Product Design Rationale
1.0 THE DIGESTIVE SYSTEM
The digestive system prepares food for use by the body’s cells. If food is not digested, it cannot reach the cells and is not in the appropriate form or chemical state. The digestive system modifies food physically and chemically through the use of exocrine and endocrine secretions as well as through the controlled movement of food through the digestive tract.
Digestion begins when food first enters the mouth. Here the first mechanical process occurs with the act of chewing. In addition, the body’s first enzymes are added to the food with saliva. This enzyme is called ptyalin and consists of amylolytic enzymes. As the food travels down the esophagus via peristaltic action, ptyalin as well as any endogenous enzymes continue the digestive process started in the mouth.
Once the food bolus has entered the stomach, it may remain in the fundus or upper region of the stomach for as long as an hour until the food is mixed with the stomach secretions. During this time salivary amylase and food enzymes continue digestion. Research has shown that salivary amylase can digest as much as 30 to 40% of the starches present before mixing occurs.
The stomach continues mechanical digestion through churning the bolus into a creamy chyme. Several enzymes (see Table 1) are secreted in the stomach including gastric lipase (tributyrase), gastric amylase, gelatinase and pepsinogen. Pepsinogen is the inactive form of the proteolytic enzyme pepsin which is activated via acid hydrolysis with the hydrochloric acid secreted by the stomach. Thus, the stomach begins the enzymatic digestion of protein and to a limited extent fats.
As the chyme moves into the duodenum, the pancreas is stimulated to produce additional digestive enzymes. Pancreatic secretions includes enzymes for the digestion of proteins, carbohydrates and fats. Secreted proteolytic enzymes include trypsin, chymotrypsin, carboxypolypeptidase, elastases and nuceleases. Proteolytic enzymes breakdown proteins into peptides of various sizes and free amino acids. Pancreatic amylase hydrolyzes starches, glycogen and other digestible carbohydrates into di- and trisaccharides. Similar in action to salivary amylase, pancreatic amylase is several times more powerful and is the major agent in the digestion of starches and other complex carbohydrates. Fats are hydrolyzed by pancreatic lipase, cholesterol esterase and phospholipase. Together these lipolytic enzymes provide for the digestion of phospholipids, cholesterol and fats. To support fat digestion and absorption, bile is secreted by the liver. The bile salts function to aid emulsification of fat particles as well as transport and absorption of fatty acids, monoglycerides, cholesterol and other lipids through the intestinal mucous membrane.
Upon entrance to the small intestine, additional enzymes are present to further digest the ingested foods. Peptidases, disaccharidases, and intestinal lipase are located within the brush border cells where they complete digestion thus allowing absorption. Disaccharidase enzymes include sucrase, maltase, isomaltase, and lactase and function to hydrolyze disaccharides into monosaccharides. It is in the small intestine that absorption of nutrients takes place. Once digested into the appropriate form, monosaccharides, amino acids, fatty acids and other nutrients are absorbed across the intestinal mucosa and transported via the blood stream for use by cells throughout the body.
| TABLE 1. Overview of Enzymes in the Healthy Human Digestive Tract | ||
|---|---|---|
| ENZYME | SUBSTRATE(s) | END PRODUCTS |
|
stomach |
||
|
amylase |
starch | maltose, dextrins |
| tributyrase | butter fats | free fatty acids, di-, monoglycerides |
| pepsin | proteins | peptides |
| gelatinase | proteins | peptides |
|
duodenum |
||
|
amylase* |
starch, glycogen, COH | maltose, dextrins |
| pancreatic lipase* | fats (triglycerides) | free fatty acids, monoglycerides |
| cholesterol esterase | cholesterol esters | free fatty acids, cholesterol |
| phospholipase | phospholipids | free fatty acids |
| trypsin* | proteins/peptides | peptides |
| chymotrypsin | proteins/peptides | peptides |
| carboxypolypeptidase | peptides | free amino acids |
| elastases | proteins/peptides | peptides |
| nucleases | proteins/peptides | peptides |
|
small intestine |
||
|
dipeptidases |
peptides | tripeptides, dipeptides |
| aminopolypeptidase | peptides | tripeptides, dipeptides |
| peptidases | tripeptides, dipeptides | free amino acids |
| intestinal lipase | tri-, diglycerides | free fatty acids |
| sucrase | sucrose | glucose, fructose |
| maltase/isomaltase | maltose | glucose |
| lactase | lactose | glucose, galactose |
| dextrinase | limit dextrins | glucose |
| *enzymes responsible for the greatest percentage of digestion of carbohydrates, fats and proteins. | ||
Table 2 — Comparion of Polyphenol Content of Grape Pip/Seed and Pine Bark Extracts
2.0 THE DIGESTIVE SYSTEM
Under optimal conditions, it could be argued that the human body needs no supplementation of enzymes. As the table above indicates, the human body is quite capable of producing the enzymes necessary to digest food and allow for the absorption of nutrients. However, with estimates that as many as twenty million Americans are suffering from various digestive disorders, optimal conditions are not the case. Digestive problems can cause improper digestion and malabsorption of nutrients that can have far reaching effects. Consequences of malabsorption can include impaired immunity, allergic reaction, poor wound healing, skin problems and mood swings. Supplemental enzymes can improve the level of digestion and help assure that the maximum level of nutrient absorption is attained.
3.0 SUPPLEMENTATION OF NON-MAMMALIAN ENZYMES
All raw food naturally contains the proper types and proportion of enzymes necessary to digest itself–whether in human consumption or in the eventual decomposition in the natural world. When raw food is eaten, chewing ruptures the cell membranes and releases the indigenous food enzymes to begin the selective breakdown of substrates. Proteases break long protein chains (polypeptides) into smaller amino acid chains and eventually into single amino acids. Amylase reduces large carbohydrates (starches and other polysaccharides) to disaccharides including sucrose, lactose, and maltose. Lipases digest fats (triglycerides) into free fatty acids and glycerol. Cellulase and CereCalase™ (not found in the human system) break the bonds found in various fibers. By disrupting the structure of the fiber matrices which envelop most of the nutrients in plants, cellulase and CereCalase™ increase the nutritional value of fruits and vegetables.
Overwhelming evidence shows that food enzymes play an important role in digestion by predigesting food in the upper stomach before hydrochloric acid has even been secreted. Supplementation of food enzymes is necessary in today’s society due to the prevalence of cooked and/or processed foods. Most food enzymes are essentially destroyed at the temperatures used to cook and process food leaving foods devoid of digestive enzyme activity. Placing the full digestive burden on the body, the body’s digestive process can become over-stressed and vital nutrients may not be released from food for assimilation by the body.
Unlike supplemental enzymes of animal origin, plant enzymes work at the pH found in the upper stomach. Food sits in the upper portion of the stomach for as long as an hour before gastric secretions begin action. Several studies conducted at major universities have shown that the enzymes in saliva continue their digestive activity in the upper stomach and can digest up to 30% of the ingested protein, 60% of ingested starch and 10% of ingested fat during the 30 to 60 minutes after consumption. Although salivary enzymes accomplish a significant amount of digestion, their activity is limited to a pH level above 5.0. Exogenous plant enzymes are active in the pH range of 3.0 to 9.0 and can facilitate the utilization of a much larger amount of protein, carbohydrates and fat before HCl is secreted in sufficient amounts to neutralize their activity. Obviously, plant enzymes can play a significant role in improving food nutrient utilization.
In addition to protease, amylase, lipase, and cellulase, it is important to provide a concentrated source of the disaccharidases Lactase, Invertase and Malt Diastase. Disaccharide intolerance occurs when insufficient levels of disaccharidase enzymes are secreted in the small intestine causing malabsorption and physical discomfort. Lactase deficiency is the most common and well-known form of carbohydrate intolerance. Lactase digests lactose (milk sugar) into glucose and galactose. Most mammals, including humans, have high intestinal lactase activity at birth. But, in some cases, this activity declines to low levels during childhood and remains low in adulthood. The low lactase levels cause maldigestion of milk and other foods containing lactose. It is estimated that approximately 70% of the world’s population is deficient in intestinal lactase with more than one-third of the U.S. population presumed to be unable to digest dairy products. Supplemental lactase has been found to decrease the symptoms of lactose intolerance associated with the consumption of dairy foods. Invertase is another disaccharidase that works to break down sucrose (refined table sugar) into glucose and fructose. The prevalence of processed and highly refined foods in the American diet means that we consume a great amount of this sugar which can contribute to undue digestive stress. It is theorized that unrecognized sucrose intolerance is a contributing factor in many allergies. Supplemental Invertase can increase the assimilation and utilization of this sugar. The additional supplementation of the carbohydrase Malt Diastase augments the breakdown of starch into glucose molecules, allowing greater absorption of this energy-giving sugar. Inclusion of these sugar-breaking enzymes gives the formula a broad base for improving nutrition.
4.0 THE DIGASE FORMULA
The enzymes and herbs contained in the New Improved Digase™ Formula are shown below:
|
NUTRIENT |
AMOUNT |
%U.S. RDA |
|---|---|---|
|
Amylase |
2,500 DU |
* |
|
Glucoamylase |
9 AGU |
* |
|
Invertase (Sucrase) |
200 SU |
* |
|
Maltase Diastase |
500 DPo |
* |
|
Protease 4.5 |
8,000 HUT |
* |
|
Peptidase FP |
2,000 HUT |
* |
|
Protease 6.0 |
4,000 HUT |
* |
|
CereCalase™ |
7.5 mg |
* |
|
Protease 3.0 (acid stable) |
8 SAPU |
* |
|
Alpha-Galactosidase |
60 GALU |
* |
|
Lipase |
250 FIP |
* |
|
Cellulase |
200 CU |
* |
|
Lactase |
250 ALU |
* |
|
Caraway Seed (Carum carvi) |
70 mg |
* |
|
Gentian (Gentiana lutea) |
70 mg |
* |
|
Ginger Rhizome (Zingiber officinale) |
70 mg |
* |
*No U.S. RDA has been established for this ingredient.
Ý Enzyme activity is specified according to standard Food Chemical Codex procedures accepted by FDA
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 &endash; sugars that are commonly found in vegetables especially of the legume and cruciferous families. Taken supplementally, alpha-galactosidase has been shown to decrease the incidence of flatulence associated with the consumption of raffinose-containing vegetables. The level of invertase in this product 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. Meanwhile, 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 thus is able to 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. Additionally, 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
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 A GENERAL NOTE ABOUT 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 KCAL high-fat meal.
|
FOOD COMPONENT |
% OF MEAL |
WEIGHT |
|---|---|---|
|
Animal Protein |
12% |
50 grams |
|
Vegetable Protein |
8% |
20 grams |
|
Animal Fat |
17.5% |
19.5 grams |
|
Vegetable Fat |
17.5% |
19.5 grams |
|
Carbohydrate |
45% |
112.5 grams |
|
Fiber (non-digestible) |
10 grams |
APPENDIX B
ORIGINS OF ENZYMES IN THE PATHWAY DIGASE™ FORMULA
|
ENZYME |
SOURCE |
|---|---|
|
Amylase |
Aspergillus oryzae ferment |
|
Protease 4.5 |
Aspergillus oryzae ferment |
|
Protease 6.0 |
Aspergillus oryzae ferment |
|
Protease 3.0 |
Aspergillus oryzae ferment |
|
Peptidase FP |
Aspergillus oryzae ferment |
|
Invertase |
Saccharomyces cerevisiae |
|
Malt Diastase |
Hordeum vulgare malt |
|
Lactase |
Aspergillus oryzae ferment |
|
Cellulase |
Trichoderma long brachiatum |
|
Lipase 21179 |
Aspergillus niger ferment |
|
Alpha-Galactosidase |
Aspergillus niger ferment |
|
CereCalase™ |
Aspergillus niger ferment |