Interactions on record — worth a quick check against your medications. Based on 7 of 13 ingredients. Check your meds →
Dietary supplement

Fibrenza Systemic Enzyme 500 mg Ingredients & Drug Interactions

by HCP Formulas

Fibrenza Systemic Enzyme 500 mg label
See full label image
Capsule Category: Non-nutrient/non-botanical
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Fibrenza Systemic Enzyme 500 mg against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Moderate

Fibrenza Systemic Enzyme 500 mg is a dietary supplement by HCP Formulas with 13 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, 308 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Nattokinase NSK-SD, Bromelain, Papain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Fibrenza Systemic Enzyme 500 mg by HCP Formulas

Ask about any prescription or over-the-counter medication and we check it for interactions with Fibrenza Systemic Enzyme 500 mg by HCP Formulas — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Fibrenza Systemic Enzyme 500 mg by HCP Formulas

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

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Aug 6, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 0 of its 13 active ingredients.
  • “Proprietary Enzyme Blend” is a proprietary blend — the label gives one combined amount (1,000 mg) without saying how much of each component you get.

Fibrenza Systemic Enzyme 500 mg contains 13 active ingredients, all digestive and systemic enzymes: amylase, papain, bromelain, protease, serratiopeptidase, lipase, peptidase, superoxide dismutase, chymotrypsin, trypsin, acid-stable protease, a proprietary enzyme blend, and nattokinase NSK-SD. These are meant to break down different substrates — carbohydrates, proteins, and fats — as they move through the digestive tract and potentially into circulation.

The product also contains inactive ingredients: cellulose, rice bran, and rice extract, which serve as fillers and capsule material.

Does it work?

Not established
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 established

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: maintain healthy joints, mobility, and cardiovascular function.
  • We looked for evidence on: Osteoarthritis, Knee pain, Sprains, Exercise-induced muscle soreness, Postoperative swelling, Postoperative pain — and 4 related terms.
  • The closest evidence on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness (Natural Medicines).
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Wound healing.
  • Also on file: Trypsin is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness, Osteoarthritis, Wound healing, Sprains, and more.

The evidence we hold for most of these enzymes is insufficient to establish whether they work for their claimed purposes. Papain's effectiveness is unrated for cancer, dental cavities, radiation skin damage, muscle soreness, shingles, and intestinal parasites.

Bromelain is similarly unrated for hay fever, burns, cancer, nerve damage from chemotherapy, vein insufficiency, and diabetes. Chymotrypsin is rated Effective for cataracts but unrated for burns, fractures, and chronic parotitis inflammation.

Trypsin, lipase, and protease have insufficient or no established evidence. Nattokinase's effectiveness is unrated for angina, atherosclerosis, cancer, heart disease, and chronic fatigue.

The evidence, ingredient by ingredient Papain Bromelain Proteolytic Enzymes (proteases) Lipase Chymotrypsin Trypsin Nattokinase

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 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 7 of 7.
  • General safety write-ups exist for 7 of 7.
  • 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 normal doses, but adverse effects are possible. Papain may irritate the digestive tract and cause allergic reactions — itchy eyes, runny nose, sneezing, stomach cramps, and diarrhea in sensitive people.

Bromelain commonly causes diarrhea, gas, upset stomach, and headache. Protease and acid-stable protease may trigger digestive upset or allergic reactions.

Trypsin in combination with other enzymes can cause mild-to-moderate nausea, heartburn, and stomach pain. Chymotrypsin is rarely reported to cause anaphylaxis (a severe allergic reaction with difficulty breathing, swelling, and shock).

For pregnancy, papain is rated possibly unsafe — concentrated papain and unripe papaya products carry safety concerns. Bromelain, chymotrypsin, trypsin, and nattokinase are best avoided in pregnancy due to insufficient safety data.

Lipase, protease, acid-stable protease, and serratiopeptidase have little or no pregnancy safety data; talk with your doctor before use. Breastfeeding safety is similarly limited across most ingredients — papain, bromelain, chymotrypsin, trypsin, lipase, and protease have insufficient data or are not recommended without medical advice.

Side effects, ingredient by ingredient Papain Bromelain Proteolytic Enzymes (proteases) Lipase Chymotrypsin Trypsin Nattokinase

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?
  • 3 of the 7 matched ingredients can interact with medications — Papain, Bromelain, Nattokinase.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs.
  • For scale: 308 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.

Check with your doctor or pharmacist before taking this product if you use blood thinners like warfarin, dabigatran, or other anticoagulants; antiplatelet drugs like aspirin or clopidogrel; blood pressure medications (antihypertensives); or tetracycline antibiotics. The Moderate-severity interactions with blood thinners and blood pressure drugs are the top concern, and a case report documented serious bleeding when nattokinase was combined with aspirin.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with no established evidence rating for its marketed use. Moderate medication interactions have been identified, and safety information is well characterized.

This is a multi-enzyme blend designed to work systemically, but most ingredient claims lack established evidence in our data. The real concern is its interaction with blood thinners, blood pressure medications, and tetracycline antibiotics — if you take any of these, check with your doctor or pharmacist before starting.

Pregnant or breastfeeding people should also talk with their healthcare provider first, as safety data is limited across most ingredients.

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

Assessment coverage: 8 of 13 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jun 22, 2023.

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 Fibrenza Systemic Enzyme 500 mg, straight from the product label.

Brand HCP Formulas
Barcode (UPC) 765573629514
Net contents 60 Capsule(s)
Market status On market
Date entered into DSLD Jun 22, 2023
DSLD ID 287148
Product type Non-nutrient/non-botanical
Supplement form Capsule
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 Fibrenza Systemic Enzyme 500 mg by HCP Formulas, 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 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
30
UPC/BARCODE
765573629514
IngredientAmount% DV
Amylase0 NP--
Papain0 NP--
Bromelain0 NP--
Protease0 NP--
Serratiopeptidase0 NP--
Lipase0 NP--
Peptidase0 NP--
Superoxide Dismutase0 NP--
Chymotrypsin0 NP--
Trypsin0 NP--
acid stable Protease0 NP--
Proprietary Enzyme Blend1000 mg--
Nattokinase NSK-SD0 NP--
Seaprose-S0 NP--

Other ingredients: Cellulose, Rice Bran, Rice extract

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.
Suggested/Recommended/Usage/Directions

Suggested Use: Adults take 2 capsules twice daily on an empty stomach (at least 45 minutes before or 60 minutes after meals) with water or as recommended by your healthcare provider.

Precautions

Caution: As with any dietary supplement, consult your healthcare provider before using this product, especially if you are pregnant, nursing, or are taking medication.

Keep out of reach of children

FDA Disclaimer Statement

These statements made herein have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Formulation

Fibrin defense Maintain healthy joints & mobility Detoxification Cardiovascular support

No Phthalates, no dairy, no wheat, no yeast, no gluten, no fish, no magnesium stearate, no talc, no artificial colors or flavors, non-GMO

Encapsulated in the USA

Formula

AcidDefenz Time Release Capsule

FDA Statement of Identity

Dietary Supplement

Storage

Store in a cool, dry place with lid tightly closed

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Fibrenza Systemic Enzyme 500 mg by HCP Formulas label

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

Fibrenza Systemic Enzyme 500 mg label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Fibrenza Systemic Enzyme 500 mg by HCP Formulas

These are the 13 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container30 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.

Proprietary Enzyme Blend

1000 mg per serving

Other (inactive) ingredients: Cellulose, Rice Bran, Rice extract. These complete the product’s ingredient list but are not active constituents.

Interaction report

Fibrenza Systemic Enzyme 500 mg by HCP Formulas Drug Interactions

Want to check YOUR meds against Fibrenza Systemic Enzyme 500 mg?

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
308Drugs
289 Moderate 19 Minor

Ingredients driving the most interactions

Nattokinase NSK-SD 289
Bromelain 141
Papain 2

Individual Drug Interactions

The ingredients in Fibrenza Systemic Enzyme 500 mg interact with 308 drugs. Click any drug to see the details.

3 of the 13 ingredients in Fibrenza Systemic Enzyme 500 mg interact with drugs. Each result below shows which ingredient is responsible. Nattokinase NSK-SD Bromelain Papain

Each ingredient & the kinds of drugs it affects

For each ingredient in Fibrenza Systemic Enzyme 500 mg 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.

Nattokinase NSK-SD2 drug types · 289 drugs

Anticoagulant/Antiplatelet Drugs

Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
Nattokinase has thrombolytic and anticoagulant effects. There is a case report of intracranial hemorrhage in a patient who added nattokinase to aspirin therapy.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, nattokinase might increase the risk of hypotension when used with antihypertensive drugs.
Some clinical research suggests that nattokinase may reduce systolic and diastolic blood pressure.

Likelihood Possible Evidence D
Nattokinase NSK-SD full monograph & interactions

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
Bromelain full monograph & interactions

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
Papain full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Fibrenza Systemic Enzyme 500 mg, from the product label.

HCP Formulas

See all HCP Formulas products
Name
HCP Formulas
Street Address
9830 S. 51st St. A129
City
Phoenix
State
AZ
ZipCode
85044
Phone Number
800-710-2585
Web Address
www.fibrenza.com
Pharmacist Counseling Corner

Fibrenza Systemic Enzyme 500 mg by HCP Formulas: Common Questions

Does Fibrenza Systemic Enzyme 500 mg by HCP Formulas interact with any medications?
Yes. Based on its ingredients, Fibrenza Systemic Enzyme 500 mg has a known interaction with 308 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Fibrenza Systemic Enzyme 500 mg contains 13 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 are all these enzymes supposed to do?
They're digestive and systemic enzymes meant to break down different food components — carbohydrates, proteins, and fats — as they move through your gut and potentially into the bloodstream. Nattokinase is a clot-busting enzyme extracted from fermented soy. The product is marketed as a systemic enzyme therapy, but the evidence for most of these claims is not established in our data.
Is this safe if I'm pregnant or breastfeeding?
Not enough safety data exists for most of these ingredients during pregnancy and breastfeeding. Papain is rated possibly unsafe in pregnancy. Talk with your doctor or pharmacist about whether this product is right for you.
Can papain really affect my warfarin?
Yes. One case report documented a patient who was stable on warfarin but developed dangerously high blood-thinning levels (INR of 7.4) after taking a supplement with papain. This product contains papain, so if you take warfarin or another blood thinner, you must check with your doctor or pharmacist first.
What side effects might I get from taking this?
Most common are digestive complaints — diarrhea, gas, upset stomach, nausea, and heartburn — especially if enzymes are taken in combination. Allergic reactions are possible but uncommon in non-sensitive people; they can range from mild (itching, sneezing, runny nose) to severe (anaphylaxis with swelling and difficulty breathing).
Will this interfere with my tetracycline antibiotic?
Possibly. Bromelain, one of this product's ingredients, may increase how much tetracycline your body absorbs — though one human study found no change in blood levels. It's a Minor-severity interaction, but talk to your pharmacist to be sure.
Does this product have any fillers?
Yes. In addition to the 13 active enzymes, it contains cellulose, rice bran, and rice extract as inactive ingredients.

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

Not sure if Fibrenza Systemic Enzyme 500 mg 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.

Fibrenza Systemic Enzyme 500 mg label
Go deeper

The Full Monographs Behind Fibrenza Systemic Enzyme 500 mg’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

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

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 → 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

Nattokinase

Interacts with 289 drugs

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulatio...

Read the full Nattokinase monograph →
Sources

Sources & How We Checked

Fibrenza Systemic Enzyme 500 mg'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 66 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
  18. Hasham S, Riyat H, Fletcher A, O'Boyle CP, Alexander S. To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries. Scars Burn Heal 2023;9:20595131231168333. PubMed
  19. Leelakanok N, Petchsomrit A, Janurai T, Saechan C, Sunsandee N. Efficacy and safety of bromelain: A systematic review and meta-analysis. Nutr Health 2023. PubMed

See these in context on the Bromelain monograph →

Proteolytic Enzymes (proteases) 3 references
  1. Weeks JA, Harper RA, Simon RA, Burdick JD. Assessment of sensitization risk of a laundry pre-spotter containing protease. Cutan Ocul Toxicol. 2011;30(4):272-9. PubMed
  2. Marquès LI, Lara S, Abós T, Bartolomé B. Occupational rhinitis due to pepsin. J Investig Allergol Clin Immunol. 2006;16(2):136-7. DOI
  3. Cartier A, Malo JL, Pineau L, Dolovich J. Occupational asthma due to pepsin. J Allergy Clin Immunol. 1984;73(5 Pt 1):574-7. PubMed

See these in context on the Proteolytic Enzymes (proteases) monograph →

Lipase 1 reference
  1. Casper C, Hascoet JM, Ertl T, et al. Recombinant bile salt-stimulated lipase in preterm infant feeding: A randomized phase 3 study. PLoS One. 2016;11(5):e0156071. PubMed

See these in context on the Lipase monograph →

Chymotrypsin 6 references
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. Dukes, MNG. Meyler's Side Effects of Drugs. 13th ed. Elsevier: Amsterdam, 1997.
  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
  5. McCue FC, Webster TM, Gieck J. Clinical effects of proteolytic enzymes after reconstructive hand surgery. Int Surg 1972;57:479-82.
  6. Sun HJ, Xiao JQ, Qiao QH, et al. Chymotrypsin with sialendoscopy-assisted surgery for the treatment of chronic obstructive parotitis. Int J Oral Maxillofac Surg 2017;46(7):877-82. doi: 10.1016/j.ijom.2017.02.1267. PubMed

See these in context on the Chymotrypsin monograph →

Trypsin 17 references
  1. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
  2. Latha B, Ramakrishnan M, Jayaraman V, Babu M. The efficacy of trypsin: chymotrypsin preparation in the reduction of oxidative damage during burn injury. Burns 1998;24:532-8. PubMed
  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. Klein, G., Kullich, W., Schnitker, J., and Schwann, H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp
  5. Dale, P. S., Tamhankar, C. P., George, D., and Daftary, G. V. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemother.Pharmacol 2001;47 Suppl:S29-S34. PubMed
  6. 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
  7. Miller, P. C., Bailey, S. P., Barnes, M. E., Derr, S. J., and Hall, E. E. The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. J Sports Sci 2004;22(4):365-372. PubMed
  8. Bolten WW, Glade MJ, Raum S, Ritz BW. The safety and efficacy of an enzyme combination in managing knee osteoarthritis pain in adults: a randomized, double-blind, placebo-controlled trial. Arthritis 2015;2015:251521. PubMed
  9. US Department of Justice. U.S. Files Complaint Against Texas-Based Healthpoint Ltd. Under the False Claims Act. https://www.justice.gov/opa/pr/us-files-complaint-against-texas-based-healthpoint-ltd-under-false-claims-act. (Accessed June 19, 2019).
  10. Grabs V, Kersten A, Haller B, et al. Rutoside and hydrolytic enzymes do not attenuate marathon-induced inflammation. Med Sci Sports Exerc. 2017;49(3):387-395. PubMed
  11. Baumhackl U, Kappos L, Radue EW, et al. A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis. Mult Scler. 2005;11(2):166-8. PubMed
  12. 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 Chemother Pharmacol. 2001;47 Suppl:S23-8. PubMed
  13. Kempf K, Manzo G, Hanifi-Moghaddam P, et al. Effect of combined oral proteases and flavonoid treatment in subjects at risk of Type 1 diabetes. Diabet Med. 2009;26(12):1309-10. PubMed
  14. Kerkhoffs GM, Struijs PA, de Wit C, Rahlfs VW, Zwipp H, van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. Br J Sports Med. 2004;38(4):431-5. PubMed
  15. Popiela T, Kulig J, Klek S, Wachol D, Bock PR, Hanisch J. Double-blind pilot-study on the efficacy of enzyme therapy in advanced colorectal cancer. Przegl Lek. 2000;57 Suppl 5:142.
  16. Shetty V, Mohan A. A prospective, randomized, double-blind, placebo-controlled clinical trial comparing the efficacy of systemic enzyme therapy for edema control in orthognathic surgery using ultrasound scan to measure facial swelling. J Oral Maxillofac S PubMed
  17. Comparison of Chronic Wound Care Products. Pharmacist's Letter/Prescriber's Letter 2008;12(3):1203.

See these in context on the Trypsin monograph →

Nattokinase 9 references
  1. Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-98.. PubMed
  2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43.
  3. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
  4. Kim, J. Y., Gum, S. N., Paik, J. K., Lim, H. H., Kim, K. C., Ogasawara, K., Inoue, K., Park, S., Jang, Y., and Lee, J. H. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens.Res 2008;31(8):1583-1588. PubMed
  5. <p>Maruyama M, Sumi H (eds): Effect of natto diet on blood pressure, in Basic and Clinical Aspects of Japanese Traditional Food Natto II. Japan Technology Transfer Association (JTTAS), 1998, pp 1–3.</p>
  6. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. PubMed
  7. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Mohamed Djirdeh T. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2021;13(12):e20074. PubMed
  8. Awatani-Yoshidome K, Hashimoto T, Satoh T. Anaphylaxis from nattokinase in a patient with fermented soybean (natto) allergy. Allergol Int 2022;71(1):153-4. PubMed
  9. Suzuki K, Nakamura M, Sato N, Futamura K, Matsunaga K, Yagami A. Nattokinase, a subtilisin family serine protease, is a novel allergen contained in the traditional Japanese fermented food natto. Allergol Int 2022.

See these in context on the Nattokinase 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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