Scientific Name: Papain
Other Names: Carica papaya, Vegetable pepsin

Who is this for?

Uses

Enzymes accelerate reactions within body cells. In the human body, the pancreas usually produces enzymes that break down foods into nutrients that the body can use for energy and other functions. Enzyme deficiencies are rare, but individuals who have cystic fibrosis or diseases of the pancreas may not produce enough natural enzymes to digest foods properly. Papain, an enzyme produced by the tropical fruit, papaya, is proteolytic, which means that it digests inert (non-living) proteins. While it breaks down proteins in foods, it will not harm living tissue in the body. Frequently, papain is included in prescription combinations of digestive enzymes to replace what individuals with cystic fibrosis or pancreas conditions cannot produce naturally. Because it improves digestion in general, papain has also been used orally to treat less serious digestion disorders such as bloating and chronic indigestion. Since parasitic organisms are largely proteins, papain has sometimes been taken internally to eliminate intestinal worms, but this use is rare today.

In several studies of cancer patients, oral enzyme supplements containing papain helped to relieve treatment side effects such as mouth sores and difficulty swallowing. Additionally, chemicals in papain may increase the function of the immune system and they may also promote the release of natural chemicals that attack tumor cells. Papain may lessen overall inflammation, as well. All of these potential effects may make papain-containing preparations useful as a supplement to cancer therapy. In fact, an oral prescription product containing papain and other enzymes has orphan drug status in the United States for the treatment of multiple myeloma, a form of bone marrow cancer. An orphan drug has received approval from the U.S. Food and Drug Administration (FDA) because it shows effectiveness for treating severe or rare diseases that usually have few other treatment options.

In other research, papain and related enzymes have been studied for oral use in several conditions. Some evidence shows that they may help to prevent complications of diabetes, possibly by lessening protein deposits in the kidneys. Proteolytic enzymes such as papain may also decrease pain and inflammation associated with rheumatoid arthritis, improve healing of injuries, and reduce swelling after surgery. In Europe, papain is available as an ingredient in several non-prescription products that are sold for relieving inflamed and swollen tissue in the respiratory tract. General stimulation of immune response and decreases in inflammation produced by papain are thought to be responsible for some of these observed effects, but other possible causes are not clear. Results of some studies are inconclusive, and more study is needed before papain can be recommended for these conditions.

Topically, papain has been used for many skin conditions. Its ability to break down proteins is used to remove dead tissue from burns, to help skin injuries heal, to relieve psoriasis, to remove warts, and to treat ringworm. Cold sores caused by Herpes zoster virus have been treated successfully with both oral and topical papain-containing products. In one small study of individuals with Herpes zoster, an oral papain product was as effective as a prescription antiviral medication in resolving pain, but not redness. A year-long observational study of more than 400 women found that those who ate papaya at least once a week were less likely to have chronic infections with human papilloma virus (HPV), a common sexually transmitted disease. In laboratory studies, topical application of papain has also shown some antibacterial properties, which may be due to papain’s interference with an enzyme made by certain bacteria. Further study is needed to prove or disprove its possible antibacterial effects, however.

An injectable form of chymopapain, an enzyme closely related to papain, has been used to treat herniated (“slipped”) discs in the spine. It is used more in Europe and other countries than it is in the United States.

Some evidence from animal studies may relate taking papain with causing birth defects in the unborn offspring of pregnant animals who were fed papain. In other studies, ripe papaya — the fruit that produces papain — did not affect pregnant animals or their babies, but chemicals in unripe papaya fruits or sap caused contractions of the uterus in some pregnant animals. Uterine contractions could result in miscarriage. Although no further studies support these results, pregnant women are advised to avoid taking large amounts of papain-containing products, unless such use is medically necessary and supervised by a healthcare professional.

Precautions

Cases of sores in the esophagus have been reported in individuals who consumed large amounts of papaya fruit. No similar effects have been reported from the medicinal use of papain, but esophageal irritation is possible.

In a condition known as “ficus-fruit syndrome” individuals who are allergic to tropical fruits such as bananas, figs, or kiwi fruit may also be allergic to papaya or to papain, which is derived from the papaya fruit. Allergic reactions to papain have also been reported in individuals who are sensitive to latex or to the ornamental houseplant, weeping fig (Ficus benjamina).

What side effects should I watch for?

Major Side Effects

Eating the raw sap of papaya fruits may cause irritation, pain, or sores in the mouth, esophagus, stomach, or intestines.

Due to its ability to digest proteins, papain may also damage skin or mucous membranes - especially if tissue is already damaged by sores or other injuries. Inflammation or irritation of the mouth, esophagus, stomach, or intestines could result from taking papain orally. Skin may blister or itch intensively, when papain is applied topically.

Less Severe Side Effects

Taking papain or touching papaya plants may cause sensitive individuals to experience general allergy symptoms such as diarrhea, runny nose, sneezing, sweating, and watering eyes. Pollen from the papaya plants is also known to be a significant cause of allergic responses — especially among individuals who work in cultivating, harvesting, or processing the plants.

What interactions should I watch for?

Prescription Drugs

In studies and case reports, papain has been shown to increase the time blood needs to clot. When it is taken with antiplatelet or anticoagulant drugs, the effect of the drug may be increased, resulting in uncontrolled bleeding.

• Antiplatelets include clopidogrel and Ticlid
• Anticoagulants include heparin and warfarin

Non-prescription Drugs

Papain can affect the ability of blood to clot after an injury. Aspirin can also delay clotting, so papain should not be taken orally at the same time as aspirin.

Herbal Products

Theoretically, if papain is taken orally with other herbs that affect blood clotting, bleeding may occur. Some of the most common herbal products that might inhibit blood clotting are:

• Danshen
• Devil's Claw
• Eleuthero
• Garlic
• Ginger (in high amounts)
• Ginkgo
• Horse Chestnut
• Panax Ginseng
• Red Clover
• Saw Palmetto

Foods

Chemicals found in potatoes may decrease the ability of papain to break down proteins. No serious consequences are thought to result, but papain may not be as effective as expected if potatoes are consumed at the same time.

Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how papain interacts with drugs, other herbals, and foods and the severity of those interactions, please use our Drug Interactions Checker to check for possible interactions.

Should I take it?

Papain is derived from the sap (also called latex or milk) of unripe fruits from the papaya, a small tree-like plant that grows in tropical areas. The plants, which only live about 10 years, are often grown on plantations. Easily recognized by their straight stems topped with large multi-lobed leaves, papayas bear clusters of large fruits that are yellow-orange in color when ripe. Ripe papaya fruits are eaten raw, dried, made into jam, or processed for juice. Papaya leaves, flowers, and green fruits may be cooked as vegetables. The fibrous bark of the tree has been used for making twine and fabrics. Animal feed made from papaya fruits, fruit skins, or juice may be given to livestock to control intestinal parasites.

Papain is obtained by making shallow cuts in the surfaces of unripe fruits that are still on the trees. The white sap that oozes out is allowed to dry before being collected and refined. The rubbery sap contains several enzymes, primarily papain, that can break down certain proteins. As a group, these chemicals are known as proteolytic enzymes. Commercially, papain is included in meat tenderizers. In the cosmetics industry, it is used as a softener in hand and face creams and as a conditioner in shampoo. Papain or related enzymes from papaya are also included in chewing gum, soaps, toothpastes, and contact lens cleaners.

Dosage and Administration

Today, many prescription and non-prescription medications that contain papain are available.

To replace digestive enzymes, large doses of enzyme combinations must be taken several times a day. These are prescription medications and each has specific directions that must be followed carefully.

Papain is also available without a prescription by itself or, more commonly, in combinations with other enzymes, such as bromelian (which is derived from pineapples). Doses of these over-the-counter forms of papain vary greatly depending on the condition being treated and the other ingredients in the product. Individuals who choose to take papain should follow the directions on the package that is purchased.

Summary

Papain is a proteolytic (protein-reducing) enzyme that is included in oral replacement drugs for individuals who do not produce digestive enzymes naturally. It is also used for digestive conditions such as indigestion. Papain may be taken orally to relieve inflammation and to improve healing. Additionally, it is being studied for relief of cancer therapy side effects, diabetes complications, and rheumatoid arthritis.

Papain may be applied to the skin to help burns and other injuries heal.

Risks

Due to a small chance of miscarriage or birth defects, pregnant women should take papain only with medical supervision. Individuals allergic to figs or kiwi fruit may also be allergic to papain.

Side Effects

Raw papaya sap may cause sores on skin or mucous membranes that come in contact with it. Allergic symptoms may be caused by taking papain or touching papaya plants.

Interactions

Papain may increase the effects of drugs and herbs that thin the blood. As a result, uncontrolled bleeding may occur.

Last Revised October 11, 2006

References

Adebiyi A, Adaikan PG, Prasad RN. Papaya (Carica papaya) consumption is unsafe in pregnancy: fact or fable? Scientific evaluation of a common belief in some parts of Asia using a rat model. British Journal of Nutrition. 2002;88(2):199-203.

Australian Government Department of Health and Ageing. The biology and ecology of papaya (paw paw), Carica papaya L., in Australia. April 2003. Available at: http://www.health.gov.au/ogtr/rtf/ir/papaya.rtf. Accessed August 11, 2003.

Bahl A, Chander S, Julka PK, et al. Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer: an Indian experience. Journal of the Association of Physicians of India. 2006;54:191-195.

Beuth J, Ost B, Pakdaman A, et al. Impact of complementary oral enzyme application on the postoperative treatment results of breast cancer patients--results of an epidemiological multicentre [sic] retrolective cohort study. Cancer Chemotherapy and Pharmacology. 2001;47 Suppl:S45-S54.

Bienen H, Raus I. Therapeutic comparison of throat lozenges; (author's translation). [Article in German]. MMW Muenchener Medizinische Wochenschrift. 1981;123(18):745-747.

Billigmann P. Enzyme therapy--an alternative in treatment of herpes zoster. A controlled study of 192 patients. [Article in German] Fortschritte Der Medizin. 1995;113(4):43-48.

Chakraborty P, Ghosh D, Chowdhury I, et al. Aerobiological and immunochemical studies on Carica papaya L. pollen: an aeroallergen from India. Allergy. 2005;60(7):920-926.

Chaudhry AS. Comparing two commercial enzymes to estimate in vitro proteolysis of purified or semi-purified proteins. Journal of Animal Physiology and Animal Nutrition (Berlin). 2005 Dec;89(11-12):403-12.

Dale PS, Tamhankar CP, George D, Daftary GV. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemotherapy and Pharmacology. 2001;47(Suppl):S29-S34.

Dawkins G, Hewitt H, Wint Y, Obiefuna PC, Wint B. Antibacterial effects of Carica papaya fruit on common wound organisms. West Indian Medical Journal. 2003;52(4):290-292.

Diez-Gomez ML, Quirce S, Aragoneses E, Cuevas M. Asthma caused by Ficus benjamina latex: evidence of cross-reactivity with fig fruit and papain. Annals of Allergy, Asthma and Immunology, 1998;80(1):24-30.

Dominguez de Maria P, Sinisterra JV, Tsai SW, Alcantara AR. Carica papaya lipase (CPL): an emerging and versatile biocatalyst. Biotechnology Advances. 2006;24(5):493-499.

Duke JA. Carica papaya L. Handbook of Energy Crops. 1983. Unpublished. Available at: http://www.hort.purdue.edu/newcrop/duke_energy/Carica_papaya.html. Accessed August 11, 2003.

Food and Drug Administration. FDA grants orphan drug status to wobe-mugos for multiple myeloma. [press release] August 10, 2000.

Giuliano AR, Siegel EM, Roe DJ, et al; for the Ludwig-McGill HPV Natural History Study. Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV Natural History Study. Journal of Infectious Diseases. 2003;188(10):1508-1516.

Gujral MS, Patnaik PM, Kaul R, et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemotherapy and Pharmacology. 2001;47 Suppl:S23-S28.

HealthNotes, Inc. Digestive enzymes. 2002. Available at: http://www.mycustompak.com/healthNotes/Supp/Enzymes.htm Accessed August 15, 2003.

Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. American Journal of Health System Pharmacy. 2000;57(13):1221-1230.

Hemmer W, Focke M, Gotz M, Jarisch R. Sensitization to Ficus benjamina: relationship to natural rubber latex allergy and identification of foods implicated in the Ficus-fruit syndrome. Clinical and Experimental Allergy. 2004;34(8):1251-1258.

Hewitt H, Whittle S, Lopez S, Bailey E, Weaver S. Topical use of papaya in chronic skin ulcer therapy in Jamaica. West Indian Medical Journal. 2000;49(1):32-33.

Jellin JM, Gregory P, Batz F, Hitchens K, et al, eds. Pharmacist's Letter/Prescriber's Letter. Natural Medicines Comprehensive Database, 3rd Edition. Stockton CA: Therapeutic Research Facility, 2000.

Kamaruzzaman M, Chowdhury SD, Podder CK, Pramanik MA. Dried papaya skin as a dietary ingredient for broiler chickens. British Poultry Science. 2005;46(3):390-393.

Leipner J, Iten F, Saller R. Therapy with proteolytic enzymes in rheumatic disorders. BioDrugs. 2001;15(12):779-789.

Leipner J, Saller R. Systemic enzyme therapy in oncology: effect and mode of action. Drugs. 2000;59(4):7697-80.

Lubec G, Forster O, Coradello H, Maxa E, Pollak A. Proteolytic degradation of the glomerular basement membrane and immunochemical characterization of split products. Renal Physiology. 1980;3(1-6):126-132.

Lubec G, Pollak A. Reduced susceptibility of nonenzymatically glucosylated glomerular basement membrane to proteases: is thickening of diabetic glomerular basement membranes due to reduced proteolytic degradation? Renal Physiology. 1980;3(1-6):4-8.

Mahattanatawee K, Manthey JA, Luzio G, Talcott ST, Goodner K, Baldwin EA. Total antioxidant activity and fiber content of select Florida-grown tropical fruits. Journal of Agricultural and Food Chemistry. 2006 Sep 20;54(19):7355-7363.

Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Annals of Allergy. 1985;55(4):541-543.

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. Radiotherapy in Oncology. 2002;65(1):17-22.

Mikhalchik EV, Ivanova AV, Anurov MV, et al. Wound-Healing Effect of Papaya-Based Preparation in Experimental Thermal Trauma. Bulletin of Experimental Biology in Medicine. 2004;137(6):560-562.

Oderinde O, Noronha C, Oremosu A, Kusemiju T, Okanlawon OA. Abortifacient properties of aqueous extract of Carica papaya (Linn) seeds on female Sprague-Dawley rats. Nigerian Postgraduate Medical Journal. 2002;9(2):95-98.

Pieper B, Caliri MH. Nontraditional wound care: A review of the evidence for the use of sugar, papaya/papain, and fatty acids. Journal of Wound, Ostomy and Continence Nursing. 2003;30(4):175-183.

Popiela T, Kulig J, Hanisch J, Bock PR. Influence of a complementary treatment with oral enzymes on patients with colorectal cancers--an epidemiological retrolective cohort study. Cancer Chemotherapy and Pharmacology. 2001;47 Suppl:S55-S63.

Raus I. Clinical studies on Frubienzyme in a controlled double-blind trial. [Article in German] Fortschritte Der Medizin.1976;94(28):1579-1582.

Roep BO, van den Engel NK, van Halteren AG, Duinkerken G, Martin S. Modulation of autoimmunity to beta-cell antigens by proteases. Diabetologia. 2002;45(5):686-692.

Runnie I, Salleh MN, Mohamed S, Head RJ, Abeywardena MY. Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed. Journal of Ethnopharmacology. 2004;92(2-3):311-316.

Sakalova A, Bock PR, Dedik L, et al. Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma. Cancer Chemotherapy and Pharmacology. 2001;47 Suppl:S38-S44.

Savickiene N, Dagilyte A, Lukosius A, Zitkevicius V. Importance of biologically active components and plants in the prevention of complications of diabetes mellitus. [Article in Lithuanian] Medicina (Kaunas). 2002;38(10):970-975.

Starley IF, Mohammed P, Schneider G, Bickler SW. The treatment of paediatric burns using topical papaya. Burns. 1999;25(7):636-639.

Steffen C, Menzel J. In vivo degradation of immune complexes in the kidney by orally administered enzymes. [Article in German] Wiener Klinische Wochenschrift. 1987;99(15):525-531.

Stepek G, Lowe AE, Buttle DJ, Duce IR, Behnke JM. In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against the rodent gastrointestinal nematode, Trichuris muris. Parasitology. 2006;132(Pt 5):681-689.

Tavares FX, Deaton DN, Miller AB, Miller LR, Wright LL, Zhou HQ. Potent and selective ketoamide-based inhibitors of cysteine protease, cathepsin k. Journal of Medicinal Chemistry. 2004;47(21):5049-5056.

van Kampen V, Merget R, Bruning T. Occupational allergies to papain. [Article in German] Pneumologie. 2005;59(6):405-410. .

Wald M, Zavadova E, Pouckova P, Zadinova M, Boubelik M. Polyenzyme preparation Wobe-Mugos inhibits growth of solid tumors and development of experimental metastases in mice. Life Sciences. 1998;63(8):PL43-48.

Zavadova E, Desser L, Mohr T. Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. Cancer Biotherapy 1995;10(2):147-152.

Last Revised October 11, 2006

Note: The above information is not intended to replace the advice of your physician, pharmacist, or other healthcare professional. It is not meant to indicate that the use of the product is safe, appropriate, or effective for you.

In general, herbal products are not subject to review or approval by the U.S. Food and Drug Administration (FDA). They are not required to be standardized, meaning that the amounts of active ingredients or contaminants they contain may vary between brands or between different batches of the same brand. Not all of the risks, side effects, or interactions associated with the use of herbal products are known because few reliable studies of their use in humans have been done.

This information is provided for your education only. Please share this information with your healthcare provider and be sure that you talk to your doctor and pharmacist about all the prescription and non-prescription medicines you take before you begin to use any herbal product.

Back