What are enzymes?
Enzymes are specialized proteins that accelerate chemical reactions that otherwise would not occur under conditions to sustain life. The enzyme itself does not change during the reaction, but changes one compound (known as the "substrate") into another (known as the "product").
Enzymes are involved in almost every metabolic function in any living organism. There are over 10,000 separate and distinct enzymes that have been characterized. Each enzyme usually has only one function, or works on one substrate to produce one product; therefore, enzymes demonstrate specificity in their function.
Not all enzymes are useful when taken orally. Metabolic enzymes are types of enzymes that work inside of specific cells and taken orally cannot be directed to enter the correct cell from the digestive tract. Digestive enzymes, however, are active orally as they do not need to enter a specific cell to perform their function.
How do digestive enzymes work?
Digestive enzymes include proteases/peptidases (break down proteins/peptides), carbohydrases (break down carbohydrates), and lipases (break down triglyceride fats). Proteins are degraded to peptides and amino acids, carbohydrates to sugars, and triglycerides to fatty acids by breaking specific chemical bonds within the compound.
Are enzymes safe?
Yes. Studies have determined that the great majority of orally available enzymes produce no toxicity or adverse side effects, even when taken in extremely large doses1-10.
Which enzymes are in dietary supplements?
Most dietary enzyme supplements are derived from plants such as papaya, pineapple, and Aspergillus fungi. The fungal derived enzymes constitute the majority of enzymes in dietary supplements, and are highly purified from the fungal organism. These fungi are not the same as yeast (Candida albicans), and cannot promote or cause any kind of fungal infection. Many people who are sensitive to molds can take the enzymes with no problems. Often, fungal enzymes are better tolerated than enzymes from plant latex sources, such as papaya and pineapple. The enzymes available include different proteases, carbohydrases and lipases.
- Peptidases (DPP IV, PEPs, etc.)
- Protease 6.0
- Protease 4.5
- Lipase (various)
Pancreatic enzymes derived from cattle and pork are also available, usually by medical prescription only. They consist of protease, amylase (breakdown starch), and lipase.
What is the difference between plant enzymes and pancreatic enzymes?
Pancreatic enzymes are found in the small intestine, where they are released by the pancreas. They only work in a narrow pH range, and do not survive the acid environment of the stomach. Therefore, oral pancreatic enzymes must be enteric-coated to protect the enzyme from stomach acid. Once in the neutral pH of the small intestine, the enzymes are activated. Pancreatic enzymes are usually available only by prescription.
Plant enzymes are acid-stable, and so start to work in the stomach. Some plant enzymes work best at the low pH found in stomach. Plant enzymes are regulated as a food by the FDA, so are available without prescription.
What happens if I take an enzyme supplement and don't eat?
Nothing. An enzyme is specific for one substance, if that substance is not present, the enzyme does nothing. For example, if one is lactose intolerant and takes the enzyme lactase, but then consumes no dairy or lactose-containing food, then the lactase enzyme simply continues along the digestive tract, eventually being degraded by enzymes in the GI tract.
Will oral enzymes affect my pancreatic enzymes?
Not usually. Most studies show no effect on pancreatic enzyme production or release when volunteers take oral enzyme supplements. One recent study, however, showed a slight decrease in certain pancreatic enzymes when an oral pancreatic enzyme supplement was given, but the effect was only seen when taking large doses of pancreatic enzymes and was temporary. Normal pancreatic enzyme release returned within 3 days. This study did not use plant-based enzyme supplements, so it may well be that the observed decrease occurs only with pancreatic enzyme supplements, not plant-derived enzymes.
Who should take enzyme supplements?
The best answer is: Anyone who eats food! Seriously, though, anyone can benefit from a good enzyme product. Because of the amounts and diversity of the foods we consume, and our hectic lifestyle, digestion can be less than optimal. Maldigestion can produce severe bloating and gas, cramping, diarrhea or constipation, and food intolerances. Incomplete digestion of food proteins may be linked to food allergies.
Taking plant enzymes with meals allows digestion to start in the stomach, and helps the pancreatic enzymes do the "finishing" work. More thorough digestion of foodstuffs prevents foods from being fermented in the gut. Food fermentation can cause "bad" bacteria and yeast to proliferate at the expense of "good" intestinal bacteria. More complete digestion of carbohydrates removes a potential food source for bad bacteria.
Another benefit of enzymes is that more nutrition can be derived from the food we eat, and less waste is generated. Regular bowel movements are also a byproduct of better digestion.
What about children?
Enzymes are fine for children and even infants. Adjust the enzyme dosage based on meal size, not age or body weight, since enzymes are not absorbed from the gut in appreciable amounts. The enzymes can be added to foods or drinks and even baby formula, and will help breakdown the proteins, complex carbohydrates, and fats in food for easier assimilation by the GI tract.
Children with food intolerances often have special dietary needs. Many have intolerances to proteins such as gluten (in wheat) and casein (in dairy). Dietary enzymes can help break down these proteins such that the incomplete peptides, which often are the source of the intolerances, are either not produced or are broken down into inactive compounds. A by-product of better protein digestion is often noted as better mood and disposition in these children. However, it should be noted that enzymes are not a cure or treatment for any medical condition. Enzymes simply support good digestive function, which can help anyone's mood and disposition!
- Ciafalo V, et al. Safety evaluation of an alpha-amylase enzyme preparation derived from the archaeal order Thermococcales as expressed in Pseudomonas fluorescens biovar I. Regul. Toxicol. Pharmacol. 37:149 2003.
- Coenen TM, et al. Safety evaluation of a lactase enzyme preparation derived from Kluyveromyces lactis. Food Chem. Toxicol. 38:671. 2000.
- Lissau BG, et al. Safey evaluation of a fungal pectinesterase enzyme preparation and its use in food. Food Addit. Contam. 15:627. 1998.
- Coenen TM, et al. Safety evaluation of amino peptidase enzyme preparation derived from Aspergillus niger. Food Chem. Toxicol. 36:781. 1998.
- Bergman, A, et al. An overview of the safety evaluation of the Thermomyces lanuginosus xylanase enzyme (SP 628) and the Aspergillus aculeatus xylanase enzyme (SP 578). Food Addit. Contam. 14:389. 1997.
- Lane, RW. Safety evaluation of tannase enzyme preparation derived from Aspergillus oryzae. Food Chem. Toxicol. 35:207. 1997.
- Modderman JP, et al. Safety evaluation of pullulanase enzyme preparation derived from B. lichenformis containing the pullulanase gene from B. deramificans. Regul. Toxicol. Pharmacol. 21:375. 1995.
- Broadmeadow A, et al. An overview of the safety evaluation of the Rhizomucor miehei lipase enzyme. Food Addit. Contam. 11:105. 1994.
- Greenough RJ, et al. Safety evaluation of a lipase expressed in Aspergillus oryzae. Food Chem. Toxicol. 34:161. 1996.
- Nevalainen H, et al. On the safety of Trichoderma reesei. J Biotechnol. 37:193. 1994.
Oral Enzymes Are Active in vivo:
Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell. Mol. Life Sci. 58:1234 2001. Engwerda CR, et al. Bromelain modulates T cell and B cell immune responses in vitro and in vivo. Cell Immunol. 210:66 2001.
Glade MJ, et al. Improvement in protein utilization in nursing-home patients on tube feeding supplemented with an enzyme product derived from Aspergillus niger and bromelain. Nutrition 17:348 2001.
Sumi H, et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 84:139 1990.
Sandberg AS, et al. Dietary Aspergillus niger phytase increases iron absorption in humans. J. Nutr. 126:476 1996.
Sandberg AS, et al. Effect of dietary phytase on the digestion of phytate in the stomach and small intestine of humans. J. Nutr. 118:469. 1988.
Moskovitz M, et al. Does oral enzyme replacement therapy reverse intestinal lactose malabsorption? Am. J. Gastroenterol. 82:632 1987.
DiPalma JA, et al. Enzyme replacement for lactose malabsorption using a B-D-galactosidase. J. Clin. Gastroenterol. 11:290 1989.
Lettieri JT, et al. Effects of beano on the tolerability and pharmacodynamics of acarbose. Clin. Ther. 20:497 1998.
Ganiats TG, et al. Does Beano prevent gas? A double-blind crossover study of oral alpha-galactosidase to treat oral dietary oligosaccharide intolerance. J. Fam. Pract. 39:441 1994.
Castell JV, et al. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am. J. Physiol. 273:G139 1997.
Exorphin Peptides Are Opioids and Produced by Pancreatic Enzymes:
Teschemacher H, et al. Milk protein-derived opioid receptor ligands. Biopoly. 43:99 1997.
Fukudome S, et al. Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS Lett. 412:475 1997.
Chabance B, et al. Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie 80:155 1998.
Jinsmaa Y, et al. Enzymatic release of neocasomorphin and beta-casomorphin from beta-casein. Peptides 20:957 1999.
Froetschel MA. Bioactive peptides in digesta that regulate gastrointestinal function and intake. J. Anim. Sci. 74:2500 1996.
Dipeptidyl Peptidase IV Breaks Down Casomorphin
Tiruppathi C, et al. Hydrolysis and transport of proline-containing peptides in renal brush border membrane vesicles from dipeptidyl peptidase IV-positive and dipeptidyl peptidase IV-negative rat strains. J. Biol. Chem. 265:1476 1990.
Kikuchi M, et al. Soluble dipeptidyl peptidase IV from terminal differentiated rat epidermal cells: purification and its activity on synthetic and natural peptides. Arch. Biochem. Biophys. 266:369 1988.
Kreil G, et al. Studies on the enzymatic degradation of beta-casomorphins. Life Sci. 33 (supp. 1):137 1983.
Links Between Autism, Digestive Enzymes, and Opioids
Moles A, et al. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science 304(5679):1983 2004. Hunter LC, et al. Opioid peptides and dipeptidyl peptidase in autism spectrum disorder. Dev. Med. Child Neurol. 45:121 2003.
Millward C, et al. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst. Rev. 2004;(2):CD003498 2004.
Goldberg EA. The link between gastroenterology and autism. Gastroenterol. Nurs. 27:16 2004.
Reichelt KL, et al. Can the pathophysiology of autism be explained by the nature of the discovered urine peptides? Nutr. Neurosci. 6:19 2003.
Garvey J. Diet in autism and associated disorders. J Fam. Health Care 12:34 2002.
Knivsberg AM, et al. A randomized, controlled study of dietary intervention in autistic syndromes. Nutr. Neurosci. 5:251 2002.
Wakefield AJ, et al. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment. Pharmacol. Ther. 16:663 2002.
Mercer ME, et al. Food cravings, endogenous opioid peptides, and food intake: a review. Appetite 29:325 1997.
Chabrol H, et al. Psychopharmacology of autism. Encephale. 22:197 1996.
Scifo R, et al. Opioid-immune interactions in autism: behavioural and immunological assessment during a double-blind treatment with naltrexone. Ann. 1st Super Sanita. 32:351 1996.
Stefano GB, et al. A novel view of opiate tolerance. Adv. Neuroimmunol. 6:265 1996.
Chamberlain RS, et al. A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism. Biol. Psychiatry. 28:773 1990.
Kalat JW. Speculations on similarities between autism and opiate addiction. J. Autism Child Schizophr. 8:477 1978.
Enzymes as Modifiers of Phenolic Compounds and Yeast Cell Wall Components
Chung K-T, et al. Reduction of azo dyes by intestinal anaerobes. Appl. Env. Micro. 35:558. 1978.
Brown JP. Reduction of polymeric azo and nitro dyes by intestinal bacteria. Appl. Env. Micro. 41:1283. 1981.
De Vries RP, et al. Synergy between enzyme from Aspergillus involved in the degradation of plant cell wall polysaccharides. Carb. Res. 327:401. 2000.
De Vries, RP, et al. Aspergillus enzymes involved in degradation of plant cell wall polysaccharides. Micro Mol. Biol. Rev. 65:497. 2001
Silveira FQP, et al. Hydrolysis of xylans by enzyme systems from solid cultures of Trichoderma harzianum strains. Braz. J Med. Biol. Res. 32:947. 1999.
La Grange DC, et al. Degradation of xylan to d-xylose by recombinant Saccharomyces cerevisiae coexpressing the Aspergillus niger beta-xylosidase (xlnD) and the Trichoderma reesei xylanase II (xyn2) genes. Appl. Environ. Micro. 67:5512. 2001.
Fry SC. Phenolic components of the primary cell wall. Feruloylated disaccharides of D-galactose and L-arabinose from spinach polysaccharide. Biochem. J. 203:493. 1982.
Enzymes and Celiac Disease
Stepniak D, Spaenij-Dekking L, Mitea C, Moester M, de Ru A, Baak-Pablo R, van Veelen P, Edens L, Koning F. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol. 2006 Oct;291(4):G621-9. Epub 2006 May 11.
Mitea C, Havenaar R, Drijfhout JW, Edens L, Dekking L, Koning F. Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for celiac disease. Gut. 2007.
Vora H, McIntire J, Kumar P, Deshpande M, Khosla C. A scaleable manufacturing process for pro-EP-B2, a cysteine protease from barley indicated for celiac sprue. Biotechnol Bioeng. 2007 Mar 26.
Siegel M, Bethune MT, Gass J, Ehren J, Xia J, Johannsen A, Stuge TB, Gray GM, Lee PP, Khosla C.Rational design of combination enzyme therapy for celiac sprue. Chem Biol. 2006 Jun;13(6):649-58.
Pyle GG, Paaso B, Anderson BE, Allen DD, Marti T, Li Q, Siegel M, Khosla C, Gray GM. Effect of pretreatment of food gluten with prolyl endopeptidase on gluten-induced malabsorption in celiac sprue. Clin Gastroenterol Hepatol. 2005 Jul;3(7):687-94.
Matysiak-Budnik T, Candalh C, Cellier C, Dugave C, Namane A, Vidal-Martinez T, Cerf-Bensussan N, Heyman M. Limited efficiency of prolyl-endopeptidase in the detoxification of gliadin peptides in celiac disease. Gastroenterology. 2005 Sep;129(3):786-96.
Gass J, Ehren J, Strohmeier G, Isaacs I, Khosla C. Fermentation, purification, formulation, and pharmacological evaluation of a prolyl endopeptidase from Myxococcus xanthus: implications for Celiac Sprue therapy. Biotechnol Bioeng. 2005 Dec 20;92(6):674-84.