Interactions on record — worth a quick check against your medications. Based on 8 of 12 ingredients. Check your meds →
Dietary supplement

Proto-Zyme Ingredients & Drug Interactions

by Priority One Nutritional Supplements

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

Proto-Zyme is a dietary supplement by Priority One Nutritional Supplements with 12 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, 274 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Bromelain, Rutin, Zinc. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Proto-Zyme by Priority One Nutritional Supplements

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

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 9 of its 12 active ingredients.
  • “Pancreatin 8x” is listed as a grouped ingredient — the label gives one combined amount (200 mg) without saying how much of each component you get.

Proto-Zyme contains 12 active ingredients—mostly digestive enzymes plus zinc and rutin. The enzyme blend includes amylase and lipase (which break down starches and fats), bromelain and papain (fruit-derived proteases), protease, trypsin, chymotrypsin, and lysozyme (all break down proteins), plus pancreatin 8x (a concentrated blend of pancreatic enzymes).

Zinc supports immune function and wound healing, while rutin is a bioflavonoid. Inactive ingredients include dicalcium phosphate, vegetable stearic acid, and microcrystalline cellulose as binders and fillers.

Does it work?

Strong evidence
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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Cataracts — rated "Effective" (Chymotrypsin) (Natural Medicines).
  • On file: Zinc deficiency — rated "Effective" (Zinc) (Natural Medicines).
  • On file: Wilson disease — rated "Likely Effective" (Zinc) (Natural Medicines).
  • On file: Acne — rated "Possibly Effective" (Zinc) (Natural Medicines).
  • On file: Acrodermatitis enteropathica — rated "Possibly Effective" (Zinc) (Natural Medicines).

The evidence for most of Proto-Zyme's ingredients is not established in our data. Zinc is rated effective for zinc deficiency and likely effective for Wilson disease, and possibly effective for acne and age-related macular degeneration.

Chymotrypsin is rated effective for cataracts. For the other ingredients—papain, bromelain, protease, lipase, trypsin, and rutin—the evidence we hold is insufficient to rate their effectiveness for any condition.

If you're considering this product for a specific health goal, ask your doctor or pharmacist what the current evidence actually supports.

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 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these enzymes are generally well tolerated at typical doses, but digestive upset (nausea, diarrhea, heartburn, stomach pain) can occur, especially at high doses or when multiple enzymes are combined. Allergic reactions are possible, particularly in people sensitive to papaya or pineapple (sources of papain and bromelain).

Papain may irritate the digestive tract and is possibly unsafe in pregnancy; bromelain, protease, trypsin, and chymotrypsin lack adequate safety data in pregnancy and should be avoided. Zinc is likely safe in pregnancy at recommended amounts, but high doses above 40 mg daily may raise the risk of copper deficiency.

Breastfeeding safety data are limited or absent for most ingredients; talk to your doctor or pharmacist before use while nursing.

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?
  • 4 of the 8 matched ingredients can interact with medications — Papain, Rutin, Bromelain, Zinc.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications.
  • For scale: 274 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 Proto-Zyme, check with your doctor or pharmacist if you take warfarin or other blood thinners (papain and bromelain increase bleeding risk). If you're on quinolone antibiotics, cephalexin, tetracycline antibiotics, or penicillamine, zinc will reduce their absorption—these must be spaced 2–6 hours apart from this product.

Anyone on HIV medications (ritonavir, integrase inhibitors like dolutegravir, or biktarvy) should confirm it's safe first. If you take diabetes medications, rutin may add to their blood-sugar-lowering effect.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with strong clinical evidence behind its ingredients' uses. Moderate medication interactions have been identified, and safety information is well characterized.

Proto-Zyme is a multi-enzyme digestive aid, but its effectiveness for any particular condition isn't established in our data. If you take warfarin, any blood thinner or antiplatelet drug, antibiotics, HIV medications, or diabetes drugs, you'll need to clear this with your own doctor or pharmacist first—several ingredients here have documented interactions.

If you're pregnant or nursing, talk it over with your healthcare provider before starting, since safety data are sparse or negative for most of these enzymes.

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

Assessment coverage: 8 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 24, 2022.

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 Proto-Zyme, straight from the product label.

Brand Priority One Nutritional Supplements
Barcode (UPC) 815354021164
Net contents 180 Tablet(s)
Market status On market
Date entered into DSLD Oct 24, 2022
DSLD ID 277407
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
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 Proto-Zyme by Priority One Nutritional Supplements, 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:
2 Tablet(s)
Maximum serving Sizes:
2 Tablet(s)
Servings per container
90
UPC/BARCODE
815354021164
IngredientAmount% DV
Amylase0 NP--
Papain100 mg--
Bromelain75 mg--
Protease0 NP--
Lipase0 NP--
Cellulase2 mg--
Zinc4 mg36%
Trypsin35 mg--
Lysozyme10 mg--
Pancreatin 8x200 mg--
Rutin60 mg--
Alpha-Chymotrypsin1 mg--
Thymus35 mg--

Other ingredients: Dicalcium Phosphate, Vegetable Stearic Acid, Croscarmellose Sodium, Microcrystalline Cellulose, Silicon Dioxide, Methylcellulose, Water, Purified, Lysozyme

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

Warning: If you are pregnant or breast feeding, consult your physician before using this product.

Keep out of reach of children.

For professional use only.

Suggested/Recommended/Usage/Directions

Recommendations: Take two (2) tablets three times daily, or as directed by your physician.

Storage

Keep container tightly closed, store in a cool, dry place.

General Statements

Bisphenol-A (BPA) & Phthalate free

Seals/Symbols

GMP Certified

Brand IP Statement(s)

Priority One Nutritional Supplements Inc since 1988

FDA Statement of Identity

Dietary Supplement

Formulation

Contains no preservatives. Non-GMO

FDA Disclaimer Statement

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

See for yourself

Proto-Zyme by Priority One Nutritional Supplements label

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

What’s inside

The Ingredients in Proto-Zyme by Priority One Nutritional Supplements

These are the 12 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Tablet(s) Dosage formTablet Or Pill Servings per container90 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
100 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

Bromelain

Interacts with
141 drugs
75 mg per serving

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early st...

Bromelain monograph & interactions

Cellulase

2 mg per serving

Zinc

Interacts with
67 drugs
4 mg per serving Form: Zinc Gluconate

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but suppleme...

Zinc monograph & interactions

Trypsin

No known
interactions
35 mg per serving

Trypsin is a protein-digesting enzyme usually taken from the pancreas of animals and used either by mouth (often combined with other enzymes like chym...

Trypsin monograph & interactions

Lysozyme

10 mg per serving

Pancreatin 8x

200 mg per serving

Rutin

Interacts with
86 drugs
60 mg per serving Form: Japanese Sophora Flower Extract

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins...

Rutin monograph & interactions

Alpha-Chymotrypsin

No known
interactions
1 mg per serving

Chymotrypsin is a protein-digesting (proteolytic) enzyme, usually taken from the pancreas of cattle or pigs, that is mainly used to help reduce swelli...

Alpha-Chymotrypsin monograph & interactions

Thymus

35 mg per serving

Other (inactive) ingredients: Dicalcium Phosphate, Vegetable Stearic Acid, Croscarmellose Sodium, Microcrystalline Cellulose, Silicon Dioxide, Methylcellulose, Water, Purified, Lysozyme. These complete the product’s ingredient list but are not active constituents.

Interaction report

Proto-Zyme by Priority One Nutritional Supplements Drug Interactions

Want to check YOUR meds against Proto-Zyme?

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
274Drugs
270 Moderate 4 Minor

Ingredients driving the most interactions

Bromelain 141
Rutin 86
Zinc 67
Papain 2

Each ingredient & the kinds of drugs it affects

For each ingredient in Proto-Zyme 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.

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Likelihood Possible Evidence B

Rutin1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that rutin has hypoglycemic effects.

Likelihood Possible Evidence D

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Theoretically, zinc might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after zinc containing products.

Likelihood Probable Evidence D
Cephalexin (Keflex)

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Likelihood Possible Evidence D
Integrase Inhibitors

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Likelihood Probable Evidence B
Quinolone Antibiotics

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Likelihood Probable Evidence B
Ritonavir (Norvir)

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Likelihood Probable Evidence B
Amiloride (Midamor)

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Likelihood Probable Evidence B
Atazanavir (Reyataz)

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Likelihood Probable Evidence B

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 Proto-Zyme, from the product label.

Priority One Nutritional Supplements

See all Priority One Nutritional Supplements products
Name
Priority One Nutritional Supplements, Inc.
Web Address
www.priorityonevitamins.com
Pharmacist Counseling Corner

Proto-Zyme by Priority One Nutritional Supplements: Common Questions

Does Proto-Zyme by Priority One Nutritional Supplements interact with any medications?
Yes. Based on its ingredients, Proto-Zyme has a known interaction with 274 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Proto-Zyme contains 12 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 is papain, and why is it in here?
Papain is a protein-digesting enzyme from papaya. It's included to help break down proteins during digestion. However, it can interact with warfarin and may irritate your digestive tract or trigger allergic reactions in sensitive people.
Can I take this with my antibiotics?
It depends on which antibiotic. Zinc in this product reduces absorption of quinolone antibiotics (like ciprofloxacin), cephalexin, and tetracyclines—these should be taken 2 to 6 hours before or after this supplement. Talk to your pharmacist about your specific medication to time them safely.
Is it safe to take if I'm pregnant?
Most of these enzymes lack adequate safety data in pregnancy. Papain is rated possibly unsafe. Zinc is likely safe at recommended doses, but high doses are a concern. Talk with your doctor or pharmacist before taking this while pregnant.
What side effects might I notice?
Digestive upset is most common—nausea, diarrhea, heartburn, or stomach cramps. Allergic reactions (itchy eyes, runny nose, rash) are possible, especially if you're sensitive to papaya or pineapple. High doses of any enzyme can make these worse.
Does this actually help with digestion?
Zinc is effective for zinc deficiency and possibly helpful for some conditions, and chymotrypsin is effective for cataracts. For the enzyme ingredients in this blend—papain, bromelain, protease, trypsin, and lipase—the evidence we have is insufficient to rate whether they help digestion or any other condition.
What if I'm on diabetes medication?
Rutin in this product theoretically may increase the risk of low blood sugar when combined with diabetes drugs. Check with your doctor or pharmacist before using it if you take antidiabetes medications.

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

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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.

Proto-Zyme label
Go deeper

The Full Monographs Behind Proto-Zyme’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Papain

Interacts with 2 drugs

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 and laboratory uses, strong human evidence...

Read the full Papain monograph →
Herb & supplement monograph

Bromelain

Interacts with 141 drugs

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early studies are promising, but the overall evi...

Read the full Bromelain monograph →
Herb & supplement monograph

Zinc

Interacts with 67 drugs

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a defici...

Read the full Zinc monograph →
Herb & supplement monograph

Trypsin

Trypsin is a protein-digesting enzyme usually taken from the pancreas of animals and used either by mouth (often combined with other enzymes like chymotrypsin and bromelain) for swelling and...

Read the full Trypsin monograph →
Herb & supplement monograph

Proteolytic Enzymes (proteases)

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), trypsin, chymotrypsin, and pancreatin. Peo...

Read the full Proteolytic Enzymes (proteases) monograph →
Herb & supplement monograph

Lipase

Lipase is a digestive enzyme that helps your body break down dietary fats. It is well established as part of prescription pancreatic enzyme therapy for people who cannot make enough of their...

Read the full Lipase monograph →
Herb & supplement monograph

Rutin

Interacts with 86 drugs

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins and hemorrhoids. The evidence is limite...

Read the full Rutin monograph →
Herb & supplement monograph

Chymotrypsin

Chymotrypsin is a protein-digesting (proteolytic) enzyme, usually taken from the pancreas of cattle or pigs, that is mainly used to help reduce swelling and support healing after injury or s...

Read the full Chymotrypsin monograph →
Sources

Sources & How We Checked

Proto-Zyme'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 147 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 →

Bromelain 19 references
  1. Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy 2001;56:257-8. PubMed
  2. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988;22:191-203.. PubMed
  3. Bradbrook ID, Morrison PJ, Rogers HJ. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol 1978;6:552-4. PubMed
  4. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 2007;13:30-5.
  5. Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 2006;99:841-50. PubMed
  6. Mori S, Ojima Y, Hirose T, et al. The clinical effect of proteolytic enzyme containing bromelain and trypsin on urinary tract infection evaluated by double blind method. Acta Obstet Gynaecol Jpn 1972;19:147-53.
  7. Glaser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets 2006;17:37-41. PubMed
  8. Heinicke R M, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia 1972;28:844-5. PubMed
  9. Gailhofer, G., Wilders-Truschnig, M., Smolle, J., and Ludvan, M. Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988;18(5):445-450. PubMed
  10. Mattei, O., Fabri, G., and Farina, G. [Occupational health experience regarding four cases of asthma due to bromelain (author's transl)]. Medicina del Lavoro 1979;70(5):404-409.
  11. Galleguillos, F. and Rodriguez, J. C. Asthma caused by bromelin inhalation. Clin Allergy 1978;8(1):21-24. PubMed
  12. Perez-Camo I, Quirce S, Duran MA, and et al. Latex allergy: evidence of cross-reactivity with papain and bromelain [abstract]. Allergy 1996;51(suppl 31):48.
  13. Martin GJ, Ehrenreich J, and Asbell N. Bromelain: pineapple proteases with anti-edema activity. Exp Med Surg 1962;20:227-247.
  14. Kasemsuk T, Saengpetch N, Sibmooh N, Unchern S. Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis. Clin Rheumatol. 2016 Oct;35(10):2531-40. PubMed
  15. Kutlu Ö, DemirbaS A, Elmas ÖF, Güvenç U, Metin A. Fixed drug eruption: a new side effect of bromelain. Contact Dermatitis 2020. Online ahead of print. PubMed
  16. Shoham Y, Shapira E, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial. Wound Repair Regen 2021;29(6):899-907. PubMed
  17. Pfister P, Garcia Wendel PD, Kim BS, et al. Coagulation side effects of enzymatic debridement in burned patients. Burns 2022. PubMed
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Lipase 1 reference
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Trypsin 17 references
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Rutin 2 references
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  2. Sun C, Wang L, Sun J, Wang Z, Tang Z. Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. J Tradit Chin Med. 2020;40(4):640-645.

See these in context on the Rutin monograph →

Chymotrypsin 6 references
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  3. Latha B, Ramakrishnan M, Jayaraman V, Babu M. Serum enzymatic changes modulated using trypsin: chymotrypsin preparation during burn wounds in humans. Burns 1997;23:560-4. PubMed
  4. Shaw PC. The use of a trypsin-chymotrypsin formulation in fractures of the hand. Br J Clin Pract 1969;23:25-6. DOI
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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.

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