Each capsule contains: Proprietary Blend 401 mg: Pancreatin 4X USP, Papain (from papaya), Anise fruit (pimpinella anisum), fennel seed (foeniculum vulgare), Rutin , Bromelain (from pineapple), Trypsin , Amylase , Lipase , L-Chymotrypsin . Other Ingredients: Gelatin, Vegetable Stearate, Stearic Acid.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Digestive Enzymes. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Digestive Enzymes. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in amounts commonly found in food. Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when anise powder is used orally and appropriately in medicinal amounts. Anise powder has been used with apparent safety in clinical research at doses of up to 9 grams daily for up to 4 weeks (94944,94945). ...when anise oil is used orally and appropriately in medicinal amounts. Anise oil has been used with apparent safety in clinical research at doses of up to 600 mg daily for up to 4 weeks (94946,94947).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in food.
Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when used by children in medicinal amounts.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food.
Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when taken orally in medicinal amounts during pregnancy or breast-feeding.
POSSIBLY SAFE ...when used orally and appropriately. Doses up to 240 mg daily have been used safely for up to a year (6252,6253,10622,11457,18281,18284,91104,91105,91106,91111)(96449,103298). Higher doses up to 3200 mg daily have been used safely, short-term (18283,110546). ...when used topically and appropriately. Bromelain has been used safely as a debriding agent for up to 4 hours (18275,91113,103297,108148,108149,113899). Additionally, a retrospective cohort study in critically ill patients with severe burns suggests that use of bromelain as a debriding agent for up to 4 hours is not associated with a greater risk of bacteremia (113899).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used ophthalmically, as approved by the US Food and Drug Administration (9).
POSSIBLY SAFE ...when used orally in combination with trypsin for up to 10 days (716). There is insufficient reliable information available about the safety of chymotrypsin when administered by other routes.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).
CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week.
Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).
LACTATION: POSSIBLY UNSAFE
when used orally.
Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.
There is insufficient reliable information available about the safety of lipase.
CHILDREN: POSSIBLY UNSAFE
when recombinant human bile salt-stimulated lipase (rhBSSL) is used orally by premature infants.
Adding rhBSSL to infant formula or pasteurized breast milk increases the risk for serious gastrointestinal adverse effects in premature infants (101940).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when prescription pancreatic enzyme products are used orally and appropriately under the guidance of a healthcare professional (98667,98674,98676,98677,99115,99116,99118,99120,99122,99124)(99125,99126,99127). Prescription pancreatic enzyme products are typically initiated at a dose of 500-1000 lipase units/kg body weight per meal to a maximum of 2500 lipase units/kg body weight per meal or 4000 lipase units/gram of fat daily. Doses higher than 2500 lipase units/kg body weight per meal are prescribed only if medically necessary (99130).
POSSIBLY UNSAFE ...when prescription pancreatic enzyme products are used orally at doses over 2500 lipase units/kg body weight per meal or 10,000 lipase units/kg body weight daily. Higher doses, especially those greater than 6000 lipase units/kg body weight per meal, have been associated with fibrosing colonopathy (99130). There is insufficient reliable information available about the safety of supplemental forms of pancreatic enzyme products.
CHILDREN: LIKELY SAFE
when prescription pancreatic enzyme products are used orally and appropriately under the guidance of a healthcare professional (99118,99119,99120,99121,99122,99124,99125,99126).
Prescription pancreatic enzyme products are usually initiated at a dose of 500-1000 lipase units/kg body weight per meal to a maximum of 2500 lipase units/kg body weight per meal or 4000 lipase units/gram fat daily. Doses higher than 2500 lipase units/kg body weight per meal are prescribed only if medically necessary (99130).
CHILDREN: POSSIBLY UNSAFE
when prescription pancreatic enzyme products are used orally at doses over 2500 lipase units/kg body weight per meal or 10,000 lipase units/kg body weight daily.
Higher doses, especially those greater than 6000 lipase units/kg body weight per meal, have been associated with fibrosing colonopathy (99130). There is insufficient reliable information available about the safety of supplemental forms of pancreatic enzyme products.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using unless essential for replacement therapy (15).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Papain has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes, short-term. Papain has been used in combination with other proteolytic enzymes at a dose of up to 1200 mg daily for up to 9 weeks (964,965,968,67831,67834). ...when used topically as a diluted solution in appropriate doses for up to 20 minutes (67835,67843,67845).
POSSIBLY UNSAFE ...when used orally in large amounts. In excessive doses, papain can cause significant side effects including esophageal perforation (6). ...when raw papain is used topically. Raw papain or papaya latex is a severe irritant and vesicant (6).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
There is some concern that crude papain is teratogenic and embryotoxic (6).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts found in foods, such as fruits and vegetables.
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Rutin has been used with apparent safety at doses of up to 600 mg daily for up to 12 weeks (6252,24560,91104,96766,105298). ...when applied topically as a cream (92236,99258,99260).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the use of supplemental rutin; avoid amounts greater than those found in foods.
POSSIBLY SAFE ...when used topically by healthcare professionals trained in wound debridement (506). There is insufficient reliable information available about the safety of trypsin for its other uses. Although trypsin has been safely used in clinical research in doses of up to 288 mg orally daily in combination with other enzymes for up to 3 months, it is unclear if trypsin taken orally alone is safe (37193,92235,99473).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Digestive Enzymes. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, anise oil might decrease the levels and clinical effects of acetaminophen.
 Details
Animal research shows that taking anise oil with acetaminophen decreases peak plasma levels of acetaminophen but does not reduce overall bioavailability (94951). Whether this interaction will occur in humans is unclear.
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Theoretically, anise seed might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
A small clinical study shows that anise seed powder decreases fasting blood glucose levels by 36% when compared to baseline (94953).
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Theoretically, anise oil might decrease the efficacy of caffeine.
Details
Animal research shows that taking anise oil with caffeine decreases the bioavailability of caffeine (94951). Whether this interaction will occur in humans is unclear.
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Theoretically, anise oil might increase the effects and adverse effects of codeine.
Details
Animal research shows that anise oil increases the analgesic effects of codeine, possibly by inducing its phase I metabolism and increasing conversion to morphine (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with contraceptive drug therapy.
Details
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Theoretically, anise oil might increase the effects and adverse effects of diazepam.
Details
Animal research shows that taking anise oil with diazepam increases the motor impairment associated with diazepam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with estrogen-based hormone replacement therapy.
Details
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Theoretically, anise oil might decrease the efficacy of fluoxetine.
Details
Animal research shows that taking anise oil with fluoxetine reduces the antidepressant effects of fluoxetine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise oil might decrease the efficacy of imipramine.
Details
Animal research shows that taking anise oil with imipramine reduces the antidepressant effects of imipramine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise oil might increase the effects and adverse effects of midazolam.
Details
Animal research shows that taking anise oil with midazolam increases the motor impairment associated with midazolam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with tamoxifen therapy.
Details
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Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen (14806). Bromelain is thought to have antiplatelet activity (10639,14806,18285,18286,37234). 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 (110547).
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Theoretically, bromelain might increase levels of tetracycline antibiotics.
Details
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 (14296).
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Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
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Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.
Details
Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135). |
Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.
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Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.
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Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.
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Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.
Details
Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen. |
Theoretically, pancreatic enzyme products may reduce the effects of acarbose.
Details
The digestive enzymes present in pancreatic enzyme products may break down acarbose, reducing its effects (9).
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Theoretically, papain might increase the effects and side effects of warfarin.
Details
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 (613).
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Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Animal research suggests that rutin has hypoglycemic effects (105299).
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Below is general information about the adverse effects of the known ingredients contained in the product Digestive Enzymes. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, anise seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.
Dermatologic ...Topically, anise, in combination with other herbs, has been reported to cause localized pruritus (13483).
Immunologic ...Anise can cause allergic reactions in sensitive individuals. Orally or by inhalation, anise can cause rhinoconjunctivitis, occupational asthma, and anaphylaxis (13484). Topically, anise can cause contact dermatitis, rhinitis, and asthma (31319,31341). Contact dermatitis and cheilitis have also been reported following the use of toothpaste containing anethole, a constituent of anise (31403,31528).
General
...Orally, bromelain seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, flatulence, gastric upset, headache.
Topically: Pruritus, urticaria.
Dermatologic
...Topically, bromelain may cause dermal allergic reactions including urticaria, pruritus, and skin swelling (9184).
Redness, swelling, burning, pain at the application site, and cellulitis have also been reported rarely (108148,113513). In one case, a fixed drug eruption with pruritis near the groin was reported in a 33-year-old male taking bromelain 50 mg orally daily for 10 days. After discontinuation of bromelain and treatment with topical corticosteroid, the lesion resolved. Upon re-challenge with bromelain, the lesion reappeared in the same area (103300).
In another case report, a 61-year-old male with a history of chronic lower leg ulceration secondary to chronic venous hypertension and recurrent deep vein thrombosis on rivaroxaban presented with a deep-dermal burn on his lower calf. Bromelain-based topical enzymatic debridement agent Nexobrid 2 grams was applied to the burn site. Thirty minutes later, the patient experienced two instances of hemorrhage at the site of debridement. The patient was stabilized and treated with fluids, packed red cells, and tranexamic acid, and then the Nexobrid was removed (111656). Caution should be used in patients with underlying coagulopathies.
Gastrointestinal ...Orally, bromelain may cause gastrointestinal disturbances, including diarrhea, nausea, vomiting, flatulence, and abdominal pain (9184,18274,18282,96216,113513).
Immunologic
...Immunoglobulin E (IgE)-mediated allergic reactions to bromelain may occur (9184).
If inhaled, bromelain may cause sensitization and allergic reactions such as asthma (37199,37215,37233). In case reports of occupational inhalation of bromelain, additional allergic symptoms included difficulty swallowing, throat itching, eye irritation, and rhinitis (37214).
General ...There is currently a limited amount of information available about the adverse effects of chymotrypsin. Orally, hypersensitivity reactions, including anaphylaxis, have been reported (9). When injected into the eye, chymotrypsin has been reported to cause increased intraocular pressure and uveitis (9,509).
Immunologic ...Rarely, chymotrypsin has been reported to cause anaphylactic reactions characterized by dyspnea, urticaria, edema, shock, vascular collapse, and unconsciousness, which can lead to death (9,509).
Ocular/Otic ...Intraocular injections of chymotrypsin have been reported to cause increased intraocular pressure, corneal edema, striation, uveitis, iridoplegia, and filamentary keratitis (9,509).
General
...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.
Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).
Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).
Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).
Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).
Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.
Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).
General
...No adverse effects have been reported in adults.
However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal adverse effects, such as necrotizing enterocolitis, when recombinant human bile salt-stimulated lipase is used in premature infants.
Gastrointestinal ...Orally, when added to the formula or pasteurized breast milk consumed by premature infants, recombinant human bile salt-stimulated lipase (rhBSSL) can cause gastrointestinal adverse effects, including abdominal distension, flatulence, constipation, colic, abdominal pain, gastroenteritis, vomiting, regurgitation, and rectal bleeding (101940). Premature infants receiving rhBSSL also had a slightly higher rate of necrotizing enterocolitis (NEC) when compared with those receiving placebo. After review by a panel of experts, it was determined that the rate of confirmed or suspected NEC in infants consuming rhBSSL was 3.3%, compared with 0.5% in those receiving placebo. Although this rate of NEC is lower than the historical rate of occurrence in premature infants (11%), a possible increased risk for NEC cannot be ruled out (101940).
General
...Orally, prescription pancreatic enzyme products are generally well tolerated when used at prescribed doses in adults and children.
Most Common Adverse Effects:
Orally: Prescription pancreatic enzyme products can cause abdominal pain, constipation, diarrhea, dry mouth, flatulence, irritation of the skin around the mouth and anus, nausea, steatorrhea, and vomiting.
Topically: Pancreatic enzyme product powder is irritating to the skin, eyes, mucus membranes, and respiratory tract. Pancreatic enzyme products that are held in the mouth prior to swallowing can cause irritation of the mucosa, including ulceration and stomatitis.
Serious Adverse Effects (Rare):
Orally: Prescription pancreatic enzyme products can worsen glucose control. Extremely high doses have been associated with fibrosing colonopathy and high uric acid levels in blood and urine.
Topically: Inhalation of dust containing pancreatic enzyme products has been associated with asthma, bronchospasm, and pulmonary hypersensitivity reactions.
Dermatologic
...Orally, rash or skin conditions have been reported rarely in individuals taking prescription pancreatic enzyme products (67709,98667).
A pruritic rash occurred in one patient taking a prescription pancreatic enzyme product in one clinical trial; this event was considered by the investigators to be possibly related to treatment (98667). Erythema also occurred in an 84-year-old patient who had taken a digestive enzyme supplement containing pancreatic enzymes and other enzymes (67709). In a case report, taking a supplemental form of pancreatic enzymes also containing hemicellulose and dried ox bile extract powder (Festal, Handok Inc) was thought to be the cause of an acute generalized exanthematous pustulosis (AGEP). The patient required an antihistamine and an oral and topical corticosteroid. Since this product contained more than one ingredient, the role of the pancreatic enzymes in this specific adverse event is unclear (98675).
Topically, exposure to pancreatic enzyme product powder is irritating to the skin. Hypersensitivity reactions such as skin rash have been reported (15).
Endocrine ...Orally, prescription pancreatic enzyme products may cause hypoglycemia or hyperglycemia in some patients (67622,98676,98677). In a double-blind trial of a prescription pancreatic enzyme product compared with placebo in patients with unresectable pancreatic cancer and associated pancreatic duct obstruction, one patient developed diabetes during the study period (67708).
Gastrointestinal
...Orally, prescription pancreatic enzyme products can cause abdominal pain, constipation, diarrhea, dry mouth, irritation of the skin around the mouth and anus, flatulence, nausea, steatorrhea, and vomiting.
However, these symptoms can be controlled by following prescription dosing recommendations (67617,67618,67645,67648,67651,67653,67657,67666,67714,98667)(98676,99115,99117,99123,99130). Doses of higher than 2500 lipase units/kg body weight per meal are not recommended unless medically necessary in order to prevent serious side effects, including fibrosing colonopathy and colonic strictures. These side effects are associated with the higher doses of lipase in prescription pancreatic enzyme products (2382,67677,67678,67679,67680,67682,67689,67690,67696,67701,99130).
Topically, pancreatic enzyme products that are held in the mouth prior to swallowing can cause irritation of the mucosa, including ulceration and stomatitis (15).
Hematologic ...Orally, severe neutropenia has been reported with a pancreatic enzyme product. In one case report, a 61-year-old patient taking a prescription pancreatic enzyme product for chronic pancreatitis developed agranulocytosis that persisted despite a trial of filgrastim. Upon discontinuation of the pancreatic enzyme product, marked improvement in neutropenia occurred within 7 days, with full resolution within 6 weeks (107411).
Neurologic/CNS ...Orally, headache and dizziness have been reported rarely in individuals taking prescription pancreatic enzyme products (67618,98667,99120).
Ocular/Otic ...Topically, exposure to pancreatic enzyme product powder is irritating to the eyes. Hypersensitivity reactions such as watery eyes have been reported (15).
Pulmonary/Respiratory ...Topically, exposure to pancreatic enzyme product powder is irritating to the respiratory tract. Hypersensitivity reactions such as sneezing have been reported (15). Inhalation of dust containing pancreatic enzyme products has been associated with allergic rhinitis, asthma, bronchospasm, and pulmonary hypersensitivity reactions (11768,11769,67641).
Renal ...Orally, extremely high doses of pancreatic enzyme products containing more than 10,000 lipase units/kg body weight daily have been associated with high uric acid levels in blood and urine (67673,67693,67705). Rarely, kidney pain has been reported (98667).
General
...Orally and topically, papain seems to be well tolerated when used short-term at appropriate doses.
Taking high oral doses may be unsafe.
Most Common Adverse Effects:
Orally: Allergic reactions in sensitive individuals.
Topically: Urticaria and pruritus in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Esophageal perforation and severe gastritis with high doses.
Dermatologic ...Topically, papain can cause itching (966). Urticarial reactions and itching have been reported in people occupationally exposed to papain, with papain confirmed as the causative agent by skin prick tests or radioallergosorbent tests (RAST) (95533,95534). In a randomized controlled trial assessing the effects of papain, trypsin, and chymotrypsin on adverse effects from radiotherapy, moderate to severe epitheliolysis was more frequent in the enzyme-treated group than the placebo group (67834). It is unclear if this adverse effect is due to papain, other enzymes, or the combination.
Gastrointestinal ...Orally, papain has been associated with diarrhea. In a randomized controlled trial assessing the effects of papain, trypsin, and chymotrypsin on adverse effects from radiotherapy, moderate to severe diarrhea was more frequent in the enzyme-treated group than the placebo group (67834). However, it is unclear if this adverse effect is due to papain, other enzymes, or the combination. Papain has also been associated with gastric ulcers and esophageal perforation in case reports of phytobezoars treated with papain (67848). In general, large amounts of papain can cause esophageal perforation (6). Ingestion of papaya latex (raw papain) can cause severe gastritis.
Genitourinary ...Orally, papain has been associated with hypernatremia in case reports of phytobezoars treated with papain (67848).
Immunologic ...Orally, papain may cause allergic reactions, including itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea, in individuals sensitive to papain (6,967). Occupational exposure to airborne papain dust may also cause respiratory allergic reactions (95532,95533,95534,95535,95536).
Pulmonary/Respiratory ...Occupational exposure to airborne papain dust may cause respiratory allergic reactions. Symptoms include rhinitis, sneezing, conjunctivitis, dyspnea, wheezing, cough, and asthma. In most cases, papain is confirmed as the causative agent by skin prick tests, radioallergosorbent tests (RAST), or detection of papain-specific immunoglobulin E (IgE) and IgG (95532,95533,95534,95535,95536).
General ...Orally, rutin is generally well tolerated.
Dermatologic ...Orally, rutin may cause flushing and rashes in some people (313).
Gastrointestinal ...Orally, rutin may cause gastrointestinal disturbance in some people (313).
Neurologic/CNS ...Orally, rutin may cause headache in some people (313).
General ...Topically, trypsin can cause localized pain and transient burning (506). Orally, trypsin taken in combination with other enzymes can cause mild-to-moderate gastrointestinal symptom such as nausea, heartburn, and stomach pain (37193,92235). It is not known if trypsin or other enzymes causes these adverse effects.
Dermatologic ...Topically, trypsin can cause localized pain and transient burning (506).
Gastrointestinal ...Orally, trypsin taken in combination with other enzymes can cause mild-to-moderate gastrointestinal symptom such as nausea, heartburn, and stomach pain (37193,92235). It is not known if trypsin or other enzymes causes these adverse effects.
