Health & Dietary Supplements

Foods modified by and containing (animal, plant and microbial) enzymes prior to ingestion have been consumed by man for millennia. Early examples of enzyme applications are cheese and bread-making, dry aging of meats, and a variety of fermentation processes including brewing, wine and vinegar production and lactic acid fermentations. Yeast has been used medically not only as a source of vitamins but also to combat constipation and to stimulate normal digestion by the action of yeast proteases and amylases.[1]

The enzyme industry as it exists today began in the late 19th century. By 1894, Dr. Jokichi Takamine had been granted U.S. Patent 525,823 Process of making diastatic enzyme” which detailed the process and extraction of amylases from koji (Aspergillus oryzae). His patented product, Taka-diastase, was marketed by Parke, Davis & Company as a digestive aid throughout the world.

By 1932, Dr. Edward Howell formed a company in Illinois to provide supplemental enzymes to replace those destroyed in cooking, canning and food processing. Dr. Howell’s 1947 survey “Status of Food Enzymes in Digestion and Metabolism” cites use of papain as an aid to digestion and a benefit to “digestive disturbances of widely different kinds.”[2]  Fungal amylase is similarly cited as used in digestive tract therapy, as are lipases and pancreatic extracts.[3]

The use of enzymatic digestive aids is documented in medical reference texts going back at least six decades. For example, in the 1948 Physician’s Desk Reference (“PDR”), 9 enzyme compounds were listed including products such as Winthrop Stearns “Stamyl,” containing trypsin, amylopsin, lipase and hemicellulase.[4]  By 1966, the PDR contained 37 “gastro-intestinal” use enzymes, with preparations that included proteases, plant derived amylases and cellulases.[5]  However, many enzyme supplements were available through health food and other non-pharmaceutical providers that are not captured in PDR references.

In his 1972 review, Dr. Irwin Sizer recognized that enzymatic “digestive aids effective in the small intestine have been extensively used for a long period of time.”[6]  Dr. Sizer noted that digestive aid enzymes were “most often fungal in origin” and preparations from Aspergillus oryzae and Aspergillus niger were most commonly used due to their high content of amylase and protease.[7]  Similarly, Dr. Sizer noted that cellulases were being used to aid digestion of foods containing indigestible cellulose fibers such as cucumbers, cabbage, and radishes. Cellulases from Aspergillus oryzae and Tricoderma viride are cited in publications dating to 1962.[8]  Lipases from Aspergillus oryzae or Candida lipolytica were taken orally by individuals with fatty stools as early as 1958.[9]

More recently, McGrath and Walsh list amylase, cellulase, invertase, alpha-galactosidase, papain, pepsin, bromelain, superoxide dismutase, lactase and pancreatin as enzymes widely used as digestive aids.[10]

The use of enzymatic digestive aids has continued to flourish to the present.

Selected Enzymes Marketed as Digestive Aids in North America Prior to 1994*

Alpha-galactosidase – Aspergillus nigerAmylase – Aspergillus oryzae

Amylase – Bacillus subtilis, Bacillus amyloliquefaciens, Aspergillus niger

Amylase (ß-amylase) (Malt diastase) – barley malt

Cellulase – Aspergillus niger, Trichoderma longibrachiatum (reesei)

Invertase – Saccharomyces cerevisiae

Lactase – Aspergillus oryzae

Lactase – Kluyveromyces lactis

Lipase – Aspergillus oryzae

Lipase – Aspergillus niger, Rhizopus oryzae, R. japonicus

Lipase – Arthrobacter ureafaciens, Candida cylindracea, Rhizomucor miehei, Rhizopus delemar

Pancreatin – Porcine pancreas

Pancreatin – bovine

Pancrelipase – Bovine and porcine pancreas

Protease, botanical – Bromelain (Ananas comosus) and Papain (Carica papaya)

Protease, animal – porcine pepsin

Protease, animal – bovine or porcine (trypsin), bovine or porcine (chymotrypsin), bovine (pepsin)

Protease, microbial – Aspergillus niger, Aspergillus oryzae, Bacillus subtilis

Protease, microbial – Aspergillus oryzae, Aspergillus melleus, Bacillus licheniformis, Bacillus thermoproteolyticus, Rhizopus niveus

SuperOxide Dismutase – Bacillus spp.

 

*This list was prepared for submission to Health Canada’s Natural and Non-prescription Health Products (formerly “Natural Health Product Directorate”), and should not be relied upon for any other purpose.

Based on industry estimates, in 1994 the market (wholesale) for enzymes used as digestive aids was U.S. $35 million in the U.S. and Japan each; U.S. $47 million in France/Italy/UK/Germany; and roughly U.S. $55 million for the rest of the world.[1]  According to the Nutritional Business Journal’’s 2011 supplement business report, digestive enzymes now rank as 20th of the top 100 nutritional supplements and make up 4% of the U.S. nutritional supplement market. The digestive enzyme category has grown consistently over the last 10 years from approximately U.S. $80 million in 2000 to U.S. $209 million in 2010.

[1] Market estimate by ETA member in 1994.

 

[1] 15, IRWIN W. SIZER, MEDICAL APPLICATIONS OF MICROBIAL ENZYMES; ADVANCES IN APPLIED MICROBIOLOGY, (D. Perlmaned.) (1972).
[2] EDWARD HOWELL, THE STATUS OF FOOD ENZYMES IN DIGESTION AND METABOLISM (The National Enzyme Company 1946).
[3] Id.
[4] PHYSICIAN’S DESK REFERENCE (J. Jones et al. eds. Medical Economics Inc.) (1948).
[5] PHYSICIAN’S DESK REFERENCE (H. Bull et al. eds. Medical Economics Inc.) (12th ed. 1966).
[6] 15, IRWIN W. SIZER, MEDICAL APPLICATIONS OF MICROBIAL ENZYMES; ADVANCES IN APPLIED MICROBIOLOGY, (D.Perlmaned.) (1972).
[7] Id.
[8] Id.
[9] Id.
[10] GARY WALSH, DIRECTORY OF THERAPEUTIC ENZYMES 278-279 (Barry M. McGrath ed. 2006).

 

Orally Administered Enzyme Food Supplement Safety Overview