Each 1/2 tsp serving contains: Proprietary Blend 2.5 mL: European Elderberry , Echinacea purpurea root, Isatis root, Honeysuckle flower, Forsythia flower, Platycodon root, Boneset aerial parts, Licorice root, Apricot seed. Other Ingredients: Honey, Vegetable Glycerin, Purified Water, Potassium Benzoate.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Echinacea Elderberry Syrup. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
There is insufficient reliable information available about the effectiveness of apricot.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Echinacea Elderberry Syrup. 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 apricot fruit or juice is consumed as food. There is insufficient reliable information available about the safety of apricot fruit, juice, or leaves when used orally for medicinal purposes.
PREGNANCY AND LACTATION: LIKELY SAFE
when apricot fruit or juice is consumed as food.
There is insufficient reliable information available about the safety of apricot fruit, juice, or leaves when used orally for medicinal purposes; avoid use.
POSSIBLY UNSAFE ...when used orally. Boneset can cause severe diarrhea and vomiting. Hepatotoxic pyrrolizidine alkaloids (PAs) are common in this genus of plants; however, the alkaloids in boneset have not been adequately characterized to determine their toxic potential (12842,102557).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
Hepatotoxic PAs are common in this genus of plants; however, the alkaloids in boneset have not been adequately characterized to determine their toxic potential (12842,102557). Hepatotoxic PAs might be teratogenic; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Various liquid extracts of Echinacea purpurea have been used safely for up to 10 days, including EchinaGuard (Madaus AG) 20 drops every 2 hours for 1 day, then three times daily (10320), or Echinilin (Inovobiologic Inc.) 40 mL in divided doses for 1 day, then 15 mL in divided doses daily thereafter (12355,20062). Other liquid extracts have been used safely for relatively longer periods, including Echinaforce (A. Vogel Bioforce AG) 2.4 grams daily for 4 months or 1.6 grams daily for 6 months (7087,18225), and Echinacin (Madaus AG) 5 mL twice daily for 10 days, or 4 mL twice daily for 8 weeks (3282,10802). Specific solid dosage forms of echinacea that have been used safely for up to 10 days include Echinacea purpurea above-ground parts (EchinaFresh, Enzymatic Therapy) 300 mg daily (11970), and mixtures of Echinacea purpurea and Echinacea angustifolia herb in divided doses of 6 grams to 10.5 grams for 1 day then 3 grams to 5.1 grams daily (10800,17519,20059). A specific Echinacea angustifolia extract (ExtractumPharma ZRT) has also been used with apparent safety at a dose of 40 mg once or twice daily for up to 7 days (20064,103233). An Echinacea purpurea product (Natures Resource) has been used safely at a dose of 1.8 grams daily for 8 weeks (17521), and echinacea (Puritan's Pride) has been used safely at 8 grams daily for 28 days (20066).
POSSIBLY SAFE ...when used topically, short-term. A specific cream (Linola Plus Cream, Dr. August Wolff GmbH & Co.) containing echinacea extract (WO 3260) has been applied to the skin safely 2-3 times daily for up to 12 weeks (97499). There is insufficient reliable evidence about the safety of echinacea when used parenterally.
CHILDREN: POSSIBLY SAFE
when used orally, short-term.
Some clinical research shows that an extract of the above-ground parts of Echinacea purpurea (EC31J2, Echinacin Saft, Madaus AG) in a dose of 3.75 mL twice daily (for ages 2 years to 5 years) or 7.5 mL twice daily (for ages 6 years to 11 years) is safe when used for up to 10 days (4989). However, about 7% of children experienced a rash after taking echinacea, which might have been caused by an allergic reaction (4989). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). In contrast, another clinical study in children 4-12 years old shows that a specific Echinacea purpurea product (Echinaforce Junior, A. Vogel) does not cause allergic or urticarial reactions more frequently than vitamin C (105719).
PREGNANCY: POSSIBLY SAFE
when used orally, short-term.
There is preliminary evidence that mothers can safely use echinacea in the form of E. purpurea or E. angustifolia solid dosage forms, 250-1000 mg daily, or tinctures, up to 30 drops daily, for 5 days to 7 days during the first trimester without adversely affecting the fetus (7056,13418,15123). There is insufficient reliable information available about the safety of echinacea when used for longer than 7 days.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in the amounts typically found in foods. Elderberry has generally recognized as safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when elderberry fruit extract is used orally, short-term. One specific elderberry fruit extract (Sambucol, Nature's Way) has been used with apparent safety for up to 5 days (5260,12235,103831); another (BerryPharma, Iprona AG) has been used with apparent safety for up to 15 days (91374). A specific elderberry fruit extract lozenge (ViraBLOC, HerbalScience) has been used with apparent safety for 2 days (17022). Other elderberry fruit extracts have been used with apparent safety for up to 12 weeks (21141,21142).
POSSIBLY UNSAFE ...when elder tree leaves and stems, or unripe or uncooked elderberries, are consumed. The unripe green fruit, as well as the leaves and stems of the elder tree, contain a cyanide-producing chemical, which can cause serious toxicity (17020,17021,21143,21144,91374). Cooking eliminates the toxin.
CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.
CHILDREN: POSSIBLY SAFE
when used orally for up to 3 days.
A specific fruit extract (Sambucol, Nature's Way) has been used in doses of 15 mL twice daily for 3 days in children 5 years and older (5260,103831).
CHILDREN: POSSIBLY UNSAFE
when unripe or uncooked elderberries are consumed.
The unripe green fruit, as well as the leaves and stems of the elder tree, contain a cyanide-producing chemical , which can cause serious toxicity (17020,17021,21143,21144,91374). Cooking eliminates the toxin.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods.
There is insufficient reliable information available about the safety of elderberry when used for medicinal purposes; avoid using in amounts greater than those found in foods.
POSSIBLY SAFE ...when used topically and appropriately, short-term. A specific product containing indigo naturalis, an isatis leaf extract, in olive oil (Lindioil), applied topically in doses of 0.05-0.1 mL to the skin around the fingernails twice daily, has been used with apparent safety for 24 weeks (88276,108089). There is insufficient reliable information available about the safety of isatis when used orally.
PREGNANCY AND LACTATION:
Insufficient reliable information is available; 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.
Below is general information about the interactions of the known ingredients contained in the product Echinacea Elderberry Syrup. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Boneset belongs to the genus Eupatorium, and many species of this genus contain hepatotoxic pyrrolizidine alkaloids (PAs). Hepatotoxic PAs are substrates of cytochrome P450 3A4 (CYP3A4) (12841,12860). Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites. Some drugs that induce CYP3A4 include carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), rifampin, rifabutin (Mycobutin), and others.
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Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
 Details
Echinacea seems to increase plasma concentrations of caffeine by around 30% (12155). This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.
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Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Details
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30% (12155). Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.
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Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Details
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir (13712,48618,88164,88165). However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4 (48618). The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4 (12155). In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate (6450,11026,88162,88167).
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Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.
Details
Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients (88163,93578).
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Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.
Details
Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study (88164).
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Echinacea may increase levels of etoposide.
Details
In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism (20082). Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme (6450,11026,12155,88162,88167).
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Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.
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Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.
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Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.
Details
Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers (48618,93578).
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Theoretically, echinacea may increase the metabolism of intravenous midazolam.
Details
Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam (12155). Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.
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Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.
Details
Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR (20083).
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Theoretically, elderberry might interfere with immunosuppressant therapy due to its immunostimulant activity.
Details
Elderberry has immunostimulant activity, increasing the production of cytokines, including interleukin and tumor necrosis factor (10796).
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Theoretically, taking forsythia with anticoagulant or antiplatelet drugs might increase the risk of bleeding due to decreased platelet aggregation. Forsythia might reduce platelet aggregation by inhibiting platelet activating factor (12619). Some of these drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.
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Theoretically, taking forsythia with azithromycin might increase the risk of adverse effects. Animal research in rats shows that taking a single dose of forsythia with azithromycin decreases the clearance and increases the area under the curve of both forsythiaside, a constituent of forsythia, and azithromycin. The mechanism of this interaction is not well understood (106675).
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Theoretically, honeysuckle might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
In vitro research shows that polyphenols extracted from honeysuckle can inhibit platelet aggregation (12610).
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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 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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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Below is general information about the adverse effects of the known ingredients contained in the product Echinacea Elderberry Syrup. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
General ...Orally, boneset is reported to cause nausea and severe diarrhea and vomiting (12842). Additionally, other plants in the Eupatorium genus contain the hepatotoxic pyrrolizidine alkaloids (PAs). However, the alkaloids in boneset have not been adequately characterized to determine their toxic potential (12842,102557). Liver toxicity and liver damage may be possible in high doses.
Gastrointestinal ...Orally, boneset has been reported to cause nausea and severe diarrhea and vomiting (12842).
Hepatic ...Other plants in the Eupatorium genus contain hepatotoxic pyrrolizidine alkaloids (PAs). However, the alkaloids in boneset have not been adequately characterized to determine their toxic potential (12842,102557). Liver toxicity and liver damage may be possible in high doses.
General
...Orally, echinacea is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, heartburn, nausea and vomiting, rashes, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions and hepatitis have been reported.
Dermatologic ...Itching, urticaria, tingling, and allergic rashes have been reported with various echinacea preparations (8225,12355,17519,20059,20077,101592,111530,111540). In a study of children aged 2-11 years, rash occurred in about 7% of children treated with an extract of the above-ground parts of E. purpurea (EC31J2, Echinacin Saft, Madaus AG), compared with about 3% of those treated with placebo (4989,95652). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). However, another study in children 4-12 years old shows that a specific E. purpurea product (Echinaforce Junior, A. Vogel) did not cause allergic or urticarial reactions more frequently than vitamin C (105719).
Gastrointestinal ...Gastrointestinal adverse effects include nausea and vomiting, abdominal pain, stomach upset, heartburn, diarrhea, and constipation (10802,11970,12355,13419,17519,20059,48680,105719,106626). An unpleasant taste, dry mouth, and burning, tingling or numbness of the tongue also occur (11970,12355,17519,20059,20070,20077).
Hematologic ...A 51-year-old female presented with leukopenia after taking echinacea 450 mg three times daily for 2 months, along with ginkgo biloba, multivitamins, and calcium. Her leukocyte count recovered upon stopping these supplements, but dropped again when she restarted echinacea alone about a year later. The problem resolved when echinacea was stopped permanently (48533). A 32-year-old male presented with severe thrombotic thrombocytopenic purpura (TTP) about 2 weeks after using an extract of E. pallida to treat a cold. He required admission to an intensive care unit and extensive plasmapheresis. The authors speculate that immunostimulant effects of echinacea induced or exacerbated the TTP (48572).
Hepatic
...Although uncommon, cases of echinacea-induced hepatitis have been reported.
One case report describes acute cholestatic autoimmune hepatitis in a 45-year-old male who had been taking an echinacea root extract 1500 mg daily for about 2 weeks. He presented with significantly elevated liver function tests (LFTs), elevated immunoglobulin G (IgG) levels, and a positive test for anti-smooth muscle antibodies, indicating an autoimmune process. Elevated LFTs and IgG levels returned to normal within one month of stopping echinacea (17518). Another case report describes acute cholestatic hepatitis in a 44-year-old male who had taken echinacea root tablets 600 mg daily for 5 days to treat flu-like symptoms. He presented with elevated LFTs, prothrombin time, and international normalized ratio (INR). His condition gradually improved after stopping echinacea, and his LFTs normalized within 3 months (91528).
Seven cases of hepatitis associated with echinacea use were reported to the Australian Adverse Drug Reactions Advisory Committee between 1979 and 2000, but specific details are lacking (8225).
One case report describes acute liver failure in a 2 year-old child who had been given about 100 mg of echinacea daily for 2 weeks. The patient presented with jaundice, diarrhea, lethargy, anorexia, and significantly elevated LFTs. A liver biopsy showed hepatocyte swelling, spotty necrosis, and inflammatory infiltrate with eosinophils. A full recovery was made over a 2-week period (88166).
Immunologic
...Allergic reactions, including urticaria, runny nose, dyspnea, bronchospasm, acute asthma, angioedema, and anaphylaxis, have been reported with various echinacea preparations (638,1358,8225).
Atopic individuals and those sensitive to other members of the Asteraceae family (ragweed, chrysanthemums, marigolds, daisies) seem to be at higher risk for these reactions (1358,8225).
A case report describes a 36-year-old female who presented with muscle weakness, electrolyte abnormalities, renal tubular acidosis, fatigue, and dry mouth and eyes after taking echinacea, kava, and St. John's Wort for 2 weeks., She also had a positive antinuclear antibody (ANA) test, with elevated anti-dsDNA antibodies SSA and SSB. Sjogren syndrome was diagnosed; the authors hypothesize that it may have been triggered by the immunostimulant effects of echinacea (10319). A 55-year-old male with a history of pemphigus vulgaris in remission for about a year experienced a flare of the disease after taking an echinacea supplement for one week. After stopping echinacea, medical treatment resulted in partial control of the disease (12171). Another case report describes a 58-year-old male who presented with marked eosinophilia and elevated immunoglobulin E (IgE) levels while taking an echinacea supplement. He required prednisone therapy until he stopped taking echinacea 3 years later, at which time his eosinophils and IgE normalized (48623). A 41-year-old male experienced four episodes of erythema nodosum, each occurring after he had taken echinacea for early symptoms of influenza. After stopping echinacea, he had no further exacerbations of erythema nodosum, suggesting that it had been triggered by the immunostimulant effects of echinacea (7057).
Musculoskeletal ...Reports of arthralgia and myalgia have been associated with echinacea (13418).
Neurologic/CNS ...Headache has been reported in people taking various echinacea preparations orally (3282,11970,17519,20059,20064). Dizziness has also been reported (3282,8225,11970). In one study using an alcoholic extract of the above-ground parts of E. purpurea (EC31J0, Echinacin, Madaus AG), somnolence and a tendency to aggressiveness were reported (3282).
General
...Orally, elderberry extracts prepared from ripe fruit seem to be well tolerated.
Most Common Adverse Effects:
Orally: When adverse effects occur, they are likely due to ingestion of raw and unripe elderberries, or seeds, leaves, and other plant parts. Due to cyanogenic glycosides, these may cause nausea, vomiting, severe diarrhea, weakness, dizziness, numbness, and stupor. Cooking eliminates the toxin.
Gastrointestinal
...Orally, nausea and vomiting have been reported after consuming a specific elderberry and echinacea product
Vogel Bioforce AG) (95650). However, it is unclear if this was due to the elderberry or Echinacea contained in the product.
Raw and unripe elderberries, and the seeds, leaves, and other elder tree parts might cause nausea, vomiting, or severe diarrhea due to cyanogenic glycosides (17020,17021). Cooking eliminates the toxin.
Hepatic ...In one case report, a 60-year-old female with underlying autoimmune disease presented with autoimmune hepatitis after taking elderberry at an unknown dose for several years. The patient presented with nausea, jaundice, abdominal pain, and abdominal distention. Liver function tests returned to baseline 4 weeks after initiating treatment with prednisone 40 mg daily and discontinuing elderberry (110123).
Immunologic ...Elder tree pollen might cause an allergic reaction characterized by rhinitis and dyspnea in some patients who are allergic to grass pollen. These patients might also experience an allergic reaction to elderberry extracts (11095).
Neurologic/CNS ...Raw and unripe elderberries might cause weakness, dizziness, numbness, and stupor due to cyanogenic glycosides (17020,17021). Cooking eliminates the toxin.
General ...Adverse effects of forsythia have not been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General ...Orally, honeysuckle seems to be well tolerated. No adverse effects have been reported. There is insufficient reliable information available about the safety of honeysuckle when used topically. However, a thorough evaluation of safety outcomes has not been conducted.
Immunologic ...Topically, applying honeysuckle to the skin has been associated with contact dermatitis in a case report (12611). Orally, a case of biopsy-confirmed allergic drug eruption is reported in a young adult male after taking honeysuckle granules 30 grams over a 24-hour period. Symptoms resolved with discontinuation of honeysuckle and 2-weeks of antihistamine and glucocorticoid therapy (112866).
General ...Orally and topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
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).
