Quercetin

Quercetin is a yellow plant pigment. Its name is derived from the Latin word for oak forest—quercetum—because it was originally identified in oaks. Quercetin is a flavonol, which is one of the polyphenol categories. Polyphenols play important roles in the plant kingdom. One of these roles is protecting plants from environmental stress such as pests and UV irradiation from the sun. Because of this role, they tend to concentrate in parts of the plant that come into more contact with the outside world. Red onions are one of the better food sources of quercetin. But the quercetin isn’t uniformly spread through red onions; it concentrates in the outer skins (which are usually thrown away when onions are peeled before use) and the part closest to the root. Capers may be the best dietary source of quercetin.*


TOP BENEFITS OF QUERCETIN

Supports brain function*

Supports antioxidant defenses*

Supports cellular health*


NEUROHACKER’S QUERCETIN SOURCING

Quercetin is supplemented as quercetin dihydrate because this is a stable form of the ingredient suitable.

Quercetin is sourced from the bud of Sophora japonica.

Quercetin is Non-GMO and Vegan.


QUERCETIN FORMULATING PRINCIPLES AND RATIONALE

The amount of quercetin used in a formula will vary significantly depending on its role in that particular formula. Many flavonoid molecules are part of plants’ protective responses to mild environmental stress. Because of this, we don’t think of flavonols like quercetin as being “more is better” ingredients. Instead, we think it’s better to use them following hormetic dosing principles (see Qualia Dosing Principles). Quercetin is an interesting ingredient when it comes to formulating, because the oral amount commonly used in animal research is high (the same is true in many human studies), but healthspan has been extended in mice by a dose 80- to 400 times lower [1]. Despite the common practice of using high amounts of quercetin in dietary supplements, for long-term use, very low amounts may possibly be a better choice. There are several factors we consider for determining the amount of quercetin in a formula. Since we consider it hormetic, we might use low amounts in a formulation intended to be taken most days, but much higher amounts for a formulation which would only be taken intermittently for a few days at a time. We also consider timing. We are more comfortable with higher amounts of quercetin early in the day but lower amounts in the evening, because the impact of taking high amounts of quercetin at night on sleep in humans has not been studied. With quercetin, like all of our ingredients, we also consider its role in a formula. Quercetin has influenced the function of many enzymes and processes in preclinical research. It’s also been the focus of human studies. If its role in a formula is to solely support enzymes/processes, our serving will be low. If the role is based on a structure or function benefit from a human study, our serving is likely to be higher. The last thing we consider is what else is in the formula. It’s useful to think of polyphenols like quercetin as being somewhat akin to recommendations to eat a variety of fruits and vegetables. It's prudent to consume a variety of polyphenol compounds (rather than just one in very high amounts) because they tend to have complementary interactions, often supporting the absorption and use of other polyphenols. So, one of the factors we consider when determining the serving of quercetin is the amount of other polyphenols it will be combined within a formula.*


QUERCETIN KEY MECHANISMS

Supports brain function*

Supports learning and memory (in animals)* [2–9]

Supports motor activity* [5,7,10]

Supports healthy behavioral and physiological responses to stress* [5,8,11–19]

Supports brain-derived neurotrophic factor (BDNF) levels* [4,9,12,18,20–22]

Supports serotonin signaling* [7]

Supports dopamine signaling* [7]

Supports noradrenaline signaling* [7]

Influences MAO-A activity* [7,23,24]

Influences acetylcholinesterase (AChE) activity* [8,25,26]

Influences adenosine deaminase (ADA) activity* [26,27]

Supports ectonucleotidase activity* [26–29]

Supports brain insulin signaling* [16]

Supports long-term potentiation (LTP)* [30]

Supports neural stem/progenitor cell proliferation and neurogenesis (in animals)* [9]

Supports neuroprotective functions* [10,19,25,26,30–34]

Supports free radical scavenging and antioxidant defenses* [4,5,8,14,25,26,32]

Supports Nrf2 signaling and phase II detox enzymes* [6,33]

Supports brain mitochondrial function* [3,33]

Supports neural AMPK signaling* [3,31,33]

Supports hippocampal SIRT1 levels* [7]


Supports a healthy gut microbiota*

Supports the composition of the gut microbiota* [21,35–40]

Supports gut microbial metabolism* [36]

Supports gut-immune communication* [35,37]


Promotes musculoskeletal health*

Supports joint health* [41]

Supports muscle recovery and contraction* [42,43]


Supports cellular signaling*

Influences PI3K/AKT signaling* [44–46]

Influences mTOR signaling* [47,48]

Influences AMPK signaling* [49,50]

Influences SIRT1 signaling* [50–53]

Influences NF-κB signaling* [54]

Influences HIF-1α signaling* [45–47,49,55]


Promotes healthy aging and longevity*

Supports stem cell proliferation and differentiation* [9,56–58]

Supports the management of senescent cells* [52,56,59]

Supports cellular functions involved with pruning stressed cells* [44,54,60–65]

Supports autophagy* [47,48,51,66–69]

Supports mitophagy* [52,53,70,71]

Supports adaptive immunity* [72]

Supports immune system communication* [41]


Complementary ingredients*

With palmitoylethanolamide for joint health* [73]

With glucosamine and chondroitin for joint health* [74]

With Mangifera indica leaf extract for ergogenic support* [75]


*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.


REFERENCES

[1] L. Geng, Z. Liu, S. Wang, S. Sun, S. Ma, X. Liu, P. Chan, L. Sun, M. Song, W. Zhang, G.-H. Liu, J. Qu, Protein Cell 10 (2019) 770–775.

[2] A. Priprem, J. Watanatorn, S. Sutthiparinyanont, W. Phachonpai, S. Muchimapura, Nanomedicine 4 (2008) 70–78.

[3] D.-M. Wang, S.-Q. Li, W.-L. Wu, X.-Y. Zhu, Y. Wang, H.-Y. Yuan, Neurochem. Res. 39 (2014) 1533–1543.

[4] S.-F. Xia, Z.-X. Xie, Y. Qiao, L.-R. Li, X.-R. Cheng, X. Tang, Y.-H. Shi, G.-W. Le, Physiol. Behav. 138 (2015) 325–331.

[5] V. Mehta, A. Parashar, M. Udayabanu, Physiol. Behav. 171 (2017) 69–78.

[6] F. Dong, S. Wang, Y. Wang, X. Yang, J. Jiang, D. Wu, X. Qu, H. Fan, R. Yao, Biochem. Biophys. Res. Commun. 491 (2017) 636–641.

[7] F. Sarubbo, M.R. Ramis, C. Kienzer, S. Aparicio, S. Esteban, A. Miralles, D. Moranta, J. Neuroimmune Pharmacol. 13 (2018) 24–38.

[8] N. Samad, A. Saleem, F. Yasmin, M.A. Shehzad, Physiol. Res. 67 (2018) 795–808.

[9] M. Karimipour, R. Rahbarghazi, H. Tayefi, M. Shimia, M. Ghanadian, J. Mahmoudi, H.S. Bagheri, Int. J. Dev. Neurosci. 74 (2019) 18–26.

[10] J. Chakraborty, R. Singh, D. Dutta, A. Naskar, U. Rajamma, K.P. Mohanakumar, CNS Neurosci. Ther. 20 (2014) 10–19.

[11] D. Kambe, M. Kotani, M. Yoshimoto, S. Kaku, S. Chaki, K. Honda, Brain Res. 1330 (2010) 83–88.

[12] Y. Hou, M.A. Aboukhatwa, D.-L. Lei, K. Manaye, I. Khan, Y. Luo, Neuropharmacology 58 (2010) 911–920.

[13] M. Rahvar, A.A. Owji, F.J. Mashayekhi, Bratisl. Lek. Listy 119 (2018) 28–31.

[14] M. Lv, S. Yang, L. Cai, L.-Q. Qin, B.-Y. Li, Z. Wan, Mol. Nutr. Food Res. 62 (2018) e1800621.

[15] K. Selvakumar, S. Bavithra, G. Krishnamoorthy, J. Arunakaran, Interdiscip. Toxicol. 11 (2018) 294–305.

[16] F. Ke, H.-R. Li, X.-X. Chen, X.-R. Gao, L.-L. Huang, A.-Q. Du, C. Jiang, H. Li, J.-F. Ge, Front. Pharmacol. 10 (2019) 1544.

[17] S. Yoshino, A. Hara, H. Sakakibara, K. Kawabata, A. Tokumura, A. Ishisaka, Y. Kawai, J. Terao, Nutrition 27 (2011) 847–852.

[18] L. Saaby, H.B. Rasmussen, A.K. Jäger, J. Ethnopharmacol. 121 (2009) 178–181.

[19] L.A. Pattanashetti, A.D. Taranalli, V. Parvatrao, R.H. Malabade, D. Kumar, Indian J. Pharmacol. 49 (2017) 60–64.

[20] R.M. Maciel, F.B. Carvalho, A.A. Olabiyi, R. Schmatz, J.M. Gutierres, N. Stefanello, D. Zanini, M.M. Rosa, C.M. Andrade, M.A. Rubin, M.R. Schetinger, V.M. Morsch, C.C. Danesi, S.T.A. Lopes, Biomed. Pharmacother. 84 (2016) 559–568.

[21] V. Mehta, A. Parashar, A. Sharma, T.R. Singh, M. Udayabanu, Horm. Behav. 89 (2017) 13–22.

[22] Y. Yao, D.D. Han, T. Zhang, Z. Yang, Phytother. Res. 24 (2010) 136–140.

[23] E. Braganhol, A.S.K. Tamajusuku, A. Bernardi, M.R. Wink, A.M.O. Battastini, Biochim. Biophys. Acta 1770 (2007) 1352–1359.

[24] F.H. Abdalla, A.M. Cardoso, L.B. Pereira, R. Schmatz, J.F. Gonçalves, N. Stefanello, A.M. Fiorenza, J.M. Gutierres, J.D. da S. Serres, D. Zanini, V.C. Pimentel, J.M. Vieira, M.R.C. Schetinger, V.M. Morsch, C.M. Mazzanti, Mol. Cell. Biochem. 381 (2013) 1–8.

[25] J. Baldissarelli, A. Santi, R. Schmatz, F.H. Abdalla, A.M. Cardoso, C.C. Martins, G.R.M. Dias, N.S. Calgaroto, L.P. Pelinson, K.P. Reichert, V.L. Loro, V.M.M. Morsch, M.R.C. Schetinger, Cell. Mol. Neurobiol. 37 (2017) 53–63.

[26] J. Lu, D.-M. Wu, Y.-L. Zheng, B. Hu, Z.-F. Zhang, Q. Shan, Z.-H. Zheng, C.-M. Liu, Y.-J. Wang, J. Pathol. 222 (2010) 199–212.

[27] F.H. Abdalla, R. Schmatz, A.M. Cardoso, F.B. Carvalho, J. Baldissarelli, J.S. de Oliveira, M.M. Rosa, M.A. Gonçalves Nunes, M.A. Rubin, I.B.M. da Cruz, F. Barbisan, V.L. Dressler, L.B. Pereira, M.R.C. Schetinger, V.M. Morsch, J.F. Gonçalves, C.M. Mazzanti, Physiol. Behav. 135 (2014) 152–167.

[28] D. Wang, J. Zhao, S. Li, G. Shen, S. Hu, Nutr. Neurosci. 21 (2018) 123–131.

[29] P.-C. Paula, S.-G. Angelica Maria, C.-H. Luis, C.-G. Gloria Patricia, Molecules 24 (2019).

[30] M. Kosari-Nasab, G. Shokouhi, A. Ghorbanihaghjo, M. Mesgari-Abbasi, A.-A. Salari, Behav. Pharmacol. 30 (2019) 282–289.

[31] S. Merzoug, M.L. Toumi, A. Tahraoui, Naunyn. Schmiedebergs. Arch. Pharmacol. 387 (2014) 921–933.

[32] J.M. Davis, E.A. Murphy, J.L. McClellan, M.D. Carmichael, J.D. Gangemi, Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (2008) R505–9.

[33] K. Kawabata, Y. Kawai, J. Terao, J. Nutr. Biochem. 21 (2010) 374–380.

[34] V. Kumar, PPIJ 2 (2015).

[35] P. Anggreini, C. Ardianto, M. Rahmadi, J. Khotib, J. Basic Clin. Physiol. Pharmacol. 30 (2019).

[36] R. Lin, M. Piao, Y. Song, Front. Microbiol. 10 (2019) 1092.

[37] D.-N. Wu, L. Guan, Y.-X. Jiang, S.-H. Ma, Y.-N. Sun, H.-T. Lei, W.-F. Yang, Q.-F. Wang, Cardiovasc Diagn Ther 9 (2019) 545–560.

[38] D. Porras, E. Nistal, S. Martínez-Flórez, S. Pisonero-Vaquero, J.L. Olcoz, R. Jover, J. González-Gallego, M.V. García-Mediavilla, S. Sánchez-Campos, Free Radic. Biol. Med. 102 (2017) 188–202.

[39] J. Nie, L. Zhang, G. Zhao, X. Du, J. Appl. Microbiol. 127 (2019) 1824–1834.

[40] U. Etxeberria, N. Arias, N. Boqué, M.T. Macarulla, M.P. Portillo, J.A. Martínez, F.I. Milagro, J. Nutr. Biochem. 26 (2015) 651–660.

[41] J. Firrman, L. Liu, L. Zhang, G. Arango Argoty, M. Wang, P. Tomasula, M. Kobori, S. Pontious, W. Xiao, Anaerobe 42 (2016) 130–141.

[42] L. Geng, Z. Liu, W. Zhang, W. Li, Z. Wu, W. Wang, R. Ren, Y. Su, P. Wang, L. Sun, Z. Ju, P. Chan, M. Song, J. Qu, G.-H. Liu, Protein Cell 10 (2019) 417–435.

[43] Z. Yuan, J. Min, Y. Zhao, Q. Cheng, K. Wang, S. Lin, J. Luo, H. Liu, Am. J. Transl. Res. 10 (2018) 4313–4321.

[44] X.-G. Pang, Y. Cong, N.-R. Bao, Y.-G. Li, J.-N. Zhao, Biomed Res. Int. 2018 (2018) 4178021.

[45] A. Casado-Díaz, J. Anter, G. Dorado, J.M. Quesada-Gómez, J. Nutr. Biochem. 32 (2016) 151–162.

[46] S.R. Kim, K. Jiang, M. Ogrodnik, X. Chen, X.-Y. Zhu, H. Lohmeier, L. Ahmed, H. Tang, T. Tchkonia, L.J. Hickson, J.L. Kirkland, L.O. Lerman, Transl. Res. 213 (2019) 112–123.

[47] J. Mlcek, T. Jurikova, S. Skrovankova, J. Sochor, Molecules 21 (2016).

[48] F. Javadi, A. Ahmadzadeh, S. Eghtesadi, N. Aryaeian, M. Zabihiyeganeh, A.R. Foroushani, S. Jazayeri, Journal of the American College of Nutrition 36 (2017) 9–15.

[49] I. Bazzucchi, F. Patrizio, R. Ceci, G. Duranti, P. Sgrò, S. Sabatini, L. Di Luigi, M. Sacchetti, F. Felici, Nutrients 11 (2019).

[50] D. Britti, R. Crupi, D. Impellizzeri, E. Gugliandolo, R. Fusco, C. Schievano, V.M. Morittu, M. Evangelista, R. Di Paola, S. Cuzzocrea, BMC Veterinary Research 13 (2017).

[51] N. Kanzaki, K. Saito, A. Maeda, Y. Kitagawa, Y. Kiso, K. Watanabe, A. Tomonaga, I. Nagaoka, H. Yamaguchi, Journal of the Science of Food and Agriculture 92 (2012) 862–869.

[52] M. Gelabert-Rebato, J.C. Wiebe, M. Martin-Rincon, N. Gericke, M. Perez-Valera, D. Curtelin, V. Galvan-Alvarez, L. Lopez-Rios, D. Morales-Alamo, J.A.L. Calbet, Front. Physiol. 9 (2018) 740.