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Dietary supplement

Papaya Enzyme Ingredients & Drug Interactions

by GNC Natural Brand

Tablet Or Pill Category: Other Combinations
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

Papaya Enzyme is a dietary supplement by GNC Natural Brand with 2 active ingredients. Its ingredients are commonly taken for digestive support for protein digestion, wound cleaning (debridement of dead tissue), sore throat and inflammation.Based on those ingredients, 92 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Papaya fruit powder, Papain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Papaya Enzyme by GNC Natural Brand

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 2 of its 2 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

This product contains 2 active ingredients: papain (an enzyme from papaya) and papaya fruit powder. Papain is a protease—a type of enzyme that breaks down proteins—and is the main digestive component in many enzyme supplements.

The papaya fruit powder supplies additional enzymes and the fruit's other compounds. The tablet also contains several inactive ingredients (fillers and binders) including sucrose, dextrose, maltodextrin, stearic acid, talc, artificial colors, and various flavoring agents.

Does it work?

Couldn't assess
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Not assessable

We hold no graded evidence for this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: digestive enzymes support healthy digestive function.
  • We looked for evidence on: indigestion, dyspepsia.
  • Our graded evidence for these ingredients doesn't cover that particular purpose.

The evidence we hold rates papain and papaya fruit powder as having insufficient reliable evidence for the uses listed—cancer, dental cavities, radiation skin damage, exercise muscle soreness, shingles, intestinal parasites, aging skin, hair loss, colorectal cancer, and diabetes. That means studies haven't established whether they work for these purposes; it doesn't mean they don't, just that solid proof isn't yet in our data.

The evidence, ingredient by ingredient Papain Papaya

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 2 of the 2 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 2 of 2.
  • General safety write-ups exist for 2 of 2.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Short-term use of papain at standard doses is generally well tolerated, though high oral doses may be unsafe. The most common side effects are allergic reactions in sensitive people—itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea.

Rare serious effects include esophageal perforation and severe stomach inflammation at high doses. Papaya fruit is generally safe when eaten as food, but concentrated supplements are less well studied.

Unripe (green) papaya, papaya latex, and papaya seeds should be avoided. For pregnancy, the safety data advises against concentrated papain and unripe papaya products.

Papaya fruit itself is rated likely safe in pregnancy, but unripe forms are possibly unsafe. There isn't enough data to know whether supplemental papain is safe while breastfeeding—talk with your pharmacist or doctor for personalized advice.

Side effects, ingredient by ingredient Papain Papaya

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 2 of the 2 matched ingredients can interact with medications — Papain, Papaya.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications.
  • For scale: 92 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, check with your doctor or pharmacist if you take blood thinners like warfarin—papain may increase their effects. Also double-check if you're on diabetes medications, amiodarone (a heart rhythm drug), or levothyroxine (thyroid medication), since moderate interactions are documented with all three.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with no assessable stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

If you're looking for digestive support and have no medication concerns, this product is generally well tolerated. But if you take blood thinners, diabetes drugs, heart medications, or thyroid replacement, you'll need to check with your doctor or pharmacist first—the interactions are documented and real.

Anyone with a papain or papaya allergy should skip it, and pregnant people should avoid the papain component.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 2 of 2 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 26, 2020.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Papaya Enzyme, straight from the product label.

Brand GNC Natural Brand
Barcode (UPC) 048107062422
Net contents 240 Chewable Tablet(s)
Market status On market
Date entered into DSLD Feb 26, 2020
DSLD ID 214210
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Papaya Enzyme by GNC Natural Brand, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
3 Tablet(s)
Maximum serving Sizes:
9 Tablet(s)
Servings per container
80
UPC/BARCODE
048107062422
IngredientAmount% DV
Calories5 Calorie(s)--
Total Carbohydrates1.5 Gram(s)1%
Papain6 mg--
Added Sugars1.5 Gram(s)3%
Total Sugars1.5 Gram(s)--
Papaya fruit powder45 mg--

Other ingredients: Sucrose, Dextrose, Maltodextrin, Stearic Acid, Talc, Artificial Color, Natural & Artificial Papaya flavor, Protease, Alpha-Amylase, Natural & Artificial Black Cherry flavor, Artificial Fruit flavor, Ethyl Maltol

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Precautions

Keep out of reach of children.

Warning: Consult your physician prior to using this product if you are pregnant, nursing, taking medication, or have a medical condition.

Discontinue use two weeks prior to surgery.

Storage

Store in a cool, dry place.

FDA Disclaimer Statement

This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

FDA Statement of Identity

Dietary Supplement

Formulation

Digestive enzymes help to ease digestion, release vital nutrients and support healthy digestive function

Conforms to USP <2091> for weight.

No Preservatives, No Wheat, Gluten Free, No Soy, No Dairy.

Formula

GNC Natural Brand Papaya Enzyme supplies the proteolytic enzyme papain, derived from papaya fruit, in a great-tasting chewable tablet.

Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, chew three to nine tablets as desired.

See for yourself

Papaya Enzyme by GNC Natural Brand label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

What’s inside

The Ingredients in Papaya Enzyme by GNC Natural Brand

These are the 2 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Tablet(s) Dosage formTablet Or Pill Servings per container80 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Papain

Interacts with
2 drugs
6 mg per serving

Papain is a protein-digesting enzyme from the papaya plant that is used in digestive supplements and some topical products. While it has clear food an...

Papain monograph & interactions

Papaya fruit powder

Interacts with
92 drugs
45 mg per serving

Papaya is a tropical fruit that is nutritious and generally safe to eat as food, and it contains an enzyme called papain used as a digestive aid and m...

Papaya fruit powder monograph & interactions

Other (inactive) ingredients: Sucrose, Dextrose, Maltodextrin, Stearic Acid, Talc, Artificial Color, Natural & Artificial Papaya flavor, Protease, Alpha-Amylase, Natural & Artificial Black Cherry flavor, Artificial Fruit flavor, Ethyl Maltol. These complete the product’s ingredient list but are not active constituents.

Interaction report

Papaya Enzyme by GNC Natural Brand Drug Interactions

Want to check YOUR meds against Papaya Enzyme?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

Go to the checker
92Drugs
92 Moderate

Ingredients driving the most interactions

Papain 2

Each ingredient & the kinds of drugs it affects

For each ingredient in Papaya Enzyme with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Papaya fruit powder4 drug types · 92 drugs

Amiodarone (Cordarone)

Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70%. This interaction has not been reported in humans.

Likelihood Probable Evidence D
Antidiabetes Drugs

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D

Papain1 drug type · 2 drugs

Warfarin (Coumadin)

Theoretically, papain might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D
The maker

Brand information

Manufacturer and brand details for Papaya Enzyme, from the product label.

GNC Natural Brand

See all GNC Natural Brand products
Name
General Nutrition Corporation
City
Pittsburgh
State
PA
ZipCode
15222
Phone Number
1-888-462-2548
Web Address
gnc.com
Pharmacist Counseling Corner

Papaya Enzyme by GNC Natural Brand: Common Questions

Does Papaya Enzyme by GNC Natural Brand interact with any medications?
Yes. Based on its ingredients, Papaya Enzyme has a known interaction with 92 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Papaya Enzyme contains 2 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
What does papain actually do?
Papain is a protein-digesting enzyme from papaya that's used in many digestive enzyme supplements. While it breaks down proteins in the digestive tract, we don't yet have strong evidence that the supplement itself works for the conditions it's marketed for.
Can I take this if I'm allergic to latex?
Be cautious—people allergic to latex have a higher risk of allergic reactions to papaya because of cross-reactivity between the two. Talk with your pharmacist or doctor before taking it.
Is this safe to take long-term?
The safety data we have covers short-term use at normal doses. High doses may be unsafe, and long-term safety isn't well established in our data. Ask your pharmacist or doctor about duration if you're thinking of using it regularly.
Are there any common side effects?
Most adverse effects happen in people sensitive to papain. You might experience itchy watery eyes, runny nose, sneezing, stomach cramps, sweating, or diarrhea. Serious side effects are rare but can include stomach perforation or severe inflammation at very high doses.
What's the difference between papain and papaya fruit powder in this product?
Papain is a concentrated enzyme extracted from papaya, while papaya fruit powder is the whole dried fruit. Papain is the stronger and more concentrated form—it's also the one with the documented drug interactions, so it carries more caution.
Is it safe to take while pregnant or breastfeeding?
Concentrated papain and unripe papaya are advised against in pregnancy. Ripe papaya fruit is rated likely safe, but the supplement form isn't well studied. While breastfeeding, there's not enough data to know either way—talk with your doctor or pharmacist for personalized advice.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Not sure if Papaya Enzyme is safe with your meds?

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Papaya Enzyme label
Sources

Sources & How We Checked

Papaya Enzyme's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 25 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Papain 11 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. 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.
  3. 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.
  4. 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.
  5. Martin, T., Uhder, K., Kurek, R., Roeddiger, S., Schneider, L., Vogt, H. G., Heyd, R., and Zamboglou, N. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial PubMed
  6. Walker-Renard, P. Update on the medicinal management of phytobezoars. Am J Gastroenterol. 1993;88(10):1663-1666.
  7. Tymoszuk D, Wiszniewska M, Walusiak-Skorupa J. Papain-induced occupational rhinoconjunctivitis and asthma - A case report. Med Pr 2016;67(1):109-12. PubMed
  8. Soto-Mera MT, López-Rico MR, Filgueira JF, et al. Occupational allergy to papain. Allergy 2000;55(10):983-4. PubMed
  9. Tarlo SM, Shaikh W, Bell B, et al. Papain-induced allergic reactions. Clin Allergy 1978;8(3):207-15. PubMed
  10. Baur X, König G, Bencze K, Fruhmann G. Clinical symptoms and results of skin test, RAST and bronchial provocation test in thirty-three papain workers: Evidence for strong immunogenic potency and clinically relevant proteolytic e?ects of airborne papain. C
  11. Novey HS, Keenan WJ, Fairshter RD, Wells ID, Wilson AF, Culver BD. Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies. Clin Allergy 1980;10(6):721-31. PubMed

See these in context on the Papain monograph →

Papaya 14 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. 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.
  4. 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.
  5. Blanco C, Diaz-Perales A, Collada C, et al. Class I chitinases as potential panallergens involved in the latex-fruit syndrome. J Allergy Clin Immunol 1999;103(3 Pt 1):507-13. PubMed
  6. Diaz-Perales A, Collada C, Blanco C, et al. Cross-reactions in the latex-fruit syndrome: A relevant role of chitinases but not of complex asparagine-linked glycans. J Allergy Clin Immunol 1999;104:681-7. PubMed
  7. Castillo, R., Delgado, J., Quiralte, J., Blanco, C., and Carrillo, T. Food hypersensitivity among adult patients: epidemiological and clinical aspects. Allergol.Immunopathol.(Madr.) 1996;24(3):93-97.
  8. Oderinde, O., Noronha, C., Oremosu, A., Kusemiju, T., and Okanlawon, O. A. Abortifacient properties of aqueous extract of Carica papaya (Linn) seeds on female Sprague-Dawley rats. Niger.Postgrad.Med J 2002;9(2):95-98. DOI
  9. Danese, C., Esposito, D., D'Alfonso, V., Cirene, M., Ambrosino, M., and Colotto, M. Plasma glucose level decreases as collateral effect of fermented papaya preparation use. Clin Ter. 2006;157(3):195-198.
  10. Iliev, D. and Elsner, P. Generalized drug reaction due to papaya juice in throat lozenges. Dermatology 1997;194(4):364-366. PubMed
  11. Andersen HA, Bernatz PE, Grindlay JH. Perforation of the esophagus after use of a digestant agent: report of case and experimental study. Ann Otol Rhinol Laryngol 1959;68:890-6. PubMed
  12. Deiana L, Marini S, Mariotti S. Ingestion of large amounts of papaya fruit and impaired effectiveness of levothyroxine therapy. Endocr Pract 2012;18(1):98-100. PubMed
  13. Rodrigues M, Alves G, Francisco J, Fortuna A, Falcão A. Herb-drug pharmacokinetic interaction between Carica papaya extract and amiodarone in rats. J Pharm Pharm Sci 2014;17(3):302-15. PubMed
  14. Rajapakse S, de Silva NL, Weeratunga P, Rodrigo C, Sigera C, Fernando SD. Carica papaya extract in dengue: a systematic review and meta-analysis. BMC Complement Altern Med. 2019;19(1):265. PubMed

See these in context on the Papaya monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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