Could The Increase In Autoimmune Diseases Be Related To The Increase In Processed Foods?

It is well documented that there has been an increase in auto-immune diseases over the last three decades. Epidemiological data provides strong evidence that autoimmune diseases are definitely on the rise throughout westernized societies. Autoimmune diseases such as multiple sclerosis, type 1 diabetes, Crohn's disease, systemic lupus erythematosus, primary biliary cirrhosis, myasthenia gravis, autoimmune thyroiditis, hepatitis and rheumatic disease, bullous pemphigoid, and celiac disease are examples.

The increased incidence of autoimmune diseases is a world-wide trend but is seen mainly in western countries. During this period there has also been an increase in the amount of processed foods available for sale, particularly in western countries.  Living in westernized countries has a significant influence on nutritional intake. The “Western diet” includes regular consumption of high fat, trans fatty acids, cholesterol, proteins, sugars, salt intake, as well as the regular consumption of processed and fast-foods. 

Major shifts in dietary patterns are continually occurring. In fact, some studies have shown that the contribution of ultra-processed food to total household diet has increased by about 50% over recent years, and has replaced the intake of unprocessed and minimally processed foods. Whilst because of socioeconomic conditions this is happening more in western countries, it is a world-wide process is happening in both developing as well as in developed countries.

It is thought that this increase in autoimmune diseases is caused by some sort of environmental impact rather than genetic factors. The two major environmental factors thought to play a role in the development of autoimmune diseases are infections and nutrition. When you consider the geo-epidemiological distribution of autoimmune diseases - the world-wide North–south and West–east gradients in Europe, their relationship to socioeconomic status, their rapid increase in developed countries and observations in migrant populations it is understandable that scientist believe that environmental factors are driving these recent and rapid evolutionary changes.

So is there a link between auto immune disease and processed foods? Could the use of industrial food additives explain the rising incidence of autoimmune diseases?

The intestinal epithelial barrier consists of an intercellular tight junction which controls the equilibrium between tolerance of a particular food and immunity to non-self-antigens. It is well known that tight junction dysfunction is common in many autoimmune diseases, where the body forms abnormal antibodies against self-antigens. This link is understandable when you think that only a single layer of epithelial cells separates the gut contents from the layer of immune cells in the intestinal wall which are responsible for the production of antibodies. If this single layer of protective epithelial cells is breached, it can lead to pathological exposure of the highly immune-reactive sub-epithelium, to the large number of foreign antigens found in our food.

The tight junctions in our intestine have multiple roles. They are dynamic structures that are involved in developmental, physiological and pathological processes in the gut. Via a barrier mechanism, they control the movement of fluid, macromolecules and leukocytes from the intestinal lumen to the blood stream and vice versa. They protect the epithelial cells of the intestine against colonization by microorganisms. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, the tight junction also controls the equilibrium between tolerance and immunity to non-self-antigens and therefore they control the development of allergic responses and autoimmune responses to food.

It is not surprising, therefore, that if the function of the tight junction is affected, the physiological state of epithelial and/or endothelial cells is dramatically changed as well. Tight junction dysfunction seems to be a primary defect in people who have autoimmune diseases such as ulcerative colitis, Crohn's disease, celiac disease, inflammatory joint disease, ankylosing spondylitis, juvenile onset arthritis, psoriatic arthritis, type 1 diabetes mellitus and primary biliary cirrhosis. It is thought that in addition to genetic predisposition, the loss of the protective function of mucosal barriers that interact with the gut is necessary for autoimmunity to develop.

One hypothesis put forward in an article in Science Direct suggests that commonly used industrial food additives could cause some sort of dysfunction in the tight junction which allows leakage from the gut into the bloodstream.  The article suggests that food additives such as glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles which are extensively and increasingly used by the food industry may improve the qualities of food, but they may also increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. This increased intestinal permeability through the opened tight junction, could therefore result in the entry of foreign immunogenic antigens such as gluten and activation of the autoimmune cascade.

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So far there are seven food additives which when ingested regularly in large amounts, are known to induce or which are associated with increased intestinal permeability:

1. Sugars (eg glucose)
2. Salt
3.  Emulsifiers and Surfactants
4. Organic Solvents (eg ethanol)
5.  Microbial transglutaminase (mTG). Transglutaminase is an extracellular enzyme and is biosynthesized by several microbes which is a very useful tool for modifying the functionality of proteins in food products.
6. Gluten
7.  Nanoparticles. Due to their unique properties and surface characteristics, can protect drugs from the destructive factors in the GI tract and can increase the permeability of macromolecules through the gastrointestinal barrier. 

Many of these additives can be combined, thus potentially combining their effect on tight junction permeability.

Summary

The diet of the industrialized and urbanized parts of the world today is vastly different from what it was even two or three decades ago, with a whole new range of processed and fast food experiences, which rely of food additives to improve taste and quality. There is also a number of genetically modified crops in use which this article has not addressed. Over recent decades, a significant increase in the incidence of autoimmune diseases in western and other industrialized countries has led to the hypotheses that diet is a potential environmental risk factor for such disorders. This article in the Science Direct http://www.sciencedirect.com/science/article/pii/S1568997215000245   has not definitively proven this link, evidence shows that increases in the usage of the abovementioned food additives have paralleled increased incidences and prevalence of autoimmune diseases during the last decades, as evidenced in the figure below. Where A and B (r2 = 0.9829, 0.886, respectively).

The parallel net increase % per year in various countries of: A. Food additives usage and B. AD frequencies over the last decades. Source Science Direct 

The confirmed facts are, however: 

1. Incidence of autoimmune diseases and food additive consumption is increasing.
2.  Commonly used industrial food additives enhance intestinal junction leakage.
3.  Glucose, salt, emulsifier, gluten, microbial mTG, nanoparticle increase tight junction leakage.

It is easy to conclude, therefore, that the intestinal entry of foreign antigens due to increased tight junction permeability could be caused by the increased of food additives found in processed foods. In turn this could activate the autoimmune cascade which could indeed lead you to believe that the increase in autoimmune diseases is definitely related to the increase in processed foods. However, further research on food additives exposure causing intestinal permeability leading to autoimmune diseases is required to clarify our understanding of the common mechanisms associated with the causes of autoimmune diseases.

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What Is An Autoimmune Disease?

 Celiac disease (also spelt coeliac disease) is an autoimmune disease. But what is an autoimmune disease and what other disorders are in this group?

 Broadly speaking an autoimmune disease is caused when a person's immune system produces an inappropriate response where it mistakenly attacks the body's own cells, tissues and/or organs, resulting in inflammation and damage to otherwise healthy tissue. There are a broad range of related diseases which can be described under this label. In fact there are at least 80 different autoimmune disorders ranging in severity from mild to disabling, depending on which system of the body is under attack and to what degree. Autoimmune disorders can affect nearly every organ and system of the body. There is generally no cure, but the symptoms of these various disorders can be managed.

 Find out how to transform your kitchen into 100% gluten free production  

Autoimmune diseases affect many more people than cancer and heart disease, but yet they still remain a mystery to the medical profession. Diseases such as celiac disease,  rheumatoid arthritis, lupus erythematosus (LE), multiple sclerosis (MS), inflammatory bowel disease, rheumatic fever and even the problematic skin condition of psoriasis are just some of the autoimmune diseases which affect a multitude of the population. And of course, the people reading this blog will be all too familiar with the autoimmune disease which affects their ability to consume gluten, celiac disease.

Autoimmune disorders are broadly grouped into two categories. 'Organ-specific' where one organ is affected, and 'non-organ-specific' disorders where multiple organs or systems may be affected.  Some of the major types of autoimmune disease are:

Celiac disease – affects the small intestine. Symptoms include weight loss, nutrient deficiency, abdominal pain and failure to thrive.

Type I Diabetes - affects the pancreas. Symptoms include thirst, frequent urination, weight loss and an increased susceptibility to infection.

Graves' disease - affects the thyroid gland. Symptoms include weight loss, elevated heart rate, anxiety and diarrhoea.

 Inflammatory bowel disease - includes ulcerative colitis and possibly, Crohn's disease. Symptoms include diarrhoea and abdominal pain.

Multiple sclerosis - affects the nervous system. Depending on which part of the nervous system is affected, symptoms can include numbness, paralysis and vision impairment.

 Psoriasis - affects the skin. Features include the development of thick, reddened skin scales.

Rheumatoid arthritis - affects the joints. Symptoms include swollen and deformed joints. The eyes, lungs and heart may also be targeted.

Scleroderma - affects the skin and other structures, causing the formation of scar tissue. Features include thickening of the skin, skin ulcers and stiff joints.

Systemic lupus erythematosus - affects connective tissue and can strike any organ system of the body. Symptoms include joint inflammation, fever, weight loss and a characteristic facial rash.

What does a healthy immune system do?

Before you can understand what and autoimmune disease is you need to understand what a healthy immune system does, what it is designed to do. The immune system is the most amazing and complex system of cells, antibodies and other chemicals designed to keep you healthy and well. It is designed to recognise and attack foreign invaders such as bacteria, viruses and even rogue body cells which could turn into cancer cells.  Special immune cells are constantly scanning your body to ensure it keeps these invaders out.

Your immune system is an army of soldiers and weapons inside your body which go into action each time an invader, such as a tasty tummy bug  enters your body.  Each soldier has a specific job to do and is programmed to attack only a specific type of bug.  This is because there are so many invaders to monitor that each soldier has to be focussed on its own target. When it detects the target the soldier multiplies and heads into battle with the intention to root out the enemy and destroy it.

The soldiers of our immune system are immune cells and the weapons are a variety of chemicals such as antibodies which are produced by the immune cells to inhibit and/or destroy the invaders

The first phase in the fight against infection certain immune cells, called phagocytes and macrophages, ingest and kill the enemy.  You can see the result of this immune response when you have an infected wound which becomes pus-filled, such as with a boil.

Other immune cells called T lymphocytes (T cells) use special receptors on their surfaces to identify foreign microbes, such as bacteria and viruses. They then present these invaders to the immune system and the fight begins. When the immune system is exposed to a foreign invader, either through natural infection or through immunisation programmes, B lymphocytes produce specific antibodies against that specific enemy. This is called humoral immunity.  Other cells turn into killer cells to eradicate the enemy. This is called cell-mediated immunity.

When the fight is over some of the T lymphocytes turn into memory cells so that the next time that specific invader enters our body it can quickly raise the immune response and eradicate the invader before it has a chance to establish and infection.

So why do autoimmune diseases occur?

Your immune system can usually tell the difference between your normal body cells and the foreign invaders. But sometimes it go horribly wrong and gets the message muddled and starts targeting normal healthy cells by mistake. This results in chronic inflammation to organ damage which is not so good.

Normally rogue T cells that target the normal tissues of the body are destroyed by the thymus, an organ of the immune system located behind the breastbone. Unfortunately, in some people, these 'self-attacking' T cells escape destruction and can then be activated by a trigger. The exact triggers are unknown, but viral infections and hormones are among the suspects. The rogue T cells then instruct B lymphocytes (B cells) to make antibodies against the particular tissue, organ or system. Such antibodies are called 'autoantibodies'.

But the reason why this happens is not clearly understood. Many autoimmune related conditions appear spontaneously and there is not a clear trigger. Whereas others such as rheumatic fever and celiac disease have a very clear trigger.

Rheumatic fever, for example, occurs when a person (usually a child) develops Strep throat infection. As the untreated child is recovering from the Strep throat (about 2-3 weeks later) their immune system forms antibodies against the Strep bacteria to kill it and prevent it from invading again. Unfortunately, however, these same antibodies can also attack the muscles of the heart in some people which causes rheumatic fever. Sometimes these Strep antibodies attack the kidneys and cause glomerular nephritis.

And those of you reading this blog will be well aware of the role gluten has in triggering celiac disease.  

So how does gluten act as a trigger in provoking an autoimmune response?

A recent study in The Lancet found that gluten could stimulate the production of a chemical called zonulin.  Zonulin controls what can enter the intestinal tract by opening up the spaces between the cells of the intestinal lining. Its role is to let good nutrients in and keep larger food molecules (such as gluten) and foreign invaders out.

 However, when leaky gut is present, the spaces between the cells open up too much allowing larger protein molecules such as gluten to get into the bloodstream where an immunologic reaction can take place. This has led to the theory that the overproduction of zonulin may allow the absorption of gluten to occur, and this, in turn, leads to autoimmune antibodies to form against a gluten/cellular complex. This is because the immune system thinks the larger protein molecules are foreign invaders and mount an immune response leading to food sensitivities and/or celiac disease.

 In addition, this immune activation leads to more damage to the intestinal cells and the gut becomes more inflamed and more permeable or "leaky".  As the damage continues, the microvilli that line the intestines and absorb nutrients become damaged, leading to other nutrient deficiencies.

Other causes of increased Zonulin production leading to leaky gut syndrome are an overgrowth of harmful organisms, like bacteria or yeast in the intestine, as well as parasite infections.

What are the risk factors for an autoimmune disease?

For many of the autoimmune diseases, women are more susceptible than men, particularly during their childbearing years. It is thought that sex hormones may be at least partly responsible. There is generally no cure, but the symptoms of autoimmune disorders can be managed. The exact causes of most autoimmune disorders are not known but the risk factors seem to include:

Genetics - a tendency to develop autoimmune disorders seems to run in families. However, family members can be affected by different disorders; for example, one person may have diabetes while another has rheumatoid arthritis. It seems that genetic susceptibility alone is not enough to trigger an autoimmune reaction, and other factors must contribute. If your first-degree relative (sibling or parent) has an autoimmune disease you are more likely to develop one too

Environmental factors - a family's susceptibility to developing autoimmune disorders may be linked to environmental factors which make work together with genetic factors. Factors such as infection, smoking, toxins in food, UV light and pollution may act as a trigger to activate the autoimmune disease in a genetically susceptible person. But what pulls the actual trigger is still a mystery.

Chronic stress – can affect the body's inflammation regulator and because inflammation plays a role in the development of autoimmune disorders, stress may be considered a trigger.

 Gender – about 75% of people with autoimmune disorders are women

Sex hormones - autoimmune disorders tend to strike when a woman is in her childbearing years. It is thought that the female sex organs can increase the production of autoantibodies. Some disorders may also change – sometimes for better sometimes for or worse, by major hormonal changes such as pregnancy, childbirth and menopause.

Infection – some autoimmune disorders may be caused, triggered or worsened by particular infections. For example, rheumatic fever as described above. There is also a theory that celiac disease is caused by a previous rotavirus infection. My daughter who has celiac disease had a severe rotavirus infection which required hospitalisation when she was two. When she was 17 she developed a severe case of whooping cough (despite being immunised when she was young) I firmly believe that the rotavirus was the cause of her celiac disease and the whooping cough was the trigger.

How could rotavirus cause celiac disease? 

Viruses have 2 phases of growth related to infections, latent and lytic, and it is easiest explained with cold sores caused by the herpes virus. When the virus is in the lytic phase the sufferer has an active infection and develops a cold sore on the lips or other areas of the face. In this phase, the virus is actively multiplying and is highly infectious. When the virus is in the latent phase it lives within the nerve cells and becomes part of the cell reproducing with the genetic material of the host cell. Does the latent existence of the rotavirus genetic material within the gut cells target it as being foreign by the immune system and the antibodies against gluten attack the cell as foreign?

Diagnosis of autoimmune disease

It can be hard to diagnose an autoimmune disorder, especially in its earlier stages and if multiple organs or systems are involved. Depending on the disorder, diagnosis methods may include physical examination, medical history, blood tests, biopsy and x-rays. Blood tests depend on the symptoms but include testing for autoantibodies and specific antibodies (celiac) and raised levels of chemicals like high sugar levels (diabetes) or nutritional defects (celiac.  A person may have more than autoimmune disease at one time. For example, it is common for a person to have both celiac disease and diabetes type I.

It is interesting to note that often there is a significant lag time between the development of autoimmune antibodies and the onset of disease. Autoantibodies can exist for years in some people before they begin to develop symptoms. Some people may never develop symptoms.

Treatment for autoimmune disease

Autoimmune disorders, in general, cannot be cured, but the condition can be controlled and managed to reduce the symptoms. Treatments plans include:

Dietary Control - e.g. a gluten free diet for celiacs, reduced sugar diet for diabetes. Some studies have linked too much salt and high kilojoule food to more rapid development of autoimmune disease so those at risk should work on their diets.

Anti-inflammatory drugs - to reduce inflammation and pain

Corticosteroids - to reduce inflammation. They are sometimes used to treat an acute flare of symptoms

Pain-killing medication - such as paracetamol and codeine

Immunosuppressant drugs - to inhibit the activity of the immune system

Physical therapy - to encourage mobility

Treatment for the deficiency - for example, insulin injections in the case of diabetes, iron injects for celiac disease

Surgery - for example, to treat bowel blockage in the case of Crohn's disease

Other than a gluten free diet for celiac disease and a reduced sugar intake for diabetes, there is no compelling evidence that diet or exercise has a significant effect on the symptoms caused by an autoimmune disease. Obviously choosing a healthier lifestyle has health benefits overall and will make you feel better. For example, if an arthritis sufferer loses 20 kg their joints will benefit from having to carry less weight about.  It is also good to avoid inflammatory foods and eat more foods with anti-inflammatory properties.

Foods which are considered to be inflammatory foods include things like  farmed seafood, fast foods, foods with a high GI, processed dressings,  saturated fats, soft drinks, white bread and white rice.

Foods with anti-inflammatory properties include avocado, balsamic vinegar, broccoli, cabbage, cinnamon, dark chocolate, flax seeds, garlic, ginger, green tea, legumes, mushrooms, olive oil, onions, red sweet potato and strawberries.

Science is still in the dark about so much concerning autoimmune disease.  Most have only been described in the past 50 years and the difficulty is that unlike infectious diseases the cause cannot be pinpointed. The exact cause of an autoimmune disease is often unknown. Because there are few specific diagnostic tests, diagnosis of many of these disorders is delayed and there is often confusion over exactly what the patient has. There is an urgent need for more research so the answers to the many questions can be found.