of glucocorticoids, i.e. cortisol.


In this study, research was conducted on people aged 50-70 with elevated cortisol levels. Impaired cognitive function and greater hippocampal atrophy were detected in this study group, leading to memory impairment in the elderly and accelerating the progression of Alzheimer's disease. Properly utilized caffeine can positively affect circadian rhythms. By blocking adenosine receptors, it is particularly effective in situations of an overactivated HPA axis and prevents its degenerative effects on the body.


Chronic stress and its effect on the overproduction of cortisol leads to exhaustion of the organism. Burnout syndrome is a well-known bogeyman in today's society and although we know about this health risk, we do not take preventive steps.

Cortisol is always trying to gather energy tofight or flight to save us from stressors, but we don't use this stored energy. Because the energy is ready to solve the problem, it is missing elsewhere. With prolonged energy deprivation, the body then collapses.


Apart from the most perfect way, i.e. solving the problem - the stressor, we can support our body (and mind) with the right lifestyle. With healthy food and adequate exercise. With moderate physical activity, i.e. one that does not cause too much exertion and thus additional stress,serotonin, dopamine and endorphin are released into the body . These substances reduce excess cortisol. Among the best stress fighters are meditation, yoga and proper sleep.

You can support your body by taking antioxidants to deal with oxidative stress.Roasted coffee is among the first on the list of the most effective antioxidants . A walk or a stay in nature, which Japanese scientists call shinrin-yoku therapy, also has a beneficial effect on our immune system . It is therefore advisable to combine these healthy and more than pleasant activities and go for a walk in the woods with your coffee in a thermos.