Did you know that the word hormones comes from the Greek (from horman) and means “to drive, to move”? I think that fits perfectly, because hormones and neurotransmitters actually play a decisive role in the process of anxiety. I wrote about their brain circuitry in the last blog (here). Hormones and neurotransmitters are so-called “messenger substances”. While hormones are produced at a specific location in the body and transported in the blood to their site of action. In contrast, neurotransmitters are messenger substances that act between two nerve cells, either activating them or blocking them. The distinction is not as sharp as described here, however, because some substances can act as both hormones and neurotransmitters. This applies, for example, to the neurotransmitters serotonin and (nor)adrenalin, which are important in the anxiety process.

The messenger substances and the brain have a very close relationship, because the entire brain is flown through by numerous messenger substances. All messenger substances in our body interact with each other in a way that is still not fully understood. We do know, however, that their communication with each other works via so-called heteroreceptors (a receptor that recognises not only its own neurotransmitters but also those of neighbouring cells). Here they inform each other about the current state of release. In other words, as soon as the secretion of one neurotransmitter changes, so does that of the others. The extreme complexity results from the numerous different forms of the receptors, the different dependence of the individual neurotransmitters on each other and the often shared starting substances for the synthesis of different neurotransmitters.

Are there also anxiety circuits in the hormonal system?

There are actually two interrelated circuits:

In a fearful situation, the hormone CRH (corticotropin-releasing hormone) is first released in the hypothalamus. This stimulates the production of the hormone ACTH (adrenocorticotropic hormone) in the anterior pituitary, a part of the diencephalon. And this in turn stimulates the production of cortisol in the adrenal cortex located at the top of the kidney.
Simultaneously with the information from the hypothalamus to the pituitary gland, the amygdala also activates the autonomic sympathetic nervous system in such a situation, which in turn triggers the release of adrenaline and noradrenaline in the adrenal medulla in a ratio of 80:20.

The first of these circuits accompanies anxiety and stress – brain-guided – in the long term. Whereas the activation of the autonomic nervous system is basically intended for acute situations. When stress or anxiety keep the first circuit going for a long time, the autonomic process starts at a higher level of activation. As a result, situations that do not actually seem threatening trigger an extreme fear reaction – which in turn increases the stress level. In addition, the body needs cortisol as a precursor for the production of adrenalin. With a high cortisol content, there is always enough material for an excessive fear reaction.

What do we know about the messengers of these cycles?

Cortisol

Cortisol is known as THE stress hormone par excellence. It is the body’s most important glucocorticoid and, like all other hormones in this group, is produced in the adrenal cortex. The hypothalamus, which controls the release of cortisol, also contains the suprachiasmatic nucleus (SCN) – the centre of our chronobiology. (For more on sleep, see my sleep guide). The SCN also influences the release of cortisol. In the rhythm of the day, it activates cortisol secretion with the onset of light and continuously reduces it throughout the day. Thus, stress-induced elevated cortisol levels disrupt this control function and lead to worsened sleep. And this, in turn, increases the stress level – a self-reinforcing loop is created.

Almost every cell in our body has tens of thousands of receptors for glucocorticoids. You can see how important this hormone is for numerous processes in our body. Cortisol increases the heartbeat and blood pressure and thus the number of breaths. It provides energy by increasing the blood sugar level (via the hormone insulin). Using the hormone adrenaline, it regulates the release of energy from the fat cells. It prevents excessive reactions of the immune system and has an anti-inflammatory effect. And finally, it increases our attention and influences how we process information.

These numerous functions explain why there are other lifestyle factors besides stress that increase cortisol levels: Coffee, white flour products and sugar, as well as unhealthy fats.

Adrenaline or epinephrine

Adrenaline is secreted in the adrenal medulla during physical or mental stress. Two amino acids (tyrosine and phenylalanine) are necessary for its production. From these, first noradrenaline and finally adrenaline are produced via the intermediate stage dopamine (see below) and with the help of cortisol.

Similar to cortisol, it has the same function in the body – in its role in the fight-or-flight reflex, it increases blood pressure, heartbeat and respiration, as well as dilating the pupils, and at the same time immobilises the intestines and bladder. Furthermore, like cortisol, it is responsible for providing energy from the body’s fat and sugar stores. Because of its connection to cortisol, it is influenced like the latter by stress and lifestyle.

Adrenaline not only acts as a hormone, but also exists in the brain as a neurotransmitter. This is apparently produced there, because the hormone cannot cross the blood-brain barrier. As a neurotransmitter, adrenaline seems to be involved in the activation of adrenaline hormone production from the hypothalamus to the adrenal medulla.

Noradrenalin

As an intermediate stage in the production of adrenaline, this hormone is also a neurotransmitter and plays a major role in increasing blood pressure. Unlike adrenaline, however, the main sphere of action of this neurotransmitter is in the brain. There, it is primarily involved in the activation of the sympathetic nervous system. It also controls attention as well as stress and anxiety. In the meantime, one has even identified the brain region that is considered the most important region for this neurotransmitter (the locus coeruleus). Activation of this region leads to significantly more symptoms of stress and anxiety. Therefore, it is considered the brain region whose activity we can best read our reaction to stress. For some professions, it would certainly be quite helpful to know this measure – e.g. for policemen or even doctors in the emergency room. However, it is not yet possible to put every candidate in an MRI while stimulating this brain region 😉 (source).

So, what can you do to prevent a self-reinforcing effect of these circuits?

In addition to the measures presented in the last blog to stabilise the corresponding brain regions, it is helpful to strengthen the function of the adrenal glands. To do this, it is helpful to ensure a sufficient intake of pantothenic acid, tyrosine, magnesium and vitamin C. Good sources of pantothenic acid and tyrosine are meat, fish and eggs, but also legumes, and for vitamin C especially citrus fruits and berries.

In addition, it is a good idea to optimise the production of the corresponding neurotransmitters through an adapted lifestyle, since the so-called lifestyle components are the main cause of excessively high cortisol and/or adrenaline levels.

Well, I am not an ascetic and I do not believe that nature has destined us to be ascetics. However, she didn’t design us for excessive consumption of sugar, white flour, coffee and alcohol either. And she had an anything but sedentary lifestyle in mind for us. Therefore, in addition to avoiding the above-mentioned foods as far as possible, it is important to take moderate (important: no extremely strenuous) exercise, e.g. yoga, cycling or hiking.

Well, you probably already know this advice. They are not surprisingly new. BUT: they are the factors that can best be influenced by yourself to reduce your anxiety and stress symptoms.

Are the messenger substances of these circuits the only ones relevant to anxiety?

No, as described above, the system is very complex. Therefore, numerous other messenger substances are involved in this process.

GABA, glutamate and serotonin

It has been found that the balance of the neurotransmitters serotonin, GABA and noradrenalin is disturbed in people with anxiety. So let’s take a closer look at these too.

GABA and glutamate

Let’s start with GABA (gamma-aminobutyric acid). 70% (!!) of the neurons in the brain work with either GABA or glutamate. Both messengers are synthesised from the same substance – glutamine – but glutamate is the precursor of GABA. They are responsible for such different tasks that they can be described as opponents. While GABA has mainly a mentally relaxing function, glutamate is responsible for keeping us alert, learning and remembering. Both also have other functions that are irrelevant to our context, but they are interdependent and can inhibit each other. This is especially important with regard to glutamate, because brain cells die when the glutamate level in the brain is too high.

Studies on the question of whether glutamate – which is often used in food production as a flavour enhancer – can enter the brain from the blood are confusing and controversial. It seems to be the case that in a healthy body the blood-brain barrier is closed to glutamate, but that different framework conditions can create opportunities for it to penetrate (source).

Serotonin

Another messenger substance is important for GABA, glutamate and, incidentally, (nor)adrenaline synthesis: serotonin, which is produced from the starting substance tryptophan. This neurotransmitter increases the ability of certain receptors to absorb messenger substances. Serotonin also has its own part in the anxiety-stress process, but rather – like GABA – as a helpful antidote. It is also called the “happiness hormone” because it has a mood-lifting effect. Serotonin is the precursor of melatonin and thus responsible for good sleep. Unfortunately, serotonin is mainly produced in the deep sleep phase, so that a further vicious circle opens up here in the case of sleep disorders.

It is not for nothing that research concentrates on the messenger substance serotonin for the production of medicines. A lack of serotonin is considered essential for triggering anxiety, panic attacks, depression and aggression. Researchers are particularly interested in the genetically determined different types of serotonin receptors. For example, it is known that a shortened variant of the gene 5-HTTLPR leads to an increased reaction in anxiety-inducing situations (source). However, as in all other cases, this does not mean that we are helplessly in the hands of our genes, but only that we may have to take even better care of ourselves.

A surplus of serotonin can also cause anxiety because of the possibility of hallucinations. However, this excess cannot be achieved naturally. It can occur with an overdose of psychopharmaceuticals to increase the serotonin level (so-called serotonin reuptake inhibitors – SSRI) or the intake of LSD.

How can you detect a deficiency of serotonin and GABA?

Determining a deficiency through a blood test is difficult, because – due to the blood-brain barrier – a statement about the concentration of these substances in the blood is not really helpful. On the other hand, the vitamins that support the production process can also be detected very well in the blood test.

You can also suppose a deficiency of GABA or serotonin on the basis of some symptoms. Problems falling asleep and sleeping through the night can indicate a lack of serotonin, but also of GABA. If you also suffer from muscle tension and cramps as well as increased pain despite an adequate supply of magnesium and sodium, it could indeed be a GABA deficiency. If the sleep problems are accompanied by mental changes such as exhaustion, irritability or depressed mood as well as a decline in sexual desire, a serotonin deficiency is more likely.

And what can you do about a recognised deficiency?

In order to positively influence the levels, it makes sense to consume the starting substances for this in a useful quantity. Glutamate is an exception. Because glutamate is used as a flavour enhancer in food, you have to be careful not to take too much of it. So try to get a good supply of tryptophan. A treat for all sweet lovers: Bananas, chocolate and dates contain a lot of tryptophan.

Vitamins B6 and D are also essential as supporting factors for serotonin synthesis. According to studies, omega 3 also increases the sensitivity of the serotonin receptors. Food with a high B6 content is mainly meat – vegetarians and vegans should therefore keep an eye on their supply of B vitamins. Omega 3 is practically unobtainable for us today through food – due to mercury, lead and increasingly microplastic contamination of fish. For the same reason, you should question the production of appropriate food supplements for purification from these residues. Alternatively, you can use omega-3 oil from algae for this purpose.

Dopamine

Another neurotransmitter is involved in the development of anxiety – dopamine. Anxious people have an above-average concentration in the amygdala. As already explained above, the amino acid tyrosine is the starting material not only for the synthesis of dopamine, but also of (nor)adrenaline. Two centres in the brain are known for the synthesis of dopamine according to its tasks. The first is located in the substantia nigra of the midbrain and controls voluntary movements. The second centre is located in the ventral tegmentum, also in the midbrain, and functions as a reward system. If the amount of dopamine in this part of the brain is increased, it has a stimulating effect – but also very quickly produces addiction.

Researchers are also using these properties to help people unlearn fears – but this research is still in its early stages.

There are also genetic predispositions for our dopamine levels. For example, the genetic disposition for specific dopamine receptors has something to do with how willing one is to engage in high-risk sports (source). In addition, researchers have found that a specific gene responsible for dopamine transport in the brain is five times more common in top athletes than in the control group (source).

This makes dopamine another neurotransmitter for which it is important to keep a balance between too much and too little – depending on your own disposition. Too much dopamine makes you anxious, too frequent stimuli of the dopamine centre make you addicted and too little dopamine makes you listless and reduces your attention.

How can you balance your dopamine levels?

Since the starting material is a non-essential amino acid, but it is often made from the essential amino acid phenylalanine, it makes sense have a balanced diet of foods that contain both of these amino acids. These are mainly eggs and dairy products, turkey and beef, but also some legumes. Sorry for the vegans among my readers, but that’s just the way it is – we are designed to be omnivores.

Sport is a very sensible measure, especially for our reward system. After only 10 minutes of aerobic exercise (i.e. below 80% of your heart rate), an improvement in mood has already been observed. It is highest after 20 minutes. In one study, participants who did a one-hour yoga session a day, six days a week, were able to significantly increase their dopamine levels. However, given today’s lack of time, even the small 20min sessions may be sufficient.

Another great way to increase dopamine levels in the brain is to listen to music without words that gives you goosebumps. In one study, this increased dopamine levels in the brain by 9%. Source

 Oestrogen (estradiol)

One of the three hormones grouped under the general term oestrogen is estradiol, which also seems to be related to anxiety and depression symptoms. For example, studies have shown that high levels of estradiol protect against strong expressions of anxiety. The study involved men and women with and without taking hormonal contraceptives. It was noteworthy that the difference in estradiol levels between the women played a greater role in reducing anxiety than the difference between men and women (source). The women taking hormonal contraceptives had reduced levels of their own oestrogen secretion. In addition to all the other known side effects, which also result from the extreme complexity of our hormonal balance, hormonal contraceptives are certainly not a good choice in cases of anxiety. See also this study from Denmark (source).

Thyroid hormones

The thyroid gland and thyroid hormones also play an important role in the development of anxiety. We know from studies, for example, that autoimmune inflammation of the thyroid gland is apparently an underlying factor in many anxiety disorders (source). A factor that is often not recognised and therefore not treated appropriately. So if you have an anxiety disorder (if you’re not sure, my questionnaire might help), it’s important to have your doctor check all of your blood values that could indicate autoimmune inflammation of the thyroid gland.

Also, hyperthyroidism can lead not only to symptoms we commonly associate with anxiety – sweats, rapid heartbeat and insomnia. It can also lead to anxiety disorders due to the disturbed balance of thyroid hormones and the resulting imbalances in the overall hormonal balance. Hypothyroidism, on the other hand, can be the first sign of autoimmune inflammation of the thyroid gland.

So, what can you do to protect your thyroid?

Important: Take selenium – a totally underestimated metalloid. It is involved in numerous processes for the production of various proteins in our body, including the necessary thyroid hormones (T3/T4). Due to the insufficient supply of selenium in our soils – and consequently in all foodstuffs grown on them – the population in Germany has in the meantime become significantly undersupplied with selenium. Such an undersupply can lead to Hashimoto’s thyroiditis – an autoimmune inflammation of the thyroid gland. This is particularly relevant in Germany, because as many as 10% of Germans carry the genetic predisposition for it. Interestingly, selenium also has a mood-lifting effect – yet another reason to pay attention to an optimal intake. A good source of selenium is, for example, Brazil nuts (organic only, please). However, too much selenium is also harmful, so you should only take selenium for a short time and after consulting a therapist. (More information about selenium can be found here: Source).

In principle, the same applies to iodine intake. Here, too, a balance must be maintained between too much and too little, as both extremes lead to problems with the thyroid gland (source).

What other general recommendations can I give you on this topic?

Especially with regard to the hormonal balance in your body for recognising, avoiding or reducing anxiety, it is important to have your blood tested regularly for the necessary minerals and vitamins. And even though there are already self-tests for some substances, I recommend that you have your blood taken by a doctor or non-medical practitioner. Even though not all tests are paid for by the public health insurances, this is, in my opinion, always money well invested, because otherwise you will have to use supplements on suspicion, which can turn out to be much more expensive in the end. When discussing the results, please note that the values for vitamins, minerals and proteins are often only oriented towards ensuring that no deficiency symptoms occur. Doctors and non-medical practitioners specialising in environmental medicine are therefore a safe choice for evaluation.

Conclusion:
The balance of messenger substances in our body is best maintained with a natural diet and lifestyle – which is difficult for most to maintain due to societal conditions. Paying attention to the situation and following the results of the research is therefore the obvious next choice.

I hope to have given you a few tips and more knowledge and remain as always

Yours, Claudia

P.S.

For all the dietary supplements I have mentioned in this blog, you will soon find on my site the dietary supplements I have tested and found to be good, with a short description – helpful if you don’t feel like working your way through the sheer confusing jungle of offers.