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	Curcumin - Turmeric Extract	Darrell Miller	8/19/05
	Quercetin and Bromelain - for better health.	Darrell Miller	7/4/05

Date: August 19, 2005 12:47 PM
Author: Darrell Miller (dm@vitanetonline.com)
Subject: Curcumin - Turmeric Extract

Curcumin

Turmeric- History and Traditional Usage

Native to Southeast Asia, Curcuma longa is a tall
tropical shrub with large oblong leaves and pale yellow flowers.
The genus “Curcuma” belongs to the Zingiberaceae family, which
includes ginger.1 The plant possesses a large root structure
with fleshy, bulbous underground parts called “rhizomes.” These
rhizomes, known as turmeric root, are harvested at maturity,
dried and cured for commercial use. Chemical analysis shows that
dried turmeric contains essential and volatile oils, with a
curcuminoid content of 2.5 to 5.0 %.2

In addition to its
popularity as a spice, turmeric is used as a dye for cloth and
coloring agent in foods and cosmetics, thanks to its rich yellow
color. Turmeric also serves as a preservative, probably owing to
the antioxidant and antimicrobial properties of curcumin.
Extracts of Curcuma longa have demonstrated in vitro
antibacterial and anti-fungal effects.3

Turmeric is named in
ancient Ayurvedic and Chinese herbal texts as a traditional folk
remedy. Historically, turmeric was used externally for wounds,
and sprains, and internally for digestive complaints,
rheumatism, liver disorders, coughs and colds.4
Benefits

Protects cells and tissues by fighting free radicals.*

Supports joint function*

The numerous beneficial
effects attributed to turmeric stem in large measure from the
antioxidant properties of curcumin. Antioxidants neutralize free
radicals, which are highly unstable molecules that can damage
cellular structures through abnormal oxidative reactions.
Curcumin is a potent “scavenger” of the superoxide radical, a
free radical that initiates potentially harmful oxidative
processes such as lipid peroxidation.5 Through this activity,
curcumin has been shown to protect skin cells from the injurious
effect of nitroblue tetrazolium, a toxin that generates
superoxide radicals. Curcumin also increases survival of cells
exposed in vitro to the enzyme hypoxanthine/xanthine oxidase,
which stimulates superoxide and hydrogen peroxide production.
Curcumin itself is not toxic to cells, even at high
concentrations. Pure curcumin was shown to be less protective
than a mixture of curcuminoids, indicating a possible synergism
among curcuminoids.6 Because free radicals are involved in aging
and exert harmful effects on skin, these results suggest
curcumin may help slow skin aging.

Curcumin demonstrates
several other in vitro effects linked to free radical
scavenging. Curcumin scavenges nitric oxide, a compound
associated with the body’s inflammatory response.7 Pure curcumin
and turmeric extracts protect red blood cells from lipid
peroxidation induced by hydrogen peroxide.8 Curcumin has been
shown to protect DNA from oxidative damage, inhibit binding of
toxic metabolites to DNA, and reduce DNA mutations in the Ames’
test.9 Although additional studies suggest an anticarcinogenic
effect of curcumin, through protection of DNA,10 one in vitro
study found that curcumin induced DNA damage in human gastric
mucosal cells.11 It is speculated that curcumin may act as a
pro-oxidant in the presence of transition metal ions such as
copper and iron. (This is true for other antioxidants, including
vitamin C.) Curcumin also demonstrates in vitro inhibition of
COX-I and COX-II enzymes, which are involved in the inflammatory
reaction.12 Together these results strongly suggest that
curcumin is a potent bioprotectant with a potentially wide range
of therapeutic applications.

Animal studies- In vivo protective effects

Through its free radical scavenging
properties, curcumin has shown bioprotective effects in animals.
In one study, rats were treated with isoproterenol, a chemical
that causes cardiac hypertrophy (enlargement of the heart) due
to abnormal collagen metabolism. Co-treatment with curcumin
reversed the degradation of collagen and cardiac hypertrophy
induced by isoproterenol.13 Curcumin protects mice from
detrimental effects of radiation, by stabilizing the glyoxalase
system, a biological system that regulates cell division.14
Curcumin protects livers of rats from the damaging effects of
carbon tetrachloride (CCl4), a potent hepatoxin that injures the
liver via its free radical metabolite, CCl3.15,16 Curcumin
protected rats from alcohol-induced brain damage, in a study in
which oral administration of curcumin reversed lipid
peroxidation, reduced levels of free-radical metabolites and
increased levels of glutathione, a major physiologic
antioxidant.17 Curcuma longa extracts have shown
anti-inflammatory effects in rats.18

Human Trials

Curcumin exhibits free-radical scavenging ability when
administered to humans. In an open trial (uncontrolled), 18
healthy individuals ranging in age from 27 to 67 years consumed
a Curcuma longa extract, at a dose supplying 20 mg curcuminoids,
for 45 days. Before and after blood tests showed a statistically
significant decrease in lipid peroxides.19 Preliminary trials
have tested the anti-inflammatory action of curcumin, with
results that verify the traditional use of turmeric as an
anti-rheumatic herb. In a short-term double-blind, cross-over,
comparative study, 18 people received curcumin (1200 mg daily)
or phenylbutazone for two week periods. Both curcumin and
phenylbutazone produced measurable improvements in joint
flexibility and walking time. The subjects reported results only
with phenylbutazone, which may be explained by the short
duration of the trial.20 In a small placebo-controlled trial
comparing curcumin to phenylbutazone, 45 patients with
post-operative inflammation received curcumin, phenylbutazone or
placebo. The anti-inflammatory effects of curcumin and
phenylbutazone were comparable and superior to placebo.21
Curcumin has not been found to produce an analgesic (pain
relieving) effect.

Bioperine-Nature’s Absorption Enhancer
Boosts Curcumin Absorption*

Traditional Ayurvedic herbal
formulas often include black pepper and long pepper as
synergistic herbs. The active ingredient in both black pepper
and long pepper is the alkaloid, piperine. Experiments carried
out to evaluate the scientific basis for the use of peppers have
shown that piperine significantly enhances bioavailability when
consumed with other substances.22 Several double-blind clinical
studies have confirmed that Bioperine® increases absorption of
nutrients.23

Curcumin is poorly absorbed in the intestinal
tract, limiting its therapeutic effectiveness. Oral doses are
largely excreted in feces, and only trace amounts appear in the
blood. Concomitant administration of 20 mg of piperine with 2
grams of curcumin increases the bioavailability of curcumin by
2000%.24

Scientific References

1. Majeed, M., Badmaev,
V., Shivakumar, U., Rajendran, R. Curcuminoids. 1995.
Piscataway, NJ: NutriScience Publishers.
2. Srimal, R.C.
Turmeric: a brief review of its medicinal properties.
Fitoterapia 1997;68(6):483-93.
3. Ammon, H.P.T., Wahl, M.A.
Pharmacology of Curcuma longa. Planta Medica 1991;57:1-7.
4.
Snow, J.M. Herbal Monograph: Curcuma longa L. (Zingiberaceae).
The Protocol Journal of Botanical Medicine, Autumn
1995:43-46.
5. Rao, N.S., Rao, M.N.A. Free radical scavenging
activity of curcuminoids. Arzneim.-Forsch./Drug Res.
1996;46(2):169-171.
6. Bonté. F. et al. Protective effect of
curcuminoids on epidermal skin cells under free oxygen radical
stress. Planta Medica 1997;63:265-66.
7. Rao, S., Rao, M.N.A.
Nitric oxide scavenging by curcuminoids. J Pharm. Pharmacol.
1997;49:105-7.
8. Lalitha, S., Selvam, R. Prevention of
H2Os-induced red blood cell lipid peroxidation by aqueous
extracted turmeric. Asia Pacific J Clin Nutr
1999;8(2):113-14.
9. Deshpande, S.S., Maru, G.B. Effects of
curcumin on the formation of benzo[a]pyrene derived DNA adducts
in vitro. Cancer Letters 1995;96:71-80.
10. Subramanian, M., et
al. Diminution of singlet oxygen-induced DNA damage by curcumin
and related antioxidants. Mutation Research
1994;311:249-55.
11. Blasiak, J., Trzeciak, A., Kowalik, J.
Curcumin damages DNA in human gastric mucosa cells and
lymphocytes. Journal of Environmental Pathology, Toxicology and
Oncology 1999;18(4):271-76.
12. Ramsewak, R.S., DeWitt, D.L.,
Nair, M.G. Cytotoxicity, antioxidant, and anti-inflammatory
activities of Curcumins I-III from Curcuma longa. Phytomedicine
2000;7(4):303-308.
13. Nirmala, C. Anand, S., PuvanaKrishnan,
R. Curcumin treatment modulates collagen metabolism in
isoproterenol induced myocardial necrosis in rats. Molecular and
Cellular Biochemistry 1999;197:31-37.
14. Choudhary, D.,
Chandra, D. Kale, R.K. Modulation of radioresponse of glyoxalase
system by curcumin. Journal of Ethnopharmacology
1999;64:1-7.
15. Park, E-J. et al. Protective effect of
curcumin in rat liver injury induced by carbon tetrachloride. J
Pharm. Pharmacol. 2000;52:437-40.
16. Deshpande, U.R. et al.
Protective effect of turmeric (Curcuma longa L.) extract on
carbon tetrachloride-induced liver damage in rats. Indian
Journal of Experimental Biology 1998;36:573-77.
17.
RajaKrishnan, V. et al. Neuroprotective role of curcumin from
Curcuma longa on ethanol-induced brain damage. Phytotherapy
Research 1999;13:571-74.
18. Arora, R.B. Basu, N., Kapoor, V.,
Jain, A.P. Anti-inflammatory studies on Curcuma longa
(Turmeric). Indian J Med Res 1971;59(8):1289-95.
19.
Ramirez-Bosca, A. et al. Antioxidant curcuma extracts decrease
the blood peroxide levels of human subjects. Age
1995;18:167-69.
20. Deodhar, S.D., Sethi, R. Srimal. R.C.
Preliminary study on antirheumatic activity of curcumin
(diferoyl methane). Indian J Med Res 1980;71:632-34.
21.
Satoskar, R.R., Shah, S J. Shenoy, S.G. Evaluation of
anti-inflammatory property of curcumin (diferoyl methane) in
patients with postoperative inflammation. International Journal
of Clinical Pharmacology, Therapy and Toxicolgy
1986;24(12):651-54.
22. Atal, C., Zutshi, U., Rao, P.
Scientific evidence on the role of Ayurvedic herbals on
bioavailability of drugs. Journal of Ethnopharmacology
1981;4:229-232.
23. Bioperine®–Nature's Bioavailability
Enhancing Thermonutrient. Executive Summary. 1996; Sabinsa
Corporation, Piscataway, N.J.
24. Shoba, G., et al. Influence
of piperine on the pharmacokinetics of curcumin in animals and
human volunteers. Planta Medica 1998;64(4):353-6.

© 2002
Doctor's Best, Inc. Revised 8/13/02

*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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Date: July 04, 2005 10:28 AM
Author: Darrell Miller (dm@vitanetonline.com)
Subject: Quercetin and Bromelain - for better health.

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.

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

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