Interactions on record — worth a quick check against your medications. Based on 7 of 9 ingredients. Check your meds →
Dietary supplement

Systemic Enzyme Complex Ingredients & Drug Interactions

by Pure Encapsulations

Systemic Enzyme Complex label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 23, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Systemic Enzyme Complex 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

Systemic Enzyme Complex is a dietary supplement by Pure Encapsulations with 9 active ingredients. Its ingredients are commonly taken for varicose veins and chronic venous insufficiency, hemorrhoids, easy bruising and fragile capillaries.Based on those ingredients, 1,097 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Indian Frankincense (Boswellia serrata) extract, Bromelain, Rutin. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Systemic Enzyme Complex by Pure Encapsulations

Ask about any prescription or over-the-counter medication and we check it for interactions with Systemic Enzyme Complex by Pure Encapsulations — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Systemic Enzyme Complex by Pure Encapsulations

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 Sep 17, 2026

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 9 of its 9 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Systemic Enzyme Complex contains 9 active ingredients: rutin, papain, bromelain, protease 6, Boswellia serrata extract (also called Indian frankincense), trypsin, pancreatin, serrazimes, and chymotrypsin. These are mostly proteolytic enzymes—protein-digesting compounds derived from fruits (papaya and pineapple) and animal sources—along with rutin, a plant compound, and Boswellia serrata gum resin.

The capsule itself (vegetarian) and ascorbyl palmitate are inactive ingredients.

Does it work?

Moderate 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
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: Inflammation, swelling, and post-injury recovery.
  • We looked for evidence on: Postoperative swelling, Postoperative pain, Sprains, Exercise-induced muscle soreness, Wound healing, Osteoarthritis — and 4 related terms.
  • The strongest evidence on file: Boswellia Serrata is rated "Possibly Effective" for Osteoarthritis (Natural Medicines).
  • Also on file: Boswellia Serrata is rated "Insufficient Reliable Evidence To Rate" for Allergic rhinitis (hay fever), Asthma, Exercise-induced muscle soreness, Postoperative pain, and more.
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness.

For most conditions this product may be used for, the evidence isn't strong enough to establish whether it works. Rutin, papain, bromelain, and trypsin all have insufficient reliable evidence for their intended uses.

Boswellia serrata extract is possibly effective for osteoarthritis, though data quality and dose vary between products. Chymotrypsin is rated effective for cataracts, but the rest of its uses lack reliable evidence.

Overall, if you're considering this product for a specific condition, there's little solid data backing most of its ingredients for that purpose.

The evidence, ingredient by ingredient Rutin Papain Bromelain Proteolytic Enzymes (proteases) Boswellia Serrata Trypsin Chymotrypsin

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.

These enzymes are generally well tolerated for short-term use, though long-term safety data are limited. Common side effects include digestive upset (diarrhea, gas, nausea, heartburn, abdominal pain) and, less often, headache.

Rutin may cause headache, flushing, or rashes in some people. Papain can trigger allergic reactions—itchy eyes, runny nose, sneezing, or abdominal cramps—especially in sensitive individuals, and high doses may cause serious stomach damage.

Bromelain may cause similar allergic reactions, and occupational exposure to airborne enzyme dust can cause respiratory symptoms. For pregnancy: papain and bromelain are best avoided; rutin and Boswellia serrata are rated likely safe; and trypsin, protease 6, chymotrypsin, and serrazimes lack enough safety data.

For breastfeeding: rutin should be avoided; papain, bromelain, Boswellia serrata, trypsin, protease 6, and chymotrypsin all lack safety data. Talk with your doctor or pharmacist about whether this product is right for you during pregnancy or breastfeeding.

Side effects, ingredient by ingredient Rutin Papain Bromelain Proteolytic Enzymes (proteases) Boswellia Serrata Trypsin Chymotrypsin

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 7 matched ingredients can interact with medications — Boswellia Serrata, Papain, Rutin, Bromelain.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications.
  • For scale: 1,098 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 warfarin or other blood thinners (anticoagulants), antidiabetes drugs, antiplatelet drugs like aspirin, tetracycline antibiotics, immunosuppressant drugs, or any medication broken down by your liver, including drugs that interact with CYP2D6, CYP2C19, CYP1A2, CYP2C9, or CYP3A4 enzymes. Altogether, these interactions span 1,098 individual medications.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence for its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

This is a multi-ingredient enzyme supplement with documented interactions, particularly with blood thinners, antidiabetes drugs, and drugs metabolized by certain liver enzymes. Effectiveness for most conditions isn't well established.

If you take any prescription medications—especially blood thinners, antidiabetes drugs, or drugs broken down in the liver—check your exact list with your doctor or pharmacist before starting. This product is generally well tolerated short-term but may cause digestive upset or allergic reactions in some people.

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

Assessment coverage: 7 of 9 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Apr 25, 2019.

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 Systemic Enzyme Complex, straight from the product label.

Brand Pure Encapsulations
Barcode (UPC) 766298008622
Net contents 180 Capsule(s)
Market status On market
Date entered into DSLD Apr 25, 2019
DSLD ID 188685
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten 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 Systemic Enzyme Complex by Pure Encapsulations, 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 Capsule(s)
Maximum serving Sizes:
3 Capsule(s)
Servings per container
60
UPC/BARCODE
766298008622
IngredientAmount% DV
Rutin100 mg--
Papain120 mg--
Bromelain120 mg--
Protease 6120 mg--
Indian Frankincense (Boswellia serrata) extract250 mg--
Trypsin75 mg--
Pancreatin176 mg--
Serrazimes17 mg--
Chymotrypsin3 mg--

Other ingredients: Vegetarian Capsule, Ascorbyl Palmitate

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.
Storage

Store in a cool, dry place.

Suggested/Recommended/Usage/Directions

Recommendations: As a dietary supplement, take 3 capsules, 1–2 times daily, between meals.

Precautions

Warning: Not to be taken by pregnant or lactating women. If you have any health condition or are taking any medication, consult your health professional before use.

Keep out of the reach of children.

Use only if safety seal is intact.

General Statements

Contents may not fill packaging in order to accommodate required labeling. Please rely on stated quantity.

Scan to learn about our hypoallergenic supplements

Support for muscle, joint and tissue health

Formulation

Certified Gluten-Free by the Gluten-Free Certification Organization, www.gluten.org

Gluten-free & Non-GMO

FDA Statement of Identity

Dietary Supplement

Seals/Symbols

GF

Brand IP Statement(s)

Serrazimes is a registered trademark of National Enzyme Company.

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.

General

v8 code: SYC1

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

See for yourself

Systemic Enzyme Complex by Pure Encapsulations label

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

Systemic Enzyme Complex 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 Systemic Enzyme Complex by Pure Encapsulations

These are the 9 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Capsule(s) Dosage formCapsule Servings per container60 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.

Rutin

Interacts with
86 drugs
100 mg per serving

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

Papain

Interacts with
2 drugs
120 mg per serving Form: Papaya

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
120 mg per serving Form: Pineapple

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

Protease 6

No known
interactions
120 mg per serving

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

Protease 6 monograph & interactions

Indian Frankincense (Boswellia serrata) extract

Interacts with
952 drugs
250 mg per serving Form: Boswellic Acids

Boswellia serrata is a tree resin used in traditional medicine, mainly for joint pain and inflammation. Some studies suggest it may help with osteoart...

Indian Frankincense (Boswellia serrata) extract monograph & interactions

Trypsin

No known
interactions
75 mg per serving Form: Porcine

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

Pancreatin

176 mg per serving Form: Porcine

Serrazimes

17 mg per serving Form: Protease

Chymotrypsin

No known
interactions
3 mg per serving Form: Bovine

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

Chymotrypsin monograph & interactions

Other (inactive) ingredients: Vegetarian Capsule, Ascorbyl Palmitate. These complete the product’s ingredient list but are not active constituents.

Interaction report

Systemic Enzyme Complex by Pure Encapsulations Drug Interactions

Want to check YOUR meds against Systemic Enzyme Complex?

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
1,097Drugs
1,079 Moderate 18 Minor

Ingredients driving the most interactions

Indian Frankincense (Boswellia serrata) extract 952
Bromelain 141
Rutin 86
Papain 2

Individual Drug Interactions

The ingredients in Systemic Enzyme Complex interact with 1,097 drugs. Click any drug to see the details.

4 of the 9 ingredients in Systemic Enzyme Complex interact with drugs. Each result below shows which ingredient is responsible. Indian Frankincense (Boswellia serrata) extract Bromelain Rutin Papain

Each ingredient & the kinds of drugs it affects

For each ingredient in Systemic Enzyme Complex 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.

Indian Frankincense (Boswellia serrata) extract6 drug types · 952 drugs

Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, Boswellia serrata might increase the levels of CYP1A2 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes.

Likelihood Possible Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, Boswellia serrata might increase or decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes. Other in vitro research shows that Boswellia serrata extract inhibits CYP3A4 enzymes at most concentrations, although it may modestly induce enzyme activity at low concentrations.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.
Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity. However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways.

Likelihood Possible Evidence D
Indian Frankincense (Boswellia serrata) extract 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

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
Rutin 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 Systemic Enzyme Complex, from the product label.

Pure Encapsulations

See all Pure Encapsulations products
Name
Pure Encapsulations
Street Address
490 Boston Post Road
City
Sudbury
State
MA
Phone Number
1-800-753-2277
Web Address
www.PureEncapsulations.com
Pharmacist Counseling Corner

Systemic Enzyme Complex by Pure Encapsulations: Common Questions

Does Systemic Enzyme Complex by Pure Encapsulations interact with any medications?
Yes. Based on its ingredients, Systemic Enzyme Complex has a known interaction with 1,097 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Systemic Enzyme Complex contains 9 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.
Is Systemic Enzyme Complex safe during pregnancy?
Not entirely—it depends on the ingredient. Papain should be avoided; rutin and Boswellia serrata are likely safe. Papain and bromelain lack enough pregnancy data to recommend them. Pancreatin and serrazimes have no safety data on file. Talk with your doctor before taking it during pregnancy.
Can I take this if I'm breastfeeding?
It's best to check with your doctor or pharmacist first. Rutin should be avoided during breastfeeding, and most of the other enzymes—bromelain, Boswellia serrata, trypsin, protease 6, chymotrypsin, and serrazimes—lack enough safety data. Only pancreatin has data not on file.
What are these enzymes supposed to do?
They're intended to help digest protein and reduce inflammation. However, the evidence for most of them in treating specific conditions is insufficient or lacking. Boswellia serrata extract is possibly effective for osteoarthritis, and chymotrypsin is effective for cataracts, but for other uses listed, the data aren't strong.
What side effects might I experience?
The most common are digestive—diarrhea, gas, nausea, heartburn, or stomach pain. Headache, flushing, and rashes can occur. If you're sensitive to these enzymes (especially those from papaya or pineapple), you may have allergic reactions like itchy eyes, runny nose, sneezing, or abdominal cramps.
Can I take this with my blood thinner (warfarin)?
Not without checking first. Papain in this product can increase warfarin's effect and boost your bleeding risk—this is documented in case reports. Bromelain also raises bleeding risk with blood thinners. Ask your doctor or pharmacist before combining them.
Will this interact with my diabetes medication?
Possibly. Rutin may increase the risk of low blood sugar when taken with antidiabetes drugs. Check the medication checker below with your specific drug, and ask your doctor or pharmacist if it's safe to combine.

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.

Systemic Enzyme Complex label
Go deeper

The Full Monographs Behind Systemic Enzyme Complex’s Ingredients

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

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

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

Boswellia Serrata

Interacts with 952 drugs

Boswellia serrata is a tree resin used in traditional medicine, mainly for joint pain and inflammation. Some studies suggest it may help with osteoarthritis symptoms, but the overall evidenc...

Read the full Boswellia Serrata 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

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

Systemic Enzyme Complex'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 74 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.

Rutin 2 references
  1. Mehta DK (Ex Ed). British National Formulary, Number 37. British Medical Association and Royal Pharmaceutical Society of Great Britain: London, England, March 1999.
  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 →

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 →

Boswellia Serrata 16 references
  1. Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res 1998;3:511-4.
  2. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  3. Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003;10:3-7. PubMed
  4. Liu JJ, Nilsson A, Oredsson S, et al. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002;23:2087-93. PubMed
  5. Wildfeuer A, Neu IS, Safayhi H, et al. Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis. Arzneimittelforschung 1998;48:668-74.
  6. Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67:391-5. PubMed
  7. Sengupta K, Alluri KV, Satish AR, et al. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin. Arthritis Res Ther 2008;10:R85.
  8. Sengupta K, Krishnaraju AV, Vishal AA, et al. Comparative efficacy and tolerability of 5-Loxin and Aflapin against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Int J Med Sci 2010;7:366-77.
  9. Ernst E. Frankincense: systematic review. BMJ 2008;337:a2813. PubMed
  10. Kirste S, Treier M, Wehrle SJ, et al. Boswellia serratea extract acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer 2011;117:3788-95.
  11. Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. J Chromatogr A 2006;111 PubMed
  12. Altmann A, Poeckel D, Fischer L, et al. Coupling of boswellic acid-incuded Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol 2004;141:223-32.
  13. El Fortia, M., Badi, H., Elalem, Kh, Kadiki, O., and Topov, Y. Olibanum bezoar: complication of a traditional popular medicine. East Mediterr.Health J 2006;12(6):927-929.
  14. Meshkat S, Mahmoodi Baram S, Rajaei S, et al. Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury. Brain Inj 2022;36(4):553-559. PubMed
  15. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  16. Valente IVB, Garcia D, Abbott A, et al. The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer. Breast Cancer Res Treat 2024;204(3):521-530. PubMed

See these in context on the Boswellia Serrata 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 →

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 →

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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