10 Benefits of Papaya Enzyme (Papain) + Side Effects

You’ll find papaya enzyme (papain) in papayas and in a number of dietary supplements. Not only does it enhance digestion and lower inflammation, but it may also help fight infections and improve wound healing. Keep reading to learn about its health benefits, dosage, and side effects.

What Is Papain?

Definition

Papain is a digestive enzyme naturally found in papaya (Carica papaya). It is a protease: an enzyme that breaks down proteins into amino acids, which aids digestion. Thanks to its protein-degrading action, papain is also often used as a meat tenderizer [1, 2].

Papain is extracted from papaya latex, a milky fluid that oozes from the fruit, stem, and leaves of the plant. The fruit is the richest in it: the more unripe the papaya, the more active the papain [3, 4, 5].

People have long known about the papaya enzyme, using it to improve digestion and to lower pain, swelling, and inflammation. Papain can reduce bloating, gas, and diarrhea. According to recent research, it may also combat inflammation and infections [6, 7, 8].

You can get papaya enzyme by eating papayas… but you would need to eat plenty of mostly unripe fruits. You can spot unripe papayas by the green color of their skin. Alternatively, various papain supplements are widely available [9].

What Does It Do?

Overall, the papaya enzyme or papain digests proteins, freeing amino acids the gut can absorb. Next, it blocks the growth of harmful gut bacteria, maintaining a healthy microbiome.

Plus, it degrades gliadin: a component of gluten that causes problems in people with celiac disease [10, 9, 6, 11]:

Papain is also an antioxidant and anti-inflammatory. As such, it can neutralize excess free radicals that can build up and contribute to a number of chronic diseases [7, 12, 13, 8, 14].

Snapshot

Here is an overview of the health benefits and risks of papaya enzyme [6, 7, 8, 9, 1]:

Proponents:

• May improves digestion
• May speed up wound healing
• May lower oxidative stress & inflammation
• May help with infections & sore throat
• May reduce pain & muscles soreness
• May support dental health
• May protect the brain
• May reduce shingles symptoms

Skeptics:

• Insufficient evidence for some benefits
• Mild side effects, such as stomach pain
• Possible allergic reactions
• Likely unsafe for pregnant women
• Possible drug interactions

Health Benefits

Possibly Effective

1) Improving Digestion

Overall, the papaya enzyme enhances digestion by breaking down proteins into amino acids, which helps the body absorb nutrients. Therefore, it can improve symptoms in people with various digestive disorders [1, 15, 9, 16, 17].

Celiac Disease

Papain can break down parts of gliadin, a component of gluten. As such, it has the potential to help people with celiac disease. In 3 people with celiac disease, papain supplements improved nutrient absorption and reduced loose stools [16, 18, 10].

Indigestion & Heartburn

In a clinical study of 200 people with indigestion, papain reduced stomach inflammation. Compared to the placebo, it relieved symptoms such as stomach pain, vomiting, nausea, heartburn, burping, and bloating [19].

IBS

In two clinical studies of over 150 people in total, either with constipation-dominant IBS or chronic stomach inflammation (gastritis), papaya enzyme improved symptoms such as constipation, bloating, painful bowel movements, flatulence, and stomach pain, while reducing inflammation [9, 6].

Papaya enzyme can also block the growth of harmful gut bacteria that cause IBS and other stomach and gut disorders [20, 11].

Stomach Ulcers

Papain also decreased stomach acidity and ulcer size in rats with stomach ulcers [21, 22].

All in all, the evidence suggests that papain may help with digestive issues such as indigestion, IBS, and stomach inflammation. You may discuss with your doctor if it may help as an add-on to your treatment regime. Importantly, never use papain as a replacement for what your doctor recommends or prescribes.

2) Wound Healing

In multiple clinical studies with over 350 people and 30 children, papaya enzyme applied to the skin sped up the healing of skin ulcers or burns. It reduced wound size, removed damaged tissue, accelerated wound closure, and shortened the hospital stay. It worked better than collagenase, hydrogen peroxide dressing, or placebo [23, 24, 25, 26, 27, 28].

In animal and cell-based studies, topical papain removed dead cells and tissue, stimulated wound healing, and decreased scarring and inflammation. And aside from helping new tissue form, it may also prevent bacterial infection [29, 30, 31, 32, 33, 34, 35, 36].

Again, the existing evidence backs the use of papain for wound healing. You may use it for this purpose if your doctor determines that it may be helpful in your case.

3) Inflammation & Oxidative Stress

In 3 clinical studies with over 250 people, papaya enzyme lowered gut and stomach inflammation and improved symptoms such as nausea, stomach pain, and constipation [9, 6, 19]

A combination of papain with other enzymes (bromelain, trypsin, and chymotrypsin) decreased high TGF-beta levels, thus lowering inflammation in 130 people [37].

In rats, papain lowered inflammation as good as the NSAID indomethacin [38, 39].

What is more, papaya enzyme increased regulatory T cells, which can fight inflammation and normalize the immune response. It also lowered inflammatory cytokines (TNF, IL-8, IL-6) in human cells [40].

Finally, papain offered the following benefits in animal and cell-based studies [41, 42, 43, 44]:

• Lowered oxidative stress similar to vitamin E and vitamin C
• Increased antioxidant enzymes (glutathione, SOD, CAT)

Although a bit limited, the evidence suggests that papain reduces inflammation. Further clinical research is needed to determine how to use it therapeutically for inflammatory issues. Its potential antioxidant activity requires validation in clinical studies.

Insufficient Evidence

1) Dental Health

In a clinical trial on 52 people with braces and gum inflammation, toothpaste with papain, bromelain, miswak, and neem limited dental plaque and tooth decay better than standard toothpaste. Papaya enzyme gel cleared tooth cavities, lowered bacterial counts, and reduced pain and costs in 7 clinical studies on 159 children [45, 46, 47, 48, 49, 50, 51, 52].

In the lab, papaya enzyme gel resolved tooth decay without affecting the bone structure of teeth. It also prevented the growth of plaque-causing bacteria and their biofilms [53, 54, 55, 56, 57, 58].

Although the results are promising (especially concerning its effects on cavities removal), only a few small clinical trials have been carried out. More studies on larger populations are needed to confirm these preliminary findings.

2) Infections

In 3 clinical studies with over 400 people with dengue fever, papaya leaf extract increased the number of platelets and reduced the hospital stay compared to placebo. However, it is unclear if the effect was due to papaya enzyme or other compounds in the leaves [59, 60, 61].

In a 3-year study on 62 women with vaginal yeast infections (candidiasis), a supplement containing papaya enzyme, bromelain, and rutin improved symptoms and reduced infection recurrence [62].

In animal and cell studies, papain destroyed biofilms, a sticky mass of bacteria that resists common treatments. It also blocked the growth of the following bacteria, fungi, and parasites [63, 11, 64, 43, 65]:

• Bacteria that cause food-borne illnesses, respiratory, gut, stomach and urinary infections, and IBD (Staphylococcus aureus, Bacillus cereus, E.coli, Pseudomonas aeruginosa, Shigella)
• Candida
• Schistosoma mansoni, a parasite causing bilharzia

Because the clinical trials used papain in combination with other papaya compounds or herbal extracts and the only studies using papain alone were done in animals and cells, there is insufficient evidence to claim that this enzyme helps fight infections in humans. More clinical trials using papain alone are needed to evaluate its effects.

3) Pain and Muscle Soreness

In a clinical trial on 80 people who underwent surgery, a supplement containing papaya enzyme, bromelain, and rutin reduced pain quicker than placebo. It also lowered the participants’ need for painkillers [66].

In another 30 healthy people, a multi-enzyme supplement including papain reduced muscle pain and soreness after intense exercise slightly better than placebo. Additionally, supplementation prevented muscle damage and enhanced post-exercise recovery [67, 68].

Two clinical trials testing papain in combination with other enzymes and compounds cannot be considered sufficient evidence that papain helps with pain and muscle soreness. Further clinical research with papain alone is required.

4) Autism Symptoms

Digestive enzymes may improve the symptoms of some children with autism. Papain and pepsin improved emotional response, general behavior, and gut symptoms in a clinical study of over 100 children with autism [12].

A single clinical trial cannot be considered sufficient evidence to attest to the effectiveness of papain at improving the emotional symptoms of autism. Larger, more robust clinical trials are needed to validate this preliminary result.

5) Shingles

In a clinical study on 192 people with shingles, digestive enzymes including papaya enzyme relieved pain and skin lesions as effectively as the antiviral drug acyclovir. However, it’s difficult to say how much papain (and not the other digestive enzymes used in the therapy) contributed to the benefits [69].

6) Sore Throat

In a clinical study on 100 people with a sore throat and/or tonsils inflammation, multi-ingredient lozenges with papaya enzyme reduced swelling, mucus, coughing, redness, and pain better than the placebo. But these lozenges also contained lysozyme and bacitracin, both of which can kill bacteria, so the specific contribution of papain to the effects observed is difficult to estimate [13].

7) Fighting Cancer

In a clinical study on 120 people with advanced cervical cancer, papaya enzyme together with trypsin and chymotrypsin reduced radiotherapy side effects (vaginal, genital, urinary and gut problems) [70].

In animal and cell studies, papaya enzyme blocked the growth, spread, and survival of various cancer cells (liver, colon, gut, lung, skin) [8, 71, 72, 73, 74].

Larger clinical studies have yet to determine the effects of papaya enzyme in cancer prevention and fight.

Limitations and Caveats

The evidence about the benefits and risks of the papaya enzyme is largely based on animal and cell-based studies. The few published clinical trials had a limited number of participants.

Furthermore, a number of studies used multi-enzyme supplements, making the contribution of papain unclear.

Side Effects & Precautions

This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.

Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.

Common Side Effects

Side effects reported after using papaya enzyme are mild and include [24, 75]:

• Stomach pain
• Diarrhea
• Throat irritation
• Skin rash
• Itching

Allergy

If you are allergic to papaya or latex, avoid papain supplements; they may trigger an allergic reaction [76].

Pregnancy/ Fertility

In pregnant rats, unripe or semi-ripe papayas stimulated contractions. In male rats and mice, papaya extracts lowered sperm motility and fertility [77, 78, 79, 80, 81].

Based on this preliminary evidence, pregnant women or couples trying to conceive should probably avoid papain supplements.

Drug interactions

Supplement/Herb/Nutrient-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.

The combination of papaya enzyme together with diabetes drugs may excessively lower blood sugar levels [82].

Papaya leaf extracts may increase platelets. Papaya enzyme or purees may have a similar effect. Their combination with blood thinners (such as heparin, aspirin, and warfarin) should be avoided [83, 84].

Dosage & Supplement Forms

Choose a Formulation

Depending on your health goals, you can take papaya enzyme by mouth or apply it to your skin.

Unripe papayas contain papain, but it’s hard to know how much. For more precise dosing, papaya enzyme is available as fruit mash/puree, powder, capsules, chewable tablets, and lozenges [6, 85, 13].

It is also formulated into creams, gels, and wound dressings.

Remember that papaya enzyme supplements have not been approved by the FDA for medical use due to the lack of solid clinical research. Regulations set manufacturing standards for supplements but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Supplement Combinations

• Bromelain: by far the most popular combination. Bromelain may also improve digestion and reduce inflammation. Plus, toothpaste with papain and bromelain removed teeth stains better than standard toothpaste in the lab [86].
• Other digestive enzymes: multi-enzyme formulas may further enhance digestion. Probiotics and/or bile are sometimes added as well [87].
• Chlorophyll: a less-known combination. Cream with papain and chlorophyll for wound care helped remove dead tissue and heal wounds quicker [88, 89].

Dosage

Because papain is not approved by the FDA for any condition, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if papain may be useful as a complementary approach in your case and which dose you should take.

You can take papain fruit mash straight or mix it with water, juice, food, or smoothies. Capsules or chewable tablets contain between 20mg to 40mg papain and should be taken according to the specifications of each brand, as the supplements are not standardized. Papain powder is also available.

Caricol is a concentrate from the pulp of unripe papayas. It also contains natural flavors and mango and plum concentrate, which improve its taste. Clinical studies used 20 mL/20 g of Caricol once to twice a day. The manufacturers recommend taking 1-3 portions (21 mL each) after meals or as needed [9, 6].

For sore throat, people can take lozenges (Frubienzym) containing 2 mg papain, 5 mg lysozyme, and 200 I.U. bacitracin for 4 days [13].

For Dogs

Papaya enzyme gel removed dead tissue and accelerated wound healing better than sunflower oil in 3 dogs [90].

Papain was well tolerated by dogs, but did not affect their digestion or bowel movements [91].

Some sources suggest that papain can enhance digestive health and lower inflammation, especially in older dogs. Since processed dog food may be harder to digest, papain and other digestive enzymes might help.

Due to the limited research, it would be best to consult a vet before giving enzyme supplements to your dog.