What is Quercetin?

Quercetin: How does it work? And why is it good for you?

Quercetin is one of the most well-known antioxidants found in our diets. It has numerous health benefits including protection against age-related diseases, allergies, virus and bacterial infection and cardiovascular disease. Various studies have been done to research these benefits and to find how they work and what their optimal form is, to work.  

What is Quercetin?

Flavonoids are found in plants and are one of four groups of polyphenols. They protect plants from ultraviolet sun rays and harmful organisms (pathogens). They make up plant pigmentation and are communication molecules for growth and ripening of fruit and vegetables.  

Quercetin is found in fruits, vegetables, grains, seeds, tea, and wine.  Onions, leeks, and broccoli are amongst the consumable plants that contain the highest amount of this flavonoid (its subclass is called flavanol). Quercetin’s use has been of interest due to its various amazing health benefits with studies suggesting that some of its advantages include allergy prevention, improved immunity, and support for exercise performance. Further benefits will be mentioned throughout the article. In food, quercetin is found in different forms and has different uptake in the gut, termed bioavailability.  The consumption of any product varies, and their advantages are dose-dependent, with varying bioavailability. Bioavailability refers to the amount of product that will be absorbed and made available for the body’s use, compared to how much is consumed.

The interest in quercetin as an anti-inflammatory has arisen in addition to it playing a part in cardiovascular protection, and a key element in the ‘Mediterranean diet’. The ‘Mediterranean diet’ is associated with a decrease in cardiovascular disease when compared to other diets.

Figure 1: The chemical structure of Quercetin

Quercetin’s scientific name is: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one and has 5 hydroxyl groups (oxygen-hydrogen groups), which are modified in the derivatives of quercetin. These derivatives give the molecules varying functions. It is also used as a dietary food supplement as bioactive quercetin, while quercetin itself, has the highest antioxidant properties. In plants it is needed for seed germination, and growth of pollen and due to its antioxidant nature, it helps plants tolerate different stress conditions. 

Antioxidants and oxygen reactive species

Quercetin is an antioxidant. Antioxidants are found in the body to help remove oxidants. This sounds obvious, but what are oxidants? Oxidants are molecules that react with other molecules in the body, including proteins, cell membranes, lipids, lipoproteins, and DNA causing damage. The damage leads to inflammation, disease, and aging. Oxidants are naturally produced in the body, but they can also be introduced into the body by the environment we are exposed to and the foods that we eat. Damage caused by oxidation is called oxidative stress, where more oxygen-reactive species are being produced or are present than the amount being cleared by the cells. So why are these oxygen reactive species present in the body in the first place? This is a good question. They are needed for different physiological roles, including cell signalling, which is how cells ‘communicate’ with one another. They are also produced as a by-product of oxygen metabolism, which happens regularly in cells. Their production is increased in the presence of environmental stressors such as pollutants, UV rays, and heavy metals. Some antioxidants including quercetin, vitamin E, and other polyphenols, have been found to be beneficial against oxidative stress. 

What are senescent cells? 

The process of aging, what and how organisms age, has been of interest to humans for many years. Looking back as far as 1881, an essay written by the German evolutionary biologist August Weismann called ‘The Duration of Life’ described a theory of why we age, which was considered to be radical for his time. It said, “Death takes place because a worn-out tissue cannot forever renew itself, and because a capacity for increase by means of cell division is not ever-lasting but finite.” The idea that aging was due to an inherent limit of cell division was not studied further, until 80 years later in 1961 when Leonard Hayflick, who is a professor of anatomy at UCSF School of Medicine, showed that Weismann’s theory was true. Mammalian cells can’t divide infinitely. This concept is now known as the ‘Hayflick Limit’.

The biologists Weismann and Hayflick claimed that tissue ages because of the non-dividing cells within tissue that are now called senescent cells, losing their ability to repair. These cells are additionally harmful because they disrupt the functioning of normal cells by making them cause inflammation, induce cell death, and disrupt stem cell function. Stem cells are cells which do not have a function yet. They have the potential to become any cell in the body. Studies have shown that by removing the senescent cells, an organism has a longer time in which it lives without diseases of aging, including cancers, atherosclerosis, and osteoarthritis. The elimination of these cells is called senolysis. Mice models have been used to show this. Mice that had been treated to remove these cells showed an increase in their lifespan, and improved conditions of atherosclerosis, osteoarthritis, tumorigenesis, cardiac hypertrophy, renal problems, cataracts, sarcopenia, and lipodystrophy. 

Quercetin as an antiviral and improved immunity.

In addition to previously mentioned properties quercetin has also been studied in relation to its antiviral properties. It reacts by donating two electrons to free radicals, in vitro and in vivo - this means that the reaction can occur both outside of an organism, for example in cells in a petri dish, and within the organism. Quercetin’s antioxidant properties are increased in the presence of vitamin C.  Evidence suggests that the presence of quercetin inhibits various respiratory diseases when tested on cells. The viruses included rhinovirus, echovirus, and poliovirus, amongst others. While mice that had been infected with meningoencephalitis virus, their symptoms did not persist when they were treated with the quercetin for 4 days. The antioxidant/ vitamin C is antiviral because it disrupts the entry of the virus into the cell, which means that the virus cannot replicate. It disrupts the enzyme activity and assembly of the virus. Moreover, it is an effective antivirus because it strengthens the immune system. 

The immune system response can be divided into two, the innate immune response, and the adaptive immune response. The innate immune response is the first to be triggered in the presence of a foreign organism in the body, which then signals the adaptive immune response. The latter is responsible for long term protection against infection, should you be reinfected with the same foreign body.

Vitamin C which is ascorbic acid, is water soluble and a natural antioxidant. It has antiviral properties as well and supports lymphatic activity and cellular function. Vitamin C reacts with the oxygen reactive species changing it to a less reactive chemical species, reducing the risks of oxidative stress. 

Research shows that when administered together, vitamin C and quercetin provide synergistic antiviral effects. In brief, this is due to the antiviral and by promoting the activation of the immune system (immunomodulatory). These properties are especially of interest due to the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) i.e., COVID-19 pandemic.

Quercetin and vitamin C work by promoting the early immune response: the production of natural killer cells and natural killer T cells, followed by the promotion of T cell maturation: adaptive immune response. 

It is important that quercetin is administered with vitamin C due to the following reactions:

When No Vitamin C present: 

Quercetin → O-semiquinone and O-quinone/quinone methide (QQ) [→ can bind with some proteins forming toxic compounds]

When Vitamin C present: QQ is recycled

Quercetin ⇆ O-semiquinone and O-quinone/quinone methide (QQ)

It is important that the correct dosage of quercetin is consumed due to the above reactions. In excess, quercetin is converted to O-semiquinone and O-quinone/quinone methide which bind to proteins in the cells, forming other compounds which are toxic to the cell. Vitamin C helps in recycling the O-semiquinone and O-quinone/quinone methide and converting it back to quercetin.       

Figure 2: Free radical scavengers (slideshare.net)

Quercetin’s effect on blood glucose

For the body to function properly, it is important for the body to maintain homeostasis, which is keeping levels of products in the body constant for example water, waste, and glucose levels. In diabetes, which is considered a metabolic disease, glucose levels in the blood are increased due to the lack or reduced insulin levels. This leads to variations of protein, fats, and carbohydrate metabolisms. Furthermore, oxidative stress effects the glucose levels. 

Studies have shown that the administered anti-hyperglycemic drugs, successfully reduce levels of blood glucose but not the oxygen reactive species that cause oxidative stress. Studies have indicated that the addition of antioxidants like quercetin help in the reduction of this oxidative stress, helping to manage diabetes better by decreasing the damage done to liver cells through the oxidative stress. 

Quercetin’s effect on neurodegeneration, depression, and anxiety

With improvements in medicine and health care, the age expectancy of humans has increased, meaning that age-related diseases are on the rise. Neurodegeneration can be life threatening, and nutritional care can be used as a preventative measure of age-related health issues. Quercetin has shown properties that reduce the risks of neurodegenerative diseases. Such diseases include Alzheimer's disease, Parkinson’s disease, and Huntington's disease amongst others. These diseases show progressive deterioration of neuron structure, resulting in cognitive damage. The triggers include oxidative stress and mitochondrial dysfunction, both of which can be helped using quercetin. Mitochondria are the powerhouse of the cell. When oxygen reactive species are formed in the cell, ATP which is needed to power the cell, is depleted. In the brain this leads to a reduced ability for cells to reform. The presence of antioxidants improves cognitive function, protecting as well as enhancing cells to function and reform. Flavonoids also help memory and learning in the part of the brain called the hippocampus. They also help in the signaling processes in the brain. 

Another disorder related to brain health is depression, a common mental illness that may have effects. It is estimated that 5% of the world's adult population is affected by depression. Studies have also been performed on animal models to research the effects of flavonoids on depression and anxiety. The experiments were conducted on brains, using quercetin and other flavonoids showed antidepressant -like activity. The consumption of supplements varies, and their advantages are dose dependent, with varying bioavailability. Bioavailability refers to the amount of the product that will be absorbed, and made available for the body’s use, compared to how much is consumed. 

Conclusion

Quercetin being the most bioavailable supplement in the flavonoid group, is an important molecule in our diet. A diet rich in this flavonoid helps in maintaining a healthy lifestyle and reversing as well as protecting against various types of diseases and disorders. Its antioxidant and anti-inflammatory properties are what help allergies, viral infections, bacterial infections, neurodegeneration, and cardiovascular diseases. Studies have also shown that quercetin in the presence of vitamin C made the quercetin more effective. Try out NMN Bio’s Quercetin with Vitamin C and citrus Bioflavonoids that enhance absorption and boost your immune system and overall health, click HERE.

References

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