Quercetin, Bromelain and Vitamin C: Environmental Sensitivity-Support and More

by James South, MA

Quercetin (QRC) is a bright yellow flavanol widely found throughout the plant kingdom. Flavanols are one form of the better-known bioflavonoids. QRC occurs in various common foods, including red and yellow onions, apples, berries, black tea, broccoli, Italian squash, and some nuts and seeds.^1,2 It is estimated that the average daily human diet provides about 25 mg QRC.3 QRC is also the “backbone” for many other flavonoids, including rutin, hesperidin, quercetin, isoquercetrin, and hyperoside.^1,4 These flavonoids are formed when a specific sugar molecule (rhamnose, glucose, galactose, etc.) replaces the OH-group in the center ring of QRC. QRC is the “superstar” of the flavonoids. As Murray notes: “Quercetin is consistently the most active of the flavonoids in experimental studies, and many medicinal plants owe much of their activity to their high quercetin content.”⁴

Quercetin vs. Immune sensitivities

Environmental sensitivities represent an unbalanced immune response to otherwise harmless substances, such as ragweed pollen, cat dander, house dust, wheat protein, etc., that get into the body or on the skin through air, food or water. Some sensitivities are mediated through the antibody IgE, while some are not. What all sensitivities have in common is the antigen (the cause) stimulation of two related cell types: mast cells and basophils.⁵ Mast cells line the blood vessels in the connective tissue of the lungs, inner eyelids, gut, ear, nose, throat and skin.⁵ Basophils are a type of white blood cell. Both mast cells and basophils are full of granules of histamine and other chemical mediators.⁵ When environmental antigens in the blood contact mast cells or basophils in sufficient numbers, a burst of histamine and other sensitivity mediators are released into the bloodstream. It is the histamine and other immune mediators that trigger the misery of an environmental sensitivity reaction: runny, itchy nose and sneezing; watery, itchy red eyes; tickling and itching in ears, nose and throat; skin rash; occasional headache; impacts on breathing, etc.

QRC is a powerful balancer of antigen-stimulated histamine release from basophils and mast cells,^5,6,7,8 even at low levels of QRC (5-50 micromoles, or 1.51-15.1 mcg/ml).⁶ Unlike most anti-sensitivity substances, QRC is highly effective at supporting balanced histamine release during both the first and second stage of basophil histamine release: “quercetin is unique in exhibiting activity in both stages.”⁶ Pearce and colleagues also note that “…quercetin appears to possess a broader spectrum of [anti-sensitivity] activity than [popular remedies]….”⁵ Middleton and coworkers describe QRC as being “instantaneous in onset of action” and they report that “… addition of quercetin during early stages of an ongoing histamine release reaction results in an abrupt cessation of further histamine release….”⁶ Thus, QRC can both support normal immune reactions to environmental sensitivities and balance immune reactions that are already underway.

The Quercetin-Bromelain Connection

Bromelain is the general name for a group of proteolytic enzymes derived from pineapple stems.⁹ Bromelain is a protein-digesting enzyme that is active at a broad range of pHs, and thus can promote digestion of protein in both the stomach and small intestine.⁹ When taken on an empty stomach approximately 40 percent of the bromelain is absorbed into the bloodstream intact.¹⁰ Through its action on the blood clotting-related substances fibrinogen and fibrin, bromelain stimulates the production and release of anti-inflammatory prostaglandins (PGs), while simultaneously reducing the production and release of proinflammatory PGs.^9,10

Environmental sensitivity reactions typically involve an excess of inflammatory PGs being released, which contributes to the swelling, redness and itching. QRC also helps to balance formation and release of inflammatory PGs and thromboxanes.⁷

Thus, QRC and bromelain are synergistic in suppressing the inflammation of environmental sensitivity reactions, as well as the excessive inflammation that results from bruising and tissue damage from sports injuries, accidents, surgery, etc.⁹

Bromelain also potentiates QRC through another route. By itself, QRC is somewhat poorly absorbed from the GI tract.³ Bromelain is well known for its enhancement of absorption of various compounds, including tetracycline and amoxicillin.⁹ Bromelain also enhances the absorption of QRC.^4,11

The Quercetin-Vitamin C Connection

Vitamin C, also known as “ascorbate” (ASC), supports normal histamine response. It both balances histamine release and the detoxification of histamine. A 1992 study found that taking 2 grams ASC daily lowered blood histamine levels 38 percent in healthy adults in just one week. However, a single dose of ASC failed to lower histamine levels, indicating that the histamine balancing effect of ASC requires regular ongoing use.¹³

ASC and QRC have a mutual sparing effect on each other. ASC “…inhibits the oxidative degradation of … quercetin…”.⁸ In fact, “Flavonoids such as quercetin… were shown to enhance the reduction of dehydroascorbic acid [oxidized ASC] by glutathione,”⁸ thus recycling “used” ASC. Oxidized QRC is also reduced (recycled) by ASC back to QRC.⁸ Thus ASC and QRC are mutually supporting factors in dealing with environmental sensitivities.

Magnesium ASC is the best form of vitamin C in an anti-environmental sensitivity formula. Once into the blood and tissues, the magnesium and ASC will separate. Magnesium serves to activate bromelain.¹⁴ Also, magnesium is “nature’s calcium channel-blocker.”¹⁵ It helps to prevent entry of calcium into various cells, and calcium entry into mast cells and basophils is a key part of triggering histamine release.⁶

Quercetin: More Benefits

A combination of QRC, magnesium ASC and bromelain makes a great anti-sensitivity/ respiratory supporting supplement. But there are other potential benefits from this combination.

QRC has been extensively studied for its healthy cell proliferation and turnover activity. A 1989 report found that QRC strongly supported healthy cell activity when cells were transplanted into immunocompetent rats.¹⁶ “In several in vitro experiments, quercetin showed beneficial effects on human cells: colon, breast, ovarian, gastrointestinal and blood cells.”³ Verma and collaborators reported a significant benefits for cells and tissues in rats given QRC, compared to controls.¹⁶

Hofmann and coworkers found that QRC enhanced the effect of several types of compounds supporting healthy cell growth.¹⁸ They also noted that “quercetin… is a licensed [healthy cell growth and turnover compound] in many countries and is non-toxic at the required dose range.”¹⁸

Bromelain has also shown some support for healthy cell growth and turnover in both human clinical and animal experimental studies.⁹

QRC and bromelain both have shown positive effects in heart health long term. Bromelain is an effective promoter of platelet movement and a strong lytic enzyme capable of supporting normal clotting.^9,10 Because it helps support normal clotting and optimal blood flow, it promotes healthy heart and cardiovascular function. QRC also helps balance the production of inflammatory prostaglandins/thromboxanes, thereby promoting healthy blood flow/normal clotting and a healthy heart, as well.¹⁹ Trans-resveratrol (10-40 mg/day) is a potent synergist with QRC’s healthy cell/healthy heart promoting activity.¹⁹

The Zutphen Elderly Study published in 1993 provides eloquent evidence of the heart-protective power of QRC.20 This five-year study investigated the dietary flavonoid intake and heart function status in 805 men ages 65-84. The study found that most (74 percent) of the dietary flavonoid intake came from three foods: tea, onions and apples. Mean daily flavonoid intake was 26 mg, about two-thirds of which was QRC. Compared to those in the bottom third of flavonoid intake, those in the top third of flavonoid intake had 42 percent better supported heart health long-term during the five-year study.

A Personal Note

I have suffered from environmental sensitivities and respiratory concerns since early childhood. In 1971, at age 23, I began taking megadose nutrients, which immediately made a difference. Yet at times I still suffered—especially during the grass pollen season.

Megadose ASC was especially helpful to me, but still did not give me complete relief. In 1986, I added QRC to my regimen. This brought much more relief, but still not total. In 1988, I used a QRC/bromelain/magnesium ASC formula that finally brought the relief I needed. For the past 16 years my sensitivity to environmental factors have been almost completely controlled through regular use of that combination. On the rare occasion I might still have a reaction, taking an “attack” dose of three to six capsules at once will usually quickly halt the reaction. I find the QRC/ASC/bromelain combination to be far more effective than any conventional remedy I’ve ever tried, without their nasty side effects.

Cautions

QRC, bromelain and magnesium ASC are all generally safe compounds. However, anyone allergic to bee stings, olive tree pollen or pineapple should probably avoid bromelain.⁹ Anyone with a history of serious heart palpitations should limit bromelain intake to 460 mg/day.⁹ Although magnesium ASC is generally more “gut friendly” than ascorbic acid, sensitive individuals still might experience gas, diarrhea or gut cramping from high dose magnesium ASC. Taking QRC/bromelain/magnesium ASC with food should reduce the risk of gut effects, although for rapid and maximum environmental sensitivity relief, taking them on an empty stomach is best.

Dosage

How much QRC/bromelain/magnesium ASC to take depends on one’s sensitivity situation. Those with only mild or occasional environmental sensitivities might only need one capsule three or four times daily of a formula providing 1,000 mg QRC, 300 mg (720 GDU) bromelain, and 664 mg ASC per three capsules. For those with severe environmental sensitivities, or during a certain season, it may be necessary to take two or three capsules four to six times daily. During a severe attack it may be necessary to take up to six capsules to halt the attack. For those who have no trouble taking high dose vitamin C, taking extra vitamin C may increase the anti-sensitivity effect. For those wanting to support respiratory health, adding four fish oil caps/day may enhance the protective effect.

References

1. “Quercetin” (Monograph) Alt Med Rev 3 (1998): 140-43.

2. Leighton, T. Univ. Calif. Berkeley Quercetin Project, preliminary report, 1988.

3. Stavric, B. “Quercetin in our diet: from potent mutagen to probable anticarcinogen: Clin Biochem 27 (1994): 245-48.

4. Murray, M. Encyclopedia of Nutritional Supplements. Roseville, CA: Prima Pub.;1996:320.

5. Pearce, F. et al “Mucosal mast cells III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells” J Allergy Clin Immunol 73 (1984):819-23.

6. Middleton, E. et al “ Quercetin: an inhibitor of antigen-induced human basophil histamine release” J Immunol 127 (1981):546-50.

7. Foreman, J. “Mast cells and the actions of flavonoids” J Allergy Clin Immunol 73 (1984):769-73.

8. Middleton, E. et al “ The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer” Pharmacol Rev 52 (2000):673-751.

9. Kelly, G. “Bromelain: A literature review and discussion of its therapeutic applications” Alt Med Rev 1 (1996): 243-57.

10. Taussig, S. “ The mechanism of the physiological action of bromelain” Med Hypoth 6 (1980):99-104.

11. Shoskes, D. et al “Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial” Urol 54 (1999):960-63.

12. Murray, op. cit. 329.

13. Johnston, C. et al “ Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis” J Am Coll Nutr II (1992):172-76.

14. Jellin, J. et al Pharmacist’s Letter / Prescriber’s Letter Natural Medicines Comprehensive Database. 5th ed. Stockton, CA: Therapeutic Research Faculty; 2003:224.

15. Murray, op. cit. 162.

16. Castillo, M. et al “The effects of the bioflavonoid quercetin on squamous cell carcinoma of head and neck origin” Am J Surg 158 (1989):351-55.

17. Verma, A. et al “Inhibition of 7, 12- dimethylbenz(a) anthracene- and N-nitrosomethylurea- induced rat mammary cancer by dietary flavonol quercetin” Cancer Res 48 (1988):5754-58.

18. Hofmann, J. et al “Enhancement of the antiproliferative effect of cis-diamminedichloroplatinum (II) and nitrogen mustard by inhibitors of protein kinase C” Int J Cancer 42 (1988): 382-88.

19. South, J “Resveratrol and quercetin: anti heart attack and anticancer dynamic duo” www.antiaging-systems.com/extract/resveratrol.htm.

20. Hertog, M. et al “Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study” Lancet 342 (1993): 1007-11.