Gabor Szendi:
Allergy - a man-made epidemic

Is there anything more natural than flowers? Yet millions of people suffer from pollen allergies in the spring and summer. If we want to understand atopic diseases, we must start from this paradox.

 

 

If we want to understand atopic diseases (see box), we must start from this paradox. The incidence of atopic diseases, especially since the 1960s, has steadily increased at a very high rate. Hay fever now affects 19% of the European population (Szilasi et al., 2012), In northern and eastern Europe, the incidence of asthma is about 10% and eczema is 5% among 13-14 year olds, but in Western Europe the situation is even worse (Mallol et al., 2013). Asthma has become 2-4 times more common in different countries since the 1960s (Grant et al., 1999). The same increase can be observed for eczema (Schäfer, 2006). Researchers and clinicians assume genetic and environmental causes as the cause of atopic diseases, but this is questioned by the data. The graph below shows how the incidence of asthma, eczema and hay fever increased between 1964 and 2000 in the Scottish port city of Aberdeen, but we are experiencing this anywhere in the developed countries.

It is evident that in just thirty to forty years there cannot be such a rapid genetic change in the population to explain why the incidence of atopic diseases is increasing from generation to generation. On the other hand, in Aberdeen, Scotland, the oil industry - which causes serious pollution that has not diminished over the years - would explain the dramatic increase in the incidence of atopic diseases there (Devenny et al., 2004). The first approach as an explanation is that of the Western lifestyle, which can be supported by numerous arguments (Devereux, 2006). The question is, which components of the Western lifestyle can be associated with atopic diseases?

Western lifestyle and atopy

Most diseases were sporadic in earlier times. Augustus Caesar had asthma, and Nero's nephew, Britannicus, was allergic to horses. In 1565, Leonardo Botallo reported an allergic case called "rose catarrh" (Cockcroft, 2014), but hay fever really only became more common in the 19th century and when it began to be described and researched (Emanuel, 1988). Generally, the rule can observed: that a disease becoming common can be seen from more and more doctors and researchers describing it independently.

Diseases of civilization, such as atopic diseases, began to become more common in the 19th century. Disposition, genetic differences, individual sensitivity are all meaningless answers to the question of why one person gets sick, when everyone else could be affected by the same triggers. Pollen, food allergens, or environmental pollution generally affect everyone, but not everyone gets sick. Of course, the possibility should not be excluded that certain "silent" genes that have not previously caused disease, when confronted with certain environmental hazards, will then cause disease. However, if we look at the main features of "civilization," it may turn out that they alone can explain atopic diseases and their increasing incidence.

The hygiene hypothesis

In 1989, Epidemiologist David Strachan published his famous study on the hygiene hypothesis (Strachan, 1989). In this, he showed that hay fever is directly related to higher living standards and inversely related to the number of siblings. In other words, the better - cleaner - the circumstances, the more likely it is that you will become an atopic patient. But the more older siblings a person has, the less likely they are to have atopy. The explanation is simple: in our world, sterility and protection against infections are proportional to well-being (clean environment, good quality food, enhanced personal hygiene, etcetera), but if someone has many siblings, it is guaranteed that infections brought home from kindergarten and school will pass through the family. The hygiene hypothesis launched a series of further research. It turned out that children growing up on a farm are more vulnerable to asthma (Genuneit, 2012), but infections acquired in early childhood communities (Matricardi and Hamelmann, 2009), or the hepatitis A virus infection common before the 1970s also represent a significant reduction in the risk of atopic disease (McIntire et al., 2003).

The discovery of IgE immunoglobulin was a major turning point in the study of atopic diseases (Johansson, 1997). Indeed, in most atopic patients, IgE levels were found to be well above average. The hereditary factor of atopic tendency seemed to have been found. Examining the IgE levels and atopic disease of twins raised together and separately, it was concluded that disease is determined more by hereditary factors than by the environment (Hanson et al., 1991). However the discovery immediately came to a riddle: Ethiopian children have twenty times the level of IgE compared to European children. However, Ethiopian children did not suffer from atopic diseases (Johansson et al., 1968). Natural peoples untouched by civilization were studied one by one, and it turned out that the IgE level of these people is ten times higher than the European average, in fact, some tribes have a hundred times higher IgE levels, and yet they show no signs of atopic disease (Hurtado et al., 1999).

The explanation for the strangeness of this is surprising: infections caused by various parasites (for example intestinal worms) increases IgE levels as a defense and provides protection against both parasitic infections and atopic diseases. Animal studies show that if the animal is first exposed to an intestinal worm infection and only subsequently exposed to an allergen, it will not develop atopic disease, but in reverse order, it will develop atopy. Magdalena Hurtado et al. conclude that children in the Western world are at risk from atopic disease because they are constantly exposed to allergens while being protected from parasites (Hurtado et al., 1999).

So high IgE levels in our evolutionary history have brought us many benefits, but they have turned against us in our modern, over-sterile environment. It is not good to defy nature, as indicated by a series of studies in which African children were rid of their parasites and "in return" developed atopic diseases (Matricardi and Hamelmann, 2009; Lynch et al., 1993).

According to the hygiene hypothesis, in our modern circumstances, during our development we encounter far fewer pathogens and parasites than we were used to in human evolution, whereas this would be necessary for the balanced functioning of the immune system.

Left handedness and atopy

In the 1980s, Norman Geschwind, Albert Galaburda and Peter Behan described how atopic diseases are more common among left-handed and ambidextrous people. According to their theory, hormone effects in fetal life may lead to the right hemisphere of the brain becoming overweight, which can have consequences such as various learning disabilities, a shy temperament, but also the appearance of special talents, such as musicality. Therefore, often not only left handedness, but learning and speech disorders, hyperactivity, and highly inhibited behavior can indicate that the right hemisphere is overweight. Atopic diseases are also more prevalent among musically talented children. The disposition to atopy is ultimately explained by the fact that the two hemispheres of the brain regulate the immune system differently, and that the right hemisphere is more closely related to humoral immunity, which is also responsible for IgE production (Szendi, 1997).

Intestinal flora and atopic diseases

The relationship between human intestinal flora and various diseases is an area that has been intensively researched. We know of several studies, in which the composition of intestinal flora was analyzed from stool samples of growing infants, and this has been compared with the incidence of later onset atopic diseases. The results show that some intestinal bacteria (such as Bifidobacteria) were protective but other intestinal bacterial strains (such as Clostridium difficile) represented atopy risk (Björkstén et al., 2001; Penders et al., 2007).

The intestinal flora of a newborn develops in the uterus, when passing through the birth canal, and during feeding. It is understandable that babies born to caesarean section therefore have an intestinal flora that is different from that of babies born naturally (Biasucci et al., 2008).

A pooled analysis of twenty-six studies found this to increase the risk of food allergy by 32% at a later age, hay fever by 23%, asthma by 18%, but does not cause eczema (Bager et al., 2008).

However, data on breastfeeding are extremely contradictory. One would think that breastfeeding clearly protects against later atopic diseases, since breast milk contains special prebiotics that promote the growth of friendly intestinal bacteria. Yet the investigations are controversial (Matheson et al., 2012). For example, in the case of atopic mothers, breastfeeding for more than four months increased the risk of atopic disease in the child (Sears et al., 2002). However, this is probably not due to the breast milk but to atopic mothers' pursuit of increased sterility. Studies show that the intestinal flora of nutrition-fed children is unfavorable to breast-fed infants (Fanaro et al., 2003). Children's intestinal flora builds up until the age of three, and since the different bacterial strains also regulate each other's growth, an initial abnormal composition increases the risk of developing pathological changes in the composition of the intestinal flora, which may later lead to atopic diseases, among others.

Antibiotic use and atopy

Antibiotics have also been developed in the fight against infections, and have proved to be dual-edged weapons, as they kill not only pathogens but also our "old friends", our intestinal flora, as well as promoting the growth of unwanted or diseased bacterial strains. Because the baby's intestinal flora begins to develop during fetal life, if the mother receives antibiotic treatment in the third trimester, her baby will be twice as likely to develop asthma later in life (Stensballe et al., 2013).

One study collected data on first-year antibiotic treatment from 193,000 children in 29 countries. Children who received antibiotics were twice as likely to develop asthma at 6-7 years of age and had a 60% increased risk of eczema and seasonal allergy (Foliaki et al., 2009).

In another study of 250,000 children, the risk of asthma in subsequent years increased in proportion to the number of antibiotic treatments up to one year. One or two infant antibiotic treatments between the ages of 5-9 had a risk of 20-30%, and more than four antibiotic treatments had a risk of one and a half to two times (Marra et al., 2009).

As a counter example, followers of Rudolf Steiner can be mentioned, who use antibiotics or antipyretics much less frequently for their children, appreciating more natural cures. In a pooled analysis, 4,600 children attending Waldorf schools were compared with 2,000 traditional school children, with the latter twice as likely to have seasonal allergies, and 2.8 times more likely to have asthma, with 63% more likely to have eczema. Early use of antipyretics increased the risk of asthma by 54% and eczema by 32% (Flöistrup et al., 2006).

Oral tolerance

An interesting question is, how does the composition of the intestinal flora influence the risk of developing atopic respiratory or skin diseases? The intestinal wall is our largest body surface exposed to allergens. If you inhale an allergen, it will already be at the intestinal wall within 1-2 minutes. In the early period of life, the so-called oral tolerance develops during nutrition, that is, through substances which our immune system accepts. Proper intestinal flora is essential for oral tolerance, partly because of the interaction between specific intestinal bacteria and the immune system, and partly because the intestinal bacteria, for example digestible fibers, are made into short-chain fatty acids that also have an extremely important immunomodulatory role (Shreiner et al., 2008). Oral tolerance to allergens will subsequently protect against inhaled or dermal allergens. Native Americans reduced their skin sensitivity to venom by consuming American ivy, which causes painful skin rashes (Jump et al., 2004).

Atopy and nutrition

A further consequence of the Western lifestyle is the profoundly altered diet, and consequent obesity epidemic. Being overweight (25 kg/m² <BMI <30 kg/m²) and obese (BMI> 30 kg/m²) have been shown to increase the risk of asthma (Chinn, 2003) and eczema (Silverberg et al., 2009). In proportion to the degree of being overweight, and in people who lose weight through different methods (surgery, dieting) the atopic disease disappears or the symptoms are significantly reduced (Eneli et al., 2008). One consequence of obesity is inflammation at the body level (Monteiro and Azevedo, 2010). It is increasingly accepted that the common "base" of diseases of civilization is body-level inflammation (Hunter, 2012). Fat cells release so-called adipokines (most commonly known as TNF-alpha and IL-6), which when added to inflammatory factors produced as part of atopic disease, exacerbate the underlying disease (Shore, 2006). Effective drugs for atopic diseases are anti-inflammatory cortisol derivatives. Obesity also adversely affects the intestinal flora, signaling the complex effects of Western lifestyle (Ley et al., 2006).

Can we use our knowledge?

In the prevention and suppression of atopic diseases, it would be essential to rebuild a more natural lifestyle, which includes evolutionary nutrition (that is, Paleolithic nutrition), regaining the natural environment, and a proximity to animals. Rapidly absorbed carbohydrates (cereals, rice, potatoes, sugar) are responsible for the obesity epidemic. Milk and dairy products are also common allergens, with 50% of eczema improving when these are avoided (Pourpak et al., 2004). The so-called permeable intestinal syndrome is a modern, though little researched problem. Certain proteins in legumes, lectins, gluten and WGA lectin in cereals, and non-steroidal anti-inflammatory drugs, all increase the permeability of the intestinal wall (Cordain et al., 2000), which is also related to atopic processes (Pike et al., 1986; Hijazi et al., 2004). It is important to consume a wide variety of vegetables and fruit because the diverse plant fibers nourish our intestinal flora. The consumption of anti-inflammatory omega-3 fish oil has played an important role in human evolution, and it is protective against atopic diseases, while vegetable oils are extremely harmful due to their inflammatory omega-6 and trans fat content (Duchén and Björkstén, 2001; Miles et al., 2014). Probiotics containing bifidobacteria may be useful in atopic diseases.

Not everyone can live in the countryside, but it is possible to do a lot of hiking, and go on holiday in natural environments. Studies show that children with dogs and cats have a significantly reduced risk of atopy (Ownby et al., 2002). It's hard to draw a line between harmful and useful dirt, but probably over-worrying on this issue is not useful. And finally, think twice about using antibiotics, sometimes they do more harm than good.

 

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