Major interaction on record — check this product against your medications before combining. Based on 9 of 16 ingredients. Check your meds →
Dietary supplement

Megazyme Forte Ingredients & Drug Interactions

by Biophix

Megazyme Forte label
See full label image
Tablet Or Pill Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Megazyme Forte 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: Major

Megazyme Forte is a dietary supplement by Biophix with 16 active ingredients. Its ingredients are commonly taken for varicose veins and chronic venous insufficiency, hemorrhoids, easy bruising and fragile capillaries.Based on those ingredients, 475 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Nattozimes, Calcium, Bromelain. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Megazyme Forte by Biophix

Ask about any prescription or over-the-counter medication and we check it for interactions with Megazyme Forte by Biophix — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Megazyme Forte by Biophix

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 20, 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 16 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (2,036 mg) without saying how much of each component you get.

Megazyme Forte is a 16-ingredient formulation centered on digestive and systemic enzymes. The active ingredients include pancreatic enzymes (pancreatin, trypsin, and alpha-chymotrypsin), plant-derived enzymes (papain and bromelain), and others such as lipase, amylase, catalase, and nattokinase.

The product also contains zinc, calcium, rutin, and supportive substances like superoxide dismutase and thymus substance. The remaining ingredients — microcrystalline cellulose, stearic acid, magnesium stearate, silica, croscarmellose sodium, and pharmaceutical glaze — are inactive excipients that serve as fillers, binders, and capsule materials.

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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: support healthy immune system and optimal digestion.
  • We looked for evidence on: Allergic rhinitis (hay fever), Dyspepsia, Exercise-induced muscle damage, Exercise-induced muscle soreness, inflammation, wound healing — and 1 related terms.
  • The strongest evidence on file: Calcium is rated "Effective" for Dyspepsia (Natural Medicines).
  • Also on file: Papain is rated "Insufficient Reliable Evidence To Rate" for Exercise-induced muscle soreness, Wound healing.
  • Also on file: Lipase is rated "Insufficient Reliable Evidence To Rate" for Dyspepsia.

Evidence for this product's effectiveness is limited across the board. Zinc is effective for zinc deficiency and likely effective for Wilson disease, and possibly effective for acne and diabetes, but no effectiveness data on file confirm benefits for the other ingredients' stated uses.

Rutin, papain, bromelain, lipase, trypsin, and chymotrypsin all lack sufficient reliable evidence to support claims for their listed conditions. Most of the product's ingredient uses — from anti-inflammatory to wound-healing roles — are not established in the data we hold.

The evidence, ingredient by ingredient Rutin Zinc Papain Bromelain Calcium Lipase 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 9 of the 9 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 9 of 9.
  • General safety write-ups exist for 9 of 9.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at recommended doses. Zinc is safe in amounts below 40 mg daily for adults; higher doses raise concern for copper deficiency and anemia.

Calcium is generally safe at recommended intakes, though high chronic doses (over 1,500 to 2,000 mg daily) have been weakly linked to prostate cancer risk and cardiovascular concerns in some studies. Rutin and papain may cause headache, flushing, rashes, or allergic reactions in sensitive people.

Bromelain commonly causes diarrhea, flatulence, or gastric upset. Nattokinase carries a rare but serious risk of bleeding, especially with concurrent blood thinners.

Trypsin and chymotrypsin can cause mild gastrointestinal upset or, rarely, allergic reactions including anaphylaxis. Pregnancy and lactation safety data are sparse or absent for most ingredients; rutin is rated likely safe in pregnancy, but papain is possibly unsafe, and bromelain, trypsin, chymotrypsin, and nattokinase lack sufficient data — talk with your doctor or pharmacist about use during pregnancy or breastfeeding.

Side effects, ingredient by ingredient Rutin Zinc Papain Bromelain Calcium Lipase Trypsin Chymotrypsin

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 6 of the 9 matched ingredients can interact with medications — Papain, Rutin, Calcium, Bromelain, Zinc, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 475 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.

If you take HIV integrase inhibitors (dolutegravir, elvitegravir, raltegravir), quinolone or tetracycline antibiotics, cephalexin, the antiviral ritonavir, the thyroid medication levothyroxine, the heart drugs sotalol or diltiazem, blood thinners (warfarin, aspirin, or other anticoagulants or antiplatelets), blood pressure medications, or penicillamine, check with your doctor or pharmacist before using this product. The calcium, zinc, papain, bromelain, and nattokinase content all carry documented or theoretical risks with these drug classes.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Megazyme Forte is a multi-enzyme supplement with limited effectiveness evidence for its stated uses. The biggest concern is its interaction potential — particularly calcium and zinc with HIV medications, antibiotics, and thyroid drugs, and nattokinase with blood thinners.

If you take any prescription medication, especially antivirals, antibiotics, or blood pressure or blood-thinning drugs, check with your own doctor or pharmacist before starting this product. Most people tolerate the ingredients well at standard doses, but long-term safety data are limited.

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

Assessment coverage: 9 of 16 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 Megazyme Forte, straight from the product label.

Brand Biophix
Barcode (UPC) X0014Z002J
Net contents 200 Tablet(s)
Market status On market
Date entered into DSLD Oct 24, 2022
DSLD ID 276059
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Megazyme Forte by Biophix, 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
100
UPC/BARCODE
X0014Z002J
IngredientAmount% DV
Proprietary Blend2036 mg--
L-Glutathione0 NP--
Rutin0 NP--
Zinc0 NP--
Papain0 NP--
Bromelain0 NP--
Calcium0 NP--
Lipase0 NP--
Superoxide Dismutase0 NP--
Amylase0 NP--
Pancreatin 4X0 NP--
Trypsin0 NP--
Catalase0 NP--
Alpha-Chymotrypsin0 NP--
Thymus Substance0 NP--
Nattozimes0 NP--
Serrazimes0 NP--

Other ingredients: Microcrystalline Cellulose, Stearic Acid, Magnesium Stearate, Silica, Croscarmellose Sodium, Pharmaceutical Glaze

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 Usage: As a dietary supplement take 2 tablets 3 times daily, two hours after each meal.

Formulation

Scientifically engineered with an extensive blend of essential plant and proteolytic enzymes, Megazyme Forte is a complete formula designed to support a healthy immune system and optimal digestion.

Optimized Supports healthy digestion & immunity Complete natural enzyme formula

GMP tested

Not manufactured with wheat, gluten, milk, or egg.

Formula

This is a unique formula containing Serrazimes and Nattozimes.

Containing 500 CFU of Nattozimes and 10,000 U of Serrazimes

Precautions

Do not eat freshness packet. Keep in bottle.

Not manufactured with wheat, gluten, milk, or egg. Produced in a GMP facility that processes other ingredients containing these allergens.

Caution: For adults only.

Consult physician if pregnant/nursing, taking medication, or have a medical condition.

Keep out of reach of children.

Storage

Store in a cool, dry place after opening.

General Statements

Please recycle.

10 years 1 best seller First choice

FDA Disclaimer Statement

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

Seals/Symbols

Manufactured in a GMP Inspected Facility Made in USA

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Megazyme Forte by Biophix label

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

Megazyme Forte 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 Megazyme Forte by Biophix

These are the 16 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Tablet(s) Dosage formTablet Or Pill Servings per container100 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 Blend

2036 mg per serving

Other (inactive) ingredients: Microcrystalline Cellulose, Stearic Acid, Magnesium Stearate, Silica, Croscarmellose Sodium, Pharmaceutical Glaze. These complete the product’s ingredient list but are not active constituents.

Interaction report

Megazyme Forte by Biophix Drug Interactions

Want to check YOUR meds against Megazyme Forte?

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
475Drugs
7 Major 464 Moderate 4 Minor

Ingredients driving the most interactions

Nattozimes 289
Calcium 168
Bromelain 141
Rutin 86
Zinc 67

Individual Drug Interactions

The ingredients in Megazyme Forte interact with 475 drugs. Click any drug to see the details.

6 of the 16 ingredients in Megazyme Forte interact with drugs. Each result below shows which ingredient is responsible. Nattozimes Calcium Bromelain Rutin Zinc Papain

Each ingredient & the kinds of drugs it affects

For each ingredient in Megazyme Forte 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.

Nattozimes2 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
Nattozimes full monograph & interactions

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Likelihood Probable Evidence B
Aluminum

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Likelihood Possible Evidence B
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

Taking calcipotriene with calcium might increase the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Likelihood Probable Evidence B
Lithium

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Likelihood Possible Evidence B
Quinolone Antibiotics

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Likelihood Probable Evidence B
Raltegravir (Isentress)

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Likelihood Possible Evidence B
Sotalol (Betapace)

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Likelihood Possible Evidence B
Tetracycline Antibiotics

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Likelihood Probable Evidence C
Thiazide Diuretics

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Likelihood Probable Evidence C
Verapamil (Calan, Others)

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Likelihood Probable Evidence D
Calcium Channel Blockers

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Likelihood Unlikely Evidence D
Calcium 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

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
Zinc 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 Megazyme Forte, from the product label.

Biophix

See all Biophix products
Name
Biophix Health & Nutrition
Street Address
4131 SW 47th Ave., Suite 1404
City
Davie
State
FL
ZipCode
33314
Phone Number
305-861-0898
Web Address
www.biophix.com
Pharmacist Counseling Corner

Megazyme Forte by Biophix: Common Questions

Does Megazyme Forte by Biophix interact with any medications?
Yes. Based on its ingredients, Megazyme Forte has a known interaction with 475 medications, including 7 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Megazyme Forte contains 16 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 this safe during pregnancy or breastfeeding?
Safety data are limited or absent for most ingredients in this product. Rutin is rated likely safe in pregnancy, but papain is possibly unsafe, and bromelain, trypsin, chymotrypsin, and nattokinase lack enough data to know either way. Talk with your doctor or pharmacist about your individual situation before using it during pregnancy or while breastfeeding.
Does this product actually work for digestion?
Evidence is not established in the data we hold for most of the digestive enzymes in this formula. While individual enzymes like pancreatin and lipase play roles in digestion, the product's effectiveness for dyspepsia or other digestive complaints lacks reliable clinical support.
What's the difference between the enzymes in here — papain, bromelain, trypsin, and chymotrypsin?
These are all proteases (enzymes that break down protein). Papain and bromelain come from plants; trypsin and chymotrypsin are derived from animal pancreas. They work similarly but come from different sources, though evidence for their benefit in supplement form is limited.
Can I take this with my diabetes medication?
Rutin in this product theoretically increases the risk of low blood sugar (hypoglycemia) when used with diabetes drugs. Check with your doctor or pharmacist about whether it's safe to combine.
What are the most common side effects?
The most frequent issues reported are from zinc (nausea, diarrhea, metallic taste, abdominal cramps), bromelain (diarrhea, flatulence, gastric upset), and trypsin or chymotrypsin taken together (nausea, heartburn, stomach pain). Allergic reactions are rare but possible with papain, bromelain, chymotrypsin, and nattokinase in sensitive individuals.
Why does this product have so many ingredients?
It's formulated as a broad-spectrum digestive and systemic enzyme blend, combining pancreatic enzymes, plant proteases, cofactors like zinc and calcium, and supportive substances. The intent is a multi-targeted approach, though evidence backing all these ingredients together is not established in the data we hold.

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.

Megazyme Forte label
Go deeper

The Full Monographs Behind Megazyme Forte’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

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

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

Calcium

Interacts with 168 drugs

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet falls short. Most people do best getting...

Read the full Calcium 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

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 → 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

Megazyme Forte'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 215 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 →

Zinc 88 references
  1. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.
  2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. DOI
  3. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
  4. Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40. PubMed
  5. Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.
  6. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PubMed
  7. Hebel SK, ed. Drug Facts and Comparisons. 52nd ed. St. Louis: Facts and Comparisons, 1998.
  8. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  9. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. PubMed
  10. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
  11. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. PubMed
  12. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  13. Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14. PubMed
  14. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54.. PubMed
  15. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. Ear Nose Throat J 2000;79:778-82.. DOI
  16. Simkin PA. Oral zinc sulphate in rheumatoid arthritis. Lancet 1976;2:539-42. PubMed
  17. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed
  18. Douglas RM, Miles HB, Moore BW, et al. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Antimicrob Agents Chemother 1987;31:1263-5. PubMed
  19. Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999;54:284-90. PubMed
  20. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr 1991;45:507-10.
  21. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  22. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Oph
  23. Greenberg JE, Lynn M, Kirsner RS, et al. Mucocutaneous pigmented macule as a result of zinc deposition. J Cutan Pathol 2002;29:613-5. PubMed
  24. Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med 2001;7:49-56.
  25. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70. PubMed
  26. Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med 2001;111:103-8. PubMed
  27. Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. QJM 2003;96:35-43. DOI
  28. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 2003;95:1004-7.. PubMed
  29. Jafek BW, Linschoten M, Murrow BW. Zicam Induced Anosmia. American Rhinologic Society 49th Annual Fall Scientific Meeting abstract. Orlando, Florida. September 20, 2003. http://app.american-rhinologic.org/programs/2003ARSFallProgram071503.pdf (Accessed 24
  30. Uebayashi H, Hatanaka T, Kanemura F, Tonosaki K. Acute anosmia in the mouse: behavioral discrimination among the four basic taste substances. Physiol Behav 2001;72:291-6.. PubMed
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  32. Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:181-90.. PubMed
  33. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33:1841-4. PubMed
  34. Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7. PubMed
  35. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4.
  36. Kondo Y, Yamagata K, Satoh M, et al. Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein. J Urol 2003;170:2467-70. PubMed
  37. Doz F, Berens ME, Deschepper CF, et al. Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 1992;29:219-26.
  38. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. PubMed
  39. Golik A, Modai D, Weissgarten J, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42-4. PubMed
  40. Leary WP, Reyes AJ, Van der Byl K. Urinary magnesium and zinc excretion after two different single doses of amiloride in healthy adults. Curr Ther Res 1983;34:205-16.
  41. McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 2003;28:659-70. PubMed
  42. Burd GD. Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. Microsc Res Tech 1993;24:195-213. PubMed
  43. Ducray A, Bondier JR, Michel G, et al. Recovery following peripheral destruction of olfactory neurons in young and adult mice. Eur J Neurosci 2002;15:1907-17. PubMed
  44. Mayer AD, Rosenblatt JS. Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior. Physiol Behav 1993;53:587-92. PubMed
  45. DeCook CA, Hirsch AR. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  46. Tisdall FF, Brown A, Defries RD. Persistent anosmia following zinc sulfate nasal spraying. JPed 1938;18:60-2. DOI
  47. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  48. Public Health Advisory. Loss of sense of smell with intranasal cold remedies containing zinc. U.S. Food and Drug Administration, June 16, 2009. Available at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm166059.htm (Accessed 16 June 2009)
  49. Dooren JC. FDA warns against use of Zicam. The Wall Street Journal, June 16, 2009. Available at: http://online.wsj.com/article/SB124516778692319231.html#mod=djemHL?mg=com-wsj (Accessed 16 June 2009).
  50. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20.
  51. Health Canada / GlaxoSmithKline Consumer Healthcare. Association of long-term, excessive use of zinc-containing Poli-Grip products with myeloneuropathy and blood dyscrasias. February 18, 2010. Available at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medef
  52. GlaxoSmithKline Consumer Advisory. GlaxoSmithKline (GSK) warns about a potential health risk associated with long-term, excessive use of GSK's zinc-containing denture adhesives Super Polygrip Original, Ultra Fresh and Extra Care. February 18, 2010. Availa
  53. Science M, Johnstone J, Roth DE, et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551-61. PubMed
  54. Castilla-Higuero, L., Romero-Gomez, M., Suarez, E., and Castro, M. Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease. Hepatology 2000;32(4 Pt 1):877. PubMed
  55. Sharquie, K. E., Najim, R. A., Farjou, I. B., and Al Timimi, D. J. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clin.Exp.Dermatol. 2001;26(1):21-26. PubMed
  56. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., and Poli, F. Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of
  57. Moore, R. Bleeding gastric erosion after oral zinc sulphate. Br.Med J 3-25-1978;1(6115):754. PubMed
  58. Jafek, B. W., Linschoten, M. R., and Murrow, B. W. Anosmia after intranasal zinc gluconate use. Am J Rhinol. 2004;18(3):137-141. DOI
  59. Simonart, T. and de, Maertelaer, V. Systemic treatments for cutaneous warts: a systematic review. J Dermatolog.Treat. 2012;23(1):72-77. PubMed
  60. Cochran, R. J., Tucker, S. B., and Flannigan, S. A. Topical zinc therapy for acne vulgaris. Int.J Dermatol. 1985;24(3):188-190. DOI
  61. Morgan, A. A. Bleeding gastric erosion after oral zinc sulphate. Br.Med.J. 5-13-1978;1(6122):1283-1284. PubMed
  62. Murphy, J. V. Intoxication following ingestion of elemental zinc. JAMA 6-22-1970;212(12):2119-2120.
  63. Lang, C. J., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., and Konig, H. J. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol. 1993;50(10):1007-1008. PubMed
  64. Fjellner, B. Drug-induced lupus erythematosus aggravated by oral zinc therapy. Acta Derm.Venereol. 1979;59(4):368-370. DOI
  65. Varas Lorenzo, M. J. Zinc acexamate and ranitidine in the short- and mid-term management of gastroduodenal ulcers. Curr Ther Res 21986;39:19-29.
  66. Bosch, F. and Jimenez, E. Post-marketing surveillance of zinc acexamate in peptic ulcer treatment. Clin Trials J 1990;27:301-312.
  67. DeCook, C. A. and Hirsch, A. R. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  68. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. 2012 Feb;105(2):39-40, 42.
  69. Dadamio J, Van Tournout M, Teughels W, Dekeyser C, Coucke W, Quirynen M. Efficacy of different mouthrinse formulations in reducing oral malodour: a randomized clinical trial. J Clin Periodontol. 2013 May;40(5):505-13. PubMed
  70. Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug PubMed
  71. Zittel S, Ufer F, Gerloff C, Münchau A, Rosenkranz M. Severe myelopathy after denture cream use--is copper deficiency or excess zinc the cause? Clin Neurol Neurosurg. 2014 Jun;121:17-8. PubMed
  72. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
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  74. Ding Y, Jia YY, Li F, et al. The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin. Br J Clin Pharmacol. 2012 Mar;73(3):422-7. PubMed
  75. Fallah R, Sabbaghzadegan S, Karbasi SA, Binesh F. Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in children with normal serum zinc level: A randomised clinical trial. Nutrition. 2015;31(11-12):1358-61. PubMed
  76. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12:CD005436. PubMed
  77. Mahmoud AM, Al-Alem U, Dabbous F, et al. Zinc intake and risk of prostate cancer: Case-control study and meta-analysis. PLoS One. 2016;11(11):e0165956. PubMed
  78. Nagraj SK, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A. Interventions for managing taste disturbances. Cochrane Database Syst Rev. 2017 Dec 20;12(12):CD010470. PubMed
  79. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020:e14252. PubMed
  80. Janyajirawong R, Vilaichone RK, Sethasine S. Efficacy of zinc supplement in minimal hepatic encephalopathy: A prospective, randomized controlled study (Zinc-MHE Trial). Asian Pac J Cancer Prev 2021;22(9):2879-2887. PubMed
  81. Nakano M, Nakamura Y, Miyazaki A, Takahashi J. Zinc pharmacotherapy for elderly osteoporotic patients with zinc deficiency in a clinical setting. Nutrients 2021;13(6):1814. PubMed
  82. Tolino E, Skroza N, Mambrin A, et al. An open-label study comparing oral zinc to lymecycline in the treatment of acne vulgaris. J Clin Aesthet Dermatol 2021;14(5):56-58.
  83. Hunter J, Arentz S, Goldenberg J, et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(11):e047474. PubMed
  84. Yamazaki K, Kageyama H, Fujiyama T, Ito T, Urano S, Honda T. A case of systemic contact dermatitis due to zinc supplements. Int J Dermatol 2022. PubMed
  85. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed
  86. Sivakumar RR, Chinnaiah Govindareddy D, Sahoo J, Bobby Z, Chinnakali P. Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial. J Pedi PubMed
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See these in context on the Zinc monograph →

Papain 11 references
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  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
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  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
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  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
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  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 →

Calcium 62 references
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  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
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  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
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Lipase 1 reference
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Nattokinase 9 references
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See these in context on the Nattokinase monograph →

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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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