Quercetin for Nerves, Allergies, Immunity, and Metabolism

Byron J. Richards, Board Certified Clinical Nutritionist

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Quercetin for Nerves, Allergies, Immunity, and Metabolism
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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 vine 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. Another October 2009 study demonstrated that quercetin protects against liver injury by antioxidant 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 study with diabetic rats found that quercetin reduced free radical damage and offered significant cardiovascular protection6 in terms of the amount of damage done by experimentally induced heart attacks (they were much smaller in quercetin treated animals). A study with healthy men found that 200 mg of quercetin7 enhanced friendly nitric oxide production and endothelial cell function (cells lining arteries), indicating improved circulation and natural support for blood pressure health. A mouse study also showed that quercetin increased the friendly form of nitric oxide8 in the circulation, in this case supporting male erection. A rat study showed that quercetin improved cognitive function in rats with occluded carotid arteries9, partly by helping circulation and partly by helping nerves in the brain.

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, reducing the number of bone deteriorating osteoclasts being formed as well as helping manage existing osteoclasts so that their bone resorption activity did not become excessive.

Another example is an August 2009 study that involved experimentally induced rheumatoid arthritis11, which showed that animals that took quercetin had no more inflammation than control animals – demonstrating quercetin's ability to suppress inflammation. A combination of quercetin, glucosamine, and chondroitin given to patients with osteoarthritis12 found a significant reduction in joint pain, improved range of motion, and documented changes to the synovial fluid of their joints reflecting improvement in lubrication.

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.”

One study with mice showed that pretreating them with quercetin prevented the anxiety response17 to experimental stress via mast cell stabilization. The researchers found that quercetin was highly protective to the nervous system. The dose used translates to 1,500 mg – 3,000 mg per day for a 150 pound adult. 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).

An April 2009 cell study showed that quercetin could prevent the formation of beta-amyloid plaque20 by a variety of mechanisms including its antioxidant function. The researchers concluded, “These findings provide motivation to test the hypothesis that quercetin may provide a promising approach for the treatment of Alzheimer's disease and other oxidative-stress-related neurodegenerative diseases.”

A September 2009 study of animals with experimentally induced spinal cord injury21 showed that 50 percent of animals that received quercetin twice daily for three or 10 days recovered the ability to walk, however, no control animals recovered. Quercetin was found to support the health of tissue bridges at the site of nerve injury, which facilitated healing.

Collectively, this data shows a wide range of nervous system support by quercetin. Since many problems today involve overheated nerves from stress that lead to other health problems, quercetin is an ideal tool to help calm down overexcited nerves as well as protect nerves from free radical decline due to wear and tear.

Quercetin and Immunity

While quercetin's ability to modulate mast cells and allergy is significant, it has also been shown to decrease the proliferation of and knock out prostate cancer cells22. Additionally, an animal study showed that quercetin prevented early lesions in the digestive tract that lead to colon cancer, plus reduced the proliferation of colon cancer cells23, once again knocking them out. While such cell and animal studies are preliminary, they still point to quercetin's multiple roles in health protection.

Of significant current interest is quercetin's potential anti-flu properties. In 2009 an animal study showed that quercetin24 significantly reduced susceptibility to the flu. Mice were exposed to the influenza virus A/Puerto Rico/8/34 (H1N1) flu virus under various conditions, including increased stress from exercise. The mice given quercetin offset the adverse effects of stress and showed much less susceptibility to the flu.

A number of studies show that quercetin directly interacts with different types of viral infections, reducing their ability to infect. An August 2009 cell study showed that quercetin interfered with the gene signals that enable hepatitis C virus production25. The researchers concluded that “Quercetin may allow for dissection of the viral life cycle and has potential therapeutic use to reduce virus production with low associated toxicity.”

A June 2009 study showed that quercetin could reduce viral replication of influenza A26 by directly interacting with viral particles. A 2005 study showed that quercetin significantly boosted the respiratory antioxidant defense27 system in mice exposed to influenza A, offering significant protection for the lungs during a time of high stress.

Immunometabolism: Linking Immunity and Obesity

In 2010 the journal Nature Medicine published three groundbreaking articles linking the function of immune cells to obesity and diabetes – data that opens the door to solve all kinds of health problems, including obesity.

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.
Antihistamines Prevent Obesity and Diabetes30 – A study that shows one way to help address this issue is with antihistamines (one of the drugs tested is a synthetic version of quercetin, nature's most potent natural antihistamine).

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.

Furthermore, a lack of T Helper 2 cells, especially if the body is tilted to T Helper 1 excess by obesity, would impair the formation of antibodies needed to fight an infection such as the flu.

The researchers also identified that mast cells were far more abundant in fat tissue from obese and diabetic humans and mice compared to those of normal weight. Giving antihistamine drugs (Zaditor and Cromolyn) to mice significantly improved their metabolism. Cromolyn is a drug patterned after the quercetin molecule, which is the best natural antihistamine available.

In their experiments the mice were divided into four groups. The first was the control group; the second group was simply switched to a healthy diet; the third was given Cromolyn or ketotifen fumarate; the fourth was given the drug and switched to a healthy diet.

While symptoms of the second group, that switched to a healthy diet, improved moderately, the third group, given Cromolyn or ketotifen fumarate, demonstrated dramatic improvements in both body weight and diabetes. The fourth group exhibited nearly 100 percent recovery in all areas.

To bolster these findings, researchers then took a group of mice that had genetically impaired ability to produce mast cells. Despite three months of a diet rich in sugar and fat, these mice neither became obese nor developed diabetes.

These studies are indeed groundbreaking. They open the door for new strategies to help individuals manage their weight, especially those who cannot get their weight under control simply by eating better and exercising more.

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.

One study calculated obesity risk35 by the percentage of healthy plant compounds from fruits and vegetables as a percentage of the diet. There is no question that quercetin is the most abundant and definitely one of the most potent flavonoids in such a fresh food diet.

Obese Zucker rats have leptin receptor problems that result in excessive appetite, high cholesterol, high triglycerides, high blood pressure, insulin resistance, excessive numbers of fat cells, and obesity (the typical problems of obese humans). Two doses of quercetin were tested over a 10 week period (human equivalent is 136 mg or 681 mg for a 150 pound adult). Both doses lowered the blood pressure, triglycerides, cholesterol, and insulin resistance in these obese animals. The higher dose of quercetin lowered the inflammatory TNFa within adipose tissue36, where adiponectin, which prevents insulin resistance, was increased. Quercetin lowered unfriendly nitric oxide (iNOS) while boosting circulatory friendly nitric oxide (eNOS). These are amazing findings for any study.

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. Indeed, flavonoids in grapes such as quercetin38 are associated with less risk for developing type 2 diabetes.

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. Recently, researchers demonstrated that much of quercetin's anti-obesity effects40 are due to activation of AMPK.

Quercetin helps reduce inflammation and free radical problems that occur 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 issues, 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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