| Ingredients | Amount Per Serving |
|---|---|
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Amylase
(Amylase Note: 6,500 DU )
|
|
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Glucoamylase
(Glucoamylase Note: 12 AGU )
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|
|
(Lipase Note: 250 FIP )
|
|
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(Protease 4.5 Note: 13,500 HUT )
|
|
|
Cellulase
(Cellulase Note: 360 CU )
|
|
|
Pectinase
(Pectinase Note: 7.5 endo-PGU )
|
|
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(Bromelain Note: 250,000 FCCPU )
|
|
|
(Lactase Note: 100 ALU )
|
|
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Invertase
(Invertase Note: 250 SU )
|
|
|
(Zingiber officinale )
(rhizome)
|
25 mg |
|
(Cinnamomum verum )
(bark)
|
10 mg |
|
(Pimpinella anisum )
(seed)
|
5 mg |
|
(Carum carvi )
(seed)
|
5 mg |
|
(Capsicum annuum )
|
5 mg |
|
(Foeniculum vulgare )
(seed)
|
5 mg |
Rice Bran PlantPart: bran, Vegetable Cellulose, Water
Below is general information about the effectiveness of the known ingredients contained in the product Enzyme Complex. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.
Below is general information about the safety of the known ingredients contained in the product Enzyme Complex. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in amounts commonly found in food. Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when anise powder is used orally and appropriately in medicinal amounts. Anise powder has been used with apparent safety in clinical research at doses of up to 9 grams daily for up to 4 weeks (94944,94945). ...when anise oil is used orally and appropriately in medicinal amounts. Anise oil has been used with apparent safety in clinical research at doses of up to 600 mg daily for up to 4 weeks (94946,94947).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in food.
Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when used by children in medicinal amounts.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food.
Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when taken orally in medicinal amounts during pregnancy or breast-feeding.
POSSIBLY SAFE ...when used orally and appropriately. Doses up to 240 mg daily have been used safely for up to a year (6252,6253,10622,11457,18281,18284,91104,91105,91106,91111)(96449,103298). Higher doses up to 3200 mg daily have been used safely, short-term (18283,110546). ...when used topically and appropriately. Bromelain has been used safely as a debriding agent for up to 4 hours (18275,91113,103297,108148,108149).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts typically found in food. Capsicum has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used topically and appropriately (7038,10650,105345). The active capsicum constituent capsaicin is an FDA-approved ingredient used in certain over-the-counter, topical preparations (272).
POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. A specific sustained-release chili extract (Capsifen) has been used safely in doses of up to 200 mg daily, for up to 28 days (105196). ...when used intranasally and appropriately, short-term. Capsicum-containing nasal sprays, suspensions, and swabs seem to be safe when applied multiple times over 24 hours or when applied daily or every other day for up to 14 days. Although no serious side effects have been reported in clinical trials, intranasal application of capsicum-containing products can be very painful (14322,14324,14328,14329,14351,14352,14353,14356,14357) (14358,14359,14360,15016,105204). POSSIBLY UNSAFE when used orally, long-term or in high doses. There is concern that long-term use or use of excessive doses might be linked to hepatic or kidney damage, as well as hypertensive crisis (12404,40569,40606). There is insufficient reliable information available about the safety of capsicum when injected.
CHILDREN: POSSIBLY UNSAFE
when used topically in children under 2 years old (272).
There is insufficient reliable information available about the safety of capsicum when used orally in children.
PREGNANCY: LIKELY SAFE
when used topically and appropriately (272).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Capsicum 5 mg daily has been used for up to 28 days during the latter half of the second trimester and the third trimester (96457).
LACTATION: LIKELY SAFE
when used topically and appropriately (272).
LACTATION: POSSIBLY UNSAFE
when used orally.
Dermatitis can sometimes occur in infants when foods heavily spiced with capsicum peppers are ingested during lactation (739). Also, observational research suggests that intake of raw capsicum peppers during pregnancy is associated with an increased risk of sensitization to inhalant allergens in children by the age of 2 years (41021).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Caraway has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when caraway oil is used orally in medicinal amounts. Caraway oil has been used with apparent safety at a dose of up to 150 mg daily for up to 4 weeks, in combination with peppermint oil (6740,6741,6742,10075,96344). ...when caraway seed is used orally, short-term. An aqueous caraway seed extract has been used with apparent safety at a dose of 3 grams daily for up to 3 months (94086,94087,94088). ...when used topically and appropriately. A heated poultice containing caraway oil 2% has been used with apparent safety for up to 3 weeks (94085).
PREGNANCY: POSSIBLY UNSAFE
when used in medicinal amounts (4912,6746).
Caraway oil has been used to stimulate menstruation (6746); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Ceylon cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Ceylon cinnamon 0.5-3 grams daily has been safely used in studies lasting up to 6 months (4,12,97248,97250,99874). ...when used as a mouth rinse for up to 15 days (92071). There is insufficient reliable information available about the safety of Ceylon cinnamon when used orally in greater amounts or for longer periods. Ceylon cinnamon contains trace amounts of coumarin (108260). In very high doses, coumarin can cause hepatotoxicity (15302). However, since the amount of coumarin in Ceylon cinnamon is negligible, it is unlikely to cause toxic effects (89652,92072,92073).
PREGNANCY: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in foods.
Fetal abnormalities have been reported in animals (4,12).
LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of Ceylon cinnamon in amounts greater than those found in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).
CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week.
Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).
LACTATION: POSSIBLY UNSAFE
when used orally.
Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.
LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).
POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).
CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).
PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods.
Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes.
Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).
LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods.
There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.
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.
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.
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.
Below is general information about the interactions of the known ingredients contained in the product Enzyme Complex. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, anise oil might decrease the levels and clinical effects of acetaminophen.
 Details
Animal research shows that taking anise oil with acetaminophen decreases peak plasma levels of acetaminophen but does not reduce overall bioavailability (94951). Whether this interaction will occur in humans is unclear.
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Theoretically, anise seed might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
A small clinical study shows that anise seed powder decreases fasting blood glucose levels by 36% when compared to baseline (94953).
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Theoretically, anise oil might decrease the efficacy of caffeine.
Details
Animal research shows that taking anise oil with caffeine decreases the bioavailability of caffeine (94951). Whether this interaction will occur in humans is unclear.
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Theoretically, anise oil might increase the effects and adverse effects of codeine.
Details
Animal research shows that anise oil increases the analgesic effects of codeine, possibly by inducing its phase I metabolism and increasing conversion to morphine (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with contraceptive drug therapy.
Details
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Theoretically, anise oil might increase the effects and adverse effects of diazepam.
Details
Animal research shows that taking anise oil with diazepam increases the motor impairment associated with diazepam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with estrogen-based hormone replacement therapy.
Details
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Theoretically, anise oil might decrease the efficacy of fluoxetine.
Details
Animal research shows that taking anise oil with fluoxetine reduces the antidepressant effects of fluoxetine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise oil might decrease the efficacy of imipramine.
Details
Animal research shows that taking anise oil with imipramine reduces the antidepressant effects of imipramine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise oil might increase the effects and adverse effects of midazolam.
Details
Animal research shows that taking anise oil with midazolam increases the motor impairment associated with midazolam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.
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Theoretically, anise might interfere with tamoxifen therapy.
Details
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Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen (14806). Bromelain is thought to have antiplatelet activity (10639,14806,18285,18286,37234). Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement (110547).
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Theoretically, bromelain might increase levels of tetracycline antibiotics.
Details
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg (14296).
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Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
Details
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI (12414). However, it is unclear if this interaction is clinically significant.
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Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
In vitro research shows that capsicum might increase the effects of antiplatelet drugs (12406,12407). Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin (12405,20348). However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin (92990). It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.
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Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo (40453,40614). Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes (96457).
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Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
Details
Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability (22617). This has not been shown in humans.
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Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
Details
Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70% (22613).
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Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
Details
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Theoretically, caraway might increase the risk of hypoglycemia when used with antidiabetes drugs.
Details
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Theoretically, caraway might increase the effects and adverse effects of CNS depressants.
Details
Animal research suggests that (S)-(+)-carvone, a major constituent of caraway seed extract, has sedative effects (39800).
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Theoretically, caraway might increase the levels and clinical effects of CYP1A1 substrates.
Details
In vitro evidence suggests that caraway extract can inhibit the activity of CYP1A1 in a dose-dependent manner (39780). This interaction has not been reported in humans.
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Theoretically, caraway might increase the risk of hypokalemia when used with diuretics that deplete potassium.
Details
Animal research suggests that a single dose of caraway fruit extract can promote diuresis and increase the urinary excretion of sodium and potassium. However, sub-chronic use of caraway fruit extract does not seem to significantly increase potassium excretion, although urine output continues to be increased for up to 6 days (39797).
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Theoretically, caraway might increase the effects and adverse effects of isoniazid.
Details
Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of isoniazid when administered concomitantly (25529). This interaction has not been reported in humans.
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Theoretically, caraway might reduce excretion and increase levels of lithium due to diuretic effects.
Details
Animal research suggests that caraway fruit extract has diuretic properties (39797).
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Theoretically, caraway might increase the effects and adverse effects of pyrazinamide.
Details
Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of pyrazinamide when administered concomitantly (25529). This interaction has not been reported in humans.
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Theoretically, caraway might increase the effects and adverse effects of rifampin.
Details
Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of rifampin when administered concomitantly (25529). This interaction has not been reported in humans.
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Theoretically, Ceylon cinnamon may have additive effects with antidiabetes drugs.
Details
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Theoretically, Ceylon cinnamon might have additive effects with antihypertensive drugs and increase the risk of hypotension.
Details
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Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
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Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.
Details
Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135). |
Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.
Details
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Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.
Details
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Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.
Details
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Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.
Details
Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen. |
Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Details
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
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Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Details
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Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Details
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).
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Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
Details
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).
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Theoretically, ginger might increase the levels of CYP1A2 substrates.
Details
In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2B6 substrates.
Details
In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2C9 substrates.
Details
In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.
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Ginger might increase or decrease the levels of CYP3A4 substrates.
Details
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans. |
Theoretically, ginger might increase levels of losartan and the risk of hypotension.
Details
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.
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Theoretically, ginger might increase levels of metronidazole.
Details
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).
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Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Details
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).
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Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
Details
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
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Ginger might increase the risk of bleeding with phenprocoumon.
Details
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).
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Ginger might increase the risk of bleeding with warfarin.
Details
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.
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Below is general information about the adverse effects of the known ingredients contained in the product Enzyme Complex. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, anise seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.
Dermatologic ...Topically, anise, in combination with other herbs, has been reported to cause localized pruritus (13483).
Immunologic ...Anise can cause allergic reactions in sensitive individuals. Orally or by inhalation, anise can cause rhinoconjunctivitis, occupational asthma, and anaphylaxis (13484). Topically, anise can cause contact dermatitis, rhinitis, and asthma (31319,31341). Contact dermatitis and cheilitis have also been reported following the use of toothpaste containing anethole, a constituent of anise (31403,31528).
General
...Orally, bromelain seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, flatulence, gastric upset, headache.
Topically: Pruritus, urticaria.
Dermatologic
...Topically, bromelain may cause dermal allergic reactions including urticaria, pruritus, and skin swelling (9184).
Redness, swelling, burning, pain at the application site, and cellulitis have also been reported rarely (108148,113513). In one case, a fixed drug eruption with pruritis near the groin was reported in a 33-year-old male taking bromelain 50 mg orally daily for 10 days. After discontinuation of bromelain and treatment with topical corticosteroid, the lesion resolved. Upon re-challenge with bromelain, the lesion reappeared in the same area (103300).
In another case report, a 61-year-old male with a history of chronic lower leg ulceration secondary to chronic venous hypertension and recurrent deep vein thrombosis on rivaroxaban presented with a deep-dermal burn on his lower calf. Bromelain-based topical enzymatic debridement agent Nexobrid 2 grams was applied to the burn site. Thirty minutes later, the patient experienced two instances of hemorrhage at the site of debridement. The patient was stabilized and treated with fluids, packed red cells, and tranexamic acid, and then the Nexobrid was removed (111656). Caution should be used in patients with underlying coagulopathies.
Gastrointestinal ...Orally, bromelain may cause gastrointestinal disturbances, including diarrhea, nausea, vomiting, flatulence, and abdominal pain (9184,18274,18282,96216,113513).
Immunologic
...Immunoglobulin E (IgE)-mediated allergic reactions to bromelain may occur (9184).
If inhaled, bromelain may cause sensitization and allergic reactions such as asthma (37199,37215,37233). In case reports of occupational inhalation of bromelain, additional allergic symptoms included difficulty swallowing, throat itching, eye irritation, and rhinitis (37214).
General
...Orally, capsicum is generally well tolerated in amounts typically found in food or when the extract is used in doses of up to 200 mg daily.
Topically and intranasally, capsaicin, a constituent of capsicum, is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, burning, diarrhea, dyspepsia, gas, headache, mild constipation, nausea, rhinorrhea, skin flushing, and sweating.
Serious Adverse Effects (Rare):
Orally: Cases of myocardial infarction and hypertensive crisis have been reported.
Cardiovascular
...Orally, palpitation was reported in one clinical trial (105196).
One case of myocardial infarction has been reported in a 41-year-old male without cardiovascular risk factors; the event was attributed to the use of an oral capsicum pepper pill that the patient had been taking for weight loss (40768). Another case of coronary vasospasm and acute myocardial infarction has been reported for a healthy 29-year-old male; the event was attributed to the use of a topical capsicum-containing patch that the patient had been applying to the middle of the back for 6 days (40658). Two cases of arterial hypertensive crisis have been reported for individuals who ingested a large amount of peppers and chili peppers the day before. One of the patients also had an acute myocardial infarction, and the other had high levels of thyroid stimulating hormone (40569,40606).
Dermatologic
...Orally, capsicum or its constituent capsaicin may cause urticaria and skin wheals in rare cases (96457,105203).
Topically, capsicum can cause a prickling sensation, itching, pain, burning, edema, stinging, irritation, rash, and erythema. About 1 in 10 patients who use capsaicin topically discontinue treatment because of adverse effects. These effects seem to occur more often with topical formulations containing higher concentrations of capsaicin, the active constituent of capsicum. Side effects tend to diminish with continued use (12401,15260,15261,40358,40439,40483,40547,40676,40682,40719)(40784,40847,92979,92983,92984,96453,105193,105197,105202,111514). In one case, application of a capsaicin 8% patch (Qutenza) for 60 minutes caused a second-degree burn, characterized by burning, erythema, severe pain, and blistering at the administration site. The burn was treated with topical corticosteroids, but 9 months later neuropathic pain persisted, resulting in limited mobility. It is unclear whether the mobility sequalae were caused by topical capsaicin or the patient's pre-existing neurological disorders (111514). Skin contact with fresh capsicum fruit can also cause irritation or contact dermatitis (12408).
Intranasally, capsaicin can cause nasal burning and pain in most patients. It also often causes lacrimation, sneezing, and excessive nasal secretion; however, these side effects appear to diminish with repeat applications (14323,14329,14358). In some cases, the burning sensation disappears after 5-8 applications (14351,14358). In some cases, patients are pretreated with intranasal lidocaine to decrease the pain of intranasal capsaicin treatment. However, even with lidocaine pretreatment, patients seem to experience significant pain (14324).
Gastrointestinal
...Orally, capsicum can cause upper abdominal discomfort, including irritation, fullness, dyspepsia, gas, bloating, nausea, epigastric pain and burning, anal burning, diarrhea, mild constipation, and belching (12403,12410,40338,40427,40456,40503,40560,40584,40605,40665)(40718,40725,40745,40808,40828,96456,96457,105194,105196).
There is a case report of a 3-year-old female who experienced a burning and swollen mouth and lips after touching the arm of a parent that had been treated with a capsaicin patch and then placing the fingers in the mouth (105199). Excessive amounts of capsaicin can lead to gastroenteritis and hepatic necrosis (12404). In a case report, a 40-year-old male with diabetes consumed white wine daily and chewed cayenne which was thought to result in black teeth stains and loss of enamel (40809). Some preliminary research links ingestion of capsaicin with stomach and gallbladder cancer; however the link may be due to contamination of capsaicin products with carcinogens (40771).
Topically, capsaicin can cause diarrhea and vomiting (105202).
Immunologic ...In a case report, a 34-year-old female had anaphylaxis involving difficulty breathing and stupor and also urticaria after consuming a red bell pepper, which is in the capsicum genus. The causal chemical was theorized to be 1,3-beta-glucanase (92978). In another case report, a 33-year-old female experienced angioedema, difficulty breathing and swallowing, and urticaria after ingesting raw green and red peppers (92982).
Neurologic/CNS ...Orally, capsicum can cause sweating and flushing of the head and neck, lacrimation, headache, faintness, and rhinorrhea (7005,12410,105196,105203). Topically, applying capsaicin can cause headache (96450,105202). Injection of capsaicin into the intermetatarsal space has also been associated with headache (96454).
Ocular/Otic
...Topically, capsicum can be extremely irritating to the eyes and mucous membranes.
Capsicum oleoresin, an oily extract in pepper self-defense sprays, causes intense eye pain. It can also cause erythema, blepharospasm, tearing, shortness of breath, and blurred vision. In rare cases, corneal abrasions have occurred (12408,12409,40345,40348,40383,40720,40857).
Inhalation of capsicum can cause eye irritation, and allergic alveolitis (5885). In a case report, a 38-year-old female had acute anterior uveitis that developed about 12 hours after using a specific patch (Isola Capsicum N Plus) that contained capsaicin 1.5 mg per patch and methyl salicylate 132 mg per patch for neck pain. The uveitis was controlled with topical steroids and did not recur (92977).
Oncologic ...Population research suggests that moderate to high intake of capsaicin, the active constituent of capsicum, is associated with an increased risk of gastric cancer, while low intake is associated with a decreased risk. It is not clear from the study what amount of capsaicin is considered high versus low intake (92988). Additionally, some research suggests that any link may be due to contamination of capsaicin products with carcinogens (40771).
Pulmonary/Respiratory
...Orally, difficulty breathing was reported in a clinical trial (105196).
Topically, nasopharyngitis related to the use of a cream containing capsaicin has been reported (105202).
Inhalation of capsicum and exposure to capsicum oleoresin spray can cause cough, dyspnea, pain in the nasal passages, sneezing, rhinitis, and nasal congestion (5885,15016,40522,40546,40647). In rare cases, inhalation of the capsicum oleoresin or pepper spray has caused cyanosis, apnea, respiratory arrest and death in people. Death was caused by asphyxiation probably due to acute laryngeal edema and bronchoconstriction from inhalation of the capsicum oleoresin spray (40546,40672,40837,40879).
In a case report, a 47-year-old female who was exposed to capsaicin gas for more than 20 minutes experienced acute cough, shortness of breath, short-term chest pain, wheezing, and difficulty breathing for months afterwards (92980). In rare cases, exposure to capsicum oleoresin spray resulted in apnea, pulmonary injury, cyanosis, and even respiratory arrest (40383,40546).
General ...Orally, caraway oil seems to be well tolerated.
Gastrointestinal ...Orally, caraway oil, when used in combination with peppermint oil, may cause a substernal burning sensation, belching, nausea, and vomiting (6741,6742,10075,96344). It is unclear if these adverse effects are due to caraway oil, peppermint oil, or the combination. Peppermint oil, when used alone, has been reported to cause similar adverse effects.
Immunologic ...Orally, an allergic reaction has been reported after use of caraway oil in combination with peppermint oil in a patient with a history of bronchial asthma (96344). It is unclear if this adverse effect is due to caraway oil, peppermint oil, or the combination.
General
...Orally, Ceylon cinnamon is generally well tolerated, and adverse reactions are uncommon.
Most Common Adverse Effects:
Orally: Bloating, dyspepsia, nausea.
Topically: Allergic dermatitis, irritation of mucous membranes and skin.
Dermatologic
...Orally, a case of systemic contact dermatitis has been reported in a patient who consumed cinnamon (type not specified) after being previously sensitized to cinnamyl alcohol via cutaneous exposure (95599).
In a small study of oral Ceylon cinnamon, two patients reported itching (104520). In another small study, two patients reported rashes (108263).
Topically, cinnamon oil can cause skin irritation and allergic dermatitis, probably due to cinnamaldehyde which makes up 60% to 80% of cinnamon oil (2537,12635,92071,95596,95599). In one case report, a 16-year-old female experienced worsening dermatitis after using a homemade facial scrub containing cinnamon powder (type not specified). Symptoms improved after discontinuation of the scrub (95596). Several cases of intraoral allergic contact dermatitis have been reported in patients consuming cinnamon (type not specified) or using products containing constituents of cinnamon (95598).
Gastrointestinal ...Orally, gastrointestinal side effects such as heartburn, nausea, bloating, and dyspepsia have been reported (97250).
Hematologic ...Orally, a case of postoperative hemorrhage is reported in a 49-year-old patient after taking Ceylon cinnamon 1 tablespoon daily for 10 months. One day post-colectomy, the patient had an INR of 1.59 and intraabdominal bleeding that required exploratory laparotomies, blood transfusion, and fresh frozen plasma. Ultimately, the patient was discharged (112421).
Hepatic ...While there is concern about the coumarin content in cassia cinnamon increasing the risk for hepatic adverse effects and bleeding, the amount of coumarin in Ceylon cinnamon is negligible and unlikely to cause toxic effects (89652,92072,92073). In one case report, a 73-year-old female taking rosuvastatin for several months developed elevated liver function tests (LFTs), abdominal pain, nausea, and vomiting after taking cinnamon (unknown dose and type) for 7 days. The acute hepatitis and elevated LFTs resolved after stopping both cinnamon and rosuvastatin. The patient was later able to resume rosuvastatin without recurrence (97249).
General
...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.
Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).
Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).
Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).
Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).
Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.
Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).
General
...Orally, ginger is generally well tolerated.
However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.
Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).
Dermatologic
...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).
Gastrointestinal
...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076).
Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).
Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).
Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).
Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).
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).
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, 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).
