Autoimmune Diseases, Cancer, Obesity and Polyunsaturated Fats
Immunosuppression and “auto” immune diseases such as multiple sclerosis
Immunosuppression is typically a treatment approach that involves suppressing the immune system to reduce the activity of the immune system. This approach is notable in organ transplants to avoid rejection of tissue that is not considered “self) and sometimes used in the treatment of, a chronic autoimmune disorders, such as multiple sclerosis (MS) that affects the central nervous system.
One type of immunosuppressive treatment used for MS for example is high-dose corticosteroids, such as methylprednisolone, manufactured by Pfizer and affectionally know as the Devil’s Tic Tac’s (A UK sweet) which are often given during a relapse to reduce inflammation and speed up so called recovery.
Another type of immunosuppressive therapy used in MS is disease-modifying therapies (DMTs), which work by suppressing the immune system to prevent the immune cells from “attacking" the myelin sheath that covers the nerves in the brain and spinal cord. These drugs can help to reduce the frequency and severity of relapses, slow the progression of disability, and theoretically improve overall quality of life for people with MS.
Some of the commonly used DMTs for MS include interferon beta-1a, interferon beta-1b, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab, alemtuzumab, ocrelizumab, and cladribine. Each of these drugs has different mechanisms of action, side effects, and risks, and the choice of treatment will depend on factors such as the individual's MS subtype, disease severity, and medical history.
It is important to note that immunosuppressive treatments can increase the risk of infections (c19 for example) and other complications, and individuals taking these drugs should be closely monitored by their healthcare provider. It is also important to weigh the potential benefits and risks of these treatments on a case-by-case basis and to discuss any concerns with a healthcare provider.
Do omega-6 PUFA inhibit the immune system?
There is evidence to suggest that high levels of omega-6 polyunsaturated fatty acids (PUFAs) in the diet can have a suppressive effect on the immune system. Omega-6 PUFAs are classed as “essential” fatty acids because we are born “deficient” possibly because we do not require them, and they are found in many things modern humans now class as foods, including vegetable (seed) oils (such as corn, soybean, and sunflower oil), nuts, and other seeds.
The immune system theoretically requires a balance of omega-6 and omega-3 PUFAs for optimal function, and excessive consumption of omega-6 PUFAs can lead to an imbalance that can negatively impacts immune function. My take on it was and remains that omega-6 should be reduced or eradicated rather than attempting to counter its inflammatory action by the use of omega-3.
Omega-6 PUFAs are metabolised into eicosanoids, which are signalling molecules that can have pro-inflammatory or anti-inflammatory effects on the body. While some inflammation suggested to necessary for the immune system to function properly (theoretically to keep it trained, my view would be that cells able to effectively generate energy are able to respond appropriately and do not need regular exposure to inflammation to keep trained), excessive inflammation can lead to tissue damage and disease. Remember the inflammation caused by c19 inoculation was called an immune response, and greater inflammatory state was viewed weirdly as better immune response…unless of course that inflammation hospitalised an individual.
Studies have suggested that a high omega-6 to omega-3 PUFA ratio in the diet can increase the production of pro-inflammatory eicosanoids and decrease the production of anti-inflammatory eicosanoids, which can contribute to chronic inflammation and a weakened immune system. In addition, some research has suggested that diets high in omega-6 PUFAs may be associated with an increased risk of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, which are characterised by an overactive immune system.
Some researchers suggest that autoimmune disease is the immune system cleaning up diseased tissue, rather than the immune system attacking the individual.
Autoimmune diseases are a complex group of disorders that occur when the immune system supposedly mistakenly attacks the body's own cells and tissues. This theory of autoimmune diseases, sees the immune system fails to distinguish between "self" and "non-self" cells and tissues, leading to the production of antibodies and immune cells that target and attack the body's own cells and tissues. This can result in chronic inflammation, tissue damage, and a range of symptoms that vary depending on the specific disease and the organs or tissues affected.
Autoimmune theory diseases can have a variety of causes, including genetic factors, environmental triggers (such as infections, toxins, or drugs), and dysregulation of the immune system. While the precise cause of autoimmune disease is not fully understood, treatment for autoimmune diseases typically involves managing symptoms and suppressing the immune system to try and prevent further damage to the body's tissues. While there is ongoing research into new treatments and therapies, there is currently no cure for autoimmune diseases, and management often involves a lifelong commitment to medication, “lifestyle” changes, and ongoing medical monitoring.
Danger theory is another theoretical framework (self versus non self is also theoretical) proposed to explain how the immune system recognises and responds to threats in the body, including infection, injury, and disease. According to the danger theory, the immune system does not distinguish between "self" and "non-self" cells and tissues, but instead responds to signals of danger or damage in the body.
In the context of danger theory, inflamed or diseased tissue may be identified as a target for the immune system because it is sending signals of danger or damage to the immune system. These signals can come in the form of molecules called danger-associated molecular patterns (DAMPs), which are released by damaged or dying cells and can trigger an immune response.
Once the immune system is activated in response to a signal of danger or damage, it can initiate a variety of responses, including inflammation, cell recruitment, and tissue repair. Inflammation is a key component of the immune response to danger or damage, as it helps to isolate and eliminate the threat, but chronic or excessive inflammation can contribute to tissue damage and disease.
Self versus non-self is also a theoretical framework despite being the commonly held view
The concept of "self" versus "non-self" in the immune system is a theoretical framework that has been the subject of ongoing debate and revision in the field of immunology, despite this as we saw from 2020 onwards it is widely believed by most true despite no formal evidence.
The self versus non-self model proposes that the immune system can distinguish between the body's own cells and tissues (self) and foreign cells and tissues (non-self) and only attacks the latter. This model was been a useful starting point for understanding the immune system and has guided much of the research in immunology over the past century.
However, the self versus non-self model has been challenged by a growing body of research suggesting that the immune system is not solely dependent on the recognition of non-self antigens, but also recognises and responds to "altered self" antigens, which may include modified or abnormal self-components that have been altered by stress, injury (including foods), or disease. My favoured alternative framework to the self versus non-self model is the "danger theory" mentioned earlier, which proposes that the immune system responds to signals of danger or damage in the body rather than distinguishing between self and non-self. Other theoretical frameworks have also been proposed, such as the "immune tolerance" model, which suggests that the immune system is capable of tolerating self-antigens through a process of education and training. This seems weak given that aged subjects would have had greater time to become immune educated, unless the theory also included immune dementia.
In summary, while the self versus non-self model has been a useful framework for understanding the immune system, it is not the only theoretical framework, and ongoing research is continuing to refine our understanding of how the immune system functions.
Why would the immune system attack an individual? What benefit does this give? Danger theory seems more logical
The immune system is a complex and highly evolved (apart from when it apparently goes rogue and attacks an individual) system that has evolved to protect the body from infectious agents and other threats, such as cancer cells and tissue damage. However, in the case of autoimmune diseases, the immune system “mistakenly” attacks the body's own cells and tissues.
There is no proposed clear benefit to the immune system attacking the body in autoimmune diseases via the self versus non self model. Instead, autoimmune diseases are believed to be the result of a breakdown in the normal processes that regulate the immune system, leading to an inappropriate immune response against the body's own cells and tissues.
Danger theory provides a more holistic and dynamic framework for understanding the immune system's response to disease and damage. In the danger theory, the immune system responds to signals of danger or damage in the body, regardless of whether those signals come from self or non-self components. This allows the immune system to respond to a wide range of threats and adapt its response to changing conditions. In autoimmune diseases, the immune system may perceive the body's own cells and tissues as "dangerous" and launch an attack against them, or simply be clearing up dangerous tissue. This can result in chronic inflammation, tissue damage, and a range of symptoms that vary depending on the specific threat (maybe PUFA) to organs or tissues affected.
While the danger theory does not fully explain the mechanisms underlying autoimmune diseases, it provides a useful framework for understanding how the immune system responds to a wide range of threats and how this response can sometimes go awry, or even actually be appropriate as long as the stimuli is also removed. Ongoing research is continuing to refine our understanding of the immune system and autoimmune diseases, and may lead to new treatments and therapies for these complex and challenging conditions.
Why would it make that mistake?
It seems more likely that tissue gets damaged, for instance by oxidative stress and the immune system identifies it as a danger and acts accordingly. If the external stimuli keeps getting presented then the immune system keeps having to act. For those that stick to self versus non self they are never entirely clear why the immune system sometimes mistakes the body's own cells and tissues as foreign or dangerous, leading to autoimmune diseases. There are several factors proposed that are believed to play a role in the development of autoimmune diseases, including genetics (eugenics), environment, and immune dysregulation.
In some cases, autoimmune diseases may be triggered by external stimuli such as infection, injury, or oxidative stress, which can cause damage to cells and tissues and release molecules called damage-associated molecular patterns (DAMPs) that can trigger an immune response. However, in autoimmune diseases, the immune response is not appropriately regulated and can result in an attack against the body's own cells and tissues, unless of course you suspect that this is an immune response to eradicate diseases cells/tissue. Environmental factors such as infections, toxins (PUFA), and stress (cortisol) may also contribute to the development of autoimmune diseases by triggering an “inappropriate” immune response or by altering the immune system's ability to regulate itself.
In summary, the development of autoimmune diseases is a complex process that likely involves a combination of genetic, environmental, and immune factors. While external stimuli such as oxidative stress may contribute to the development of autoimmune diseases, the underlying mechanisms are still the subject of ongoing research and debate in the field of immunology.
PUFA omega-6 causes inflammation, surely this is a significant systemic danger that would potentially cause localised immune activity?
Excessive (and excessive is contextual) consumption of omega-6 polyunsaturated fatty acids (PUFAs) contribute to inflammation and immune dysregulation. While infants are born “deficient” in omega-6 fatty acids, the modern world is rife with exposure to many many sources. Omega-6 PUFAs are essential fatty acids that the body supposedly needs for many important functions, including cell membrane (see my previous post about Ling’s work disproving membrane theory) structure, hormone production, and immune function. However, when consumed in excess, omega-6 PUFAs can contribute to chronic inflammation by increasing the production of pro-inflammatory molecules called eicosanoids.
Chronic inflammation can contribute to the development of many chronic diseases, including cardiovascular disease, diabetes, and autoimmune diseases. In autoimmune diseases, chronic inflammation can contribute to tissue damage and dysfunction, leading to a range of symptoms and complications.
Some suggest that not all omega-6 PUFAs are harmful., omega-6 PUFAs, such as gamma-linolenic acid (GLA) and arachidonic acid (AA), have been indicated to have anti-inflammatory properties and may regulate the immune system. The standard guidance was to maintain a healthy balance of omega-6 and omega-3 PUFAs, I always opted to reduce or remove omega-6 as a safer strategy.
When were omega-6 oils produced on an industrial scale and how much has their use increased during the last 100 years?
Omega-6 polyunsaturated fatty acids (PUFAs) will have been a part of the human diet for thousands of years, but in tiny amounts. The production of omega-6 oils on an industrial scale began in the early 20th century. The development of new technologies for refining vegetable oils, such as cottonseed, soybean, and corn oils, allowed for the large-scale production of omega-6 oils and their incorporation into a wide range of processed foods.
The use of omega-6 oils in the food supply has increased dramatically over the past century, largely due to the increased consumption of processed and fast foods that are often high in omega-6 oils. In addition, the use of vegetable oils as a cooking oil has also increased, displacing traditional sources of fats such as butter and lard, which are higher in saturated fats and monounsaturated fats.
According to a study published in the journal Nutrients in 2019, the consumption of omega-6 oils in the US diet increased from approximately 9 grams per day in the early 20th century to approximately 20-25 grams per day in the late 20th century. This increase in consumption is largely due to the increased use of soybean oil and corn oil, which are high in omega-6 PUFAs, in processed foods and as a cooking oil. The increase in omega-6 oil consumption has been linked to a range of health problems, including chronic inflammation, cardiovascular disease, and autoimmune diseases.
What is the process required to process industrial PUFA?
The process of refining vegetable oils to produce polyunsaturated fatty acids (PUFAs) on an industrial scale typically involves several steps:
Extraction: The first step is to extract the oil from the plant material. This can be done using mechanical methods such as pressing or using solvents such as hexane to extract the oil.
Degumming: The extracted oil is then treated with water and/or acids to remove any gums or other impurities.
Neutralisation: Next, the oil is treated with an alkaline solution to neutralise any free fatty acids and remove any other impurities.
Bleaching: The oil is then treated with activated clay or other adsorbent materials to remove any pigments, trace metals, or other impurities that may affect the colour, odour, or flavour of the oil.
Deodorisation: Finally, the oil is subjected to high temperature and vacuum conditions to remove any volatile compounds that may give the oil an undesirable odour or flavour.
Throughout this process, the fatty acid composition of the oil can be modified by adjusting the temperature, pressure, and other processing conditions. For example, hydrogenation can be used to convert some of the unsaturated fatty acids into more stable, saturated fatty acids. This process can help increase the shelf life and stability of the oil but can also result in the formation of trans-fatty acids, which have also been linked to a range of health problems.
It is important to note that the exact process used to refine vegetable oils and produce PUFAs can vary depending on the type of oil and the manufacturer. Additionally, some oils, such as cold-pressed or minimally processed oils, may not undergo the same level of processing as highly refined oils.
How have rates of autoimmune disease increased in the same time period?
There is evidence to suggest that rates of autoimmune diseases have increased over the past several decades, which coincides with the increased use of industrial polyunsaturated fatty acids (PUFAs) such as omega-6 oils in the food supply. For example, a study published in the journal Clinical Reviews in Allergy and Immunology in 2018 examined trends in the incidence of autoimmune diseases in the United States over a 25-year period. The study found that the incidence of autoimmune diseases increased significantly during this time period, with the highest increases seen in diseases such as multiple sclerosis, inflammatory bowel disease, and type 1 diabetes.
Other studies have also reported similar trends in autoimmune disease incidence in other countries, suggesting that this is a global phenomenon. While the exact reasons for the increase in autoimmune diseases are not fully understood, a number of factors have been proposed, including changes in diet, lifestyle, and environmental exposures.
One theory is that the increased consumption of omega-6 PUFAs may contribute to the development of autoimmune diseases by promoting chronic inflammation and oxidative stress in the body. Chronic inflammation and oxidative stress are known to play a role in the development of many chronic diseases, including autoimmune diseases. While more research is needed to fully understand the relationship between omega-6 PUFAs and autoimmune diseases, the evidence suggests that reducing the intake of omega-6 oils may help promote optimal health and reduce the risk of chronic disease.
Israel provides some unique insight as it has one of the highest dietary polyunsaturated/saturated fat ratios in the world; the consumption of omega-6 polyunsaturated fatty acids (PUFA) is about 8% higher than in the USA, and 10-12% higher than in most European countries. In fact, Israeli Jews may be regarded as a population-based dietary experiment of the effect of a high omega-6 PUFA diet, a diet that until recently was widely recommended. Despite such national habits, there is paradoxically a high prevalence of cardiovascular diseases, hypertension, non-insulin-dependent diabetes mellitus and obesity-all diseases that are associated with hyperinsulinemia (HI) and insulin resistance (IR), and grouped together as the insulin resistance syndrome or syndrome X. There is also an increased cancer incidence and mortality rate, especially in women, compared with western countries. Studies suggest that high omega-6 linoleic acid consumption might aggravate HI and IR, in addition to being a substrate for lipid peroxidation and free radical formation. Thus, rather than being beneficial, high omega-6 PUFA diets may have some long-term side effects, within the cluster of hyperinsulinemia, atherosclerosis and tumorigenesis. (1)
To summerise:
High Omega-6 PUFA Diet in Israel: Israel is said to have one of the highest dietary ratios of polyunsaturated to saturated fats in the world. This means that the consumption of omega-6 PUFA is notably higher in Israel compared to the USA and most European countries.
Health Paradox: Despite the high consumption of omega-6 PUFA in Israel, there is a paradoxical prevalence of various health issues, including cardiovascular diseases, hypertension, non-insulin-dependent diabetes mellitus, obesity, and certain cancers, especially in women.
Insulin Resistance Syndrome (Syndrome X): These health issues are often associated with hyperinsulinemia (excessive insulin levels) and insulin resistance. They are collectively referred to as the insulin resistance syndrome or Syndrome X.
Potential Negative Effects of Omega-6 PUFA: The passage suggests that high consumption of omega-6 linoleic acid, a type of PUFA, may exacerbate hyperinsulinemia and insulin resistance. Additionally, it mentions that omega-6 PUFA can serve as a substrate for lipid peroxidation and free radical formation, which can have detrimental effects on health.
Long-term Side Effects: The passage raises the concern that high omega-6 PUFA diets in Israel may have long-term side effects, potentially contributing to a cluster of health problems that include hyperinsulinemia, atherosclerosis (hardening of the arteries), and tumorigenesis (the formation of tumours).
Do Israelis have a high incidence of autoimmune disease?
The prevalence of autoimmune diseases in Israel, like in other countries, varies depending on the specific autoimmune condition and various factors, including genetics, environmental factors, and lifestyle.
Variation Among Autoimmune Diseases: The prevalence of autoimmune diseases can vary widely among different conditions. Some autoimmune diseases are more common than others. For example, autoimmune conditions like Hashimoto's thyroiditis and celiac disease are relatively common worldwide, while others may be less prevalent.
Genetic and Environmental Factors: Genetic predisposition plays a significant role in autoimmune diseases. Some autoimmune diseases have a higher prevalence in certain ethnic or population groups. Environmental factors, such as infections, exposure to toxins, and dietary habits, can also influence the development of autoimmune diseases.
Research and Epidemiological Studies: To understand the specific prevalence of autoimmune diseases in Israel, researchers conduct epidemiological studies. These studies provide data on the occurrence and distribution of diseases in a population. The prevalence of autoimmune diseases may be influenced by factors such as the population's genetic makeup, healthcare infrastructure, and access to medical care.
Rheumatoid Arthritis and Multiple Sclerosis: Israel has been reported to have a relatively high prevalence of certain autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. These conditions have been the focus of epidemiological research in Israel.
It's important to note that the field of autoimmune diseases is continuously evolving, and new research may provide updated insights into their prevalence and risk factors in Israel and other regions.
References:
1. Yam, D., Eliraz, A., & Berry, E. M. (1996). Diet and disease--the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Israel journal of medical sciences, 32(11), 1134–1143.
