Ingredients | Amount Per Serving |
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Proprietary Extract Blend
(Extraction rate: about 1/3-4. We used up to 333 mg of raw material to produce 1 ml of extract. )
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1156 mg |
(Borage Flower Extract, Dry, Borage Herb Extract, Dry)
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(Arctium lappa )
(root)
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(Glycyrrhiza glabra )
(root)
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(Urtica dioica )
(leaf)
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Ethyl Alcohol, Water, Glycerin
Below is general information about the effectiveness of the known ingredients contained in the product Adrenal Gland Support. 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
Below is general information about the safety of the known ingredients contained in the product Adrenal Gland Support. 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 borage seed oil is used orally or topically and appropriately. Borage seed oil has been used with apparent safety in clinical trials at a dose of up to 4 grams daily for up to 12 weeks (7632,8458,11341,13305,36804,88185,5244).
LIKELY UNSAFE ...when products containing hepatotoxic pyrrolizidine alkaloids (PA) are used orally. Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic and mutagenic (12841,12842). Tell patients not to use borage preparations that are not certified and labeled as hepatotoxic PA-free.
CHILDREN: POSSIBLY SAFE
when borage seed oil is used orally and appropriately.
Borage seed oil has been used with apparent safety at a dose of 2 grams daily for 12 weeks (11341).
CHILDREN: LIKELY UNSAFE
when products containing hepatotoxic PAs are used orally.
Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic and mutagenic (12841,12842). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free.
PREGNANCY AND LACTATION: LIKELY UNSAFE
when products containing hepatotoxic pyrrolizidine alkaloids (PA) are used orally.
Borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic, mutagenic, and teratogenic. These constituents are also excreted in breast milk (12841,12842). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free.
There is insufficient reliable information available about the safety of borage seed oil when used orally or topically during pregnancy or lactation.
LIKELY SAFE ...when used in amounts commonly found in foods (12659,12660). Burdock root is commonly eaten as a vegetable (37422,92153,92154)
POSSIBLY SAFE ...when used topically, short-term. An emulsion containing burdock fruit extract 1.2% has been safely applied to the face twice daily for 4 weeks (37420). There is insufficient reliable information available about the safety of burdock when used orally in supplemental doses.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Stinging nettle root 360-600 mg has been used safely for up to 1 year (5093,11230,15195,76406,96744). ...when used topically and appropriately (12490).
PREGNANCY: LIKELY UNSAFE
when used orally due to possible abortifacient and uterine-stimulant effects (4,6,19).
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Adrenal Gland Support. 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, borage seed oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
In healthy individuals, borage seed oil supplementation does not seem to affect platelet aggregation (36823). However, gamma-linolenic acid, a constituent of borage seed oil, seems to decrease platelet aggregation by 45% and increase the risk of bleeding by 40% in animal and clinical research (1979).
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Theoretically, taking borage with drugs that induce CYP3A4 might increase levels of pyrrolizidine alkaloid (PA) toxic metabolites.
Details
Although borage seed oil contains little to no PAs, some borage plant parts, such as the leaf, flower, and seed, can contain hepatotoxic PAs. Hepatotoxic PAs are substrates of CYP3A4, which converts these chemicals into toxic metabolites (12841,12860). Tell patients to avoid borage preparations that are not certified and labeled as hepatotoxic PA-free.
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Theoretically, taking borage sed oil with phenothiazines might increase the risk of seizures.
Details
Borage seed oil contains gamma-linolenic acid (GLA). There is concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines. This is based on limited data from two reports published in the 1980s. In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with evening primrose, another source of GLA. However, none experienced an actual seizure (21013). In the other report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose 4 grams daily was added. One of these patients had a prior history of seizures (21010). It is unclear whether evening primrose had any additive epileptogenic effects with the phenothiazines, but there is no evidence that taking GLA-containing supplements alone can cause seizures (88187).
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Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
Details
In vitro research shows that lignans from burdock reduce rabbit platelet aggregation by inhibiting platelet activating factor (12619). This interaction has not been reported in humans. |
Theoretically, licorice might reduce the effects of antihypertensive drugs.
Details
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Theoretically, licorice might reduce the effects of cisplatin.
Details
In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
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Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Details
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).
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Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
Details
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
Details
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
Details
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
Details
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Details
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Details
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Details
Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Details
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Details
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
Details
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.
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Theoretically, licorice might decrease levels of midazolam.
Details
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.
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Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
Details
In vitro research shows that licorice can increase P-glycoprotein activity (104561).
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Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Details
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Details
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Theoretically, stinging nettle might have additive effects with antidiabetes drugs.
Details
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Theoretically, combining stinging nettle with diuretic drugs may have additive effects.
Details
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Theoretically, stinging nettle might reduce excretion and increase levels of lithium.
Details
Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium (76402). The dose of lithium might need to be decreased.
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There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.
Details
Stinging nettle contains a significant amount of vitamin K (19). When taken in large quantities, this might interfere with the activity of warfarin.
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Below is general information about the adverse effects of the known ingredients contained in the product Adrenal Gland Support. 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, borage seed oil seems to be well tolerated.
However, borage plant parts, such as the leaf, flower, and seed, that contain hepatotoxic pyrrolizidine alkaloid (PA) constituents should be avoided.
Most Common Adverse Effects:
Orally: Belching, bloating, diarrhea, and soft stools.
Serious Adverse Effects (Rare):
Orally: Borage plant parts that contain PA constituents can be hepatotoxic.
Gastrointestinal ...Orally, borage seed oil can cause soft stools, diarrhea, belching, and bloating (8013,11341).
Hepatic ...The pyrrolizidine alkaloid (PA) constituents of borage can cause significant hepatotoxicity (12841,12842). PAs can occur in borage leaf, flower, and seed; borage seed oil contains little to no PAs. Chronic exposure to other plants containing hepatotoxic PA constituents has been associated with veno-occlusive disease (VOD). Subacute VOD causes vague symptoms with persistent liver enlargement (4021). Symptoms of acute VOD include colicky pains in epigastrium, vomiting and diarrhea, and ascites within several days. Enlargement and induration of the liver occurs within a few weeks (12842).
Oncologic ...The pyrrolizidine alkaloid (PA) constituents of borage are potentially carcinogenic and mutagenic (12841,12842).
Pulmonary/Respiratory ...The pyrrolizidine alkaloid (PA) constituents of borage are potentially pneumotoxic (12841,12842).
General
...Orally, burdock is well tolerated when consumed as a food.
Although a thorough evaluation of safety outcomes is lacking, there has been long-standing historical use of burdock with few noted adverse effects.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions, including contact dermatitis and anaphylaxis.
Dermatologic ...Contact dermatitis has been reported secondary to burdock, especially after prolonged use of the root oil (37422). There are cases of allergic dermatitis secondary to using burdock plasters. Two males and a 14 year-old female developed erythematous and vesicular, pruritic, and exudative reactions in areas corresponding to the application of burdock root plasters (12667). Reactions occurred up to 7 days after initial use. Patch testing was positive for burdock sensitivity in all three patients and was nonreactive in matched controls.
Hematologic ...In one case report, a 38-year-old female developed immune-mediated thrombocytopenia after consuming a "cleansing" tea containing unknown amounts of burdock and yellow dock. The patient presented with bruising, mild weakness, and fatigue, which started 2-3 days after consuming the tea, and was found to have a platelet count of 5,000 per mcL. Symptoms resolved after platelet transfusion and treatment with oral dexamethasone (108971). It is unclear if these effects were caused by burdock, yellow dock, the combination, or other contributing factors.
Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing burdock and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to burdock, other ingredients, or the combination.
Immunologic ...There is one case of anaphylactic shock secondary to eating boiled burdock. One hour after eating boiled burdock the patient presented with redness over the entire body and dyspnea. He was found to have low blood pressure and was treated with subcutaneous epinephrine 1 mg and intravenous lactated ringer's solution containing hydrocortisone 100 mg and dexamethasone 8 mg. The cause of anaphylactic shock was attributed to allergenicity to burdock based on positive skin prick test results. Previously, the patient had experienced urticaria after eating boiled burdock (12660).
Neurologic/CNS ...Anticholinergic reactions including dry mouth, dizziness, blurred vision, weakness, dilated pupils, inability to urinate, and bradycardia have been reported following the consumption of burdock products (12662,37421,37431,37434,37435). However, these anticholinergic reactions are believed result from contamination of burdock with belladonna alkaloids. Burdock itself does not contain atropine or other constituents that would be responsible for these reactions.
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, stinging nettle seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea.
Topically: Contact with the raw plant causes itching, rash, and stinging.
Dermatologic ...Topically, fresh stinging nettle leaves and stalk can cause localized rash, itching, and stinging (12490,76399,76412,76414,76417,76428,76448,96746). Usually, short exposure to stinging nettle results in a transient urticarial reaction and a stinging sensation which may persist for more than 12 hours (76399,76414,76417,96746). In one report, a patient placed a fresh stinging nettle leaf on the tongue to suck out the sap of the leaf. Severe tongue edema, pain, and urticaria developed within 5 minutes. Symptoms continued for several hours after the leaf was removed (15197). In another case report, a young couple intoxicated with methamphetamine fell and laid in a stinging nettle bush for 20 minutes, after which urticaria and pain continued for 2-3 weeks, and a heightened sensitivity to cold persisted for several months (96746).
Endocrine
...A case of gynecomastia has been reported for a 33-year-old male who consumed stinging nettle tea 2 cups daily for one month prior to symptom onset.
The condition subsided one month after discontinuing stinging nettle tea (76410).
There have been two cases of galactorrhea associated with the consumption of stinging nettle for one month (76410,108902). In one case, a 33-year-old female consuming stinging nettle tea showed high levels of estradiol and low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones normalized 6 weeks after discontinuing stinging nettle tea (76410). In the other case report describing a 30-year-old female self-treating with stinging nettle 500 mg daily, hormone levels were not reported; however, a mammogram showed scattered areas of fibroglandular density and benign-appearing calcifications. This patient had complete resolution of symptoms 1 week after discontinuation of stinging nettle (108902).
Gastrointestinal ...Orally, stinging nettle root can cause gastrointestinal complaints, including diarrhea and constipation (1,7,11230). Stinging nettle above ground parts may cause mild gastrointestinal discomfort when taken on an empty stomach (7035). Stinging nettle juice may cause diarrhea (1). One patient taking a combination product containing stinging nettle root extract and pygeum bark extract (Prostatonin, Pharmaton) experienced continual gastrointestinal pain and hyperperistalsis. It is not clear if this effect was due to stinging nettle or pygeum (70230).
Genitourinary ...There is a case report of decreased ejaculatory volume associated with an herbal blend product containing stinging nettle root extract, saw palmetto extract, pumpkin seed oil extract, lemon bioflavonoid extract, and beta-carotene (5093). It is unclear if this was due to stinging nettle, other ingredients, or the combination.
Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing stinging nettle and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to the stinging nettle, other ingredients, or the combination.
Other ...Orally, stinging nettle root can cause sweating (1,7).