Do you suffer from constant fatigue, a feeling of exhaustion, weight gain, irritability or inability to enjoy yourself? At first glance, banal difficulties that we wave our hands over. Whether you are a manager by profession or "just" the manager of your life in today's hectic times, it can be a so-called the broom of managers or adrenal fatigue.

Do we have in our DNA how to manage stress? Why choose genetic analysis for these problems?

 Simply put, adrenal fatigue or adrenal fatigue describes a condition caused by chronic exposure to stressful situations. These lead to "overloading" of the adrenal glands, and they respond by increasing the production of cortisol, the stress hormone. Currently, we face several challenges - economic, environmental, health or psychosocial, and we are exposed to pressure, chronic stress, which stimulates the constant production of stress hormones. However, our adrenal glands were not designed for that much cortisol. If we are constantly under stress, which builds up and stressors increase, the adrenal glands are slowly exhausted and their fatigue occurs. You may be troubled by non-specific problems such as fatigue and a feeling of exhaustion even after sufficient sleep and regeneration, difficult getting up, sleep problems, anxiety, easy irritability and mood swings, weight gain and inability to lose weight, etc.

We live in a time full of stressors

A more complex view suggests that the symptoms of adrenal fatigue result from the body's normal response to stress (regardless of its cause). The hypothalamic-pituitary-adrenal (HPA) axis is set in motion, releasing hormones and other substances produced to cope with stress. At the end of this axis are the adrenal glands, which secrete the hormone cortisol. Its purpose is to limit the effects of stress on the body. Normally, when the stress is gone, cortisol levels drop and the adrenal glands have a chance to recover. But if the stress persists, the demands on the adrenal glands are pushed to an extreme level. At a certain point, the adrenal glands are no longer able to secrete the required amount of cortisol. The stress response system becomes irregular and the production of cortisol but also other substances such as adrenaline or noradrenaline is disturbed, and ultimately leads to hormonal imbalance.

Adrenal fatigue is also referred to as a syndrome precisely because of the different symptoms that often go together, although at first glance they do not seem to come from a single cause. Officially, this condition is not considered a disease and we would look for it in the list of medical diagnoses in vain.

Cause and effect

The main cause of adrenal fatigue is stress, especially chronic, unrelenting stress.

Stress can be defined as any change that causes physical, emotional or psychological strain. It is your body's response to anything that requires attention or action. Everyone experiences stress to some degree, and the way we react to it greatly affects our overall well-being.

Stress reaction it is mediated by an interplay of neural, hormonal and immune mechanisms that include activation of the sympathetic-adreno-medullary (SAM) axis, the hypothalamic-pituitary-adrenal (HPA) axis and the immune system.

The stress response has two components – a fast response mediated by the SAM axis and a slow response mediated by the HPA axis. A rapid response will increase the secretion of catecholamines (dopamine, epinephrine, norepinephrine, etc.) from the adrenal medulla into the circulation and from the sympathetic nerves, leading to an increased level of catecholamines in the brain. By activating the sympathetic nerves, the adrenal glands are activated and the HPA kicks in.

The slow response is triggered by activation of the HPA axis, which leads to the release of corticotropin-releasing hormone (CRH) from the hypothalamus into the circulation. CRH stimulates the anterior pituitary gland to release adrenocorticotropin hormone (ACTH) into the bloodstream. ACTH stimulates the adrenal cortex to secrete glucocorticoid hormones such as cortisol, into circulation.

Our body's ability to recover from stress is absolutely essential for our health.

The body carries out this process in the background - we are not aware of it, of course, but there are certain problems, such as mutation of the COMT gene, which may limit this process. You may struggle with a deteriorating health condition for a long time without an obvious cause. This, combined with chronic stress, can create ideal conditions for health problems such as adrenal fatigue syndrome.

The warrior gene

COMT gene, fight/flight gene or "warrior gene" (as it can be found in a DNA test BODY4FIT+) helps create the essential enzyme catechol-O-methyltransferase, one of the two main enzymes responsible for breaking down catecholamines, drugs, and substances that have the same catechol structure. The COMT gene is expressed in the brain and is associated with anxiety, pain and stress response.

This gene determines how you react to stressors and predicts whether you are more of a fighter or a fearful type of person.

In stressful situations, elevated dopamine levels in GG (fighter) genotype homozygotes provide an emotional advantage compared to AG (more fearful) or AA (worried) genotype carriers, who show increased reactivity to stressful stimuli.

So, if you are a carrier of the AG or AA genotype, your body will have difficulty processing and getting rid of substances with a catechol structure. This means that you can experience higher levels of these substances and their metabolites for a longer period of time (longer coping with stress = longer persistence of stress).

The enzyme COMT is essential in methylation, a biochemical process in which hydrogen and carbon atoms are transferred from one substance to another. It is part of cellular repair, where it plays a major role in the synthesis of nucleic acids and the production of DNA and mRNA. It helps in the production of neurotransmitters and detoxification by converting amino acids. Methylation is critical in blood formation and in maintaining a healthy immune system.

Approximately 20–30% people of Caucasian and European ancestry have the COMT mutation.

This mutation limits the body's ability to break down and remove neurotransmitters (responsible for e.g. planning, changes in behavior, short-term memory or reactions to stress) three to four times. So, if you have a COMT mutation, your body will struggle to cope with the high levels of neurotransmitters that occur during times of stress. Neurotransmitter levels can remain elevated for a longer period of time, so you will experience stress for a longer period of time.

Ultimately, the COMT gene affects:

• your stress level,
• how you react to negative and positive emotions,
• how you react to stress
• your resistance to stress.

A mutation in the COMT gene is associated with high cortisol levels and HPA axis dysfunction. It has a powerful effect on your stress reactivity and ability to de-stress. It may play an important role in adrenal fatigue syndrome.

A mutation in the COMT gene can have a big impact on adrenal fatigue because it changes the way the body responds to stress. Adrenal fatigue syndrome occurs when we are under stress for a long time.

Our neuro-endo-metabolic (NEM) response to stress usually happens behind the scenes to help us cope with current stress, and then "turns off" when stress levels drop. But chronic stress can result in continued activation of the NEM stress response, and when it is active for a long period of time, two things happen:

•  The adrenal glands become fatigued because the body needs high levels of cortisol to cope with stress. Each person's adrenal glands have different tolerance levels for this kind of overwork, but when you reach your individual limit, the adrenal glands gradually stop working as they should.
•  The six circuits that make up the NEM stress response become unbalanced when your NEM stress response is active for too long. An unnatural level of activity causes health degradation of individual components (circuits), which affects the functioning of the entire organism.

COMT and MTHFR

Methylenetetrahydrofolate reductase (MTHFR) is the enzyme responsible for methylating proteins in every single cell of your body. If you have a history of chronic migraines, irritable bowel syndrome, depression, multiple miscarriages, or a family history of heart attack or stroke, this little enzyme could be the cause.

It is ideal to know the result for both genes - COMT and MTHFR. Studies suggest that they are closely related and can influence each other and also affect the stress response. Both enzymes are involved in the methylation pathway, and MTHFR can also significantly affect the functioning of COMT. For example, if MTHFR activity is lower than normal (CT and TT genotype), it will also reduce COMT processes. And if the activity of both is reduced due to mutations, it can have health consequences, the most often proven are the disruption of psychological well-being and health.

A mutation in the MTHFR gene reduces the specific activity of the MTHFR enzyme and increases homocysteine levels. This polymorphism impairs the regulation of homocysteine and folate levels. Elevated homocysteine is considered a risk factor for atherothrombotic disease independent of other conventional risk factors.

But is adrenal fatigue real?

Many resources provide information on how to diagnose and treat adrenal fatigue. But the endocrinology society and other medical branches do not consider this condition as a nosological unit or they don't recognize him. Their statement is clear: "There is no scientific evidence to support adrenal fatigue as an actual medical condition.”

A recent review of 58 studies concluded that there is no scientific basis to consider adrenal dysfunction as a cause of fatigue. However, the authors report that the studies had some limitations. Questions arise regarding what should be tested (blood, urine and/or saliva), the best time to test, how often to test, what ranges are considered normal, or how reliable the tests are. In summary, there are no formal criteria for defining and diagnosing adrenal fatigue. So no, there is officially no such thing as adrenal fatigue.

The lack of a biological explanation can be disappointing. The overwhelming amount of information on the Internet that recommends various treatments causes even more stress.

So what can we do?

Symptoms associated with adrenal fatigue are likely to have multiple causes. Alternative and complementary medicine or preventive personal health care often have better results because appointments with a practitioner usually last longer and take into account holistic treatment.

"Our body's ability to recover from stress is not automatic, especially not nowadays. A personalized lifestyle change is essential." Pavol Pavlovič, CEO DNA4FIT

Therefore, no matter what we call it, millions of people suffer from similar symptoms and it could work for many personalized plan, which would include professional advice - lifestyle changes, especially diet and exercise. It is the basis nutritionally rich diet, with lots of brightly colored vegetables, lean proteins and whole grain sources of carbohydrates, with a limitation of simple sugars (sweets). By inclusion regular movement into our everyday life, we support the production of monoamine neurotransmitters such as dopamine, norepinephrine or serotonin, which improve our mood and mental health.

If necessary, ideally after the previous one biochemical examination, can be considered tailor-made supplementation program. By supplementing the diet, e.g. o tryptophan, it is possible to help the body in the production of serotonin and also melatonin to achieve faster falling asleep and better quality sleep. The mentioned substances play an important role in improving mental health and sleep. They can be supplemented with B vitamins₃ and B_6. But that is only one of many possible solutions.

Hormone therapy or other medications should be a last resort (after consulting a doctor, of course).

Authors: Ing. Kristína Jančichová, PhD., MUDr. Danica Bezáková, general practitioner's clinic, MUDr. Monika Bartošová, clinic for preventive and consultative examinations, Pavol Pavlović, CEO of DNA4FIT

Literature:

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