Caffeine Sensitivity: Symptoms and Treatment

Why does a person fall asleep?

Humanity has been dealing with sleep issues for a very long time, but this topic (like any other) has not been fully studied, although there are a number of good concepts. Pioneers in sleep research hypothesized that there was a sleep factor, a substance that accumulated during the day and caused drowsiness [1]. It is believed that the Japanese physiologist Kuniomi Ishimori was the first to try to isolate the sleep factor [2]. Also among the first were René Legendre and Henri Piéron, who induced sleep in dogs by injecting them with a substance obtained from the brains of other sleep-deprived dogs [3].

Modern scientific evidence suggests that adenosine is well suited for the role of a sleep factor. Adenosine, a ribonucleoside consisting of adenine and ribose [4], plays a huge role in our body. It is a component of the genetic material of cells, in addition, it is part of the “energy” compounds in our body - such as adenosine triphosphate (ATP). It has a number of other functions, but for the purposes of this article, the interesting one is its role as a signaling molecule with broad physiological effects, both in the brain and beyond. For its functions, adenosine was even nicknamed the signal of life [5] and the body's natural defense [6].

Diagnosis of coffee allergy

Before talking about the fight against coffee allergies, it is necessary to finally and unambiguously diagnose intolerance by performing special tests. Modern technologies allow testing for specific allergens. After consultation with a doctor, you should be offered the best diagnostic option. Patients may be asked to undergo skin testing, computer-based bioenergetic diagnostics, or diagnostic hair and blood tests.

Allergy skin testing involves injecting small doses of an intolerant substance under the skin to test for a reaction. Allergy symptoms will certainly appear if antibodies are present in the body. If an allergen is detected, the enzymatic desensitization technique can be used - this is a special procedure for minimizing the sensitivity of the allergen to drugs.

In hair testing, a small number of immunoglobulins (that is, antibodies) are added to the patient's hair. After this, it is necessary to determine whether the reaction occurred or not. An allergic reaction can be detected using a computer examination or a special microscope. When diagnosing by blood, it is necessary to take into account all immunosorbents. Such diagnostics are quite complex; during the procedure, the competition of natural and specific immunoglobulins that are found in the body is determined.

With such a diagnostic method as radionics, you need to be very prudent and careful. This method can only be used if the other diagnostic procedures described above have been previously carried out.

[10], [11]

Where does adenosine come from in the brain?

There are several sources:

1. ATP hydrolysis [7].
2. The result of the activity of glial cells [1].
3. Others [7].

But the main supplier is ATP. The human brain consumes up to 25% of the body’s total energy [8]. He gets it mainly from adenosine triphosphate. From the abbreviation you can understand the structure of the molecule: adenosine and three phosphate molecules. Energy is released through the hydrolysis of ATP. In one of his lectures at Postnauka, Vyacheslav Dubynin gave a good analogy with this process [9]. He compared ATP hydrolysis to shooting from a pistol. There are only three shots (three opportunities to split off the phosphate molecules), and each shot releases energy that the body's cells use for various processes. And after three shots, as you might guess, only an adenosine molecule remains. During the day, adenosine accumulates, both intracellularly and extracellularly. Intracellular adenosine leaves the cell using special transport systems.

Next, adenosine begins to interact with adenosine receptors (Fig. 1) [7], [10]. There are four types of receptors in total: A1, A2A, A2B, A3. They are located on neurons, as well as on cells of other organs (heart, kidneys, etc.). All four types are combined into the superfamily of G protein-coupled receptors (GPCRs) [7], about which there are many interesting articles on Biomolecule. You can read more about the 3D structure of adenosine receptors in the article “Structures of GPCR receptors in the piggy bank” [11]. Each of these receptors has its own ligands (substances that bind to the receptor) - agonists and antagonists. “So, what else is this?” - you ask. Nothing complicated really. Agonists are substances that can bind to a receptor and lead to a specific effect (positive or negative). Antagonists can only bind to the receptor, but this will not lead to any effect. So, essentially, they block the receptor from binding to the agonist. What are the agonists and antagonists for adenosine receptors? In fact, there are many substances (if you are interested, you can read about it in [4]), but I will consider two of them: adenosine and caffeine. The former is an agonist and the latter an antagonist of adenosine receptors [7], [10].

Another article about adenosine receptors is participating in the competition: “Adenosine receptors: the story of the great deception” [12]. - Ed.

Figure 1. Structure of adenosine and its mechanism of action. The chemical formula of adenosine is presented, where oxygen molecules are indicated in red and nitrogen molecules in blue. As depicted in the figure, the receptor consists of exactly seven domains—a distinctive feature of all four types of adenosine receptors. The pink flow reflects the effect of adenosine on the cell.

drawing by the author of the article

So, what effect does adenosine have when it binds to receptors? The role of adenosine in sleep induction has been well studied [1], [13–16]. Essentially, it makes us sleepy, albeit with some caveats, and this is a very interesting mechanism. Brain cells work for a long time, a lot of adenosine accumulates, it binds to adenosine receptors, and the cells receive a signal that it is time to “rest.” These processes allow neurons not to overstrain.

However, if you go deeper, everything is more complicated. Not all mechanisms are still understood. By interacting with different receptors, adenosine leads to different effects. Moreover, there is evidence that by interacting with the same receptor (for example, with A1A) in one region of the brain, adenosine can induce sleep, and by binding in another - awakening [1].

Treatment of allergy to coffee

• You should completely avoid coffee and other drinks containing caffeine.

• It is necessary to take sorbents orally, for example, Polysorb, Enterosgel. These drugs perfectly remove toxins from the body, but in this case they will additionally help get rid of the allergen. Which will promote recovery and cleansing.

• For severe itching and headache, it is recommended to take any sedative. It is permissible to use drugs in tablets, or brew your own decoction from a collection of herbs (motherwort, mint, etc.)

• Also apply antiallergic ointment (Lorinden, Flucinar) to the skin, or use natural remedies (decoction of oak bark, chamomile, string).

Herbal preparations are used only if there is no allergy to them, otherwise the situation may worsen.

• In case of serious disorders in the digestive system (prolonged diarrhea, vomiting), it is necessary to take enzymes (Pancreatin, Festal), these drugs will help the functioning of housing and communal services and the absorption of food.

• When vomiting, it is recommended to take Regidron powder and Lactofiltrum tablets orally. These remedies will eliminate dysbiosis and restore intestinal function.

• In severe cases of allergies, angioedema and bronchial spasms, hormonal drugs are prescribed in combination with complex antihistamine treatment.

But in any case, if such an allergy is detected, you must completely and forever stop drinking coffee. You should replace this drink with any other that does not contain caffeine.

Let's get down to business

What do you think coffee, tea, chocolate, energy drinks and cocoa have in common? They all contain caffeine. Yes! After a little background, I’ll move on to it. Caffeine is a chemical compound from the class of alkaloids [17]. It is the most widely used psychostimulant substance [18–22] and has a number of physiological and biochemical effects. Caffeine affects the nervous, cardiovascular, respiratory, excretory systems, and components of the gastrointestinal tract.

Caffeine is found in seeds, beans, and leaves of a large number of plants (coffee, tea, cocoa, etc.). It is consumed mainly in the form of drinks (coffee, tea, energy drinks), chocolate and chewing gum, but is also found in toothpastes. Currently, the caffeine content in various food products has been calculated [23].

Up to 99% of consumed caffeine is absorbed into the blood within 45 minutes [24]. In plasma, its concentration peaks between 15 and 120 minutes after oral administration [24].

How does caffeine affect the human body? Its effects are concentration dependent. In moderate doses, it causes such positive subjective effects as a surge of energy, increased activity, sociability, and general well-being. In large doses, it can lead to a strong increase in blood pressure and other bad phenomena. What are the recommendations for caffeine consumption? Up to 400 mg/day for adults, up to 300 mg/day for pregnant women, up to 2.5 mg/kg/day for children and adolescents [20].

Almost all of caffeine's effects are due to its role as an adenosine receptor antagonist (Figure 2). The fact is that caffeine has a similar structure to adenosine, due to which it can bind to its receptors. But it does not have any stimulating or suppressive effect on cells. Caffeine simply blocks the receptors for adenosine. The latter does not realize its effects and “artistically yearns from his grief,” as Andrei Kurpatov writes (though he is not entirely talking about caffeine). This point is key to understanding the physiological effects of caffeine. It doesn’t add any energy, it simply doesn’t allow the neurons to receive the signal that it’s time to take a break and rest. At this time, a person feels an incredible surge of strength... But, as one might guess, it is imaginary. All this lasts approximately 2.5–4.5 hours [24]. Why exactly so much? This is the so-called half-life , or half-life , - the period of elimination of half of the substance entering the body. Once it expires, the effects of this “energizing drink” quickly wear off. Adenosine binds to receptors freed from caffeine, and the person is tired again and wants to sleep.

Figure 2. Structure of caffeine and its mechanism of action. The chemical formula of caffeine is presented, where oxygen molecules are indicated in red and nitrogen molecules in blue. There is no pink stream, as in the previous figure - caffeine has no effect on cells, it only blocks the adenosine receptor.

drawing by the author of the article

As I wrote above, adenosine receptors are not only found in the brain. They are present in both the heart and kidneys. The physiological effects of caffeine on the activity of these organs may also be explained by blocking adenosine receptors. If adenosine interacts with receptors in the heart and kidneys, it leads to inhibition of their activity. If caffeine blocks the receptors, this manifests itself as tachycardia (increased heart rate) and polyuria (increased urination). These effects are most likely familiar to you from personal experience.

Recently, the therapeutic potential of caffeine in relation to neurodegenerative diseases such as Alzheimer's, Parkinson's, etc. has been widely discussed in the scientific community [25], [26].

Symptoms of coffee allergy in adults

How does a coffee allergy manifest? The signs are very varied...

From the skin side (see photo):

• reddish rashes on the skin, of varying diameters, from small dots to huge spots;
• itching and burning in the affected areas;
• sometimes peeling of the skin on the face occurs: around the nose, in the corners of the lips, on the cheeks and chin;
• in some cases, if you do not stop drinking the drink, dermatitis appears.

From the respiratory system:

• inflammation of the nasal mucosa, congestion;
• release of nasopharyngeal moisture;
• frequent sneezing;
• swelling of the throat;
• worsening breathing;
• in rare cases - Quincke's edema;
• If you have asthma, there is a risk of spasms in the bronchi.

From the digestive system:

• there is discomfort in the stomach or intestines;
• heartburn;
• nausea and vomiting;
• diarrhea.

• increased drowsiness or excessive excitability appears;
• chills;
• headache and dizziness;
• arrhythmia is clearly expressed (increased heart rate, increased pulse).

Is caffeine addictive?

If you follow the latest ISD-11 (International classification of diseases, 11th revision - ICD-11, International Classification of Diseases 11th revision) from the World Health Organization, then yes, caffeine addiction is a mental disorder [25]. The DSM-5 (Diagnostic and statistical manual of mental disorders, 5th edition) from the American Psychiatric Association identifies caffeine use disorders as an area for further research [28], [29]. . Also, the DSM-5 describes a diagnostic scheme with nine criteria for making a diagnosis of Caffeine Use Disorder [29], [30]. Below are three main ones:

1. Constant and unsuccessful attempts to reduce and control caffeine intake.
2. Continued use of caffeine despite knowledge of a physical or psychological problem.
3. Withdrawal syndrome or the use of caffeine to relieve this syndrome.

It is important to note that not all people become addicted to caffeine. For its development, certain conditions are necessary (high dosages of caffeine, simultaneous consumption of various caffeine-containing products, etc.) [30].

What is withdrawal syndrome ? WHO defines it as follows: it is a group of symptoms of varying clustering and severity that occur when the use of a psychoactive substance that has been used repeatedly, usually over a long period and/or in large doses, is stopped or reduced [31]. That is, in essence, this is a “breaking”, excuse the jargon. So, when a person does not consume caffeine for several hours (from 12 hours [22]), he begins to experience the following symptoms (Fig. 4):

• headache;
• fatigue;
• decreased energy;
• decreased attentiveness;
• drowsiness;
• irritability;
• problems with concentration;
• depressed mood;

and others [23].

Figure 3. Basic symbols for the following pictures

drawing by the author of the article

Figure 4. The mechanism of withdrawal syndrome formation in caffeine addiction. In the picture, 45 minutes and 2.5–4.5 hours correspond to the absorption time of caffeine into the blood and the half-life of caffeine, respectively. 12–24 hours reflects the average amount of time a person goes without consuming caffeine before experiencing withdrawal symptoms.

drawing by the author of the article

On the Internet, caffeine is often called a drug, but scientists have not reached a consensus on this issue. But we can say for sure that caffeine does not have the same impact on a person’s social life as drugs like opioids [32] or LSD [33].

Signs of a coffee allergy

Can you be allergic to coffee? And why, in fact, not, an allergy to coffee is simply a type of food allergy associated with individual intolerance to caffeine contained in any invigorating drink.

Causes significant inconvenience and forces you to partially or completely stop drinking coffee. There are both one-time symptoms and a chronic form.

In the first case, they disappear within a few hours after consuming the drink and do not occur regularly; in the second, they persist permanently and progress after repeated use.

Are tolerance and addiction the same thing?

It is necessary to distinguish between these two concepts. If addiction means the body's need for caffeine, then tolerance means the body's immunity to caffeine. What does it mean? This means that caffeine does not exhibit its physiological effects for a number of reasons.

How does caffeine tolerance develop? There are a number of concepts for its formation. A striking example is the concept of an increase in the number of adenosine receptors in response to long-term intake of high doses of caffeine [14], [34]. How does all this happen? See Figure 5 and read the text below.

Figure 5. Mechanism of caffeine tolerance formation. The picture shows the consistent change in the effect of caffeine on the body. At first, caffeine has an invigorating effect, but then has no effect on the body due to the formation of new adenosine receptors. An increase in the number of filled circles reflects an increase in the amount of adenosine, caffeine and improved well-being. A decrease in the number of filled circles reflects the opposite processes.

drawing by the author of the article

I'll use one of the main sources of caffeine - coffee. Caffeine tolerance is typical for people who drink coffee in large quantities and on a regular basis. This usually happens in the morning or during a break between work/study. They drink it for various reasons: it helps them wake up, it smells delicious, it gives them energy, or they want to feel like they’re part of that crowd running around the metropolis (fashionable, in short). Well, in general, after drinking coffee, a person feels like “king of the hill.” You don’t want to sleep, your heart starts beating faster, you feel an incredible surge of energy, and sometimes you want to go to the restroom. The mechanism here is still the same - blocking adenosine receptors.

The fact is that with chronic caffeine consumption, adenosine cannot attach to its receptors. The body sees that there is a lot of adenosine, which means it has nowhere to cling to - there are few receptors! In response to this, new adenosine receptors are synthesized in the brain. This is where adenosine successfully interacts with them, and the person begins to feel drowsiness and fatigue, although he continues to drink coffee in relatively large quantities.

So, one regular dose of caffeine is no longer enough. The person begins to drink more. And everything goes the same way. At first it will help, but then it won’t (new receptors are formed again). I hope you get the point.

Causes of coffee allergies

It does not appear often, because caffeine is not a strong allergen. But the appearance of such a reaction may indicate excessive coffee consumption, or internal disorders in the body, such as:

• diseases of the digestive system;
• immune system disorders;
• improper metabolism.

What's the result?

Caffeine is the most widely used psychostimulant substance, which has both positive and negative effects on our body, therefore its consumption should be approached rationally. Therefore, the next time you have a deadline, before you drink a couple of cups of coffee or energy drinks, think, maybe it’s better to sleep? (This is if the deadline is not tomorrow morning, God himself ordered it, of course.) Well, if you drink several cups of coffee a day, then I hope this article will be the impetus for you to create a new useful habit (reduce caffeine consumption)!

To better understand and consolidate this information, I highly recommend re-reading this article again, going to the cited literature, watching videos on YouTube (for example, this one: original in English and version in Russian translation) or printing out my poster (Fig. 6).

In conclusion, I would like to thank all the people who helped me identify and correct errors in this article.

Figure 6. Effect of caffeine. You can download the poster in pdf format from this link.

drawing by the author of the article

Preventing coffee allergies

To prevent an allergy to coffee, simply follow some instructions. This:

• Reduce drink intake to 2 cups per day, especially if it is a grain drink;
• Do not abuse products containing caffeine;
• Reduce consumption of cola and the like;
• It is recommended to monitor the functioning of the digestive system;
• In the presence of chronic diseases, regularly carry out maintenance treatment.

So, we have decided that coffee, like any other food product, can cause allergies. Symptoms can most often be found on the face and other skin, but they also occur in the respiratory and digestive systems. If all precautions and recommendations are followed, coffee allergies can be treated quickly, without complications.

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