522/PROBIOTICS PDR FOR NUTRITIONAL SUPPLEMENTS

Hilton E, Isenberg HD, Alperstein P, et aI. Ingestion of yogurtcontaining Lactobacillus acidophilus. Ann Int Med. 1992;116:353-357.

Jahn HU, Ullrich R, Schneider T, et aI. Immunological andtrophical effects of Saccharomyces boulardii on the smallintestine in healthy human volunteers. Digestion. 1996; 57:95-104.

Kimoto H, Kurisaki MN, Tsuji, et aI. Lactococci as probioticstrains: adhesion to human enterocyte-like Caco-2 cells andtolerance to low pH and bile. Leu Applied Microbiol. 1999;29:313-316.

Kirjavainen PV, Ouwehand AC, Isolauri E, Salminen SJ. Theability of probiotic bacteria to bind to human intestinal mucus.FEMS Microbiol Leu. 1998; 167:185-189.

Lactobacillus GG. Nutrition Today. 1996; 31:IS-52S.

Lin M-Y, Yen C-L. Antioxidative ability of lactic acid bacteria.J Agric Food Chem. 1999; 47:1460-1466.

Mack DR, Michail S, Wei S, et aI. Probiotics inhibitenteropathogenic E. coli adherence in vitro by inducingintestinal mucin gene expression. Am J. Physio/. 1999; 276(4 PtI):G941-G950.

Majamaa H, Isolauri E. Probiotics: a novel approach in themanagement of food allergy. J Allergy Clin Immunol. 1997;99: 179-185.

Matilla-Sandholm T, Blum S, Collins JK, et aI. Probiotics:towards demonstrating efficacy. Trends Food Sci Technol. 1999;10:393-399.

Mattila-Sandholm T. The PROBDEMO project: demonstrationof the nutritional functionality of probiotic foods. Trends FoodSci Techno/. 1999; 10:385-386.

McFarland LV, Surawicz CM, Greenberg RN, et aI. Arandomized placebo-controlled trial of Saccharomyces boulardiiin combination with standard antibiotics for Clostridium difficiledisease. JAMA. 1994; 271:1913-1918.

Metchnikoff E. The Prolongation of Life: Optimistic Studies.The English translation. Mitchell PC, ed. 1908; New York:GP6

O'Brien J, Crittenden R, Ouwehand AC, Salminen S. Safetyevaluation of probiotics. Trends Food Sci Techno/. 1999;10:418-424.

Ouwehand AC, TOikko S, Kulmala J, et aI. Adhesion ofinactivated probiotic strains to intestinal mucus. Leu AppliedMicrobio/. 2000; 31:82-86.

Pletinex M, Legein J, Vandenplas Y. Fungemia withSaccharomyces boulardii in a I-year old girl with protracteddiarrhea. J Pediatr Gastroenterol Nutr. 1995; 21:113-115.

Saavedra J. Probiotics and infectious diarrhea. Am JGastroentero/. 2000; 95 (I Suppl):S 16-S18.

Saxelin M, Grenov B, Svensson U, et aI. The technology ofprobiotics. Trends Food Sci Technol. 1999; 10:387-392.

Shortt C. The probiotic century: historical and currentperspectives. Trends Food Sci Techno/. 1999; 10:411-417.

Symposium: Probiotic Bacteria: Implications for Human Health.J Nutr. 2000; 130:382S-409S.

Todorov S, Onno B, Sorokine 0, et aI. Detection andcharacterization of a novel antibacterial substance produced byLactobacillus plantarum ST31 isolated from sourdough. Int JFood Microbiol. 1999; 48:167-177.

Turner DL, Brennan L, Meyer HE, et aI. Solution structure ofplantaricin C, a novel lantibiotic. Eur J Biochem. 1999; 264:833-839.

Vaughan EE, Heilig HGHJ, Zoetendal EG, et aI. Molecularapproaches to study probiotic bacteria. Trends Food SciTechnology. 1999; 10:400-404.

Wollowski I, Ji S-T. Bakalinsky AT, et aI. Bacteria used forthe production of yogurt inactivate carcinogens and preventDNA damage in the colon of rats. J Nutr. 1999; 129:77-82.

PropolisDESCRIPTION

Propolis, also known as bee glue and bee propolis, is abrownish resinous substance collected by bees, mainly frompoplar and conifer buds, and used to seal their hives.Because of antimicrobial properties of propolis, it helps keephives free of germs. Propolis has a long history of use in folkmedicine and was even used as an official drug in London inthe 1600s. Over time, propolis has been used for manypurposes and marketed as lozenges, cough syrups, tooth-pastes, mouth rinses, lipsticks, cosmetics and even for thevarnishing of Stradivarius violins. It appears to haveantimicrobial and anti-inflammatory activities.

The composition of propolis is variable, depending on thelocale and variety of trees and other plant species used forthe collection. For example, unique constituents have beenidentified in propolis collected in Cuba and Brazil. The mainchemical classes found in propolis are flavonoids, phenolicsand terpenes. The flavonoids include quercetin, apegenin,galangin, kaempferol, luteolin, pinocembrin, pinostrobin andpinobanksin. The phenolic ester (caffeic acid phenethyl esteror CAPE)' present in propolis is receiving much attention inthe medical research community because of its potential forthe treatment of a number of disorders, including spinal cordinjury. Most of the substances in propolis are poorly solublein. water.

ACTIONS AND PHARMACOLOGY

ACTIONS

A list of possible actions of propolis includes: antibacterial,antifungal, antiviral (including anti HIV-I activity), antioxi-dant, anticarcinogenic, antithrombotic and immunomodula-tory.

SUPPLEMENT MONOGRAPHS PROPOLIS /523

MECHANISM OF ACTION

The mechanism of the possible actions of propolis may beunderstood by reviewing research findings on some of theindividual compounds found in it. It is difficult to study themechanism of actions of more than one compound at a time.Therefore, the following descriptions apply only to singlecompounds. The contribution of any single compound to thepossible action of such a complex substance as propolis isdifficult to know.

Caffeic acid phenethyl ester (CAPE) inhibits the lipoxygen-ase pathway of arachidonic acid, resulting in anti-inflamma-tory activity. CAPE is also known to have anticarcinogenic,antimitogenic and immunomodulatory properties. CAPE hasbeen found to completely inhibit the activation of the nucleartranscription factor NF-Kappa B by tumor necrosis factor(TNF), as well as by other pro-inflammatory agents. Theinhibition of NF-Kappa B activation may provide themolecular basis for its immunomodulatory, anticarcinogenic,anti-inflammatory and antiviral activities. It is possible thatCAPE exerts its effects by inhibiting reactive oxygen species(ROS) production. ROS are known to playa major role inthe activation of NF-Kappa B.

Compounds in propolis found to have antibacterial activityinclude a polyisoprenylated benzophenone, galangin, pino-banksin and pinocembrin. The exact mechanism of antimi-crobial action of these compounds is not known.

INDICATIONS AND USAGE ,

There is evidence that propolis has some broad antimicrobialactivity and that it may have anti-inflammatory effects thatcould make it useful in the treatment of some forms ofarthritis, among other disorders. There is also some evidenceof anti-cancer activity.

RESEARCH SUMMARY

In vitro and animal studies of propolis and derivativeconstituents have shown anti-bacterial, anti-viral and anti-fungal effects. It shows activity in culture against a broadspectrum of pathogens, including influenza and herpesviruses, as well as HIV and various fungal and bacterialorganisms.

In a study of school children, an aqueous propolis extractwas judged effective in reducing the incidence and intensityof acute and chronic rhinopharyngitis. In another studyinvolving 10 volunteers, it exerted activity against oralbacteria. A Cuban study concluded that propolis is moreeffective than tinidazole against giardia.

Propolis has a high concentration of caffeic acid esters thatsome believe may give it some antitumor properties. In twostudies, extracts of propolis fed to rats have inhibitedazoxymethane-induced colonic tumors.

In vitro studies have shown propolis-related anti-inflamma-tory effects. Various extracts of propolis have also shownanti-inflammatory activity in animal models, particularlyagainst adjuvant-induced arthritis.

More research is needed to further explore these preliminaryfindings.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICA TIONS

Propolis is contraindicated in those who are allergic orhypersensitive to any of its components.

PRECAUTIONS

Pregnant women and nursing mothers should avoid usingpropolis supplements.

ADVERSE REACTIONS

There are reported adverse reactions in those using topicalpreparations of propolis. These reactions are manifested as adermatitis. There are reports of hypersensitivity reactions toingested propolis, including rhinitis, conjunctivitis, skinrashes and bronchospasm.

OVERDOSAGE

No reported overdosage of propolis.

DOSAGE AND ADMINISTRATION

No typical dose. Propolis is available in several differentpreparations, including lozenges, tablets, creams, gels, mouthrinses, toothpastes and cough syrups.

LITERATURE

Burdock GA. Review of the biological properties and toxicityof bee propolis (propolis). Food Chern Toxieo/. 1998; 36:347-363.

Chopra S, Pillai KK, Husain SZ, Giri OK. Propolis protectsagainst doxorubicin-induced myocardiopathy in rats. Exp MolPathol. 1995; 62: 190-198.

EI-Ghazaly MA, Khayyal MT. The use of aqueous propolisextract against radiation-induced damage. Drugs Exp C/in Res.1995; 21:229-236.

Grange JM, Davey RW. Antibacterial properties of propolis(bee glue). l.R Soc Med. 1990; 83:159-160.

Harish Z, Rubinstein A, Golodner M, eI al. Suppression ofHIV-I replication by propolis and its immunoregulatory effect.Drugs Exp C/in Res. 1997; 23:89-96.

Khayyal MT, el-Ghazaly MA, el-Khatib AS. Mechanisminvolved in the anti-inflammatory effect of propolis extract.Drugs Exp C/in Res. 1993; 19:197-203.

Kujumgiev A, Tsverkova I, Serkedjieva Y, et al. Antibacterial,antifungal and antiviral activity of propolis of differentgeographic origins. 1 Ethnopharmaeol. 1999; 64:235-240.

Ledon N, Casaco A, Gonzales R, et al. Antipsoriatic, anti-inflammatory and analgesic effects of an extract of red propolis.Chung Kuo Yao Li Hsueh Pao. 1997; 18:274-276.

524 I PROPOLIS PDR FOR NUTRITIONAL SUPPLEMENTS

Un SC, Lin YH, Chen CF, et aI. The hepatoprotective andtherapeutic effects of propolis ethanol extract on chronicalcohol-induced liver injuries. Am J Chin Med 1997; 25:325-332.

Matsuno T, Jung SK, Matsumoto Y, et aI. Preferentialcytotoxicity to tumor cells of 3, 5-diprenyl-4-hydroxycinnamicacid (artipillin C) isolated from propolis. Anticancer Res. 1997;17(5A):3565-3568.

Mirzoeva OK, Calder Pc. The effect of propolis and itscomponents on eicosanoid production during the inflammatoryresponse. ProstaglandinsLeukot Essent Fatty Acids. 1996;55:441-449.

Mirzoeva OK, Grishanin RN, Calder PC. Antimicrobial actin ofpropolis and some of its components: the effects on growth,membrane potential and motility of bacteria. Microbiol Res.1997; 152:239-246.

Natarajan K, Singh S, Burke TR Jr, et aI. Caffeic acidphenethyl ester is a potent and specific inhibitor of activation ,of nuclear transcription factor NF-Kappa B. Proc Natl AcadSci. 1996; 93:9090-9095.

Ozturk F, Kurt E, Cerci M, et aI. The effect of propolis extractin experimental chemical corneal injury. Ophthalmic Res. 2000;32: 13-18.

Park EH, Kahng JH. Suppressive effects of propolis in ratadjuvant arthritis. Arch Pharm Res. 1999; 22:554-558.

Rao CY, Desai D, Simi B, et aI. Inhibitory effect of caffeicacid esters on azoxymethane-induced biochemical change andaberrant crypt foci formation in rat colon. Cancer Res. 1993;53:4182-4188.

PsylliumDESCRIPTION

In 1998, the Food and Drug Administration (FDA) issued itsfinal rule allowing health claims to be made on the labels offoods containing soluble fiber from whole oats (see OatBeta-D-Glucan), noting that these foods, in conjunction witha diet low in saturated fat and cholesterol, may reduce therisk of heart disease. Shortly afterward, the FDA amendedthis to include the soluble fiber psyllium in the health claim.The FDA requires that there be at least 1.7 grams of solublefiber from psyllium seed husk per serving in any food forwhich this health claim is made. To achieve heart-healthbenefits, the consumption of 7 grams of soluble fiber frompsyllium are required.

.

Psyllium or Plantago ovala Forsk is an annual plant grownprimarily in India, southern Europe and the United States.Psyllium is cultivated primarily for its use as a laxative or asa dietary fiber ingredient in foods, such as ready-to-eatcereals. It is also known as blond psyllium, Indian psylliumand plantain. Although the seed alone contains the bioactive

mucilage polysaccharide, the refined psyllium seed husk,known as the Ispaghula husk, is the psyllium componentprincipally used as the soluble fiber source for laxatives,ready-to-eat cereals and nutritional supplements.

The term psyllium is used interchangeably for the seed husk,the seed and the plant. Psyllium seed husk is comprisedprimarily of xylans. Xylans are polysaccharides built fromthe five-carbon sugar D-xylose. Xylans in psyllium seedhusk occur in association with cellulose. The soluble fiberderived from psyllium seed husk is also known as psylliumhydrophilic mucilloid, psyllium hydrocolloid and psylliumseed gum. It is a white to cream-colored, slightly granularpowder with a slight acid taste.

ACTIONS AND PHARMACOLOGY

ACTIONS

Psyllium may have hypocholesterolemic, glucose-regulatoryand bowel-regulatory actions.

MECHANISM OF ACTION

The mechanism of psyllium's possible hypocholesterolemicactivity is not fully understood. The bioactive agent ofpsyllium is a soluble, viscous xylan fiber. It is thought thatthis polysaccharide stimulates the conversion of cholesterolto bile acids and that it stimulates fecal excretion of bileacids. Psyllium may also decrease the intestinal absorption ofcholesterol.

Some studies indicate that psyllium may improve glycemiccontrol in type 2 diabetics. The mechanism of the effect isunclear. Psyllium may delay the absorption of carbohydratesby increasing gastric-emptying time and/or decreasing smallintestinal transit time.

The laxative effect of psyllium is thought to be due to theswelling of psyllium from absorption of water with conse-quent increase in stool bulk and stimulation of peristalsis.

PHARMACOKINETICS

Following ingestion of psyllium, very little is digested in thesmall intestine. The psyllium polysaccharides are resistant tohydrolysis by the digestive enzymes. Some fermentation ofthe psyllium polysaccharides takes place in the largeintestine via the action of colonic bacteria. The products offermentation include the short-chain fatty acids acetate,propionate and butyrate, as well as hydrogen and carbondioxide. The short-chain fatty acids that escape colonicmetabolism are transported via the portal circulation to theliver, where they undergo metabolism.

INDICATIONS AND USAGE

The FDA allows a health claim for psyllium to the effectthat, in conjunction with a low-fat diet, it may reduce risk ofheart disease if used in adequate amounts. Numerous studieshave shown that psyllium is effective in lowering total