Quercetin for Nerves, Allergies, Immunity, and Metabolism

April 15, 2013 | Byron J. Richards, Board Certified Clinical Nutritionist

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 Quercetin for Nerves, Allergies, Immunity, and Metabolism
Quercetin is a common flavonoid found in many fresh fruits and vegetables. It has been in widespread use in the dietary supplement industry for the past two decades due to its natural antihistamine properties. Research is dramatically expanding our understanding of this nutrient, including its nervous system support, immune support, and weight management properties.

Quercetin is highly concentrated in apples, onions (especially red onions), and green tea. It is also in red grapes, citrus fruit, tomato, broccoli, leafy greens, cherries, raspberries, cranberries, and many other fruits and vegetables. One tree ripened apple, for example, contains 50 mg of quercetin.

Quercetin possesses unique antioxidant activity. A study in October 2009 demonstrated how quercetin activates the key step leading to the production of cellular glutathione1 (a cell's primary antioxidant). The researchers showed how this mechanism protected the insulin producing beta cells of the pancreas, contributing to healthier blood sugar function. A January 2009 study showed that quercetin offered significant antioxidant protection for cells lining the sinuses3. And a March 2009 study shows that quercetin offers significant antioxidant protection to the mitochondria4 (cellular engines).

Quercetin's antioxidant effects also extend to the cardiovascular system5.  A mouse study showed that quercetin increased the friendly form of nitric oxide8 in the circulation, in this case supporting male erection.

Researchers demonstrated that quercetin modulates the key anti-inflammatory gene signal known as NF-kappaB. For example, quercetin was shown to lower NF-kappa B in bone10.

Mast Cells, Allergy, and Nerves

The original interest in quercetin as a dietary supplement ingredient was based on its ability to stabilize mast cells, which release histamine and other inflammatory signals. It became a popular and widely used remedy for sinus congestion, sneezing, the pollen season, and other issues where the immune system seemed to behave in an excessive direction.

Quercetin's antihistamine properties are now well established. It has been found to stabilize mast cells13 in a way that helps lower stress induced anxiety and allergic reactions. A chain of recent discoveries helps place the significance of these discoveries into context, with far ranging implications for human health and improved nerve tolerance for managing stress.

One study shows that stress14 itself is adequate to begin the migration of immune cells toward your skin, as if preparing to deal with a wound or infection – clearly an evolutionary strategy where stress typically implied injury of some type. Another study shows that stress turns up the volume on mast cells15, priming them to release inflammatory chemicals that are typically involved with allergies, asthma, skin conditions, and digestive problems. Furthermore, the communication coming from mast cells feeds back to nerves and modulates behavior through a sense of anxiety. Mice bred with no mast cells have no fear, and thus boldly venture out and are easy prey.

Quercetin has shown that it can reduce the effects of stress16 in nerves while preventing depletion of nerve antioxidants due to stress. Researchers concluded that the “results suggest that neuroprotective properties of quercetin can be used in the treatment and management of stress and related disorders.”

Quercetin not only prevents mast cells from inappropriately releasing irritant chemicals18 like histamine, but it also reduces the inflammatory19 immune system signals like IL-6 that come from mast cells and are known to talk to nerve cells (glial cells).

Immunometabolism: Linking Immunity and Body Weight

In 2010 the journal Nature Medicine published three groundbreaking articles linking the function of immune cells to weight gain – data that opens the door to solve all kinds of health problems.

It has been known for years that the extra pounds of fat in an overweight person generate significant amounts of immune-related inflammatory signals such as TNFa and IL6. Such inflammation not only damages the stored fat so that it is less metabolically responsive, but it has also been shown to induce inflammatory damage around the body.

What hasn't been understood are the changes within stored fat that result in this inflammatory state. The research goes a long way toward explaining exactly how this happens, and the mechanism is startling. It involves the function of various T regulator cells of the immune system -- cells that until this point were never thought to have anything to do with metabolism and body weight.

For more information, link to abstracts of these studies:
Linking T cells and Glucose Uptake by Fat Cells28 – A study that explains changes in T cells that directly influence metabolism.
How Fat Inflammation Gets Going29 - A study that explains how these changes in T cells cause inflammation.

These studies show that in animals that are not overweight there is a high level of T Helper cells (CD4*) and regulatory T cells in their white adipose tissue. However, in the fat of overweight animals and obese diabetic humans this population of immune cells is virtually gone and has been replaced with a population of CD8+ T cells (also called cytotoxic T cells or T killer cells), cytotoxic T cells kill cancerous cells and virally infected cells. Here they are in excess amounts within stored fat – apparently responding to initial stress within white adipose tissue from too much extra fat.

It was shown that these cytotoxic T cells were behind the recruitment of excessive macrophages into the extra pounds of fat. The macrophages, in turn, generate the massive inflammation associated with being overweight or obese. This problem, in turn, results in even more cyctoxic T cells, and we end up with one large inflammatory party that self-perpetuates as well as damages the metabolism of calories in white adipose tissue (locking in excess pounds of stagnant fat that won't budge).

This means that the proper T helper cells and regulatory T cells are needed to keep white adipose tissue in a noninflammatory condition. The researchers also showed that when this slides out of balance then glucose uptake by fat cells is dysregulated, leading to perpetuation of obesity. This is a nasty catch-22 that most certainly applies to any person who has trouble losing weight by eating and exercising.

The researchers showed that as part of this immune cell problem, there were excessive numbers of T Helper 1 cells and a lack of T Helper 2 cells within the fat. Excess T Helper 1 cells are associated with autoimmune problems, allergy, skin problems, etc. It is quite likely that just as excess inflammation coming from fat cells can wreak havoc around the body, so it is that fat may be tilting overall immunity into T Helper 1 excess, leading to multiple health problems. Or a T Helper 1 health problem may in reverse help set the stage for obesity. Either way it is not a good situation.

Quercetin's Role In Metabolism and Weight Loss

In addition to the new discovery of excessive mast cell activity and poor metabolism, quercetin demonstrates a variety of other ways in which it helps metabolism and weight management.

One of the great problems in becoming overweight is that your fat cells expand in size and multiply in number. There appears to be no shortage of baby fat cells willing to mature into fat storing goliaths. Quercetin has been found to block baby fat cells31 from maturing as well as induce cell death (appropriately) in the baby fat cell population. Tests showed that quercetin had a 71 percent inhibitory rate on new fat cell formation, far higher than any other flavonoid. Another study using quercetin and resveratrol32 showed similar findings, suppression of fat cell formation and enhanced fat cell death.

Furthermore, quercetin has been shown to be absorbed into fat cells where it induces significant antioxidant activity33. This will lower inflammation coming from fat cells, such as the problematic excess of TNFa typically experienced by overweight individuals. A metabolic study with quercetin showed that it lowered all inflammatory markers34 tested, offsetting the stress of a high fat diet.

Another problem in overweight individuals is that glucose is too easily taken up by fat cells after a meal, which in turn stimulates excessive leptin production by fat cells and locks in leptin and insulin resistance. It has been demonstrated that quercetin directly blunts37 this inappropriate uptake of glucose by fat cells.

The proper function of leptin and adiponectin within fat is vital for healthy metabolism. When these hormones work properly they turn on a pivotal enzyme called AMP-activated protein kinase (AMPK). In turn, AMPK activates numerous metabolic signals that facilitate healthy metabolism and longevity39. One way to activate AMPK is to exercise.

Quercetin helps reduce inflammation that occurs within fat. It helps reduce the number of fat cells and prevent the development of new fat cells-- both key issues in the battle of the bulge. It also boosts adiponectin levels that support healthy blood sugar metabolism. It activates the AMPK enzyme system that facilitates healthy fat burning. And its supreme ability to stabilize mast cells indicates that it is likely to change the function of immune cells that operate within fat in a way that is conducive to having an easier time with weight management efforts.

The collective body of quercetin research shows that it is a useful tool for immune stability, immune function, cardiovascular health, bone health, joint health, nerve health, and metabolism. It helps reduce inflammation while it enhances antioxidant function, facilitating numerous metabolic signals associated with health.

Referenced Studies

  1. ^ Quercetin Boosts Cellular Antioxidant Function, Protects Beta Cells  J Cell Biochem.  Kang JH, Chang SY, Jang HJ, Cho JM, Kim DB, Lee SS, Ko SH, Park YM, Needs PW, Jo YH, Kim MJ.
  2. ^ Antioxidant Properties of Quercetin Protect Against Liver Damage  Free Radic Res.   Yokoyama A, Sakakibara H, Crozier A, Kawai Y, Matsui A, Terao J, Kumazawa S, Shimoi K.
  3. ^ Quercetin and Q10 Protect Human Sinus Cells  Anticancer Res.  Reiter M, Rupp K, Baumeister P, Zieger S, Harréus U.
  4. ^ Quercetin Protects Mitochondria  The Journal of Nutritional Biochemistry  Mara Fiorania, Andrea Guidarellib, Manuela Blasaa, Catia Azzolinia, Manila Candiraccia, Elena Piattia and Orazio Cantoni.
  5. ^ Role of Quercetin in Disease Prevention  Curr Opin Clin Nutr Metab Care  Bischoff SC.
  6. ^ Quercetin Demonstrates Cardio Protection  J Pharm Pharmacol.  Annapurna A, Reddy CS, Akondi RB, Rao SR.
  7. ^ Quercetin and Blood Pressure  American Journal of Clinical Nutrition  Wai Mun Loke, Jonathan M Hodgson, Julie M Proudfoot, Allan J McKinley, Ian B Puddey and Kevin D Croft
  8. ^ Quercetin Supports Male Health  Fundam Clin Pharmacol  Ertuğ PU, Olguner AA, Oğülener N, Singirik E.
  9. ^ Quercetin Helps Offset Occluded Carotid Arteries  Phytother Res+  Yao Y, Han DD, Zhang T, Yang Z.
  10. ^ Quercetin Helps Stop Bone Loss   Biol Pharm Bull.   Woo JT, Nakagawa H, Notoya M, Yonezawa T, Udagawa N, Lee IS, Ohnishi M, Hagiwara H, Nagai K.
  11. ^ Quercetin Lowers Inflammation in an Arthritis Model  J Med Food.   Choi EJ, Bae SC, Yu R, Youn J, Sung MK.
  12. ^ Quercetin, Chondroitin, and Glucosamine Help Osteoarthritis  Biosci Biotechnol Biochem.  Matsuno H, Nakamura H, Katayama K, Hayashi S, Kano S, Yudoh K, Kiso Y.
  13. ^ Quercetin Stabilizes Mast Cells   J Biol Regul Homeost Agents.  Shaik YB, Castellani ML, Perrella A, Conti F, Salini V, Tete S, Madhappan B, Vecchiet J, De Lutiis MA, Caraffa A, Cerulli G.
  14. ^ Stress Activates Immune Cells in Skin  Am J Pathol,   Joachim RA, Handjiski B, Blois SM, Hagen E, Paus R, Arck PC.
  15. ^ Stress Activates Mast Cells  Science  Donald Pfaff, et al.
  16. ^ Quercetin Protects Against Stress  Journal of Medicinal Food.  Anil Kumar, Richa Goyal
  17. ^ Quercetin Protects Against Stress  Journal of Medicinal Food.  Anil Kumar, Richa Goyal
  18. ^ Quercetin Is A Powerful Regulator of Mast Cells  Clin Exp Allergy.  Lee JH, Kim JW, Ko NY, Mun SH, Kim DK, Kim JD, Kim HS, Lee KR, Kim YK, Radinger M, Her E, Choi WS.
  19. ^ Quercetin Prevents Inflammatory Signal Release from Mast Cells  Br J Pharmacol.  Kandere-Grzybowska K, Kempuraj D, Cao J, Cetrulo CL, Theoharides TC.
  20. ^ Quercetin and Alzheimer's  The Journal of Nutritional Biochemistry.  Mubeen Ahmad Ansariabc, Hafiz Mohammad Abdulab, Gururaj Joshiab, Wycliffe O. Opiiab, D. Allan Butterfieldabc.
  21. ^ Quercetin Supports Nerve Healing  Spinal Cord.  Schültke E, Kamencic H, Skihar VM, Griebel R, Juurlink B.
  22. ^ Quercetin and Prostate Cancer   Prostate.   Aalinkeel R, Bindukumar B, Reynolds JL, Sykes DE, Mahajan SD, Chadha KC, Schwartz SA.
  23. ^ Quercetin Inhibits Changes that Lead to Colon Cancer  Journal of Nutrition  Cynthia A. Warren, Kimberly J. Paulhill, Laurie A. Davidson, Joanne R. Lupton, Stella S. Taddeo, Mee Young Hong, Raymond J. Carroll, Robert S. Chapkin, and Nancy D. Turner. .
  24. ^ Quercetin and the Flu  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.  J. Mark Davis, E.A. Murphy, J.L. McClellan, M.D. Carmichael, and J.D. Gangemi.
  25. ^ Quercetin Reduces Hepatitis C Virus Production  Hepatology.  Gonzalez O, Fontanes V, Raychaudhuri S, Loo R, Loo J, Arumugaswami V, Sun R, Dasgupta A, French SW.
  26. ^ Quercetin Inhibits Influenza A  Eur J Pharm Sci  Choi HJ, Song JH, Park KS, Kwon DH.
  27. ^ Quercetin Boosts Respiratory Antioxidants Upon Flu Exposure  Exp Lung Res.   Kumar P, Khanna M, Srivastava V, Tyagi YK, Raj HG, Ravi K.
  28. ^ Linking T cells and Glucose Uptake by Fat Cells  Nature Medicine  Markus Feuerer, Laura Herrero, Daniela Cipolletta, Afia Naaz, Jamie Wong, Ali Nayer, Jongsoon Lee, Allison B Goldfine, Christophe Benoist, Steven Shoelson & Diane Mathis.
  29. ^ How Fat Inflammation Gets Going  Nature Medicine  Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Koji Eto, Hiroshi Yamashita, Mitsuru Ohsugi, Makoto Otsu, Kazuo Hara, Kohjiro Ueki, Seiryo Sugiura, Kotaro Yoshimura, Takashi Kadowaki & Ryozo Nagai.
  30. ^ Antihistamines Prevent Obesity and Diabetes  Nature Medicine  Shawn Winer, Yin Chan, Geoffrey Paltser, Dorothy Truong, Hubert Tsui, Jasmine Bahrami, Ruslan Dorfman, Yongqian Wang, Julian Zielenski, Fabrizio Mastronardi, Yuko Maezawa, Daniel J Drucker, Edgar Engleman, Daniel Winer & H.-Michael Dosch.
  31. ^ Quercetin Inhibits Fat Cell Formation  Mol Nutr Food Res.  Hsu CL, Yen GC.
  32. ^ Quercetin, Genistein, and Resveratrol Inhibit Fat Cells.  J Med Food.  Park HJ, Yang JY, Ambati S, Della-Fera MA, Hausman DB, Rayalam S, Baile CA.
  33. ^ Quercetin Provides Antioxidant Function for Fat Cells  Cell Biol Toxicol.  Roche M, Tarnus E, Rondeau P, Bourdon E.
  34. ^ Quercetin Reduces Inflammation on High Fat Diet  Metabolism.  Stewart LK, Soileau JL, Ribnicky D, Wang ZQ, Raskin I, Poulev A, Majewski M, Cefalu WT, Gettys TW.
  35. ^ Phytochemicals In Fruits and Vegetables Battle Obesity  Journal of Human Nutrition and Dietetics.  Heather K. Vincent, et al.
  36. ^ Quercetin Improves Metabolic Profile of Fat Rats  Obesity (Silver Spring).  Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M.
  37. ^ Quercetin Reduces Glucose Uptake by Fat Cells  Biochem. J.  Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F.
  38. ^ Querectin In Grapes Helps Pancreatic Health  J Nutr.   Zunino S.
  39. ^ AMPK Activation Helps Metabolism and Longevity  N Biotechnol.  Hwang JT, Kwon DY, Yoon SH.
  40. ^ Quercetin Activates AMPK to Help Prevent Obesity  Biochem Biophys Res Commun.  Ahn J, Lee H, Kim S, Park J, Ha T.

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