Chronic inflammatory diseases are increasing v.a...is steadily gaining in importance in the Western world:

• Doubling of allergy sufferers in the last 20 years (Schlaud M et al. 2008, Bundesgesundheitsblatt 50: 701-710)
• incidence of Crohn's disease more than doubled in 24 years (Jacobsen BA et al. Eur J Gastroenterol Hepatol. 2006; 18:601-6)
• multiple sclerosis Today it is almost 3 times more common than in 1970 (Alonso A, Hernan MA. Neurology 2008, 8;71:129-35)
• Autoimmune-related Diabetes mellitus increased by 70% in 12 years (Mayer-Davis E. N Engl. J Med. 2017; 13:1419-29)
• Increase in the prevalence of Periodontitis since 1997 by 26.9% (adults aged 35-44) and by 23.7% (seniors) &> 65 years) (Schiffner U et al. Community Dent Health. 2009; 26:18-22. Oral health in German children, adolescents, adults and senior citizens in 2005)

What do chronic inflammatory diseases have in common?

Inflammatory diseases are present Loss of immune tolerance underlying: A good immune system controls both attack (d.h. the ability to effectively and quickly eliminate pathogenic agents or tumor cells) as well as tolerance (d.h. the ability not to attack the body's own cells, commensal pathogens, or insignificant allergens).
They are all therefore based on immunological “overreactions” against:

• AllergensHay fever, drug allergies, etc.
• AutoantigensType 1 diabetes, Hashimoto's thyroiditis, multiple sclerosis, celiac disease, ulcerative colitis, etc.
• (commensal) Infectious agents: Periodontitis, Crohn's disease, candidiasis etc

A loss of immune tolerance can have various causes – such as: stress, biocides, electromagnetic fields, plasticizers, unhealthy diet, titanium, plastics, industrial toxins, metals, etc. (Source: Pall, Dr. (PhD) ML: Explaining ‘Unexplained Illnesses’)

How can I diagnose systemic inflammation?

Increased immune activation, measurable by:

• TNF-alpha
• IP-10
• Histamine --&evidence of mast cell-associated inflammation

Mitochondrial dysfunction, measurable by:

• ATP (Adenosine triphosphate = the “cell energy” produced in the mitochondria)  low intracellular ATP can indicate impaired mitochondrial function in leukocytes

Oxidative stress, measurable by:

• MDA-LDL: elevated MDA-modified LDL as an indication of significant lipid peroxidation as a result of oxidative stress

Nitrosative stress, measurable by:

• NitrotyrosineElevated nitrotyrosine levels indicate increased production of nitric oxide (NO).

Immune activation is at the heart of inflammation:

3 types of inflammation in relation to the immune system:

1.Inflammation caused Mast cell activation

• Mast cells are part of the innate immune system.
• Immediate defense against infection at the interfaces between the body and its environment
• Do messenger substances like histamine saved
• Histamine is a messenger substance in the inflammatory response, causing tissue to swell (blood vessels become more permeable so that immune cells can more easily enter the affected tissue; as more fluid also enters the tissue, it swells).

2. Inflammation caused by Macrophage activation

• Phagocytes belong to the leukocytes.
• Do antigens kill?
• The Tumor necrosis factor (TNF) is a signaling molecule that v.a. is secreted by macrophages

3. Inflammation caused by T helper cell activation (Lymphocytic inflammation)

• T cells are part of the acquired ("adaptive") immune system.
• A distinction is made between T killer cells ("kill"), T helper cells ("sound the alarm") and regulatory T cells (prevent excessive attacks on intact body cells).
• T helper cells produce inflammatory cytokines such as TNF-alpha, Interferon (IFN)-gamma and interleukin 2 (IL2), thereby activating macrophages, NK (natural killer cells/part of the innate immune system) and T killer cells (part of the adaptive immune system/recognize foreign cells via antigens)

Possible effects of chronic inflammation on

immune system

• Inflammation symptoms
• Oxidative/nitrosative stress through the induction of oxygen and NO radicals

nervous system

• Depression: inflammation-mediated tryptophan degradation reduces serotonin.
• Sleep disorders (melatonin is produced from serotonin)

Hormonal system

• Inflammation increases ACTH production and thus cortisol levels.
• Chronically high cortisol levels reduce testosterone and estrogen production.
• Infertility and loss of libido can therefore be indirectly attributed to chronic inflammation.

muscles

• Inflammation increases protein catabolism, lowers the transmembrane potential, and increases pain perception.
• Muscle pain (myalgia) can therefore be the result of chronic inflammation.

Bone (Osteoporosis, periodontitis etc)

• Pro-inflammatory cytokines play an important role in the destruction of inflamed joints.
• In rheumatoid arthritis, TNF, IL-1, IL-6 and IL-17 increase the activation of osteoclasts and thus induce bone destruction.

In the presence of inflammation, the immune system depletes all energy and vital nutrient reserves.

Therefore, the Therapy for chronic inflammation on two levels:

1. Identification and elimination of individually relevant triggers of inflammation
2. Diagnosis and therapy of cellular functional deficiency: Supplementation of trace elements, vitamins, antioxidants, etc.

Specific treatment approaches for chronic inflammation

1. Suppression of Toll-like receptors by adaptogens (immunomodulators)

What are Toll-like receptors (TLR)?

TLRs are part of the innate immune system, they are located i.d.R.TLRs are located on the cell surface of macrophages (but also on mast cells, B lymphocytes, the intestinal epithelium, etc.) and serve to recognize pathogens by identifying structures that are only found on disease-causing agents. This allows the immune system to distinguish between the body's own substances and foreign substances. If such a pathogenic structure is recognized, the TLRs initiate the immune response (u.a. via cytokines such as TNF-alpha, IL-1, IL-6) and modulate them.

According to current knowledge, there are 13 different TLRs that react to different pathogens.

The anti-inflammatory effect of many naturopathic preparations can be explained by the suppression of Toll-like receptors (TLRs) on macrophages:

• Turmeric extract: “Inhibition of homodimerization of Toll-like receptor 4 by curcumin.” (Biochem Pharmacol. 2006; 72:62-9)
• Cinnamon (e.g., contained in the liver and detoxification complex CLEAN): “Cinnamaldehyde suppresses toll-like receptor 4 activation mediated by the inhibition of receptor oligomerization” (Biochem Pharmacol. 2008; 75:494-502)
• Vitamin D3/K2: “Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes” (Rheumatology 2010; 49:1466-71)
• Resveratrol: “Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol.” (J Immunol. 2005; 175:3339-46)

What potent adaptogens exist in Ayurveda and Traditional Chinese Medicine?

• Ayurveda: Brahmi, Ashwagandha, Shatavari
• TCM: Medicinal mushrooms (due to their beta-glucans) such as Agaricus blazei (almond mushroom), Hericium or Reishi

2. Reduce Advanced Glycation Endproducts (AGEs): Nutrition and Antioxidants

What are AGEs?

Advanced glycation end products (AGEs) are cross-linked structural proteins and can be considered the "fuels" of systemic inflammation. They are formed by the irreversible "binding" (glycation) of proteins, lipids, and nucleic acids with sugars (fructose, glucose, and galactose).

AGEs bind to the RAGE receptor of monocytes, macrophages, and endothelial cells. This leads, via the activation of transcription factors such as NF-κB, to the formation of pro-inflammatory signaling molecules such as TNF-α, IL-1 and -6, and IGF-1 (insulin-like growth factor).

How are AGEs formed?

AGEs can either be ingested directly through certain foods (exogenous) or form in the body over several weeks (endogenous):

Exogenous:

• Foods high in saturated fat are generally rich in AGEs, such as meat, cheese, or sausage. However, the method of food preparation, such as grilling, roasting, frying, or prolonged cooking, can also increase the AGE content many times over.

Endogenous:

• Sugars ingested through food, e.g. in grains (wheat), cakes, chocolate, etc., react irreversibly with the body's own proteins, lipids, nucleic acids to form so-called early gluconeogenesis products, which become advanced glycation end products (AGEs) over the course of several weeks.
• Endogenous AGE formation is induced by high blood sugar levels. Therefore, all foods that significantly raise blood sugar levels should be avoided if AGEs are to be reduced. Wheat, for example, is digested very quickly by amylase, causing a sharp rise in blood sugar and thus making it a strong AGE producer.
• Regardless of blood sugar levels, oxidative stress also promotes AGE formation.Therefore, factors that trigger oxidative stress (e.g.,to identify and prevent cigarette consumption). Furthermore, the body's own enzymatic antioxidant system is affected by Supply of antioxidants to support this through diet or supplementation.

3. The gut as a potential source of inflammation: Treating leaky gut and Candida with medicinal mushrooms

Since inflammatory stimulation with antigens primarily occurs via the gut, the gut should always be considered in cases of chronic inflammation..

"Leaky Gut"Leaky gut refers to microscopic holes in the intestine. Small intestine cells have an average lifespan of only about five days, as they are constantly exposed to toxins, pathogens, etc., requiring frequent regeneration. Some substances can even reduce their lifespan to just two days. If, for example, the micronutrients necessary for the regeneration of small intestine cells are lacking, and substances like gluten disrupt the connections between the cells, undigested food proteins or toxins can pass through these microscopic holes into the body. This can contribute to various chronic diseases, such as autoimmune diseases, diabetes, allergies, and high blood pressure. Autoimmune diseases, in particular, are very often associated with leaky gut.

The medicinal mushroom Hericium can accelerate regeneration processes in cases of leaky gut syndrome.by stimulating the growth of the intestinal epithelium. However, in the case of leaky gut, it takes significantly longer than in the stomach, approximately 6-8 months, for the mucous membrane to be "repaired" and regenerated.

It is always important not to rely solely on mushrooms, but to keep all micronutrients in mind: for example, if intestinal cells lack building blocks and growth factors due to a vitamin D deficiency, the diet or lifestyle should be changed. bzw.in In this case, vitamin D should be supplemented and, for example, gluten should be eliminated from the diet.

CandidaAnother typical small intestine disease is fungal infection with Candida albicans, which can cause bloating, abdominal pain, or diarrhea. Small intestine colonization by bacteria or Candida is usually associated with large intestine dysbiosis. d.h. an imbalance in the intestinal flora, or with low stomach acidity, so that pathogens can enter the small intestine via the stomach.

In these cases the Shiitake Shiitake mushrooms are a first choice because they are a natural antibiotic and can effectively eliminate pathogens from the small intestine. Incidentally, many people experience a detoxification reaction when taking shiitake mushrooms in larger quantities or as a concentrated extract, which is often misinterpreted as an intolerance.

See also regarding the antimicrobial effect of shiitake mushrooms https://pubmed.ncbi.nlm.nih.gov/15773410/ "The juice of this mushroom at a concentration of 5% from the volume of the nutrient medium was found to produce a pronounced antimicrobial effect with respect to C. albicans, S. aureus, E. faecalis, E. coli O-114 and to stimulate the growth of E. coli M-17. Bifidobacteria and lactobacteria exhibited resistance to the action of L. edodes juice."

4. Reduce oxidative stress with antioxidants

We will discuss the topic of antioxidants in more detail in a separate article.

Therefore, it should only be mentioned here that the body possesses an enzymatic antioxidant system whose function is to neutralize free radicals. Free radicals are highly reactive and can damage tissue and trigger inflammatory responses. If this endogenous enzymatic antioxidant system is overwhelmed by severe oxidative stress, antioxidant supplementation can provide relief.

It is always advisable to take an antioxidant complex in which the individual components work synergistically, for example by regenerating each other. Such a synergistic relationship exists z.B...between vitamins C and E. This is because, by reducing a free radical, the vitamin itself is oxidized (becoming a free radical) and can then be reduced (neutralized) again by the other vitamin. Alpha-lipoic acid is not only a powerful antioxidant itself, but is also potent in regenerating other antioxidants and should therefore be included in any good supplement.

5. Influence of unsaturated fatty acids on inflammatory processes

Unsaturated fatty acids are precursors for eicosanoids ("tissue hormones"), which have important regulatory functions: in addition to cell division and platelet aggregation (blood clotting), they are v.ainvolved in inflammatory processes.

Important Eicosanoids are

• Prostaglandins
• Prostacyclin
• Thromboxane
• Leukotrienes

Arachidonic acid (the “bad” omega-6 fatty acid) is metabolized into

• Prostaglandins 2 series
• Thromboxane
• Leukotrienes 4 series,
• ... all of which contribute to acute inflammation!

The Omega 3 fatty acid EPA In contrast, it is metabolized in

• Prostaglandins 3 series
• Leukotriene 5 series
• E-Resolvin (E1 inhibits the migration of inflammatory cells into the inflamed tissue as well as the formation of the messenger substance interleukin 12),
• ...which contribute to the active resolution of inflammation!

DHA is also metabolized into anti-inflammatory lipid mediators., v.a. in protectins and D-resolvins: Resolvin D2 causes endothelial cells to produce nitric oxide, thereby preventing leukocytes from adhering to the cells and thus from migrating into the inflamed tissue.

Despite strong similarities in molecular structure, the biological functions of Omega 3 and Omega 6 fatty acids are very different:

Omega 3 fatty acids…

• They only supply the "good" eicosanoids and inhibit the formation of "bad" eicosanoids from arachidonic acid.
• works anti-inflammatory, antirheumatic cardioprotective and promote the mental development of the embryo

Omega 6 fatty acids

Omega 6 fatty acids can have both anti-inflammatory (linoleic and linolenic acid) and pro-inflammatory (arachidonic acid/s.o.) and even form carcinogenic eicosanoids, (Omega 3, on the other hand, only forms the "good", anti-inflammatory eicosanoids (+/-))

When larger amounts of "good" omega-6 fatty acids (linoleic/linolenic acid) are present, increased amounts of pro-inflammatory arachidonic acid can be produced! Therefore, the ratio of omega-6 to omega-3 is important.

The body requires the enzymes delta-6 and delta-5 desaturase to convert plant-based ALA into EPA/DHA. These two enzymes are also needed to convert the omega-6 fatty acid linoleic acid into other omega-6 fatty acids.By reducing the proportion of omega 6 fatty acids in the diet, the body has more enzymes available to convert ALA into EPA/DHA.

Interestingly, in the Stone Age the ratio of Omega 6 to Omega 3 was at 4:1. Due to livestock farming, fattening, and agriculture, the ratio has worsened to the detriment of omega-3 fatty acids and is now around 20:1 in Western societies (the German Nutrition Society (DGE) recommends a ratio of 5:1)!