Quercetin is a potent and versatile flavonoid and phytonutrient.
Bromelain is an enzyme complex derived from the pineapple stem. (Note:
G.D.U. stands for “Gelatin-Digesting Units,” a commonly accepted measure of
enzyme activity.)
Benefits
Down-regulates the Body’s
Response to Environmental Challenges
Quercetin is a member of the flavonoid family, a diverse group of low
molecular-weight compounds found throughout the plant kingdom. Flavonoids
exhibit numerous biological activities, many of which are directly beneficial to
human health. Quercetin, which belongs to the “flavonol” subgroup, is one of the
most versatile and important flavonoids.
Quercetin has a broad range of activity, much of which stems from its
interaction with calmodulin, a calcium-regulatory protein.1
Calmodulin transports calcium ions across cellular membranes, initiating
numerous cellular processes. Quercetin appears to act as a calmodulin
antagonist.1 Through this mechanism, quercetin functions
at the cell-membrane level with a membrane-stabilizing action.2 Quercetin inhibits calmodulin-dependent enzymes present at cell membranes
such as ATPases and phospholipase, thereby influencing membrane permeability.3
Quercetin affects other calmodulin-dependent enzymes that control various
cellular functions, including the secretion of histamine from mast cells.4
A number of investigations have corroborated quercetin’s ability to
reduce histamine secretion from mast cells in various tissues, and also from
basophils.5,6,7,8,9,10
Quercetin modifies the body’s response to antigenic substances.*
Suppression of histamine secretion from mast cells is one of quercetin’s most
clinically important effects. Quercetin acts on ATPase at the membranes of
histamine-containing granules in mast cells.3 Mast-cell
degranulation and subsequent release of histamine into the bloodstream is an
integral part of the body’s response to environmental challenges.
Maintains Tissue Comfort by Regulating Enzymes*
Quercetin’s enzyme-inhibiting action extends to enzymes such as phospholipase,
which catalyzes the release of arachidonic acid from phospholipids stored in
cell membranes.4,10 Arachidonic acid serves as the key
substrate for substances such as thromboxanes, inflammatory prostaglandins and
leukotrienes. In addition, quercetin inhibits the enzymes cyclooxygenase and
lipoxygenase, which catalyze the conversion of arachidonic acid into its
metabolites.4,10,11,12 Reducing levels of these
metabolites, as well as histamine levels, is beneficial in maintaining the
normal comfort level of body tissues and structures.
Quercetin has also been shown to limit the function of adhesion molecules on
endothelial cells.13 Adhesion molecules are involved in
physiologic processes that influence tissue comfort.13
Bromelain is a complex substance derived from the pineapple stem largely
composed of proteolytic (protein-digesting) enzymes. Bromelain acts by a variety
of mechanisms to help maintain tissues in a normal state of comfort.14,15 Several investigators, including Taussig16 and Ako,
et. al.,17 have presented evidence that bromelain is a
fibrinolytic agent, i.e., it induces the breakdown of fibrin, a plasma protein
that blocks tissue drainage. The generally accepted mechanisms involve direct
proteolysis of fibrin by bromelain and activation of plasmin, a serum protease.16
Plasmin acts on fibrinogen (the precursor to fibrin), forming peptides which
stimulate PGE1, a prostaglandin that helps maintain tissue comfort.16
Helps Maintain Health of Blood Vessels by
Modifying Oxidation of LDL Cholesterol* — Quercetin’s Antioxidant Action
Quercetin is a versatile and effective antioxidant that scavenges a variety of
free-radicals such as hydroxyl and lipid peroxy radicals.18 Quercetin also chelates ions of transition metals such as iron, which can
initiate formation of oxygen free radicals.18 LDL
cholesterol is vulnerable to oxidation by lipid peroxides. Oxidized LDL is
absorbed by macrophages and arterial endothelial cells, leading to the formation
of “foam cells,” and eventually plaque deposits, in arterial walls. Quercetin
has been shown to protect LDL from oxidation, both by lipid peroxides and
transition metal ions.19
Helps Maintain Normal Blood Viscosity*
Quercetin inhibits blood platelet aggregation (clumping), by potentiating PGI2,
an anti-aggregatory prostaglandin, and by raising platelet cyclic AMP levels.20
Human studies have revealed that bromelain also reduces platelet aggregation.21
These properties qualify both quercetin and bromelain as valuable dietary
ingredients for maintaining cardiovascular health.*
Bromelain May Enhance Quercetin Absorption
In addition to the actions described above that support the effects of quercetin,
bromelain may also assist the absorption of quercetin in the G.I. tract. (Quercetin
is generally believed to be poorly absorbed, although a recent study by Hollman
et. al.,22 which concluded that humans do in fact absorb
appreciable amounts of quercetin, contradicts this assumption.) Studies have
shown that bromelain enhances absorption of antibiotics, presumably by
increasing permeability of the gut wall.23, 24 Given that
quercetin is a low molecular-weight compound, it is plausible that
simultaneously ingested bromelain likewise enhances quercetin absorption.
Safety
Suggested Use:
1 or 2 capsules three times daily, preferably 30 to 60 minutes before meals.
Does Not Contain: milk, egg, wheat, corn, sugar, sweeteners, starch,
salt, or preservatives.
Scientific
References
1. Nishino, H., et. al., “Quercetin interacts with calmodulin, a calcium
regulatory protein.” Experientia 1984;40:184-5.
2. Busse, W.W., Kopp, D.E., Middleton, E., “Flavonoid modulation of human
neutrophil function.” J. Allergy Clin. Immunol. 1984;73:801-9.
3. Havsteen, B,. “Flavonoids, a class of natural products of high
pharmacological potency.” Biochemical Pharmacology 1983;32(7):1141-48.
4. Middleton, E., “The Flavonoids.” Trends in Pharmaceutical Sciences
1984;5:335-8.
5. Otsuka, H. et. al., “Histochemical and functional characteristics of
metachromatic cells in the nasal epithelium in allergic rhinitis: Studies of
nasal scrapings and their dispersed cells.” J. Allergy Clin.
Immunol.1995;96:528-36.
6. Fox, C.C., et. al., “Comparison of human lung and intestinal mast cells.” J.
Allergy and Clin. Immunol. 1988;81:89-94.
7. Pearce, F.L., Befus, A.D., Bienenstock, J., “Mucosal mast cells III. Effect
of quercetin and other flavonoids on antigen-induced histamine secretion from
rat intestinal mast cells.” J. Allergy and Clin. Immunol. 1984;73:819-23.
8. Middleton, E. Drzewiecki, G., Krishnarao, D., “Quercetin: an inhibitor of
antigen-induced human basophil histamine release.” J. of Immunology
1981;127(2):546-50.
9. Bennett, J.P., Gomperts, B.D., Wollenweber, E.,“ Inhibitory effects of
natural flavonoids on secretion from mast cell and neutrophils.” Arzneim. Forsch/Drug
Res. 1981;31(3):433-7.
10. Middleton, E. Drzewiecki G., “Naturally occurring flavonoids and human
basophil histamine release.” Int. Archs Allergy appl. Immun. 1985;77:155-7.
11. Yoshimoto, T. et. al., “Flavonoids: potent inhibitors of arachidonate
5-lipoxygenase.” Biochemical and Biophysical Research Communications
1983;116(2):612-18.
12. Della Loggia, R., et. al., “Anti-inflammatory activity of benzopyrones that
are inhibitors of cyclo- and lipo-oxygenase.” Pharmacological Research
Communications 1988; 20(Supp. V):91-94.
13. Middleton, E., Suresh, A., “Quercetin inhibits lipopolysaccharide-induced
expression of endothelial cell intracellular adhesion molecule-1.” Int. Arch.
Allergy Immunol. 1995;107:435-6.
14. Taussig, S.J., Batkin, S., “Bromelain, the enzyme complex of pineapple (Ananas
comosus) and its clinical application.” An Update Journal of Ethnopharmacology
1988;22:191-203.
15. Lotz-Winter, H., “On the pharmacology of bromelain: An update with special
regard to animal studies on dose-dependent effects.” Planta Medica
1990;56:249-53.
16. Taussig, S.J., “The mechanism of the physiological action of bromelain”
Medical Hypothesis 1980;6:99-104.
17. Ako, H. Cheung, A.H.S., Matsuura, P.K., “Isolation of a fibrinolysis
activator from commercial bromelain.” Arch. Int. Pharmacodyn. 1981;284:157-67.
18. Afanas’ev, I.B. et. al., “Chelating and free radical scavenging mechanisms
of inhibitory action of rutin and quercetin in lipid peroxidation.” Biochemical
Pharmacology 1989;38(11):1763-69.
19. De Whalley, C.V., “Flavonoids inhibit the oxidative modification of low
density lipoproteins by macrophages.” Biochemical Pharmacology 39(11):1743-50.
20. Beretz, A. Stierle, A., Anton, R. Cazenave, J., “Role of cyclic AMP in the
inhibition of human platelet aggregation by quercetin, a flavonoid that
potentiates the effect of prostacyclin.” Biochemical Pharmacology
1981;31(22):3597-600.
21. Heinicke, R. van der Wal, L. Yokoyama, M., “Effect of bromelain (Ananase®)
on human platelet aggregation. ”Experientia 1972;28(7):844.
22. Hollma, P. et. al., “Absorption of dietary quercetin glycosides and
quercetin in healthy ileostomy volunteers.” Am. J. Clin. Nutr. 1995;62:1276-82.
23. Giller, F.B., “The effects of bromelain on levels of penicillin in the
cerebrospinal fluid of rabbits.” A., J. Pharm. 1962;134:238-244.
24. Bodi, T., “The effect of oral bromelain on tissue permeability to
antibiotics and pain response to bradykinin; double-blind studies on human
subjects.” Clin. Med. 1965;72:61-65.
