A comparative study of effect on reducing pain, inflammation and side effect of combination of enzymes (bacterial proteases, papain, bromelain, vitamin C and rutin) versus conventional non-steroidal anti-inflammatory drugs (diclofenac) in patients of closed fracture lower end radius coming at orthopaedic department of a tertiary care hospital

Tejas A. Acharya, Madhav D. Trivedi, Dimple S. Mehta, Sunita B. Chhaiya, Shreyas P. Gandhi


Background: Diclofenac and oral systemic enzymes both are commonly used for control of pain and inflammation in fracture lower end radius as well as other such conditions. Some studies have shown that combination of enzymes like bacterial proteases, papain, bromelain, vitamin C and rutin can reduce pain and Inflammation which is comparable to diclofenac but it still not definite.

Methods: Total 50 patients with closed fracture lower end radius were enrolled and randomly divided in to two groups. Group-1 with 25 patients received oral diclofenac and group-2 with 25 patients received oral preparation which contains combination of enzymes bacterial proteases, papain, bromelain, vittamin C and rutin. Effect of drug was assessed by improvement in wrist function which was evaluated by patient rated wrist evolution (PRWE) and reduction in oedema on day 1, day 3 and day 5. Both the groups were compared by unpaired Z test.

Results: Mean reduction in PRWE score was 132.08±5.01 in Group 1 and 104.4±11.78 in group 2. Mean of percentage reduction of oedema for group 1 was 8.22 while for group 2 it was 17.8. Both were statistically significant (p<0.05). Total 5 patients out of 25 complained of gastritis in group 1 patients while there was no side effect reported in group 2 patients.

Conclusions: Diclofenac was better in reducing pain, while combination of enzymes used in the study was better in reducing oedema. Combination of the enzymes used in this study is safer than diclofenac in cases of the closed fracture lower end radius.


Pain, Inflammation, Diclofenac, Oral enzymes, Bromelain

Full Text:



Nellans KW, Kowalski E, Chung KC. The epidemiology of distal radius fractures. Hand Clinics. 2012;28(2):113-25.

American academy of orthopaedic surgeons. Distal radius fractures (broken wrist). Orthoinfo org. Available at

Tripathi KD. Nonsteroidal anti-inflammatory drugs and antipyretics- analgesics. In: Essentials of medical Pharmacology. 6th ed. New Delhi: Jaypee Brothers Medical Publishers Ltd; 2008:184-201.

Mazourov VI, Lila AM, Klimko NN. The efficacy of systemic enzyme therapy in the treatment of rheumatoid arthritis. Int J immunotherapy. 1997;13:85-91.

Shahid S. Role of systemic enzymes in infections. Webmed Central Complementary Medicine. 2011;2(11):WMC002495.

The enzyme as drug: Application of enzymes as pharmaceuticals, current opinion in biotechnology. 2003;14:1-7.

Rakhimov MR. Anti-inflammatory activity of domestic papain. Eksp Klin Farmakol. 2001;64(4):48-9.

Selloum L, Bouriche H, Tigrine C, Boudoukha C. Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp Toxicol Pathol. 2003;54(4):313-8.

Hale LP, Greer PK, Sempowski GD. Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. Clinical Immunology. 2002;104:183-90.

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.

Castell JV, Friedrich G, Kuhn CS. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol. 1997;273:139-46.

Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes: a randomised, double-blind study versus Diclofenac. Clin Drug Invest. 2000;19:15-23.

Singer F, Singer C, Oberleitner H. Phlyoenzym versus diclofenac in the treatment of activated osteoarthritis of the knee. Int J Immunother. 2001;17:135-41.

Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clinical immunology (Orlando, Fla). 2008;128(1):66-74.

Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001;58(9):1234-45.

Uhlig G, Seifert J. The effect of proteolytic enzymes (traumanase) on posttraumatic oedema. Fortschr Med. 1981;99(15):554-6.

Pirotta F, de Giuli-Morghen C. Bromelain: anti-inflammatory and serum fibrinolytic activity after oral administration in the rat. Drugs Exp Clin Res. 1978;4:1-20.

Izaka K, Yamada M, Kawano T. Gastrointestinal absorption and anti-inflammatory effect of bromelain. Jpn J Pharmacol. 1972;22:519-34.

Masson M. Bromelain in blunt injuries of the locomotor system. A study of observed applications in general practice. Fortschr Med. 1995;113:303-6.

Wittenborg A, Bock PR, Hanisch J, Saller R, Schneider B. Comparative epidemiological study in patients with rheumatic diseases illustrated in a example of a treatment with non-steroidal anti- inflammatory drugs versus an oral enzyme combination preparation. Arzneimittel-Forschung. 2000;50:728-38.

Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. 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.

Rovenska E, Svik K, Stancikova M, Rovensky J. Inhibitory effect of enzyme therapy and combination therapy with cyclosporin A on collagen-induced arthritis. Clin Exp Rheumatol. 2001;19:303-9.

Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a treatment for osteoarthritis: a Review of Clinical Studies. Evidence-based Complementary and Alternative Medicine. 2004;1(3):251-7.

Changulani M, Okonkwo U, Keswani T, Kalairajah Y. Outcome evaluation measures for wrist and hand - which one to choose? International Orthopaedics. 2008;32(1):1-6.

MacDermid JC, Turgeon T, Richards RS, Beadle M, Roth JH. Patient rating of wrist pain and disability: a reliable and valid measurement tool. J Orthop Trauma. 1998;12:77-86.

Kerkhoffs G, Struijs P, de Wit C, Rahlfs V, Zwipp H, van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. British Journal of Sports Medicine. 2004;38(4):431-5.

Kamenicek V, Halon P, Franek P. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling. Acta Chir Orthop Traumatol Cech. 2001;68(1):45-9.