Chronic inflammatory diseases are increasinga Increasing in importance in the western world:
- doubling of allergy sufferers in the last 20 years (Schlaud M et al. 2008, Federal Health Gazette 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 almost 3 times more common today 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 English J Med. 2017; 13:1419-29)
- Increase in the prevalence of Periodontitis since 1997 by 26.9% (35-44 year old adults) or 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 based on a loss of immune tolerance: A good immune system controls both attack (i.e.H the ability to effectively and quickly eliminate pathogenic agents or tumor cells) as well as tolerance (i.e.H the ability not to attack the body's own cells, commensal pathogens or inconsequential allergens).
They are all based on immunological “overreactions” against:
- Allergens: hay fever, drug allergies etc
- Autoantigens: Diabetes type I, Hashimoto, 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 --> Detection of mast cell-associated inflammation
Mitochondriopathy, measurable by:
- ATP (adenosine triphosphate = the “cell energy produced in the mitochondria”) low intracellular ATP can be an indication of impaired mitochondrial function in the leukocytes
Oxidative stress, measurable by:
- MDA-LDL: increased MDA-modified LDL as an indication of significant lipid peroxidation as a result of oxidative stress
Nitrosative stress, measurable by:
- Nitrotyrosine: increased nitrotyrosine indicates increased formation of nitric oxide (NO)
Immune activation is at the center of inflammation:
3 types of inflammation related to the immune system:
1. Inflammation caused by 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
- Have stored messenger substances such as histamine
- Histamine is a messenger substance in the inflammatory reaction to cause the tissue to swell (blood vessels become more permeable so that the immune cells can get into the affected tissue more easily; as more fluid gets into the tissue, it swells)
2. Inflammation due to macrophage activation
- phagocytes, belong to the leukocytes
- Kill antigens
- The Tumor necrosis factor (TNF) is a signaling substance that primarily.a is released 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) and thus activate 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
- Inflammatory symptoms
- Oxidative/nitrosative stress through induction of oxygen and NO radicals
Nervous system
- Depression: the inflammation-mediated tryptophan breakdown reduces serotonin
- Sleep disorders (melatonin is formed 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 transmembrane potential and increases pain perception
- Muscle pain (myalgia) can therefore be the result of chronic inflammation
Bone (osteoporosis, periodontitis etc)
- Proinflammatory 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
When there is inflammation, the immune system draws on all energy and vital substance reserves.
Therefore, therapy for chronic inflammation is based on two levels:
- Search and eliminate the individually relevant triggers of inflammation
- Diagnostics and therapy of cellular functional deficiency: supplementation of trace elements, vitamins, antioxidants, etc.
Specific therapeutic approaches for chronic inflammation
1. Suppression of toll-like receptors by adaptogens (immunomodulators)
What are Toll-Like Receptors (TLR)?
TLR are part of the innate immune system, i.e.dR on the cell surface of macrophages (but also on mast cells, B lymphocytes, on the intestinal epithelium, etc.) and serve to recognize pathogens by recognizing structures that only occur on pathogens. This allows the immune system to distinguish between the body's own and foreign substances. If such a pathogenic structure is recognized, the TLRs initiate the immune reaction (e.g.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:
- Curcuma 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 through 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 are there 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 (AGE): Nutrition and Antioxidants
What are AGEs?
Advanced glycation end products are cross-linked structural proteins and can be viewed as “fuels” of systemic inflammation. They arise from the irreversible “gluing” (glycation) of proteins, lipids and nucleic acids with sugar (fructose, glucose and galactose).
AGEs bind to the RAGE receptor of monocytes, macrophages and endothelial cells. This leads to the activation of transcription factors such as NFkB for the formation of pro-inflammatory messenger substances such as TNF-alpha, IL-1 and -6, IGF-1 (insulin-like growth factor).
How do AGEs arise?
AGEs can either be supplied directly through certain foods (exogenous) or can form in the body over several weeks (endogenous):
Exogenous:
- Foods with a lot of saturated fatty acids are usually AGE-rich, such as: Meat, cheese or sausage. But also the way food is prepared, such as: Grilling, roasting, deep-frying or long cooking can increase the AG content many times over.
Endogenous:
- Sugar supplied through food, e.g. in grains (wheat), cakes, chocolate etc. reacts irreversibly with the body's own proteins, lipids and nucleic acids to form so-called early glucose products, which become AGEs over the course of several weeks
- Endogenous AGE formation is induced by high blood sugar levels. Therefore, all foods that significantly increase blood sugar levels should be avoided if AGE is to be reduced. Wheat for example is digested very quickly by amylase, causing blood sugar to rise sharply and is therefore a strong AGE generator.
- Regardless of blood sugar levels, oxidative stress also promotes AGE formation. Therefore, factors that trigger oxidative stress (e.g. Cigarette consumption) to identify and prevent. In addition, the body's own enzymatic antioxidant system must be supported by supplying antioxidants through food or through supplementation.
3. Intestine as a potential source of inflammation: Treat leaky gut and candida with medicinal mushrooms
Since inflammatory stimulation with antigens takes place primarily via the intestine, the intestine should always be considered in chronic inflammation.
"Leaky Gut": These are microscopic holes in the intestine. Small intestinal cells only have an average lifespan of about five days because they are always exposed to toxins, pathogens, etc., so they have to regenerate quite frequently. Some materials even have a lifespan of just approx. down two days. If then, for example The micronutrients required for the regeneration of the small intestinal villi are missing and substances such as Gluten breaks the connection between the cells, then undigested food proteins or toxins can enter the body through these microscopic holes, which promotes various chronic diseases, such as: Autoimmune diseases, diabetes, allergic diseases, high blood pressure. Autoimmune diseases in particular are often linked to leaky gut.
The medicinal mushroom Hericium can accelerate the regeneration processes in leaky gut by stimulating the intestinal epithelium to grow. However, with leaky gut it takes significantly longer, around 6-8 months, than in the stomach for the mucous membrane to be “patched” and regenerated.
It is always important not to just rely on the mushrooms, but to always keep an eye on all micronutrients: For example, If the intestinal cells lack building substances and growth factors due to a vitamin D deficiency, the diet or lifestyle changed orin this case vitamin D supplemented and e.g. Gluten should be eliminated from the diet.
Candida: Another typical small intestinal disease is fungal infection caused by Candida albicans, which can cause flatulence, abdominal pain or diarrhea. Colonization of the small intestine by bacteria or Candida is usually related to colon dysbiosis, i.e.H an imbalance in the intestinal flora, or with hypoacidity in the stomach, so that pathogens enter the small intestine via the stomach.
In these cases, Shiitake is the first choice because it is a natural antibiotic and can effectively remove pathogens from the small intestine. As a result, many people show a detoxification reaction when taking shiitake in large quantities or concentrated as an extract, which is often misinterpreted as intolerance.
See also 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 through antioxidants
We will go into more detail on the topic of antioxidants in a separate article.
At this point it should only be mentioned that the body has an enzymatic antioxidant system that has the task of defusing free radicals. Free radicals are highly reactive and can damage tissue and trigger inflammatory reactions. If the body's own enzymatic antioxidant system is overwhelmed by severe oxidative stress, antioxidant supplementation can provide relief.
You should always use an antioxidant complex in which the individual components work synergistically, e.g. by regenerating each other. Such a synergistic relationship exists, for example:b between vitamins C and E. By reducing a free radical, the vitamin itself is oxidized (= becoming a free radical) and can then be reduced again (= “defused”) by the other vitamin. Alpha lipoic acid is not only a strong antioxidant itself, but is also potent in the regeneration of other antioxidants and should therefore not be missing from any good preparation.
5. Influence of unsaturated fatty acids on inflammatory processes
Unsaturated fatty acids are starting materials for eicosanoids (“tissue hormones”), which have important control tasks: in addition to cell division and platelet aggregation (blood clotting), they are primarilya involved in inflammatory processes.
Important Eicosanoids are
- Prostaglandins
- Prostacyclins
- Thromboxane
- Leukotrienes
Arachidonic acid (the “bad” Omega 6 fatty acid) is metabolized into
- Prostaglandins 2 series
- Thromboxane
- Leukotriene 4 series,
- . all of which contribute to acute inflammation!
The Omega 3 fatty acid EPA on the other hand is metabolized into
- Prostaglandins 3 series
- Leukotriene 5 series
- E-Resolvin (E1 inhibits the migration of inflammatory cells into the inflammatory tissue and the formation of the messenger substance interleukin 12),
- .which contribute to the active resolution of the inflammation!
DHA is also metabolized into inflammation-resolving lipid mediators, esp.a in protectins and D-resolvins: Resolvin D2 causes endothelial cells to produce nitric oxide, which prevents the attachment of leukocytes and thus their migration 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…
- provide only the “good” eicosanoids and inhibit the formation of “bad” eicosanoids from arachidonic acid
- have an anti-inflammatory effect, antirheumatic effect, cardioprotective effect and promote the intellectual 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 (+/-))
If larger amounts of “good” Omega 6 fatty acids (linoleic/linolenic acid) are produced, increased amounts of inflammatory arachidonic acid can be formed! Therefore, the ratio of Omega 6 to Omega 3 is important.
The body needs the enzymes delta-6 and delta-5 desaturase to convert plant 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.
Interesting: In the Stone Age, the ratio of Omega 6 to Omega 3 was 4:1. Through livestock breeding, fattening and agriculture, the ratio has continued to deteriorate to the detriment of omega 3 fatty acids and is now ~20:1 in western societies (the DGE recommends a ratio of 5:1)!