Each softgel contains: Proprietary Blend 200 mg Alcohol free concentrated extracts of: Pau d'Arco inner bark, Quassia inner bark, Licorice root, Echinacea angustifolia root, Myrrh gum resin, Yerba Mansa root, Fresh green Black Walnut hull, Fresh Thuja leaf, Astragalus root, Fresh Garlic herb. Other Ingredients: Grain Alcohol, Purified Water, Vegetable Glycerine.
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 Yeast ReLeaf Liquid. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of yerba mansa.
Below is general information about the safety of the known ingredients contained in the product Yeast ReLeaf Liquid. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately. Doses of astragalus up to 60 grams daily for up to 4 months have been used without reported adverse effects (32920,33038,95909,114804). ...when used intravenously. Infusion of doses up to 80 grams daily for up to 4 months under the supervision of a medical professional have been used with apparent safety (32811,32812,32828,95909,114688,114804). There is insufficient reliable information available about the safety of astragalus when used topically.
PREGNANCY AND LACTATION:
There is insufficient reliable information in humans.
However, astragaloside, a constituent of astragalus, has maternal and fetal toxic effects in animals (32881). Avoid using.
LIKELY SAFE ...when the fruit (nut) is consumed in amounts normally found in food.
POSSIBLY UNSAFE ...when the bark is used orally or topically, due to its juglone content (2). When applied topically, juglone-containing bark can cause skin irritation. When used orally on a daily basis, the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12). There is insufficient reliable information available about the safety of the leaf or hull when used orally as a medicine or when applied topically.
PREGNANCY AND LACTATION: LIKELY SAFE
when the fruit (nut) is consumed in amounts normally found in foods.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the bark is used orally or topically (12); avoid using.
There is insufficient reliable information available about the safety of black walnut leaf or hull when used orally in medicinal amounts during pregnancy or lactation; 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 and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity (1873,4782,4783,4784,4785,4786,4787,4789,4790,4797)(4798,6457,6897,14447,96008,96009,96014,102016,102670,103479)(107238,107239,107352,108607,110722,111763).
POSSIBLY SAFE ...when used topically. Garlic-containing gels, lipid-soluble garlic extracts, garlic pastes, and garlic mouthwashes have been safely used in clinical research for up to 3 months (4766,4767,8019,15030,51330,51386). ...when used intravaginally. A vaginal cream containing garlic and thyme has been safely used nightly for 7 nights (88387).
POSSIBLY UNSAFE ...when raw garlic is used topically (585). Raw garlic might cause severe skin irritation when applied topically.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Garlic is reported to have abortifacient activity (11020). One study also suggests that garlic constituents are distributed to the amniotic fluid after a single dose of garlic (4828). However, there are no published reports of garlic adversely affecting pregnancy. In clinical research, garlic 800 mg daily was used during the third trimester of pregnancy with no reported adverse outcomes (9201,51626). There is insufficient reliable information available about the safety of topical garlic during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
LACTATION: POSSIBLY UNSAFE
when used orally in amounts greater than those found in foods.
Several small studies suggest that garlic constituents are secreted in breast milk, and that nursing infants of mothers consuming garlic are prone to extended nursing (3319,4829,4830). There is insufficient reliable information available about the safety of topical garlic during lactation.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 8 weeks.
Garlic extract 300 mg three times daily has been used with apparent safety for up 8 weeks in children ages 8-18 years (4796). There is insufficient reliable information available about the safety of garlic when used over longer durations or in higher doses.
CHILDREN: POSSIBLY UNSAFE
when raw garlic is used topically.
Raw garlic might cause severe skin irritation when applied topically (585,51210).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when consumed in amounts commonly found in food. Myrrh is approved for use in foods as a flavoring agent in the US (11).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Myrrh 400 mg three times daily has been safely used for up to 12 months (93653,104593). Myrrh 500 mg three times daily has been used with apparent safety for 2 weeks (104840). ...when used topically and appropriately (2,4,5,11,18). As a diluted bath, myrrh has been used with apparent safety for up to 7 days (104838,104839).
POSSIBLY UNSAFE ...when used orally in excessive doses. Myrrh may cause kidney irritation and diarrhea when used in doses of 2-4 grams (12).
PREGNANCY: LIKELY UNSAFE
when used orally.
Myrrh stimulates uterine tone and blood flow and may have an abortifacient effect (4,12,19,93645). There is insufficient reliable information available about the safety of the topical use of myrrh during pregnancy.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE ...when used orally. The safety of pau d'arco in typical doses is unclear. Serious toxicities have been found with high doses of the lapachol constituent (91939). In patients with cancer, doses of lapachol above 1.5 grams daily were associated with significant gastrointestinal toxicities and an increased risk of bleeding (91939). However, in patients with dysmenorrhea, doses of pau d'arco 1050 mg plus rutin 75 mg daily for up to 8 weeks did not lead to serious adverse effects (114012). There is insufficient reliable information available about the safety of pau d'arco when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally in typical doses.
Animal studies have found that lapachol, a constituent of pau d'arco, has teratogenic and abortifacient effects (68314,68315); avoid using. There is insufficient reliable information available about the safety of pau d'arco when used topically in pregnancy; avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Quassia has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used topically and appropriately. A 4% quassia gel has been safely used twice daily for up to 45 days (99995).
POSSIBLY UNSAFE ...when used orally in medicinal amounts. Quassia wood contains cardioactive glycosides (4), but toxicity is likely limited by emetic effects of large doses (4). There is insufficient reliable information available about the safety of rectal use of quassia.
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally; avoid using.
Quassia has cytotoxic and emetic properties (4,18,19). There is insufficient reliable information available about the safety of rectal or topical use during pregnancy or lactation; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Thuja that is thujone-free has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY UNSAFE ...when used orally in medicinal amounts. Large doses of thuja have been reported to cause seizures, severe vomiting, organ toxicity, and death in some cases (6002,40888). There is insufficient reliable information available about the safety of thuja when used topically.
PREGNANCY: LIKELY UNSAFE
when used orally due to abortifacient activity (12); avoid using.
LACTATION: LIKELY UNSAFE
when used orally due to toxicity (11); avoid using.
There is insufficient reliable information available about the safety of yerba mansa.
PREGNANCY AND LACTATION:
Insufficient reliable information is available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Yeast ReLeaf Liquid. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, astragalus might interfere with cyclophosphamide therapy.
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Theoretically, astragalus might interfere with immunosuppressive therapy.
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Theoretically, astragalus might increase levels and adverse effects of lithium.
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Animal research suggests that astragalus has diuretic properties (15103). Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.
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Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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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Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, garlic might decrease levels and effects of atazanavir.
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In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4) (88388). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.
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Garlic might increase levels of drugs metabolized by CYP2E1.
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Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39% (10847). Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
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Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa (7027,93578). Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels (17221). Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days (96010). Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic might decrease levels of isoniazid.
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Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa (15031); however, the exact mechanism of this potential interaction is not known.
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Theoretically, garlic products containing allicin might decrease levels of PIs.
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Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa (7027,93578). Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic containing allicin might decrease levels of saquinavir.
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Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa (7027,93578). Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506). Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.
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Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
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Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic (109524).
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Theoretically, garlic might increase levels of tacrolimus.
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In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus (96010).
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Theoretically, garlic might increase the risk of bleeding with warfarin.
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Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397). In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use (51228,51631). However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk (15032,16416). More evidence is needed to determine the safety of using garlic with warfarin.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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, myrrh might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
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Theoretically, myrrh might decrease the effectiveness of warfarin.
Details
In one case, a patient who was previously stable on warfarin had a significant decline in international normalized ratio (INR) following consumption of an aqueous extract of myrrh (14425).
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Theoretically, pau d'arco might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
In vitro research shows that pau d'arco reduces platelet aggregation and may interfere with vitamin K (18057,68319). One clinical study shows that taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily increases the risk of bleeding (91939). The effects of whole pau d'arco or pau d'arco extract in humans are unclear.
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Theoretically, due to reports that quassia increases stomach acid, quassia might decrease the effectiveness of antacids (19).
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In animals, quassia extract reduced levels of fasting glucose (99998). Theoretically, quassia might have additive effects when used with antidiabetes drugs. This might increase the risk of hypoglycemia in some patients. Monitor blood glucose levels closely.
Details
Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), rosiglitazone (Avandia), and others.
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Quassin and neoquassin, constituents of quassia, have been shown to inhibit cytochrome P450 1A1 (CYP1A1) enzymes in vitro (99996). This effect has not been shown in humans. Theoretically, concomitant use of quassia with drugs metabolized by CYP1A1 may decrease the clearance of these drugs and increase their effects. Some of these drugs include chlorzoxazone, theophylline, and bufuralol.
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Theoretically, concomitant use with cardiac medications might increase the risk of therapeutic and adverse effects (4).
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Overuse of quassia might compound diuretic-induced potassium loss (13). There is some concern that people taking quassia along with potassium depleting diuretics might have an increased risk for hypokalemia. Initiation of potassium supplementation or an increase in potassium supplement dose may be necessary for some patients.
Details
Some diuretics that can deplete potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), and hydrochlorothiazide (HCTZ, Hydrodiuril, Microzide), and others.
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Theoretically, due to reports that quassia increases stomach acid, quassia might decrease the effectiveness of H2-blockers (19). The H2 blockers include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid).
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Theoretically, due to reports that quassia increases stomach acid, quassia might decrease the effectiveness of PPIs (19). PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium).
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Thuja products can contain thujone, which might lower the seizure threshold (1304). Theoretically, this could decrease the effectiveness of anticonvulsants drugs.
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Thuja might stimulate immune function (1305). Theoretically, taking thuja might decrease the effects of immunosuppressive therapy. Immunosuppressant drugs include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), and other corticosteroids (glucocorticoids).
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Thuja products can contains significant amounts of thujone, a neurotoxin (1304). Theoretically, patients taking drugs that lower the seizure threshold might be at greater risk of seizure if they also take thuja. Advise patients taking these drugs to avoid thuja products. Some drugs that lower the seizure threshold include anesthetics (propofol, others), antiarrhythmics (mexiletine), antibiotics (amphotericin, penicillin, cephalosporins, imipenem), antidepressants (bupropion, others), antihistamines (cyproheptadine, others), immunosuppressants (cyclosporine), narcotics (fentanyl, others), stimulants (methylphenidate), theophylline, and others.
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Theoretically, concomitant use might cause additive or prolonged sedative effects (19).
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Below is general information about the adverse effects of the known ingredients contained in the product Yeast ReLeaf Liquid. 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 and intravenously, astragalus root seems to be well tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: A case report raises concerns about liver and kidney cysts with astragalus use.
Cardiovascular ...Orally, astragalus has reportedly been associated with lacunar angina in one clinical trial. However, this may not have been caused by astragalus (17355). In addition, rapid intravenous administration of astragalus has resulted in temporary palpitations (32812).
Dermatologic ...Intravenously, astragalus may cause rash, eczema, and pruritus (33034).
Gastrointestinal ...Orally, astragalus has reportedly been associated with enterocolitis and nausea in one clinical trial. However, these effects may not have been caused by astragalus (17355).
Genitourinary ...Orally, astragalus has reportedly been associated with vulvitis in one clinical trial. However, this effect may not have been caused by astragalus (17355).
Hepatic ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).
Musculoskeletal ...Orally, astragalus has been associated with reports of musculoskeletal pain in one clinical trial. However, these effects may not have been caused by astragalus (114803).
Neurologic/CNS ...Intravenously, administration of astragalus has been associated with temporary dizziness in patients with heart failure in clinical research (32812,114804). Orally, astragalus has also been associated with dizziness in one clinical study. However, these effects may not have been caused by astragalus (114803).
Pulmonary/Respiratory ...Orally, astragalus has reportedly been associated with rhinosinusitis and pharyngitis in one clinical trial. However, these effects may not have been caused by astragalus (17355).
Renal ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).
General
...Orally, black walnut fruit (nut) is well tolerated.
However, the leaf, bark, and hull of black walnut contain high quantities of tannins, which may cause adverse effects when used orally or topically.
Most Common Adverse Effects:
Orally: The leaf, bark, and hull can cause gastrointestinal upset.
Topically: Hull preparations may cause a temporary yellow or brown discoloration at the site of application. The leaf, bark, and hull can cause skin irritation.
Serious Adverse Effects (Rare):
Orally: The bark may increase the risk for tongue cancer or lip leukoplakia when used long-term.
All routes of administration: Allergic reactions, including anaphylaxis.
Dermatologic ...Topically, black walnut leaf, bark, or hull may have an irritating effect on the skin due to tannin content. Black walnut hull preparations might cause a temporary yellow or brown discoloration of the skin at the site of application (12).
Gastrointestinal ...Orally, black walnut leaf, bark, or hull may cause gastrointestinal upset due to tannin content (12). Also, daily use of the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12).
Hepatic ...Orally, black walnut leaf, bark, or hull may cause liver damage if taken for extended periods of time due to tannin content (12).
Immunologic ...Tree nuts, which include black walnuts, can cause allergic reactions in sensitive individuals. Due to the prevalence of this allergy in the general population, tree nuts are classified as a major food allergen in the United States (105410).
Renal ...Orally, black walnut leaf, bark, or hull may cause kidney damage if taken for extended periods of time due to tannin content (12).
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, garlic is generally well tolerated.
Topically, garlic seems to be well tolerated. Intravenously, there is insufficient reliable information available about adverse effects.
Most Common Adverse Effects:
Orally: Abdominal pain, body odor, flatulence, malodorous breath, and nausea. Allergic reactions in sensitive individuals.
Topically: Burns and dermatitis with fresh garlic.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with garlic.
Dermatologic
...Orally, garlic may cause pruritus (51316,51474,107239), flushing, and acne (107239).
Oral intake of a specific garlic product containing allicin (Allimax) has been associated with a case of pruritic rash (51474). Enteric-coated garlic tablets standardized to 1.5% allicin have also been associated with a case of pruritus (51316). Garlic has also been associated with a case of superficial pemphigus in a 49-year-old male with type 2 diabetes (51564). Garlic-induced oral ulcers have also been reported (51467).
Topically, garlic may cause contact dermatitis and urticaria (4833,5004,12635,51258,51265,51375,51403,51412,51459,51483)(51511,51512,51530,51616,51617,51618,111769), as well as contact cheilitis (51384). Fresh garlic may be more likely to elicit a reaction than garlic extract. Most reactions have resolved following withdrawal of garlic therapy. In one case report, applying crushed garlic on the neck to help ease a sore throat resulted in an itchy, burning, erythematous lesion in a young female patient. The lesion healed after one week of treatment with topical antibiotics, steroids, and antihistamine ointments (88390). Cases of occupational eczema or dermatitis have been reported in cooks (51303,51210), food handlers (51292), and caterers (51304). According to one case report, dermatitis appeared in chefs exposed to garlic (15033). Treatment with acitretin 25 mg daily or topical psoralen-ultraviolet A (PUVA) for 12 weeks proved effective in mitigating the symptoms. A 34-year-old female with a history of hand dermatitis and paronychia had a worsening of these conditions after peeling raw garlic. She had a positive skin patch test to fresh, raw garlic but not to any other tested allergens, and the conditions resolved when she avoided contact with garlic (105528). Topically, garlic may also cause chemical burns, usually within 12 hours of application. Second- and third-degree chemical burns have been reported in adults, children, and infants exposed to topical garlic, often as an unintended consequence of using garlic medicinally on the skin (585,4832,51226,51230,51252,51281,51377,51418,51468,51495,51536)(51558,51576,51577,88409,96006). A case of painful blisters on the soles of the feet of a 23-year-old Chinese female has been attributed to chemical burns caused by applying crushed raw garlic for 3 hours (51440). Topically, garlic may also cause hyperpigmentation, ulcers, necrotic lesions, facial flushing, and local irritation (4832,15030,51268,51269,108606). In one case report, applying crushed raw garlic to the palatal mucosa for several minutes to relieve mouth pain resulted in a chemical burn that produced a 3 cm necrotic ulcer in an adult female with trigeminal neuralgia (108606).
Gastrointestinal
...Orally, dehydrated garlic preparations or raw garlic may cause malodorous breath (51438,51444), body odor (732,1873,4784,4793,4795,4798,9201,10787,42692,49769)(51269,51316,51467,51602), abdominal pain or fullness, anorexia, diarrhea, constipation, flatulence, belching, heartburn, nausea, unpleasant taste, reflux, and bowel obstruction (1884,6457,6897,9201,49769,51269,51343,51380,51438,51442)(51450,51457,51466,51471,51474,51520,51593,51602,51623,88398)(88405,111766).
Large quantities of garlic may damage the gastrointestinal tract. In one case report, a patient taking garlic for hypertension reported odynophagia and retrosternal pain after taking garlic without any water the previous day. An esophageal lesion 3 cm in length was detected upon endoscopy. The symptoms resolved 3 days after starting a liquid diet and taking lansoprazole 30 mg twice daily and sucralfate four times daily (88389). One case of bowel obstruction was reported in a 66-year-old male who ingested an entire garlic bulb (51525). Esophageal perforation has been reported in at least 17 individuals who consumed entire garlic cloves. In one case the perforation led to mediastinitis and death (102672).
Garlic has also been associated with eosinophilic infiltration of the gastrointestinal tract. In one case report a 42-year-old female presented with symptoms of eosinophilic gastroenteritis, which included pollinosis, asthma, diarrhea, heart burn, peripheral eosinophilia, and urticaria. After stopping use of garlic and sesame, the patient improved (51441). In a case report of eosinophilic esophagitis, garlic was determined to be the causative agent in a patient with long-standing gastrointestinal symptoms. The patient had attempted to treat upper gastrointestinal symptoms as gastrointestinal reflux disease without success for many years. Skin prick testing showed a positive reaction to garlic, of which the patient noted frequent consumption. Marked symptom improvement was noted within 3 weeks of garlic avoidance (88393).
Intravenously, garlic 1 mg/kg of body weight daily diluted into 500 mL saline and administered over 4 hours has been reported to cause abdominal discomfort, vomiting, diarrhea, nausea, anorexia, flatulence, weight loss, and garlicky body odor (51462).
Clinical research suggests that patients with metabolic syndrome taking 1600 mg of powdered garlic by mouth daily for 3 months may experience improved intestinal transit time when compared with placebo, suggesting that garlic powder may reduce symptoms of constipation (110722).
Genitourinary ...Orally, garlic might cause dysuria, hematuria, or polyuria (51438,51450,51467,113618). In one case, an older male with high dietary and supplemental garlic intake at doses of 300-5400 mg daily for 3-4 years developed severe hematuria with clots after undergoing a minimally invasive prostate procedure (113618).
Hematologic
...Oral use of dietary garlic or supplements containing garlic has caused platelet dysfunction, increased fibrinolytic activity, prolonged bleeding time, retrobulbar hemorrhage (bleeding behind the eye) postoperative bleeding, and spinal epidural hematoma (586,587,4801,4802,11325,51397,51473,51491,51532,51534)(51570,51584,51593,51594,113618).
Also, a case of kidney hematoma following extracorporeal shock-wave lithotripsy (SWL) has been reported in a patient with nephrolithiasis who took aged garlic (51630). A case of increased bleeding time that complicated epistaxis management has been reported in a patient taking garlic, aspirin, and milk thistle (51426).
Intravenously, garlic has been associated with the development of thrombophlebitis at the injection site (51462).
Immunologic
...There is a case report of an immediate sensitivity reaction to oral raw garlic, resulting in wheals, in a 31-year-old female.
The patient did not react to cooked garlic, and skin prick tests showed allergy only to raw garlic (96015). Researchers note that at least some allergens in raw garlic are heat labile (88392,96012,96015). This suggests that consuming cooked rather than raw garlic may help avoid this reaction in patients allergic to raw garlic. However, different people react to different allergens in garlic. At least some of these allergens are heat stable (96012). While rare, garlic-induced anaphylaxis has been reported (88392,96012).
Topically, allergic contact dermatitis has been reported in case reports (51406,51498,51510,51519,51560).
Musculoskeletal ...Orally, garlic has been associated with individual cases of gout and low back pain (51474,51467), but it is not clear if these adverse events can be attributed to garlic.
Neurologic/CNS ...Orally, dizziness, insomnia, headaches, diaphoresis, fever, chills, somnolence, increased appetite, euphoria, and weight loss have been reported with garlic (15032,42692,51316,51467,51471,51520). In one case, the smell of garlic was identified as a trigger for migraines in a 32-year-old female. The subject reported fortification spectra along with visual spots for a few seconds followed by instantaneous biparietal, crushing level (10/10) headaches upon exposure to the scent of garlic or onion (88404).
Pulmonary/Respiratory ...Garlic exposure, most notably in occupational settings, may cause asthma and other symptoms such as sneezing, nasal obstruction, rhinorrhea, and sinusitis (40661,51218). A case of minor hemoptysis has been reported for one patient with cystic fibrosis following intake of garlic capsules orally once daily for 8 weeks (51438). A 77-year-old female developed pneumonia related to the intake of one whole black garlic clove daily. The cloves were prepared by heating a whole garlic bulb in a pot for one month. Symptoms included dyspnea and coughing, and test results were positive for lymphocyte-induced stimulation by black garlic and raw garlic. The patient required treatment with oral steroids and was told to avoid garlic (96011).
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, myrrh seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Kidney impairment and heart rate changes at high doses.
Cardiovascular ...Orally, myrrh taken at doses of 2-4 grams may cause heart rate changes in some patients (12,19).
Dermatologic ...Topically, myrrh has been reported to cause dermatitis (6).
Gastrointestinal ...Orally, myrrh may cause diarrhea in some patients when taken at doses of 2-4 grams (12,19).
Genitourinary ...Severe lower abdominal pain has been reported in a pregnant woman drinking myrrh resin dissolved in 500 mL of water twice daily as prescribed by a traditional practitioner. This adverse effect resolved one day after discontinuing myrrh. The investigators suggest that this acute abdominal pain was related to myrrh's activity as a uterine stimulant (93645).
Immunologic ...Orally, myrrh has been reported to cause severe allergic skin reactions, with redness, swelling, and itching, in two case reports of individuals using oral traditional Chinese medicines containing myrrh (101114).
Renal ...Orally, myrrh may cause kidney impairment in some patients when taken at doses of 2-4 grams (12,19).
General ...A thorough evaluation of safety outcomes with pau d'arco has not been conducted. However, taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily is regarded as unsafe.
Gastrointestinal ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause severe nausea, vomiting, and diarrhea (91939).
Hematologic ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause anemia and increased risk of bleeding (91939).
Immunologic ...Occupational exposure to sawdust from the pau d'arco tree and related species may cause asthma and dermatitis. The fresh sawdust can produce erythema and papules which progress to a severe weeping and crusting dermatitis (92184).
Neurologic/CNS ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause dizziness (91939).
General
...Orally, quassia can cause mucous membrane irritation, nausea, and vomiting when used in medicinal amounts (4,18).
Long-term use can cause vision changes and blindness (18).
Topically, quassia seems to be well tolerated (99995). No adverse effects have been reported.
Gastrointestinal ...Orally, quassia has been reported to cause mucous membrane irritation, nausea, and vomiting when used in medicinal amounts (4,18).
Ocular/Otic ...Orally, long-term use of quassia can cause vision changes and blindness (18).
General ...Orally, large doses of thuja have been reported to cause toxicity involving headache, nervous agitation, seizures, gastric irritation, vomiting, abdominal pain, and diarrhea. Thuja toxicity has also been reported to cause liver damage, renal toxicity, and death in some cases (6002,40888).
Dermatologic
...Contact dermatitis, presenting as an itchy papular squamous eruption on the hands, developed in a 46-year-old female who handled thuja plants while gardening.
It resolved when contact with thuja was avoided. The causative ingredient of thuja was identified as limonene (113415).
In one case report, a 5-year-old female presented with a papillary eccrine adenoma. In an effort to avoid excisional biopsy, an ointment containing thuja was applied to the lesion for 6 months, resulting in peripheral extension and central necrosis of the lesion, eventually necessitating complete excision (106048).
Gastrointestinal ...Orally, large doses of thuja have been reported to cause toxicity involving gastric irritation, vomiting, abdominal pain, and diarrhea (6002,40888).
Hepatic ...Orally, large doses of thuja have been reported to cause toxicity involving liver damage and death (6002,40888). In one case report, a healthy 40-year-old female taking thuja and black cohosh for 1 month presented with 3 days of severe abdominal pain and AST and ALT levels exceeding 5 times the upper limit of normal. Symptoms improved within 5 days of supplement discontinuation and levels normalized within 2 weeks (106047). It is unclear if this reaction was due to thuja, black cohosh, or other factors.
Neurologic/CNS ...Orally, large doses of thuja have been reported to cause toxicity involving nervous agitation, seizures, and death (6002,40888).
Renal ...Orally, large doses of thuja have been reported to cause toxicity involving renal toxicity and death (6002,40888).
General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
