| Ingredients | Amount Per Serving: 2250 mg |
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Proprietary Blend
(Proprietary Blend Note: per tablet )
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750 mg |
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Xanthium
(Xanthium )
(fruit)
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Cinnamon
(twig)
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(root)
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Ligusticum
(Ligusticum )
(root)
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(Angelica )
(root)
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(Eucalyptus )
(leaf)
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(Cimicifuga )
(rhizome)
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(root)
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(leaf)
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Vegetable Gum, Silicon Dioxide (Alt. Name: SiO2), Stearic Acid (Alt. Name: C18:0), Cellulose
Below is general information about the effectiveness of the known ingredients contained in the product Nasal Tabs 2. 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 Nasal Tabs 2. 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 foods. Angelica archangelica has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of Angelica archangelica when used orally or topically for medicinal purposes.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Black cohosh has been safely used in some studies lasting up to a year (15036,15158,17091,19553,35908); however, most studies have lasted only up to 6 months (141,4614,4620,7054,9437,9494,13143,13184,14330,14423)(14424,15037,15889,15893,35824,35852,35853,35858,35865,35897)(35902,35904,35946,35964,95525,103269). There is concern that black cohosh might cause liver damage in some patients. Several case reports link black cohosh to liver failure or autoimmune hepatitis (4383,10692,11906,12006,13144,14469,15160,16721,16722,16723)(16724,16725,16726,16727,35857,107906). However, the evidence that black cohosh causes liver damage is not conclusive (17085). Until more is known, monitor liver function in patients who take black cohosh.
PREGNANCY: POSSIBLY UNSAFE
when used orally in pregnant patients who are not at term.
Black cohosh might have hormonal effects and menstrual and uterine stimulant effects (15035). Theoretically, this might increase the risk of miscarriage; avoid using during pregnancy. There is insufficient reliable information available about the safety of black cohosh when used to induce labor.
LACTATION: POSSIBLY UNSAFE
when used orally.
Black cohosh might have hormonal effects. Theoretically, maternal intake of black cohosh might adversely affect a nursing child (15035). Until more is known, nursing patients should avoid taking black cohosh.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Eucalyptus has Generally Recognized As Safe status (GRAS) for use in foods as a flavoring in the US (4912).
POSSIBLY SAFE ...when eucalyptol, a constituent of eucalyptus oil, is used orally and appropriately. Eucalyptol appears to be safe for up to 12 weeks (13302).
POSSIBLY UNSAFE ...when the undiluted oil is used topically. Prolonged or widespread exposure has caused neurotoxicity (12869). There is insufficient reliable information available about the safety of diluted eucalyptus oil when used topically.
LIKELY UNSAFE ...when the undiluted oil is ingested orally. Ingesting 3.5 mL of undiluted oil can be fatal in adults (12867). There is insufficient reliable information available about the safety of eucalyptus oil when inhaled as aromatherapy or when eucalyptus leaf is used orally in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods.
Eucalyptus has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
CHILDREN: LIKELY UNSAFE
when eucalyptus oil is used orally (12867,49002,107493,107495).
...when eucalyptus oil is used topically in infants and young children. There are reports of neurotoxicity in infants and young children exposed to topical eucalyptus oil. In one of these cases, a 12-month-old child was bathed in water containing eucalyptus oil and other essential oils; in another case, a child had a dressing containing eucalyptus oil applied every 2-4 hours daily for 2 days (12868,12869). ...when eucalyptus solutions are inhaled using a vaporizer (49002).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of medicinal amounts of eucalyptus oil; avoid using.
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.
POSSIBLY SAFE ...when used orally and appropriately, short term. Total glucosides of peony has been used with apparent safety in doses of up to 1800 mg daily for up to 12 months (92786,97949,97950,98466,100992,110432,112861,112862). Peony root extract has been used with apparent safety at a dose of 2250 mg daily for up to 3 months (97216). There is insufficient reliable information available about the safety of peony when used orally, topically, or rectally, long-term.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Total glucosides of peony has been used with apparent safety in children 1.5-4 years of age at doses up to 180 mg/kg daily or 1.2 grams daily for up to 12 months (92785). Peony root extract 40 mg/kg daily has also been used with apparent safety in children 1-14 years of age for 4 weeks (106851).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Preliminary research suggests that peony can cause uterine contractions (13400). However, other preliminary research suggests a combination of peony and angelica with or without motherwort, banksias rose, and ligustica, might be safe (11015,48433). Until more is known, avoid use.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used in amounts commonly found in foods. Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when thyme is used orally and appropriately in supplemental amounts. Orally, thyme, in combination with other herbs, has been used safely for up to 23 days (13557,49219,49223,78133). ...when diluted thyme oil is used topically, short-term. Diluted thyme oil has been used with apparent safety for up to 7 months (5177). There is insufficient reliable information available about the safety of thyme oil when used orally or when inhaled.
CHILDREN: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
CHILDREN: POSSIBLY SAFE
when thyme is used orally in medicinal amounts in combination with English ivy.
Thyme has been used with apparent safety in combination with English ivy for up to 10 days (78181).
There is insufficient reliable information available about the safety of thyme oil when used orally or topically in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of thyme when used in medicinal amounts during pregnancy and breast-feeding; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Nasal Tabs 2. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
 Details
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued (16725). It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.
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Theoretically, black cohosh may reduce the clinical effects of cisplatin.
Details
Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells (13101).
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Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Details
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme (13536). However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers (16848). Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.
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Theoretically, black cohosh may alter the effects of estrogen therapy.
Details
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Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
Details
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Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
Details
In vitro research shows that black cohosh modestly inhibits OATP2B1 (35450). OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
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Theoretically, inhaling eucalyptol may reduce the effectiveness of amphetamines.
Details
Animal research suggests that inhaling eucalyptol may reduce the levels of amphetamines in the blood (48987).
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Theoretically, eucalyptus leaf might increase the risk of hypoglycemia.
Details
Animal research suggests that eucalyptus leaf might have hypoglycemic activity, and might have additive effects when used with antidiabetes drugs (12871).
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Theoretically, eucalyptus might increase the levels of CYP1A2 substrates.
Details
In vitro research suggests that eucalyptus oil might inhibit CYP1A2, although this has not been reported in humans (12479).
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Theoretically, eucalyptus might increase the levels of CYP2C19 substrates.
Details
In vitro research suggests that eucalyptus oil might inhibit CYP2C19, although this has not been reported in humans (12479).
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Theoretically, eucalyptus might increase the levels of CYP2C9 substrates.
Details
In vitro research suggests that eucalyptus oil might inhibit CYP2C9, although this has not been reported in humans (12479).
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Theoretically, eucalyptus might increase the levels of CYP3A4 substrates.
Details
In vitro research suggests that eucalyptus oil might inhibit CYP3A4, although this has not been reported in humans (12479).
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Theoretically, inhaling eucalyptol might reduce the effectiveness of pentobarbital.
Details
Animal research suggests that inhaling eucalyptol reduces the level of pentobarbital that reaches the brain (48987).
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
Details
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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 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.
Details
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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, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
Details
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).
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Theoretically, peony might increase the levels and clinical effects of clozapine.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
Details
In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
Details
In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.
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Theoretically, peony might reduce the levels and clinical effects of phenytoin.
Details
Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).
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Theoretically, concurrent use of anticholinergic drugs and thyme essential oil might reduce the effects of anticholinergic drugs.
Details
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme leaf extract might have additive effects with anticoagulant or antiplatelet drugs.
Details
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Theoretically, concurrent use of cholinergic drugs and thyme essential oil might cause additive cholinergic effects.
Details
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme might competitively inhibit the effects of estrogen replacement therapy.
Details
In vitro research shows that thyme has estrogen receptor-binding activity and phytoestrogen content (3701). However, this effect has not been observed in humans.
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Below is general information about the adverse effects of the known ingredients contained in the product Nasal Tabs 2. 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, Angelica archangelica is generally well tolerated in food amounts.
There is limited information available about the adverse effects of Angelica archangelica when used as medicine.
Most Common Adverse Effects:
Orally: Constipation, photosensitivity.
Dermatologic ...Orally or topically, Angelica archangelica might cause photosensitivity reactions (13406). Patients who take Angelica archangelica orally or apply it topically should be advised to avoid prolonged exposure to the sun. Some constituents of the leaves have a strong irritant effect on the skin and mucous membranes, referred to as "angelica dermatitis" (18).
Gastrointestinal ...Orally, Angelica archangelica has been reported to cause constipation in one out of 21 patients taking a specific Angelica archangelica leaf extract (SagaPro, SagaMedica) (92461).
General
...Orally, black cohosh is generally well tolerated when used in typical doses.
Most Common Adverse Effects:
Orally: Breast tenderness, dizziness, gastrointestinal upset, headache, irritability, rash, tiredness.
Serious Adverse Effects (Rare):
Orally: Endometrial hyperplasia and hepatotoxicity, although data are conflicting for both.
Cardiovascular
...A single case of reversible bradycardia has been reported for a 59-year-old female who took one tablet of a specific black cohosh product (Remifemin, Schaper & Brümmer) daily for 2 weeks.
The adverse event was considered probably related to black cohosh use, although the exact mechanism by which black cohosh exerted this effect was unclear (35920).
There has been concern that, if black cohosh has estrogen-like effects, it could also potentially cause estrogen-like side effects including increased risk for thromboembolism and cardiovascular disease. These outcomes have not been specifically assessed in long-term trials; however, some research shows that a specific black cohosh extract (CimiPure, PureWorld) does not significantly affect surrogate markers for thromboembolism and cardiovascular risk such as fibrinogen, cholesterol, triglycerides, glucose, or insulin levels compared to placebo (16850).
Dermatologic ...Black cohosh has been associated with skin irritation and rashes (7054,10987,14330,15889,35853). A case report describes a patient who developed cutaneous pseudolymphoma 6 months after starting a specific black cohosh extract (Remifemin). Symptoms resolved within 12 weeks of discontinuing black cohosh (15890).
Gastrointestinal ...Orally, black cohosh can commonly cause gastrointestinal upset (4383,4615,4616,10988,13184,35824,35853,35965,103269,111714). Constipation and indigestion have also been reported (7054,35852).
Genitourinary
...Orally, black cohosh, including the specific black cohosh product Remifemin, may cause vaginal bleeding and breast tenderness in some postmenopausal patients (15889,35824).
However, the frequency of these events seems to be less than that of tibolone, a prescription hormone medication used to treat symptoms of menopause (15889,35904).
Due to the potential estrogen-like effects, there is concern that black cohosh might increase the risk of endometrial hyperplasia. However, a specific black cohosh extract CR BNO 1055 (Klimadynon/Menofem, Bionorica AG) does not appear to cause endometrial hyperplasia. Clinical research in postmenopausal adults shows that taking 40 mg daily of this extract for 12 weeks does not significantly increase superficial cells when compared with placebo, and causes significantly fewer superficial cells when compared with conjugated estrogens (Premarin) (14330). Additional clinical research shows that taking 40 mg daily of this extract for a year does not increase the risk of endometrial hyperplasia or endometrial thickening in postmenopausal adults (15036). Another specific combination product containing black cohosh extract plus St. John's wort (Gynoplus, Jin-Yang Pharm) also does not significantly increase superficial cells compared to placebo after 12 weeks of treatment (15893). Some patients taking tamoxifen plus black cohosh have experienced endometrial hyperplasia and vaginal bleeding. However, these effects are more likely due to tamoxifen than black cohosh (7054).
Hepatic
...There is concern that black cohosh might cause liver disease, hepatotoxicity, or hepatitis.
Adverse effects on the liver have not been documented in clinical studies. However, multiple case reports of liver toxicity, hepatitis, and abnormal liver function have been described in females taking black cohosh products alone or in combination with other herbs or drugs. In some cases, patients developed liver failure and required immediate liver transplantation (4383,10692,11909,12006,13144,14469,15160,16721,16722,16723) (16724,16727,35883,35888,35890,35895,89465,101592,107906). In one case, a female developed autoimmune hepatitis after 3 weeks of taking black cohosh. Symptoms resolved 2 weeks after discontinuing black cohosh (11906). In at least three cases, females have developed elevated liver enzymes and symptoms of hepatotoxicity after taking black cohosh products. Symptoms resolved and liver enzymes normalized within a week of discontinuing black cohosh (16725,16726). Analysis of two liver biopsies suggests that hepatotoxicity associated with black cohosh use results from the accumulation of 4HNE protein adducts in the cytoplasm of liver cells, which promotes the migration of lymphocytes to the affected area and induces an autoimmune response leading to troxis necrosis (89469).
However, many of these cases are poorly documented. Causality is possible based on some reports; however, other reports do not indicate that black cohosh is the probable cause of the events (15891,15892,16722,16723,16727,89465). Hepatitis can occur with no identifiable cause, raising the possibility that black cohosh and hepatitis might have been coincidental in some cases. Also, plant misidentification can occur, resulting in accidental substitution of a hepatotoxic plant (11910). Therefore, some experts argue that these cases do not provide conclusive evidence that black cohosh is responsible for liver disease (17085,35882,111634). Nonetheless, some countries require cautionary labeling on black cohosh products suggesting a risk of liver toxicity. The United States Pharmacopeia also recommends cautionary labeling on black cohosh products (16722). Until more is known about this potential risk, consider monitoring liver function in patients who take black cohosh.
Musculoskeletal
...One patient treated with black cohosh in a clinical trial discontinued treatment due to edema and arthralgia (35897).
Black cohosh has been linked to asthenia and muscle damage in one case. A 54-year-old female experienced asthenia with elevated creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels while taking black cohosh. The patient had taken a specific black cohosh extract (Remifemin) for 1 year, discontinued it for 2 months, restarted it, and then experienced symptoms 2 months later. Symptoms began to resolve 10 days after discontinuing black cohosh (14299).
Neurologic/CNS
...Orally, black cohosh may cause headache, dizziness, or tiredness (35852,35886).
There is one case report of seizures in a female who used black cohosh, evening primrose oil, and chasteberry (10988).
Also, there has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
In another case report, orobuccolingual dyskinesia, including tongue-biting, eating difficulties, and speech problems, was reported in a 46-year-old female who took two tablets containing black cohosh 20 mg and Panax ginseng 50 mg daily for 15 months. The patient's condition improved after stopping treatment with the herbs and taking clonazepam 2 mg daily with baclofen 40 mg daily (89735).
Ocular/Otic ...There is some concern that black cohosh might increase the risk of retinal vein thrombosis due to its estrogenic activity. In one case, a patient with protein S deficiency and systemic lupus erythematosus (SLE) experienced retinal vein thrombosis 3 days after taking a combination product containing black cohosh 250 mg, red clover 250 mg, dong quai 100 mg, and wild yam 276 mg (13155). It is unclear if this event was due to black cohosh, other ingredients, the combination, or another factor.
Oncologic ...There is some concern that black cohosh may affect hormone-sensitive cancers, such as some types of breast or uterine cancer, due to its potential estrogenic effects. However, evidence from a cohort study suggests that regular use of black cohosh is not associated with the risk of breast or endometrial cancer (17412,111634).
Psychiatric ...A 36-year-old female with a 15-year history of depression developed mania with psychotic and mixed features after taking a black cohosh extract 40 mg daily. The patient gradually recovered after stopping black cohosh and receiving treatment with antipsychotics (104517).
Pulmonary/Respiratory ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Renal ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Other ...While rare, weight gain has been reported in some patients taking black cohosh. However, in most cases the causality could not be established. A review of the literature, including published case reports, spontaneous reports to adverse event databases, and clinical trials, suggests that black cohosh does not cause weight gain (107907).
General
...Orally, diluted eucalyptus oil is generally well tolerated, but the undiluted oil can cause toxicity.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, vomiting.
Topically: Burning, itching, redness, stinging.
Serious Adverse Effects (Rare):
Orally: Signs of toxicity can occur with the undiluted oil at doses as low as 1 mL and include central nervous system depression, shallow respiration, rapid pulse, apnea, coma, and death.
Topically: Prolonged exposure or large amounts of eucalyptus oil can cause agitation, ataxia, drowsiness, muscle weakness, seizures, and slurred speech. The risk of toxicity may be greater in children.
Inhalation (as aromatherapy): Seizures.
Cardiovascular ...Orally, one case of premature ventricular contractions has been reported in a previously healthy 29-year-old male who ingested approximately one ounce of eucalyptus oil (48983).
Dermatologic ...Topically, eucalyptus pollen, leaves, oil, and the constituent eucalyptol can cause contact dermatitis in sensitive people (13303,48931,92856,92858,92859,98497). In some cases, symptoms respond to treatment with topical corticosteroids and tacrolimus (92856). In one case report, transient local redness, burning, and irritation was reported in a 4-year-old child who was bathed in water containing eucalyptus oil. The symptoms resolved within one hour of rinsing the skin with clear water (48983). In a clinical study, treatment with a combination of eucalyptus oil and lemon tea tree oil caused burning, redness, itching, or stinging in up to 20% of the patients. Stinging usually resolved within 10 minutes of application and redness within 30 minutes (19188,98492).
Gastrointestinal ...Orally, eucalyptus oil can cause nausea, vomiting, and diarrhea (48983,48993,48995). Abdominal pain has been reported in a trial of the eucalyptus constituent eucalyptol for inflammatory bowel disease (IBD) (48936).
Immunologic
...A case of IgE-mediated exacerbation of asthma and rhinitis symptoms has been reported in a patient who consumed eucalyptus.
Similar worsening of symptoms occurred when the patient inhaled eucalyptus pollen (48957).
Occupational exposure to eucalyptus may cause allergic dermatitis (98497).
Neurologic/CNS
...Orally, eucalyptus oil can cause central nervous system depression, coma, and status epilepticus (12867,48946,48983).
Topically, orally, and by inhalation, eucalyptus oil has been associated with seizures. A systematic review describes the characteristics of 49 children and 61 adults with seizures associated with various routes of administration. Patients with no seizure history were classified as a eucalyptus oil-induced seizure (EOIS), while patients with a history of seizure or susceptibility to seizure were defined as a eucalyptus oil-provoked seizure (EOPS). In EOIS cases, topical use was reported in 74%, inhalation in 22.5%, and ingestion in 3.5%; for EOPS cases, topical use was reported in 79%, inhalation in 16%, and ingestion in 5%. Generalized tonic-clonic seizures are the most prominent type of seizure in EOIS cases (96%). Among EOPS patients, 37% had focal onset motor seizures with impaired awareness, 24% had focal onset aware motor seizures, 13% had focal to bilateral tonic-clonic seizures, and 26% had generalized onset tonic-clonic seizures (107494). One prospective observational study that was included in this systematic review provided additional details on eucalyptus-induced seizures. This study included 18 reports of EOIS and 28 reports of EOPS in adults and children after topical or inhaled use of eucalyptus oil, either alone or in combination with camphor. The time to seizure onset was 0.5-48 hours after topical application, 2-30 minutes after inhalation, and 0.5-6 hours after ingestion. (105028).
One prospective observational study and one case series have described 20 case reports of seizures occurring in children after ingestion of eucalyptus oil. Most of these seizures are generalized tonic-clonic in nature, occur 15-30 minutes after exposure, and do not reoccur following the discontinuation of eucalyptus oil. Seizures have been reported with both overdoses and therapeutic doses (107493,107495) and include cases of both EOIS and EOPS (107495). Additionally, children appear more likely to require intensive care and mechanical ventilation when compared with adult cases (107494).
A case of fever and headache has been reported in a patient who routinely applied a teaspoon of gel containing eucalyptus extract in his throat or nose to treat sore throat or rhinitis (48946).
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, peony seems to be well tolerated when used alone and as part of Chinese herbal formulas.
Most Common Adverse Effects:
Orally: Abdominal distension, anorexia, diarrhea, gastrointestinal discomfort, nausea.
Topically: Dermatitis.
Dermatologic ...Topically, peony has been reported to cause contact dermatitis (13555).
Endocrine ...Orally, a specific traditional Chinese medicine preparation called DDT has been reported to lower follicle-stimulating hormone (FSH) levels and increase estradiol levels. It is not known if this effect is due to peony or the other ingredients (48404). Another specific traditional Chinese medicine preparation, Toki-shakuyaku-san, has been reported to increase plasma progesterone levels in some patients. It is not known if this effect is due to peony or the other ingredients (15294).
Gastrointestinal ...Orally, peony and total glucosides of peony (TGP) have been reported to cause gastrointestinal discomfort, including abdominal distension, anorexia, diarrhea, and nausea, in some patients (13538,92785,97949,98466,100992). In one clinical study, diarrhea was reported in 5% of patients taking TGP 600 mg three times daily for 24 weeks versus 1% of patients taking placebo (100992).
Hematologic ...Orally, there is one case report of easy gum bleeding, epistaxis, and skin bruising with an international normalized ratio (INR) above 6 in a 61-year-old male who was previously stable on warfarin therapy. This patient had switched from one brand of quilinggao, a popular Chinese herbal product, to another brand 5 days prior. This product contained Fritillaria spp. (beimu), Paeonia rubra, Chinese peony (chishao), Lonicera japonica (jinyinhua), and Poncirus trifoliata (jishi). The patient's INR decreased to 1.9 after temporary withdrawal of warfarin therapy. Upon re-initiation of quilinggao, his INR increased to 5.2. It is not known if the increased INR is due to peony or the other ingredients (68343).
General
...Orally, thyme is well tolerated when used in food and seems to be well tolerated when used medicinally.
Topically, thyme seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic reactions, diarrhea, dizziness, headache, heartburn, nausea, or vomiting.
Topically: Contact dermatitis and skin irritation.
Dermatologic ...Topically, thyme, thyme oil, or the constituent thymol can cause contact dermatitis and skin irritation (13463,78252,78362,78384,77982,78154,78310,78313,78384). In one study of 100 patients with contact allergies, 5% were attributed to thyme oil as an allergen contained in wound dressings (78362). Toothpastes containing thymol have been associated with cheilitis and glossitis (13463).
Gastrointestinal
...Orally, thyme and thyme oil may cause heartburn, nausea, vomiting, stomach upset, or diarrhea (13557,94033).
In a clinical study, two patients using extracts of thyme herb and ivy leaves experienced temporary stomach ache and mild nausea (78181).
Intravaginally, cream containing thyme and garlic has been associated with reports of nausea and vomiting in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Genitourinary ...Intravaginally, cream containing thyme and garlic has been associated with reports of vaginal dryness and vaginal irritation in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Immunologic ...Orally, thyme can cause allergic reactions; however, this is uncommon (13463). Allergic reactions to thyme might be more common in people who are also allergic to oregano and other Lamiaceae species (3808).
Neurologic/CNS ...Orally, thyme may case headache or dizziness (94033).
Pulmonary/Respiratory ...By inhalation, occupational exposure to thyme dust can cause acute airway obstruction (783,13463,13464,77982,78098).
