Digestive Multi Enzymes [Discontinued] by Peak Performance

EFFECTIVE

• Cardiovascular disease diagnosis. Adenosine intravenous infusion is FDA-approved for use in cardiac stress testing to diagnose coronary artery disease (CAD). Details: Adenosine is infused at a dose of 0.14 mg/kg/minute for 6 minutes as an adjunct to thallium stress testing in patients who are unable to exercise adequately (15). Caffeine is a competitive antagonist at adenosine receptors and should be avoided for 24 hours prior to the test (9157,11770).
• Paroxysmal supraventricular tachycardia. Adenosine intravenous injection is FDA-approved for acute management of paroxysmal supraventricular tachycardia (PSVT). Details: Adenosine is indicated for termination of PSVT. It is given intravenously as a bolus of 6 mg over 1-2 seconds, followed by 1 or 2 further boluses of 12 mg at 1-2 minute intervals if necessary (15).

POSSIBLY EFFECTIVE

• Cachexia. Intravenous adenosine triphosphate may be beneficial in cachexic patients with various cancers. Oral adenosine has not been evaluated for this purpose. Details: Administering adenosine triphosphate (ATP) intravenously, up to 75 mcg/kg/minute for 30 hours every 2-4 weeks for up to 28 weeks, seems to stabilize body composition, appetite, and dietary intake, and to improve quality of life in people with advanced non-small-cell lung cancer and other tumors (9149,9151,9152).

POSSIBLY INEFFECTIVE

• Myocardial Infarction (MI). Intravenous or intracoronary adenosine does not seem to be beneficial for acute coronary syndrome. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 17 clinical studies in patients with acute coronary syndrome undergoing revascularization shows that administration of intracoronary or intravenous adenosine does not reduce major adverse cardiac events when compared with placebo. Adenosine also does not reduce all-cause death, non-fatal MI, or heart failure when compared with placebo. However, adenosine is associated with an increased risk of atrioventricular block (111744). The interpretation of these findings is limited by the heterogeneity of the included studies. In addition, most studies were in patients treated with percutaneous coronary intervention; the generalizability of these results to patients treated with thrombolysis is unclear.
• Postoperative nausea and vomiting (PONV). Parenteral adenosine does not seem to be beneficial for PONV. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 4 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce PONV when compared with placebo (97981).
• Postoperative pain. Parenteral adenosine does not seem to be helpful for postoperative pain. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 9 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce postoperative pain scores when compared with placebo (97981).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if topical adenosine is beneficial in patients with androgenic alopecia. Details: Preliminary clinical research shows that topical application of adenosine 0.75% solution to the scalp twice daily for 6 months does not improve hair growth in males with androgenic alopecia. However, patients applying topical minoxidil 5% (Rogaine) also experienced no improvement at 6 months, with over 97% of patients in each group reporting less than 30% hair growth in the affected area (93689).
• Athletic performance. It is unclear if oral adenosine triphosphate is beneficial for improving athletic performance. Details: Preliminary clinical research in healthy males performing 10 repeated sprinting bouts shows that taking adenosine triphosphate (PEAK ATP, TSI USA, Inc) 400 mg orally daily for 2 weeks prior to the exercise increases muscle excitability during the first two bouts and attenuates reductions in power output and muscle excitability during the final three bouts when compared with placebo (97982).
• Erectile dysfunction (ED). Oral adenosine monophosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking adenosine monophosphate 200 mg plus arginine aspartate 8 grams orally 1-2 hours prior to sexual intercourse improves erectile function and sexual satisfaction scores when compared with placebo in patients with erectile dysfunction (93690). It is not clear if this effect is due to adenosine, arginine, or the combination.
• Hearing loss. Oral adenosine triphosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with idiopathic sudden sensorineural hearing loss shows that taking adenosine triphosphate 300 mg orally daily with vitamin B12 1.5 mg orally daily for 8-16 weeks is associated with modestly reduced hearing loss after 4-6 months when compared with taking this combination for less than 8 weeks (104924). The validity of this finding is limited by the observational nature of the study and the lack of a control group.
• Herpes labialis (cold sores). It is unclear if intramuscular adenosine monophosphate is beneficial in patients with herpes labialis. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research shows that a gel formulation of adenosine monophosphate 1.5-2 mg/kg IM every other day for a total of 9-12 injections might accelerate the healing of cold sores and reduce the risk of recurrence (9590). The validity of these findings is limited by the lack of a control group.
• Herpes zoster (shingles). It is unclear if intramuscular adenosine monophosphate is beneficial in adults with herpes zoster. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in adults with shingles shows that giving adenosine monophosphate in a gel formulation, 100 mg IM three times weekly for 4 weeks, increases the number of patients classified as pain-free at 4 weeks by 45% and might also accelerate viral clearance when compared with placebo (9155,10067).
• Lung cancer. Intravenous adenosine triphosphate does not seem to be beneficial in patients with advanced non-small-cell lung cancer (NSCLC). Oral adenosine has not been evaluated for this purpose. Details: One very small clinical study in adults with advanced NSCLC shows that giving adenosine triphosphate in at least 3, 96-hour infusions at a dose of 50 mcg/kg/min or more does not induce complete or partial responses when compared to baseline (9154).
• Neuropathic pain. It is unclear if intrathecal adenosine is beneficial for experimentally-induced neuropathic pain. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in healthy volunteers with areas of allodynia and hyperalgesia induced by topical capsaicin shows that giving single doses of intrathecal adenosine 0.5-2 mg modestly reduces these areas (9157). The clinical significance of this finding is unclear.
• Porphyria cutanea tarda. It is unclear if oral adenosine monophosphate is beneficial in patients with porphyria cutanea tarda. Details: A case series of 21 patients with porphyria cutanea tarda shows that taking adenosine monophosphate 160-200 mg orally daily for at least 4 weeks resolves or reduces symptoms, including photosensitivity, hyperpigmentation, and hypertrichosis, and decreases urinary and fecal excretion of porphyrins, when compared to baseline (106423). The validity of these findings is limited by the lack of a control group.
• Pulmonary hypertension. Adenosine given by central venous infusion might be beneficial in patients who develop pulmonary hypertension during cardiac surgery. Details: Preliminary clinical research in patients who develop pulmonary hypertension during cardiac surgery shows that giving a central venous infusion of adenosine, 50 mcg/kg/minute for 15 minutes after weaning from cardiopulmonary bypass, produces pulmonary vasodilation and reduces mean pulmonary arterial pressure (106424). The validity of these findings is limited by the lack of a control group. More evidence is needed to rate adenosine for these uses.

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EFFECTIVE

• Lactose intolerance. Lactase is effective for reducing gastrointestinal symptoms from consuming lactose in lactose intolerant individuals. Details: Multiple clinical trials show that taking lactase orally is effective for reducing GI symptoms in lactose-intolerant people when used before the consumption of lactose or when added to milk prior to consumption (2371,2372,2373,106669).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Colic. It is unclear if oral lactase is beneficial in infants with colic. Details: Preliminary clinical research in infants with colic shows that supplementing human milk or formula with lactase (Crosscare Ltd) for 10 days reduces breath hydrogen levels, but not time spent crying, when compared with placebo. However, approximately 30% of infants in this study were considered to be noncompliant. When only infants considered to be compliant were included in the analysis, time spent crying during the 10-day treatment period was reduced by about 6 hours in the lactase group when compared with placebo (96347). In two other small trials, giving 5 drops of a specific lactase formulation (Colibid, RG Pharmaceutica or Yamoo, Walter Bushnell) to infants aged 0-6 months with colic before each feed, or 4 times a day, for 2-4 weeks significantly reduces crying time and fussing time when compared with placebo (104107,112190). However, measures of crying time were based on subjective parent recall only.
• Prematurity. It is unclear if oral lactase is beneficial in premature patients. Details: Clinical research shows that giving fortified human milk or preterm formula treated with lactase drops (Lactaid, McNeil Consumer Products Company) to preterm infants does not improve weight gain, feeding tolerance, weekly length gain, or gain in head circumference by 36 weeks' gestational age or discharge from the hospital (whichever comes first) when compared with giving untreated milk or formula (96346). More evidence is needed to rate lactase for these uses.

(Read more about LACTASE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Celiac disease. Although there has been interest in using oral lipase for celiac disease, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Dyspepsia. It is unclear if oral lipase is beneficial for improving symptoms of postprandial distress syndrome. Details: A small clinical trial shows that taking a specific acid-resistant lipase (Amano Enzyme USA) 280 mg immediately before a high-fat meal does not reduce postprandial bloating and nausea when compared with placebo in individuals with postprandial distress syndrome (101900).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral lipase for IBD, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Prematurity. It is unclear if adding a specific form of lipase, recombinant human bile salt-stimulated lipase (rhBSSL), to infant formula improves outcomes in premature infants. Some research suggests a potential increased risk for adverse effects. Details: Human breast milk contains rhBSSL, but it is inactivated when breast milk is pasteurized for donation. Clinical research in infants born before 32 weeks' gestation shows that adding rhBSSL as 8700 units per 100 mL formula or pasteurized breast milk, for 4 weeks does not increase growth velocity, body length, or head circumference over the next 12 months when compared with formula or pasteurized breast milk devoid of lipase. However, the infants who were small for gestational age (SGA), which made up approximately 15% of the study population, grew by an additional 1.9 grams/kg daily on average when compared with placebo (101940). More evidence is needed to rate lipase for these uses.

(Read more about LIPASE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there has been interest in using oral papain for cancer, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Dental caries. It is unclear if topical papain gel is beneficial for reducing procedure time or pain in children having caries removed by a dentist. Details: A small clinical study in children 3-9 years of age with dental caries shows that application of a specific papain gel (Brix3000, Brix Medical Science) 3000 U/mg during atraumatic restorative treatment (ART) by a dentist actually increases the time required to remove caries tissue, with no effect on pain, when compared with ART alone (107434).
• Diabetic foot ulcers. Although there has been interest in using topical papain for diabetic foot ulcers, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Exercise-induced muscle soreness. Oral papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy males shows that taking a combination enzyme tablet containing papain 50 mg, trypsin 75 mg, bromelain 50 mg, amylase 10 mg, lipase 10 mg, lysosome 10 mg, and chymotrypsin 2 mg, four times in one day before downhill running, improves recovery of contractile muscle function and decreases muscle soreness when compared with placebo (67838). It is unclear if these findings are due to papain, other ingredients, or the combination.
• Herpes zoster (shingles). Although there has been interest in using oral papain for shingles, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Insect bite. It is unclear if topical papain is beneficial in individuals with fire ant stings. Details: A small clinical study in individuals with fire ant stings shows that applying gauze soaked with a specific papain-containing meat tenderizer (Adolph's meat tenderizer) to the sting for 20 minutes does not reduce pain or itching when compared with placebo (67845).
• Intestinal parasite infection. Although there has been interest in using oral papain for intestinal parasite infections, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Jellyfish stings. It is unclear if topical papain is beneficial in individuals with jellyfish stings. Details: A small clinical study in individuals with jellyfish stings shows that submerging affected skin into a solution with a papain-containing meat tenderizer (Adolph's meat tenderizer), starting two minutes after a jellyfish sting and continuing for at least 20 minutes, is less effective than hot water alone in decreasing pain caused by the jellyfish sting (67835).
• Pressure ulcers. Although there has been interest in using topical papain for pressure ulcers, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Radiation dermatitis. Oral papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients receiving pelvic radiotherapy shows that taking three capsules of a specific combination product (Wobe-Mugos E, Mucos Pharma) containing papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg per capsule, four times daily, beginning 3 days prior to radiotherapy and continuing until the last day of therapy, does not attenuate skin deterioration when compared with placebo (67834). However, another small, open-label clinical study in patients with uterine carcinoma shows that taking three capsules of the same combination product four times daily, beginning 7 days before radiotherapy and continuing for 9 weeks, reduces skin reactions when compared with control (67831). It is unclear if these findings are due to papain, other ingredients, or the combination.
• Radiation-induced cystitis. Oral papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with uterine carcinoma receiving radiotherapy shows that taking three capsules of a specific combination product (Wobe-Mugos E, Mucos Pharma) containing papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg per capsule, four times daily, beginning 7 days before radiotherapy and continuing for 9 weeks, reduces genitourinary symptoms when compared with control (67831).
• Radiation-induced nausea and vomiting. Oral papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients receiving pelvic radiotherapy shows that taking three capsules of a specific combination product (Wobe-Mugos E, Mucos Pharma), containing papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg per capsule, four times daily, beginning 3 days prior to radiotherapy and continuing until the last day of therapy, does not reduce radiation-related nausea or vomiting when compared with placebo (67834).
• Tonsillopharyngitis. Oral papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small clinical studies in patients with pharyngitis and/or tonsillitis shows that use of throat lozenges containing papain 2 mg, lysozyme 5 mg, and bacitracin 200 IU daily for 4 days reduces pain and inflammation of the throat and lymph nodes when compared with placebo or disinfectant alone (964,968). It is unclear if these findings are due to papain, other ingredients, or the combination.
• Traumatic oral ulcers. Although there has been interest in using topical papain for traumatic oral ulcers, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Venous leg ulcers. Although there has been interest in using topical papain for venous leg ulcers, there is insufficient reliable information about the clinical effects of papain for this purpose.
• Wound healing. Topical papain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with purulent wounds shows that applying papain 1% solution plus dimethylsulfoxide (DMSO) followed by phonophoresis, a process by which ultrasound is used to increase topical drug delivery, improves wound healing when compared to baseline (67843). The validity of this finding is limited by the lack of a comparator group. Also, it is unclear if these findings are due to papain, DMSO, or the combination. More evidence is needed to rate papain for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. In patients with deep wrinkles, preliminary clinical research shows that taking zinc citrate 50 mg and phytase 3,000 units daily for four days prior to a botulinum toxin treatment increases the patient-reported duration of botulinum toxin effects by approximately 25%, compared with no improvement in patients taking zinc gluconate 10 mg or placebo. The efficacy of botulinum treatment was also improved (101913). Whether this reported benefit is due to the dose or form of zinc, citrate, phytase, the combination, or other factors, is unclear (101913,101914).
• Blepharospasm. In patients with blepharospasm, preliminary clinical research shows that taking zinc citrate 50 mg and phytase 3,000 units daily for four days prior to a botulinum toxin treatment increases the patient-reported duration of botulinum toxin effects by approximately 25%, compared with no improvement in patients taking zinc gluconate 10 mg or placebo. The efficacy of botulinum treatment was also improved (101913). Whether this reported benefit is due to the dose or form of zinc, citrate, phytase, the combination, or other factors, is unclear (101913,101914).
• Child growth. Clinical research in infants consuming a corn-based diet shows that taking a fat- and micronutrient-based food supplement containing phytase, docosahexaenoic acid (DHA), arachidonic acid, and lysine increases linear growth at age 8 and 10 months and improves locomotor development when compared with not taking this supplement. In contrast, a similar fat- and micronutrient-based supplement without phytase, DHA, arachidonic acid, and lysine does not improve these indices when compared with not taking a supplement. The phytase-containing supplement did not affect linear growth, weight for age, or hand-eye coordination at 12 months (101902). These reported benefits to child growth are likely to be due to the combination of provided essential and non-essential nutrients. Any role of phytase is expected to be minimal.
• Iron deficiency anemia. Taking phytase with a meal containing phytate and iron increases iron absorption (101903,101904,101906). However, the effect of phytase specifically for the treatment of iron deficiency anemia remains unclear (101902). Phytase is sometimes added to the diet to increase the absorption of iron from food. In a small study of women, some with iron deficiency anemia, incubating wheat as a source of phytase with a traditional grain high in phytate increased iron absorption from the meal to 8.3% from 2.6% (101904). Also, adding microbial phytase to whole wheat rolls containing phytate increases iron absorption from a meal by approximately 82% when compared with rolls without added phytase (101906). In another small study, the addition of a microbial phytase to a single corn meal with added micronutrients increases iron absorption and incorporation into red blood cells after 14 days by 1.85-fold when compared with the meal without added phytase (101903). However, consuming white wheat rolls with added wheat bran as a source of phytase does not increase iron absorption from the meal when compared to consuming rolls with added wheat bran with deactivated phytase (101906). The use of phytase as treatment for iron deficiency, with or without anemia, has rarely been investigated. However, clinical research in infants consuming a corn-based diet shows that taking a fat- and micronutrient-based food supplement containing phytase, docosahexaenoic acid (DHA), arachidonic acid, and lysine for 6 months does not seem to be more effective for reducing anemia than taking the food supplement without phytase (101902).
• Zinc deficiency. Preliminary clinical research shows that adding phytase 20.5 units to a millet-based porridge with added zinc immediately prior to consumption increases zinc absorption by approximately 68% in children aged 12-24 months (101911). Some of these children had low plasma levels of zinc at baseline. However, the use of phytase specifically for the treatment of zinc deficiency has not been investigated. More evidence is needed to rate phytase for these uses.

(Read more about PHYTASE)

Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.

(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

LIKELY SAFE ...when adenosine is used intravenously and appropriately. Adenosine injection (Adenocard, Adenoscan) is an FDA-approved prescription drug (15).

POSSIBLY SAFE ...when adenosine triphosphate (ATP) is used intravenously and appropriately. ATP appears to be safe in intravenous doses of 75 mcg/kg per minute for 30 hours given every 2 weeks for 28 weeks (9149,9154). There is insufficient reliable information available about the safety of adenosine when used orally or intramuscularly.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately with lactose-containing foods. Lactase has Generally Recognized as Safe (GRAS) status in the US when prepared from Candida pseudotropicalis or Kluyveromyces lactis (104108,104109). Lactase has been used safely in doses up to 9900 international units (IU) and up to 13,500 food chemical codex (FCC) units (2371,2372,2373,106669).

CHILDREN: LIKELY SAFE
when used orally and appropriately with lactose-containing foods.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately with lactose-containing foods.

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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.

(Read more about LIPASE)

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.

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LIKELY SAFE ...when consumed in the amounts commonly found in foods. There is insufficient reliable information available about the safety of phytase when used orally as a supplement.

PREGNANCY AND LACTATION:
Insufficient reliable information is available; avoid using.

(Read more about PHYTASE)

POSSIBLY SAFE ...when used orally and appropriately. Various proteolytic enzymes have been safely used orally in clinical research (716,964,965,968,969,6252,6253,10622,11457,18281,18284) (91104,91105,91106,91111,96449). Side effects are typically mild to moderate and most often include gastrointestinal effects. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes. ...when used topically and appropriately. Various proteolytic enzymes have been safely used topically in clinical research (67835,67843,67845,91113). Some proteolytic enzymes might cause allergic reactions when used topically. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Carbamazepine might increase the risk of heart block when used concomitantly with adenosine.  Details Carbamazepine and adenosine can both cause heart block. Giving them concurrently might produce an additive effect (15).

DIPYRIDAMOLE (Persantine) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = D Dipyridamole can increase the therapeutic and toxic effects of adenosine.  Details Dipyridamole decreases the metabolism of adenosine. Intravenous infusion of adenosine in patients who are taking dipyridamole can cause dizziness, bradycardia, and syncope. Dipyridamole should be discontinued for several days prior to a cardiac stress test using adenosine (12209).

METHYLXANTHINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.  Details The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors (9157). It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests (11770).

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WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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).

(Read more about PAPAIN)

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(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

General ...Intravenously, the prescription form of adenosine can cause cardiovascular and respiratory adverse effects. When used orally or intramuscularly, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Intravenously: Chest pain, dizziness, dyspnea, facial flushing, headache, hypotension, nausea, nervousness, numbness, paresthesias, and tingling.
Serious Adverse Effects (Rare):
Intravenously: Arrhythmias, first- and second-degree heart block, hypersensitivity reactions, myocardial infarction, ST segment depression, and ventricular tachycardia.

Cardiovascular ...Intravenously, adenosine causes chest pain, palpitations, hypotension, and supraventricular tachycardia (15,9148). Intravenous adenosine has also been associated with arrhythmias, fatal or nonfatal cardiac arrest, ventricular tachycardia, and myocardial infarction (15). Intravenously, adenosine triphosphate (ATP) causes chest pain, particularly at doses greater than 50 mcg/kg per minute (9154).

Dermatologic ...Intravenously, adenosine causes flushing in up to 44% of patients in clinical research (15). Topically, folliculitis and pruritus can occur after application of adenosine to the scalp (93689).

Gastrointestinal ...Intravenously, adenosine can cause abdominal discomfort (15).

Neurologic/CNS ...Rapid intravenous injection of adenosine can cause headache, lightheadedness, insomnia, and anxiety (9148,9151,9152,9154,9158). New onset seizures, including tonic-clonic seizures, have also occurred (15). Intrathecally, adenosine has been reported to cause headache (9157).

Pulmonary/Respiratory ...Intravenously, adenosine can cause dyspnea, bronchospasm, bronchoconstriction, and respiratory arrest (15). Intravenously, adenosine triphosphate (ATP) causes dyspnea, which can be severe, particularly at doses greater than 50 mcg/kg/minute (9154).

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General ...Orally, lactase is generally well tolerated.

Immunologic ...A case of lactase-induced contact dermatitis and immunoglobulin E (IgE)-mediated allergic rhinoconjunctivitis has been reported in a worker exposed to powdered lactase. Allergy to lactase was confirmed by prick test, open application test, and chamber challenge test (96348).

(Read more about LACTASE)

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).

(Read more about LIPASE)

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).

(Read more about PAPAIN)

General ...Orally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Workplace immunological responses to airborne powdered phytase have been reported (101901,101908,101909,101910).

Immunologic ...There are numerous reports of immunologic responses to airborne powdered phytase in the animal-feed industry (101901,101908,101909,101910). Examples of reactions include allergic occupational asthma and hypersensitivity pneumonitis (101901,101908). In one case report of a 43-year-old male, hypersensitivity pneumonitis related to phytase was diagnosed following a 6-month history of coughing, shortness of breath, fever, and dyspnea (101908). In an analysis of 53 people occupationally exposed to phytase, 28% had IgE antibodies and 45% had IgG antibodies specific to phytase. Symptoms included dyspnea, rhinitis, and eye and skin reactions (101909). In another analysis of patients with IgE-mediated occupational respiratory allergy, wheezing, chest tightness, shortness of breath, cough, and asthmatic symptoms were reported (101910).

(Read more about PHYTASE)

General ...Orally, proteolytic enzymes are generally well tolerated. See specific monographs for detailed safety information related to individual proteolytic enzymes.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Serious Adverse Effects (Rare):
Topically: Allergic reactions.

Gastrointestinal ...Orally, some patients taking proteolytic enzymes may have gastrointestinal complaints (101517).

Immunologic ...Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical (102705). In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma (102706,102707).

(Read more about PROTEOLYTIC ENZYMES (PROTEASES))