Ingredients | Amount Per Serving |
---|---|
(Methylcobalamin)
(Vitamin B-12 (Form: as Methylcobalamin) )
|
54 mcg |
(ChromeMate Chromium Polynicotinate)
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600 mcg |
((USP) (Standardized for))
(Pancreatin Note: (USP) (Standardized for) )
|
100 mg |
Amylase
(Amylase Note: 14985 Units )
|
|
(Lipase Note: 1200 Units )
|
|
(Protease Note: 14985 Units )
|
|
(Pepsin Note: 1:3000 )
|
390 mg |
150 mg | |
30 mg | |
30 mg | |
15 mg |
Calcium Phosphate (Alt. Name: Ca Phosphate), Veg. Cellulose, Stearic Acid (Alt. Name: C18:0), Veg. Magnesium Stearate, Silica, Vanillin
Below is general information about the effectiveness of the known ingredients contained in the product Dyzime-ACM. 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
Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Dyzime-ACM. 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 found in foods (94500).
POSSIBLY SAFE ...when aspartic acid is used orally and appropriately, short-term. D-aspartic acid 3-6 grams daily has been used with apparent safety in clinical trials for up to 3 months (94497,97576). L-aspartic acid has been used in doses up to 8 grams daily, short-term, without reports of adverse effects (94500).
CHILDREN: POSSIBLY UNSAFE
when aspartic acid is used orally in infants.
In rodents, aspartic acid given orally within a few days of birth caused neuronal necrosis in the hypothalamus. This adverse effect was not seen in nonhuman newborn primates and has not been assessed in humans. Until more data is available, the Institute of Medicine (IOM) and the Food and Nutrition Board advise that aspartic acid be avoided in infants (94500).
There is insufficient reliable information available about the use of aspartic acid supplements in children and adolescents; avoid using in amounts exceeding those found in food.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (94500).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when aspartic acid is used orally.
In rodents, aspartic acid given orally within a few days of birth caused neuronal necrosis in the hypothalamus. This adverse effect was not seen in nonhuman newborn primates and has not been assessed in humans. Until more data is available, the Institute of Medicine (IOM) and the Food and Nutrition Board advise that pregnant or breast-feeding women avoid the use of aspartic acid (94500).
POSSIBLY SAFE ...when taken orally as a single dose of up to 1500 mg (93328,93329). There is insufficient reliable information available about the safety of betaine hydrochloride when used in multiple doses.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chromium has been safely used in doses up to 1000 mcg daily for up to 6 months (1934,5039,5040,6858,6859,6860,6861,6862,6867,6868)(7135,7137,10309,13053,14325,14440,17224,90057,90061)(90063,94234,95095,95096,95097,98687); however, most of these studies have used chromium doses in a range of 150-600 mcg. The Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, long-term. Chromium has been safely used in a small number of studies at doses of 200-1000 mcg daily for up to 2 years (7060,7135,42618,42628,42666,110605,110607,110609). However, the Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts not exceeding the daily adequate intake (AI) levels by age: 0-6 months, 0.
2 mcg; 7-12 months, 5.5 mcg; 1-3 years, 11 mcg; 4-8 years, 15 mcg; males 9-13 years, 25 mcg; males 14-18 years, 35 mcg; females 9-13 years, 21 mcg; females 14-18 years, 24 mcg (7135). POSSIBLY SAFE...when used orally and appropriately in amounts exceeding AI levels. Chromium 400 mcg daily has been used safely for up to 6 weeks (42680).
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for pregnancy is 28 mcg daily for those 14-18 years of age and 30 mcg daily for those 19-50 years of age (7135).
PREGNANCY: POSSIBLY SAFE
when used orally in amounts exceeding the adequate intake (AI) levels.
There is some evidence that patients with gestational diabetes can safely use chromium in doses of 4-8 mcg/kg (1953); however, patients should not take chromium supplements during pregnancy without medical supervision.
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for lactation is 44 mcg daily for those 14-18 years of age and 45 mcg daily for those 19-50 years of age (7135). Chromium supplements do not seem to increase normal chromium concentration in human breast milk (1937). There is insufficient reliable information available about the safety of chromium when used in higher amounts while breast-feeding.
LIKELY SAFE ...when used orally and appropriately. Glutamine has been safely used in clinical research in doses up to 40 grams per day or 1 gram/kg daily (2334,2337,2338,2365,5029,5462,7233,7288,7293), (52288,52307,52308,52311,52313,52337,52349,52350,96516,97366). A specific glutamine product (Endari) is approved by the US Food and Drug Administration (FDA) (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 600 mg/kg daily in clinical trials (2363,2366,5448,5452,5453,5454,5458,7293,52272,52275), (52283,52289,52304,52306,52316,52341), (52359,52360,52371,52377,52381,52284,52385,52408,96637,96507,96516).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Glutamine has been shown to be safe in clinical research when used in amounts that do not exceed 0.7 grams/kg daily in children 1-18 years old (11364,46657,52321,52323,52363,86095,96517). A specific glutamine product (Endari) is approved by the US Food and Drug Administration for certain patients 5 years of age and older (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 0.4 grams/kg daily in clinical research (52338,96508). There is insufficient reliable information available about the safety of glutamine when used in larger amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of glutamine when used in larger amounts as medicine during pregnancy or lactation.
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.
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.
LIKELY SAFE ...when used orally, topically, intravenously, intramuscularly, or intranasally and appropriately. Vitamin B12 is generally considered safe, even in large doses (15,1344,1345,1346,1347,1348,2909,6243,7289,7881)(9414,9416,10126,14392,15765,82832,82949,82860,82864,90386)(111334,111551).
PREGNANCY: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA for vitamin B12 during pregnancy is 2.6 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA of vitamin B12 during lactation is 2.8 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 while breastfeeding.
Below is general information about the interactions of the known ingredients contained in the product Dyzime-ACM. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
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Betaine hydrochloride increases stomach acidity and could decrease the effects of H2-blockers.
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Betaine hydrochloride increases stomach acidity and could decrease the effects of PPIs.
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Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
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Theoretically, aspirin might increase chromium absorption.
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Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood (21055).
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Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
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Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
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Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone (16012). Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.
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NSAIDs might increase chromium levels in the body.
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Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention (7135).
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Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
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Theoretically, pancreatic enzyme products may reduce the effects of acarbose.
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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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Below is general information about the adverse effects of the known ingredients contained in the product Dyzime-ACM. 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 ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General ...Orally, betaine hydrochloride is generally well tolerated when taken as a single dose.
Gastrointestinal ...Theoretically, the hydrochloric acid produced from betaine hydrochloride might irritate gastric or duodenal ulcers or impede ulcer healing. It might also cause heartburn.
General
...Orally, chromium is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal irritation, headaches, insomnia, irritability, mood changes.
Serious Adverse Effects (Rare):
Orally: Rare cases of kidney and liver damage, rhabdomyolysis, and thrombocytopenia have been reported.
Dermatologic
...Orally, chromium-containing supplements may cause acute generalized exanthematous pustulosis (42561), skin rashes (42679), and urticaria (17224).
Also, chromium picolinate or chromium chloride may cause systemic contact dermatitis when taken orally, especially in patients with contact allergy to chromium (6624,90058). In one clinical study, a patient taking chromium nicotinate 50 mcg daily reported itchy palms that improved after the intervention was discontinued. It is unclear of this effect was due to the chromium or another factor (95096).
Topically, hexavalent chromium, which can be present in some cement, leather products, or contaminated soil, may cause allergic contact dermatitis (42645,42789,90060,90064,110606).
A case of lichen planus has been reported for a patient following long-term occupational exposure to chromium (42688).
Endocrine ...Orally, cases of hypoglycemia have been reported for patients taking chromium picolinate 200-1000 mcg daily alone or 200-300 mcg two or three times weekly in combination with insulin (42672,42783). Chromium picolinate has also been associated with weight gain in young females who do not exercise and in those following a weight-lifting program (1938).
Gastrointestinal
...Orally, chromium in the form of chromium picolinate, chromium polynicotinate, chromium-containing brewer's yeast, or chromium-containing milk powder may cause nausea, vomiting, diarrhea, decreased appetite, constipation, flatulence, or gastrointestinal upset (14325,42594,42607,42622,42643,42679).
Long-term exposure to heavy metals, including chromium, has been associated with increased risk of gallbladder disease and cancer (42682,42704).
Genitourinary ...Orally, chromium polynicotinate has been associated with disrupted menstrual cycles in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Hematologic ...Anemia, hemolysis, and thrombocytopenia were reported in a 33 year-old female taking chromium picolinate 1200-2400 mcg daily for 4-5 months (554). The patient received supportive care, blood product transfusions, and hemodialysis and was stabilized and discharged a few days later. Lab values were normal at a one-year follow-up.
Hepatic ...Liver damage has been reported for a 33-year-old female taking chromium picolinate 1200 mcg daily for 4-5 months (554). Also, acute hepatitis has been reported in a patient taking chromium polynicotinate 200 mcg daily for 5 months (9141). Symptoms resolved when the product was discontinued. Two cases of hepatotoxicity have been reported in patients who took a specific combination product (Hydroxycut), which also contained chromium polynicotinate in addition to several herbs (13037).
Musculoskeletal ...Acute rhabdomyolysis has been reported for a previously healthy 24-year-old female who ingested chromium picolinate 1200 mcg over a 48-hour time period (42786). Also, chromium polynicotinate has been associated with leg pain and paresthesia in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Neurologic/CNS ...Orally, chromium picolinate may cause headache, paresthesia, insomnia, dizziness, and vertigo (6860,10309,14325,42594). Vague cognitive symptoms, slowed thought processes, and difficulty driving occurred on three separate occasions in a healthy 35-year-old male after oral intake of chromium picolinate 200-400 mcg (42751). Transient increases in dreaming have been reported in three patients with dysthymia treated with chromium picolinate in combination with sertraline (2659). A specific combination product (Hydroxycut) containing chromium, caffeine, and ephedra has been associated with seizures (10307). But the most likely causative agent in this case is ephedra.
Psychiatric ...Orally, chromium picolinate has been associated with irritability and mood changes in patients taking the supplement to lose weight, while chromium polynicotinate has been associated with agitation and mood changes in patients taking the supplement to prevent weight gain during smoking cessation (6860,42643).
Renal
...Orally, chromium picolinate has been associated with at least one report of chronic interstitial nephritis and two reports of acute tubular necrosis (554,1951,14312).
Laboratory evidence suggests that chromium does not cause kidney tissue damage even after long-term, high-dose exposure (7135); however, patient- or product-specific factors could potentially increase the risk of chromium-related kidney damage. More evidence is needed to determine what role, if any, chromium has in potentially causing kidney damage.
Intravenously, chromium is associated with decreased glomerular filtration rate (GFR) in children who receive long-term chromium-containing total parenteral nutrition - TPN (11787).
Topically, burns caused by chromic acid, a hexavalent form of chromium, have been associated with acute chromium poisoning with acute renal failure (42699). Early excision of affected skin and dialysis are performed to prevent systemic toxicity.
Other ...Another form of chromium, called hexavalent chromium, is unsafe. This type of chromium is a by-product of some manufacturing processes. Chronic exposure can cause liver, kidney, or cardiac failure, pulmonary complications, anemia, and hemolysis (9141,11786,42572,42573,42699). Occupational inhalation of hexavalent chromium can cause ulceration of the nasal mucosa and perforation of the nasal septum, and has been associated with pneumoconiosis, allergic asthma, cough, shortness of breath, wheezing, and increased susceptibility to respiratory tract cancer and even stomach and germ cell cancers (42572,42573,42601,42610,42636,42667,42648,42601,42788,90056,90066). Although rare, cases of interstitial pneumonia associated with chromium inhalation have been reported. Symptoms resolved with corticosteroid treatment (42614).
General
...Orally and intravenously, glutamine is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, constipation, cough, diarrhea, flatulence, gastrointestinal pain, headache, musculoskeletal pain, nausea, and vomiting.
Endocrine ...One case of hot flashes has been reported in a patient taking glutamine 5-15 grams orally twice daily for up to 1 year (96520).
Gastrointestinal ...Orally, glutamine has been associated with belching, bloating, constipation, flatulence, nausea, vomiting, diarrhea, and gastrointestinal (GI) pain. Nausea, vomiting, constipation, diarrhea, and GI pain have been reported in clinical trials using high-dose glutamine 10-30 grams (0.3 grams/kg) in two divided doses daily to treat sickle cell disease (99414). One case of dyspepsia and one case of abdominal pain have been reported in patients taking glutamine 5-15 grams twice daily orally for up to 1 year (96520). In a small trial of healthy males, taking a single dose of about 60 grams (0.9 grams/kg of fat free body mass [FFM]) was associated with a 50% to 79% incidence of GI discomfort, nausea, and belching, compared with a 7% to 28% incidence with a lower dose of about 20 grams (0.3 gram/kg FFM). Flatulence, bloating, lower GI pain, and urge to regurgitate occurred at similar rates regardless of dose, and there were no cases of heartburn, vomiting, or diarrhea/constipation (105013). It is possible that certain GI side effects occur only after multiple doses of glutamine.
Musculoskeletal ...Orally, glutamine 30 grams daily has been associated with cases of musculoskeletal pain and non-cardiac chest pain in clinical trials for patients with sickle cell disease (99414).
Neurologic/CNS ...Orally, glutamine has been associated with dizziness and headache. A single case of dizziness has been reported in a patient treated with oral glutamine 0.5 grams/kg. However, the symptom resolved after reducing the dose to 0.25 grams/kg (91356). Mania and hypomania have been reported in 2 patients with bipolar disorder taking commercially purchased glutamine up to 4 grams daily (7291). Glutamine is metabolized to glutamate and ammonia, both of which might have neurological effects in people with neurological and psychiatric diseases or in people predisposed to hepatic encephalopathy (7293).
Oncologic ...There is some concern that glutamine might be used by rapidly growing tumors and possibly stimulate tumor growth. Although tumors may utilize glutamine and other amino acids, preliminary research shows that glutamine supplementation does not increase tumor growth (5469,7233,7738). In fact, there is preliminary evidence that glutamine might actually reduce tumor growth (5469).
Other ...Orally, glutamine has been associated with cough when a powdered formulation is used. It is unclear if this was due to accidental inhalation. One case of a burning sensation and one case of hypersplenism has been reported in a patient taking glutamine 5-15 grams twice daily orally for up to 1 year (96520).
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, 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).
General
...Orally, intramuscularly, and topically, vitamin B12 is generally well-tolerated.
Most Common Adverse Effects:
Intramuscular: Injection site reactions.
Serious Adverse Effects (Rare):
Intramuscularly: Severe hypokalemia has been rarely linked with correction of megaloblastic anemia with vitamin B12.
Cardiovascular ...In human clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (12150). Hypertension following intravenous administration of hydroxocobalamin has been reported in human research (82870,82864).
Dermatologic
...Orally or intramuscularly, vitamin B12 can cause allergic reactions such as rash, pruritus, erythema, and urticaria.
Theoretically, allergic reactions might be caused by the cobalt within the vitamin B12 molecule (82864,90373,90381,103974). In one case report, oral methylcobalamin resulted in contact dermatitis in a 59-year-old Japanese female with a cobalt allergy (103974). In another case report, a 69-year-old female developed a symmetrical erythematous-squamous rash for 5 years after oral vitamin B12 supplementation for 10 years. A patch test confirmed that the systemic allergic dermatitis was due to vitamin B12 supplementation, which resolved 3 months after discontinuation (114578).
Vitamin B12 (intramuscular or oral) has also been associated with at least 19 cases of acneiform eruptions which resolved upon discontinuation of vitamin B12 (90365,90369,90388). High-dose vitamin B12 (20 mcg daily) and vitamin B6 (80 mg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may last up to four months after the supplement is stopped and can be treated with systemic corticosteroids and topical therapy (10998,82870,82871).
Gastrointestinal ...Intravenously, vitamin B12 (hydroxocobalamin) 2. 5-10 grams can cause nausea and dysphagia (82864).
Genitourinary ...Intravenously, vitamin B12 (hydroxocobalamin) 5-15 grams has been associated with chromaturia in clinical research (82870,82871,112282,112264).
Hematologic ...According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (82914).
Musculoskeletal ...According to case report data, correction of megaloblastic anemia with vitamin B12 has precipitated gout in susceptible individuals (82879).
Neurologic/CNS ...Treatment with vitamin B12 has been rarely associated with involuntary movements in infants with vitamin B12 deficiency (90370,90385,90397). In some cases these adverse reactions were misdiagnosed as seizures or infantile tremor syndrome (90370,90385). These adverse reactions presented 2-5 days after treatment with vitamin B12 and resolved once vitamin B12 was discontinued (90370,90385,90397).
Oncologic ...Although some epidemiological research disagrees (9454), most research has found that elevated plasma levels of vitamin B12 are associated with an increased risk of various types of cancer, including lung and prostate cancers and solid tumors (50411,102383,107743). One study found, when compared with blood levels of vitamin B12 less than 1000 ng/mL, plasma vitamin B12 levels of at least 1000 ng/mL was strongly associated with the occurrence of solid cancer (107743). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of cancer. It is possible that having cancer increases the risk of vitamin B12 elevation. However, one observational study has found that the highest quintile of dietary intake of vitamin B12 is associated with a 75% increased incidence of developing esophageal cancer when compared with the lowest quintile in never drinkers, but not drinkers (107147).
Renal ...There is a case report of oxalate nephropathy in a 54-year-old male which was determined to be related to the use of intravenous hydroxocobalamin as treatment for cyanide poisoning. Intermittent hemodialysis was started 5 days after admission, along with a low-oxalate diet, oral calcium acetate, and pyridoxine 5 mg/kg daily (107148). A review of the use of intravenous hydroxocobalamin for suspected cyanide poisoning in 21 intensive care units in France between 2011 and 2017 resulted in a 60% increased odds of acute kidney injury and a 77% increased odds of severe acute kidney injury in the first week. However, biopsies were not conducted and a direct link with use of hydroxocobalamin could not be made (107139).
Other ...Several studies have found that higher vitamin B12 levels may be associated with increased mortality or decreased survival rates in hospitalized elderly patients (82889,82812,82857,82895). Human research has also found a positive correlation between vitamin B12 status and all-cause mortality in Pima Indians with diabetes (82863).