Citrus Bioflavonoids (from Citrus sinensis Fruit Extract)

Bioflavonoids were discovered in 1936 by Nobel-prize winning scientist Albert Szent-Gyorgi. He originally named the group of compounds "vitamin P," because his experiments revealed that they positively influenced the permeability of capillaries (i.e, strengthened blood vessels). Szent-Gyorgi was also a pioneer in early vitamin C research: He discovered that vitamin C alone was not always as effective as a crude bioflavonoid and vitamin C-containing extract from oranges, lemons, or paprika. This and other research is why citrus bioflavonoids are often combined with vitamin C—think of bioflavonoids as being a complement to vitamin C for supporting some of its functions.* Citrus bioflavonoids are found in citrus fruits (oranges, tangerines, grapefruit, etc.), where they concentrate in areas like the skin, white material, and pulp. Citrus × sinensis, which includes sweet oranges and blood oranges,  is the source for the citrus bioflavonoids. Citrus sinensis contains a variety of bioflavonoids, including hesperidin, diosmin, narirutin, naringin, nobiletin, rutin, and quercetin. 

TOP BENEFITS OF CITRUS BIOFLAVONOIDS

Supports brain function*

Supports healthy gut microbiota*  

Supports healthy metabolism*

NEUROHACKER’S CITRUS BIOFLAVONOIDS SOURCING

Citrus sinensis Fruit Extract is standardized to supply not less than 90% bioflavonoids, as a wide range of citrus bioflavonoids. The product is made from 100% whole citrus fruit from sweet orange.

This standardized extract is supplied by Brewster Nutrition, a leader in citrus bioflavonoids since 1950. 

Citrus sinensis Fruit Extract is a gluten-free, non-GMO, and vegan ingredient.

CITRUS BIOFLAVONOIDS FORMULATING PRINCIPLES AND RATIONALE

Citrus bioflavonoids have been used in a wide range of doses in human studies, depending on the intended use and whether they have been used alone or combined with other ingredients. Cognitive studies, as an example, where citrus flavonoids have been used alone, have used doses ranging from about 70 to 380 mg [1–3]. A single medium-sized orange has about 20 mg of flavanones (the most predominant type of citrus bioflavonoids) [4]. Since we are using citrus bioflavonoids to complement vitamin C, our 50 mg recommended serving was selected to provide approximately an amount that would be consumed by eating a couple of oranges.* 

CITRUS BIOFLAVONOIDS KEY MECHANISMS

Supports healthy brain function*

Supports neuroprotective functions* [5–11]

Supports cognitive function (in animals)* [12–15]

Supports neural immune signaling* [16,17]

Supports hippocampal mitochondrial bioenergetics* [18]

Supports BDNF signaling* [8,19]

Supports healthy stress hormone levels* [20–27]

Supports healthy gut microbiota*

Supports healthy gut microbiota composition* [28–31]

Supports healthy gut microbial metabolism* [30]

Supports gut barrier function* [28]

Supports mitochondrial function*

Supports healthy mitochondrial function [9,10]

Supports electron transport chain activity and ATP production* [13,18,32] 

Supports the activity of transcription factors of mitochondrial biogenesis (PGC-1α)* [32–35]

Promotes healthy metabolism*

Supports maintenance of healthy blood glucose levels* [33,35–39]

Supports healthy body composition* [33,35–37,39]

Supports maintenance of healthy blood and liver fat levels* [33,35,36,39–41]

Supports maintenance of healthy blood triglyceride and cholesterol levels* [35,40–42]

Supports adiponectin levels* [37,38]

Supports the differentiation of brown adipose tissue and thermogenesis* [34,39]

Supports UCP-1 and UCP-2 activity* [34,35,37,39]

Helps balance the respiratory quotient* [36]

Supports a healthy urea cycle* [43]

Supports circadian rhythms*

Supports the activity of the circadian system* [12,36,44]

Supports metabolic function through a circadian-dependent mechanism* [32,36]

Enhances antioxidant defenses*

Supports antioxidant defenses* [6,10,45,46]

Counters ROS production and oxidative stress* [9,10,32,45,46]

Supports Nrf2 signaling and phase II antioxidant defenses* [6,45,47,48]

Supports signaling pathways*

Supports AMPK signaling* [32,45,49,50]

Influences mTOR signaling* [5]

Supports SIRT1 signaling* [32,34]

Supports PPARα, PPARδ, and PPARγ signaling* [34,37,38,40,45,47,49]

Influences GSK-3β activity* [5,13,32]

Promotes general health*

Supports healthy cardiovascular structure and function* [33,35,51–53]

Supports healthy liver structure and function* [45]

Supports healthy gastrointestinal structure and function* [46]

Supports healthy immune cell activity* [35,54]

Supports healthy immune signaling* [5,6,16,17,35,37,38,40,45–48]

Complementary ingredients*

Citrus bioflavonoids support bioavailability and the accumulation of vitamin C in some tissues* [55–59]

Citrus bioflavonoids may be needed to support some of Vitamin C’s functional benefits* [60–62]

*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]D.J. Lamport, D. Pal, A.L. Macready, S. Barbosa-Boucas, J.M. Fletcher, C.M. Williams, J.P.E. Spencer, L.T. Butler, Br. J. Nutr. 116 (2016) 2160–2168.

[2]M.H. Alharbi, D.J. Lamport, G.F. Dodd, C. Saunders, L. Harkness, L.T. Butler, J.P.E. Spencer, Eur. J. Nutr. 55 (2016) 2021–2029.

[3]R.J. Kean, D.J. Lamport, G.F. Dodd, J.E. Freeman, C.M. Williams, J.A. Ellis, L.T. Butler, J.P.E. Spencer, Am. J. Clin. Nutr. 101 (2015) 506–514.

[4]J.J. Peterson, J.T. Dwyer, G.R. Beecher, S.A. Bhagwat, S.E. Gebhardt, D.B. Haytowitz, J.M. Holden, J. Food Compost. Anal. 19 (2006) S66–S73.

[5]Y. Zheng, J. Bu, L. Yu, J. Chen, H. Liu, Biomed. Pharmacother. 91 (2017) 494–503.

[6]L. Zhang, X. Zhang, C. Zhang, X. Bai, J. Zhang, X. Zhao, L. Chen, L. Wang, C. Zhu, L. Cui, R. Chen, T. Zhao, Y. Zhao, Brain Res. 1636 (2016) 130–141.

[7]N. Yasuda, T. Ishii, D. Oyama, T. Fukuta, Y. Agato, A. Sato, K. Shimizu, T. Asai, T. Asakawa, T. Kan, S. Yamada, Y. Ohizumi, N. Oku, Brain Res. 1559 (2014) 46–54.

[8]L. Zhang, H. Zhao, X. Zhang, L. Chen, X. Zhao, X. Bai, J. Zhang, Brain Res. Bull. 96 (2013) 45–53.

[9]J.H. Lee, K. Amarsanaa, J. Wu, S.-C. Jeon, Y. Cui, S.-C. Jung, D.-B. Park, S.-J. Kim, S.-H. Han, H.-W. Kim, I.J. Rhyu, S.-Y. Eun, Korean J. Physiol. Pharmacol. 22 (2018) 311–319.

[10]K. Tamilselvam, N. Braidy, T. Manivasagam, M.M. Essa, N.R. Prasad, S. Karthikeyan, A.J. Thenmozhi, S. Selvaraju, G.J. Guillemin, Oxid. Med. Cell. Longev. 2013 (2013) 102741.

[11]Y. Yabuki, Y. Ohizumi, A. Yokosuka, Y. Mimaki, K. Fukunaga, Neuroscience 259 (2014) 126–141.

[12]J. Gile, B. Scott, T. Eckle, Crit. Care Med. 46 (2018) e600–e608.

[13]D. Wang, L. Liu, X. Zhu, W. Wu, Y. Wang, Cell. Mol. Neurobiol. 34 (2014) 1209–1221.

[14]A. Nakajima, Y. Aoyama, T.-T.L. Nguyen, E.-J. Shin, H.-C. Kim, S. Yamada, T. Nakai, T. Nagai, A. Yokosuka, Y. Mimaki, Y. Ohizumi, K. Yamada, Behav. Brain Res. 250 (2013) 351–360.

[15]J. Kang, J.-W. Shin, Y.-R. Kim, K.M. Swanberg, Y. Kim, J.R. Bae, Y.K. Kim, J. Lee, S.-Y. Kim, N.-W. Sohn, S. Maeng, J. Nat. Med. 71 (2017) 181–189.

[16]Y. Cui, J. Wu, S.-C. Jung, D.-B. Park, Y.-H. Maeng, J.Y. Hong, S.-J. Kim, S.-R. Lee, S.-J. Kim, S.J. Kim, S.-Y. Eun, Biol. Pharm. Bull. 33 (2010) 1814–1821.

[17]S.-C. Ho, C.-T. Kuo, Food Chem. Toxicol. 71 (2014) 176–182.

[18]N. Jojua, N. Sharikadze, E. Zhuravliova, E. Zaalishvili, D.G. Mikeladze, Nutr. Neurosci. 18 (2015) 225–231.

[19]J. Li, Y. Zhou, B.-B. Liu, Q. Liu, D. Geng, L.-J. Weng, L.-T. Yi, Evid. Based. Complement. Alternat. Med. 2013 (2013) 359682.

[20]Cai L., Li R., Wu Q.-Q., Wu T.-N., Zhongguo Zhong Yao Za Zhi 38 (2013) 229–233.

[21]C.-F. Li, S.-M. Chen, X.-M. Chen, R.-H. Mu, S.-S. Wang, D. Geng, Q. Liu, L.-T. Yi, Brain Res. Bull. 124 (2016) 40–47.

[22]S. Merzoug, M.L. Toumi, EXCLI J. 16 (2017) 400–413.

[23]M. Li, H. Shao, X. Zhang, B. Qin, Inflammation 39 (2016) 1681–1689.

[24]L.-T. Yi, J. Li, H.-C. Li, D.-X. Su, X.-B. Quan, X.-C. He, X.-H. Wang, Prog. Neuropsychopharmacol. Biol. Psychiatry 39 (2012) 175–181.

[25]Y. Bansal, R. Singh, P. Saroj, R.K. Sodhi, A. Kuhad, Toxicol. Appl. Pharmacol. 355 (2018) 257–268.

[26]S.R. Maratha, N. Mahadevan, Neurochem. Res. 37 (2012) 2206–2212.

[27]M. Kwatra, A. Jangra, M. Mishra, Y. Sharma, S. Ahmed, P. Ghosh, V. Kumar, D. Vohora, R. Khanam, Neurochem. Res. 41 (2016) 2352–2366.

[28]D. Li, H. Wu, H. Dou, L. Guo, W. Huang, Biochem. Biophys. Res. Commun. (2018).

[29]Y.-C. Tung, W.-T. Chang, S. Li, J.-C. Wu, V. Badmeav, C.-T. Ho, M.-H. Pan, Food Funct. 9 (2018) 3363–3373.

[30]T. Unno, T. Hisada, S. Takahashi, J. Agric. Food Chem. 63 (2015) 7952–7957.

[31]A. Cuervo, A. Hevia, P. López, A. Suárez, B. Sánchez, A. Margolles, S. González, Nutrients 7 (2015) 1301–1317.

[32]G. Qi, R. Guo, H. Tian, L. Li, H. Liu, Y. Mi, X. Liu, Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1863 (2018) 549–562.

[33]E.E. Mulvihill, J.M. Assini, J.K. Lee, E.M. Allister, B.G. Sutherland, J.B. Koppes, C.G. Sawyez, J.Y. Edwards, D.E. Telford, A. Charbonneau, P. St-Pierre, A. Marette, M.W. Huff, Diabetes 60 (2011) 1446–1457.

[34]J. Lone, H.A. Parray, J.W. Yun, Biochimie 146 (2018) 97–104.

[35]A.C. Burke, B.G. Sutherland, D.E. Telford, M.R. Morrow, C.G. Sawyez, J.Y. Edwards, M. Drangova, M.W. Huff, J. Lipid Res. 59 (2018) 1714–1728.

[36]B. He, K. Nohara, N. Park, Y.-S. Park, B. Guillory, Z. Zhao, J.M. Garcia, N. Koike, C.C. Lee, J.S. Takahashi, S.-H. Yoo, Z. Chen, Cell Metab. 23 (2016) 610–621.

[37]Y.-S. Lee, B.-Y. Cha, S.-S. Choi, B.-K. Choi, T. Yonezawa, T. Teruya, K. Nagai, J.-T. Woo, J. Nutr. Biochem. 24 (2013) 156–162.

[38]Y.-S. Lee, B.-Y. Cha, K. Saito, H. Yamakawa, S.-S. Choi, K. Yamaguchi, T. Yonezawa, T. Teruya, K. Nagai, J.-T. Woo, Biochem. Pharmacol. 79 (2010) 1674–1683.

[39]Y.-C. Chou, C.-T. Ho, M.-H. Pan, J. Agric. Food Chem. 66 (2018) 9697–9703.

[40]Y.-J. Kim, M.-S. Choi, J.T. Woo, M.J. Jeong, S.R. Kim, U.J. Jung, Mol. Nutr. Food Res. 61 (2017).

[41]E.M. Kurowska, J.A. Manthey, J. Agric. Food Chem. 52 (2004) 2879–2886.

[42]J.M. Roza, Z. Xian-Liu, N. Guthrie, Altern. Ther. Health Med. 13 (2007) 44–48.

[43]K. Nohara, Y. Shin, N. Park, K. Jeong, B. He, N. Koike, S.-H. Yoo, Z. Chen, Nutr. Metab. 12 (2015) 23.

[44]A. Shinozaki, K. Misawa, Y. Ikeda, A. Haraguchi, M. Kamagata, Y. Tahara, S. Shibata, PLoS One 12 (2017) e0170904.

[45]B.-K. Choi, T.-W. Kim, D.-R. Lee, W.-H. Jung, J.-H. Lim, J.-Y. Jung, S.H. Yang, J.-W. Suh, Phytother. Res. 29 (2015) 1577–1584.

[46]W. Li, X. Wang, W. Zhi, H. Zhang, Z. He, Y. Wang, F. Liu, X. Niu, X. Zhang, Immunopharmacol. Immunotoxicol. 39 (2017) 354–363.

[47]S. Namkoong, J. Sung, J. Yang, Y. Choi, H.S. Jeong, J. Lee, J. Med. Food 20 (2017) 873–881.

[48]X. Wu, M. Song, Z. Gao, Y. Sun, M. Wang, F. Li, J. Zheng, H. Xiao, J. Nutr. Biochem. 42 (2017) 17–25.

[49]Y. Choi, Y. Kim, H. Ham, Y. Park, H.-S. Jeong, J. Lee, J. Agric. Food Chem. 59 (2011) 12843–12849.

[50]T. Yuk, Y. Kim, J. Yang, J. Sung, H.S. Jeong, J. Lee, Evid. Based. Complement. Alternat. Med. 2018 (2018) 7420265.

[51]N. Zhang, W.-Y. Wei, Z. Yang, Y. Che, Y.-G. Jin, H.-H. Liao, S.-S. Wang, W. Deng, Q.-Z. Tang, Cell. Physiol. Biochem. 42 (2017) 1313–1325.

[52]P. Cirillo, S. Conte, G. Cimmino, G. Pellegrino, F. Ziviello, G. Barra, F.C. Sasso, F. Borgia, R. De Palma, B. Trimarco, Biochem. Pharmacol. 128 (2017) 26–33.

[53]N.A. Parkar, L.K. Bhatt, V. Addepalli, Food Funct. 7 (2016) 3121–3129.

[54]G. Yang, S. Li, Y. Yang, L. Yuan, P. Wang, H. Zhao, C.-T. Ho, C.-C. Lin, J. Agric. Food Chem. 66 (2018) 8299–8306.

[55]E. Papageorge, G.L. Mitchell, The Journal of Nutrition 37 (1949) 531–540.

[56]C.D. Douglass, G.H. Kamp, J. Nutr. 67 (1959) 531–536.

[57]H.K. Wilson, C. Price-Jones, R.E. Hughes, J. Sci. Food Agric. 27 (1976) 661–666.

[58]Vinson, Bose, Nutr. Rep. Int. (n.d.).

[59]J.A. Vinson, P. Bose, Am. J. Clin. Nutr. 48 (1988) 601–604.

[60]Elmby, Warbueg, Lancet (n.d.).

[61]H. Cotereau, M. Gabe, Nature 161 (1948) 557.

[62]S.T. Rusznyák, A. Szent-Györgyi, Nature 138 (1936) 27–27.