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Proteolytic Enzymes

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usesPrincipalOther Proposed Uses


Supplement Forms/Alternate Names

  • Bromelain
  • Chymotrypsin
  • Digestive Enzymes
  • Pancreatin
  • Papain
  • Serrapeptase
  • Trypsin
Proteolytic enzymes (proteases) help you digest the proteins in food. Although your body produces these enzymes in the pancreas, certain foods also contain proteolytic enzymes.
Papaya and pineapple are two of the richest plant sources, as attested by their traditional use as natural "tenderizers" for meat. Papain and bromelain are the respective names for the proteolytic enzymes found in these fruits. The enzymes made in your body are called trypsin and chymotrypsin.
The primary use of proteolytic enzymes is as a digestive aid for people who have trouble digesting proteins. However, proteolytic enzymes may also be absorbed internally to some extent and may reduce pain and inflammation. 

Sources

You don't need to get proteolytic enzymes from food, because the body manufactures them (primarily trypsin and chymotrypsin). However, deficiencies in proteolytic enzymes do occur, usually resulting from diseases of the pancreas (pancreatic insufficiency). Symptoms include abdominal discomfort, gas, indigestion, poor absorption of nutrients, and passing undigested food in the stool.
For use as a supplement, trypsin and chymotrypsin are extracted from the pancreas of various animals. You can also purchase bromelain extracted from pineapple stems and papain made from papayas.

Therapeutic Dosages

When you purchase an enzyme, the amount is expressed not only in grams or milligrams but also in activity units or international units. These terms refer to the enzyme's potency (specifically, its digestive power).
Recommended dosages of proteolytic enzymes vary with the form used. Because of the wide variation, we suggest following label instructions.
Proteolytic enzymes can be broken down by stomach acid. To prevent this from happening, supplemental enzymes are often coated with a substance that doesn't dissolve until it reaches the intestine. Such a preparation is called enteric coated.

Therapeutic Uses

The most obvious use of proteolytic enzymes is to assist digestion. However, a small double-blind, placebo-controlled trial found no benefit from proteolytic enzymes as a treatment for dyspepsia (indigestion). 1
Proteolytic enzymes can also be absorbed into the body whole and may help reduce inflammation and pain; 2,44-46 however, the evidence is inconsistent. Several studies found that proteolytic enzymes might be helpful for neck pain , osteoarthritis , and post-herpetic neuralgia (an aftereffect of shingles). 15,16,41-43,51 However, all of these studies suffer from significant limitations (such as the absence of a placebo group ), and none provide substantially reliable information.
Studies performed decades ago suggest that proteolytic enzymes may help reduce the pain and discomfort that follows injuries (especially sports injuries ). 3-7,14 However, a more recent, better-designed, and far larger study failed to find benefit. 50
Proteolytic enzymes have also been evaluated as an aid to recovery from the pain and inflammation caused by surgery , but most studies are decades old and, in any case, the results were mixed. 8-13,36-40
A double-blind, placebo-controlled trial published in the 1960s found that use of proteolytic enzymes helped reduce the discomfort of breast engorgement in lactating women . 47
A study tested bromelain for enhancing recovery from heavy exercise by decreasing delayed-onset muscle soreness, but found no benefits. 48 Another study, this one using a mixed proteolytic enzyme supplement, also failed to find benefits. 56
Two studies failed to find proteolytic enzymes helpful for reducing side effects of radiation therapy for cancer. 49, 55
Some alternative medicine practitioners believe that proteolytic enzymes may help reduce symptoms of food allergies , presumably by digesting the food so well that there is less to be allergic to; however, there is no scientific evidence for this proposed use.
Another theory popular in certain alternative medicine circles suggests that proteolytic enzymes can aid rheumatoid arthritis , multiple sclerosis , lupus , and other autoimmune diseases. Supposedly, these diseases are made worse when whole proteins from foods leak into the blood and cause immune reactions. Digestive enzymes are said to help foil this so-called leaky gut problem. Again, however, there is no meaningful evidence to substantiate this theory. Furthermore, one fairly large (301-participant) study failed to find proteolytic enzymes helpful for multiple sclerosis. 52

What Is the Scientific Evidence for Proteolytic Enzymes?

Most of the studies described in this section used combination products containing various proteolytic enzymes plus other substances, such as the bioflavonoid rutin.

Osteoarthritis and Other Forms of Chronic Musculoskeletal Pain

Several studies provide preliminary evidence that proteolytic enzymes might be helpful for various forms of chronic pain, including neck pain and osteoarthritis.
Neck Pain
A double-blind, placebo-controlled trial of 30 people with chronic neck pain found that use of a proteolytic enzyme mixture modestly reduced pain symptoms as compared to placebo. 41
Osteoarthritis
Studies enrolling a total of more than 400 people compared proteolytic enzymes to the standard anti-inflammatory drug diclofenac for the treatment of osteoarthritis -related conditions of the shoulder, back, or knee. 42-43,53-54 The results generally showed equivalent benefits with the supplement as with the medication. However, all of these studies suffered from various flaws that limit their reliability; the most important was the absence of a placebo group .

Shingles (Herpes Zoster)

Herpes zoster ( shingles ) is an acute, painful infection caused by the varicella-zoster virus, the organism that causes chickenpox. Proteolytic enzymes have been suggested as treatment. However, there is little evidence to support their use.
A double-blind study of 190 people with shingles compared proteolytic enzymes to the standard antiviral drug acyclovir. 32 Participants were treated for 14 days and their pain was assessed at intervals. Although both groups had similar pain relief, the enzyme-treated group experienced fewer side effects. However, since acyclovir offers minimal benefit at most, these results don't mean very much.
Similar results were seen in another double-blind study in which 90 people were given either an injection of acyclovir or enzymes, followed by a course of oral medication for 7 days. 33

Sports Injuries

Several small studies have found proteolytic enzyme combinations helpful for the treatment of sports injuries . However, the best and largest trial by far failed to find benefit.
A double-blind, placebo-controlled study of 44 people with sports-related ankle injuries found that treatment with proteolytic enzymes resulted in faster healing and reduced the time away from training by about 50%. 17 Based on these results, a very large (721-participant), double-blind, placebo-controlled trial of people with sprained ankles was undertaken. 50 Unfortunately, this study failed to find benefit with rutin, bromelain, or trypsin, separately or in combination.
Three other small, double-blind studies, involving a total of about 80 athletes, found that treatment with proteolytic enzymes significantly speeded healing of bruises and other mild athletic injuries as compared to placebo. 18-20 In another double-blind trial, 100 people were given an injection of their own blood under the skin to simulate bruising following an injury. Researchers found that treatment with a proteolytic enzyme combination significantly speeded up recovery. 21 In addition, a double-blind, placebo-controlled trial of 71 people with finger fractures found that treatment with proteolytic enzymes significantly improved recovery. 22 However, these studies were performed decades ago and are not quite up to modern standards.

Surgery

Numerous studies have evaluated various proteolytic enzymes as an aid to recovery from surgery , but the results have been mixed. Again, most of these studies are not up to modern standards.
A double-blind, placebo-controlled trial of 80 people undergoing knee surgery found that treatment with mixed proteolytic enzymes after surgery significantly improved rate of recovery, as measured by mobility and swelling. 23
Another double-blind, placebo-controlled trial evaluated the effects of a similar mixed proteolytic enzyme product in 80 individuals undergoing oral surgery. 24 The results showed reduced pain, inflammation, and swelling in the treated group as compared to the placebo group. Benefits were also seen in another trial of mixed proteolytic enzymes for dental surgery, 36 as well as in one study involving only bromelain. 13
A double-blind, placebo-controlled study of 204 women receiving episiotomies during childbirth found evidence that a mixed proteolytic enzyme product can reduce inflammation. 37 Bromelain was also found helpful for reducing inflammation following episiotomy in one double-blind, placebo-controlled trial of 160 women, 11 but a very similar study found no benefit. 38
Other double-blind, placebo-controlled studies have found that bromelain reduces inflammation and pain following nasal surgery, 25 cataract removal, 12 and foot surgery. 39 However, a study of 154 individuals undergoing facial plastic surgery found no benefit. 40
A small double-blind, placebo-controlled trial of 24 people having surgical extraction of third molars found serrapeptase given during the procedure reduced postoperative pain and swelling (significant differences on days 2, 3 and 7). 57

Safety Issues

In studies, proteolytic enzymes are believed to have  proven to be quite safe, although they can occasionally cause digestive upset and allergic reactions.
One proteolytic enzyme, pancreatin, may interfere with folate absorption. 34 In addition, the proteolytic enzyme papain might increase the blood-thinning effects of warfarin and possibly other anticoagulants. 35
The proteolytic enzyme bromelain might also cause problems if combined with drugs that thin the blood. In addition, there are concerns that bromelain should not be mixed with sedative drugs. Finally, bromelain may increase blood concentrations of certain antibiotics. For more information, see the full Bromelain article.  

Interactions You Should Know About

If you are taking:
  • The proteolytic enzyme pancreatin: You may need extra folate.
  • Warfarin (Coumadin), aspirin ,  or other drugs that "thin" the blood: You should not take the proteolytic enzymes papain or bromelain except under a doctor's supervision.
  • Sedative drugs: Do not take bromelain, except under a physician's supervision.

References

1 Kleveland PM, Johannessen T, Kristensen P, et al. Effect of pancreatic enzymes in non-ulcer dyspepsia. A pilot study. Scand J Gastroenterol. 1990;25:298-301.

2 Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple ( Ananas comosus ) and its clinical application. An update. J Ethnopharmacol. 1988;22:191-203.

3 Zuschlag JM. Double-blind clinical study using certain proteolytic enzyme mixtures in karate fighters. Working paper. Mucos Pharma GmbH (Germany). 1988;1-5.

4 Baumuller M. The application of hydrolytic enzymes in blunt wounds to the soft tissue and distortion of the ankle joint: a double-blind clinical trial [translated from German]. Allgemeinmedizin. 1990;19:178-182.

5 Rathgeber WF. The use of proteolytic enzymes (Chymoral) in sporting injuries. S Afr Med J. 1971;45:181-183.

6 Shaw PC. The use of a trypsin-chymotrypsin formulation in fractures of the hand. Br J Clin Pract. 1969;23:25-26.

7 Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: a double-blind study. Pa Med. 1965;68:35-37.

8 Rahn HD. Efficacy of hydrolytic enzymes in surgery. Paper presented at: 24th FIMS World Congress of Sports Medicine; May 27-June 1, 1990; Amsterdam.

9 Vinzenz K. Treatment of edema with hydrolytic enzymes in oral surgical procedures [translated from German]. Quintessenz. 1991;42:1053-1064.

10 Seltzer AP. Minimizing post-operative edema and ecchymoses by the use of an oral enzyme preparation (bromelain): a controlled study of 53 rhinoplasty cases. Eye Ear Nose Throat Mon. 1962;41:813-817.

11 Zatuchni GI, Colombi DJ. Bromelains therapy for the prevention of episiotomy pain. Obstet Gynecol. 1967;29:275-278.

12 Spaeth GL. The effect of bromelains on the inflammatory response caused by cataract extraction: a double-blind study. Eye Ear Nose Throat Mon. 1968;47:634-639.

13 Tassman GC, Zafran JN, Zayon GM. Evaluation of a plant proteolytic enzyme for the control of imflammation and pain. J Dent Med. 1964;19:73-77.

14 Blonstein JL. Control of swelling in boxing injuries. Practitioner. 1969;203:206.

15 Billigmann VP. Enzyme therapy—an alternative in treatment of herpes zoster. A controlled study of 192 patients [translated from German]. Fortschr Med. 1995;113:43-48.

16 Kleine MW, Stauder GM, Beese EW. The intestinal absorption of orally administered hydrolytic enzymes and their effects in the treatment of acute herpes zoster as compared with those of oral acyclovir therapy. Phytomedicine. 1995;2:7-15.

17 Baumuller M. The application of hydrolytic enzymes in blunt wounds to the soft tissue and distortion of the ankle joint: a double-blind clinical trial [translated from German]. Allgemeinmedizin. 1990;19:178-182.

18 Zuschlag JM. Double-blind clinical study using certain proteolytic enzyme mixtures in karate fighters. Working paper. Mucos Pharma GmbH (Germany). 1988;1-5.

19 Rathgeber WF. The use of proteolytic enzymes (Chymoral) in sporting injuries. S Afr Med J. 1971;45:181-183.

20 Deitrick RE. Oral proteolytic enzymes in the treatment of athletic injuries: a double-blind study. Pa Med. 1965;68:35-37.

21 Kleine MW, Pabst H. The effect of an oral enzyme therapy on experimentally produced hematomas [translated from German]. Forum des Prakt und Allgemeinarztes. 1988;27:42,45-46,48.

22 Shaw PC. The use of a trypsin-chymotrypsin formulation in fractures of the hand. Br J Clin Pract. 1969;23:25-26.

23 Rahn HD. Efficacy of hydrolytic enzymes in surgery. Paper presented at: 24th FIMS World Congress of Sports Medicine; May 27-June 1, 1990; Amsterdam.

24 Vinzenz K. Treatment of edema with hydrolytic enzymes in oral surgical procedures [translated from German]. Quintessenz. 1991;42:1053-1064.

25 Seltzer AP. Minimizing post-operative edema and ecchymoses by the use of an oral enzyme preparation (bromelain): a controlled study of 53 rhinoplasty cases. Eye Ear Nose Throat Mon. 1962;41:813-817.

26 Blonstein JL. Control of swelling in boxing injuries. Practitioner . 1969;203:206. 26. Zatuchni GI, Colombi DJ. Bromelains therapy for the prevention of episiotomy pain. Obstet Gynecol. 1967;29:275-278.

27 Zatuchni GI, Colombi DJ. Bromelains therapy for the prevention of episiotomy pain. Obstet Gynecol. 1967;29:275-278.

28 Spaeth GL. The effect of bromelains on the inflammatory response caused by cataract extraction: a double-blind study. Eye Ear Nose Throat Mon. 1968;47:634-639.

29 Tassman GC, Zafran JN, Zayon GM. Evaluation of a plant proteolytic enzyme for the control of imflammation and pain. J Dent Med. 1964;19:73-77.

30 Howat RC, Lewis GD. The effect of bromelain therapy on episiotomy wounds—a double-blind controlled clinical trial. J Obstet Gynaecol Br Commonw. 1972;79:951-953.

31 Gylling U, Rintala A, Taipale S, et al. The effect of a proteolytic enzyme combinate (bromelain) on the postoperative oedema by oral application. A clinical and experimental study. Acta Chir Scand. 1966;131:193-196.

32 Billigmann VP. Enzyme therapy—an alternative in treatment of herpes zoster. A controlled study of 192 patients [translated from German]. Fortschr Med. 1995;113:43-48.

33 Kleine MW, Stauder GM, Beese EW. The intestinal absorption of orally administered hydrolytic enzymes and their effects in the treatment of acute herpes zoster as compared with those of oral acyclovir therapy. Phytomedicine. 1995;2:7-15.

34 Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci. 1980;25:369-373.

35 Shaw D, Leon C, Kolev S, et al. Traditional remedies and food supplements. A 5-year toxicological study (1991-1995). Drug Saf. 1997;17:342-356.

36 Cameron IW. An investigation into some of the factors concerned in the surgical removal of the impacted lower wisdom tooth, including a double blind trial of chymoral. Br J Oral Surg. 1980;18:112-124.

37 Soule SD, Wasserman HC, Burstein R. Oral proteolytic enzyme therapy (Chymoral) in episiotomy patients. Am J Obstet Gynecol. 1966;95:820-823.

38 Howat RC, Lewis GD. The effect of bromelain therapy on episiotomy wounds—a double blind controlled clinical trial. J Obstet Gynaecol Br Commow. 1972;79:951-953.

39 Frank SC. Use of chymoral as an anti-inflammatory agent following surgical trauma. J Am Podiatr Assoc. 1965;55:706-709.

40 Gylling U, Rintala A, Taipale S, et al. The effect of a proteolytic enzyme combinate (bromelain) on the postoperative oedema by oral application. A clinical and experimental study. Acta Chir Scand. 1966;131:193-196.

41 Tilscher H, Keusch R, Neumann K. Results of a double-blind, randomized comparative study of Wobenzym-placebo in patients with cervical syndrome [translated from German]. Wien Med Wochenschr. 1996;146:91-95.

42 Singer F, Oberleitner H. Drug therapy of activated arthrosis. On the effectiveness of an enzyme mixture versus DiclofenacŴ [translated from German]. Wien Med Wochenschr. 1996;146:55-58.

43 Klein G, Kullich W. Reducing pain by oral enzyme therapy in rheumatic diseases [translated from German]. Wien Med Wochenschr. 1999;149:577-580.

44 Smyth RD, Brennan R, Martin GJ. Studies establishing the absorption of bromelains (proteolytic enzymes) from the gastrointestinal tract. Exp Med Surg. 1964;22:46-59.

45 Miller JM, Ginseberg M, McElfatrick GC, et al. The administration of bromelain orally in the treatment of inflammation and edema. Exp Med Surg. 1964;22:293-299.

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-G146.

47 Murata T, Hunzow M, Nomura Y. The clinical effects of 'protease complex' on postpartum breast engorgement. J Jap Obstet Gynaecol Soc. 1965;12:139-147.

48 Stone MB, Merrick MA, Ingersoll CD, et al. Preliminary comparison of bromelain and ibuprofen for delayed onset muscle soreness management. Clin J Sport Med. 2002;12:373-378.

49 Martin T, Uhder K, Kurek R, et al. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial. Radiother Oncol. 2002;65:17-22.

50 Kerkhoffs GM, Struijs PA, De Wit C, et al. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. Br J Sports Med. 2004;38:431-435.

51 Klein G, Kullich W, Schnitker J, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24:25-30.

52 Baumhackl U, Kappos L, Radue EW, et al. A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis. Mult Scler. 2005;11:166-168.

53 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;23:410-415.

54 Klein G, Kullich W, Schnitker J, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24:25-30.

55 Dorr W, Herrmann T. Efficacy of Wobe-Mugos® E for reduction of oral mucositis after radiotherapy : results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study. Strahlenther Onkol. 2007;183:121-127.

56 Beck TW, Housh TJ, Johnson GO, et al. Effects of a protease supplement on eccentric exercise-induced markers of delayed-onset muscle soreness and muscle damage. J Strength Cond Res. 2007;21:661-667.

57 Al-Khateeb TH, Nusair Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg. 2008; 37:264-268.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.

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