Certified Organically Grown Rue fruiting tops extract (ruta graveolens) • Certified Organically Grown fennel seed extract (foeniculum vulgare) • Custom Wildcrafted Eyebright flowering herb extract (euphrasia officinalis) • Certified Organically Grown Goldenseal rhizome and roots extract (hydrastis canadensis) • Certified Organically Grown Mullein leaf and flower extract (verbascum olympicum and thapsus) • Boric Acid USP (1%). Other Ingredients: Certified Organic Grain Alcohol, Distilled Water, Vegetable Glycerine.
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Below is general information about the effectiveness of the known ingredients contained in the product Rue Fennel Compound. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Rue Fennel Compound. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately. Boron is safe in amounts that do not exceed the tolerable upper intake level (UL) 20 mg daily (7135). ...when used vaginally. Boric acid, the most common form of boron, has been safely used for up to six months (15443,15444,15445,15446,15458,15449,15451,15453,15454). ...when used topically. Boron, in the form of sodium pentaborate pentahydrate 3% gel, has been applied to the skin with apparent safety up to four times daily for up to 5 weeks (95660,109557).
POSSIBLY UNSAFE ...when used orally in doses exceeding the UL of 20 mg daily. Higher doses might adversely affect the testes and male fertility (7135). Poisoning has occurred after ingestion of boron 2.12 grams daily for 3-4 weeks (17). Death has occurred after ingesting a single dose of 30 grams (36848,36863).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Boron is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL by age is 3 mg daily at 1-3 years, 6 mg daily at 4-8 years, 11 mg daily at 9-13 years, and 17 mg daily at 14 years or older (7135). The UL for infants has not been determined (7135).
CHILDREN: POSSIBLY UNSAFE
when used orally in doses exceeding the age-based UL (7135).
...when applied topically in large quantities. Infant deaths have occurred after the use of topical boric acid powder to prevent diaper rash (36873,36874).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Boron is safe in amounts that do not exceed the UL during pregnancy or lactation, which is 20 mg daily in those 19-50 years of age or 17 mg daily for those 14-18 years of age (7135).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL.
Higher doses might impair growth and cause adverse effects in the developing fetus (7135,102058). ...when used vaginally. Intravaginal boric acid has been associated with a 2.7- to 2.8-fold increased risk of birth defects when used during the first 4 months of pregnancy (15443,15645).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Eyebright is listed by the Council of Europe as a natural source of food flavoring (4).
POSSIBLY UNSAFE ...when applied into the eyes. Avoid using due to hygienic concerns; eyebright ophthalmic products may be subject to contamination (8,11). There is insufficient reliable information available about the safety of eyebright when used orally in medicinal amounts.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).
CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week.
Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).
LACTATION: POSSIBLY UNSAFE
when used orally.
Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.
POSSIBLY SAFE ...when used orally and appropriately as a single dose (260,261). There is insufficient reliable information available about the safety of goldenseal when used as more than a single dose.
CHILDREN: LIKELY UNSAFE
when used orally in newborns.
The berberine constituent of goldenseal can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).
PREGNANCY: LIKELY UNSAFE
when used orally.
Berberine is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to goldenseal (2589).
LACTATION:
LIKELY UNSAFE when used orally.
Berberine and other harmful constituents can be transferred to the infant through breast milk (2589). Use during lactation can cause kernicterus in the newborn and several resulting fatalities have been reported (2589).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Rue and rue oil have Generally Recognized as Safe (GRAS) status for use in foods at concentrations that do not exceed 2 parts per million (ppm) (12,4912).
POSSIBLY SAFE ...when products containing dried rue leaves are used medicinally in appropriate doses (6,12,18,515). However, therapeutic doses can cause drowsiness, dizziness, and gastrointestinal irritation and cramps (12).
LIKELY UNSAFE ...when fresh rue and rue oil are used orally, or when large doses of the dried herb are used orally (2,12,18). Overdose is associated with severe abdominal pain, vomiting, liver damage, kidney damage, vertigo, respiratory distress, and delirium, and can be fatal (12,18). ...when fresh rue is applied topically. Rue can cause contact dermatitis and severe photodermatitis (2,6,11,19,104119,107948).
PREGNANCY: LIKELY UNSAFE
when used orally.
Rue has uterine stimulant and abortifacient effects (12,19); avoid using. Deaths have been reported in women who used rue as an abortifacient (2).
LACTATION:
There is insufficient reliable information available about the use of rue when breast-feeding; avoid use.
Below is general information about the interactions of the known ingredients contained in the product Rue Fennel Compound. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Preliminary research in animal models of diabetes suggests that eyebright lowers blood glucose levels (49393). Theoretically, concomitant use of eyebright might require dosing adjustment of anti-diabetes drugs; monitor closely. Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
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Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
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Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.
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Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135). |
Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.
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Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.
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Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.
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Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.
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Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen. |
Theoretically, goldenseal might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
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Theoretically, goldenseal might increase the risk of hypoglycemia when used with antidiabetes drugs.
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Theoretically, goldenseal might increase the risk of hypotension when taken with antihypertensive drugs.
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Goldenseal contains berberine. Animal research shows that berberine can have hypotensive effects (33692,34308). Also, an analysis of clinical research shows that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone (91956). However, this effect has not been reported with goldenseal.
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Theoretically, goldenseal might increase the sedative effects of CNS depressants.
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Theoretically, goldenseal might increase serum levels of drugs metabolized by CYP2C9.
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In vitro research shows that goldenseal root extract can modestly inhibit CYP2C9. This effect may be due to its alkaloid constituents, hydrastine and berberine (21117). However, this effect has not been reported in humans.
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Goldenseal might increase serum levels of drugs metabolized by CYP2D6.
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Theoretically, goldenseal might increase serum levels of drugs metabolized by CYP2E1.
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In vitro research shows that goldenseal root extract can inhibit the activity of CYP2E1 (94140). However, this effect has not been reported in humans.
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Goldenseal might increase serum levels of drugs metabolized by CYP3A4.
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Most clinical and in vitro research shows that goldenseal inhibits CYP3A4 enzyme activity and increases serum levels of CYP3A4 substrates, such as midazolam (6450,13536,21117,91740,111725). However, in one small clinical study, goldenseal did not affect the levels of indinavir, a CYP3A4 substrate, in healthy volunteers (10690,93578). This is likely due to the fact that indinavir has a high oral bioavailability, making it an inadequate probe for CYP3A4 interactions (13536,91740) and/or that it is primarily metabolized by hepatic CYP3A, while goldenseal has more potential to inhibit intestinal CYP3A enzyme activity (111725). Both goldenseal extract and its isolated constituents berberine and hydrastine inhibit CYP3A, with hydrastine possibly having more inhibitory potential than berberine (111725).
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Theoretically, goldenseal might increase serum levels of dextromethorphan.
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Goldenseal contains berberine. A small clinical study shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279).
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Goldenseal might increase serum levels of digoxin, although this effect is unlikely to be clinically significant.
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Clinical research shows that goldenseal modestly increases digoxin peak levels by about 14% in healthy volunteers. However, goldenseal does not seem to affect other pharmacokinetic parameters such as area under the curve (AUC) (15132). This suggests that goldenseal does not cause a clinically significant interaction with digoxin. Digoxin is a P-glycoprotein substrate. Some evidence suggests that goldenseal constituents might affect P-glycoprotein; however, it is unclear whether these constituents inhibit or induce P-glycoprotein.
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Theoretically, goldenseal might decrease the conversion of losartan to its active form.
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Goldenseal contains berberine. A small clinical study shows that berberine inhibits cytochrome P450 2C9 (CYP2C9) activity and reduces the metabolism of losartan (34279). However, this effect has not been reported with goldenseal.
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Theoretically, goldenseal might reduce blood levels of metformin.
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In vitro research shows that goldenseal extract decreases the bioavailability of metformin, likely by interfering with transport, intestinal permeability, or other processes involved in metformin absorption. It is unclear which, if any, of metformin's transporters are inhibited by goldenseal. Goldenseal does not appear to alter the clearance or half-life of metformin (105764).
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Theoretically, goldenseal might reduce the therapeutic effects of oseltamivir by decreasing its conversion to its active form.
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In vitro evidence suggests that goldenseal reduces the formation of the active compound from the prodrug oseltamivir (105765). The mechanism of action and clinical relevance is unclear.
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Theoretically, goldenseal might increase or decrease serum levels of P-glycoprotein (P-gp) substrates.
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There is conflicting evidence about the effect of goldenseal on P-gp. In vitro research suggests that berberine, a constituent of goldenseal, modestly inhibits P-gp efflux. Other evidence suggests that berberine induces P-gp. In healthy volunteers, goldenseal modestly increases peak levels of the P-gp substrate digoxin by about 14%. However, it does not seem to affect other pharmacokinetic parameters such as area under the curve (AUC) (15132). This suggests that goldenseal is not a potent inhibitor of P-gp-mediated drug efflux. Until more is known, goldenseal should be used cautiously with P-gp substrates.
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Theoretically, goldenseal might increase the sedative effects of pentobarbital.
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Animal research shows that berberine, a constituent of goldenseal, can prolong pentobarbital-induced sleeping time (13519). However, this effect has not been reported with goldenseal.
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Theoretically, goldenseal might increase serum levels of tacrolimus.
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Goldenseal contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of tacrolimus dosing to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL (91954).
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Theoretically, rue might increase the risk for phototoxicity when used with photosensitizing drugs.
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Below is general information about the adverse effects of the known ingredients contained in the product Rue Fennel Compound. 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, boron is generally well tolerated when used in doses below the tolerable upper intake level (UL) of 20 mg.
Vaginally, boron is well tolerated.
Most Common Adverse Effects:
Orally: Anorexia, dermatitis, erythema, indigestion.
Vaginally: Burning and pain.
Dermatologic
...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause dermatitis and alopecia (7135).
Larger doses can result in acute poisoning. Symptoms of poisoning in adults and children may include skin erythema, desquamation, and exfoliation (17).
Gastrointestinal
...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause anorexia and indigestion (7135).
Larger doses can result in acute poisoning. Children who have ingested 5 grams or more of borates can have persistent nausea, vomiting, and diarrhea leading to acute dehydration, shock, and coma. Adults who have ingested 15-20 grams of borate can exhibit nausea, vomiting, diarrhea, epigastric pain, hematemesis, and a blue-green discoloration of feces and vomit (17).
Genitourinary ...Vaginally, boric acid can cause vulvovaginal burning and dyspareunia in males if intercourse occurs shortly after vaginal treatment (15447).
Neurologic/CNS ...Orally, large doses can result in acute poisoning. Poisoning with boron can cause hyperexcitability, irritability, tremors, convulsions, weakness, lethargy, and headaches (17).
Ocular/Otic ...Exposure to boric acid or boron oxide dust has been reported to cause eye irritation (36852).
Pulmonary/Respiratory ...Exposure to boric acid and boron oxide dust has been reported to cause mouth and nasal passage irritation, sore throat, and productive cough (36852).
General ...There is a limited amount of information on the adverse effects of eyebright. Orally, eyebright has been reported to cause mental confusion, headache, nausea, constipation, cough, dyspnea, insomnia, and polyuria (4). Topically, eyebright applied to the eye has been reported to cause increased eye pressure, itching, redness, vision changes, and photophobia (4). Ophthalmic eyebright products should be used with caution due to the potential for contamination (8,11).
Gastrointestinal ...Orally, eyebright has been reported to cause nausea and constipation (4).
Genitourinary ...Orally, eyebright has been reported to cause polyuria (4).
Neurologic/CNS ...Orally, eyebright has been reported to cause confusion and headache (4).
Ocular/Otic ...Topically, eyebright has been reported to cause increased ocular pressure, lacrimation, pruritus, redness, swelling of eyelid margins, vision changes, and photophobia when applied to the eyes (4). Ophthalmic eyebright products should be used with caution due to the potential for contamination (8,11).
Pulmonary/Respiratory ...Orally, eyebright has been reported to cause cough, dyspnea, and nasal congestion (4).
General
...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.
Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).
Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).
Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).
Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).
Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.
Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).
General
...There is limited reliable information available about the safety of goldenseal when used in more than a single dose.
Berberine, a constituent of goldenseal, is generally well tolerated when used orally.
Most Common Adverse Effects:
Orally: Berberine, a constituent of goldenseal, can cause abdominal distension, abdominal pain, bitter taste, constipation, diarrhea, flatulence, headache, nausea, and vomiting.
Dermatologic ...Orally, berberine, a constituent of goldenseal, may cause rash. However, this appears to be rare (34285). A case of photosensitivity characterized by pruritic, erythematous rash on sun-exposed skin has been reported in a 32-year-old female taking a combination product containing goldenseal, ginseng, bee pollen, and other ingredients. The rash resolved following discontinuation of the supplement and treatment with corticosteroids (33954). It is not clear if this adverse effect is due to goldenseal, other ingredients, or the combination.
Endocrine ...A case of severe, reversible hypernatremia has been reported in an 11-year-old female with new-onset type 1 diabetes and diabetic ketoacidosis who took a goldenseal supplement (52592).
Gastrointestinal ...Orally, berberine, a constituent of goldenseal, may cause diarrhea, constipation, flatulence, vomiting, abdominal pain, abdominal distention, and bitter taste (33648,33689,34245,34247,34285,91953). Theoretically, these effects may occur in patients taking goldenseal. However, this hasn't been reported in clinical research or case reports.
Neurologic/CNS ...Orally, berberine, a constituent of goldenseal, may cause headache when taken in a dose of 5 mg/kg daily (33648). Theoretically, this may occur with goldenseal, but this hasn't been reported in clinical research or case reports.
General ...Information regarding the adverse effects of mullein is limited. A thorough evaluation of safety outcomes has not been conducted.
Dermatologic ...Two case reports have described dermatitis, with positive patch tests, after topical exposure to the whole plant, or by occupational inhalation of plant dust (92839,97316). In the case of topical exposure, the patient also had positive patch tests to other plants.
General
...Orally, rue is well tolerated when taken in the amounts found in foods.
The dried herb seems to be generally well tolerated when taken in medicinal doses; however, a thorough evaluation of safety outcomes has not been conducted. Fresh rue is generally considered unsafe.
Most Common Adverse Effects:
Orally: Cramps, drowsiness, depression, dizziness, gastrointestinal irritation, and sleep disturbances with medicinal use of the dried herb.
Topically: Contact dermatitis and phototoxic skin reactions with the fresh plant.
Cardiovascular ...Orally, large doses of rue have been associated with bradycardia (2).
Dermatologic ...Topically, rue can cause contact dermatitis (2). Exposure to the fresh rue plant followed by sun exposure within 48 hours can lead to severe phototoxic reactions (2,6). Multiple case reports describe patients who developed pruritus, erythema, and severe blistering on the back of the hands and wrists, equivalent to a partial thickness burn, after contact with the fresh plant leaves and exposure to sunlight (104119,107948). One patient was successfully treated with cetirizine and oral and topical corticosteroids (107948).
Gastrointestinal ...Orally, rue can cause gastrointestinal irritation and cramps at therapeutic doses (2,12). When taken in large doses, it causes severe abdominal pain and vomiting (2,12,18).
Genitourinary ...Orally, rue can cause uterine stimulation and abortion (2).
Hepatic ...Orally, high doses of rue can cause liver damage (2,12,18).
Neurologic/CNS ...Orally, therapeutic doses of rue can cause tremor, dizziness, drowsiness, sleep disorders, and depression. High doses can cause vertigo, seizures, and delirium (2,12,18).
Pulmonary/Respiratory ...Orally, high doses of rue can cause respiratory distress (2,12,18).
Renal ...Orally, high doses of rue can cause kidney damage (2,12,18).