The Surprising Role of Amyloids, Oxalates, Sulfur, and Stress in Autoimmune Conditions

The prevalence of autoimmune diseases is on the rise. The United States healthcare system spends an estimated $100 billion annually on autoimmune disorders (Roberts & Erdei, 2020). Even by conservative estimates, autoimmune disorders affect approximately 15-20 million people, with nearly one in every 14 U.S. citizens living with a diagnosed autoimmune condition. Research suggests that many more may go undiagnosed (Roberts & Erdei, 2020). To understand why a once-rare condition has become so widespread, it is essential to explore the underlying causes driving this multifactorial epidemic. The Cochrane Method®–which explores genetic expression, pathogenic reactivation, and the body's stress response–suggest that stress is often the catalyst that triggers this cascade of disruptions. 

How Stress Triggers Autoimmunity

Stress, in many cases, is the firestarter for this cascade of disruptions. Stress often acts as the spark that ignites this chain reaction of immune disruptions. Autoimmunity occurs when the immune system mistakenly identifies the body’s own cells as threats and attacks them. The Cochrane Method® suggests that stress, physical trauma, environmental factors like food, or pathogenic loads such as viruses, parasites, bacteria, and mold may all trigger autoimmune responses. Common dietary components—sulfur, oxalates, and amyloids—can further fuel this process by influencing the stress response and reactivating latent pathogens.

The Stress Response

The Cochrane Method® identifies the stress response as the initial trigger for a wide range of immune system problems. The stress response is modulated by the hypothalamic-pituitary (HPA) axis and the sympathetic nervous system. The HPA axis is a network of glands that manage your body’s reaction to stress by releasing specific hormones, while the sympathetic nervous system controls your 'fight-or-flight' response. The release of stress hormones may trigger states of autoimmunity and exacerbate the symptoms associated with autoimmune diseases (Morey et al., 2015). Hormones like epinephrine, norepinephrine, corticotropin-releasing hormone, adrenocorticotropic hormone, and cort isol reduce the effectiveness of the immune response when released in response to stress.

Stress and Systemic Inflammation

Studies have also linked stress to systemic inflammation, which is a key marker of autoimmune conditions such as rheumatoid arthritis (Ilchmann-Diounou et al., 2020). Stress can alter DNA methylation, a process that controls gene expression, potentially triggering harmful changes in the body (Saunderson, 2016; Vidrascu at al., 2019). For instance, the stress hormone epinephrine can stimulate virulent gene expression in the gastrointestinal tract, increasing the risk of infection (Liao et al., 2015; Moreira et al., 2016). Additionally, epinephrine promotes the overgrowth of harmful gut bacteria, which rapidly form biofilms on intestinal walls, further damaging gut health (Cambronel et al., 2019).

Gut Dysbiosis and Autoimmune Disease

This cycle of autoimmune dysfunction consists of three key elements: the stress response, altered gene expression, and the reactivation of pathogens. When the stress response is initiated, a waterfall effect ensues. Stress hormones can activate virulent gene expression, leading to an increase in pathogenic load, which disrupts the gut's balance (known as dysbiosis). This dysbiosis weakens the gut’s protective tight junctions—structures that prevent harmful substances from leaking into the bloodstream. Additionally, fungal imbalances and stress hormones feed biofilm in the gut. This impairs the body's ability to metabolize sulfur, oxalates, and amyloids, which further feed the biofilm and cause even higher levels of epinephrine.

It is no coincidence that several autoimmune diseases are directly linked to gut dysbiosis. Increased intestinal permeability through gut dysbiosis has been linked to Type I diabetes, rheumatoid arthritis, celiac disease and multiple sclerosis (Kinashi et al., 2021). Inflammatory Bowel Disease (IBD), one of the most prevalent autoimmune conditions, stems from the chronic inflammation of part or all of the gastrointestinal system. Research has shown that in cases of IBD, the body’s histamine receptor activity becomes irregular, disrupting the function of toll-like receptors that normally help control harmful bacteria in the gut (Smolinska et al., 2016).

The Role of Candida and Mast Cells in Autoimmunity

At the heart of autoimmunity is the body's inability to distinguish between foreign invaders and its own cells. Because over 70% of our immune system lives in the gut, immune function is particularly sensitive to the presence of pathogenic imbalances in the GI system and the genetic expressions they incur (Vighi et al., 2008). Chief among the common fungal and yeast imbalances that contribute to and thrive in states of gut dysbiosis is Candida albicans. Candida overgrowth could be linked to an immune response (Cavalheiro et al., 2018). Additionally, immune cells called mast cells can worsen inflammation and fuel Candida growth (Lopes et al., 2015). This process may initiate mast cell degranulation, releasing excess histamine into the body, which further degrades GI health by creating openings in the tight junctions of the gut (Zhang et al., 2016).

Hydrogen Sulfide and Other Dietary Disruptors

Another significant but often overlooked factor in cases of gut dysbiosis is Hydrogen Sulfide gas (H2S). H2S plays a role in regulating gut inflammation and motility, oxidative stress, ulcer healing, apoptosis, vascular tone and hormone secretion. Imbalances in H2S due to gut dysbiosis may lead to Crohn’s, IBS, IBD, ulcerative colitis, obesity and sepsis. Stress, diet, and infection can trigger these imbalances. For instance, meat consumption and a diet high in sulfur could exacerbate H2S in the gut, particularly if an individual has genetic predispositions that impair sulfur metabolism (Singh et al., 2015).

Oxalates and Their Impact on Autoimmunity

In addition to sulfur, oxalates are another dietary disruptor that may intensify states of autoimmunity. Gut dysbiosis that opens up the tight junctions of the gut may induce the increased absorption of oxalates. Normally, oxalates are excreted from the body as waste, but when absorption increases, they can disrupt the immune system. This excess of oxalates may contribute to kidney stone formation, chronic kidney disease, or cardiovascular issues (Sharma et al., 2020). Oxalate metabolism impairment may also exacerbate the activation of inflammatory pathways in the body, creating an environment that further supports an autoimmune response (Ermer et al., 2016).

Amyloids and Their Role in Autoimmune Disruption

Amyloids, which are misfolded protein structures, are another factor that contributes to autoimmune dysfunction. Amyloid accumulation may be found in domestically raised and slaughtered cattle, especially in chickens that have received vaccinations or other treatments (Ibi et al., 2015; Tojo et al., 2005). Unfortunately, cooking, freezing or the use of disinfectants may not be enough to destroy these amyloids in the tissues of these animals prior to consumption (Greger, 2008). Once consumed, amyloids can significantly strengthen biofilm production in the gut, further exacerbating gut dysbiosis and contributing to autoimmune issues.

The gut microbiota, or the community of microbes in our digestive system, can release both amyloids and lipopolysaccharides (LPS), which may be linked to a plethora of inflammatory mechanisms. Several factors, such as dietary changes, food additives, excessive use of probiotics, and nonsteroidal anti-inflammatory drugs, can disrupt the gut's balance and trigger the release of these compounds. Bacteria in the gut microbiota that release amyloids may increase pathogenic colonization due to the formation and aggregation of biofilm in the gut (Pistollato et al., 2016). Individuals who are most susceptible to amyloid-induced autoimmunity are generally those with a weakened stomach lining. Because the cells of the intestinal lining replicate every three to five days, amyloid-producing pathogens are provided with a fertile environment, using the abundance of dead cells to create stronger biofilms (Gallo et al., 2015).

Viral Reactivation and Its Impact on Autoimmune Conditions

Viruses of the Herpesviridae family, such as cytomegalovirus (CMV) and Epstein Barr Virus (EBV), can have a significant impact on autoimmune conditions. High levels of CMV could be associated with lupus, HIV, heart disease, and cancer, while the EBV could be linked to autoimmune conditions such as multiple sclerosis, lupus, rheumatoid arthritis, and autoimmune thyroid diseases Hashimoto’s (dos Santos Nunes et al., 2017; Michaelis et al., 2009; Wang et al., 2017). EBV, in particular, modifies the way our immune system responds to infection and is often present in individuals suffering from Hashimoto’s thyroiditis (Dittfield et al., 2016). It is important to note that the viral load of EBV, even when latent, remains relatively the same throughout its life in hosts, and elevated cortisol and epinephrine could reactivate EBV (Coskun et al., 2009). For example, EBV remains latent in approximately 90% of people infected (Coskun et al., 2009). This is because external stress signals the body to release stress hormones that could dysregulate the immune system and certain genes to support the reactivation of EBV in the body. Studies have shown that cortisol and epinephrine may also modulate genetic expression for the Herpes Simplex Virus (HSV).

Addressing Autoimmunity: A Multifactorial Approach

In summary, stress hormones promote the reactivation of pathogenic loads, affect genetic expression, and degrade gut health, leading to a state of dysbiosis. This gut imbalance weakens the body’s ability to regulate immune responses and properly metabolize potential dietary disruptors like sulfur, oxalates, and amyloids. As a result, the combination of genes, pathogens, and stress creates a perfect storm for autoimmune dysfunction. Addressing these factors—particularly by managing stress and making dietary changes—can be crucial in mitigating the onset and progression of autoimmune conditions.

The Modern Autoimmune Epidemic

A combination of factors may explain why autoimmunity is more common today than it was twenty years ago, and stress may be one of the primary underlying influences. The stressors of our modern lives, from financial burdens to certain social pressures, are compounded by the stressors on our plates. An already stressed system has been further taxed where the multiple stressors of the pandemic have contributed to a firestorm of autoimmunity.

Our food supply has been degraded, much like the body's cells in autoimmune diseases. Factory farming practices, widespread use of herbicides and endocrine disruptors in the water supply, and the billions of pounds of glyphosate sprayed on U.S. crops each year, all make it increasingly difficult for the body to process sulfur, oxalates, and proteins. This nutritional stress, combined with the unrelenting pressures of the modern American lifestyle, has created a perfect storm for autoimmune dysfunction. As a result, the Standard American Diet, in conjunction with pandemic-related stress, has significantly increased the burden on our immune systems.

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