Papain

Papain is extracted from the fruit of the papaya tree and is used to make medicine.

Papain is used to treat inflammatory pain and swelling, as well as water retention following trauma or surgery. It is also used as a digestive aid and to treat worm infections, inflammation of the throat and pharynx, herpes zoster symptoms, persistent diarrhea, hay fever, a runny nose and psoriasis. In addition to this, papain is also used in conjunction with conventional treatments for tumors. Some people apply papain directly to the skin to treat infected wounds and ulcers. In the industrial manufacturing sector, papain is used in cosmetics, toothpaste, enzymatic cleaners for soft contact lenses, meat tenderizers and meat products. It is also used as a stabilizer and in the production of frost-proof beer.

How does papain work?

The papaya enzyme papain digests protein and releases amino acids that the intestine can absorb. It also blocks the growth of harmful intestinal bacteria, helping to maintain a healthy intestinal flora. As an added bonus, it breaks down gliadin: a component of gluten that causes problems for people with coeliac disease (1, 2). Papain also has antioxidant and anti-inflammatory properties. This allows it to neutralize excessive amounts of free radicals, which can contribute to a number of chronic diseases (3, 4).

Potential health benefits of papain

Papain can improve digestion

Papain aids digestion by breaking down proteins into amino acids, which can help the body absorb nutrients. For this reason, it can reduce symptoms of a range of digestive problems (5).

Celiac disease

Papain can break down parts of gliadin - a component of gluten. It therefore has the potential to help people with coeliac disease. Studies have shown that papain supplementation can improve nutrient absorption and reduce thin stools in people with coeliac disease (1).

Digestive problems and heartburn

In a clinical study involving 200 subjects with digestive problems, papain reduced inflammation of the stomach. Compared to a placebo, it alleviated symptoms such as abdominal pain, vomiting, nausea, heartburn, belching and flatulence (6).

Irritable bowel syndrome

In two clinical trials involving a total of 150 participants with constipation-dominant irritable bowel syndrome or chronic gastritis, papain relieved symptoms such as constipation, bloating, painful bowel movements and abdominal pain, while reducing inflammation (7). Papain can also block the growth of harmful gut bacteria that can cause irritable bowel syndrome and other digestive problems (8).

Gastric ulcers

In rats with gastric ulcers, papain was able to reduce the acidity of gastric juices and the size of gastric ulcers (9).

Papain could support wound healing

In clinical studies involving over 350 adults and 30 children, papain was applied to the skin to accelerate the healing of skin ulcers and burns. It reduced wound size, removed damaged skin, accelerated wound closure and shortened hospital stays. It worked better than collagenase, hydrogen peroxide or a placebo (10). In cell-based and animal studies, papain applied to the skin removed dead cells and tissue, stimulated wound healing and reduced scarring and inflammation. And apart from helping the formation of new tissue, it also prevented bacterial infections (11, 12).

Papain can reduce inflammation and oxidative stress

In three clinical studies involving over 250 subjects, papain reduced inflammation of the stomach and intestines and improved symptoms such as nausea, stomach pain and constipation (13). A combination of papain and other enzymes (bromelain, trypsin and chymotrypsin) reduced high TGF-beta levels and reduced inflammation in a study involving 130 volunteers (14). In rats, papain was able to reduce inflammation as well as the non-steroidal anti-inflammatory drug indomethacin (15). In addition, papain increased the amount of regulatory T cells that can fight inflammation and normalize the immune response. It also reduced the levels of pro-inflammatory cytokines (TNF, IL-8, IL-6) in human cells (16).

Finally, papain has been shown to have the following benefits in cell studies and animal studies (17, 18):

It reduced oxidative stress as well as vitamin E and vitamin C
It increased the levels of antioxidant enzymes (glutathione, SOD, CAT)

Papain could have a positive effect on dental health

In a clinical study of 52 subjects with braces and inflammation of the gums, a toothpaste containing papain, bromelain, miswak and neem was able to limit plaque and tooth decay better than a standard toothpaste (19). In 7 clinical studies with children, a papain gel was able to clean cavities in teeth and reduce the amount of bacteria, pain and cost (20). In the laboratory, a papain gel removed tooth decay without affecting the bone structure of the teeth. It also prevented the growth of plaque-causing bacteria and their biofilms (21).

Papain could help against infections

In 3 clinical trials involving over 400 patients with dengue fever, a papaya leaf extract increased platelet counts and reduced the length of hospital stay compared to a placebo. However, it is unclear whether this effect can be attributed to papain or other compounds in the leaves (22). In a three-year study of 62 women with vaginal yeast infections, a supplement containing papain, bromelain and rutin improved symptoms and reduced the recurrence of infection (23).

In cell studies and animal studies, papain destroyed biofilms - a sticky mass of bacteria that resists common treatments. It also blocked the growth of bacteria, fungi and parasites such as the following (24, 25):

Bacteria that cause food poisoning or respiratory, digestive or urinary tract infections, as well as irritable bowel syndrome (Staphylococcus aureus, Bacillus cereus, E. coli, Pseudomonas aeruginosa, Shigella)
Yeasts
Schistosoma mansoni, a parasite that causes schistosomiasis

Papain can relieve pain and muscle soreness

In a clinical study of 80 patients who had undergone surgery, a supplement containing papain, bromelain and rutin reduced pain faster than a placebo. It also reduced the need for painkillers (26).

In another study of 30 healthy volunteers, a multi-enzyme supplement reduced muscle pain and soreness after intense exercise slightly better than a placebo. In addition, supplementation prevented muscle damage and improved recovery after exercise (27, 28).

Papain could alleviate autism symptoms

Digestive enzymes could reduce the symptoms of children with autism. In a clinical study of 100 children with autism, papain and pepsin improved emotional response, general behavior and digestive tract symptoms (29).

Papain could help with herpes blisters

In a clinical trial involving 192 patients with cold sores, digestive enzymes including papain were as effective as the antiviral drug acyclovir in relieving pain and skin lesions. However, it is difficult to say how much papain and how much the other digestive enzymes used contributed to this result (30).

Papain could relieve sore throat

In a clinical trial involving 100 patients with sore throat and/or tonsillitis, lozenges containing papain reduced swelling, mucus production, redness and pain better than a placebo. However, these lozenges also contained iysozyme and bacitracin, both of which can kill bacteria, so it is difficult to estimate how large a contribution papain made (31).

Papain could have anti-cancer effects and reduce side effects of radiation therapy

In a clinical trial involving 120 patients with advanced cervical cancer, papain in combination with trypsin and chymotrypsin reduced the side effects of radiotherapy (32).

In addition, papain was able to block the growth, spread and survival of various cancer cells (liver cancer, colon cancer, lung cancer, skin cancer, stomach cancer) in cell studies and animal studies (33, 34).

Safety and side effects

Papain is probably safe and harmless when used in normal food quantities. It is also potentially safe and harmless for most adults in medicinal quantities, although it may cause irritation around the mouth and stomach. Skin contact with raw papain can cause skin irritation and blisters. Oral ingestion of large amounts of papain may not be safe and harmless. In excessive amounts, papain can cause serious damage to the throat. There have also been some reports of severe allergic reactions.

Precautions and warnings

Pregnancy and lactation: Oral intake of papain may not be safe during pregnancy. There are concerns that papain may cause birth defects and miscarriages. Not enough is known about the safety of using papain while breastfeeding, so breastfeeding women should avoid papain. Allergies to figs or kiwis: A case report suggests that people who are allergic to figs or kiwis may also be allergic to papain.

Blood clotting disorders: There are concerns that papain may increase the risk of bleeding in people who suffer from blood clotting disorders.

Interactions

At this time, there is no information on interactions of papain with medications or supplements.

Dosage

The following dosages have been investigated in scientific studies. Oral:

For the treatment of inflammatory swellings after accidents or operations: 1500 mg (2520 FIP units) papain per day.

References

Further sources

Bienen H, Raus I. [Therapeutic comparison of throat lozenges; (author's transl)]. MMW Munch Med Wochenschr 1981;123:745-7.
Billigmann P. [Enzyme therapy-an alternative in treatment of herpes zoster. A controlled study of 192 patients]. Fortschr Med 1995;113:43-8.
Desser L, Rehberger A, Paukovits W. Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro. Cancer Biother 1994;9:253-63.
Diez-Gomez ML, Quirce S, Aragoneses E, Cuevas M. Asthma caused by Ficus benjamina latex: evidence of cross-reactivity with fig fruit and papain. Ann Allergy Asthma Immunol 1998;80:24-30.
Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid= 786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:3.0.1.1.13&idno=21
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. Ann Allergy 1985;55:541-3.
Raus I. [Clinical studies on Frubienzyme in a controlled double-blind trial]. Fortschr Med 1976;94:1579-82.
Reinecke M. [Treatment of inflammatory diseases of the mouth and throat with Larypront in ENT practice; (author's transl)]. MMW Munch Med Wochenschr 1976;118:1253-4.
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.
Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaesthetic agents. Br J Dermatol 1988;119:535-40.
Valueva TA, Revina TA, Mosolov VV. Potato tuber protein proteinase inhibitors belonging to the Kunitz soybean inhibitor family. Biochemistry (Mosc) 1997;62:1367-74.
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 Biother 1995;10:147-52.