Man has tried to combat the onerous symptoms of illnesses for millennia – particularly pain and fever. Over time, natural means were replaced by drugs. Unfortunately, the drugs commonly available are frequently overused and many of them in combination with other substances have undesirable effects that can lead to serious illnesses.

dr Edyta Adamczyk-Kutera
Dr Edyta Adamczyk-Kutera

Dr Edyta Adamczyk-Kutera, doctor of aesthetic medicine, LEAPProgram Consultant

To survive, each organism has had to develop mechanisms enabling defense against threats and adaptation to changing living conditions. Guarding our organism are three interconnected systems: nervous, hormonal and immune. In case of bacteria, virus, or parasitological infection as well as injuries, the basic weapon is the triggering of an acute inflammatory state. Its role is to create a protective barrier, fight ‘the intruder’, get rid of dead cells and repair damage.

The organism can deal with most infections itself, although situations occur in which the intruder is too strong, the organism is weakened, or the triggered inflammatory state is too acute and too rapid. Serious tissue and organ damage can occur and a transition into a chronic state, gradually leading to more and more irreversible damage. Pain ailments and disability are exacerbated, and – in extreme cases – death may result.

An acute inflammatory state is characterized by typical symptoms: edema, redness, an increase in body temperature, soreness and the loss of function of the affected organ or tissue. Their exacerbation depends on the threat, the extent of damage and the strength of reaction of the immune system. While these are defensive elements, they are also onerous symptoms.

Combating onerous symptoms

For millennia man has tried to combat or weaken symptoms of illnesses, in particular pain and fever. Ancient physicians, shamans, folk healers meticulously observed plants and animals, thanks to which they acquired valuable information about their curative or poisonous properties. They used this knowledge in applying different parts of plants, insects and reptile venom as well as other gifts of nature to relieve pain, lower fever, heal wounds and many other ailments, but sometimes for malign objectives, e.g. poisoning. Garlic, onion, cranberry, raspberries, mint, black berries, blueberries, honey, willow bark, linden flower and many others were classified as natural drugs.

The causes of most illnesses were unknown and only the most burdensome and dangerous symptoms were cured, while the human organism had to manage itself.

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Willow bark – pharmaceutical muse

Gathered for centuries with their accumulated knowledge passed among generations, the arduous work – or perhaps the curiosity – of chemists stands at the heart of current pharmacy. The notes of a Sumerian doctor from around 5 000 BC refer to the curative properties of willow bark, while the ancient Egyptians used it for curing cough, rheumatic pain and otitis. Willow bark was used by Greek and Roman physicians. Hippocrates (5th century BC) recommended it as a drug for fever and labor pains, while Celsus (1st century AD) advocated it for inflammatory states, as did his contemporary the Greek physician PedaniosDioskurydes, as well asthe most famous physician of Roman times – Galen (2nd century AD). The curative properties of plants have interested chemists who since Paracelsus’ times have tried to isolate active substances from them. The 19th century was an era of successes, during the first 30 years of which morphine, strychnine, caffeine, nicotine, quinine and salicine were isolated – the last obtained from willow bark. A few years later, the hydrolysis of salicin to saligenin was successfully conducted, followed by the oxidation of the latter to salicylic acid, a much stronger substance. Physicians started prescribing the new drug primarily for rheumatic pain, but patients took it unwillingly because it was particularly unsavory and in high dosage it irritated the lips, gullet and stomach.

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W poszukiwaniu żyły złota

At the end of the 19th century an effective drug was sought for breathing ailments, troublesome cough and, most importantly, tuberculosis from which hundreds of thousands of people suffered. If it also had an analgesic activity, then undoubtedly it would become pay dirt for the pharmaceutical company that first introduced such a product to the market.

Dr Felix Hoffmann, working in the pharmaceutical department of the Bayer Company, sought an effective drug for his father whose rheumatic pain had him taking sodium salicylate which was appalling in taste, triggered nausea and irritated the stomach lining. He tried to purify salicylic acid and eliminate its properties that irritated the mucous membrane. He succeeded in the autumn of 1897 when he produced a new chemical compound acetylsalicylic acid (ASA)from salicylic and acetic acids, which was later named aspirin.

Two weeks later, however, he synthesized another substance – diacetylmorphine, soon called heroin – which relegated aspirin to second place. Run by Heindrich Dreser, the Bayer Company laboratory handled the testing of both substances. The synthetic derivative of morphine (heroin) performed significantly better as according to Dreser, ASA weakened the heart and could have had undesirable side effects. Heroin was supposed to relieve patients, allowing those suffering from tuberculosis to sleep without cough through the night, coupled with amazing painkilling benefits. Bayer immediately implemented mass production. It was demonstrated that heroin as cough medicine was ten times stronger than codeine and did not have side effects. The company planned to sell it as a remedy for newborns’ colic, colds, flu and aching joints.

In November 1898 heroin was registered as a drug. One year later Bayer produced a ton of the substance and shipped it to 23 countries. It was sold in the form of pills, syrup, and powder. A new cough syrup conquered the United States. Heroin sold brilliantly generating colossal profits for the company. Unfortunately, information began to appear about patients for whom it was necessary to constantly increase doses because of weakening curative effects. Although physicians noted classic addiction symptoms, it was not until 1913, however, that Bayer decided to withdraw heroin from the market.

Aspirin – two sides of the coin

In that time aspirin had already conquered the world. The drug was secretly tested by Felix Hoffmann and patented in Berlin in March 1899. Profits from its sale soon started reducing the losses connected with heroin. Within the next 15 years aspirin became one of the most frequently used drugs. Although it was thought to serve mainly to cure rheumatic pains, it quickly turned out that it also worked for headaches, toothaches, migraines, colds, flu, hangover, tonsillitis, hay fever and many other ailments. The popularity of the drug was not limited by the fact that for more than 70 years since its invention nobody had known how ASA worked. Only John Vane’s research in 1971 contributed to clarifying this mystery. Widely valued, aspirin again took the world by surprise in the mid-eighties, when it was determined that ASA taken every second day in a small dose lowers the risk of heart attack by 50 percent.

Undesirable reactions

Unfortunately, it is not an ideal drug. Only three years after launching aspirin on the market, the case of a patient was described who after taking it got a generalized rash and, in subsequent years, there were reports of patients who experienced acute asthmatic dyspnea. During more than 100 years of use many undesirable reactions were recorded. The Bayer Company itself notes the record of people who cannot take ASA and includes a long list of undesirable reactions in a leaflet attached to the drug.

Among the side effects are vomit that looks like coffee grounds, tarry stools, angioedema, breathing difficulty, dyspnea, asthma attacks, tachycardia, pressure drop, gastro-intestinal disorders, heart burn, nausea, dizziness, rash, urticaria, erythema, nasal mucous membrane inflammationor hyperemia, and many others.

ASA wasn’t authorized for use in children under the age of 12.

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The mother of nonsteroidal anti-inflammatory drugs

The disclosure of undesirable reactions and the prohibition on ASA use for children prompted pharmaceutical companies to search for other pain-relieving and anti-inflammatory drugs. In 1955 paracetamol (acetaminophen) appeared on the American market as an alternative to aspirin. It had been waiting for its big day since its invention 70 years earlier. It was promoted as a drug devoid of side effects in the digestive tract, which could also be used in the case of fever in kids. One year later when it arrived in the United Kingdom, it also became popular among the elderly in whom it wasn’t sup-posed to cause stomach upset. However, side effects were reported in the 1960s. If taken too frequently and in too high dosage, paracetamol damaged the liver and also contributed to the exacerbation of asthma symptoms. Liver damage connected with the overuse of paracetamol was an indirect cause for the development of a drug more effective and less burdensome for the organism. This is how ibuprofen was created, developed at the beginning of the ‘60s. Employees of the British company Boots discovered that the anti-inflammatory proper-ties of acetylsalicylic acid were connected with the presence of the carboxylic acid group. After testing 6,000 different carboxylic acids, they developed a substance initially named ‘Brufen’. Its anti-inflammatory action was twice as strong as the popular aspirin. Ibuprofen combined many desirable functions and turned out to be a bull’s eye. It was effective in pain-relief, fever prevention and anti-inflammation, and it could also be given to children. Yet at the same time, compared with paracetamol, it showed much lower risk of undesirable effects in respect to liver function and only a slightly higher risk of troublesome reactions in the digestive tract. Besides ibuprofen, other drugs in the NSAIDs group appeared on the market: naproxen, ketoprofen, diclofenac, indomethacin and many others .

Wonderful drugs or wonderful poisoners?

The market offered more and more wonderful drugs including a vast array available without prescription. In Poland NSAIDs can be bought even in sizeable doses not only at every chemist but also at petrol stations, food stores, and newsstands. Radio advertisements and TV commercials lavish praise on the action of aspirin and other NSAIDsin bringing immediate relief to both adults and children.

We live in times when the pace and conditions of living don’t allow us to be ill, namely absenteeism at work. We have to be nonstop capable, healthy and ready to tackle challenges. What do we do then when we or our children are affected by an infection, or our functionality is taken away by our worst enemy – pain? We reach out for NSAIDs, which are generously offered by pharmaceutical companies, and we swallow them or rub them in painful places. After antibiotics, NSAIDsconstitute the second most frequently used group of drugs and Poland occupies a prominent place among the top ten European countries with the highest consumption. The best remedies – sick leave and bed, even though the most justified – don’t find many followers.

We therefore swallow doses of aspirin or another drug for a few days, which allows us to persevere without leave and, on top of that, we unconsciously combine it with high salicylate food, benzoic acidor its derivatives – commonly used in all products as preservatives, as well as azo dyes, exacerbating the undesirable effects of the salicylates. Unfortunately, nobody apprises us of the fact that when our ancestors used willow bark or other plants containing salicylates and/or benzoates, nature itself protected people and animals against the use of too high doses. The bitter taste successfully discouraged their overuse. Using natural plant products, apart from salicin, the patient also took other components of polyphenol nature such as flavonoids, proanthocyanidins and phenolic acids with strong antioxidation and anti-inflammatory properties. Probably because of the lower dosage, the natural precursor of salicylic and acetylsalicylic acid brought about curing effects. It needs to be noted that plants regarded as healing, back in the day, were used in case of illness and weren’t often consumed in large quantities.

Hypersensitivity to aspirin

Since the beginning of the 20th century physicians have systematically recorded cases of hypersensitivity to acetylsalicylic acid. Many years of research have allowed researchers to distinguish various hypersensitivities to ASA, the first of which has a bronchi form, defined as aspirin asthma (ASA-asthma), which manifests itself by bronchi dyspnoea, tightness of the chest, wheezing and cough. The second form – rhinitisand sinusitis with hypersensitivity to aspirin (CRS) – results in rhinorrhea, nasal congestion, tearing, coughing, pain in the area of the forehead and ears, and nasal, sinus and ethmoidal polyps.

CRS occurs most frequently together with ASA-asthma. Since 2002 two forms have been defined as AERD – aspirin exacerbated respiratory disease. However, the most common definition for the respiratory type of hypersensitivity to ASA is the ‘aspirin triad’. It occurs in 10-20% of asthmatics and in 30-40% of those suffering from asthma and nasal polyps.

The third type of hypersensitivity to ASA is the form of skin hypersensitivity defined as hives and angioedema or aspirin urticaria. In terms of skin reactions, there occur urticaria, pruritus, erythema appearing in the vicinity of face and neck, lip, tongue and larynx swelling, as well as facial and neck edema. In people hypersensitive to ASA or other NSAIDs,syndromes affecting the digestive tract such as severe abdominal pain, nausea, vomiting, and diarrhea might also occur. The most severe form of hypersensitivity is hypotension (significant lowering of blood pressure) with loss of consciousness and full-blown shock.

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Do only aspirin and NSAIDs trigger symptoms?

The majority of people suffering from aspirin and other NSAID hypersensitivity are aware of the necessity to avoid these drugs. However, a large group of people with asthma, COPD (chronic obstructive pulmonary disease), chronic inflammatory states, nasal and sinus polyposis, digestive tract ailments, or skin changes are not aware of the fact that they might have a problem with tolerance to ASA, salicylic acid and derivatives. Additionally, neither physicians nor patients consider that substances naturally occurring in food and a large group of food additives may also trigger undesirable reactions in the case of hypersensitivity to ASA. Natural salicylates and benzoates (derivatives of ben-zoic acid) as well as azo-food colors (tartrazine, quinoline yellow, sunset yellow, azoru-bine, cochineal red, Allura red or patent blue) belong to ASA-related substances. Not surprising are the reports appearing in scientific literature of ongoing inflammatory state, polyposis recurrence, sustained skin and gastrointestinal symptoms, and the exacerba-tion of asthmatic symptoms in the upper respiratory tract in most patients despite avoid-ance of aspirin and NSAIDs. Full-blown salicylate triad develops over years. For a long period of time, the only symptom of hypersensitivity might be attacks of watery rhinor-rhea, non-specific gastrointestinal or skin symptoms. Fifteen percent of patients with hypersensitivity to aspirin confirmed by provocative tests weren’t aware of non-tolerance to this substance.

Diagnostics – provocation or in vitro tests?

Oral, nasal, inhalatory and conjunctival provocation tests last a few hours, require con-ducting additional examinations, and constitute a direct threat to the life of the patient. Therefore, physicians recommend them only in case of recurring nasal and sinus polyps or severe asthma. Skin tests are also used when there is suspicion of hypersensitivity to other products from the group of nonsteroidal anti-inflammatory drugs. The possibility of detecting hypersensitivity to aspirin via in vitro methods has been sought, by which a direct threat to life is avoided. Worthy of note are tests examining the response of the immune system to ASA contact: the leukotriene release test, the basophils activation or the ASPI test. However, diagnosing hypersensitivity only to ASA or NSAIDs and avoid-ing these drugs doesn’t bring about a significant improvement. In most patients, despite avoiding aspirin and NSAIDs, the symptoms of a chronic in-flammatory state of the upper respiratory tract and other ailments don’t subside. This is most frequently connected with the fact that physicians don’t inform patients about the necessity of limiting high salicylate foods and beverages in the diet, avoiding food pre-served with benzoic acid derivatives and colored with azo dyes. Both acetylsalicylic acid as well as other NSAIDs irritate and damage the intestinal mu-cosa and negatively change the microbiota composition (intestinal bacteria flora), which leads to the unsealing of the intestine. Bacterial lipopolysaccharides get through the damaged intestinal barrier into the bloodstream – a component of bacteria casing which triggers endotoxaemia and, consequently, a chronic inflammatory state. The unsealing of the intestine is the cause of not fully digested food particles moving outside the lumen and the development of hypersensitivity to other food ingredients. The diagnosis of undesirable reactions is one of the greatest problems in contemporary medicine. This stems from the variety of ’actors’ playing a part in these reactions, the possibility of their coexistence and the occurrence of cross-reactions. Consequently, methods that provide the possibility of detecting the reaction closest to the moment of its initiation should be chosen without analyzing possible development routes. This facili-tates identifying the greatest number of potential actors.

Help of specialists

Therefore, it is worth conducting the MRT test (Mediator Release Test), which will detect hypersensitivity to salicylates as well as to 149 other foods and food additives. The test automatically measures the change in the volume of leukocytes after contact with food antigens, which is proportional to the exacerbation of the hostile reaction. It enables mediators to be identified that are released at the beginning of the reaction regardless of which mechanisms will be engaged in its later stages. The advantage of the test is that defining the intensity of the reaction not only indicates foods which are harmful but also the ones which are the safest for the patient. It also examines the response of white blood cells to food additives and some drugs (salicylic acid, ibuprofen, acetaminophen), which significantly increases the efficiency of a modified nutrition model. The MRT test constitutes a base for the development of an individual nutritional program (Lifestyle, Eating and Performance). The Program is not just a simple elimination diet, but a new way of nutrition facilitating the elimination from the diet of foods harmful to us, quieting the immune system and preventing the occurrence of new hypersensitivities. Everyone who conducts the MRT test and enters the LEAP Program has the guaranteed help of Certified Consultants (physicians or dietitians). In the case of hypersensitivity to salicylic acid and NSAIDs, the consultants will also tell the patient what kind of foods to avoid because of a high content of natural salicylates. It should be noted that high content characterizes a large group of commonly used and regarded as health-promoting plant products: olives and olive oil, coconut, honey, herbal spices, avocado, almost all fruits, some vegetables, as well as herbal infusions, coffee and tea.

One can live with hypersensitivity

One can still live even with hypersensitivity to ASA and NSAIDs, although one needs to live wisely. A low-salicylate diet, although bothersome, facilitates keeping a tight rein on ailments and prevents the development of severe aspirin asthma. One needs to re-member though that the sooner hypersensitivity is diagnosed and a proper diet is set, the lesser will be the damage that occurs to our organism. Therefore, it is worth con-ducting the MRT test, entering the LEAP Program and, at the same time, not overusing aspirin or other NSAIDs.

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