Supplementation to enhance the colonization of the colon with lactic acid bacteria (such as the Lactobacillus plantarum, LactobacUlus acidophilus, LactobacUlus case! and Bifidobacterium longum found in FLORASE) has been found to effectively relieve constipation in humans\

INTESTINAL PARASITES

The value of the "friendly bacteria" normally found in the human digestive tract, such as L plantarum, L. acidophUus, L. case/and B. longum is well established.

L. plantarum is actually used as protective cultures to improve microbial safety of foods. This usage comes from their secretion of "bacteriocins" which are proteins which are lethal to certain other bacteria^. L. plantarum has also been found in animal models to inhibit the translocation of bacteria from the gut to other organs (e.g., liver, lymph nodes'. Oral supplementation with L acidophUus can enhance antiinfective mechanisms of defense^. Research has suggested that one mechanism for the beneficial effects of ingesting L. acidophUus is stimulation of the production of inter-leukin-1 alpha and tumor necrosis factor-alpha, which have potent cytoci-dal and cytostatic effects on tumor cells'. The mechanisms of immune support by B. longum have been widely studied in animal models. It has been found that B. longum stimulates the immune system by enhancing the activity of natural killer cells in the spleen of rats^ and by stimulating intestinal IgA production. L. casei has been demonstrated to have an immunostimu-latory effect in human subjects by the intestinal secretion of igA and thus promoting the gut immunological barrier. FLORASE also contains lactofer-rin, which is currently the object of considerable study. Lactoferrin is the iron containing (heme) constituent of mother's milk. Lactoferrin has been shown to be an effective antibacterial agent, being found even in tears as one component of the defense of the outer eye". Supplementation with lactoferrin has been found to inhibit bacterial translocation (from the digestive tract to other organs and systems), probably due to its suppression of bacterial overgrowth.

pH/BACTERIAL IMBALANCES

Short chain fatty acids are produced by the normal metabolism of coionic lactic acid bacterial One consequence of this is the normalization of the coionic pH. Another result of active coionic colonization with lactic acid bacteria is a shift in the balance of coionic microflora in favor of healthy (gram-positive) bacteria^ . FLORASE contains true-tool igosaccharides (FOS), which have been shown to be an effective nutrient for intestinal probiotic bacteria (such an activity is sometimes called 'prebioticO. FOS is indigestible to normal human digestive enzymes, and therefore passes whole into the colon where it becomes available as a nutrient to friendly" bacteria^

1. Salminen, S. & Salminen, E. Uactu lose, lactic acid bacteria, intestinal microecology and mucosal protection" Scand I Castroenterol Suppi 1997; 222: 45-8.

2. Olasupo, W.A. "Bacteriocins of Lactobacaillus plantarum strains from fermented foods" Folia Microbiol 1996; 41: 130-136.

3. Adawi, D., et al. "Effect of Lactobacillus supplementation with and without arginine on liver damage and bacterial translocation in an acute liver injury model in the rat" Hepatologv 1997; 25:642-7.

4. Schiffrin, E.J. et al. "Immune modulation of blood leukocytes in humans by lactic acid bacteria: criteria for strain selection" Am I Clin Nutr 1997; 66: 515S-20S.

5. Rangavajhyala, N. et al. "Nonlipopolysaccharide com

PROTEASE 375K contains proprietary, highly concentrated proteolytic enzymes from Aspergillus oryzae. Proteolytic enzyme supplements taken by mouth (on an empty stomach) have been shown to be absorbed in substantial quantities into the blood to bind to serum proteins, especially alpha 2-macroglobulin, and to be delivered to sites of immune function^. One of the best established functions served by AspergUlus pro tease is in the maintenance of normal blood flow by breaking down blood clots (fibrinolysis). Years of clinical experience has shown that toxins are also removed from the blood, perhaps as a result of an overall improvement in blood flow.

WEAKENED IMMUNITY

There is a change in the conformation of (when protease is bound to it which is evident as an increase in mobility in polyacrylamide gel electrophoresis, referred to as a shift from the "slow" to the "fast" form. Accompanying this shift is a dramatic increase in the tendency of activated macrophages, fibroblasts and hepatocytes to bind the a2m complex. Moreover, a2M complexes also exhibit an increased binding of several very important cytokines (hormone-like molecules which have a powerful influence on immune cells) such as transforming growth factor-beta (TGF-P) and tumor necrosis factor-alpha (TNF-a)^5. By modulating, and potentially delivering such cytokines to sites of immune system activity, the (a2M/protease complexes which result from oral protease supplementation have a powerful immune-strengthening effect.

HORMONAL IMBALANCES

Years of clinical experience have led to the conclusion that hormonal imbalances may be helped by oral protease supplementation. The mechanism by which this takes place is not known precisely, but there is a well recognized linkage between the neuroendocrine and immune systems. It may be that correcting hormonal imbalances is the result of strengthening

IMPAIRED KIDNEY FUNCTION

• remodeling,

(1 ) Absorption of Orally Administered Enzymes MI.G. Gardner and K.-J. Steffens, eds. Springer-Verlag, Berlin, 1995.

(2) Castell J.V„ Friedrich G., Kuhn C.-S. & Poppe G.E. "Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake" Am I Physiol 1997; 273: G139-G146.

(3) Larsson L.J.; Frisch E.P.;Torneke K.; Lindblom T. & Bjork 1. "Properties of the complex between alpha 2-macroglobulin and brinase, a proteinase from Aspergillus oryzae with throm-bolytic effect" Thromb Res 1988; 49:55-68.

(4) Nouza K. "Outlooks of systemic enzyme therapy in rheumatoid arthritis and other immunopathological diseases" Acta Univ Carol FMedl 1994; 40:101-4.

(5) LaMarre J., Wollenberg G.K., Gonias S.L. & Hayes M.A. "Biology of Disease: Cytokine binding and clearance properties of proteinase-activated 02-macroglobulins" Lab Inv 1991; 65:3-14

(6) Gesualdo L, Ricanati S„ Hassa M.O., Emancipator S.N., & Lamm M.E. "Enzymolysis of glomerular immune deposits in vivo with dextranase/protease ameliorates proteinuria, hema-turia, and mesangial proliferation in murine experimental IgA nephropathy" I Clin Invest 1990; 86:715-722

(7) Moulin V. "Growth factors in skin wound healing" Eur I Cell Biol 1995; 68: 1-7.

ANTIOXIDASE provides a wide variety of antioxidants:

• Catalase — an antioxidant enzyme which converts the pro-oxidant hydrogen peroxide to water and oxygen.

• Dunaleilla — an algae rich in beta-carotene, which has a number of immune enhancing effects'. There is evidence that beta-carotene derived from dunaleilla is significantly more effective as an antioxidant in vivo than synthetic beta-carotene.

• Acerola Cherries — a rich natural source of Vitamin C and bioflavonoids, including anthocyanidins and proanthocyanidins. Vitamin C and bioflavonoids are recognized for their potent antioxidant and antiinflammatory properties. Bioflavonoids are generally found in association with Vitamin C, and they work synergistically.

• Vitamin E (natural) — probably the most intensively studied of the antioxidants, exhibits strong antioxidant activity in the body. Vitamin E is fat soluble, and its antioxidant actions occur primarily within biological membranes. The end results of its antioxidant activity include support for the immune system.

* SeaSel Kelp — a good natural source of selenium. This mineral is a vital cofactor for the enzyme glutathione peroxidase, which removes lipid hydroperoxides and acts synergistically with catalase and Cu/Zn-superoxide dismutase.

• Zinc — is effective as a membrane antioxidant".

• Querdtin — a bioflavonoid, has been shown to modify eicosanoid biosynthesis (antiprostanoid and anti-inflammatory responses). It has been found to inhibit membrane lipid peroxidation.

• Turmeric Extract — contains coumarin, which is a powerful antioxidant".

• Crape Seed Extract (Activin®) — contains concentrated procyanidolic oligomers (PCO), which are mixtures of dimers, trimers, and larger polymers of proanthocyanidins. PCO's are among the best studied and most effective bioflavonoids, based in part on their powerful antioxidant activity".

Lycopenes — the predominant carotenoid found in tomatoes. It is the most efficient scavenger of singlet oxygen (a harmful species of oxygen) among the carotenoids.

• Creen tea — is a very rich source of a variety of polyphenolic substances, including flavonols and flavonoids. Catechins are one type of flavonol, which have demonstrated exceptional antioxidant activity.

• alpha-Lipoic acid — is readily absorbed, remains functional in both its oxidized and reduced forms, has the ability to scavenge a wide variety of free radicals, and chelates metals'.

ANTIOXIDASE provides a broad spectrum of digestive enzymes including protease, amylase, lipase and cellulase to assist in the digestion of food, thereby liberating metabolic resources needed for a strong immune system.

CELLULAR DAMAGE

Cellular membranes are composed of proteins and lipids, principally phospholipids and cholesterol, in the form of a lipid bilayer. For the cellular membrane to support all its necessary functions it must have a well defined "fluidity" which in turn depends upon the appropriate degree of unsaturation in the fatty acids of the phospholipids. These unsaturated fatty acids are susceptible to oxidative attack, and therefore must be defended by cellular antioxidants.

PREMATURE AGING

The signs and symptoms of aging appear at an accelerated pace in individuals exposed to a highly oxidative environment. This is most clearly seen when the symptoms are externally visible, as in the premature aging of the skin when it is overexposed to an oxidative

environment (such as excess sunlight).

ENVIRONMENTAL TOXINS

The damaging effect of a variety of environmental toxins is brought about by oxidative reactions. To maintain the necessary balance between pro-oxidants and antioxidants in the face of the challenge of environmental toxins, it is necessary to provide supplemental antioxidants.

Selected References

1. Harper's Biochemistry. RK Murray, DK Granner, PA Mayes & VW Rodwell, eds. Appleton & Lange, Stamford, CT, 1996, p. 736.

2. Jacob, R.A. and Burri, B.J. "Oxidative damage and defense" Am I Clin Nutr 1996: 63:985S-90S.

3. Bendich, A. "Beta-Carotene and the immune response" Proc Nutr Soc 1991 ; 50: 263-74.

4. Ben-Amotz, A. and Levy, Y. "Bioavailability of a natural iso-mer mixture compared with synthetic all-trans beta-carotene in human serum" Am I Clin Nutr 1996; 63:729-34.

5. The Encyclopedia of Medicinal Plants A. Chevallier, DK Publishing, New York, 1996, p. 54.

6. Sies, H. and Stahl, W. "Vitamins E and C, b-carotene, and other carotenoids as antioxidants" Am I Clin Nutr 1995;62S:1315S-21S.

7. Meydani, S.N. et al. "Vitamin E supplementation and in vivo immune response in health elderly subjects" J Am Med Assoc 1997; 277:1380-1386.

Wiseman H. "Dietary influences on membrane function: Importance in protection against oxidative damage and disease" Nutr Biochem 1996; 7:2-15.

9. Formica J.V.; Regelson W. "Review of the biology of Quercetin and related bioflavonoids" Food Chem Toxicol 1995; 33:1061-80.

10. Laughton, M.J., Halliwell, B., Evans, P.J., and Hoult, J.R. "Antioxidant and pro-oxidant actions of the plant phenol ics quercetin, gossypol and myricetin. Effects on lipid per-oxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA" Biochem Pharmacol 1989; 38: 2849-2865.

11. Murray,M.T. "PCO sources: Grape seed vs. pine bark" Am I Nat Med 1995:2:6-9.

12. Picard, D. "The biochemistry of green tea polyphenols and thier potential application in human skin cancer" Alt Med Rev 1996; 1: 31 -42.

13.Nichols,T.W. "alpha-Lipoic acid: Biological effects and clinical implications" Alt Med Rev 1997; 2:177-183.

These statements have not been evaluated by the U.S. Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.

Flatulence results from bacterial fermentation of any undigested carbohydrates, not just beans. Chronic flatulence results from chronic failure to" fully digest carbohydrates. Therefore, CARBOHYDRASE contains an array of enzymes specific for carbohydrates plus carminative herbs to relieve gas:

• Amylase and glucoamylase — are two complex carbohydrate-digesting enzymes from Aspergillus oryzae. Supplementation with amylase and glucoamylase allows digestion of carbohydrates to proceed during the time food is held in the stomach, usually about one hour.

• Malt-diastase — closely related to amylase, attacks complex carbohydrates at their ends, cleaving off disaccharides.

• Cellulase — digests a main component of plant fiber, cellulose, and is not produced by the human body.

• Pectinase/phytase — respectively break down pectin, a non-cellulose polysaccharide commonly found in fruits and vegetables,and phytic acid (inositol hexaphosphoric acid) found in grains, seeds, rhizomes and other food.

• Lipase — is the lipid (fat) digesting enzyme from AspergUlus oryzae. Incomplete digestion of fat allows fat to coat food particles and therefore interferes with the digestion of other food components such as protein and carbohydrates.

• Ginger root extract — is an excellent remedy for many digestive complaints, including indigestion, nausea, and gas. Its beneficial effects are largely due to its volatile oil and oleoresin content. One mechanism by which ginger achieves its effects is through support for mucin production (which protects the digestive tract).

CHILDREN'S COLIC

It is widely believed that, in many cases, one important contributor to colic is food allergy^. Since food antigens are destroyed if food is thoroughly digested, the array of digestive enzymes found in CARBOHYDRASE is of benefit for colic in children where food allergy is an important cause of the condition.

LOW BLOOD SUGAR

Chronic inability to fully digest complex carbohydrates often leads to the consumption of large quantities of simple sugars. This in turn leads to sudden, large spikes in blood sugar levels. In some individuals, the resulting rise in blood insulin levels is excessive and causes a sudden fall in blood sugar. By supporting thorough digestion of complex carbohydrates, these enzymes lead to a more gradual release of the resulting simple sugars into the blood, resulting in a more gradual release of insulin thus reducing or eliminating the high/low blood sugar cycles.

MENTAL/EMOTIONAL IMBALANCES

Cyclic surges and deficiencies in blood sugar can result in metabolic instability in sensitive brain regions, including areas regulating emotional and hormonal balance. As discussed above, CARBOHYDRASE contains enzymes which facilitate the complete digestion of food and particularly of complex carbohy drates. By allowing the reduction of simple sugar intake and facilitating a shift toward complex carbohydrates, sensitive individuals mayexperience a leveling out of blood sugar levels and, therefore, a normalization of mental and emotional factors influenced by blood sugar levels.

GASTRASE is designed to provide comprehensive digestive and palliative support for individuals with gastrointestinal irritation. Consequently, GASTRASE contains a broad spectrum of digestive enzymes. GASTRASE also provides a variety of protective nutrients and soothing herbal extracts to help alleviate problems associated with gastrointestinal irritation. The enzymatic constituents of GASTRASE are: