Dihydroquercetin Plus: instructions for use, reviews

The drug, produced from environmentally friendly natural raw materials - the bark of Siberian and Dahurian larches, is called “Dihydroquercetin”. Reviews from doctors about this unique dietary supplement are optimistic - the product helps people who have been experiencing chronic fatigue and malaise for a long time to regain health and feel full of strength.

In addition to its excellent healing effect, this drug has another advantage - a very affordable price. Domestic manufacturers, obtaining environmentally friendly extract from coniferous trees, have significantly reduced the cost of this process. Until recently, foreign companies produced dihydroquercetin from exotic ginkgo biloba stems, grape seeds and rose petals. The cost of one gram of this unique substance reached $1,000. Today, an identical drug of natural origin can be bought for a budget amount. But how do experts characterize it?

Giver of long life: Dihydroquercetin Plus

Don't close the door through which nature comes in,

to restore the imbalanced balance in the body.

Vanga

Until recently, only a small group of large party workers could use this substance to maintain a healthy body in our country. It was impossible to obtain it in large quantities. Because of this, the price of the natural elixir of life was very high. We are talking about a compound from the group of bioflavonoids – dihydroquercetin. Today everything has changed. Scientists have discovered a way to obtain a unique substance from practically waste material - stumps left after cutting down larch trees, and based on it they created a drug for health and longevity, Dihydroquercetin Plus. What benefits does taking it give to a person?

Dispensing of the drug and its cost

You can purchase dietary supplements in pharmacies without a prescription. Reviews from doctors call the price of Dihydroquercetin relatively inexpensive.

So, 20 tablets of 25 mg can be bought in various regions of the country in the range of 180-200 rubles. A package with 60 identical tablets will cost the buyer 390-430 rubles. For capsules with dihydroquercetin and flaxseed oil (30 pieces) you can pay 230 rubles. However, there are offers on the Internet from unscrupulous sellers who can inflate the cost of dietary supplements several times (up to 1,800 rubles). The antioxidant complex must be purchased from reliable medical institutions.

Powerful antioxidant protection

Twice Nobel Prize laureate Linus Pauling, who lived to be 93 years old and proved by his own example that it is possible to cope with illness and disease without the help of drugs, argued that annual consumption of dihydroquercetin in the amount of several grams per year, especially in combination with vitamin C, contributes to real prolongation. active life for 20-25 years [1].

The fact is that according to one of the most popular theories of aging these days (its authors are D. Harman, 1956, N. Emanuel, 1958), the latter occurs due to the accumulation of damage in cells caused by free radicals with over time [2-4]. The formation of reactive oxygen species – also called free radicals – constantly accompanies oxidation reactions in the body. Normally, the antioxidant system easily copes with violators: their excess amount is neutralized by special enzymes - dismutase, catalase and peroxidase. The same radicals that escape from vigilant defenders are caught in the cell by vitamin C, and outside it by vitamins A and E. (That’s why dihydroquercetin is produced with these vitamins.)

However, the problem of modern man is that the factors that increase the number of free radicals in the body (radiation exposure, smoking, stress, taking certain medications, poor ecology, poor nutrition and others) are becoming more and more from year to year, and antioxidants in our food - less and less.

In this situation, taking dihydroquercetin can become a real lifesaver. Two independent American laboratories proved in 2008-2009 that the substance is 11 times or more superior in its antioxidant activity to its closest competitors [5].

How does a bioflavonoid fight free radicals? It turns out that the substance is capable of intercepting reactive oxygen species, and also forming complexes with metal ions that accelerate oxidative processes [6].

Contraindications, side effects, overdose and interactions with other drugs

Due to the natural composition of the described drug, no side effects were identified during clinical trials. The only contraindication may be individual intolerance to any of the components of the dietary supplement. But before taking Dihydroquercetin, doctors' reviews advise consulting with a specialist.

Pregnant women and nursing mothers should avoid taking the supplement. It is also not recommended to give the antioxidant complex to children under 12 years of age. If you take an excessive dose of dihydroquercetin, you must rinse your stomach and call a doctor. The negative impact of other drugs on the human body is reduced if they are taken in combination with the described dietary supplement.

Improving the functional state of the cardiovascular system

Healthy blood vessels are one of the most important conditions for a person’s well-being. They deliver nutrients and oxygen to the cells of the body. Experts say that any disease is in one way or another associated with impaired blood circulation, slowing down or stopping its flow and simultaneous inhibition of the movement of intercellular fluids. It is easier for pathogenic microorganisms to penetrate tissues and organs if the blood flows barely. The famous domestic scientist and researcher A. S. Zalmanov wrote: “The key to all cellular degenerations of general pathology is the insufficiency of capillary irrigation in the body” [7].

Restoring blood flow in capillaries, their permeability, strengthening blood vessels, as well as improving the rheological properties of blood (viscosity and stability) is the key to the successful treatment of any disease. And here the help that dihydroquercetin can provide is truly invaluable. It has been proven that the substance:

• inhibits the development of any inflammatory process, including inflammation of the vascular wall - the main cause of the development of atherosclerosis and cardiovascular diseases according to D. Lundell [8];
• reduces blood viscosity [9];
• prolongs the life of capillaries and activates their work by protecting cell membranes [10];
• restores the permeability of the walls of blood vessels and capillaries [10];
• improves blood circulation, including in capillaries [11];
• protects cell membranes, including blood cells and cells lining the inside of blood vessels, from destruction [10];
• reduces by almost 50% the activity of the enzyme responsible for the synthesis of “bad” cholesterol (low-density lipoproteins), thereby reducing the concentration of the latter in the blood [12];
• significantly reduces blood glucose levels and increases the resistance of blood vessels to its damaging effects (A. A. Uminsky, 2007) [13].

Blood thinning: how dihydroquercetin beats aspirin

To understand how dihydroquercetin and aspirin, painfully familiar to all heart patients, affect blood viscosity, let us remember what this physiological fluid is.

Blood is a kind of suspension that consists of a liquid medium - plasma and a suspension of cells. 93% of these cells are red blood cells - red blood cells that deliver oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs. Normally, the membranes of red blood cells and the inner wall of blood vessels carry negative charges. This prevents blood cells from approaching each other and the vascular wall (electrodispersal). The fact is that, according to the laws of physics, like charges (+ and +, – and –) repel, and unlike charges (+ and –) attract. If the surface of the red blood cell loses its charge of negative polarity, the red blood cells begin to stick together (aggregate) with each other, and congestion forms in the capillaries, blocking the flow of blood. The delivery of nutrients and oxygen to the tissue is disrupted. The result of combining red blood cells is an increase in blood viscosity, thrombus formation and a slowdown in blood flow. And this, as we have already said, is an impetus for the development of many diseases.

It has been proven that dihydroquercetin blocks the removal of charge from the erythrocyte, thereby preventing the clumping of red blood cells and the formation of blood clots [14]. At the Central Military Clinical Sanatorium "Arkhangelskoe" of the Ministry of Defense of the Russian Federation, a study was conducted on the effectiveness of the use of dihydroquercetin in the rehabilitation of patients with coronary heart disease who underwent coronary surgery to restore blood circulation [15]. It was found that the bioflavonoid accelerates the movement of blood through microvessels, reduces the number of pathological inclusions in red blood cells, reduces the adhesion of red blood cells, weakens congestion, and helps eliminate microscopic vascular lesions.

The effect of therapeutic doses of aspirin on blood viscosity was studied by researchers from the Yaroslavl State Pedagogical University. K. D. Ushinsky I. A Tikhomirova, E. P. Petrochenko, S. G. Mikhailova [16]. It turned out that a substance widely used in modern cardiology:

• increases the degree of erythrocyte adhesion (aggregation) by 24.3%;
• increases blood viscosity by 17.9%;
• Reduces blood flow by 44.6%.

Scientists were able to discover only one positive effect of aspirin, which, however, had no effect on blood fluidity: an increase in the deformability of red blood cells. The fact is that the diameter of red blood cells is 2 times the lumen of the capillary. In order to reach remote areas of the circulatory system, red blood cells have to change their shape, deform and literally crawl one by one through the capillaries, pushing their walls apart. As scientists A. A. Kubatiev and N. A. Tyukavkina proved in 1999, bioflavonoid reduces platelet aggregation, which is important for preventing heart attack. All this makes Dihydroquercetin Plus an effective means of preventing a number of vascular diseases!

The advantages of dihydroquercetin over aspirin are obvious.

Methods and dosage

In an adult, the intake rate of dihydroquercetin varies from 25 mg to 100 mg per day. The instructions for use of the drug recommend sticking to the minimum dose and taking one tablet a day.

With increased mental and physical stress, the dosage is increased by 4-6 times. In this case, take the dietary supplement 1-2 capsules (tablets) 2 times a day. After a two to three week course, you need to take a short break (1.5-2 weeks).

In case of a serious illness, when it is necessary to use Dihydroquercetin in complex treatment, reviews from doctors advise colleagues to prescribe:

• to stimulate microcirculation of blood flow in vessels in diseases of the heart and circulatory system (arrhythmia, ischemia, heart failure, angina) - 50 mg (2 tablets) four times a day;
• for hypertension - 50 mg three times a day;
• for heart attack, stroke, acute renal failure,
• for diseases of the respiratory system - 75 mg three times a day;
• during the rehabilitation period after a heart attack or stroke - 100 mg twice a day;
• for dysfunctions of the nervous system (migraines, VSD) - 125 mg once, repeated dose - no earlier than 2-3 hours later;
• for visual disturbances – 50 mg twice a day;
• after poisoning, smoking or exposure to radiation - 75 mg three times a day;
• to increase the therapeutic effect after physiotherapy - take 50-100 mg one and a half to two hours before manipulation.

Improved bone metabolism

Some studies of dihydroquercetin show that the substance can have a positive effect on bone metabolism - the process of gradual bone tissue renewal.

Thus, a scientific experiment by scientists from Austria, Sweden and Spain M. Satue, M. delMarArriero, M. Monjo, JM Ramis in 2013 made it possible to establish that bioflavonoid inhibits the formation of bone cells that destroy bone tissue - osteoclasts - and their activity. At the same time, it promotes the formation of osteoblasts – bone cells that carry out restoration work in bone tissue [17].

A 2022 study (YJ Wang, HQ Zhang et al) also showed that dihydroquercetin is able to stimulate the conversion of bone marrow mesenchymal stem cells into osteoblasts [18].

In November 2022, a group of Chinese scientists C. Cai, C. Liu, L. Zhao and colleagues conducted an experiment on mice [19]. Both ovaries were removed from female animals. A month later, a significant loss of trabecular bone tissue mass was noted in the rodents. One part of the animals was given saline solution, the other – dihydroquercetin. Taking the bioflavonoid by the experimental group contributed to a noticeable increase in bone tissue density, which was not observed in the control group. An in vitro study by the same specialists showed that dihydroquercetin suppresses the formation of osteoclasts and inhibits the function of the said cell. Scientists believe that the substance can be used in the treatment of postmenopausal osteoporosis.

Arguments of doctors approving the drug

Dihydroquercetin is one of the most active and effective representatives of the vitamin P group. Doctors often recommend it to people with chronic illness, suffering from a loss of general body tone, feeling sluggish, and not getting enough sleep.

Reviews from patients who have completed at least one therapeutic course of taking the dietary supplement confirm that it has a positive effect on well-being and the course of cardiovascular diseases, endocrine and nervous disorders. They noted improved sleep, increased appetite and general activity of the body. Doctors recommend taking dihydroquercetin in courses, taking breaks. The drug is most active after the second stage of treatment, although some patients testify that the dietary supplement has a beneficial effect just a week after the start of treatment.

Protecting nerve cells and normalizing cognitive functions

It has been established that dihydroquercetin helps to increase the quantity and quality of connections between nerve cells in the main areas of the brain and thereby prevents the progression of neurodegenerative pathologies and helps improve attention, memory, and thinking.

At the Institute of Human Brain of the Russian Academy of Medical Sciences, a study was organized on the effectiveness of using a bioflavonoid in people with chronic cerebrovascular insufficiency. 29 people aged 66–69 years took the named substance at 80 mg per day for 3 weeks. A decrease in the severity of emotional disorders, headaches, dizziness, manifestations of neuropsychic exhaustion and physical exhaustion was noted. Indicators of attention, working memory, intellectual and associative activity improved [20].

British scientists from the University of Reading J. Robert, A. Williams, P.E. Jeremy and colleagues, in experiments on animals (male rats), showed that oral administration of dihydroquercetin has the same effect on the brain (causes similar changes in the electrical activity of the brain) as taking well-known drugs for the treatment of degenerative and mental diseases of the brain (senile dementia, Parkinson's disease, Alzheimer's disease, depression) - selegiline, galantamine, tacrine, amantadine, amitriptyline, imipramine and memantine [21]. These substances have a wide range of side effects. In contrast, bioflavonoid is absolutely safe. These results allow us to classify dihydroquercetin as a compound with antidepressant and antiparkinsonian properties.

Specialists from the Tomsk National Research Medical Center of the Russian Academy of Sciences M. B. Plotnikov, S. V. Logvinov, N. V. Pugachenko, having conducted experiments on rats, proved that a bioflavonoid in combination with vitamin C significantly reduces the number of irreversible changes in neurons during cerebral ischemia, improves the performance of the thinking organ [22]. And for brain damage caused by cerebrovascular accidents, the substance in combination with ascorbic acid can reduce dizziness and fatigue, and improve cognitive function.

Indications

Experts call Dihydroquercetin “vitamin number one” for the heart and blood vessels. Instructions for use recommend using it for arrhythmias, ischemic heart disease, myocarditis, strokes, heart attacks, hypertension and atherosclerosis, varicose veins and thrombophlebitis. This drug is also prescribed for nervous diseases: neuralgia and neuritis, neurasthenia and Parkinson's disease, senile dementia (Alzheimer's syndrome) and multiple sclerosis.

In addition, doctors prescribe this drug to rejuvenate the body, as a supporting agent for immunodeficiency (secondary), for allergic reactions of various etiologies or chronic fatigue syndrome. “Dihydroquercetin” makes it easier to tolerate: ARVI, otitis, pharyngitis, rhinitis, sinusitis, tonsillitis, as well as respiratory diseases - pneumonia and bronchitis, asthma and tuberculosis.

It is used in gynecological practice for the treatment of: colpitis, mastopathy, vulvitis, fibroids, infertility, ovarian cysts or cervical erosion; for diseases of the urinary system (including infectious diseases) - cystitis, pyelonephritis or glomerulonephritis; urological problems – prostatitis (chronic), erectile dysfunction and prostate adenoma; gastrointestinal diseases: gastritis, colitis, cholelithiasis and pancreatitis, ulcerative lesions of the stomach or duodenum; for rheumatism or rheumatoid arthritis; skin injuries and diseases (furunculosis, herpes and psoriasis, dermatitis and trophic ulcers, purulent wounds, frostbite or burns).

Doctors' reviews recommend taking "Dihydroquercetin" to maintain the functionality of the musculoskeletal system - for osteochondrosis, arthritis and arthrosis, as well as for endocrine disorders (hypothyroidism and thyrotoxicosis, chronic adrenal insufficiency). In addition, it is recommended for visual disorders - glaucoma, retinopathy, cataracts, myopia and farsightedness.

Improved vision

Dihydroquercetin can provide invaluable assistance in the treatment of ophthalmic diseases. The substance increases visual acuity, improves sensitivity and conductivity of the optic nerve, restores damaged eye tissue, strengthens its muscles and ligaments, prevents hemorrhages in the retina of the organ of vision, promotes its rapid resorption, relieves fatigue and spasm of accommodation, improves twilight vision.

Professor, Doctor of Medical Sciences I. G. Ovechkin and colleagues proposed the use of dietary supplements with dihydroquercetin to correct functional disorders of the visual organs [23]. Scientists conducted a study with the participation of 152 people: 30 of them were patients with visual fatigue (asthenopia), 122 were representatives of professions that require significant visual strain (drivers, fighter pilots, professional PC users). Some of them formed the experimental group. They were prescribed a course of taking a supplement with dihydroquercetin. The other part - participants in the control group - continued to do their usual work and did not take anything. In the first group, there was an increase in distance visual acuity (noted by 71% of participants), a subjective feeling of improved vision (noted by 81% of subjects), improvement in twilight vision and adaptation to darkness (71%), an increase in the “quality of visual life” (90%), a decrease visual fatigue (69%). The level of visual performance increased by 1.2-8.4%.

In 2005, The Journal of biological chemistry published a study by BF Godley, FA Shamsi and other scientists on the protective effect of dihydroquercetin on retinal cells of the human eye under ultraviolet radiation [24]. Cultures of human retinal epithelial cells were exposed to visible light wavelengths (390-550 nm at a power of 2.8 mW/cm2) for 6 hours. Dihydroquercetin in an amount of 10 mg was previously added to some of these cells. It turned out that the bioflavonoid provided complete protection of the proteins of the eye lens throughout the experiment. The fact is that the lens consists of 98% proteins. These proteins are easily damaged by free radicals and coagulate. The lens loses transparency and cataracts develop. Dihydroquercetin, as mentioned above, is a powerful antioxidant.

"Dihydroquercetin": negative reviews from doctors

Skeptical experts advise not to consider dietary supplements a panacea for all ailments. Its use, like most medications, is possible only after approval by a doctor and a thorough diagnosis of your body.

When analyzing reviews from Internet users and based on their observations, practicing doctors express doubts about the obvious changes in patients’ bodies in a short period of time. Not all people who take the supplement report improved performance. Hypotonic people, for example, still feel sleepy during the day. Acceleration of rejuvenation processes over a short distance is difficult to notice. Doctors and patients do not show a negative attitude towards the drug “Dihydroquercetin”, but they believe that not everyone experiences visible results from treatment with the dietary supplement. In addition, for a positive therapeutic effect, a long course is required with breaks under the supervision of a specialist.

Destruction of pathogenic bacteria and viruses

Famous scientist, naturopath, gerontologist, MD. A. S. Zalmanov said regarding the treatment of infectious diseases: “Before using antibiotic treatment, let polybiotics act. To do this, you need to restore blood circulation in the capillaries, that is, cleanse the blood, restore its circulation, remove harmful substances from the blood, open the way for phagocytosis, wash the microbes with circulating plasma; then it will glue, precipitate (transfer the molecules of foreign microorganisms, viruses into sediment), neutralize and eliminate the invading microbes, just as water in a river eliminates its impurities, because in every drop of blood there are more antibodies than in all the laboratories in the world.” Dihydroquercetin also easily copes with these tasks.

The substance not only improves blood circulation in the capillaries, cleanses it of harmful impurities (“bad” cholesterol, glucose), but also has the ability to kill some types of pathogenic bacteria and viruses, and also favors the development and growth of lactic acid microflora. This was proven by the results of a study by specialists from the All-Russian Research Institute of the Dairy Industry [25].

Scientists infected samples of sterilized cream with a mass fraction of fat of 10% with various types of pathogenic or lactic acid bacteria. Then dihydroquercetin was added to one part of the resulting product (experimental samples) at the rate of 200 mg/kg (0.02%). In the other (control samples), the bioflavonoid was not introduced. The results are shown in the table.

No. Microorganisms Results

(experimental samples)

Pathogenic

1. Escherichia coli (pathogen of genitourinary diseases) death of 11.8% of bacteria
2. Salmonella (the causative agent of salmonellosis) no death
3. Staphylococcusaureus (pathogen of purulent-inflammatory processes) death – 91%
4. Listeria monocytogenes (the causative agent of listeriosis) death – 30%

Lactic acid The structure of bacterial cells remains unchanged; There was a higher rate of cell viability compared to control samples. The number of surviving cells corresponded to GOST R 5133199

1. Lactobacillus bulgaricus ("Bulgarian stick")
2. Streptococcus thermophilus
3. Combination of Lactobacillusbulgaricus and Streptococcusthermophilus in a ratio of 1:4

In a 2009 study conducted by H. Kuspradini and TJ Mitsunaga, it was shown that at a concentration of 9.3-42.7 μg/ml dihydroquercetin inhibits the growth of the caries pathogen bacterium Streptococcus sorbinus, and at a concentration of 27.4-57.3 μg/ml ml inhibits the activity of the GTase enzyme produced by cariogenic bacteria [26]. This enzyme produces highly viscous, insoluble polysaccharides that, like glue, firmly adhere microbes to the surface of the teeth. Scientists recommend using bioflavonoid as an effective means of preventing dental caries.

Specialists from the Influenza Research Institute of the North-Western Branch of the Russian Academy of Sciences O. I. Kiselev, V. A. Babkin and colleagues studied the antiviral properties of dihydroquercetin in 2010 [27]. 20 white mice were previously infected with lethal influenza A and B viruses. Ten animals (experimental group) were injected with dihydroquercetin. The remaining rodents (control group) did not receive the bioflavonoid. After 15 days, the results of the observations were summed up. It turned out that in the experimental group, mortality among experimental animals was significantly lower than in the control group, and life expectancy, on the contrary, was higher. The protective effect of dihydroquercetin was comparable to the activity of the reference drug Remantadine, and in the case of influenza A even surpassed it. The protective activity of the bioflavonoid against the influenza B virus was comparable to that of Ribavirin. Scientists note that in practice it is extremely rare to deal with such high doses of influenza - this suggests the high protective activity of dihydroquercetin in the treatment of influenza in humans.

Boosting immunity

The immunomodulatory properties of dihydroquercetin are carried out through the normalization of the body's antioxidant system. The bioflavonoid has been found to promote:

• activation of the production of antibodies and interferon, as well as special cells of the immune system - T-hellers and neutrophils (provide an immune response to the attack of viruses and bacteria);
• protecting cell DNA from metabolic products;
• increasing the resistance of mucous membranes and skin to infections;
• reducing the damaging effect of infection on body tissue and the activity of the inflammatory process;
• partial restoration of impaired functions of phagocytes (cells of the immune system that absorb bacteria, viruses, dying and dead cells) and the concentration of dendritic cells (indicate foreign antigens to other cells of the immune system), as well as specific proteins of the immune system.

Specialists of the Oncological Research Center named after. N. N. Blokhin of the Russian Academy of Medical Sciences, as well as the Moscow Medical Academy named after. I.M. Sechenov recommends the use of antioxidants in the complex therapy of cancer [28]. Dihydroquercetin can improve the quality of life of patients, reduce the toxic side effects of chemotherapy, regulate the formation and neutralization of free radicals, and have an immunomodulatory effect [29].

According to a study by a mammologist, oncologist, Ph.D. S. Ch. Maykoparova, when using chemotherapy in combination with dihydroquercetin, patients experienced symptoms much less frequently: loss of appetite, nausea, vomiting, sleep disturbances, infectious complications, sweating, general weakness, heart rhythm disturbances, pain in the heart, stomach, hypochondrium areas. Efficiency and motor activity increased, a feeling of increased strength appeared, mood improved, and interest in the environment appeared [30].

The action of a powerful natural antioxidant and angioprotector in the drug Dihydroquercetin Plus is supplemented and enhanced by antioxidant vitamins E and C. The biocomplex provides reliable prevention of diseases caused by free radicals and vascular pathologies, slows down the aging process in the body, and prolongs the period of active life.

Composition of dietary supplement "Dihydroquercetin": instructions for use

Reviews from doctors about this dietary supplement are mixed. One group of specialists is confident in the strengthening and rejuvenating effect of dietary supplements, while the other claims that tablets or capsules only invigorate for a short time, so it is difficult to track the long-term dynamics of the results. Domestic companies such as Pharma GMC PN, RUSKAPS and Flavit produce the strengthening and prophylactic drug Dihydroquercetin.

Each capsule or tablet contains at least 25 mg of the active substance, which is a natural flavonoid - dihydroquercetin. The antioxidant complex “Dihydroquercetin Plus” (doctors’ reviews especially recommend it for older people), in addition to the main component, contains: 4 mg of vitamin E (alpha-tocopherol) and 10 mg of vitamin C (ascorbic acid). These substances in combination enhance the rejuvenating, decongestant and detoxifying effects of each other. Of the auxiliary components in tablets or capsules of the drug “Dihydroquercetin Plus”, manufacturers add: lactose (milk sugar) as a filler; methylcellulose and Tween 60 as emulsifiers; calcium stearate, which blocks the formation of lumps from active substances; titanium dioxide (dye). The additional components of the drug "Dihydroquercetin Evalar" contain additives that prevent caking of the main components (calcium stearate and aerosil), as well as a filler - microcrystalline cellulose. Capsules or tablets, which, along with flaxseed oil, contain the anti-aging medicine “Dihydroquercetin”, the instructions describe as a complex of substances containing glycerin (E422) for plasticization, as well as food coloring: Ponceau (E124) and caramel color (E150d).

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Dihydroquercetin as a potential immunonutrient in complex therapy of COVID-19

Introduction

In a pandemic, the issue of creating effective antiviral drugs for the treatment of a new coronavirus infection is most acute, since effective treatment methods have not yet been developed and therapy often comes down to symptomatic treatment, relying mainly on the repurposing of existing drugs (such as ritonavir, remdesivir , favipiravir) and antibiotics for the treatment of secondary infections that rapidly develop against the background of COVID-19. The shortage of drugs with clinically proven effectiveness has contributed to the fact that natural products have begun to attract more and more attention due to their low toxicity and lack of side effects [1–4].

Pleiotropic properties of dihydroquercetin

Dihydroquercetin (DHA) is a bioflavonoid found in some coniferous trees that has a number of unique medicinal properties. DHA has attracted the attention of researchers due to its ability to prolong the life of the higher plants in which it was found.

In 1814, the French researcher Chevreul isolated the first flavonoid, later named quercetin. In Russia, the study of flavonoids was initiated by the famous botanist Ivan Parfenevich Borodin in 1873. A new stage in the study of bioflavonoids began in 1936, when American scientists of Hungarian origin, Albert Szent-Gyorgyi and István Rusnjak, established that a complete cure for scurvy is possible only if vitamin C is combined with another substance that increases the stability of capillaries, and isolated this substance (from citrus fruits), calling it vitamin P. Subsequently, it turned out that vitamin P is not one substance, but a whole series of compounds, and the name “vitamin P” was replaced by the term “bioflavonoids”.

In the late 40s of the 20th century, forest products laboratories in Oregon, USA (Oregon Forest Products Laboratory, US) began researching the chemical composition of the bark of western pine trees in order to determine the possibility of its use. The bark of the Douglas fir (Douglas - fir) was one of the first to be studied. DHA was found to be a commercially important ingredient in Douglas fir bark (Pew, John C., 1947).

Currently, the main raw material for the production of DHA on an industrial scale is the wood of Siberian larch (Larix sibirica Ledeb) and Dahurian larch (Larix dahurica Turcz). Larch wood contains up to 2.5% flavonoids, among which DHA accounts for up to 90-95% of the total amount of flavonoids [5, 6]. DHA is widely used in the medical, food, pharmaceutical and perfume industries [7–10]. As a preservative, DHA is added to milk powder, confectionery products, butter, etc. To demonstrate the antioxidant effect, DHA is added to various ointments.

Dihydroquercetin is a bioflavonoid with a wide range of pharmacological properties, has antiradical and antioxidant activity that exceeds known natural analogues (vitamins B, C, etc.) by more than 10 times [11, 12], and has antibiotic, radioprotective and immunomodulatory properties. A bactericidal effect has been established against pathogenic bacteria, fungi and viruses and a positive effect on the lactic acid microflora of the intestine [13].

In earlier studies, the antiviral properties of DHA were studied in vitro [14, 15] and in vivo [15] against a member of the picornavirus family, Coxsackievirus B4 (one of the main causes of type 1 diabetes). It is noted that the effect of DHA in the treatment of viral pancreatitis was comparable to or greater than the effect of ribavirin (previously approved for the treatment of COVID-19). The work [16] found that the antiviral activity of dihydroquercetin against influenza A and B viruses is comparable or higher than that of rimantadine.

DHA has a positive effect on the molecular mechanisms underlying the regulation of vascular permeability and resistance of the vascular wall, as well as on the metabolism of arachidonic acid, which allows the use of DHA in inflammatory diseases, allergic and hemorrhagic syndromes. DHA helps reduce the level of circulating pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6).

With long-term use, DHA helps maintain the functions of the immune system, prevents exacerbation of chronic respiratory diseases and the occurrence of acute respiratory viral infections.

The first clinical trials of DHA in the treatment of patients with acute pneumonia were conducted more than 20 years ago [17, 18]. The use of DHA in complex therapy contributed to the rapid relief of pulmonary inflammation. An acceleration of the processes of normalization of the main indicators of blood circulation in the bronchial mucosa and a decrease in reactive oxygen species (ROS) in the blood serum were recorded.

In patients with pneumonia, whose therapy included 90% DHA at a dose of 40-60 mg 4 times a day during the acute and subacute period, there was a 1.8 times more effective clinical and radiological restoration of lung tissue, as well as a decrease in pulmonary fibrosis 3.6 times compared to the control group of patients in whom DHA was not included in the therapy [19].

Similar results were obtained in a clinical study of endobronchial microcirculation of the bronchial mucosa in patients with chronic obstructive pulmonary disease (COPD) [20].

The membrane-stabilizing effect of DHA and its redox properties contribute to the effective functioning of tissue respiration enzymes, oxygen utilization and ATP synthesis in mitochondria. Along with the stabilization of erythrocyte membranes and improvement of the oxygen transport function of erythrocytes, these effects determine the antihypoxic and antihemolytic properties of DHA, which help increase the oxygen and energy supply of cells.

DHA blocks the removal of charge from red blood cells, thereby preventing them from sticking together and forming blood clots.

The antiplatelet properties of DHA are widely known [19, 21]. The work [22] showed in vivo that DHA can dose-dependently suppress platelet aggregation activated by various inducers.

DHA has a capillary protective effect, reduces the permeability and fragility of capillaries, improves microcirculation, helps inhibit the action of enzymes that loosen the connective tissue of the walls of blood vessels and other systems, but activates an enzyme that promotes the “ripening” of collagen (synergy of the action of DHA in relation to ascorbic acid), such thus maintaining strength, elasticity and normalizing the permeability of the vascular wall.

DHA is able to reduce capillary permeability 1.3–1.4 times better than quercetin, while reducing the exudative phase of the inflammatory response [23].

As a ligand of GABA-benzodiazepine complexes in the brain, DHA promotes sedative, hypotensive and analgesic effects.

Clinical trials of drugs with DHA, which have been conducted in Russia for more than 20 years, have shown the positive effects of DHA as a prophylactic agent to reduce the risks of cardiovascular diseases, as well as in rehabilitation after a number of diseases: coronary artery disease, discirculatory encephalopathy, cerebral atherosclerosis[24], diabetes diabetes, lung diseases. [19]. A dose-dependent inhibition of cholesterol synthesis, reaching 86%, has been clinically confirmed [25].

The positive properties of DHA are manifested both in the intracellular and extracellular environment. Studies on red blood cells, white blood cells, macrophages and hepatocytes have shown that DHA contributes to their greater resistance to membrane damage. DHA stabilizes cell membranes by inhibiting free radical processes of lipid peroxidation.

Points of application of dihydroquercetin for COVID-19

Oxidative stress is a key factor in the development of COVID-19 in a significant number of patients [26–28]. This is especially true for severe cases in which pulmonary dysfunction, cytokine storm (intense inflammatory reaction) and viral sepsis are manifested.

Today, the prospects for using DHA as a regulator of oxidative stress as part of complex therapy for COVID-19 and for the prevention of possible complications are being actively discussed [29].

The process of oxidative stress in COVID-19, accompanied by the formation of ROS, leads to deep damage and bilateral inflammation of lung tissue, which is not typical for normal inflammation. The results of diagnosing patients using radiography (including computed tomography), as well as the results of pathological studies of deceased patients, showed that inflammation in COVID-19 has not only a viral, but also a biochemical etiology. The development of hypoxia during the course of COVID-19 is associated with damage to hemoglobin molecules in red blood cells, which come into contact with the surface proteins of the SARS-CoV-2 membrane. This process is accompanied by the release of toxic iron ions into the blood from hemoglobin heme, which are carried in free form throughout the body. Hemoglobin without iron, when passing through the lungs, is not able to form a bond with oxygen and deliver it to the tissues. As a result, hemoglobin stops performing its functions and becomes a carrier of coronavirus. Free iron causes peroxidation, which leads to tissue degradation at the level of cellular components - lipids, DNA and proteins, which can result in damage to the brain and nerve tissue. Some of the free iron binds to protein and forms ferritin, which is a unique marker of COVID-19.

DHA, as an antioxidant, is able to break the oxidation chain reaction [19, 30–34].

It is known that regular consumption of products with DHA protects the liver from destruction by viruses and toxic substances, improves the elimination of toxins, radionuclides and heavy metal salts. Like all other flavonoids, DHA is a chelating agent and is able to bind to iron [34, 35], inhibiting its participation in the generation of ROS [36].

A number of studies show that DHA inhibits apotosis processes caused by excess iron in the liver in rats [37]. DHA exhibits similar bioavailability in humans and rats [38, 39], and liver iron content in experimental rats was comparable to that observed in humans during iron overload. Excess iron leads to a significant increase in lipid and protein peroxidation, as well as a decrease in the overall antioxidant capacity of liver tissue.

Impaired liver function associated with the accumulation of iron in it as a result of hemoglobin degradation is accompanied by the release of a specific enzyme alanine aminotransferase (ALT) into the blood, which acts as a marker for the development of severe forms of COVID-19.

DHA, by reducing iron content in the liver, enhances the regeneration of damaged tissues. The use of DHA improves the histopathological picture of the liver; a decrease in iron-induced inflammatory reactions is confirmed by a decrease in the activity of hepatic transaminases in the blood serum.

Research conducted on volunteers revealed an improvement in the stability of the psycho-emotional state of volunteers during the COVID-19 pandemic who took a carbohydrate product enriched with freeze-dried DHA nanoemulsion. Volunteers were exposed to stress caused by exposure to information about the dynamics and consequences of the spread of coronavirus infection. Compared to the control group taking a placebo product, volunteers taking a product with DHA showed a significantly smaller increase in the value of the leukocyte index of intoxication (6.1 versus 40.9%), as well as a significantly smaller decrease in the value of the lymphocyte index (3.8 versus 8%), indirectly indicating the state of stress in the body. Volunteers who took the DHA product showed a 7.6% decrease in serum cortisol levels, while the group taking the placebo product experienced a 75.9% increase in cortisol levels during the stress factor, which allows us to conclude about increasing the resistance of volunteers’ bodies to the effects of stress factors in living conditions during the COVID-19 pandemic through the use of a product with DHA [40].

Conclusion

The biological activity of DHA is aimed at restoring the normal functioning of all the main target organs of SARS-CoV-2, such as the lungs, heart, liver, etc. In addition, DHA is an anticoagulant and a powerful antioxidant, which helps normalize hematological blood parameters. Positive results from clinical trials previously conducted in the treatment of acute pneumonia suggest that DHA may also be used to treat pneumonia caused by the novel coronavirus infection COVID-19. DHA's ability to remove toxic free iron, which is formed as a result of hemoglobin degradation under the influence of SARS-CoV-2, can significantly reduce tissue degradation and reduce the load on the liver against the background of COVID-19. All of the above allows us to consider DHA as a potential immunonutrient in the complex therapy of SARS-CoV-2, which can significantly reduce tissue degradation and reduce the load on the liver against the background of COVID-19.

The publication was supported by the RUDN Strategic Academic Leadership Program.

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Source: Tatarinov V.V., Orlova S.V., Nikitina E.A. et al. Dihydroquercetin as a potential immunonutrient in complex therapy of COVID‑19 // Medical alphabet. 2022. No. 22. pp. 28-32.

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