Each capsule contains: Choline (2-hydroxy-N,N,N-trimethylethanaminium ) 50 mg • Cynara Cardunculus l. 4:1 extract (DHE: 50 mg) 12.5 mg • Frangula purishiana 3:1 extract (DHE: 20 mg) 6.66 mg • L-Methionine 50 mg • Pancreatin 20 mg • Peumus Boldus molina 50 mg. Other Ingredients: Cellulose, Gelatin, Magnesium Octadecanoate, Myo-Inositol.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
Below is general information about the effectiveness of the known ingredients contained in the product Hepaticol. 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
Below is general information about the safety of the known ingredients contained in the product Hepaticol. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Tea prepared with alder buckthorn bark 2 grams has been used with apparent safety for up to 8 days (12). Only properly aged bark should be used, and the recommended dose should not be exceeded (12).
POSSIBLY UNSAFE ...when used orally for more than 8 to 10 days (12). In 1993 the FDA removed Generally Recognized As Safe (GRAS) status from alder buckthorn due to lack of safety data. Chronic use of anthraquinone laxatives, such as alder buckthorn, for 9 months or longer is associated with damage to gastrointestinal epithelial cells and pigmentation of the colonic mucosa, known as pseudomelanosis coli (30743,37266). There is some data linking this condition to an increased risk of colorectal cancer (30743,37266,37269), although there is also contradictory evidence that does not show a link (6138).
CHILDREN: LIKELY UNSAFE
when used orally in children younger than 12 years of age (12); avoid using.
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally (12); avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Artichoke has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Artichoke extract has been used with apparent safety at doses up to 3200 mg daily for up to 12 weeks (6282,15204,52235,91475,91478,100934). Artichoke leaf powder has been used with apparent safety at a dose of 1000 mg daily for up to 8 weeks (104133). Cynarin, a constituent in artichoke extract, has been used with apparent safety at daily doses of 750 mg daily for up to 3 months or 60 mg daily for up to 7 months (1423,1424,52222,52223,52236).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of artichoke when used in medicinal amounts during pregnancy or lactation; avoid amounts greater than those found in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Boldo has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY UNSAFE ...when used orally in medicinal amounts. The volatile oil (2.5% in the leaf) contains the liver toxin ascaridole (4). Boldo has also been linked to a documented case of liver damage (13178). If boldo preparations are taken for medicinal purposes, only ascaridole-free preparations should be used. There is insufficient reliable information available about the safety of boldo when used topically.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts.
In animals, boldo and the constituent boldine have abortive and teratogenic effects (100302). Also, the ascaridole constituent of boldo is a liver toxin (4).
LIKELY SAFE ...when used orally and appropriately. Choline is safe in adults when taken in doses below the tolerable upper intake level (UL) of 3.5 grams daily (3094) ...when used intravenously and appropriately. Intravenous choline 1-4 grams daily for up to 24 weeks has been used with apparent safety (5173,5174).
POSSIBLY UNSAFE ...when used orally in doses above the tolerable upper intake level (UL) of 3. 5 grams daily. Higher doses can increase the risk of adverse effects (3094).
CHILDREN: LIKELY SAFE
when used orally and appropriately (3094).
Choline is safe in children when taken in doses below the tolerable upper intake level (UL), which is 1 gram daily for children 1-8 years of age, 2 grams daily for children 9-13 years of age, and 3 grams daily for children 14-18 years of age (3094).
CHILDREN: POSSIBLY UNSAFE
when used orally in doses above the UL.
High doses can increase the risk of adverse effects (3094).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Choline is safe when taken in doses below the tolerable upper intake level (UL), which is 3 grams daily during pregnancy and lactation in those up to 18 years of age and 3.5 grams daily for those 19 years and older (3094,92114). There is insufficient reliable information available about the safety of choline used in higher doses during pregnancy and lactation.
LIKELY SAFE ...when used orally in amounts commonly found in food (94500).
POSSIBLY SAFE ...when used orally or intravenously and appropriately in medicinal amounts under the supervision of a healthcare professional (2410,2411,2413).
POSSIBLY UNSAFE ...when used orally or intravenously in excessive doses. Doses larger than 100 mg/kg should be avoided to prevent severe and potentially lethal cerebral effects (9339).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (94500).
CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately (9338).
CHILDREN: POSSIBLY UNSAFE
when used intravenously in infants receiving parenteral nutrition.
In infants, blood methionine concentration can increase due to lower enzyme activity and inability to metabolize methionine. High levels of methionine can cause liver toxicity (9338).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food (94500).
There is insufficient reliable information available about the safety of methionine in medical doses during pregnancy and lactation; 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).
Below is general information about the interactions of the known ingredients contained in the product Hepaticol. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Alder buckthorn has stimulant laxative effects. Theoretically, concomitant use of corticosteroids with alder buckthorn can increase the risk of potassium depletion (2).
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Alder buckthorn has stimulant laxative effects. Theoretically, potassium depletion associated with alder buckthorn might increase the risk of digoxin toxicity (19).
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Alder buckthorn has stimulant laxative effects. Theoretically, overuse of alder buckthorn might compound diuretic-induced potassium loss (19). There is some concern that people taking alder buckthorn along with potassium depleting diuretics might have an increased risk for hypokalemia.
Details
Some diuretics that can deplete potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), and hydrochlorothiazide (HCTZ, HydroDIURIL, Microzide), and others.
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Alder buckthorn has stimulant laxative effects. Concomitant use with stimulant laxative medications might compound fluid and electrolyte loss (19).
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Alder buckthorn has stimulant laxative effects. In some people alder buckthorn can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of alder buckthorn.
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Theoretically, artichoke leaf extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
A meta-analysis of small clinical studies shows that taking artichoke leaf extract for 8-12 weeks can modestly reduce fasting plasma glucose when compared with placebo (105768).
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Theoretically, artichoke leaf extract may increase the risk of hypotension when taken with antihypertensive drugs.
Details
A meta-analysis of small clinical studies in patients with hypertension shows that taking artichoke can reduce systolic blood pressure by around 3 mmHg and diastolic blood pressure by around 2 mmHg when compared with placebo (105767).
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Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2B6.
Details
In vitro research shows that artichoke leaf extract inhibits CYP2B6 activity (97717). However, this interaction has not been reported in humans.
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Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2C19.
Details
In vitro research shows that artichoke leaf extract inhibits CYP2C19 activity (97717). However, this interaction has not been reported in humans.
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Theoretically, taking boldo with anticoagulant/antiplatelet drugs might increase the risk of bleeding.
Details
Animal and in vitro research shows that boldine, a constituent of boldo, has antiplatelet activity (5191,36789). In one case report, an adult taking a combination of boldo and fenugreek with warfarin experienced an increase in international normalized ratio (INR); however, it is unclear if this effect was due to boldo, fenugreek, the combination, or another factor (5191).
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Theoretically, taking boldo with hepatotoxic drugs might increase the risk of hepatic injury and disease.
Details
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Theoretically, taking boldo with lithium might increase the levels and clinical effects of lithium.
Details
Boldo is believed to have diuretic effects (4). Theoretically, these diuretic effects might reduce the excretion of lithium. The dose of lithium might need to be decreased.
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Taking boldo with tacrolimus may decrease the levels and clinical effects of tacrolimus, potentially increasing the risk of transplant rejection.
Details
In one case report, a patient with a long-term history of stable tacrolimus levels developed subtherapeutic levels after taking boldo 300 mg twice daily orally for several weeks. Tacrolimus levels returned to normal after discontinuing boldo. However, the mechanism of this interaction is unclear (92601).
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Theoretically, choline might decrease the effects of atropine in the brain.
Details
Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine (42240). Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.
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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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Below is general information about the adverse effects of the known ingredients contained in the product Hepaticol. 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, alder buckthorn seems to be well tolerated when properly aged bark is used appropriately for no more than 8 to 10 days (12). Adverse effects include cramp-like discomfort (2). Chronic use, especially for 9 months or longer, is associated with damage to gastrointestinal epithelial cells and pigmentation of the colonic mucosa, known as pseudomelanosis coli (30743,37266). There is some data linking this condition to an increased risk of colorectal cancer (30743,37266,37269), although there is also contradictory evidence which does not show a link (6138). Alder buckthorn has also been associated with potassium depletion, albuminuria, and hematuria when used orally (2).
Gastrointestinal ...Orally, adverse effects include cramp-like discomfort (2). Chronic use, especially for 9 months or longer, is associated with damage to gastrointestinal epithelial cells and pigmentation of the colonic mucosa, known as pseudomelanosis coli (30743,37266). The fresh bark contains free anthrone, which can cause severe vomiting. This constituent is destroyed by aging the bark naturally for one year or artificially with heat and aeration (2).
Genitourinary ...Orally, adverse effects to alder buckthorn include albuminuria and hematuria (2).
Oncologic ...Orally, there is also some data linking pseudomelanosis coli to an increased risk of colorectal cancer (30743,37266,37269), although there is also contradictory evidence which does not show a link (6138).
General
...Orally, artichoke extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, flatulence, hunger, and nausea.
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to artichoke inulin has been reported in individuals sensitive to inulin.
Topically: Chest tightness, cough, and dyspnea after occupational exposure in sensitive individuals.
Dermatologic
...Artichoke can cause an allergic reaction in some patients.
Patients sensitive to the Asteraceae/Compositae family may be at the greatest risk. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. Topically, allergic contact dermatitis can occur with the use of artichoke. This has been attributed to the constituent cynaropicrin (11,52206,52226,52230). Redness in the face (11774) and sweating (91475) have been reported rarely following oral use of artichoke extract.
Occupational or airborne exposure to artichoke may also cause allergic reactions. In one case, a 52-year-old male presented with severe spongiotic dermatitis in exposed areas that was recurrent over the past 8 years. A patch test confirmed allergies to artichokes and sesquiterpene lactones, a group of allergens from the Compositae family, and the patient confirmed occupational and airborne exposure to artichokes during the time of his symptoms. The patient improved considerably after treatment with dupilumab (111565).
Gastrointestinal
...Orally, artichoke extract might increase abdominal discomfort, flatulence, diarrhea, hunger, and nausea in some patients (2562,52238,91475).
Abdominal pain and a bitter taste in the mouth were reported by a single person following oral use of a dietary supplement containing artichoke extract, as well as red yeast rice, pine bark extract, and garlic extract (89452). It is not clear if this adverse effect was due to artichoke, other ingredients, or the combination.
In one case report, the autopsy of an 84-year-old female revealed a colonic bezoar comprised of artichoke fiber and fragments. This bezoar caused complete intestinal obstruction, leading to fatal acute peritonitis. Although rare, patients who lack adequate teeth and/or who have a history of gastric surgery are at increased risk for fibrous bezoar formation (97716).
Pulmonary/Respiratory
...Following occupational exposure, allergic symptoms including dyspnea, cough, chest tightness, and asthma symptoms or exacerbation have been reported.
The effects were attributed to sensitization to artichoke. Subsequent nasal challenge with artichoke extract caused reduced nasal patency in these patients (52210,52230).
Orally, severe anaphylactic shock in response to artichoke inulin as an ingredient in commercially available products has been reported (52217). Individuals with a noted sensitivity to artichokes should consume inulin with caution. While rare, individuals with a known inulin allergy should avoid artichoke and artichoke extract.
General
...Orally, boldo is generally well tolerated when used in amounts commonly found in foods.
However, when used in medicinal amounts, boldo can cause significant adverse effects such as hepatotoxicity. There is currently a limited amount of information on the adverse effects of topical boldo; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, nausea, vomiting.
Topically: Dermatitis.
Severe Adverse Effects (Rare):
Orally: Hepatotoxicity, jaundice.
Cardiovascular ...In one report, a 39-year-old obese female developed palpitations and syncope after taking a weight loss supplement containing a combination of boldo, dandelion, and bladderwrack for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether boldo, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.
Dermatologic ...Topically, boldo can be irritating when applied to the skin (4). In one case report, a healthy 64-year-old patient experienced allergic contact dermatitis in an airborne pattern on the face, arms, and dorsum of both hands following airborne exposure to boldo. After exposure to boldo was avoided, the dermatitis resolved (106433).
Gastrointestinal ...In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male developed abdominal discomfort with gastrointestinal upset including heartburn (13178). In another case, a 72-year-old female reported nausea, vomiting, and anorexia, which were thought to be associated with hepatotoxic effects of a boldo infusion (100304).
Hepatic ...Orally, boldo is thought to potentially cause hepatotoxicity. The volatile oil from the boldo leaf contains the liver toxin, ascaridole. In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male with mild hepatic steatosis and very small gallbladder stones developed elevated liver transaminase levels. Levels normalized following discontinuation of the herbal product (13178). Several other cases of hepatotoxicity have been reported in elderly patients who received infusions of boldo leaves. These patients presented with elevated liver transaminase and bilirubin levels, sometimes up to 200 times the upper limit of normal, as well as nausea, vomiting, anorexia, asthenia, and jaundice. Lab tests and symptoms normalized a few days after stopping boldo (100304,106431).
Immunologic ...Boldo intake has been linked to one case of IgE-mediated anaphylactic allergic reaction (13185).
General
...Orally, choline is well tolerated when used appropriately.
Adverse effects have been reported with doses exceeding the tolerable upper intake level (UL) of 3.5 grams daily.
Most Common Adverse Effects:
Orally: Fishy body odor. At high doses of at least 9 grams daily, choline has been reported to cause diarrhea, nausea, salivation, sweating, and vomiting.
Cardiovascular ...Orally, doses of choline greater than 7. 5 grams daily may cause low blood pressure (94648).
Gastrointestinal ...Orally, large doses of choline can cause nausea, vomiting, salivation, and anorexia (42275,91231). Gastrointestinal discomfort has reportedly occurred with doses of 9 grams daily, while gastroenteritis has reportedly occurred with doses of 32 grams daily (42291,42310). Doses of lecithin 100 grams standardized to 3.5% choline have reportedly caused diarrhea and fecal incontinence (42312).
Genitourinary ...Orally, large doses of choline greater than 9 grams daily have been reported to cause urinary incontinence (42291).
Neurologic/CNS ...Orally, high intake of choline may cause sweating due to peripheral cholinergic effects (42275).
Oncologic ...In one population study, consuming large amounts of choline was associated with an increased risk of colorectal cancer in females, even after adjusting for red meat intake (14845). However, more research is needed to confirm this finding.
Psychiatric ...Orally, large doses of choline (9 grams daily) have been associated with onset of depression in patients taking neuroleptics. Further research is needed to clarify this finding (42270).
Other ...Orally, choline intake may cause a fishy body odor due to intestinal metabolism of choline to trimethylamine (42285,42275,42310,92111,92112).
General
...Orally, methionine is well tolerated when used in amounts commonly found in foods.
Intravenously, methionine is generally well tolerated.
Most Common Adverse Effects:
All ROAs: Dizziness, drowsiness, hypotension, irritability, and vomiting. Methionine may also cause headache, increased homocysteine levels, increased urinary calcium excretion, and leukocytosis.
Serious Adverse Effects (Rare):
All ROAs: Cerebral edema, hepatic encephalopathy. In infants, intravenous methionine has been linked to liver toxicity.
Cardiovascular ...Orally or intravenously, methionine can cause hypotension (9339,9340). High-dose methionine (75-100 mg/kg daily) may increase plasma concentrations of homocysteine, which is a risk factor for vascular disease (63112,63114,63115). However, a study of patients with type 2 diabetes and a history of cardiovascular disease (CVD) showed that methionine loading did not increase homocysteine concentrations, and that a cause-effect relationship between increased intake of methionine and endothelial dysfunction has not been clearly established (63110).
Gastrointestinal ...Orally or intravenously, methionine can cause vomiting (9339,9340).
Genitourinary ...Orally or intravenously, methionine may increase urinary calcium excretion (9340,63112,94095).
Hematologic ...Orally or intravenously, methionine may cause leukocytosis when used at a dose of 8-13. 9 grams daily for 4-5 days (9340).
Hepatic ...A single dose of 8 grams of methionine has reportedly caused hepatic encephalopathy in patients with cirrhosis (9340). Long-term use of methionine-containing parenteral nutrition solution has been linked to liver toxicity in infants (9338).
Neurologic/CNS
...Orally or intravenously, methionine can cause dizziness, drowsiness, headache, and irritability (9339,9340,94095).
A case of cerebral edema ultimately leading to death has been reported in a patient receiving methionine 100 mg/kg orally. The post-load plasma concentrations of methionine were substantially higher in this patient than those previously reported in humans receiving this usual oral loading dose, leading the authors to postulate that an overdose of methionine may have been administered erroneously. This can occur when plasma methionine levels rise above 3000 mcmol/L (9339). Another case of progressive cerebral edema associated with high methionine levels and betaine (N,N,N-trimethylglycine) therapy in a patient with cystathionine beta-synthase (CBS) deficiency has been reported (63119). The authors stated that the cerebral edema was most likely precipitated by the betaine therapy, but that the exact mechanism is uncertain.
Oncologic ...Although one case-control study of incident, histologically-confirmed gastric cancer has indicated that a diet rich in methionine, salt, and nitrite is associated with an increased risk of gastric cancer (2409), a large observational study that adjusted for multiple factors, including sodium intake, has found no association between high dietary intake of methionine and gastric cancer (108041).
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).