Gabor Szendi:
Worm therapy

Like it or not, sooner or later medicine should consider curing based on evolutionary medicine. It means of recreating conditions, which has been triumphed over many years ago. That is sometimes we have thrown the baby out with the bath-water.

 

 

Like it or not, sooner or later medicine should consider curing based on evolutionary medicine. It means of recreating conditions, which has been triumphed over many years ago. That is sometimes we have thrown the baby out with the bath-water.

By now, diseases characterized by immune over-activity have become common. The simplest definition of autoimmune diseases in this group is that in these disorders, the immune system attacks the body's own cells. This may be limited to certain cells of a specific organ, but may also be directed at more than one organ, for example systemic lupus erythematosus. Autoimmune diseases can be cumulative, as one person may suffer from several autoimmune diseases at the same time. Western medicine is helpless against diseases affecting approximately 10% of the Western population (Cooper et al., 2009). Symptomatic treatments are primarily aimed at weakening the immune system, which in turn increases susceptibility to infectious diseases, and increases the risk of cancer (Giat et al., 2017).

The lack of an evolutionary and historical view of medicine makes it much more difficult to uncover the causes, and thus offer prevention and treatment. The fact that autoimmune diseases appeared and became prevalent in the 19th and 20th centuries proves that Western lifestyle and nutrition have played a crucial role in their development. From here it should be only a short step to study the lifestyle and nutrition of Natural People, as they are free of autoimmune diseases. This article shows only a slice of the current research, as this view is only just tolerated by medicine, despite it being highly promising. From an evolutionary point of view, four major factors can be seen as responsible for the onset and spread of autoimmune diseases in the last 150-200 years:

1. Vitamin D deficiency: Urbanization has reduced the average vitamin D levels in several autoimmune diseases, such as multiple sclerosis, and type I diabetes, where low vitamin D levels are a significant risk factor (Szendi, 2018).

2. As a result of the Western lifestyle, the intestinal wall becomes permeable, and this way protein fragments, and microorganisms enter the body and provoke the immune system (Mu et al., 2017).

3. Molecular mimicry: Some components of evolutionarily novel nutrients (for example gluten, milk, maize, and pulses) contain amino acid chains similar to certain proteins in the body, and after these get through the intestinal wall and the blood-brain barrier, the immune system starts attacking the foreign protein, then its own tissue which is similar to it (Cusick et al., 2012).

4. From the 19th century onwards, due to increased hygiene, vaccinations and the use of antibiotics, the infections and parasites that had previously balanced the immune system have largely disappeared from our lives (Rook, 2012).

The so-called 'naïve' T cells that are produced in the thymus play a major role in our immune functions, which upon exposure to immunological stimuli, are transformed into approximately four different T-cells with different functions. T-helper cells are named after the fact that they initiate and direct various immune processes, as if they were the captain of a ship. Th1 cells control cellular immunity, inducing macrophages to incorporate and digest bacteria and protozoa (unicellular pathogens) entering cells. Over-activation of the Th1 branch plays a crucial role in the development of autoimmune diseases.

The Th2 branch of the immune system is responsible for so-called humoral immunity. Th2 cells direct immune system attacks against various parasites such as worms. The pathological over-activity of this branch leads to atopic diseases (allergy, eczema, asthma).

In recent years the importance of the Th17 branch has been recognized, which also plays an important role in the development of autoimmune diseases (Zhu and Paul, 2008).

Vitamin D deficiency plays a role in many inflammatory processes and autoimmune diseases, and recent research has shown that vitamin D can inhibit Th17 cell activity (Joshi et al., 2011). A fourth variant of Th cells are the T-regulatory or T-suppressor cells, which suppress the immune response and, for example, thereby prevent the development of autoimmune diseases (Zhu and Paul, 2008). If the balance of these four immune system branches regulating each other is compromised, autoimmune diseases and atopic diseases may develop.

The hygiene hypothesis

It had been already noticed in the last third of the 19th century that pollen allergy is somehow related to urban dwellers and is much less common in farmers (Rook, 2012). These observations took an exact form in David Strachan's epidemiological research published in 1989. He followed more than 17,000 newborn babies until the age of 23 and found that the more older siblings someone had, the less chance they had of getting hay fever and eczema. Four older siblings provided 2.5 times protection against hay fever and 4 times protection against eczema, compared to only-children. Younger brothers provided much less protection (Strachan, 1989). Strachan concluded that various infections in infants and young children provide protection against atopic diseases. Because the size of families has declined over the past 150 years, and because hygiene and protection against infections have increased, the price paid is the increasing incidence of atopic diseases.

This brief announcement started intensive research, and soon the hygiene hypothesis was formulated in evolutionary medicine. According to this, the human immune system has evolved for millions of years with microorganisms and parasites living with it, and within it. There are more bacteria on our skin and in our intestines than the number of cells we have, and worm infections have been an integral part of the development of mammals for hundreds of millions of years. Destroying the host organism is not the 'goal' of micro-organisms and parasites, rather it is to live peacefully 'with each other.' However this can only be based on mutual benefits. For example, the many bacterial strains of our intestinal flora are all specialized in certain subtasks: Certain bacteria in the upper digestive tract produce short-chain fatty acids from indigestible nutrients, not only providing nutrients, but also regulating the functions of the immune system. Other bacteria produce different vitamins, while others neutralize harmful substances, etcetera. As a result of millions of years of our coexistence with various worms, these worms have learned to suppress the immune response targeted against them, which has the positive consequence that the immune system does not overreact to allergens, or to the factors that provoke autoimmunity (Rook, 2012). In fact, various infections or coexistence with parasites have, for millions of years, become a condition for the normal development of the immune system. Due to the increasing hygiene of the past 150 years, we have lost our 'old friend's' immune function regulating-activity. Animal studies have shown that the immune function of animals raised under sterile conditions is severely impaired.

Dangerous hygiene

Although improvements in hygienic conditions have reduced deaths from infectious diseases, to some degree, excessive hygiene has turned against us. We have spectacular evidence of this. For example, in more advanced Finland, people are six times more likely to have type 1 (autoimmune) diabetes than in neighboring Karelia, although the incidence of genes predisposing this disease is the same in the two countries (Kondrashova et al., 2005). The case is the same with celiac disease. Compared to Karelia, people in Finland are four times more likely to have gluten sensitivity confirmed by biopsy, despite the fact that the genes predisposing the disease have the same incidence (Kondrashova et al., 2008). Members of the mouse strain developed as a model for type 1 diabetes develop type 1 diabetes spontaneously in 80% of cases. But if they get infected with one of the two worms that live in humans, diabetes does not develop in them (Saunders et al., 2007).

As early as 1966, an Israeli study into multiple sclerosis confirmed that the more advanced the sanitary infrastructure (tap water, flush toilet, etcetera), the more frequent is the incidence of disease (Leibowitz et al., 1966).

Another study found that in a country with a high prevalence of trichuriasis, multiple sclerosis is really rare (Fleming and Cook, 2006). Systemic lupus erythematosus in West Africa is surprisingly low, probably because the very high prevalence of malaria infection protects against this disease (Symmons, 1995), and against autoimmune diseases in general (Greenwood, 1968).

Not all infections are good

After the hygiene hypothesis became known, there was a widespread belief that the more children become infected the better it is. However studies have shown that human infectious diseases such as influenza, mumps, measles, and smallpox, which have developed in the last ten thousand years, do not provide protection against the over-functioning of the immune system. The effects of these pathogens have not been embedded in our immune system, which has evolved over millions of years. In contrast, diseases transmitted with feces, worm infections or latent tuberculosis, Hepatitis A, and Helicobacter pylori infections have been shown to regulate immune functions. This is the reason why today the 'old friends' term is used, because it originates in the protective effect and not usually from bad hygiene, but rather special, nameable pathogens and parasites (Rook, 2012).

African children have been shown to be less likely allergic than non-infected children (Wickelgrencan, 2004). In a Venezuelan study, children were treated with anthelmintic, and the successful treatment increased the number of allergies among them (Lynch et al., 1993). It has long been known that Natural People have very high IgE levels, yet they do not suffer from atopic diseases. High IgE levels are a diagnostic sign of atopic diseases in the developed world. The explanation is that the various parasites that live in humans persistently cause such a high IgE response, that the immune system does not have the capacity to produce specific IgE-s against environmental allergens, thus no allergic response is developed (Lynch et al., 1993).

Worm therapy

Until the 1930s, almost everyone in the developed world 'had worms'. Since then, parasites that were previously common have been successfully eradicated in advanced societies (Elliott and Weinstock, 2009). The incidence of various autoimmune diseases has increased in direct proportion to the reduction of worm infestations. The 'old friends' hypothesis, animal experiments, and human case studies have supported the assumption that infection with a special worm in an existing autoimmune disease may improve the autoimmune disease's progression. Research has focused on which worms can be used without the risk of serious side effects or serious illness, and which worms are effective against which diseases.

For example, one type of whipworm (Trichuris suis) has been shown to treat ulcerative colitis. Chronic patients who did not respond to other treatments received either placebo or 2,500 worm eggs in capsules every two weeks. By the end of week 12, the disease of 43% of those who had consumed worm eggs had significantly improved (Summers et al., 2005a). This worm has also been successfully used in Crohn's patients, and by the end of week 12, 66% of patients had entered a stage of remission (Summers et al., 2005b). In fact Trichuris suis lives in pigs, does not cause lasting infection in humans, has zero risk of transmission and, unlike other worms, only chooses to live in the intestine.

One study compared 12 patients with multiple sclerosis with spontaneous worm infections for 5 years, with 12 non-infected patients. The worm-infected patients' disease relapsed less frequently, the symptoms were less severe, and the myelin sheath's (the 'isolating' coating on the nerves) damage measured by MRI was much milder (Correale and Farez, 2011a).

In another study, when multiple sclerosis patients with parasitic infection were treated with anthelmintic, their disease worsened after the successful anthelmintic treatment (Correale and Farez, 2011b).

Another candidate for the treatment of autoimmune and atopic diseases is Necator americanus, a species of hookworm native to humans. It penetrates the body through the skin, goes into the lungs, and when the infected person coughs it passes into the intestine. It lives in the small intestine for 2-5 years. The autoimmune response to gluten in celiac patients infected with this worm was significantly reduced (Croese et al., 2015). Analyzes have shown that this worm significantly relieves asthma symptoms and prevents the development of asthma (Leonardi-Bee et al., 2006). So far most successful studies have been conducted with animals, but more than 20 human studies have now been launched. The tests are costly and it is not easy to convince sponsors of the usefulness of these tests.

Other researchers say that the most viable way is to find out what compounds are released by each worm that modify the function of the immune system, because in principle, taking them as a medicine can be as effective as artificially infecting patients with worms (Adisakwattana et al., 2009).

However research is often contradictory and one reason for this is that patients respond differently to worm infections, but another, perhaps more important reason is that as with any researchers, experts in this field suffer from tunnel vision. That is, there is no research on autoimmune diseases associated with nutrition, shifts in the composition of the gut flora, vitamin D deficiency and changes in the permeability of the intestinal wall. In the 20th and 21st centuries, not only did we get rid of our worms, but our lifestyle changed dramatically. An approach based on all known factors would lead to quicker success.

Whatever the case, the 'old friends' hypothesis, and the worm therapy research coming out of it, target one of the root causes of autoimmune diseases, and the results of this research will certainly play a role in overcoming seemingly incurable autoimmune diseases.

 

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