| Ingredients | Amount Per Serving |
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organic Hurricane Blow Proprietary Blend
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1000 mg |
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(Cascara sagrada )
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(leaf)
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(root)
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Cellulose, Glycerin, Water Note: vegan capsule
Below is general information about the effectiveness of the known ingredients contained in the product Hurricane Blow 1000 mg. 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
Below is general information about the safety of the known ingredients contained in the product Hurricane Blow 1000 mg. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Cascara sagrada seems to be safe when used for less than one week (272,25023,40087). Cascara sagrada was formerly approved by the US Food and Drug Administration (FDA) as a safe and effective over-the-counter (OTC) laxative, but this designation was removed in 2002 due to a lack of supporting evidence (8229).
POSSIBLY UNSAFE ...when used orally, long-term. Using cascara sagrada for more than 1-2 weeks can lead to dependence, electrolyte loss, and hypokalemia (272).
CHILDREN: POSSIBLY UNSAFE
when used orally in children.
Cascara sagrada should be used cautiously in children due to the risk of electrolyte loss and hypokalemia (272).
PREGNANCY:
Insufficient reliable information available; avoid using.
LACTATION: POSSIBLY UNSAFE
when used orally.
Cascara sagrada is excreted into breast milk and might cause diarrhea (272).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when marshmallow root and leaf are used in amounts commonly found in foods. Marshmallow root has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when marshmallow root and leaf are used orally in medicinal amounts (4,12). ...when used topically (4,62020). There is insufficient reliable information available about the safety of marshmallow flower.
PREGNANCY AND LACTATION:
Insufficient reliable information available.
LIKELY SAFE ...when the ripe fruit is used orally in amounts commonly found in foods. Papaya has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when the leaf extract is used orally and appropriately in medicinal amounts, short term. The leaf extract has been used with apparent safety in doses of up to 3300 mg daily for up to 5 days (102799,102800). ...when the ripe fruit is used topically and appropriately, short term. The fruit has been applied with apparent safety to the gingiva or skin for up to 10 days (93090,93091).
POSSIBLY UNSAFE ...when the unripe fruit containing papaya latex and raw papain is used orally. Raw papain has been reported to cause esophageal perforation (6,93083). ...when papaya latex is used topically. Papaya latex, which contains raw papain, is a severe irritant and vesicant (6).
PREGNANCY: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when the unripe fruit containing papaya latex is used orally; avoid using.
There is some concern that crude papain, a constituent of papaya latex, is teratogenic and embryotoxic (6); however, this might be due to extraneous substances rather than papain (11). Some evidence also suggests that high doses of papaya seed extract have abortifacient activity and can adversely affect fetal development (67870). Theoretically, eating large amounts of papaya seeds may have similar effects.
LACTATION: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of using papaya medicinally; avoid using.
LIKELY SAFE ...when the stalk is used in amounts commonly found in foods and when the root is used as a food flavoring. Rhubarb has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when the root or rhizome is used orally and appropriately in medicinal amounts for up to 2 years (92294,92295,92297). ...when the stalk is used orally and appropriately in medicinal amounts for up to 4 weeks (71351,71363,97920). ...when used topically and appropriately (10437,97919).
POSSIBLY UNSAFE ...when the leaf is used orally. Rhubarb leaf contains oxalic acid and soluble oxalate, which can cause abdominal pain, burning of the mouth and throat, diarrhea, nausea, vomiting, seizures, and death (17).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used in medicinal amounts, rhubarb root is a stimulant laxative; avoid using (12).
LIKELY SAFE ...when used orally and appropriately, short-term. Senna is an FDA-approved nonprescription drug (8424,15429,15431,15442,40086,40088,74535,74545,74548,74562)(74567,74570,74583,74585,74586,74587,74593,74603,74606,74607)(74609,74613,74615,74624,74636,74639,74644,74650,74653,92711)(92712).
POSSIBLY UNSAFE ...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).
CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term.
Senna is an FDA-approved nonprescription drug for use in children 2 years and older. (15429,15434,15435).
CHILDREN: POSSIBLY UNSAFE
when used orally long-term or in high doses.
Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095,105956).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term (15429,24480).
POSSIBLY UNSAFE...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).
LACTATION: POSSIBLY SAFE
when used orally and appropriately, short term.
Although small amounts of constituents of senna cross into breast milk, senna has been taken while breast-feeding with apparent safety. Senna does not cause changes in the frequency or consistency of infants' stools. (6026,15429,15436,15437,24482,24484,24485,24486,24487,74545).
LIKELY SAFE ...when used in amounts commonly found in foods. Spearmint and spearmint oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally or topically for medicinal reasons (11,12). Spearmint extract up to 900 mg daily has been used safely for up to 90 days (94925,101713,101714). Spearmint tea has been consumed safely twice daily for up to 16 weeks (68500,94923).
PREGNANCY: LIKELY SAFE
when used in the amounts commonly found in foods (4912).
PREGNANCY: POSSIBLY UNSAFE
when used orally during pregnancy in excessive amounts.
Animal research suggests that spearmint tea may cause uterine damage (68448). Avoid using in amounts greater than those typically found in foods during pregnancy.
LACTATION: LIKELY SAFE
when used in the amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of spearmint during lactation. Avoid using in amounts greater than those typically found in foods.
Below is general information about the interactions of the known ingredients contained in the product Hurricane Blow 1000 mg. 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, cascara sagrada might increase the risk of hypokalemia when taken with corticosteroids.
 Details
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Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.
Details
In vitro research suggests that cascara sagrada can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).
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Theoretically, cascara sagrada might cause hypokalemia, potentially increasing the risk of digoxin toxicity.
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Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with diuretic drugs.
Details
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Theoretically, cascara sagrada might have additive adverse effects when taken with stimulant laxatives.
Details
Cascara sagrada has stimulant laxative effects and might compound fluid and electrolyte losses when taken with stimulant laxatives (19).
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Theoretically, cascara sagrada might increase the risk of bleeding when taken with warfarin.
Details
Cascara sagrada has stimulant laxative effects (19). In some people, cascara sagrada can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding.
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
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Theoretically, licorice might reduce the effects of cisplatin.
Details
In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
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Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Details
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).
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Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that licorice induces CYP1A2 enzymes (111404).
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Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
Details
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
Details
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
Details
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
Details
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Details
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Details
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Details
Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Details
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
Details
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.
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Theoretically, licorice might decrease levels of midazolam.
Details
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.
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Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
Details
In vitro research shows that licorice can increase P-glycoprotein activity (104561).
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Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Details
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Details
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Theoretically, marshmallow flower might have antiplatelet effects.
Details
Animal research suggests that marshmallow flower extract has antiplatelet effects (92846). However, the root and leaf of marshmallow, not the flower, are the plant parts most commonly found in dietary supplements. Theoretically, use of marshmallow flower with anticoagulant/antiplatelet drugs can have additive effects, and might increase the risk for bleeding in some patients.
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Theoretically, due to potential diuretic effects, marshmallow might reduce excretion and increase levels of lithium.
Details
Marshmallow is thought to have diuretic properties. To avoid lithium toxicity, the dose of lithium might need to be decreased when used with marshmallow.
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Theoretically, mucilage in marshmallow might impair absorption of oral drugs.
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Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Details
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70% (93093). This interaction has not been reported in humans.
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Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
Details
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose (67902).
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Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
Details
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya (93087).
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Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
Details
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract (613).
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Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia when taken with corticosteroids.
Details
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Theoretically, taking rhubarb with cyclosporine might reduce cyclosporine levels.
Details
Animal research shows that co-administration of rhubarb decoction 0.25 or 1 gram/kg with cyclosporine 2.5 mg/kg, decreases cyclosporine maximum plasma concentration and overall exposure levels when compared with taking cyclosporine alone. The authors theorize that rhubarb might reduce cyclosporine bioavailability by inducing of P-glycoprotein and/or cytochrome P450 3A4 (92304). However, since rhubarb was administered as a single oral dose and enzyme induction usually occurs after multiple doses, it is possible that cyclosporine absorption was actually reduced via rhubarb's stimulant laxative effects (12). Also, the composition of the rhubarb decoction was not described.
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Theoretically, overuse of rhubarb might increase the risk of adverse effects when taken with digoxin.
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Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia.
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Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.
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Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.
Details
The anthraquinone constituents of rhubarb have been shown to induce nephrotoxicity in animal research (71322). Additionally, in a case report, a 23-year old female presented with kidney failure after taking 6 tablets of a proprietary slimming agent (found to contain the anthraquinones emodin and aloe-emodin from rhubarb) daily for 6 weeks and then adding diclofenac 25 mg 4 times daily for 2 days. The authors postulate that the anthraquinone constituents of rhubarb contributed to the renal dysfunction, and the addition of diclofenac, a nephrotoxic drug, led to renal failure (15257). Until more is known, advise patients to avoid taking rhubarb if they are taking other potentially nephrotoxic drugs.
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Theoretically, rhubarb might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.
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Theoretically, excessive use of rhubarb might increase the risk of bleeding when taken with warfarin.
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Theoretically, senna might increase the risk of adverse effects when taken with digoxin.
Details
Overuse/abuse of senna increases the risk of adverse effects from cardiac glycosides, such as digoxin, due to potassium depletion (15425).
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Theoretically, senna might increase the risk of hypokalemia when taken with diuretic drugs.
Details
Overuse of senna might compound diuretic-induced potassium loss and increase the risk for hypokalemia (15425).
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Theoretically, taking senna may interfere with the absorption of exogenous estrogens.
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Theoretically, senna might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.
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Theoretically, excessive use of senna might increase the effects of warfarin.
Details
Senna has stimulant laxative effects and can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. In one case report, excessive use of senna for 3 weeks resulted in diarrhea, bloody stools, and an elevated INR of 11.9 (16530).
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Theoretically, spearmint might alter the sedative effects of CNS depressants.
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Theoretically, high doses of spearmint might increase the risk of liver damage when taken with hepatotoxic drugs.
Details
Animal research suggests that drinking spearmint tea for 30 days can increase markers of liver damage, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and cause liver degeneration and necrosis, in a dose-dependent manner (12731). This effect has not been reported in humans.
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Below is general information about the adverse effects of the known ingredients contained in the product Hurricane Blow 1000 mg. 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, cascara sagrada seem to be well tolerated when used appropriately, short-term.
Most Common Adverse Effects:
Orally: Mild abdominal discomfort and cramps.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity. Fresh or improperly aged cascara sagrada bark can cause severe vomiting.
Endocrine ...Orally, long-term use of cascara sagrada can lead to potassium depletion (4).
Gastrointestinal
...Orally, cascara sagrada can commonly cause mild abdominal discomfort, colic, and cramps (4).
In some cases, chronic use can cause pseudomelanosis coli. Pseudomelanosis coli (pigment spots in intestinal mucosa) is believed to be harmless, usually reverses with discontinuation, and is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138).
Fresh or improperly aged cascara sagrada bark can cause severe vomiting due to the presence of free anthrone constituents (2,92307).
Genitourinary ...Orally, long-term use of cascara sagrada can lead to albuminuria and hematuria (4).
Hepatic ...There is some concern about potential liver problems with cascara sagrada. In some cases, cascara sagrada bark 750-1275 mg (containing approximately 21 mg cascaroside) daily in divided doses for three days resulted in cholestatic hepatitis, ascites, and portal hypertension. Symptoms resolved following discontinuation of cascara sagrada (6895,92306).
Musculoskeletal ...Orally, long-term use of cascara sagrada can lead to muscle weakness and finger clubbing (4).
Other ...Orally, long-term use of cascara sagrada can lead to cachexia (4).
General
...Orally, licorice is generally well tolerated when used in amounts commonly found in foods.
It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.
Cardiovascular
...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest.
These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).
Dermatologic
...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912).
There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).
Endocrine
...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234).
These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).
Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).
Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).
Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).
Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).
Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).
Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).
General ...Orally and topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, papaya fruit is well tolerated when consumed in food amounts.
Papaya leaf extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Nausea and vomiting from papaya leaf extract.
Topically: Burning sensation from unripe papaya.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions.
Dermatologic
...Orally, high doses of papaya might cause yellow skin discoloration.
A case of carotenemia has been reported for a 42-year-old female who consumed 1.5-2 papayas daily for 6 months. The condition resolved when she stopped eating papayas (67929).
Topically, unripe papaya fruit may cause occasional burning sensation when applied to skin ulcers (67856).
Gastrointestinal ...Orally, the leaf extract has been reported to cause nausea and vomiting in clinical research (102799). A case of esophageal perforation has been reported for a previously healthy 27-year-old female who used papain, a constituent of papaya latex, to digest a piece of meat stuck in her esophagus (93083).
Immunologic ...Orally, papain, a constituent of raw, unripe papaya, has been reported to cause allergic reactions in sensitive individuals, including itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea (6,967). Papaya may also cause hypersensitivity reactions such as systemic contact dermatitis, which occur more commonly in people who are allergic to latex (6197,7853,57635). A case of systemic contact dermatitis has been reported for a 55-year-old female with no prior history of atopic disease or drug allergy after ingesting a throat lozenge containing papaya juice (67942).
Other ...In regions with arsenic-contaminated soil, papaya fruits contain a higher mean concentration of arsenic compared with many other forms of vegetation grown in the regions. Eating papaya from these regions is thought to contribute to higher dietary levels of arsenic (32461,67879).
General
...Orally, rhubarb root and stalk are well tolerated when used in food amounts and seem to be well tolerated when used in medicinal amounts.
Rhubarb leaf contains oxalic acid and can be toxic. Topically, rhubarb seems to be well tolerated.
Most Common Adverse Effects:
Orally: Cramps, diarrhea, gastrointestinal discomfort, nausea, vomiting.
Topically: Rash.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Cardiovascular ...Orally, chronic use or abuse of rhubarb can cause arrhythmias (12).
Dermatologic ...Orally, rhubarb taken alone or in combination with other ingredients has been reported to cause rash (71315,71342). Topically, short term application of a specific product (Pyralvex) containing rhubarb, salicylic acid, and ethanol to the gums has been reported to cause slight burning and dark discoloration of the gums in approximately 1% of patients (71369). It is unclear if this effect is due to rhubarb, other ingredients, or the combination.
Endocrine ...Orally, chronic use or abuse of rhubarb can cause electrolyte loss (especially potassium), hyperaldosteronism, albuminuria, and edema (12).
Gastrointestinal
...Orally, rhubarb can cause cramp-like or spasmodic gastrointestinal discomfort, watery diarrhea, and uterine contractions (18).
Rhubarb, alone or in combination with other ingredients, has also been reported to cause bloating, nausea, diarrhea, vomiting, and stomach upset or pain in clinical studies. Diarrhea is more common with a starting dose of at least 3 grams of extract (71315,71329,71339,71340,71341,71342,71373,92300). Chronic use or abuse of rhubarb can cause inhibition of gastric motility and pseudomelanosis coli (pigment spots in the intestinal mucosa) (12,6138).
Although some research suggests that rhubarb and other anthranoid laxatives might increase the risk of colorectal cancer due to pseudomelanosis coli (30743), more recent research suggests that this condition is harmless, typically reversed with rhubarb discontinuation, and not associated with an increased risk for colorectal adenoma or carcinoma (6138).
Hematologic ...Orally, chronic use or abuse of rhubarb can cause hematuria (12).
Hepatic ...Orally, chronic use of anthraquinone-containing products, such as rhubarb, has been associated with hepatotoxicity (15257). Use of rhubarb specifically has been linked to at least 24 reports of liver injury, although details on the dose of rhubarb and duration of use in these cases are not clear (100963). In one clinical study, rhubarb, taken in combination with other ingredients, has been reported to cause mild to moderate elevations of serum alanine aminotransferase (71315).
Immunologic ...Orally, rhubarb has rarely been reported to cause anaphylaxis (18).
Musculoskeletal ...Orally, chronic use or abuse of rhubarb can cause accelerated bone deterioration and muscular weakness (12).
Renal ...Orally, chronic use or abuse of rhubarb can cause electrolyte loss (especially potassium), albuminuria, hematuria, dehydration, and nephropathies (12). There is one case report of renal failure in a patient who took a product containing rhubarb for six weeks. The patient presented with renal failure two days after starting diclofenac, which is known to have nephrotoxic effects. It is hypothesized that the combination of diclofenac with the anthraquinone constituents of rhubarb precipitated renal dysfunction (15257).
General
...Orally, senna is generally well-tolerated when used short-term in appropriate doses.
Most Common Adverse Effects:
Orally: Abdominal pain and discomfort, cramps, diarrhea, flatulence, nausea, fecal urgency, and urine discoloration.
Serious Adverse Effects (Rare):
Orally: Skin eruptions.
Cardiovascular ...Excessive use can cause potassium depletion and other electrolyte abnormalities (15425). In theory, this could cause potentially dangerous changes in heart rhythm. A small decrease in heart rate was seen in one clinical study (74587).
Dermatologic ...In adults, there are rare case reports of skin eruptions associated with senna, including erythema multiforme, fixed drug eruption, lichenoid reaction, toxic epidermal necrolysis, urticaria, photosensitivity, and contact dermatitis (96558). Infants and young children given senna products have experienced contact reactions on the buttocks due to prolonged exposure to stool while wearing a diaper overnight. These reactions range from erythema with small blisters, to large fluid-filled blisters with skin sloughing, as occurs with second degree burns (96559). In a case series of children treated with senna for chronic constipation, burn-like reactions occurred in 2.2%, typically with higher doses (mean 60 mg/day, range 35.2 to 150 mg/day) (96558,96559). These reactions can be avoided by giving senna early in the day, so that bowel movements occur at a time when diapers can be changed quickly (96559).
Gastrointestinal ...Orally, senna can cause abdominal pain and discomfort, cramps, bloating, flatulence, nausea, fecal urgency, and diarrhea (15427,15434,15435,15436,15439,15440,15441,105955). Chronic use has also been associated with "cathartic colon," radiographically diagnosed anatomical changes to the colon such as benign narrowing, colonic dilation, and loss of colonic folds (15428). The clinical relevance of these findings is unclear. Chronic use can also cause pseudomelanosis coli (pigment spots in intestinal mucosa) which is harmless, usually reverses with discontinuation, and is not associated with an increased risk of developing colorectal adenoma or carcinoma (6138). The cathartic properties of senna leaf are greater than the fruit (15430). Thus, the American Herbal Products Association only warns against long-term use of senna leaf (12).
Hepatic ...Chronic liver damage, portal vein thrombosis, and hepatitis have been reported following oral use of senna alkaloids, such as in tea made from senna leaves (13057,13095,41431,74560,74564,74584,105956). There is a case report of hepatitis in a female who consumed moderate amounts of senna tea. The patient was a poor metabolizer of cytochrome P450 2D6 (CYP2D6). It's thought that moderate doses of senna in this patient led to toxic hepatitis due to the patient's reduced ability to metabolize and eliminate the rhein anthrone metabolites of senna, which are thought to cause systemic toxicity (13057). There is also a case of liver failure, encephalopathy, and renal insufficiency in a female who consumed 1 liter/day of senna tea, prepared from 70 grams of dried senna fruit, over 3 years (13095). In another case report, a 3-year-old female presented with hepatitis that led to pancytopenia after drinking tea made from 2-3 grams dry senna leaves three times or more weekly for over one year (105956).
Immunologic ...In one case report, a 19-year-old male developed anaphylaxis with dyspnea, facial edema, and hives. This reaction was determined to be caused by the senna content in a specific combination product (Delgaxan Plus, Pompadour Ibérica) that the patient ingested (105957).
Musculoskeletal ...Hypertrophic osteoarthropathy, finger clubbing, cachexia, and tetany have been reported from excessive oral senna use in humans (15426,74580,74582,74620,74625).
Renal ...Nephrocalcinosis has been reported as a result of oral senna overuse (74582).
General
...Orally, spearmint is well tolerated.
Most Common Adverse Effects:
Topically: Allergic contact dermatitis or cheilitis in sensitive individuals.
Cardiovascular ...Orally, taking spearmint extract 600 mg daily has been associated with one report of tachycardia in one clinical trial. However, it is not certain that this adverse event was caused by spearmint extract (94925).
Dermatologic ...Orally, drinking 2 cups of spearmint tea with normal amounts of rosmarinic acid has been associated with one report of itchy skin in clinical research (94923).
Gastrointestinal ...Orally, taking spearmint extract 600 mg daily has been associated with dyspepsia in one clinical trial (94925). Taking a higher dose of 900 mg daily has been associated with diarrhea and belching (94925). Drinking 2 cups of spearmint tea with normal amounts of rosmarinic acid has been associated with one report of dry mouth in clinical research. Drinking 2 cups of spearmint tea containing high amounts of rosmarinic acid has been associated with three reports of constipation and one report of loose bowel movements (94923). Taking 1 mL of spearmint oil equivalent to 500 mg of spearmint has been associated with reports of regurgitation in clinical research (75700).
Immunologic ...Topically, spearmint oil and leaves have caused allergic dermatitis (75711,75731,75737). Allergic contact cheilitis has also occurred from spearmint oil in toothpaste or chewing gum (31403,31528,75706,75739,75777,75790). Spearmint oil inhalation has also caused allergic dermatitis (56955). Orally, spearmint leaves have caused allergy-associated swelling of the soft palate. A specific 50 KDa protein in the spearmint was found to be the responsible allergen (94922). In some cases, spearmint allergy was associated with oral lichen planus of the tongue, lips, palate, buccal mucosa, and gingivae. Observational studies suggest that exposure to spearmint is associated with exacerbation of oral lichen planus as confirmed by patch testing (94924,112844).
Neurologic/CNS ...Orally, drinking 2 cups of spearmint tea containing high amounts of rosmarinic acid has been associated with two reports of headache in clinical research (94923).
Psychiatric ...Orally, taking spearmint extract 600 mg daily has been associated with one report of anxiety in one clinical trial. However, it is not certain that this adverse event was caused by spearmint extract (94925).
Other ...Orally, taking spearmint extract 600 mg daily has been associated with one report of increased appetite and weight gain in one clinical trial. However, it is not certain that these adverse events were caused by spearmint extract (94925).
