Quercetin

Quercetin

Description and occurrence

Quercetin is a substance from the flavonoid group. It is found in many types of food. In particular, some vegetables (most notably onions, cabbage and broccoli) contain high levels of quercetin, as do berries (blueberries, cranberries, chokeberries, chokeberries, sea buckthorn and blackcurrants), citrus fruits, soya beans, black and green tea and buckwheat. A person consuming a healthy diet takes in about 65 mg of quercetin per day, but for medicinal purposes, for example, the requirement is much higher and it is therefore advisable to consume it in the form of supplements.

Effects

Quercetin is not only a powerful antioxidant, but it also has a strong epigenetic action, thanks to which it is able to influence which of the genes of our hereditary information are actually expressed and which are not. It can thus play a significant role in the prevention and treatment of a number of conditions.

Slowing down aging

Although we do not know the exact cause of ageing, science has mapped a number of changes at the cellular level that accompany and probably contribute to ageing.

The first is negative epigenetic changes, especially in the area of gene methylation. Although we can influence the level of these changes by our lifestyle, unfortunately only partially. Their increase with age is thus inevitable (31).

The second important factor is the accumulation of so-called senescent cells. These are cells that have already exhausted their potential to divide, yet they do not disappear, but continue to survive, accumulate in the body and worsen some aspects of its functioning (read more about senescent cells here: https://www.epivyziva.cz/elixir-mladi-klic-mozna-lezi-v-senescentnich-bunkach/).

The ability to autophagy, the process by which a cell “eats itself”, also deteriorates with age. This mechanism primarily improves the ability to survive in times of extreme nutrient deficiency, but it is also a way for the body to rid itself of damaged cells, dysfunctional organelles and metabolic wastes (32). Another manifestation (and likely cause) of ageing is the deterioration of mitochondrial function, which are the organelles that convert nutrients into energy (more here: https://www.epivyziva.cz/mitochondrie-klic-k-dlouhovekosti/).

Quercetin can positively influence the aging process on all these fronts. First and foremost, it has a positive effect on senescent cells – not only does it promote their removal from the body (the so-called senolytic effect), but in cell culture studies it has even been able to restore the ability to divide in cells that have already reached the senescent stage (33, 38).

Quercetin also directly affects the intensity of epigenetic reactions in the body, and is also one of the effective activators of sirtuins. Sirtuins are enzymes that, firstly, greatly influence epigenetic processes but, in addition, play an important role in the regulation of processes that take place inside mitochondria (34, 35).

Quercetin also positively influences the process of autophagy (36), and in addition, it promotes the production of the male sex hormone testosterone, whose production decreases significantly with age.(53) An increase in its level is then reflected not only in an increase in libido, but also in overall vitality.

Tumour diseases

Quercetin is one of the substances with a very strong anti-cancer effect. One reason for this is that it is a very powerful antioxidant that helps protect DNA against free radical damage.(1) Perhaps even more important, however, is its epigenetic action, which allows it to influence various signaling processes in cancer cells without having a toxic effect on healthy cells. It is true that some genetic processes are disrupted in cancer cells that prevent healthy cells from multiplying rapidly and uncontrolled.

For example, quercetin inhibits the activity of 16 enzymes from the kinase family, some of which play an important role in cell cycle regulation. Among other things, it suppresses signaling pathways of the proliferation process, which is a rapid, uncontrolled cell proliferation typical of cancer (2, 3).

Quercetin also affects a process called histone acetylation. Histones are the proteins that form the spatial structure of DNA, and their acetylation allows DNA to be “read” and proteins to be synthesized from it. It also blocks the binding of various transactivators (e.g. p300 or NF-kB), thereby reducing the activity of the COX2 gene, which stimulates inflammatory processes. Suppression of COX2 and the associated inflammatory processes is considered to be a very important component of cancer prevention.(4, 5) Last but not least, it affects the activity of a group of enzymes called sirtuins, which also regulate the expression of some important genes, which has a positive effect not only on the aforementioned aging rate but also on the risk of cancer. (6, 7) The most well-known of these, abbreviated SIRT1, for example, regulates the ability of apoptosis, or programmed cell death, which is usually impaired in cancer. (8) However, it also counteracts the activity of the demethylase LSD1, which plays a crucial role in regulating the transcription of genes involved in cell growth and differentiation – here, too, it is a mechanism that prevents the proliferation of damaged cells, including cancer cells. (9) However, the ability of quercetin to improve autophagy is also important, as impaired autophagy increases the likelihood of cancer development.

If the cancer is already present, the fact that quercetin can limit the formation of new blood vessels necessary for the blood supply to the tumour, thus essentially helping to “starve” it, is also important in its treatment.(17) It has even been shown to have an effect in the prevention and treatment of leukaemia (10)

Anti-inflammatory action

Inflammation is not a process in itself, but plays an important role in the body, for example in fighting infection or healing wounds. However, if it goes into a chronic phase, this means a problem. In fact, an increased level of inflammatory processes is one of the factors that contribute to the development of many serious diseases – for example, certain types of cancer, cardiovascular disease and others (more here: https://www.epivyziva.cz/jak-vyhnat-zanet-z-tela/).

Quercetin helps to fight inflammation in several ways: its strong antioxidant effect is important, because high concentrations of free radicals activate genes that promote inflammatory processes.(39) It also helps to reduce the production of inflammation-promoting substances such as TNF-α or cytokines.(40, 41) Last but not least, it suppresses the COX-2 enzyme, which is essential for the production of inflammatory prostaglandins. (42)

Diseases of the heart and blood vessels

Most flavonoid family substances can slow the development of atherosclerosis, a major risk factor for heart and blood vessel disease, but quercetin appears to be the most effective of them, according to the researchers’ findings. It owes this to its antioxidant action, anti-inflammatory effect due to epigenetic action and its ability to alleviate so-called endothelial dysfunction. It can also regulate LDL cholesterol levels and prevent its oxidation by free radicals (21, 22).

However, Quercetin is also quite effective in reducing high blood pressure, which is another risk factor for cardiovascular disease. It has a positive effect on both systolic and diastolic blood pressure, with the first noticeable results appearing after just one week of taking doses of 10 mg per kilogram of body weight and persisting even after the end of use. In animal studies, significant reductions in blood pressure were also observed in rats fed a high-fat, high-sugar diet (18-20).

There are many reasons for the positive effects of quercetin on the heart and blood vessels. Important here are its function as a sirtuin activator (35), its anti-inflammatory action (42) and its ability to promote the production of the enzyme eNOS, which is involved in the formation of nitric oxide, in the vascular lining. This oxide subsequently acts as a vasodilator, i.e. a substance that relaxes and dilates blood vessels, resulting in a decrease in blood pressure and improved blood supply to the tissues (43).

Immunity

Quercetin is one of the polyphenols with extensive positive effects on the immune system. For example, its ability to inhibit the production of interleukin 6 and TNF-α, which play a key role in inflammatory processes, is important.(11) The antioxidant effect of quercetin is also involved in supporting immune function. This substance even helps against the decline in immune function after intense exercise. If a person undergoes extreme physical stress such as a marathon, his immune functions are significantly reduced up to 72 hours after the end of the exercise, which is reflected, for example, in a higher susceptibility to respiratory diseases. The use of quercetin (1000 mg per day for three weeks) significantly reduced the incidence of these diseases after exercise. (28)

Weight Loss

Obesity is not only caused by an imbalance between energy intake and energy expenditure, but obese individuals are much more likely to have various epigenetic changes in DNA and histone regions than normal-weight populations. The oft-mentioned “it’s in our genes” is therefore not just an excuse – it is not a genetic trait encoded in our DNA, but biochemical changes that occur during intrauterine development and later life that influence the extent to which individual genes in our hereditary makeup actually manifest themselves. Thus, while the basis of weight loss remains a combination of increased energy expenditure (i.e. exercise) and decreased energy intake (i.e. diet), natural substances that influence epigenetic mechanisms can also help significantly. Quercetin is one of the most effective ones. Quercetin affects the activity of DNMT1 and HDAC1 enzymes and histone acetylation, thereby preventing the proliferation of fat cells, reducing their variability and affecting their apoptosis (i.e. programmed cell death) (12-16).

However, Quercetin has other interesting effects in the field of weight loss. It can reduce the absorption of fatty acids, cholesterol and glucose from the digestive tract, so that we end up taking in slightly less energy than the food actually contains (23, 24). Its anti-inflammatory action is also important. Obesity is always accompanied by a mild, but nonetheless body-wide inflammation, which firstly increases the risk of a number of diseases and secondly complicates weight loss efforts. Quercetin effectively reduces inflammation directly in the fat cells (42).

Diabetes

Type II diabetes is manifested by so-called insulin resistance – unlike type I diabetes, the problem is not that the pancreas produces insufficient insulin, but that the tissues lose their sensitivity to this hormone. Quercetin is one of the substances that reduce insulin resistance. The reason for this is probably the fact that it can suppress the function of glucose transport substances from the small intestine.(24, 25) In addition, it also regulates the enzyme AMPK, which ensures glucose transport in skeletal muscle. In fact, our muscles normally consume up to 80% of the glucose ingested from food, and this function is impaired in diabetics.(26, 27) An important role may also be played by the positive effect of quercetin on mitochondria, as type 2 diabetes is characterised by impaired function of these organelles.(51)

Quercetin may also help prevent some complications of diabetes, such as diabetic neuropathy (55).

Sports performance

Quercetin is also among the substances that athletes should focus their attention on. For example, it can affect endurance – when a group of athletes took 500 mg of the substance daily, they experienced a 4% increase in VO2max (maximal oxygen consumption, a key indicator of endurance) and a 13% improvement in their performance in a cycle to exhaustion test. This is probably due to an increase in the number of mitochondria in the muscles (29).

As mentioned above, mitochondria are the cellular organelles that convert nutrients into energy. They play a very important role in endurance sports, where the athlete’s performance depends, among other things, on the ability of muscle cells to obtain as much energy as possible for their work in a certain period of time. Therefore, the increase in the number of mitochondria in muscles is also one of the manifestations of adaptation to training load. Research shows that taking quercetin in conjunction with training leads to both a higher increase in the number of mitochondria and a higher production of enzymes inside these organelles. The key here is that both quercetin and endurance training increase the activity of the genes that make one of the sirtuins in the body, SIRT-1, as well as the protein PGC-1α. Both of these substances have a positive effect on both mitochondrial formation and mitochondrial enzymes. It is also interesting to note that the influence of training and quercetin results in the proliferation of mitochondria not only in muscle but also in brain tissue. This translates firstly into better tolerance of physical stress in terms of better tolerance of pain and other unpleasant bodily sensations during the race, but also into better mental performance (48-50).

In addition, experiments on mice have shown that quercetin can probably speed up the above processes significantly. Changes in the concentration of mitochondrial enzymes were demonstrated in experimental animals after only 2-7 days of training! (50) This makes quercetin a substance that can be very useful for people who are new to regular exercise and want to speed up their fitness improvement.

It is probably no coincidence that one of the sirtuins, the enzymes we mentioned in the context of ageing, plays a key role in these processes. After all, regular exercise has a very important place in the fight against ageing (and also against declining brain performance), and quercetin could help significantly.

In terms of promoting athletic performance, quercetin has been shown to be more effective in combination with other substances than alone (66). Possible combinations can be found at the end of the text.

Prostate problems

The use of quercetin can also be quite effective for prostate problems such as prostate enlargement, inflammation or chronic pelvic pain. In one study, for example, 67% of patients tested experienced a significant improvement in symptoms (30).

Rheumatoid arthritis

The strong anti-inflammatory action makes quercetin a useful remedy for rheumatoid arthritis. In a study in which 50 women suffering from this disease took 500 mg of quercetin daily for 8 weeks, they experienced a significant reduction in morning stiffness and joint soreness, as well as pain relief after exertion (44).

Allergies

So far, only promising studies have been conducted in animals, pointing to the possible use of quercetin in allergies. They have shown that it is able to suppress the production of histamine, inflammatory cytokines and reduce the production of specific IgE antibodies. In experimental mice, it was even able to alleviate the anaphylactic reaction to peanuts. (44, 45)

Alzheimer’s disease

Similarly, the possible role of quercetin in the prevention and treatment of Alzheimer’s disease has so far only been investigated in animals. However, the results are very promising – in experimental mice that had previously been induced to show symptoms of the disease, there was both a significant reduction in symptoms and an improvement in learning ability (48).

The likelihood that this will work in humans is increased by the aforementioned fact that quercetin promotes mitochondrial proliferation and function. The dysfunction of these organelles is typical of Alzheimer’s disease – nerve cells suffer from a chronic lack of energy, which contributes to their degeneration.

Endometriosis

Endometriosis is one of the most common gynaecological diseases, affecting 15-20% of women of childbearing age. It is an inflammatory disease in which the uterine lining (endometrium) grows and spreads outside the uterus, into the abdominal cavity. This causes not only severe pain, but often problems getting pregnant.

Experiments in mice have shown that quercetin can effectively inhibit endometrial growth. We are still waiting for research to see if the same works in humans. (54)

Use of

For therapeutic purposes, a dose of 500-1000 mg per day is usually used, the treatment should last at least three weeks, but should not exceed one month, as long-term use is not advisable (the treatment can be repeated about 3 times a year). The use of significantly higher doses is also not recommended, as it can lead to, for example, nausea or kidney damage. Quercetin can also impair the effectiveness of antibiotics and limit the absorption of some drugs.

Possible combinations with other dietary supplements

Very effective are also combinations of quercetin with other natural substances, with which they mutually support their effect. Here are some of them.

To slow aging: quercetin + resveratrol (37), quercetin + EGCG (56)

Cancer prevention and treatment: quercetin + curcumin (63), quercetin + EGCG (58)

Immunity: quercetin + EGCG (56), quercetin + curcumin (60)

Prevention and treatment of Alzheimer’s and Parkinson’s disease: quercetin + omega-3 (65)

Weight loss support: quercetin + curcumin (62), quercetin + EGCG (57), quercetin + OPC, quercetin + resveratrol (62)

Sports performance: quercetin + vitamin D3 (53), quercetin + curcumin, quercetin + OPC (70), quercetin + omega-3 (66), quercetin + EGCG (66)

Diabetes: quercetin + curcumin (64)

Heart and blood vessels: quercetin + OPC (69), quercetin + resveratrol (37), quercetin + EGCG (59)

Testosterone production: quercetin + vitamin D3 (53), quercetin + pomegranate

Allergies: quercetin + coneflower, quercetin + rosemary

Anti-inflammatory and antioxidant action: quercetin + EGCG (57), quercetin + curcumin (60), quercetin + pomegranate (67), quercetin + rosemary (68)

In addition, when combined with curcumin and resveratrol, quercetin improves the absorption of these substances from the intestinal tract (61).