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Search Health Information    Digestive Enzymes

Digestive Enzymes

Uses

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

This supplement has been used in connection with the following health conditions:

Used for Why
3 Stars
Low Back Pain (Trypsin, Chymotrypsin)
4 to 8 tablets a day of proteolytic enzymes containing trypsin and chymotrypsin, and/or bromelain
Learn More

Three double-blind trials have investigated the effects of supplementing a combination of the enzymes trypsin and chymotrypsin for seven to ten days on severe low back pain with or without accompanying leg pain. Eight tablets per day were given initially in all trials, but in two trials the number of pills was reduced to four per day after two to three days. One of these trials reported small, though statistically significant improvements, for some measures in people with degenerative arthritis of the lower spine.1 People with sciatica-type leg pain had significant improvement in several measures in one trial,2 while another found the enzymes were not much more effective than a placebo.3 These trials included chronic low back conditions, so their relevance to acute LBP alone may be limited.

3 Stars
Low Back Pain (Trypsin, Chymotrypsin)
4 to 8 tablets a day of proteolytic enzymes containing trypsin and chymotrypsin, and/or bromelain
Learn More

Three double-blind trials have investigated the effects of supplementing a combination of the enzymes trypsin and chymotrypsin for seven to ten days on severe low back pain with or without accompanying leg pain. Eight tablets per day were given initially in all trials, but in two trials the number of pills was reduced to four per day after two to three days. One of these trials reported small, though statistically significant improvements, for some measures in people with degenerative arthritis of the lower spine.1 People with sciatica-type leg pain had significant improvement in several measures in one trial,2 while another found the enzymes were not much more effective than a placebo.3 These trials included chronic low back conditions, so their relevance to acute LBP alone may be limited.

3 Stars
Pancreatic Insufficiency
Consult a qualified medical practitioner
Learn More

The mainstay of treatment for pancreatic insufficiency is replacement of digestive enzymes , using supplements prepared from pig pancreas (pancrelipase) or fungi.7 Enzyme supplements have been shown to reduce steatorrhea8 , 9 associated with pancreatitis, while pain reduction has been demonstrated in some,10 , 11 though not all,12 , 13 double-blind studies. Digestive enzyme preparations that are resistant to the acidity of the stomach are effective at lower doses compared with conventional digestive enzyme preparations.14 Some enzyme preparations are produced with higher lipase enzyme content for improved fat absorption, but one controlled study of chronic pancreatitis found no advantage of this preparation over one with standard lipase content.15 People with more severe pancreatic insufficiency or who attempt to eat a higher-fat diet require more enzymes,16 but large amounts of pancreatic digestive enzymes are known to damage the large intestine in some people with diseases causing pancreatic insufficiency.17 , 18 , 19 Therefore, a qualified healthcare practitioner should be consulted about the appropriate and safe amount of enzymes to use.

Many otherwise healthy people suffer from indigestion , and some doctors believe that mild pancreatic insufficiency can be a cause of indigestion. A preliminary study of people with indigestion reported significant improvement in almost all of those given pancreatic enzyme supplements.20 One double-blind trial found that giving pancreatic enzymes to healthy people along with a high-fat meal reduced bloating, gas, and abdominal fullness following the meal.21

Stomach surgery patients often have decreased pancreatic function, malabsorption , and abdominal symptoms, including steatorrhea, but digestive enzyme supplementation had no effect on steatorrhea in two of three double-blind studies of stomach surgery patients,22 , 23 , 24 although some other symptoms did improve.25 , 26 Patients who have surgery to remove part of the pancreas often have severe steatorrhea that is difficult to control with enzyme supplements.27 In one double-blind study, neither high-dose nor standard-dose pancreatin was able to eliminate steatorrhea in over half of the pancreas surgery patients studied.28

3 Stars
Sprains and Strains
4 to 8 tablets a day of proteolytic enzymes containing trypsin, chymotrypsin, and/or bromelain
[3 stars] Learn More

Several preliminary trials have reported reduced pain and swelling, and/or faster healing in people with a variety of conditions using either bromelain,29 papain from papaya, 30 , 31 or a combination of trypsin and chymotrypsin.32 Double-blind trials have reported faster recovery from athletic injuries, including sprains and strains, and earlier return to activity using eight tablets daily of trypsin/chymotrypsin,33 , 34 , 35 , 36 four to eight tablets daily of papain,37 eight tablets of bromelain (single-blind only),38 or a combination of these enzymes.39 However, one double-blind trial using eight tablets per day of trypsin/chymotrypsin to treat sprained ankles found no significant effect on swelling, bruising , or overall function.40

Bromelain is measured in MCUs (milk clotting units) or GDUs (gelatin dissolving units). One GDU equals 1.5 MCU. Strong products contain at least 2,000 MCU (1,333 GDU) per gram (1,000 mg). A supplement containing 500 mg labeled “2,000 MCU per gram” would have 1,000 MCU of activity, because 500 mg is half a gram. Some doctors recommend 3,000 MCU taken three times per day for several days, followed by 2,000 MCU three times per day. Some of the research, however, uses smaller amounts, such as 2,000 MCU taken in divided amounts in the course of a day (500 MCU taken four times per day). Other enzyme preparations, such as trypsin/chymotrypsin, have different measuring units. Recommended use is typically two tablets four times per day on an empty stomach, but as with bromelain, the strength of trypsin/chymotrypsin tablets can vary significantly from product to product.

2 Stars
Celiac Disease
Consult a qualified healthcare practitioner
Learn More

People with celiac disease often do not produce adequate digestive secretions from the pancreas, including lipase enzymes 41 In a double-blind trial, children with celiac disease who received a pancreatic enzyme supplement along with a gluten-free diet gained significantly more weight in the first month than those treated with only a gluten-free diet.42 However, this benefit disappeared in the second month, suggesting enzyme supplements may only be useful at the beginning of dietary treatment.

2 Stars
Indigestion, Heartburn, and Low Stomach Acidity
Consult a qualified healthcare practitioner
Learn More

Lipase , a pancreatic enzyme , aids in the digestion of fats and may improve digestion in some people. In a double-blind trial, a timed-release form of pancreatic enzymes was shown to significantly reduce gas, bloating, and fullness after a high-fat meal.43 Participants in this study took one capsule immediately before the meal and two capsules immediately after the meal. The three capsules together provided 30,000 USP units of lipase , 112,500 USP units of protease, and 99,600 USP units of amylase. However, the amount of pancreatic enzymes needed may vary from person to person, and should be determined with the help of a doctor.

2 Stars
Osteoarthritis
90 mg of bromelain and 48 mg of trypsin, with 100 mg of rutosid, taken in enteric-coated pills three times per day
Learn More

In a double-blind study, a group of people with painful osteoarthritis of the knee received an oral enzyme -flavonoid preparation or a nonsteroidal anti-inflammatory (NSAID) for six weeks. While both treatments relieved pain and improved joint function, the enzyme-flavonoid product appeared to be slightly more effective than the NSAID. No serious side effects were seen.44 The enzyme-flavonoid product used in this study was Phlogenzym (Mucos Pharma, Geretsried, Germany). Each enteric-coated tablet contained 90 mg of bromelain, 48 mg of trypsin, and 100 mg of rutosid (a derivative of the flavonoid rutin); one tablet was given three times a day.

2 Stars
Tendinitis
Several tablets per day of proteolytic enzymes
Learn More

Alternative healthcare practitioners frequently recommend proteolytic enzymes for various minor injuries. Research demonstrates that these enzymes are well absorbed when taken by mouth,45 , 46 and preliminary47 , 48 , 49 , 50 and double-blind51 , 52 , 53 , 54 trials have shown their effectiveness for reducing pain and swelling associated with various injuries and for speeding up the healing process. Unfortunately, many of these studies did not specifically identify the patients’ injury, so it is unclear whether the positive results included improvements in tendinitis.

1 Star
Acne Rosacea
Refer to label instructions
Learn More

Some people with rosacea have been reported to produce inadequate stomach acid .55 In a preliminary trial, supplemental hydrochloric acid, along with vitamin B complex, improved some cases of rosacea in people with low stomach-acid production.56 Similarly, improvement in rosacea has been reported anecdotally after supplementation with pancreatic digestive enzymes , and a controlled study found that rosacea patients produced less pancreatic lipase than healthy people.57 Controlled trials are needed to evaluate the effects of hydrochloric acid and digestive enzyme supplements in rosacea. Hydrochloric acid supplements should not be taken without the supervision of a healthcare practitioner.

1 Star
Allergies and Sensitivities and Food Allergies
Refer to label instructions
Learn More

According to one theory, allergies are triggered by partially undigested protein. Proteolytic enzymes may reduce allergy symptoms by further breaking down undigested protein to sizes that are too small to cause allergic reactions.58 Preliminary human evidence supports this theory.59 Hydrochloric acid secreted by the stomach also helps the digestion of protein, and preliminary research suggests that some people with allergies may not produce adequate amounts of stomach acid.60 , 61 , 62 However, no controlled trials have investigated the use of enzyme supplements to improve digestion as a treatment for food allergies.

1 Star
Chronic Candidiasis
Refer to label instructions
Learn More

It is unknown if taking pancreatic enzymes or betaine HCl (hydrochloric acid) tablets is beneficial for chronic candidiasis. Nonetheless, some doctors recommend improving digestive secretions with these agents. Hydrochloric-acid secretion from the stomach, pancreatic enzymes, and bile all inhibit the overgrowth of Candida and prevent its penetration into the absorptive surfaces of the small intestine.63 , 64 , 65 Decreased secretion of any of these important digestive components can lead to overgrowth of Candida in the gastrointestinal tract. Consult a physician for more information.

1 Star
Crohn’s Disease
Refer to label instructions
Learn More

People with Crohn’s disease may be deficient in pancreatic enzymes , including lipase .66 In theory, supplementing with enzymes might improve the nutrient malabsorption that is often associated with Crohn’s disease. However, people with Crohn’s disease considering supplementation with enzymes should consult a doctor.

1 Star
Low Back Pain
Refer to label instructions
Learn More

Several preliminary trials have reported reduced pain and swelling, and/or faster healing in people with a variety of conditions using either bromelain,67 papain from papaya, 68 , 69 or a combination of trypsin and chymotrypsin.70 Double-blind trials have reported faster recovery from athletic injuries, including sprains and strains, and earlier return to activity using eight tablets daily of trypsin/chymotrypsin,71 , 72 , 73 , 74 four to eight tablets daily of papain,75 eight tablets of bromelain (single-blind only),76 or a combination of these enzymes.77 However, one double-blind trial using eight tablets per day of trypsin/chymotrypsin to treat sprained ankles found no significant effect on swelling, bruising , or overall function.78

How It Works

How to Use It

The digestive enzymes—proteolytic enzymes, lipases , and amylases—are generally taken together. Pancreatin, which contains all three digestive enzymes, is rated against a standard established by the U.S. Pharmacopeia (USP). For example, “4X pancreatin” is four times stronger than the USP standard. Each “X” contains 25 USP units of amylase, 2 USP units of lipase, and 25 USP units of protease (or proteolytic enzymes). Three to four grams of 4X pancreatin (or a lower amount at higher potency) with each meal is likely to help digest food in some people with pancreatic insufficiency.

Those with chronic pancreatitis need to discuss enzyme intakes with their physician. Under medical supervision, seriously ill people with pancreatic insufficiency caused by pancreatitis are given very high levels of enzymes to improve fat digestion. In one successful trial, enough pancreatin was used with each meal to supply slightly over 1,000,000 USP units of lipase.79 Because pancreatin is rapidly emptied from the stomach during digestion, people taking these enzymes may obtain better results by spreading out supplementation throughout the meal.80

Supplemental enzymes that state only product weight, but not activity units, may lack potency.

Where to Find It

Only small amounts of the animal-based proteolytic enzymes, trypsin and chymotrypsin, are found in the diet; however, the pancreas can synthesize these enzymes. The plant-based proteolytic enzyme bromelain comes from the stems of pineapples and is useful in many conditions. Papain comes from unripe papayas. All of these enzymes are available as supplements.

Possible Deficiencies

People with pancreatic insufficiency and cystic fibrosis frequently require supplemental pancreatic enzymes (which include proteolytic enzymes, lipases , and amylases). In addition, those with celiac disease 81 or Crohn’s disease 82 and perhaps some people suffering from indigestion 83 may be deficient in pancreatic enzymes. As bromelain and papain are not essential, deficiencies do not exist.

Interactions

Interactions with Supplements, Foods, & Other Compounds

At the time of writing, there were no well-known supplement or food interactions with this supplement.

Interactions with Medicines

Certain medicines interact with this supplement.

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • none

Reduce Side Effects

  • none

Support Medicine

  • none

Reduces Effectiveness

  • none

Potential Negative Interaction

  • Warfarin

    Papain, an enzyme extract of papaya, was associated with increased warfarin activity in one patient.84 Persons taking warfarin should avoid papain supplements until further information about this potential interaction becomes available.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required

  • none

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

Side Effects

Side Effects

The most important digestive enzymes in malabsorption diseases are usually fat-digesting enzymes called lipases . Proteolytic enzymes can digest, as well as destroy, lipases. Therefore, people with enzyme deficiencies may want to avoid proteolytic enzymes in order to spare lipases.85 If this is not possible (as most enzyme products contain both), people with malabsorption syndromes should talk with their doctor to see if their condition warrants finding products that contain the most lipase and the least protease.

In theory, too much enzyme activity could be irritating because it could start to “digest” parts of the body as the enzymes travel through the digestive system. Fortunately, that does not happen with supplemental amounts. Research has not determined the level at which such problems might arise.

A serious condition involving damage to the large intestines called fibrosing colonopathy has resulted from the use of pancreatic enzymes in children with cystic fibrosis . In some cases, the problem was linked to the use of high supplemental amounts of enzymes.86 , 87 , 88 However, the amount of enzymes used has not been linked to the problem in all reports.89 In some cases, lower amounts of enzymes have caused fibrosing colonopathy if the enzymes are enteric-coated.90 Some researchers now believe that some unknown interaction between the enteric coating and the enzymes themselves may cause damage to the intestines of children with cystic fibrosis.91 Until more is known, children with cystic fibrosis needing to take pancreatic enzymes should only do so under the careful supervision of a knowledgeable healthcare professional.

References

1. Hingorani K. Oral enzyme therapy in severe back pain. Br J Clin Pract 1968;22:209–10.

2. Gaspardy G, Balint G, Mitsuova M, et al. Treatment of sciatica due to intervertebral disc herniation with Chymoral tablets. Rheum Phys Med 1971;11:14–9.

3. Gibson T, Dilke TFW, Grahame R. Chymoral in the treatment of lumbar disc prolapse. Rheumatol Rehabil 1975;14:186–90.

4. Hingorani K. Oral enzyme therapy in severe back pain. Br J Clin Pract 1968;22:209–10.

5. Gaspardy G, Balint G, Mitsuova M, et al. Treatment of sciatica due to intervertebral disc herniation with Chymoral tablets. Rheum Phys Med 1971;11:14–9.

6. Gibson T, Dilke TFW, Grahame R. Chymoral in the treatment of lumbar disc prolapse. Rheumatol Rehabil 1975;14:186–90.

7. Scolapio JS, Malhi-Chowla N, Ukleja A. Nutrition supplementation in patients with acute and chronic pancreatitis. Gastroenterol Clin North Am 1999;28:695–707 [review].

8. Nakamura T, Tandoh Y, Terada A, et al. Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and short-chain fatty acid excretion in patients with pancreatic insufficiency resulting from chronic pancreatitis. Int J Pancreatol 1998;23:63–70.

9. Schneider MU, Knoll-Ruzicka ML, Domshke S, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology 1985;32:97–102.

10. Isaksson G, Ihse I. Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Dig Dis Sci 1983;28:97–102.

11. Slaff J, Jacobson D, Tillman CR, et al. Protease-specific suppression of pancreatic exocrine secretion. Gastroenterol 1984;87:44–52.

12. Halgreen H, Pedersen NT, Worning H. Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Scand J Gastroenterol 1986;21:104–8.

13. Mossner J. Is there a place for pancreatic enzymes in the treatment of pain in chronic pancreatitis? Digestion 1993;54 Suppl 2:35–9.

14. Schneider MU, Knoll-Ruzicka ML, Domshke S, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology 1985;32:97–102.

15. Dellhaye M, Meuris S, Gohimont AC, et al. Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis. Eur J Gastroenterol Hepatol 1996;8:699–703.

16. Malesci A, Mariani A, Mezzi G, et al. New enteric-coated high-lipase pancreatic extract in the treatment of pancreatic steatorrhea. J Clin Gastroenterol 1994;18:32–5.

17. Bansi DS, Price A, Russell C, Sarner M. Fibrosing colonopathy in an adult owing to over use of pancreatic enzyme supplements. Gut 2000;46:283–5.

18. Littlewood JM, Wolfe SP. Control of malabsorption in cystic fibrosis. Paediatr Drugs 2000;2:205–22.

19. Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Consensus committee. J Pediatr 1995;127:681–4.

20. Cruz Pinho A. Dispepsia e terapeutica enzimatica de substituicao. Cadernos Generalista (Lisboa) 1990;78:43–47 [in Portugese].

21. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci 1999;44:1317–21.

22. Bragelmann R, Armbrecht U, Rosemeyer D, et al. The effect of pancreatic enzyme supplementation in patients with steatorrhea after total gastrectomy. Eur J Gastroenterol Hepatol 1999;11:231–7.

23. Armbrecht U, Lundell L, Stockbruegger RW. Nutrient malassimilation after total gastrectomy and possible intervention. Digestion 1987;37 Suppl 1:56–60.

24. Armbrecht U, Lundell L, Stockbrugger RW. The benefit of pancreatic enzyme substitution after total gastrectomy. Aliment Pharmacol Ther 1988;2:493–500.

25. Armbrecht U, Lundell L, Stockbruegger RW. The benefit of pancreatic enzyme substitution after total gastrectomy. Aliment Pharmacol Ther 1988;2:493–500.

26. Bragelmann R, Armbrecht U, Rosemeyer D, et al. The effect of pancreatic enzyme supplementation in patients with steatorrhea after total gastrectomy. Eur J Gastroenterol Hepatol 1999;11:231–7.

27. Ghaneh P, Neoptolemos JP. Exocrine pancreatic function following pancreatectomy. Ann N Y Acad Sci 1999;880:308–18 [review].

28. Neoptolemos JP, Ghaneh P, Andren-Sandberg A, et al. Treatment of pancreatic exocrine insufficiency after pancreatic resection. Results of a randomized, double-blind, placebo-controlled, crossover study of high vs standard dose pancreatin. Int J Pancreatol 1999;25:171–80.

29. Cirelli MG. Five years experience with bromelains in therapy of edema and inflammation in postoperative tissue reaction, skin infections and trauma. Clin Med 1967;74(6):55–9.

30. Trickett P. Proteolytic enzymes in treatment of athletic injuries. Appl Ther 1964;6:647–52.

31. Sweeny FJ. Treatment of athletic injuries with an oral proteolytic enzyme. Med Times 1963:91:765.

32. Boyne PS, Medhurst H. Oral anti-inflammatory enzyme therapy in injuries in professional footballers. Practitioner 1967;198:543–6.

33. Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: A double-blind study. Pennsylvania Med J 1965;Oct:35–7.

34. Rathgeber WF. The use of proteolytic enzymes (Chymoral) in sporting injuries. S Afr Med J 1971;45:181–3.

35. Buck JE, Phillips N. Trial of Chymoral in professional footballers. Br J Clin Pract 1970;24:375–7.

36. Tsomides J, Goldberg RI. Controlled evaluation of oral chymotrypsin-trypsin treatment of injuries to the head and face. Clin Med 1969;76(11):40.

37. Holt HT. Carica papaya as ancillary therapy for athletic injuries. Curr Ther Res 1969;11:621–4.

38. Blonstein JL. Oral enzyme tablets in the treatment of boxing injuries. Practitioner 1967;198:547.

39. Baumüller M. Therapy of ankle joint distortions with hydrolytic enzymes—results from a double blind clinical trial. In Hermans GPH, Mosterd WL, eds. Sports, Medicine and Health. Amsterdam: Excerpta Medica, 1990, 1137.

40. Craig RP. The quantitative evaluation of the use of oral proteolytic enzymes in the treatment of sprained ankles. Injury 1975;6:313–6.

41. Patel RS, Johlin FC Jr, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc 1999;50:823–7.

42. Carroccio A, Iacono G, Montalto G, et al. Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective randomized study. Dig Dis Sci 1995;40:2555–60.

43. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci 1999;44:1317–21.

44. Akhtar NM, Naseer R, Farooqi AZ, et al. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee - a double-blind prospective randomized study. Clin Rheumatol 2004;23:410–5.

45. Miller JM. The absorption of proteolytic enzymes from the gastrointestinal tract. Clin Med 1968;75:35–42 [review].

46. Castell JV, Friedrich G, Kuhn CS, et al. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol 1997;273:G139–46.

47. Cirelli MG. Five years’ experience with bromelains in therapy of edema and inflammation in postoperative tissue reaction, skin infections and trauma. Clin Med 1967;74:55–9.

48. Trickett P. Proteolytic enzymes in treatment of athletic injuries. Appl Ther 1964;6:647–52.

49. Sweeny FJ. Treatment of athletic injuries with an oral proteolytic enzyme. Med Times 1963:91:765.

50. Boyne PS, Medhurst H. Oral anti-inflammatory enzyme therapy in injuries in professional footballers. Practitioner 1967;198:543–6.

51. Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: A double-blind study. Pennsylvania Med J 1965;Oct:35–7.

52. Holt HT. Carica papaya as ancillary therapy for athletic injuries. Curr Ther Res 1969;11:621–4.

53. Rathgeber WF. The use of proteolytic enzymes (Chymoral) in sporting injuries. S Afr Med J 1971;45:181–3.

54. Buck JE, Phillips N. Trial of Chymoral in professional footballers. Br J Clin Pract 1970;24:375–7.

55. Johnson L, Eckardt R. Rosacea keratitis and conditions with vascularization of the cornea treated with riboflavin. Arch Ophthamol 1940;23:899–907.

56. Allison JR. The relation of hydrochloric acid and vitamin B complex deficiency in certain skin diseases. South Med J 1945;38:235–41.

57. Barba A, Rosa B, Angelini G, et al. Pancreatic exocrine function in rosacea. Dermatologica 1982;165:601–6.

58. Oelgoetz AW, Oelgoetz PA, Wittenkind J. The treatment of food allergy and indigestion of pancreatic origin with pancreatic enzymes. Am J Dig Dis Nutr 1935;2:422–6.

59. McCann M. Pancreatic enzyme supplement for treatment of multiple food allergies. Ann Allergy 1993;71:269 [abstract #17].

60. Kokkonen J, Simila S, Herva R. Impaired gastric function in children with cow’s milk intolerance. Eur J Pediatr 1979;132:1–6.

61. Kokkonen J, Simila S, Herva R. Gastrointestinal findings in atopic children. Eur J Pediatr 1980;134:249–54.

62. Gonzalez H, Ahmed T. Suppression of gastric H2-receptor mediated function in patients with bronchial asthma and ragweed allergy. Chest 1986;89:491–6.

63. Boero M, Pera A, Andriulli A, et al. Candida overgrowth in gastric juice of peptic ulcer subjects on short- and long-term treatment with H2-receptor antagonists. Digestion 1983;28:158–63.

64. Rubinstein E. Antibacterial activity of the pancreatic fluid. Gastroenterology 1985;88:927–32 [review].

65. Sarker SA, Gyr R. Non-immunological defense mechanisms of the gut. Gut 1990;33:1331–7 [review].

66. Hegnhoj J, Hansen CP, Rannem T, et al. Pancreatic function in Crohn’s disease. Gut 1990;31:1076–9.

67. Cirelli MG. Five years experience with bromelains in therapy of edema and inflammation in postoperative tissue reaction, skin infections and trauma. Clin Med 1967;74(6):55–9.

68. Trickett P. Proteolytic enzymes in treatment of athletic injuries. Appl Ther 1964;6:647–52.

69. Sweeny FJ. Treatment of athletic injuries with an oral proteolytic enzyme. Med Times 1963:91:765.

70. Boyne PS, Medhurst H. Oral anti-inflammatory enzyme therapy in injuries in professional footballers. Practitioner 1967;198:543–6.

71. Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: A double-blind study. Pennsylvania Med J 1965;Oct:35–7.

72. Rathgeber WF. The use of proteolytic enzymes (Chymoral) in sporting injuries. S Afr Med J 1971;45:181–3.

73. Buck JE, Phillips N. Trial of Chymoral in professional footballers. Br J Clin Pract 1970;24:375–7.

74. Tsomides J, Goldberg RI. Controlled evaluation of oral chymotrypsin-trypsin treatment of injuries to the head and face. Clin Med 1969;76(11):40.

75. Holt HT. Carica papaya as ancillary therapy for athletic injuries. Curr Ther Res 1969;11:621–4.

76. Blonstein JL. Oral enzyme tablets in the treatment of boxing injuries. Practitioner 1967;198:547.

77. Baumüller M. Therapy of ankle joint distortions with hydrolytic enzymes—results from a double blind clinical trial. In Hermans GPH, Mosterd WL, eds. Sports, Medicine and Health. Amsterdam: Excerpta Medica, 1990, 1137.

78. Craig RP. The quantitative evaluation of the use of oral proteolytic enzymes in the treatment of sprained ankles. Injury 1975;6:313–6.

79. Nakamura T, Tandoh Y, Terada A, et al. Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and short-chain fatty acid excretion in patients with pancreatic insufficiency resulting from chronic pancreatitis. Int J Pancreatol 1998;23:63–70.

80. Taylor CJ, Hillel PG, Ghosal S, et al. Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis. Arch Dis Child 1999;80:149–52.

81. Patel RS, Johlin FC Jr, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc 1999;50:823–7.

82. Gullo L. Indication for pancreatic enzyme treatment in non-pancreatic digestive diseases. Digestion 1993;54(suppl 2):43–7.

83. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci 1999;44:1317–21.

84. Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Saf 1997;17:342–56.

85. Layer P, Groger G. Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency. Digestion 1993;54(suppl 2):10–4.

86. Stevens JC, Maguiness KM, Hollingsworth J, et al. Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy. J Pediatr Gastroenterol Nutr 1998;26:80–4.

87. Oades PJ, Bush A, Ong PS, Brereton RJ. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1994;343:109 [letter].

88. Campbell CA, Forrest J, Muscgrove C. High-strength pancreatic enzyme supplements and large-bowel stricture in cystic fibrosis. Lancet 1994;343:109–10 [letter].

89. Milla CE, Wielinski CL, Warwick WJ. High-strength pancreatic enzymes. Lancet 1994;343:599 [letter].

90. Jones R, Franklin K, Spicer R, Berry J. Colonic strictures in children with cystic fibrosis on low-strength pancreatic enzymes. Lancet 1995;346:499–500 [letter].

91. Powell CJ. Pancreatic enzymes and fibrosing colonopathy. Lancet 1999;354:251 [letter].

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