Digase™ (Digestive Enzyme Design Rationale) Part 2: the Formula

In Part 2 of the Product Rationale for our Digase™ enzyme formula, we present  both its various components and the functions each performs in the product.

You may also wish to read Part 1 of the Product Rationale.

4.0 THE DIGASE FORMULA

The enzymes and herbs contained in the latest, improved Digase™ formula are shown below:

* No established Daily Value
† Enzyme activity specified according to standard FDA accepted Food Chemical Codex procedures

CARBOHYDROLYTIC ENZYMES

Amylase, Glucoamylase, Malt Distase, Lactase, Invertase, Alpha-Galactosidase, Cellulase and Cerecalase™

Starch is abundant in the natural world where it serves as the primary energy source for plants, animals and humans. Starch consists of glucose polymers. These polymers exist in two basic compositions, amylose and amylopectin. Amylose, the minor constituent, consists of straight chains of glucose joined with alpha-1,4-glucosidic bonds. Amylopectin consists of branched glucose chains. The branching of the glucose chain occurs with the formation of an alpha-1,6-glucosidic bond. The ratio of amylose to amylopectin varies dependent upon the origin of the starch but is typically in the range of 1:3 to 1:4.

Starch digestion is optimized with the combination of the enzymes alpha-amylase, glucoamylase and malt diastase. While alpha-amylase breaks glucose-glucose bonds at random points within the starch chain, malt diastase hydrolyzes the starch chain from the ends to create glucose dimers (maltose) and glucoamylase breaks single glucose molecules off the ends of the chain. The hydrolytic action of both alpha-amylase and malt diastase is blocked by the alpha-1,6-glucosidic bonds of amylopectin.

The conformation of these limit dextrins prevents the active site of the enzymes from coming in contact with the glucose-glucose bonds thus inhibiting hydrolysis. Glucoamylase hydrolyzes the alpha-1,6-glucosidic bond, freeing the chain for continued hydrolysis of the alpha-1,4-bonds. The action of these three enzymes are outlined in the following three figures which clearly show the benefit of combining amylase, malt diastase and glucoamylase for the liberation of glucose.

FIGURE 1. Action of Amylase (/) without the presence of Glucoamylase for the hydrolysis of amylopectin (component of starch).

FIGURE 2. Action of Amylase and Malt Diastase (/) without the presence of Glucoamylase for the hydrolysis of amylopectin (component of starch). Spaces represent sites of Amylase action.

FIGURE 3. Action of Amylase, Malt Diastase and Glucoamylase (/) for the hydrolysis of amylopectin (component of starch). Spaces represent sites of Amylase and Malt Diastase action. Glu (underlined) represents molecules of free glucose available after hydrolysis is complete.

The ratio of amylase and glucoamylase activities is relatively standardized with the data for the development of the ratios being derived from the sugar industry.

The amount of lactase in the product is low in comparison to the original Lactaid® formulation. Individuals who do not have dairy problems are not paying for an expensive enzyme with little direct benefit to them. However, those who are lactose intolerant can increase their dosage with dairy consumption to help prevent their symptoms. In comparison to most other products on the market positioned as general digestive supplements, the proposed product is similar in lactase activity.

In regards to alpha-galactosidase, this enzyme is characterized by its ability to hydrolyze the alpha-1-6 linkages in melibiose, raffinose, and stachyose, sugars commonly found in vegetables especially of the legume and cruciferous families. Taken as a supplement, alpha-galactosidase decreases the incidence of flatulence associated with the consumption of raffinose-containing vegetables. The level of invertase in Digase™ is comparable to other general digestive products.

Cellulase and CereCalase™ enzymes offer distinct advantages for individuals consuming large amounts of grains, beans and other vegetable feedstuffs. These enzymes hydrolyze the bonds in various fibers. Cellulase hydrolyzes glucose-glucose bonds in cellulose. By disrupting the structure of the fiber matrices which envelop most of the nutrients in plants, cellulase increases the nutritional value of fruits and vegetables.

CereCalase™ is a proprietary blend of three enzymes—hemicellulase, beta-glucanase and phytase—that work together to macerate, or disrupt, the cell walls of fruits, vegetables, seeds and herbs. These three enzymes hydrolyze non-starch polysaccharides (NSPs) which can have anti-nutritive effects. NSPs have also been shown to bind digestive enzymes and inhibit mineral absorption.
PROTEOLYTIC ENZYMES

PROTEASE 3.0, PROTEASE 4.5, PROTEASE 6.0 and PEPTIDASE

The complexity of proteins and peptides requires the combination of multiple proteases to optimize digestion. Proteins are made up of over twenty different amino acids with each combination presenting different conformational characteristics. Each proteolytic enzyme has different bond specificities and thus a combination shows the greatest rate of hydrolysis. Bond specificity is an ongoing area of research in enzymology. However little has been done on the various Aspergillus proteases.

Peptidase breaks amino acids off the ends of the peptide chain. Our supplier’s (National Enzyme Company (NEC)) peptidase possesses both amino-peptidase and carboxy-peptidase activities and thereby can remove amino acids from both ends of the peptide chain. Protease 4.5 and Protease 3.0 break at points within the peptide chain dependent upon their bond specificities. While these specificities have not been fully elucidated, significant differences in the action of these enzymes have been seen both in the laboratory and in digestive product usage.

The pH optima and ranges of these two enzymes is also an important benefit of combining these proteases. Protease 4.5 has an optimal pH of 4.5 (pH range 2.0 to 6.0) while Protease 3.0’s optimum is pH 3.0 (pH range 2.0 to 7.0) and Protease 6.0 has an optimal pH of 6.0 (pH range 4.0 to 11.0). Together these proteases provide proteolytic action throughout the human digestive system.
LIPOLYTIC ENZYMES

LIPASE

The lipase included in Digase™ has a very broad range activity and is capable of hydrolyzing all three triglyceryl bonds yielding free fatty acids and glycerol. Many lipases hydrolyze only the 1- and 3-positions. In contrast, the Aspergillus niger lipase is capable of breaking the bonds at all three positions although the 2-position is hydrolyzed at a slightly slower rate.

In addition, our lipase shows an optimum pH of 5.0 with an active range of pH 3.0 to 9.0. The LU level for this formulation is in the middle to high range of modern digestive formulations and is comparable with the level used in current research.
HERBS

Gentian Root (Gentiana lutea), Ginger Rhizome (Zingiber officinale), and Caraway Seed (Carum carvi)

Three herbs have been incorporated into this formula to support the digestive action of the food enzymes. Gentian Root (Gentiana lutea) is a bitter herb which is recognized worldwide as one of the most effective gastric stimulants. This herb is widely used to improve digestion and stimulate appetite as well as being beneficial for all types of gastrointestinal disorders including dyspepsia, gastritis, heartburn, and nausea. Research shows that the bitter principles found in Gentian stimulate gastric secretions and have choleretic activity; substantiating the herbs effectiveness for digestion.

Ginger Rhizome (Zingiber officinale) is an incredibly active and effective gastrointestinal aid with the following properties: 1) Contains a digestive enzyme whose effectiveness even exceeds that of papain, 2) Stimulates the flow of saliva and increases dramatically the concentration of the digestive enzyme amylase in the saliva, and 3) Activates peristalsis and increases intestinal muscle tone.

Caraway Seed (Carum carvi) further supports healthy digestion. This herb has carminative and antispasmodic activities that help to soothe the stomach and ease digestion. Caraway also benefits this formulation by its action to increase digestion of fats. Like Gentian Root, Caraway Seed has also been shown to stimulate the appetite.

5.0 GENERAL NOTE ON ENZYME POTENCIES

Due to the catalytic nature of enzymes, any amount (no matter how small) will increase the rate of reaction. Larger potencies simply serve to increase the rate to a higher level, at least within the kinetic ability of the enzyme. Since these enzymes are safe and non-toxic, high activity levels are more cost- and marketing-driven than scientifically established. A game of “our potencies are higher than theirs” is currently one of the most common marketing ploys.

The area of greatest concern in enzyme formulation is in achieving the proper balance in the enzyme ratios. Broadening the formulation to contain multiple proteases and carbohydrases is a valid way to improve the activity of any product. The benefits relate to the specificity of each enzyme. Since each enzyme catalyzes reactions at different sites, multiple enzymes can quickly increases the rate of hydrolysis and improve the bioavailability of amino acids, sugars and fatty acids.

REFERENCES:

Beazell, J.M., “A Reexamination of the role of the stomach in the digestion of carbohydrates and protein,” American Journal of Physiology 132: 42-50 (1941).

Berkow, R.,ed. The Merck Manual, 15th edition, (Rahway, NJ: Merck Sharp & Dohme Research Laboratories, 1987).

Bradley, P.R., ed. British Herbal Compendium, Volume 1, (Dorset, England: British Herbal Medicine Association, 1992).

Cichoke, Anthony J., Enzymes & Enzyme Therapy: How to Jump Start Your Way to Lifelong Good Health, (New Canaan, CT, Keats Publishing, 1994).

Duke, J.A., Handbook of Medicinal Plants, (Boca Raton, FL: CRC Press Inc., 1985).

Ghose,T.K. and Pathak, A.N. “Cellulase-2: Applications” Process Biochemistry, 20-24, May 1973.

Guyton, A.C., Textbook of Medical Physiology, 8th edition. (Philadelphia: W.B. Saunders Company, 1991).

Howell, E, Enzyme Nutrition: The Food Enzyme Concept, (Wayne, NJ, Avery Publishing Group, Inc., 1985).

Lennard-Jones, J.E. “Functional gastrointestinal disorders.” New England Journal of Medicine 308: 431 (1983).

Murray, R.D., et. al. “Comparative absorption of [13C] glucose and [13C] lactose by premature infants,” American Journal of Clinical Nutrition 51: 59-66 (1990).

O’Keefe, S.J.D., et. al. “Milk-induced malabsorption in malnourished African patients,” American Journal of Clinical Nutrition 54: 130-135 (1991).

Prochaska, L.J.; Piekutowski, W.V. “On the synergistic effects of enzymes in food with enzymes in the human body. A literature survey and analytical report.” Medical Hypotheses 42: 355-62 (1994).

Schwimmer, S., Source Book of Food Enzymology, (Westport CT, The AVI Publishing Company, Inc., 1981).

Thacker, P.A.; Campbell, G.L.; GrootWassink, J. “The effect of enzyme supplementation on the nutritive value of rye-based diets for swine.” Canadian Journal of Animal Science 71: 489-96 (1991).

Theiss, B. and Theiss, P., The Family Herbal, (Rochester, VT: Healing Arts Press), 1989).

Weiss, R.F., Herbal Medicine, (Gothemburg, Sweden: AB Arcanum, 1988).

APPENDIX A

THE DESIGN MEAL

The following table provides details of the “typical” meal around which the Digase™ formula was designed. Two capsules of the formula provide as much as 80% of the digestive power needed to digest this 1000 kilocalorie, high-fat meal.

APPENDIX B

ORIGINS OF ENZYMES IN THE PATHWAY DIGASE™ FORMULA