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Itchy Eyes, Sneezing, Congestion – Oh No!

Vitamin C with Bioflavonoids and Allergies


It’s that time of year!

Are you suffering from a runny nose, itchy eyes, sneezing, nasal congestion, or other symptoms of seasonal allergies? If so, you are not alone! Over 40% of the US population has allergies. According to the National Health and Nutrition Examination Survey (NHANES), 44.6% of the US population has detectable Immunoglobulin E (IgE) antibodies in their blood, and we know IgE antibodies play a central role in instigating the symptoms associated with allergies.1,2 And, in a survey of a representative sample of the general American population, 41.7% of adults reported they have allergies.3 In other words, allergies are very common!

The good news is certain nutrients and food-derived bioflavonoids could reduce or even eliminate some of the uncomfortable symptoms of seasonal allergies.

It’s true!

Research shows vitamin C and hesperidin could be especially beneficial this time of year.

Pollen Season Ahead Flavo PlexC Can Help

What causes allergy symptoms?

After exposure to an allergen, such as pollen, one mechanism by which an allergic response causes symptoms is “IgE-dependent mast cell degranulation.” IgE antibodies play a central role in the allergic response and are specific for each allergen. For example, if you are allergic to ragweed, you have ragweed-specific IgE antibodies. If you are allergic to oak, then you have oak-specific IgE antibodies. Once exposure to ragweed or oak occurs, the ragweed or oak particle attaches to the specific IgE antibody. Then, once the IgE antibody is attached to the allergen and a mast cell, it causes the mast cell to de-granulate; to release inflammatory compounds, including histamine.4

Histamine release from mast cells then activates the histamine receptors on sensory nerves to cause itching and sneezing. Histamine release also stimulates mucous glands to secrete watery discharge that we experience as a “runny nose.” Histamine causes nasal congestion by increasing vascular permeability and vasodilatation in the nasal mucosa. Histamine release also affects the function of tight junctions in the nasal epithelium, which could contribute to the ‘priming effect.’ The priming effect refers to increased nasal reactivity to allergens following repeated allergen exposure, exacerbating the allergic reaction over time.5

How can the symptoms of allergies be reduced or eliminated?

Since histamine facilitates the onslaught of allergic symptoms, any substance that reduces the activity or quantity of histamine is likely to alleviate some or all allergic symptoms. Two natural substances known to impact histamine are vitamin C and hesperidin.

VitaminC and Flavo PlexC

Vitamin C

Research shows vitamin C has a potent effect on histamine levels via several mechanisms. Vitamin C not only plays a role in the degradation of histamine but also inhibits the histamine-forming enzyme known as histidine decarboxylase.6 So, vitamin C prevents histamine production and increases histamine metabolism to remove histamine from the body. In a study that assessed the effectiveness of intranasal vitamin C, 74% of subjects treated with vitamin C experienced a decrease in symptoms, including nasal congestion and runny nose.7

In general, there is a direct correlation between histamine levels and vitamin C levels in the blood. The higher the histamine level, the lower the vitamin C level. A recent study on the effects of intravenous (IV) administration of vitamin C confirmed that increased vitamin C levels lead to a reduction in the histamine level. Specifically, IV administration of 7.5 grams of vitamin C induced a significant 31.3 % decrease in serum histamine levels. The histamine-lowering effect was observed in all patients, but in individuals with allergies, the decline in the serum histamine level was more pronounced.6

VitaminC and Oranges Flavo PlexC


Hesperidin is derived from citrus fruits, such as oranges and lemons, and is also known as “Vitamin P.” Hesperidin was first isolated from the inner portion of orange peels by the French chemist Lebreton in 1828. Hesperidin is one of the safest and most important bioflavonoids. Hesperidin possesses a wide range of beneficial properties, including anti-carcinogenic, anti-allergy, and cholesterol-lowering activities.8,9

Hesperidin also significantly reduces histamine levels but not as directly as vitamin C. Research shows hesperidin affects the immune cells themselves to reduce the allergic response. While vitamin C clears histamine and inhibits the production of histamine, hesperidin reduces the production of compounds known as Th2 cytokines that enhance the production of IgE antibodies. So, when hesperidin reduces the production of Th2 cytokines, IgE antibody levels also decrease. Since IgE antibodies are required to release histamine from mast cells, the lower the IgE level, the less histamine released.4,7,10 The results of an animal study show that hesperidin not only reduces histamine release but also reduces the number of H1 histamine receptors.11 Histamine must bind to an H1 histamine receptor for the allergic response to occur, so the lower the number of histamine receptors, the better!12

The gut microbiome may also increase the efficacy of hesperidin by converting hesperidin into new biologically-active postbiotic compounds. For example, hesperetin is readily produced from hesperidin by gut bacteria, and several studies confirm that hesperetin also has extensive anti-allergic properties.11 It turns out that the postbiotic hesperetin reduces both histamine release and IgE production.9,13

Since vitamin C, hesperidin, and hesperidin metabolites reduce histamine levels individually, taking them together during allergy season could result in synergistic effects and more potent benefits.*

Synergistic Vitamin C and hesperidin are available in Flavo PlexCTM from Interplexus.*


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

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  1. Salo PM, Arbes SJ Jr, Jaramillo R, et al. Prevalence of allergic sensitization in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. J Allergy Clin Immunol. 2014;134(2):350-359. doi:10.1016/j.jaci.2013.12.1071

  2. Wollenberg A, Thomsen SF, Lacour JP, et al. Targeting immunoglobulin E in atopic dermatitis: A review of the existing evidence. World Allergy Organ J. 2021;14(3):100519. doi:10.1016/j.waojou.2021.100519

  3. Seité S, Kuo AM, Taieb C, et al. Self-Reported Prevalence of Allergies in the USA and Impact on Skin-An Epidemiological Study on a Representative Sample of American Adults. Int J Environ Res Public Health. 2020;17(10):3360. doi:10.3390/ijerph17103360

  4. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693-704. doi:10.1038/nm.2755

  5. Watts AM, Cripps AW, West NP, Cox AJ. Modulation of Allergic Inflammation in the Nasal Mucosa of Allergic Rhinitis Sufferers With Topical Pharmaceutical Agents. Front Pharmacol. 2019;10:294. doi:10.3389/fphar.2019.00294

  6. Hagel AF, Layritz CM, Hagel WH, et al. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(9):789-93. doi:10.1007/s00210-013-0880-1

  7. Thornhill SM, Kelly AM. Natural treatment of perennial allergic rhinitis. Altern Med Rev. 2000;5(5):448-54.

  8. Preedy VR, Watson RR, Srinivasan S, Murali R, Vinothkumar V. Antidiabetic Efficacy of Citrus Fruits With Special Allusion to Flavone Glycosides. In: Bioactive Food as Dietary Interventions for Diabetes. 2nd ed. San Diego, CA: Academic Press; 2019:335-346.

  9. Shimoda K, Hamada H. Production of hesperetin glycosides by Xanthomonas campestris and cyclodextrin glucanotransferase and their anti-allergic activities. Nutrients. 2010;2(2):171-180. doi:10.3390/nu2020171

  10. Kim SH, Kim BK, Lee YC. Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediators Inflamm. 2011;2011:485402. doi:10.1155/2011/485402

  11. Deshetty UM, Tamatam A, Bhattacharjee M, et al. Ameliorative Effect of Hesperidin Against Motion Sickness by Modulating Histamine and Histamine H1 Receptor Expression. Neurochem Res. 2020;45(2):371-384. doi:10.1007/s11064-019-02923-0

  12. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov. 2008;7(1):41-53. doi: 10.1038/nrd2465

  13. Lee NK, Choi SH, Park SH, Park EK, Kim DH. Antiallergic activity of hesperidin is activated by intestinal microflora. Pharmacology. 2004;71(4):174-80. doi:10.1159/000078083

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