Inflammation, due to its extreme importance, will be discussed in more detail, since the destructive effect of chronic inflammation is extraordinary among all pathological processes, including cancer * *.
Inflammation is a complex, temporary physiological process that occurs in response to a pathogen or other tissue damage *. In inflammation, the body's immune system neutralizes and removes various proteins that it considers potentially harmful to the body.
Acute inflammation is a natural defensive reaction to sudden disturbance. When foreign proteins invade (viruses, microbes, etc.), or when a mass of body cells destroyed as a result of some kind of catastrophe appears, cells of the immune system, such as lymphocytes and macrophages, recognize, mark, attack and destroy such a «biological garbage». This multi-step process is accompanied by an increase in the level of signaling molecules that control inflammatory responses.
As pathogens disappear and the threat to the body recedes, suppressor cells suppress the acute defensive response, allowing tissue to repair itself. If the cause of inflammation is not completely eliminated, or is eliminated, but the level of pro-inflammatory molecules does not return to its original level, then the inflammatory response does not properly fade away, and the acute phase of inflammation becomes chronic.
Sometimes the inflammatory signals are stronger than the challenge requires, and then the overexcited cells of the immune system are able to begin repression against the cells of their own body. There are other reasons for this pathology. The resulting conditions are called autoimmune.
Inflammation can be local or general (systemic inflammation). Local inflammation is characterized by four signs: 1) redness, 2) swelling, 3) fever, and 4) pain. Chronic local inflammation of specific organs greatly increases the risk of cancer in those organs *. Chronic low-level systemic inflammation does not show such noticeable signs as acute inflammation, but has a detrimental effect on the entire body; it increases the risk of cardiovascular and neurodegenerative diseases, and may be associated with 90% of all cancers * *.
Irritants, pathogens, damage
Persistent acute inflammation caused by non-degradable pathogens or non-degradable foreign bodies, autoimmune reaction
Neutrophils, basophils, eosinophils, monocytes, macrophages
Monocytes, macrophages, lymphocytes, fibroblasts, plasma cells
A few days
Several months or years
Resolution, abscess formation, chronic inflammation
Tissue destruction, fibrosis, tumors
Low intensity systemic inflammation is accompanied by a number of signs and symptoms: a variety of uncomfortable conditions (aching pain in the body or joints, chronic fatigue, headache, weakness); a variety of metabolic disorders (weight gain, increased glucose levels and blood pressure); a variety of psychological disorders (depression, anxiety, mood disorders, insomnia, memory impairment, «blurred» thinking); various gastrointestinal disorders (irritable/leaky bowel syndrome); various skin problems (seborrhea, skin peeling); frequent infectious diseases.
Although inflammation is a natural protective and repair biological process, a prolonged inflammatory state can be detrimental to the affected tissue.
Chronic latent systemic inflammation is the underlying cause of the most common degenerative conditions: cardiovascular disease, hypertension, arthritis, diabetes, Alzheimer's disease, atherosclerosis, multiple sclerosis, chronic kidney disease, osteoporosis, depression, and many others * *. Personally, for each of these ailments, medicine offers a scattering of synthetic drugs. But none of them eliminates the root of the problem, instead masking and hiding the further degradation of the body. At the same time, the fight against inflammation will reduce the risk of developing and the severity of not only cancer, but also all of the diseases listed above.
Studies of the last decade provide more and more evidence that chronic local inflammation * * is also the starting cause of cancer and its constant companion at the tissue level, and genetics is already involved in the tumor process as it develops. Under normal conditions, cancer could not start from a single mutated cell, or even from a group of such cells, because they would be immediately recognized and destroyed by the immune system. Only the inflammatory environment provides them with a favorable niche for conservation and reproduction. No inflammation, no cancer.
Inflammation is the central site of all neoplastic disease * *. It contributes not only to the appearance, but also to the maintenance and development of the tumor through a number of mechanisms * * *. Accumulating evidence shows that chronic inflammation contributes to the acquisition of all the hallmarks of cancer *, including genomic instability, apoptosis evasion, unrestricted replication, sustained angiogenesis, ignorance of growth limiting signals, immune evasion, invasion and metastasis to distant tissues *.
The body views the tumor as a chronic, inflamed wound, and works hard to heal it by stimulating cell division, which leads to more and more tumor growth and a steady increase in inflammatory signals. All desperate efforts of the body to restore tissue, which in fact does not need restoration, will continue until the complete exhaustion of its resources, until its death.
The simple destruction of cancer cells without weakening and normalizing the inflammatory process, without healing the underlying tissue damage, without eliminating the causes of these damage, will most likely lead to a relapse of the disease.
Eliminating a fire begins with turning off the gas, and eliminating a leak begins with shutting off the water. Only after this, operational measures begin – extinguishing the fire or pumping out the water. In the same way, you should first block the cause of inflammation, and only then proceed to eliminate its consequences.
Consider the main factors of inflammation in more detail.
Genetic predisposition. Some people are born with genetic traits that make them more susceptible to inflammation. For example, they may lack certain enzymes or other molecules needed for an adequate inflammatory response. A well-known example of a genetic predisposition to inflammation is the presence of the ApoE-ε4 allele; especially his homozygous status (when this allele is inherited from both parents).
Although we have to come to terms with the fact that we are not able to change our genotype, even in people with a genetic predisposition, reducing the causes of inflammation with the methods available to us can significantly improve the overall inflammatory status. Genetics predisposes, but does not oblige. It depends on our behavior whether genetically determined dangers will have a chance to materialize or not.
Tissue injury can be physical (mechanical, thermal, radiation), chemical, biological. The most obvious example of chronic pro-inflammatory mechanical injury is asbestos dust. Once in the lungs, sharp microcrystals of asbestos damage cells and tissues, causing low-intensity latent inflammation.
Another common example is uric acid crystals, which are deposited in the joints and cause inflammation, as occurs in gouty arthritis; or damage tissue in other organs, such as the urinary * *. Cholesterol crystals, which are deposited on the walls of blood vessels, also mechanically injure cells and tissues. Ultraviolet irradiation is another clear example of physical injury to living tissue, but this applies more to the skin than to other organs. But X-ray radiation passes through the body, injuring it at the molecular level.
The most common mechanical injury to the breast tissue is bruises. Surgical (including cosmetic) breast surgery, radiation therapy, and even an annual mammogram can also increase the risk of the disease, especially when combined with other risk factors.
Chemical damage is caused mainly by free radicals. The excess of free radicals and the damage they cause is called «oxidative stress». In fact, oxidative stress is an imbalance between the production of free radicals called oxidants (reactive oxygen or nitrogen species) and their neutralization by defense mechanisms called antioxidants. Thus, oxidative stress can be markedly reduced by taking adequate amounts of antioxidants; Fortunately, in this regard, we have a very wide choice.
Chemical damage can be caused by a wide variety of aggressive molecules, toxic chemicals and heavy metals.
A very common substance that chemically injures the epithelium is homocysteine. To reduce the level of homocysteine, a complex of vitamins and minerals * can be used: vitamins B2 (riboflavin-5-phosphate) – 25-100 mg/day, B6 (pyridoxal-5-phosphate) – 100-200 mg/day, B9 (folic acid, 5-MTHF) – 1-10 mg/day, B12 (methylcobalamin) – 0.3-1 mg/day, B16 (trimethylglycine) – 0.5-3 g/day; vitamin D3 (cholecalciferol) – 50 μg/day; N-acetyl-L-cysteine (NAC); S-adenosyl-methionine (SAMe); taurine; as well as zinc (15-50 mg/day), selenium, magnesium (400-800 mg/day), food polyphenols. Reducing the consumption of meat and physical activity helps to reduce the intake of homocysteine in the body. However, calorie restriction in general also reduces inflammatory markers *.
An excess of iron and copper contributes to an increase in oxidative stress. Supplements that can reduce excess iron include ground flax, calcium, magnesium, garlic, vitamin E, green tea, and resveratrol.
Biological damage is mainly associated with inflammation, infections, hormonal disorders, nutritional deficiencies, and stress. For the mammary gland, the main dangers of biological injury are viral infections and a violation of the ratio of estrogen to androgen.
Chronic infections can be caused by pathogenic viruses, bacteria, fungi, protozoa, and also multicellular parasites. The inability of the body to finally get rid of them will cause, albeit low-intensity, but chronic inflammation.
Infections can be in a suppressed (latent) state for a long time, and come out of it at times when the immune system is weakened. The combination of infection with injury increases the risk of cancer in the injured area. Carcinogenic viruses can circulate throughout the body, but the tumor they cause only appears in the wound and at the site of inflammation, and can be suppressed by anti-inflammatory agents *.
Infections can hide in places where it is difficult for immune cells to reach them, for example, in places of fibrosis, or in the canal of a diseased or dead (with extracted nerve) tooth *. During chewing, pressure on the base of the tooth pushes pathogens and toxins out of their hiding place and into the bloodstream and lymphatic system. Periodontitis is suspected as a serious risk factor for both breastcancer * * * and cardiovascular disease * *. Teeth with chronic occult abscesses are very common, but may remain undisturbed for many years and only be detected on X-ray.
The asymptomatic nature of many infections makes it difficult to detect. There are, however, some laboratory methods that can detect latent infections in a blood sample.
In addition, autoimmune diseases such as lupus, rheumatoid arthritis, Crohn's disease, or Hashimodo's disease create chronically elevated inflammatory levels.
Contaminants. Inflammation can be caused by certain foreign materials that have been in the body for a long time. For example, some industrial chemicals that cannot be eliminated by enzymatic degradation.
At the top of a long list of food contaminants is butylhydroxytoluene (E321), which is used as a stabilizer in baking; bisphenol, which is found in plastic utensils, plastic film and thermal paper for printing sales receipts; parabens, which are found in most antiperspirants, deodorants, sunscreens and makeup; triclosan, which is often found in toothpastes, shampoos and toilet soaps. This also includes a variety of additives that are mixed in to improve the appearance, smell and taste of food.
Almost every cooked food item is either saturated with synthetic trans fats or vegetable oils high in ω-6 fat acids, or worse, cooked with them, saturating us with free radicals.
In addition to external, there are also internal contaminants, such as certain metabolic products, advanced glycation end products, or oxidized lipoproteins.
Once recognized as a signal of foreign invasion, pollutants trigger a natural immune response. In the case of their chronic intake, or a weak possibility of their metabolic neutralization, or the impossibility of their destruction by phagocytes, a permanent inflammatory state occurs. Knowing the sources of pollution, we can try to avoid them.
Toxins enter the body with air, water, food and through the skin. To neutralize toxins, cells of the immune system are involved, which increases the inflammatory index.
Cigarette smoke contains several inflammatory factors, especially reactive oxygen species. Smoking increases the production of several pro-inflammatory cytokines (TNF-α, IL-1α, IL-6, IL-8) while decreasing the production of anti-inflammatory molecules *.
However, mycotoxins, toxins produced by fungi, seem to elicit the strongest immune response. An example would be a moisture-damaged room where the concentration of mycotoxins in the air can be extremely high.
We have the ability to reduce toxins by using personal protective equipment for work-related toxins, by not smoking, by filtering our water and indoor air, by eating organic food, and by choosing non-toxic personal care and home cleaning products. And by detoxifying, you can reduce the amount of toxins already in your body. For example, chelation binds and removes heavy metals.
Inflammation itself increases the level of oxidants and toxins in the tissues and impairs their removal, which only exacerbates the situation.
Allergens. The air we breathe may contain substances that cause an allergenic reaction, such as cigarette tar, plant pollen, animal dander, or other foreign biological material. The food we eat may contain food allergens. The leaders here are dairy, gluten, eggs, and fungi/yeast. Silicone plastic used in implants can be a source of chemicals that cause an inflammatory reaction in the most undesirable place for us – in the breast area.
It would be nice to determine the individual intolerance of many substances with the help of special tests, no matter how expensive they are. They can be carried out once, and their results can be used for the rest of your life. This would be much wiser than long and unsuccessful attempts to reduce the inflammatory potential of allergens without knowing their sources.
Antibodies designed to mark foreign molecules in the body can attach to the body's own proteins when they are coupled to some other molecules, and therefore resemble the natural target of these antibodies. As a result, immune cells attack the body's own cells, causing an inflammatory reaction of varying intensity (autoimmune reaction).
Food and drinks. Many foods consumed in the diet can regulate inflammatory levels in various ways.
Acid load. A strong factor in the effect of food on systemic inflammation is its acid load, which causes an increase in tissue acidity. There are many reasons why the acidity of the body can increase *. However, there are only two main ones. The first is a diet that produces large amounts of acidic metabolites, such as uric acid, which cause chemical cell irritation and tissue inflammation. The second is a deterioration in kidney function, which may be a pathological consequence of the first cause.
Acid metabolites are the result of an unbalanced diet common to the population of industrialized countries. Since the composition of the diet is relatively stable, then, unlike injuries and infections, acidification of tissues can be (and usually is) chronic. Thus, along with harmful working conditions, an acidogenic diet is the most common cause of chronic low-level systemic inflammation.
Food components can cause inflammatory reactions in other ways. For example, inflammation is promoted by an excess of both glucose and proteins or fats *. Eating the typical Western diet, which is overly high in fats and sugars, has been associated with post-meal metabolic stress, which includes increased production of free radicals and pro-inflammatory markers *. As early as 1 hour after a hypercaloric meal, the levels of the inflammatory cytokine and interleukin IL-17 * increase sharply in the blood serum of healthy volunteers. This, however, is mitigated if large amounts of polyphenols are taken with food.
Glucose, either supplied in finished form or formed from complex carbohydrates, is evolutionarily the main food of the cells of the human body. However, an excessive concentration of glucose in the blood is a pathological factor. The curve of cancer risk from fasting blood glucose increases exponentially *. The risk of developing almost all types of cancer is directly related to another indicator – the percentage of glycated hemoglobin (HbA1c) *. This indicator reflects not an instantaneous, but a long-term average level of glucose in the blood. More precisely, the average state of blood glucose levels over the past 3-4 months.
One large study found that elevated HbA1c correlated with diabetes, cardiovascular disease, and more than 30 cancers and non-cancers, including acute cerebral infarction, nephrotic syndrome, certain cancers, coronary heart disease, and chronic obstructive pulmonary disease *. Elevated HbA1C was also associated with an increased risk of all-cause mortality.
The body very strictly monitors the chemical composition of the blood. An increase in blood glucose levels increases the production of insulin, which, through insulin receptors, causes cells to take in excess glucose in order to keep its concentration in the blood within an acceptable range. When the supply of glucose systematically exceeds the demand for it, the function of insulin receptors is pathologically reduced. Cells refuse to take up glucose they don't need. Insulin insensitivity increases and more insulin is produced to overcome it. As a result of this struggle, the blood is saturated with both insulin and sugar, causing metabolic syndrome and type II diabetes.
Excess of both sugar and insulin has a detrimental effect on the body. Excess energy production inhibits mitochondrial respiration and cell viability *. Insulin and insulin-like growth factors are hormonal stimulators of cell growth *. And excess glucose increases oxidative stress in the mitochondria and cytosol of the cell *. Excess sugars also stick to circulating protein molecules, forming molecules that look like foreign proteins, thus stimulating the immune system. Inflammatory levels increase, and with it the risk of breast cancer * * *.
In addition, excess glucose is converted into triglycerides, which either accumulate as unwanted fat deposits or take part in the formation of atherosclerotic plaques. Another part of glucose molecules irreversibly adheres to body fats and proteins in a non-enzymatic glycation reaction, forming advanced glycation end products (AGEs). Due to glycation, enzymes and other proteins cease to perform their function. An excess of fructose and galactose in the blood is even worse than an excess of glucose, because their glycation capacity is 7 times higher than that of glucose. Recall that table sugar is made up of equal amounts of glucose and fructose. Thus, an excess of simple sugars increases the concentration of circulating inflammatory molecules (cytokines) *.
Especially rapidly the glycation reaction occurs during heat treatment, under the influence of high temperature. An example is meat baked over an open fire (barbecue). Attachment of carbohydrates to protein molecules during glycation changes the configuration of proteins and they are recognized as a foreign element, which increases the inflammatory process * * *.
A diet with a high glycemic index, compared with a diet with a low glycemic index, increases the value of such an inflammatory marker as C-reactive protein (CRP), by up to 12% *. For every 10 units increase in food glycemic index, circulating CRP levels increase by 29% *. Food containing simple saccharides ensures their rapid absorption and a sharp surge in blood glucose (and insulin) levels with all the negative consequences described above.
From here there are recommendations to refuse ready-made foods saturated with sugar and other high-glycemic foods; also to consume long-acting carbohydrates such as whole grains and legumes along with vegetables, which slow down the absorption of carbohydrates. And in general, it is recommended to reduce the volume and calorie intake of food, because this is the only reason for high blood glucose levels.
The control of blood glucose levels is extremely important for our health, so a glucometer should be as indispensable in every family as a thermometer, blood pressure monitor or pulse oximeter.
Animal protein. Red meat is rich in so-called «heme» iron, which enhances oxidative processes; in addition, the products of animal protein metabolism produce some pro-inflammatory effects. For example, meat contains many sulfuric and cationic amino acids that create acid stress.
Animal and poultry meat also contains methionine, an essential amino acid that is converted in the body to pro-inflammatory homocysteine. However, proteins from other animal organisms that are not fully digested in the gastrointestinal tract (GIT) seem to be the greatest danger. Both on their own and when combined with proteins and fats, they act as antigens and have a pro-inflammatory effect through activation of the immune system.
Meat also increases levels of the pro-inflammatory arachidonic acid. Fish and other animal-based seafood don't look like much of a better choice, even though they contain lower amounts of saturated fat. A more successful alternative is vegetable protein found in nuts and legumes, incl. in fermented soy. Meanwhile, the inflammatory effect of animal protein may be negligible compared to saturated animal fat.
Unhealthy fats. Some dietary fats (especially saturated and synthetic trans fats * *) also increase inflammation, while ω-3 polyunsaturated fats, on the contrary, reduce inflammation *. For example, a diet high in saturated fat can increase pro-inflammatory markers, especially in diabetics and overweight people *. At the same time, the addition of 15 ml of linseed oil per day (1 tablespoon) for 3 months significantly reduces the level of C-reactive protein (38%), serum amyloid A (23%) and interleukin IL-6 (10 %) compared to the original values *. A smaller dosage of linseed oil or fish oil * does not give a noticeable effect. An imbalance between ω-3 and ω-6 fatty acids is one of the most common causes of chronic low-grade inflammation.
Nevertheless, it is worth remembering that even the so-called healthy fats can significantly increase inflammation if they have lost their freshness (rancid, oxidized, aged). This primarily applies to polyunsaturated fatty acids, especially fish oil and linseed oil.
High-calorie food leads to fat deposits, which increase the level of systemic inflammation * *. However, this is a reversible effect – reduced caloric intake * and fat body loss * reduce the level of systemic inflammation. Therefore, it is so important to reduce the caloric content of food intake, for example, by increasing the proportion of fiber in food. Periodic caloric restriction of food to 200-500 kcal/day for a period of 7-21 days effectively helps in the treatment of rheumatic diseases, chronic pain syndromes, hypertension and metabolic syndrome *.
Inadequate nutrition can cause an excess of many pro-inflammatory factors such as copper or iron; or a lack of anti-inflammatory factors such as vitamins C and D. In addition, an increase in inflammatory markers has been known for several hours after ingestion of a high-calorie meal (postprandial inflammation). Thus, if we do not take long breaks between meals, and instead resort to high-calorie snacks, the number of hours the body stays in an inflammatory state increases. And vice versa.
Food intolerance affects up to 20% of the general population. This is a rather individual phenomenon, and it can be quite difficult to identify which foods are causing adverse reactions.
The difference between food sensitivity and food allergy is that food allergy causes an immediate immune response, while food sensitivity is less aggressive, but stretched over time (several hours). However, both of these causes eventually trigger a cascade of inflammatory responses.
One of the possible reasons for the rapid growth of food sensitivity may be the genetic modification of modern cultivars of plants, and even their hybridization. Changes in the configuration of amino acid chains in plant proteins of new varieties can make them more antigenic, more immunoreactive, and as a result, more pro-inflammatory.
Herbicides (such as glyphosate) chemically bind to proteins in cereals, causing gluten sensitivity. Similar effects are caused by many culinary technologies, during which the binding of proteins to fats or sugars occurs. Dyes and some other food additives can impair protein breakdown, which will also increase food sensitivities.
A special study on the inflammatory capacity of 42 common foods identified the most pro-inflammatory foods as simple carbohydrates, total and saturated fat, and cholesterol. And the most anti-inflammatory are magnesium, beta-carotene, turmeric, soy genistein and tea *. In addition, regular fasting and, as already mentioned, calorie restriction * * * provide a strong anti-inflammatory prophylaxis.
Chronic dehydration causes the release of histamine and cortisol, which suppress the immune system and cause a buildup of toxins, slow metabolism, and inflammation. You should not force yourself to drink too much, but you should also not ignore thirst, which indicates a lack of water in the body. Numerous studies, albeit with varying results, tend to favor the consumption of freshly squeezed vegetable and fruit juices; but not canned juices, because those have been heat-treated and loaded with sugar and preservatives.
Although consumption of 30 g/day of dry red wine for a month can reduce C-reactive protein levels by 21% in healthy adult males *, alcohol does not have a safe threshold for the female breast. The level of alcohol, which can be good for the heart and blood vessels, is certainly harmful to the tissue of the liver and mammary gland.
To quantify the inflammatory load of food elements, the so-called Dietary Inflammatory Index (DII). It allows you to compare the degree of influence of each food component on inciting or extinguishing inflammation. For example, for saturated fats (SFA) it is +0.37; for monounsaturated (MUFA) – 0; for fats ω-3 – -0.44; for cholesterol – +0.11; for sugar and refined flour – +0.1; for dietary fiber – -0.66 *.
Obesity aggravates the course of all diseases, with the exception of osteoporosis, and reduces life expectancy by an average of 8-10 years compared to normal weight. Every 33 kilograms of extra weight increases the risk of premature death by about 30% *. Adipose tissue is an endocrine organ that secretes inflammatory factors – cytokines * *, adipokines and growth factors * that are capable of maintaining low-grade chronic inflammation. Especially a lot of them is produced in the cells of peritoneal fat, which accumulate various toxins and immune cells with a pro-inflammatory phenotype *.
Excess body weight has been reported to be proportional to the amount of pro-inflammatory cytokines, and reduction in body fat has been reported to effectively reduce inflammatory levels * *. For example, weight loss in severely obese patients through gastric band adjustment reduced their levels of inflammatory markers: IL-6 by 22% and CRP by almost half *. No matter how difficult it is to fulfill this recommendation, body weight should be kept at the lowest mark.
Intestinal microflora. Three-quarters of the total number of immune cells work for the intestines, providing protection against the penetration of toxins and bacteria into the blood. A healthy intestinal bacterial composition greatly reduces the load on the immune system. And its violation, for example, due to the intake of antibiotics, lack of fiber, fatty and/or sweet foods, greatly affects the overall inflammatory state. Probiotics and live fermented foods help restore and enrich the intestinal microflora.
Intestinal permeability. The total surface area of the large intestine epithelium is 150 times that of the body surface. And just as much, what we eat is more important than what we come into contact with with our skin. In terms of function, the food eaten is a foreign mass of about 5-7% of body weight, containing both beneficial and harmful components.
The contents of the intestine and the blood are separated by a layer only one cell thick, which selectively passes the nutrients obtained from food. The density of the junction that binds the cells lining the gastrointestinal tract to each other may weaken, and intercellular permeability may increase. In this case, the boundary between the organism and the external environment becomes more permeable.
This condition is called «leaky gut syndrome» and occurs overtly or covertly in 15% of the general population. Due to intestinal wall leaks, many unwanted substances and bacteria in the intestines that are normally filtered out enter the bloodstream and trigger an immune response. In this case, even the consumption of quality food can cause the same inflammatory reactions as the attack of pathogenic organisms.
So, lipopolysaccharides (a combination of fats and polysaccharides), when they enter the blood from the intestines, cause a strong inflammatory reaction, even in amounts that make up one trillionth of a gram *. The two main causes of this pathological phenomenon are fatty foods and an unbalanced intestinal microflora *. In a healthy state, the intestinal/blood barrier allows protein particles decomposed into elementary fragments, amino acids, to pass through. But with a «leaky» intestine, it also begins to pass larger molecules of incompletely split food protein.
Negative factors that can increase intestinal permeability include: antibiotics; NSAIDs (such as aspirin or ibuprofen); drugs that reduce the acidity of the stomach; lack of pancreatic enzymes; intestinal infections; lack of fiber; food allergy; age-related degenerative changes and stress.
Strengthening the walls of the intestine and reducing its permeability contribute to: vitamin D *, L-glutamine (up to 30 g/day for a week) *, metformin (500-1'000 mg/day), digestive enzymes, deglycyrrhizin licorice, Althea root (Althaea officinalis), Mongolian milkvetch (Astragalus Membranaceus) *, Slippery Elm (Ulmus rubra) bark, mucus-forming food, and bentonite clay and chelating agents. Metformin reduces intestinal leakage caused by fatty foods by reducing circulating lipopolysaccharide levels and increasing the beneficial bacteria Lactobacillus and Akkermansia in the intestinal bacterial profile *.
Markedly reduces intestinal permeability monthly course of calorie restriction (800 kcal/day); at least this has been observed in overweight women *.
However, trying to get rid of leaky gut syndrome without normalizing the rest of the gastrointestinal tract may be futile. To assess the health of the gastrointestinal tract, you should ask the following questions:
- Is there enough saliva in the mouth?
- Is food chewed thoroughly?
- Is the food being swallowed too hastily?
- Is too much food and calories consumed?
- Is an adequate amount of hydrochloric acid secreted by the stomach?
- Is there an adequate amount of bile secreted by the liver, and is there any stagnation?
- Is an adequate amount of digestive enzymes produced by the pancreas?
- Is there a delay in the passage of the food mass or its return?
- Is the fiber intake sufficient and are the stools regular?
- What is the composition and balance of intestinal microflora?
Any of these disturbances in the normal functioning of the digestive tract will contribute to inflammation.
Low physical activity is associated with higher rates of inflammation. Energy expenditure during exercise reduces the amount of cytokines and other pro-inflammatory molecules. Although muscular work increases the concentration of lactic acid in the muscles and may initially provoke local pro-inflammatory conditions, eventually the level of systemic inflammation decreases *.
Stress is the operation of the system at a level exceeding the safe. Psychological stress is accompanied by the release of pro-inflammatory hormones – adrenaline, norepinephrine, cortisol and insulin. The human body is designed to deal with occasional stress, but not constant stress. A constantly high level of these hormones leads to insensitivity of the cells of the body to them, as a result of which their level in the blood rises, acting destructively on the body. Chronic stress (both physical and emotional) can lead to the release of pro-inflammatory cytokines (IL-6); it has also been linked to reduced sleep quality and increased body weight (via cortisol), all of which contribute to inflammation *.
In addition to the direct link between chronic stress and inflammation, there are also indirect ones. For example, chronic stress can cause the valves that separate the different sections of the gastrointestinal tract to malfunction. For this reason, the contents of the acid sections will fall into an environment designed for alkaline conditions, and vice versa. Such conflicts are not only accompanied by belching, heartburn and abdominal pain, but can also lead to peptic ulcers and other hidden inflammations.
Stress management can reduce the risk of inflammation caused by it, and insulin levels can be lowered by taking metformin. Beta-blockers, such as propranolol and carvedilol, blunt the hormonal response to stress and lower heart rate and blood pressure.
Circadian rhythm. The work of various organs is synchronized with the time of day. Whether we sleep at night or stay awake, our internal clock dictates tasks to our organs in accordance with its natural rhythm. The production of inflammatory cytokines (TNF-α and IL-1β) also follows a circadian rhythm and may be involved in the regulation of sleep. Sleep disruption can lead to daytime increases in these pro-inflammatory molecules *. In addition, poor sleep increases the concentration of amyloids in the tissue fluid of the brain, which are associated with Alzheimer's disease *. Thus, poor sleep may indicate an adverse effect on the brain. Taking melatonin at night (3-9 mg/day) helps to normalize sleep patterns.
Because inflammation follows a circadian rhythm, the timing of daily intake of anti-inflammatory agents can be critical. For example, in one study, mice with a breast tumor (MCF-7) graft were injected with celecoxib (20 mg/kg) at various hours after the onset of light *. Lights turned on at 6:00 and off at 18:00. Tumor regression was observed when injections were made from 5:00 to 13:00 hours, while no therapeutic response was observed when injections were made from 16:00 to 19:00 hours, and rapid tumor growth was observed when injections were made at 23:00 .
Sex hormones. Low levels of sex hormones are associated with increased markers of systemic inflammation *. In addition to many other, more important functions, sex hormones also control the inflammatory response, since the cells involved (neutrophils and macrophages) have estrogen and androgen receptors *. This, in particular, also leads to the fact that a decrease in estrogen levels (in postmenopausal women or under the influence of tamoxifen) increases the activity of osteoclasts – macrophages that destroy bone tissue, which causes osteoporosis.
Androgen and estrogen are still considered negative factors in oncology, but in fact both of these hormones can suppress the production of several pro-inflammatory markers, including IL-1β, IL-6, TNF-α, 5-LOX, CRP, as well as NF-κB activity * * * * *. Falling levels of these hormones, either with age (menopause, andropause) or due to hormone therapy, may also contribute to increased latent inflammation * *. Lower testosterone levels in older men are associated with increased markers of inflammation (IL-6) * and vice versa *.
However, the relationship between estrogen and COX-2 is controversial and not well understood. It seems that the expression and enzymatic activity of COX can change depending on the hormonal status. After spay surgery, rats showed significantly lower COX enzymatic activity than sham-operated rats. However, after the administration of estradiol, their COX activity significantly increased *.
Prostaglandin PG-E2 has also been found to stimulate estrogen synthesis by activating the aromatase enzyme, the leading enzyme in estrogen production *. Thus, a reciprocal stimulatory effect may occur in which estradiol increases COX-2 activity and the COX-2 enzymatic product (PG-E2) stimulates increased estrogen biosynthesis.
Dehydroepiandrosterone (DHEA) in postmenopausal women is able to suppress the inflammatory activity of IL-6 cytokines more strongly than dihydrotestosterone synthesized from it, and even more so estradiol *. In turn, chronic inflammation can reduce DHEA levels *. Exogenous DHEA supplementation (50 mg/day for 2 years) showed several anti-inflammatory effects in older adults: significantly reduced levels of inflammatory markers TNF-α and IL-6, reduced abdominal fat mass, and increased glucose sensitivity of cells *. Despite this, hormonal correction requires caution and continuous monitoring of hormone levels.
Autoimmune reactions. Inflammation can be the result of an inadequate reaction of the immune system, as a result of which it attacks the healthy cells of the body itself. Nevertheless, there are opportunities to extinguish an excessively violent immune response, bringing it back to normal.
Each of the above items in one way or another contributes to the regulation of the level of inflammation. Of course, any of them can be of minimal importance, but quantity always turns into quality. And it is not surprising that over the years we have a growing chronic latent systemity inflammation, accompanied by overweight, body pain, irritability and loss of energy, and which paves the way for serious illness.
But as you can see, most inflammation factors are under our control, and we can avoid them, or at least reduce their impact. Of course, if there is a sincere desire.
Having finished the consideration of anti-inflammatory prophylaxis, let's move on to consideration of measures to reduce the already existing systemic inflammatory level.
A decrease in the concentration
The intake of antioxidants, not only as a preventive measure, but also as an adjunct to the main treatment, can increase the survival rates of patients.
• Molecular hydrogen (H2) reacts with highly active oxidants inside cells (ROS, NO) without interfering with their signaling pathways * and therefore can be considered an ideal antioxidant. In addition to a direct antioxidant effect, hydrogen regulates gene expression, exhibiting anti-inflammatory effects and stimulating energy metabolism *. Due to its small size and high diffusivity *, it is easier for hydrogen to penetrate the tumor tissue and seep through the blood-brain barrier and through the cell membrane than the larger molecules of any other antioxidants.
There are several ways to introduce hydrogen into the body, including breathing 3-4% gas *, but the most practical way is to consume hydrogen dissolved in water. Hydrogenated water can be produced in several ways: saturating water with high-pressure gas, reacting magnesium with water, and electrolyzing water to form H2 (catholyte water). The first method does not change the acid and mineral composition of the treated water, unlike the latter, where along with an increase in the reduction potential of water, its acidity index also decreases. The level of redox potential (Eh) of catholyte water should be 350-450 mV, the acidity level (pH) – 9-9.5, and its daily consumption – 0.25-0.5 l *. Unfortunately, hydrogen very quickly escapes from an aqueous solution, and the reduction potential of such water is completely lost within 3-4 hours.
• Glutathione (GSH) is the main intracellular antioxidant in the body. Dosage of acetyl-glutathione: 100 mg/day. However, the use of its additives is problematic. Glutathione is poorly absorbed when taken orally, and has a very short half-life when administered intravenously.
• N-acetylcysteine (NAC) scavenges free radicals and also increases intracellular glutathione naturally. NAC may act as a precursor to GSH synthesis as well as a stimulator of cytosolic enzymes involved in glutathione regeneration. Dosage: 250-1'800 mg/day * *, (usually 600 mg/day). To improve absorption, it is recommended to take its liposomal form (2×250 mg) or S-acetylglutathione (2×100 mg). The combination of glutathione with glycine acts synergistically *.
• Vitamin C is the main extracellular antioxidant. Dosage: 100-200 mg/day. Vitamin C and glutathione work synergistically, complementing and reinforcing each other.
• Vitamin E (mixed α- and γ-tocopherol) is the main fat-soluble antioxidant in the body and prevents the oxidation of cell membrane lipids (such as cholesterol). Gamma-tocopherol inhibits the pro-inflammatory COX-2 pathway * *, and enhances the action of α-tocopherol. The combination of α-tocopherol (800 mg/day) and gamma-tocopherol (800 mg/day) supplementation was effective in suppressing oxidative stress and C-reactive protein (CRP) levels compared to placebo *. Dosage: 15 mg/day. Vitamin C supports the antioxidant effectiveness of vitamin E, and works in concert with
• Vitamin D3. Low vitamin D levels are associated with increased levels of pro-inflammatory cytokines *, C-reactive protein (CRP) *, IL-6, and NF-κB *. Vitamin D3 markedly increases plasma antioxidant capacity and reduces CRP levels *. At high doses (50'000 IU per week), vitamin D improves systemic inflammation by lowering CRP levels and altering the neutrophil to lymphocyte ratio *. After 12 weeks of supplementation, polycystic ovary syndrome patients had marked improvements in markers of metabolic, endocrine, inflammatory, and oxidative stress *. Dosage: up to 4'000 IU/day. Lower dosages (20'000 IU per week) may not have a noticeable anti-inflammatory effect *.
• VitaminВ8 (myo-inositol) is able to significantly reduce the level of C-reactive protein in patients *. Myo-inositol reduces blood clots, increases oxygen levels in tumor tissues * and increases the activity of natural killer cells *. Inositol can be taken on a chronic basis, and in addition to some anti-inflammatory effects, it also has anti-proliferative and anti-angiogenic properties. Dosage: 500-1'000 mg/day for prophylaxis *, and up to 12 g/day during therapy *.
• Alpha-lipoic acid (thioctic acid, vitamin N), is the main intramitochondrial antioxidant. It is water and fat soluble, readily crosses the blood-brain barrier, and appears to work synergistically with acetyl-L-carnitine and L-carnosine *. Dosage: 200 mg/day.
• Magnesium (Mg) is recognized as the most anti-inflammatory of the 42 dietary factors studied to reduce CRP levels in the blood * * *. Increased magnesium intake has been associated with lower levels of CRP, IL-6 and TNF-α * *. Magnesium, added to drinking water in the form of organomagnesium compounds, increases the concentration of hydrogen and reduces the level of oxidants (ROS and NO), and with long-term consumption, also the levels of pro-inflammatory cytokines IL-1β, IL-6, IFN-γ and iNOS *. Dosage: 300 mg/day magnesium citrate * as an alternative to molecular hydrogen.
• Zinc (Zn) and selenium (Se) are part of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, which, by reducing the concentration of oxidants, suppress NF-κB activity and prevent the production of inflammatory enzymes and cytokines. In addition, zinc can inhibit NF-κB directly * *. Long-term zinc supplementation (45 mg/day zinc gluconate for 6 months) reduces levels of pro-inflammatory factors CRP, TNF-α, IL-6 and IL-8 * * *. Selenium supplementation in the form of selenoproteins also reduces inflammation and improves patient outcomes *.
• A combination of magnesium (100 mg), zinc (4 mg), calcium (400 mg), and vitamin D (200 IU) twice daily for 12 weeks reduces CRP by a factor of three and increases plasma antioxidant potential severalfold in women *.
• Iodine (I) in breast cells may also have antioxidant properties. Sodium iodide (NaI) at a serum concentration of only 15 μM (which is quite achievable for humans) exhibits antioxidant activity in the thyroid and mammary glands comparable to a concentration of 50 μM ascorbic acid *. By reducing the concentration of hydrogen peroxide, it reduces lipid oxidation and DNA damage *.
• Chlorophyll is a natural plant pigment that has a pronounced antioxidant effect. In experiments on mice, a monthly oral intake of spirulina-derived chlorophylls (equiv. 10 mg/day) retarded the growth of a grafted pancreatic tumor by more than a third *.
However, the positive effect of vitamin and mineral supplementation seems to manifest itself only when their deficiency is eliminated, and not their excess is created. Otherwise, the effect can be from zero to negative. Perhaps for this reason, there is some ambiguity in the results of various studies regarding the benefits of supplements.
A sensible diet can also contribute to the reduction of oxidative stress. A study * of more than 3'100 foods, drinks, spices, herbs and supplements used worldwide found that the highest antioxidant content (in mM/g) is found in:
- from herbal supplements – triphala (7.1), arjuna (1.47) and mint (1.61);
- from spices – cloves (2.77) and cinnamon (1.2);
- from berries – amla (2.61), rose hips (0.69) and blueberries (0.48);
- from nuts – walnut (0.22);
- from sweets – 70% black chocolate (0.15);
- from drinks – green tea (0.24) and coffee (0.2) *.
Decreased levels of
Highly invasive, metastatic cancer cell lines have high levels of COX-2 protein and increased production of PG-E2, while less invasive cell lines have lower levels of COX-2 *. This fact suggests that this inflammatory agent is an important participant in breast tumor invasion of adjacent tissues and its metastasis process.
A case history analysis of 341 women with invasive breast carcinoma showed that NSAID intake was inversely related to the size of the primary tumor, the condition of the lymph nodes, and the number of affected axillary nodes. This led to the conclusion that the use of NSAIDs may favorably affect the factors that determine the prognosis and clinical outcomes in women with breast cancer *.
Other observational studies show a dose- and time-dependent reduction (up to 40%) in the risk of breast cancer in women who take NSAIDs on an ongoing basis * *. A strong therapeutic role has also been reported for selective COX-2 inhibitors in combination with radiotherapy *. NSAIDs such as celecoxib, at very high doses (1'500 mg/kg) for 6 weeks, caused regression of the tumor caused by the chemical agent in 90% of rats *. However, in human terms, this will be approximately 7'500-10'000 mg/day. This dose is 20-40 times higher than the prescription dose, and for this reason it would be extremely dangerous to use it in clinical practice.
A retrospective meta-analysis of cancer metastasis reduction with NSAID use found a significantly lower risk ratio for distant metastases for most types of cancer. For example, in breast cancer postoperative use of NSAIDs reduced their number by almost half compared to not using them * *.
• Acetylsalicylic acid (aspirin) is a classic non-steroidal anti-inflammatory drug (NSAID) * proven over the years with a wide range of therapeutic effects. Aspirin inhibits the activity of cyclooxygenase (COX) and the production of prostaglandin PG-E2. Although aspirin shows the best results against cancers of the lung, esophagus and stomach, it also significantly reduces the risk of long-term recurrence and death from all causes in breast cancer * *. Dosage: 100 mg/day.
• Indomethacin is another of the most commonly used NSAIDs, which belongs to a subclass of acetic acid derivatives. Preclinical studies confirm its high potential as a successful chemoprophylactic antitumor agent. The action of indomethacin in terms of its chemopreventive and antitumor activity is for the most part similar to that of aspirin. It induces apoptosis and inhibits cell growth in esophageal *, ovarian * and breast * cancer cells via a COX-dependent and possibly also a COX-independent pathway. Limited clinical studies show optimistic results as a preoperative treatment of patients with indomethacin in early stage breast cancer *.
• Amtolmetin guacil (niselat) is a modern COX inhibitor that is better tolerated and more gentle on the stomach compared to other NSAIDs. Dosage: 600-1'200 mg/day taken on an empty stomach.
• Ibuprofen appears to be more effective in reducing the risk of breast cancer than aspirin *, but it affects the gut microflora and increases the risk of death from cardiac arrest, as well as a number of other negative side effects. The minimum dose used to relieve pain is 200 mg.
• Acetaminophen (paracetamol) is a COX inhibitor. A widely used anti-inflammatory, antipyretic and analgesic drug with less gastrointestinal toxicity than conventional NSAIDs. In addition to reducing inflammation, paracetamol has been shown in mice to differentiate breast cancer cells *. Dosage: 1'500 mg/day, but not more than 4'000 mg/day; further increase in dose causes hepatotoxicity *. For this reason, paracetamol looks even less attractive than aspirin.
• Ketorolac is a COX inhibitor. Usually used to reduce pain in the postoperative period. Although its gastrointestinal side effects are not lower than those of other NSAIDs, it has not been reported to contribute to local bleeding after breast surgery *.
• Licofelone is an analgesic and anti-inflammatory agent. Unlike coxibs, which specifically inhibit the COX inflammatory pathway, licofelone inhibits both the COX and LOX inflammatory pathways. In preclinical studies, it extended the lifespan of ovarian tumor-grafted mice by suppressing the stem properties of cancer cells and overcoming drug resistance to paclitaxel *. Lycofelon has not yet received regulatory approval for clinical use, but it may be on the market in the near future.
All NSAIDs are not intended for long-term use. Despite proven prophylactic benefit *, long-term use of acetylsalicylic acid and other NSAIDs poses a risk of unwanted side effects, including epithelial damage, bleeding, and disruption of the intestinal microflora. The risk of peptic ulcers and upper gastrointestinal injury such as bleeding up to intestinal perforation can increase five-fold *, and affect one-third to nearly one-half of regular NSAID users *. All together, this contributes to an increase in the permeability of the intestinal wall, which can eventually have a counterproductive, systemic pro-inflammatory effect.
High doses of NSAIDs can also cause kidney failure *, and their use over a long period of time can increase blood pressure and cause a stroke *. In addition, NSAIDs inhibit the synthesis of proteins in the connective tissue (proteoglycans and collagen). On the one hand, this reduces fibrous seals, but on the other hand, it can reduce the resistance of the tissue to the spread of the tumor.
Finally, NSAIDs should not be administered simultaneously with methotrexate, because they have the ability to significantly increase the level of this drug in the blood, thereby exceeding the therapeutic dose, which leads to serious complications. Thus, the advantages of using NSAIDs are overshadowed by the disadvantages of serious complications.
At the same time, many natural anti-inflammatory agents are free from these disadvantages of NSAIDs *.
• Curcumin is found in turmeric root and makes up about 2% of its dry weight. It is a natural anti-inflammatory agent that synergistically enhances the action of other NSAIDs *. Curcumin reduces most inflammatory markers (LOX, COX, TNF-α, IL-1β, NF-κB, etc.) * * *. Extensive clinical studies of curcumin show improvement in patients with curcumin in many inflammatory diseases *. Dosage: 100-200 mg/day for a month, followed by a repeat after two months.
• Resveratrol, found in the skin of dark grapes and red wine, and its isomer, pterostilbene, found in blueberries, reduce gene expression of the pro-inflammatory proteins iNOS and COX-2 * as well as TNF-α, IL-1β, IL-6, NF-κB * *. Taking resveratrol significantly reduces the level of C-reactive protein in patients * *. Resveratrol (100mg) may also protect against inflammation caused by high-fat foods. So, within 5 hours after eating a fatty meal, the synthesis of IL-1β without resveratrol increased by 91%; while with resveratrol the increase was 29% *. No clinical studies have been reported on pterostilbene. Resveratrol dosage: 500 mg/day *; apply intermittently.
• Quercetin is found in abundance in onions, apples, broccoli and berries. Quercetin is able to suppress the expression of the pro-inflammatory cyclooxygenase COX-2 *. Long-term use of quercetin at a dosage of 500 mg/day led to an improvement in the clinical symptoms of inflammation in patients *.
• Salvinolone (6-hydroxy salvinolone) is a diterpenoid isolated from the bark of the root of Premna (Premna serratifolia). The methanol extract of the root (equiv. 30 mg/kg) acts as a dual COX/LOX inhibitor * *.
• Theaflavin and epigallocatechin gallate (EGCG), black and green tea polyphenols, respectively, suppress the NF-κB signaling pathway, reducing the expression of a number of pro-inflammatory proteins (LOX, COX, TNF-α, IL-1β, IL-6 and IL-8) *. People who regularly consume 2-4 cups of tea per day (black or green) have 20-25% lower levels of C-reactive protein compared to people who do not drink tea * * *.
• Thymoquinone is a quinone contained in the seeds of Black cumin (Nigella sativa), which has been used in traditional medicine in the Arab East for centuries. In animal studies, ingestion of plant seed oil (equiv. 40 ml/day) reduced the production of IL-4 and NO *, IL-1β *, and at higher doses also inhibited COX and LOX *. Compared to sunflower oil, nigella seed oil (2 x 2.5 ml for 8 weeks) improved blood lipoprotein profile, had a positive effect on glucose control, and also lowered blood pressure in patients with hypertension *. Unfortunately, clinical trials of thymoquinone are still limited to phase I.
• Pycnogenol®, a maritime pine (Pinus pinaster Aiton) bark extract, is a complex of polyphenols * with short and long acting. Due to their slow release, a more stable concentration of antioxidants is maintained in the blood. The anti-inflammatory action of Pycnogenol consists of inhibition of COX-1 and COX-2, as well as the «main switch» of inflammation – NF-κB *. Clinical studies have shown a positive effect of pycnogenol (150-200 mg/day) in osteoarthritis * * and atherosclerosis *, especially in combination with centella asiatica extract (450 mg/day) and cardioaspirin (100 mg/day).
• Inositol (1 g/day) in clinical studies for 12 weeks significantly reduced serum C-reactive protein *.
• Melatonin suppresses the expression of pro-inflammatory genes, and by reducing the levels of pro-inflammatory proteins such as COX-2 and iNOS *. Melatonin (equiv. 6 mg/day *) may enhance the anti-inflammatory and oncostatic effects of various therapeutic agents (such as celecoxib, indomethacin, metformin, retinoic acid and statins *.
• Proteolytic enzymes. The bromelain found in pineapple inhibits COX-2 activity, inhibits the production of prostaglandin and thromboxane, reduces circulating fibrinogen levels, and reduces the cell adhesion of pro-inflammatory leukocytes to inflammation sites *. The inhibition of the COX-dependent pathway by bromelain is superior to that of prednisone, which requires a 10-fold higher dose to achieve the same effect in rats *. Bromelain supplements (above 270 mg/day) reduce pain in inflamed areas in the joints in patients no less effectively than diclofenac * * *. Dosage of bromelain: 750-1'000 mg/day *.
Pyridoxine, niacin, magnesium, zinc, and vitamin C * are also required for normal functioning of the enzymes that shift from pro-inflammatory to anti-inflammatory fatty acid metabolites.
It is worth noting, however, that chronic inhibition of COX-2 activity or expression reduces the ability of B cells to produce antiviral antibodies, thereby theoretically increasing susceptibility to viral infection *.
In animal studies, it has been found that the expression and enzymatic activity of COX may depend on hormonal status. Ovarianized rats had significantly lower COX activity than sham-operated rats; however, their administration of estradiol resulted in a significant increase in COX activity *.
Most of the studies have studied mainly the anti-inflammatory properties of NSAIDs and selective COX-2 inhibitors, however, these substances are not able to influence alternative pathways for the synthesis of pro-inflammatory eicosanoids. Additional inhibition of lipoxygenase (LOX) and its by-products (LTB4, 5-HETE, 12-HETE) would appear to be more effective in reducing inflammation. In this regard, the use of natural, non-toxic anti-inflammatory strategies that affect both the COX and LOX pathways may be useful for both prevention and treatment of cancer.
Inhibition of signaling pathways
The transcription factor NF-κB, among hundreds of other transcription factors, is the most important in human cells. It is involved in the transcription of over 500 genes involved in the regulation of immunity, inflammation, cell growth, carcinogenesis, and apoptosis * and plays an important role in tumor evasion from the immune response. It directs the transcription of genes that are involved in encoding inflammation-related cytokines (IL-1, IL-2, IL-6, IL-12, TNF-α, GM-CSF) and chemokines (IL-8, MIP1, RANTES), acute phase proteins, adhesion molecules, inducible enzyme effectors (iNOS, COX-2).
• N-acetyl-cysteine (NAC) inhibits the NF-κB signaling pathway in vitro, reducing the expression of the cytokines IL-6 and IL-8 * *. NAC supplementation for 8 weeks has shown modest reductions in circulating IL-6 levels in patients with chronic kidney disease * and burn injuries *. The addition of NAC to food (3% of the total feed mass) reduced the rate of skin tumor development in mice by 38% *.
Human equivalent dosage: 1'200 mg/day *.
Although in mice NAC prevented stabilization of HIF-1α during hypoxia and increased blood levels of glutathione, NAC treatment significantly increased lung metastatic burden in an experimental model of breast cancer metastasis *. This finding makes NAC inappropriate for post-diagnostic cancer therapy.
• Acrichine (or quinacrine) is an antimalarial and antihelminthic agent. In cancer, the NF-κB and p53 signaling pathways act antagonistically, however, quinacrine is able to both suppress NF-κB and stimulate p53 *, which is responsible for cell apoptosis. Dosage: 0.3 g/day for up to 10 days.
• Metformin reduces the inflammatory response associated with cellular transformation and growth of cancer stem cells by suppressing the transcription factor NF-κB *. Due to this, the combination of metformin with other therapies may be effective in highly inflammatory tumors. Metformin, like quinacrine, is effective against cancer cells with loss of p53 function. Dosage: 250 mg/day for prophylaxis; 500-1'000 mg/day for long-term treatment; 1'000-2'000 mg/day short-term in severe cases.
• Andrographolide from the leaves of Creat (Andrographis paniculata) significantly inhibits NF-κB activity and exhibits a broad spectrum of anti-inflammatory and anti-cancer effects. Among a large number of natural substances that inhibit the NF-κB signaling pathway, andrographolide does not enhance inflammasome activation. Daily dosage: 3×2'000 mg of the alcoholic extract of the plant *.
• Boswellia (Boswellia carterii, Boswellia serrata, Boswellia sacra), plant resin (incense). It should be natural incense, not artificial flavor. The incense-derived boswellic acid offered by supplement distributors appears to be a reliable choice. Boswellic acid specifically inhibits 5-LOX and reduces the production of pro-inflammatory leukotrienes. It also reduces inflammatory markers such as TNF-α, IL-1β, IL-6, IFN-γ and PGE2 * *. Clinical studies confirm the anti-inflammatory properties of incense * *, however, it has poor bioavailability. To ensure physiologically relevant plasma concentrations of boswellic acids, boswellia extract (500 mg) is taken as an emulsion with lecithin (1:1 ratio) *. Taken orally for six months, a combination of Boswellia with betaine and myo-inositol, marketed as Eumastos®, has been shown in clinical studies to reduce breast density, suppress inflammation, relieve pain, and shrink benign breast tumors * *. The usual recommendation is 200-300mg of pure boswellic acids per day, but in some clinical studies dosages have been as high as 1'200 mg/day *.
• Coenzyme Q10 (CoQ10), taken in a number of clinical trials for 1-3 months, acted as an effective antioxidant and reduced levels of pro-inflammatory factors such as C-reactive protein (CRP), interleukin-6 (IL-6) * * and especially – tumor necrosis factor alpha (TNF-α) *. In addition, CoQ10 supplementation significantly reduced levels of inflammatory markers such as MMP-9, TNF-α *, as well as IL-1β and IL-18 *. Dosage: 150-500 mg/day.
• Blueberries (Vaccinium myrtillus) are rich in the antioxidant polyphenol pterostilbene. Consuming 200-350 g/day of blueberries for 4-8 weeks significantly reduces levels of CRP, IL-6, IL-12, IL-15 * *.
• Vitamin E at 1'200 IU/day reduces the production of CRP and IL-6 *.
• Burdock (Arctium lappa), root. Daily 3 cups of burdock root tea (2 g dry powder per 150 ml boiling water half an hour after eating) significantly reduced levels of inflammatory markers such as IL-6 and C-reactive protein * *.
• Nettle (Urtica dioica), leaves. Nettle extract suppresses the pro-inflammatory transcription factor NF-κB *, reducing IL-6 and C-reactive protein levels in patients *. The combination of nettle extract with diclofenac * or with rosehip and willow bark * synergistically enhances its anti-inflammatory effect.
Dosage of water-alcohol extract: 7-10 g/day *.
• Chlorophyll is plant pigment contained in leafy greens. Chlorophyll A and chlorophyll B suppress NF-κB activation, and chlorophyll A further suppresses the expression of the pro-inflammatory cytokine TNF-α gene, thereby reducing inflammatory markers *.
The STAT3 signaling protein is activated by a variety of cellular signals and, in turn, activates a variety of genes that control inflammation and tumor evasion from immune cells.
• The flavonoids quercetin *,
narinigenin *,kaempferol *,
are able to suppress STAT3 to some extent.
The combination of curcumin with EGCG specifically inhibits STAT3 phosphating and STAT3/NF-κB interaction, suppressing the CSC phenotype in the breast *.
• Metformin selectively inhibits STAT3 phosphorylation in CSC *.
Other known inflammatory molecules and transcription factors are: activating protein 1 (AP-1), hypoxia-induced growth factor (HIF-1), tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF), Wnt/β-catenin and others.
Preclinical and clinical studies indicate that all of these pro-inflammatory agents can be suppressed by phytonutrients such as resveratrol, apigenin, wogonin, catechins, curcumin, piperine, diallyl disulfide, ellagic acid, emodin, epigallocatechin gallate, escin, fisetin, flavopiridol, genistein, isoliquiritigenin, kaempferol, mangosteen, morine, myricetin, naringenin, silymarin, vitexin, xanthohumol * *. Thus, the diversity and nutritional density of plant foods can reduce the overall inflammatory index. In addition, many culinary spices at dosages that are commonly used in cooking can significantly reduce inflammatory markers.
Histamine suppression. Histamine dilates blood vessels and makes them more permeable to leukocytes and plasma, which causes an acute inflammatory response. Although natural remedies may not be as effective as antihistamines, for a mild allergic reaction, the following may help: vitamin C; bromelain; quercetin; probiotics; astragalus; nettle.
Suppression of the glycation reaction. Free sugars (mainly glucose, and especially fructose) combine with proteins and lipids in the bloodstream, forming the so-called glycation end products (AGEs). AGEs then bind to the appropriate membrane cell receptor (RAGE), the activation of which triggers the pro-inflammatory NF-κB signaling pathway * *. In addition to provoking an inflammatory response, cross-linking of proteins is also associated with loss of elasticity in the skin, blood vessels, and heart.
Inflammatory-promoting AGEs are not only formed internally, but also come pre-made from foods cooked at high temperatures, especially red meat * *. Although the presence of proteins and simple sugars in the blood is unavoidable, glycation can be greatly reduced by limiting their intake, lowering the glycemic load of food, and by taking the following substances: carnosine *, kaempferol (equiv. 50 mg/day) *, phytosomal curcumin and boswellic acid (100 mg/day) *, pinocembrin (250 mg/day) *, hesperidin (500 mg/day) * *, benfotiamine (600 mg/day) *, proanthocyanidins (1'500 mg/day) *, complex vitamins C (500 mg) and E (400 mg) *.
• Carnosine lowers blood glucose * and prevents glycation * *. Since carnosine levels steadily decline with age *, increasing inflammatory status, carnosine supplementation in older age may be beneficial. In particular, carnosine is able to protect retinal cells from inflammatory complications associated with high blood sugar *, as well as improve skin firmness and smoothness and smooth wrinkles *.
Dosage: 1'000 mg/day *.
• Benfotiamine is a fat-soluble derivative of thiamine, with greater bioavailability than thiamine (vitamin B1). Benfotiamine blocks several tissue-damaging mechanisms *, including blocking the formation of advanced glycation end products.
Dosage: from 150 mg/day in prophylactic regimen *, but during meals rich in advanced glycation end products, it can be increased up to 1'000 mg/day *.
• Gynostemma (Gynostemma pentaphyllum). Plant saponins significantly inhibit inflammatory substances such as TNF-α, IL-6 and COX-2 * and suppress macrophage activation *. Gynostemma water infusion instead of tea for 12 weeks significantly reduces plasma glucose and insulin resistance *.
• Metformin and other biguanides reduce glucose levels and exhibit anti-inflammatory effects by suppressing TNF-α, IL-1β, C-reactive protein, fibrinogen and NF-κB * *. In addition, metformin significantly reduces the entry of macrophages with a pro-inflammatory phenotype (M2) into the tumor, and promotes their switch to an anti-inflammatory phenotype (M1) *. Metformin 1'700 mg/day for 12 weeks reduces IL-6 by 27% and TNF-α by 8% from baseline *.
Lowering homocysteine levels levels can be achieved by reducing the intake of foods that contain methionine, the amino acid from which the body makes homocysteine. It is mainly animal protein; however, nuts, cheese, dairy products and legumes also contain a lot of methionine.
Homocysteine can accumulate if its metabolic pathways are impaired. Vitamins B6, B9, B12, as well as betaine (trimethylglycine) are involved in the conversion of homocysteine. Numerous randomized clinical trials show that the combination of these vitamins in daily doses exceeding the recommended 2-3 times, helps to reduce and normalize the level of homocysteine in plasma * * * *. Women who are deficient in these vitamins have benefited in particular *.
Mitochondrial dysfunction. Mitochondrial dysfunction also contributes to inflammation. In the process of energy production in mitochondria, the formation of oxidants occurs, the accumulation of which causes an increase in the permeability of mitochondrial membranes. As a result, mitochondrial components leak into the cytosol of the cell. And because mitochondria have different gene material from cells, cytoplasmic receptors detect it, recognize it as a threat within the cell, and initiate an immune response.
With age, there is a gradual extinction of the biological functions of the body, and with it the level of antioxidant enzymes decreases, the energy capacity of mitochondria decreases, the level of free radicals increases, and systemic inflammation increases. Some of the supplements discussed earlier have been shown to improve mitochondrial function, increase antioxidant status, and reduce overall inflammation.
Lower protein intake in mice without food restriction was associated with increased mitochondrial activityLifestyle changes can also benefit mitochondria. Lower protein intake in mice without food restriction was associated with increased mitochondrial activity *.
Reducing oxidative stress helps to reduce the inflammatory process. In fact, all of the anti-inflammatory measures discussed above attempt to combat the effect, the inflammatory response, rather than the cause, the inflammatory factors. The main inflammatory factor is tissue oxidation.
Recommended antioxidant plants (in descending order of estimated antioxidant potential):
• Arjuna (Terminalia arjuna), Ayurvedic powder; 0.5-1 g/day.
• Green tea, dry water extract; 2 capsules per day.
• Licorice (Glycyrrhiza glabra), root. Dry ground root in the ratio of 1 tsp. (2-3 g) in a glass of water, stand for 0.5 hours at a temperature of 99°C and allow to cool slowly. Drink in small portions like tea, 1-2 glasses per day *.
• Spices (dried) *: cloves, peppermint, cinnamon, turmeric, oregano, cumin, rosemary, ginger, black pepper, paprika, fenugreek (shambhala) – as food additives. Experiments have confirmed that some herbs and spices used since ancient times, such as cloves, cinnamon, turmeric, black pepper, fenugreek, are effective inhibitors of lipid peroxidation.
The combination of different antioxidant plants or foods can act synergistically, that is, not add up, but multiply their actions. In addition, they may act through different mechanisms, and their effectiveness may vary in different organs. Therefore, lower concentrations of a combination of antioxidant substances can have a more pronounced effect than a simple increase in the concentration of each of the elements of the mixture *.
It is worth noting that a significant proportion of studies have not found a reduction in oxidative stress due to the use of antioxidant supplements. We can assume the following reasons for this: failure of antioxidants to reach the target tissue; their insufficient dosage; short duration of their impact; inappropriate mode of their use; use for evaluation not direct, but indirect markers and some others.
Diet modifications and
An inflammation-producing diet increases breast cancer risk by 14% *, worsens prognostic chances by 75%, and increases cancer mortality by 67% *. Conversely, a low glycemic diet, reduced intake of total and saturated fat, and increased intake of fiber *, legumes, and nuts * can reduce inflammatory levels.
Anti-inflammatory dietary strategies include an adequate intake of polyphenols and ω-3 fatty acids, a reduction in saturated and trans fatty acids, and an intake of plenty of vegetables, fruits, nuts, and whole grains *. Changing the composition of the food we eat can lower your C-reactive protein levels from baseline to the same extent as statins * without causing the negative effects of the latter.
Linoleic acid and long-chain saturated fat increase C-reactive protein (CRP) levels in direct proportion *, while fiber intake is inversely proportional to CRP levels *. Between the groups with the highest and lowest fiber intake in patients, the odds ratio for elevated CRP levels (>3 mg/L) was 0.59 *. An increase in the proportion of fruits and vegetables in the diet is associated with low serum levels of CRP and homocysteine. With each additional serving of fruit and vegetables, the risk of high CRP (> 10 mg/L) and homocysteine (> 10.4 for men and > 11.4 µM for women) is reduced by 21% and 17% respectively *.
Although all whole plant foods are capable of anti-inflammatory effects, the effectiveness of each varies. Antioxidant-rich fruits and vegetables, such as berries and leafy greens, reduce systemic inflammation significantly better than antioxidant-poor fruits and vegetables, such as bananas and lettuce.
High consumption (8 servings/day) of carotenoid-rich vegetables and fruits significantly reduces CRP levels in non-smokers compared to their low intake (2 servings/day) *. High-pressure orange juice (500 ml/day) in 14 days reduces CRP levels in patients by 40-56% of baseline *. Pomegranate extract (human equiv. 100 ml/day) * reduces the expression of COX-2 and HSP90 in rats, interferes with the expression of NF-κB in the nucleus, and increases the expression of Nrf2 *.
Systemic low-intensity chronic inflammation can be caused by a variety of mechanisms from a high-calorie diet due to its high fat content *.
Diets low in animal fats and a «Mediterranean» diet (rich in olive oil and almonds) reduce inflammation as measured by CRP *.
Low-fat diets * and weight loss * reduced levels of cytokines and other signaling molecules in randomized trials.
A diet high in red meat is associated with higher circulating levels of glycated hemoglobin and CRP, while a diet high in whole grains is associated with lower levels *.
A vegan diet is associated with significantly lower levels of CRP, fibrinogen, and total white blood cell concentration compared to a non-vegetarian diet *.
Dr. Andrew Weil even developed a special anti-inflammatory diet *, however the diet suggested further in the «Diet Therapy» section † is also anti-inflammatory. It provides the following anti-inflammatory strategy:
- limiting the consumption of animal products: meat, dairy products, eggs and poultry (reduces the intake of arachidonic acid, a precursor of pro-inflammatory molecules such as PGE2, LTB4, 5-HETE and 12-HETE);
- increasing the number of food sources of PUFA ω-3, especially EPA and DGA: cold water fish and fish oil (blocks the metabolism of arachidonic acid);
- limiting the consumption of PUFA ω-6 of plant origin, focusing on the ratio of ω-3:ω-6 in the range from 1:2 to 1:3 (prevents the competition of metabolizing enzymes);
- increased intake of dietary antioxidants: 7-9 servings per day of deeply pigmented fruits and vegetables (reduces oxidative biosynthesis of pro-inflammatory molecules);
- prohibition of hydrogenated and trans fatty acids, alcohol, simple sugars and refined carbohydrates (inhibits enzymes that promote inflammation);
- ensuring adequate intake of zinc, magnesium, ascorbate, niacin and pyridoxine (coenzymes for the metabolism of PUFA ω-3);
- ensuring sufficient intake of anti-inflammatory herbal remedies (manage inflammation due to multiple and synergistic effects, including inhibition of COX and LOX);
- prevention of excess blood glucose (excess insulin promotes the synthesis of pro-inflammatory molecules) *.
Fatty acid. Reducing dietary fat intake has a greater effect on reducing inflammation in obese individuals than other dietary changes *. Some dietary fats (especially saturated and synthetic trans fats) increase inflammation, while polyunsaturated fats, on the contrary, can reduce it * * *.
A balance between ω-3 and ω-6 fatty acids is important to manage inflammation levels. While both fatty acids are required by the body, ω-3 is anti-inflammatory while ω-6 is pro-inflammatory. However, not all ω-6 promote inflammation; for example, gamma-linolenic acid has some anti-inflammatory properties. Due to the fact that each vegetable oil has its own unique composition of various fatty acids, their pro- and anti-inflammatory activity varies significantly.
• Flax (Linum usitatissimum) oil, Chia (Salvia hispanica) oil and False flax (Camelina) oil. Rich plant sources of ω-3 fatty acid precursors that inhibit the formation of arachidonic acid and inhibit the activity of 5-LOX, 15-LOX, 15-HEPE. Consuming 15 ml/day of flaxseed oil for 3 months can reduce CRP by 38%, serum amyloid A by 23%, and IL-6 by 10% from baseline *.
Dosage: 2 g/day * to 12 g/day (0.5 tsp-1 tbsp) *.
• Hemp oil (Cannabis sativa) is a rich source of gamma-linolenic acid, ω-6 fatty acids, fat-soluble vitamins, phytosterols and minerals. Hemp seed oil promotes the production of anti-inflammatory prostaglandin E1 (subject to simultaneous blocking of the production of arachidonic acid) and enhances the effect of chemotherapy drugs. Blocking the synthesis of arachidonic acid can also be provided by lignans contained in sesame, which inhibit the corresponding enzyme (δ-5-desaturase) *.
Dosage: from 500 mg/day of gamma-linolenic acid, which corresponds to approximately 20 ml *, or 1-1.5 tbsp. hemp oil per day.
• Evening Primrose Oil (Oenothera biennis) * * *, Borage Oil (Borago officinalis) and Black Currant seed Oil (Ribes nigrum) are alternative or complementary sources of GLA. However, their price is much higher than hemp oil.
Dosage: 2-3 g/day *, (0.5-1 tsp).
• Rosehip oil (Rosa canina), extracted from the seeds of its fruit *, is rich in oleic, linoleic and alpha-linolenic acids, as well as galactolipids, which inhibit COX-1 and COX-2 cyclooxygenases *. Clinical studies lasting from 3 to 6 months showed that 2.5-5 g/day of rosehip powder resulted in an 18% reduction in C-reactive protein from baseline * *.
Dosage: 2-3 g/day, or 0.5-1 tsp.
• Olive oil (Olea europaea) is preferred for cooking as it has a higher anti-inflammatory potential than other common cooking oils (sunflower, corn, soybean, rapeseed).
• Black cumin oil (Nigella sativa), due to the thymoquinone present in it, exhibits strong anti-inflammatory, anti-infective and immunomodulatory effects. Kalinji oil suppresses chronic inflammation, while promoting the normal course of acute inflammation, which allows you to fight against infections and cancer *.
Dosage: from 1 g/day * to 3 g/day *, or 0.5-1 tsp.
• Pomegranate (Pomegranate) oil, extracted from pomegranate seeds, contains high amounts of conjugated linoleic acids (ω-5). Helps reduce inflammation in vivo by activating various anti-inflammatory mechanisms *, including COX-1 and COX-2 suppression *.
All vegetable oils must be first cold pressed (Extra virgin). They oxidize quickly and should therefore be purchased fresh from the refrigerator and kept in the refrigerator for no more than 3 months.
Antioxidants such as vitamin E (from 200 mg), selenium (from 100 μg) and coenzyme Q10 (from 30 mg) help to reduce the rate of oxidation of ω-3 directly in the body. The ratio of consumed fatty acids ω-6:ω-3 should not exceed 3.5:1.
• Fish oil is a rich source of anti-inflammatory animal ω-3 fatty acids (1 g of Arctic or Antarctic fish oil contains approximately 350 mg EPA and 220 mg DHA). If several stages of metabolism are required to obtain ω-3 fatty acids from vegetable oil, then ω-3 is already contained in fish oil in finished form. Therefore, it is often recommended to combine both of these sources of ω-3. Fish oil extracted from fish tissue is expensive, while fish oil extracted from fish liver is cheaper; however, the latter contains more toxins and heavy metals.
Omega-3 intake from fish oil has been associated with a reduction in plasma concentrations of inflammatory markers * *: 300 g/week of oil-rich fish can reduce CRP levels by 33% and IL-6 levels by 21% *. All-cause mortality was 16-34% lower among women with breast cancer who reported high intakes of oily fish and long-chain ω-3 fatty acids compared to women with low intakes *.
The recommended daily dosage for combined EPA and DHA ranges from 0.25g to 5g with an average of around 2.5g *, however reaching this dose can be difficult as EPA and DHA can vary greatly in the same foods *.
Other anti-inflammatory agents.
• Fisetin is found in many fruits and berries (apples, persimmons, mangoes, kiwi, strawberries, grapes), vegetables (onions, tomatoes, cucumbers), nuts and red wine. Dosage: 100 mg/day. In a clinical study, taking this amount of fisetin for 7 weeks slightly reduced C-reactive protein levels in patients, but significantly reduced IL-8 levels *.
Recommended dosages of quercetin, determined in Phase I clinical trials, are 2-3.5 g/day *.
• Lignans found in flaxseed can significantly influence inflammatory levels. The concentration in the blood of enterolactone – the main metabolite of lignan, is inversely related to the level of CRP *.
• Pentoxifylline is a drug that improves the circulation of small blood vessels, including those in the limbs and brain. Taking pentoxifylline for one month can reduce C-reactive protein levels by 20%, erythrocyte sedimentation rate by 18%, and total white blood cell count by 11% *. Due to its cheapness, safety and very good tolerance * it is sometimes called one of the best remedies for chronic inflammatory conditions.
Dosage: 800 mg/day * *.
• Vitamins B9 andB12 help keep homocysteine levels low.
Anti-inflammatory herbs. Adding other plant foods to your diet that help reduce inflammation seems to be helpful as well.
• Turmeric (Curcuma longa) contains curcumin in its root, which has a broad anti-inflammatory effect *. Maximum dosage: 6'000 mg/day of curcumin *, which corresponds to approximately 120 g/day of dry turmeric root powder. Recommended dosage: 1-2 tbsp. per day of turmeric root powder.
• Milk thistle (Silybum marianum) contains silymarin in its seeds, which significantly reduces levels of pro-inflammatory cytokines *. Dosage: 1'000 mg/day * for a month, followed by a repeat two months later. Pure silibinin can be replaced with finely ground 1 tbsp. milk thistle seeds.
• Sesame (Sesamum indicum) rich in lignans, the consumption of which prevents the formation of pro-inflammatory arachidonic acid from fatty acids. Dosage: 50 mg/day sesame lignan (approximately 25 g/day sesame seeds) for several weeks *.
• Spices such as cloves, rosemary, turmeric, nigella, coriander, black pepper and wasabi, even at doses commonly used in cooking, can noticeably reduce various indicators of inflammation in just a few days *, while cayenne pepper, paprika, and ginger can reduce immediately three inflammatory markers (TNF-α, IL-1α and IL-6) *. Their anti-inflammatory effect has been described in a variety of degenerative diseases *. In a clinical study, cardamom (40 g/day) decreased C-reactive protein levels *.
• Screening of 1'400 commonly available natural products * revealed high in vitro anti-inflammatory potential of plants such as Laurus (Laurus nobilis), leaf; Elecampane (Inula helenium), root *; Tansy (Tanacetum vulgare), aerial part; Yerba santa (Eriodictyon californicum), leaves *; Centipede (Centipeda minima), aerial part *; Ashwagandha (Withania somnifera), root *; Feverfew (Tanacetum parthenium), aerial part *; Rosemary (Rosmarinus officinalis), leaves and flowers *; Turmeric (Curcuma Longa), root; Osha (Ligusticum porteri), root *; Tea tree (Camellia sinensis), leaf *. In vivo studies support their anti-inflammatory effect *. Some of them can be added to dishes, and some can be used as water infusions. To date, however, only turmeric * has successfully passed clinical trials from this list.
Each of the remedies discussed above to one degree or another counteracts one or another conductor of inflammation; but, apparently, a combination of several agents will be more effective and will probably require a lower dosage.
Body grounding. The surface of the earth in relation to the atmosphere has a negative potential, and is able to provide the body with a certain amount of electrons directly, without any chemical reactions. The free electrons received in the form of a charge then migrate to the place with the highest positive potential, and along the way they participate in the neutralization of free radicals *.
Direct electrical contact with the surface of the planet produces a noticeable antioxidant, anti-inflammatory and general health effect *. For therapeutic purposes, conductive bedding and pillows, floor or table pads, and electrodes similar to those used in electrocardiography are used.
Blood is a colloidal solution because all blood cells have a small negative electrical charge. This charge is called the electrokinetic potential, or ζ-potential *. Thanks to him, like-charged blood cells repel each other, which makes it possible for them to remain in a suspended state.
The value of the ζ-potential determines the ability of blood to carry various substances dissolved in it. The higher the ζ-potential, the higher the ability of various materials to dissolve and be retained in a colloidal solution; the more active the transport of nutrients and waste products of metabolism. The lower the ζ-potential, the weaker the blood cells repel each other.
When the ζ-potential is too low, the attractive force begins to exceed the repulsive force, and cells can stick together (aggregate), increasing blood viscosity and promoting thrombosis. As a result, it becomes more difficult for blood to pass through the capillaries, and the heart has to expend more energy pumping it and increase blood pressure. Grounding the body to earth very quickly increases the number of negative charges on the surface of red blood cells, thereby reducing blood viscosity *. Thanks to this, blood pressure in hypertensive patients can be reduced by 7-22% *.
Grounding the body during sleep for 8 weeks lowers nighttime levels of the hormone cortisol and helps bring its secretion into line with the natural 24-hour circadian rhythm profile *. Such changes are especially noticeable in women.
In addition, grounding the body can significantly reduce the voltage induced in it by external electromagnetic fields (electrosmog). In particular, the reduction of the voltage induced in the body from 50-60 Hz power supply networks due to grounding can reach 70% *. The time of grounding procedures can be from 40 minutes to 10 hours a day, and their duration is 3-4 months *.
Although this method is not common and practically poorly developed, objective measurements in a few studies show that it can reduce inflammation, significantly reduce blood viscosity, improve sleep quality and relieve chronic pain *.
To detect chronic systemic inflammation, and to monitor progress in its reduction, it is required to know its level. But, unfortunately, there are no principles that can assess low-intensity systemic inflammation yet. However, there are several major classes of biomarkers associated with inflammation *: cytokines/chemokines; activators associated with immunity; acute phase proteins (C-reactive protein, serum amyloid A); reactive oxygen and nitrogen species; prostaglandins and factors associated with cyclooxygenase; and mediators such as transcription factors and growth factors.
High sensitivity C-reactive protein (hs-CRP) and fibrinogen are two inexpensive blood tests that are good markers of systemic inflammation. Normal serum level of C-reactive protein should be below 0.55 mg/L in men and below 1.0 mg/L in women, and fibrinogen level should be in the range of 200-300 mg/dL. A high level of C-reactive protein indicates inflammation, but it is not a specific marker of chronic inflammation, as it may be elevated due to a recent illness or injury. Also, unlike other cancers, an association between hs-CRP levels and breast cancer risk has not been identified *. However, levels above 1.0 mg/L may indicate low-grade systemic inflammation.
A serum protein (SPE) test can also be performed, which will show concomitant hypoalbuminemia and a polyclonal increase in all gamma globulins. Serum amyloid A (SAA) is another acute phase protein that can indicate inflammation, but its analysis is not a standardized procedure. Detection of specific cytokines that cause systemic inflammation, such as tumor necrosis factor TNF-α (< 8.1 pg/mL) and interleukins IL-1β, (< 15.0 pg/mL), IL-6 (< 2-29 pg/mL), IL-8 (< 32.0 pg/mL) is expensive and also not a standardized test.
While all of these markers can provide some insight into the extent of overall inflammation, other tests will have to be performed to determine its cause.
Homocysteine measured on an empty stomach. Medical laboratory «Dila» classifies the level of 11-14 µM as a moderate risk group, and 3.7-11 μM as a low risk group. Meanwhile, many experts consider a homocysteine value of less than 7.0 μM as low risk, 9.0 μM as moderate risk, and 15.0 μM and above as high risk. Thus, the optimal level of homocysteine to which we should strive is not higher than 7.0 μM *.
Allergopanel will help identify the sources of allergic reactions and adjust your diet and lifestyle accordingly.