Quercetin: the multitasking flavonol

Quercefit from Indena has been designed and developed to translate the natural power of a great botanical into a successful supplement ingredient for human health

Quercetin is categorised as a flavonol, one of the six subclasses of flavonoids. This important class of natural products belongs to a class of plant secondary metabolites with a polyphenolic structure. Flavonoids are a natural treasure trove for human well-being, mainly because of their antioxidant activity and their ability to reduce free radical formation and scavenge free radicals.1

In Western populations, estimated daily intakes of flavonols range from 20–50 mg/day. Of this, about 13.82 mg/day is in the form of quercetin-type flavonols.2

Widely distributed in the plant kingdom, quercetin-type flavonols (mostly quercetin glycosides) are found in abundance in a variety of foods, including apples, berries, Brassica vegetables, capers, grapes, onions, shallots, tea and tomatoes, as well as many seeds, nuts, flowers and leaves.

Quercetin’s multiple biological activities

Quercetin is supported by an extensive scientific literature that demonstrates its multiple biological activities: it has antioxidant, antiageing, antiaggregation and vasodilation properties.3–5

Scientific studies have highlighted its potential use to maintain well-being in situations of fatigue or stress.6,7 As for the antioxidant effect, quercetin acts by directly inactivating free radicals, inhibiting lipid peroxidation (oxidants such as free radicals attack lipids contained in cellular membranes, lipoproteins, etc.) and blocking the oxidative stress cascade from the beginning; it also acts as an inhibitor of enzymes such as NO-synthase.

Moreover, quercetin reduces the activation and synthesis of crucial players in the inflammatory process, such as NF-kB transcription factor, enzymes including cyclo-oxygenase (COX) and lipoxygenase (LOX), which catalyse the conversion of arachidonic acid to its metabolites, proinflammatory cytokines (TNF-α) and interleukins, all of which are mediators of immunity and inflammation.

Quercetin is also able to act as a modulator of immune cells, such as lymphocytes, and is involved in the release of interferon-γ (IFN-γ), eosinophil activity (by inhibiting eosinophil peroxidase), the stabilisation of cell membranes, managing the release of histamine from mast cells — a cause of sneezing, itchy eyes, scratchy throat and itchy skin — and the inhibition of antibody IgE, which is responsible for allergic symptoms and causes the release of chemicals that determine allergic reactions in the nose, lung, throat and skin.

There is a lot of supporting evidence to promote the use of quercetin for respiratory health. Additionally, quercetin has shown in vitro activity against multiple viral targets and, very recently, was identified as a promising ingredient against COVID-19.8

Quercefit: readily bioavailable

Like many botanical extracts and natural compounds, quercetin is potentially very effective and, at the same time, poorly water soluble. As a consequence, it is barely bioabsorbable, which decreases its potential effectiveness.

For optimal bioabsorption, natural products must demonstrate a good balance between hydrophilicity to dissolve in gastrointestinal fluids and lipophilicity to cross the cell’s lipid biomembrane.

To address these challenges, Indena has long adopted a “biomimetic approach.” Biomimetics involves studying the science of nature and natural phenomena to understand their underlying mechanisms, to examine the formation, structure or function of biologically produced substances and materials, imitate them and apply those processes and concepts to solve human problems in engineering and medicine, for example.

The concept can be explained as “innovation inspired by nature.” Indena’s “Nature as Measure” represents the very notion of biomimetics in literature and its philosophical origins. The search for a biomimetic approach to optimise the absorption of natural active compounds and retain their inherent profile has been pioneered by Indena and the development of the Phytosome delivery system.

Phytosome, the 100% food-grade biomimetic delivery system, is the result of in-depth knowledge and a long history of product and process research. The system is able to retain the original properties of natural products without involving new chemical derivatives or entities, pharmacological adjuvants or structural modifications.

In a continuous process of evolution and innovation, every Phytosome is specifically designed to optimise the bioabsorption of a selected botanical.

Derived from the flower buds of Sophora japonica L., Indena’s unique Phytosome formulation of quercetin, Quercefit (standardised to 36.0–42.0% quercetin), is the most bioavailable form on the market.

According to a published human pharmacokinetic study comparing the Indena formulation with unformulated quercetin, it proved to be up to 20-fold more bioavailable, comparable with levels of a diet rich in vegetables and fruit, and able to be used at lower dosages, preserving its natural ingredient profile.9

Twelve healthy volunteers of both sexes, aged 18–50, were administered orally with a dose of quercetin (500 mg) and two different doses of Quercefit (250 and 500 mg). Pharmacokinetic samples were collected at 12 time intervals (0–24 h) after administration; plasma quercetin levels were measured by HPLC/MS/MS.

Quercefit demonstrated a significant improvement in oral absorption and raised quercetin plasma levels to those in line with a diet rich in vegetables and fruit (such as onions and apples).

Sports, allergies and respiratory health

Until now, the health benefits of Quercefit have only been explored in sport and, very recently, in respiratory applications. A controlled human study on amateur healthy triathletes (750 m swim, 20 km cycle, 5 km run) showed the effectiveness of 250 mg (twice a day) of Quercefit.10

Athletes supplemented with Quercefit maintained a higher level of physical resistance (p<0.05), measured as time to complete the race, better performance and optimised recovery (less muscle discomfort and post-event cramp).

Oxidative stress levels were also statistically lower (p<0.05) compared with the control group and no undesirable side-effects were observed, showing excellent tolerability to repeated supplementation. This study suggests that oral supplementation with Quercefit can optimise sports performance and physical recovery.

Moreover, the enhanced bioavailability of quercetin formulated with Indena’s Phytosome delivery system has recently allowed Quercefit to achieve very interesting results in the maintenance of well-being for sensitive or intolerant subjects.11,12

After 30 days of supplementation, using either one or two tablets/day of Quercefit, the subjects’ well-being and seasonal discomfort were evaluated according to the GINA (Global Initiative for Asthma) classification system. Quercefit was shown to maintain normal parameters related to diurnal and nocturnal respiration with particular regard to breath function (Peak Expiratory Flow).

The supplementary use of Quercefit, along with the use of the best available remedy — while optimising general comfort management and minimising oxidative stress — resulted in a very good safety profile.11

In a second human study focusing on local skin irritations, Quercefit was administrated for just 3 days, followed by a local histamine skin stimulus. Compared with the control group, only the healthy volunteers supplemented with Quercefit showed a statistically significant dose-dependent regulation of the local skin conditions as well as a reduction in capillary filtration (data not shown).

Excellent safety profile

A preliminary human study was conducted with Quercefit to investigate any interactions with standard synthetic drugs and control any possible harmful effects.

The results suggest that Quercefit might not alter the activity of the most common antiplatelet agents (acetylsalicylic acid, ticlopidine or clopidogrel after 10 days of supplementation), has no impact in stable patients treated with warfarin or dabigatran after 20 days of supplementation and might not influence the metabolic control of diabetic patients taking metformin.12

References

  1. A.N. Panche, et al., “Flavonoids: An Overview,” Journal of Nutritional Science 5: e47, 2016: www.ncbi.nlm.nih.gov/ pmc/articles/PMC5465813.
  2. J. Cao, et al., “The Relationship Between Fasting Plasma Concentrations of Selected Flavonoids and Their Ordinary Dietary Intake,” Br. J. Nutr. 103, 249–255 (2010).
  3. N. Chondrogianni et al., “Antiageing and Rejuvenating Effects of Quercetin,” Exp. Gerontol. 45(10), 763–771 (2010).
  4. M. Chopra, et al., “Nonalcoholic Red Wine Extract and Quercetin Inhibit LDL Oxidation without Affecting Plasma Antioxidant Vitamin and Carotenoid Concentrations,” Clin. Chem. 46(8), 1162–70 (2000).
  5. I. Erlund, et al., “Pharmacokinetics of Quercetin from Quercetin Aglycone and Rutin in Healthy Volunteers,” Eur. J. Clin. Pharmacol. 56(8), 545–553 (2000).
  6. W. Wang, et al., “The Biological Activities, Chemical Stability, Metabolism and Delivery Systems of Quercetin: A Review,” Trends Food Sci. Technol. 56, 21–38 (2016).
  7. G. D’Andrea, “Quercetin: A Flavonol with Multifaceted Therapeutic Applications?” Fitoterapia 106, 256–271 (2015).
  8. S. Khaerunnisa, et al., “Potential Inhibitor of COVID-19 Main Protease (Mpro) from Several Medicinal Plant Compounds by Molecular Docking Study,” (2020): www.preprints.org/manuscript/202003.0226/v1.
  9. A. Riva, et al., “Improved Oral Absorption of Quercetin from Quercetin Phytosome, a New Delivery System Based on Food Grade Lecithin,” Eur. J. Drug Metab. Pharmacokinet. (2018): doi: 10.1007/s13318-018-0517-3.
  10. A. Riva, et al., “Quercetin Phytosome in Triathlon Athletes: A Pilot Registry Study,” Minerva Medica 109(4), 285–289 (2018).
  11. M.R. Cesarone, et al., “Supplementary Prevention and Management of Asthma with Quercetin Phytosome: A Pilot Registry,” Minerva Medica 110(6), 524–529 (2019).
  12. A. Riva, et al., “Interaction Study Between Antiplatelet Agents, Anticoagulants, Diabetic Therapy and a Novel Delivery Form of Quercetin,” Minerva Cardioangiol. 67(1), 79–83 (2019).

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