Each capsule contains: Flaxseed lignan 96.6 mg • Soy Isoflavonoids 60 mg • Black Cohosh root/stem extract (2.5% triterpenes) 80 mg • Pine Bark extract (95% proanthocyanidins) 60 mg • Iso Hops 120 mg • VITA-FM brand Proprietary Ayurvedic Formula 760 mg: Saraca Indica, Symplocos Racemosa , Asparagus Racemosa , Ficus Racemosa, Woodfordia Florbunda , Pyrus malus , Dashmool , Asphaltum , Azadirachta Indica , Glycyrrhiza glabra , Piper longum . Other Ingredients: Microcrystalline Cellulose, Silicon Dioxide, Capsule (hypromellose, sorbitol, silicon dioxide, water).
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 Professional Series Fem Adapt. 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
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Professional Series Fem Adapt. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in food amounts. Eating apples and consuming apple juice is safe for most people. Apples are a common food source (3470,3472). However, eating apple seeds should be avoided because they can be toxic (6).
CHILDREN: LIKELY SAFE
when used orally in food amounts.
Eating apples and consuming apple juice is safe for most people. Apples are a common food source (3470,3472).
CHILDREN: POSSIBLY SAFE
when apple pectin is used orally and appropriately, short-term.
Preliminary clinical research suggests that combination products containing apple pectin and German chamomile (Diarrhoesan) are safe when used in infants for up to one week (19705,19706).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of apple in amounts greater than those found in foods during pregnancy and lactation; avoid using.
POSSIBLY SAFE ...when used appropriately in healthy individuals. Asparagus racemosus 500 mg daily has been used with apparent safety for 8 weeks in male recreational athletes (106413).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Black cohosh has been safely used in some studies lasting up to a year (15036,15158,17091,19553,35908); however, most studies have lasted only up to 6 months (141,4614,4620,7054,9437,9494,13143,13184,14330,14423)(14424,15037,15889,15893,35824,35852,35853,35858,35865,35897)(35902,35904,35946,35964,95525,103269). There is concern that black cohosh might cause liver damage in some patients. Several case reports link black cohosh to liver failure or autoimmune hepatitis (4383,10692,11906,12006,13144,14469,15160,16721,16722,16723)(16724,16725,16726,16727,35857,107906). However, the evidence that black cohosh causes liver damage is not conclusive (17085). Until more is known, monitor liver function in patients who take black cohosh.
PREGNANCY: POSSIBLY UNSAFE
when used orally in pregnant patients who are not at term.
Black cohosh might have hormonal effects and menstrual and uterine stimulant effects (15035). Theoretically, this might increase the risk of miscarriage; avoid using during pregnancy. There is insufficient reliable information available about the safety of black cohosh when used to induce labor.
LACTATION: POSSIBLY UNSAFE
when used orally.
Black cohosh might have hormonal effects. Theoretically, maternal intake of black cohosh might adversely affect a nursing child (15035). Until more is known, nursing patients should avoid taking black cohosh.
LIKELY SAFE ...when ground flaxseed is used orally and appropriately. Ground flaxseed has been safely used in numerous clinical trials in doses up to 30-60 grams daily for up to 1 year (6803,6808,8020,10952,10978,12908,12910) (16760,16761,16762,16765,16766,18224,21191,21194,21196,21198) (21199,21200,22176,22179,22180,22181,65866,66065) (101943,101949,101950).
POSSIBLY SAFE ...when flaxseed lignan extract or mucilage is used orally and appropriately. Some clinical research shows that a specific flaxseed lignan extract (Flax Essence, Jarrow Formulas) 600 mg daily can be used with apparent safety for up to 12 weeks (16768). Additional clinical research shows that other flaxseed lignin extracts can be used with apparent safety for up to 6 months (21193,21197,21200). In one clinical trial, flaxseed mucilage was used with apparent safety at a dose of up to 5120 mg daily for up to 12 weeks (108047)....when flaxseed is used topically in a warm poultice (101946).
POSSIBLY UNSAFE ...when raw or unripe flaxseed is used orally. Raw flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin); however, these glycosides have not been detected after flaxseed is baked (5899). Unripe flaxseeds are also thought to be poisonous when consumed due to cyanide content.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Flaxseed can have mild estrogenic effects. Theoretically, this might adversely affect pregnancy (9592,12907); however, there is no reliable clinical evidence about the effects of flaxseed on pregnancy outcomes.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Hops extract and hops oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when hops extract and hops-derived bitter acids are used orally and appropriately for medicinal purposes, short-term. Hops extract has been used with apparent safety in doses of up to 300 mg daily for 2-3 months. Hops-derived bitter acids have been used with apparent safety at a dose of 35 mg daily for 3 months (12,55338,55370,102899,105953,107813).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in food amounts. The fruit is commonly used in foods (101151). There is insufficient reliable information available about the safety of Indian long pepper when used in medicinal amounts.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in medicinal amounts.
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. A standardized extract of maritime pine bark (Pycnogenol, Horphag Research) has been safely used in doses of 50-450 mg daily for up to one year (2435,2451,2462,2554,2556,7693,10214,10416,12012,14899) (15424,15521,15522,15523,15524,100359,105782). The same extract has also been used with apparent safety in a dose of 800 mg daily for 16 days (103617). A different standardized extract of maritime pine bark (Oligopin, DRT Group) has been used with apparent safety in doses of up to 150 mg daily for up to 12 weeks (105781,105783). ...when applied topically as a cream or powder. A standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 0.5% cream has been used for up to 7 days (50912). Powder from a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 100 mg has been applied to the skin daily for up to 6 weeks (50887,50896).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A standardized extract of maritime pine bark (Pycnogenol, Horphag Research), administered in a dose of 1 mg/lb body weight daily, has been safely used in a clinical study of children aged 6-18 years for up to 3 months (13120).
PREGNANCY: POSSIBLY SAFE
when used orally during the third trimester of pregnancy.
In one small clinical study, a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) has been used at a dose of 30 mg daily with apparent safety during the third trimester of pregnancy (15423). However, more evidence is needed; use cautiously or avoid using.
LACTATION:
There is insufficient reliable information available regarding the safety of maritime pine when used during lactation; avoid using.
POSSIBLY SAFE ...when neem bark extract is used orally and appropriately, short-term. Neem bark extract has been used safely in clinical research at doses up to 60 mg daily for up to 10 weeks (12822). ...when neem leaf and twig extract is used orally and appropriately, short-term. Neem leaf and twig extract has been used safely in clinical research at doses up to 500 mg twice daily for up to 12 weeks (104181). ...when neem leaf extract gel is used intraorally for up to 6 weeks (12824,64845,64850,94567). ...when neem oil, cream, or face wash is used topically on the skin for up to 2 weeks (64876,64878,64882,102867,107883).
POSSIBLY UNSAFE ...when neem or neem oil is used orally in large amounts or long-term. Preliminary clinical research suggests neem might be toxic to the kidneys or liver with high-dose or chronic use. Cardiac arrest has also been reported (12835,64870,64873).
CHILDREN: POSSIBLY SAFE
when neem extract is used topically.
It has been used with apparent safety as a shampoo, with one or two total applications (97928).
CHILDREN: LIKELY UNSAFE
when neem oil or seeds are used orally.
There are reports of infants who were severely poisoned and died after oral use of neem (3473,3474,3476,64855,64875).
PREGNANCY: LIKELY UNSAFE
when neem oil or leaf is used orally.
Neem oil and leaf have been used as abortifacients (12825,12835,64884,64889).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when processed shilajit is used orally and appropriately. Processed shilajit has been used with apparent safety in doses of 2 grams daily for 45 days or up to 500 mg daily for up to 48 weeks (112613,112614,112615,112616,112617,112618,112619,112621). There is insufficient reliable information available about the safety of crude or unprocessed shilajit when used orally or shilajit when used topically.
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of shilajit when used during pregnancy and lactation.
Below is general information about the interactions of the known ingredients contained in the product Professional Series Fem Adapt. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of aliskiren.
 Details
Pharmacokinetic research shows that coadministration of apple juice 200 mL along with aliskiren 150 mg decreases the bioavailability of aliskiren by 63% (17670). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046,94413). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).
|
Theoretically, consuming apple juice with antidiabetes drugs might interfere with blood glucose control.
Details
Clinical research suggests that consuming apples or drinking apple juice can raise blood glucose levels, with the effects of drinking apple juice being more significant than consuming apples (31699).
|
Consuming apple juice with antihypertensive drugs might interfere with blood pressure control.
Details
Some clinical evidence suggests that consuming apple and cherry juice can increase blood pressure in elderly patients (31680).
|
Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of atenolol.
Details
Pharmacokinetic research shows that coadministration of apple juice 600-1200 mL decreases levels of atenolol by 58% to 82% in a dose-dependent manner (17999). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).
|
Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of fexofenadine.
Details
Pharmacokinetic research shows that coadministration of apple juice 400-1200 mL along with fexofenadine 60-120 mg decreases bioavailability of fexofenadine by up to 78% (7046,94413). Coadministration with smaller quantities of apple juice (150 mL or less) does not appear to affect the bioavailability of fexofenadine (94421). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046,94413). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).
|
There is some concern that concomitant consumption of apple juice might decrease oral absorption and blood levels of lithium.
Details
In one case report, a patient had an undetectable serum lithium level when lithium citrate was administered with apple juice. When lithium was administered with an alternative beverage, the lithium level became detectable and the patient demonstrated clinical improvement (105342).
|
Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.
Details
Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (7046,17605). Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78% (7046,94413), aliskiren by 63% (17670), and atenolol by up to 82% (17999). These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).
|
Theoretically, asparagus racemosus root might increase diuresis and electrolyte loss when used with diuretic drugs.
Details
Animal studies show that asparagus racemosus root has diuretic effects when used in high doses (106417). This effect has not been reported in humans.
|
Theoretically, Asparagus racemosus root could reduce excretion and increase levels of lithium.
Details
Animal research suggests that Asparagus racemosus root has diuretic properties when used in high doses (106417). Therefore, it might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
|
Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
Details
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued (16725). It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.
|
Theoretically, black cohosh may reduce the clinical effects of cisplatin.
Details
Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells (13101).
|
Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Details
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme (13536). However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers (16848). Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.
|
Theoretically, black cohosh may alter the effects of estrogen therapy.
Details
|
Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
Details
|
Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
Details
In vitro research shows that black cohosh modestly inhibits OATP2B1 (35450). OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
|
Theoretically, antibiotics might interfere with the metabolism of flaxseed constituents, which could potentially alter the effects of flaxseed.
Details
Some potential benefits of flaxseed are thought to be due to its lignan content. Secoisolariciresinol diglucoside (SDG), a major lignan precursor, is found in high concentrations in flaxseed. SDG is converted by bacteria in the colon to the lignans enterolactone and enterodiol (5897,8022,8023,9592). Antibiotics alter the flora of the colon, which could theoretically alter the metabolism of flaxseed.
|
Theoretically, using flaxseed in combination with anticoagulant or antiplatelet drugs might have additive effects and increase the risk of bleeding.
Details
|
Theoretically, flaxseed might have additive effects when used with antidiabetes drugs and increase the risk for hypoglycemia.
Details
|
Theoretically, flaxseed might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
Details
|
Theoretically, taking flaxseed might decrease the effects of estrogens.
Details
Flaxseed contains lignans with mild estrogenic and possible antiestrogenic effects. The lignans seem to compete with circulating endogenous estrogen and might reduce estrogen binding to estrogen receptors, resulting in an anti-estrogen effect (8868,9593). It is unclear if this effect transfers to exogenously administered estrogens.
|
Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Details
|
Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
Details
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity (10686). However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate (105954).
|
Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Details
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity (55325). However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant (105954).
|
Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
Details
|
Theoretically, Indian long pepper might increase the effects and adverse effects of amoxicillin.
Details
Evidence from animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of amoxicillin when taken concomitantly (29269).
|
Theoretically, Indian long pepper might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Details
In vitro research shows that Indian long pepper extract inhibits platelet aggregation (101151).
|
Theoretically, Indian long pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
Animal research shows that piperine, a constituent of Indian long pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
|
Theoretically, Indian long pepper might increase blood levels of carbamazepine.
Details
A small pharmacokinetic study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that a single 20 mg dose of purified piperine, which is a constituent of Indian long pepper, increases carbamazepine levels. Piperine may increase absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or by cytochrome P450 3A4 (CYP3A4) inhibition in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of cefotaxime.
Details
Animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of cefotaxime when taken concomitantly (29269).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of cyclosporine.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, increases the bioavailability of cyclosporine (29282).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP1A1 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP1A1 (29213).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP2B1 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP2B1 (29332).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4 (14375).
|
Theoretically, Indian long pepper might increase blood levels of nevirapine.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases the plasma concentration and systemic exposure of nevirapine. However, no adverse effects were associated with the elevated plasma levels of nevirapine (29209).
|
Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
Details
|
Theoretically, Indian long pepper might increase the sedative effects of pentobarbital.
Details
Animal research shows that piperine, a constituent of Indian long pepper, can increase pentobarbitone-induced sleeping time (29214).
|
Theoretically, Indian long pepper might increase blood levels of phenytoin.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases phenytoin serum levels and slows its elimination (537).
|
Theoretically, Indian long pepper might increase blood levels of propranolol.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, accelerates absorption and increases serum concentrations of propranolol (538).
|
Theoretically, Indian long pepper might increase blood levels of rifampin.
Details
|
Indian long pepper might increase blood levels of theophylline.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases serum concentrations and slows elimination of theophylline (538).
|
Theoretically, licorice might reduce the effects of antihypertensive drugs.
Details
|
Theoretically, licorice might reduce the effects of cisplatin.
Details
In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
|
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).
|
Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that licorice induces CYP1A2 enzymes (111404).
|
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.
|
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.
|
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.
|
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.
|
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.
|
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).
|
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).
|
Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Details
|
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).
|
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.
|
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.
|
Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
Details
In vitro research shows that licorice can increase P-glycoprotein activity (104561).
|
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).
|
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.
|
Theoretically, maritime pine bark extract might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
|
Theoretically, maritime pine bark extract might increase the risk of hypoglycemia when used with antidiabetes drugs.
Details
One clinical study shows that maritime pine bark extract decreases blood sugar in patients with diabetes being treated with antidiabetes agents (15522). Monitor blood glucose levels closely. Dose adjustments might be necessary.
|
Theoretically, maritime pine bark extract might decrease the effectiveness of immunosuppressant therapy.
Details
|
Neem might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
|
Theoretically, neem leaf extract might increase the levels and clinical effects of CYP2C8 substrates.
Details
In vitro research shows that neem leaf methanol extract inhibits CYP2C8 enzymes (111593). So far, this reaction has not been reported in humans.
|
Theoretically, neem leaf extract might increase the levels and clinical effects of CYP2C9 substrates.
Details
In vitro research shows that neem leaf methanol extract inhibits CYP2C9 enzymes (111593). So far, this reaction has not been reported in humans.
|
Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that neem leaf methanol extract inhibits CYP3A4 enzymes (111593). So far, this reaction has not been reported in humans.
|
Theoretically, neem might decrease the effectiveness of immunosuppressants.
Details
Animal research suggests that neem might have immunostimulant effects (12825).
|
Theoretically, neem leaf extract might increase the levels and clinical effects of P-glycoprotein substrates.
Details
In vitro research shows that neem leaf methanol extract inhibits renal P-glycoprotein transport activity (107850). So far, this reaction has not been reported in humans.
|
Taking shilajit with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Most human and animal research shows that shilajit can decrease fasting plasma glucose levels (112621,112626,112627,112630,112638). In an animal model, shilajit 100 mg per kg daily enhanced the glucose-lowering ability of both glibenclamide and metformin when given in combination over a 4 week period (112638). Monitor blood glucose levels closely. Dose adjustments might be necessary.
|
Below is general information about the adverse effects of the known ingredients contained in the product Professional Series Fem Adapt. 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, apple fruit is well tolerated.
Apple seeds, which contain cyanide, may cause serious adverse effects when consumed in large amounts.
Most Common Adverse Effects:
Orally: Bloating, flatulence.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis. Ingestion of large amounts of apple seeds may cause cyanide poisoning, leading to death.
Gastrointestinal ...Orally, apple products, including whole apples, apple puree, and apple juice, may cause bloating and flatulence in some people (104184).
Immunologic ...Patients allergic to other fruits in the Rosaceae family, including apricot, almond, plum, peach, pear, and strawberry, can also be allergic to apples (7129). Rarely, the allergy has resulted in anaphylaxis (94425).
Other ...Orally, ingestion of large amounts of apple seeds, which contain hydrogen cyanide (HCN), may cause cyanide poisoning, leading to death. One death is attributed to ingestion of a cupful of apple seeds. To release cyanide, seeds must be hydrolyzed in the stomach, and several hours may elapse before poisoning symptoms occur (6).
General ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, black cohosh is generally well tolerated when used in typical doses.
Most Common Adverse Effects:
Orally: Breast tenderness, dizziness, gastrointestinal upset, headache, irritability, rash, tiredness.
Serious Adverse Effects (Rare):
Orally: Endometrial hyperplasia and hepatotoxicity, although data are conflicting for both.
Cardiovascular
...A single case of reversible bradycardia has been reported for a 59-year-old female who took one tablet of a specific black cohosh product (Remifemin, Schaper & Brümmer) daily for 2 weeks.
The adverse event was considered probably related to black cohosh use, although the exact mechanism by which black cohosh exerted this effect was unclear (35920).
There has been concern that, if black cohosh has estrogen-like effects, it could also potentially cause estrogen-like side effects including increased risk for thromboembolism and cardiovascular disease. These outcomes have not been specifically assessed in long-term trials; however, some research shows that a specific black cohosh extract (CimiPure, PureWorld) does not significantly affect surrogate markers for thromboembolism and cardiovascular risk such as fibrinogen, cholesterol, triglycerides, glucose, or insulin levels compared to placebo (16850).
Dermatologic ...Black cohosh has been associated with skin irritation and rashes (7054,10987,14330,15889,35853). A case report describes a patient who developed cutaneous pseudolymphoma 6 months after starting a specific black cohosh extract (Remifemin). Symptoms resolved within 12 weeks of discontinuing black cohosh (15890).
Gastrointestinal ...Orally, black cohosh can commonly cause gastrointestinal upset (4383,4615,4616,10988,13184,35824,35853,35965,103269,111714). Constipation and indigestion have also been reported (7054,35852).
Genitourinary
...Orally, black cohosh, including the specific black cohosh product Remifemin, may cause vaginal bleeding and breast tenderness in some postmenopausal patients (15889,35824).
However, the frequency of these events seems to be less than that of tibolone, a prescription hormone medication used to treat symptoms of menopause (15889,35904).
Due to the potential estrogen-like effects, there is concern that black cohosh might increase the risk of endometrial hyperplasia. However, a specific black cohosh extract CR BNO 1055 (Klimadynon/Menofem, Bionorica AG) does not appear to cause endometrial hyperplasia. Clinical research in postmenopausal adults shows that taking 40 mg daily of this extract for 12 weeks does not significantly increase superficial cells when compared with placebo, and causes significantly fewer superficial cells when compared with conjugated estrogens (Premarin) (14330). Additional clinical research shows that taking 40 mg daily of this extract for a year does not increase the risk of endometrial hyperplasia or endometrial thickening in postmenopausal adults (15036). Another specific combination product containing black cohosh extract plus St. John's wort (Gynoplus, Jin-Yang Pharm) also does not significantly increase superficial cells compared to placebo after 12 weeks of treatment (15893). Some patients taking tamoxifen plus black cohosh have experienced endometrial hyperplasia and vaginal bleeding. However, these effects are more likely due to tamoxifen than black cohosh (7054).
Hepatic
...There is concern that black cohosh might cause liver disease, hepatotoxicity, or hepatitis.
Adverse effects on the liver have not been documented in clinical studies. However, multiple case reports of liver toxicity, hepatitis, and abnormal liver function have been described in females taking black cohosh products alone or in combination with other herbs or drugs. In some cases, patients developed liver failure and required immediate liver transplantation (4383,10692,11909,12006,13144,14469,15160,16721,16722,16723) (16724,16727,35883,35888,35890,35895,89465,101592,107906). In one case, a female developed autoimmune hepatitis after 3 weeks of taking black cohosh. Symptoms resolved 2 weeks after discontinuing black cohosh (11906). In at least three cases, females have developed elevated liver enzymes and symptoms of hepatotoxicity after taking black cohosh products. Symptoms resolved and liver enzymes normalized within a week of discontinuing black cohosh (16725,16726). Analysis of two liver biopsies suggests that hepatotoxicity associated with black cohosh use results from the accumulation of 4HNE protein adducts in the cytoplasm of liver cells, which promotes the migration of lymphocytes to the affected area and induces an autoimmune response leading to troxis necrosis (89469).
However, many of these cases are poorly documented. Causality is possible based on some reports; however, other reports do not indicate that black cohosh is the probable cause of the events (15891,15892,16722,16723,16727,89465). Hepatitis can occur with no identifiable cause, raising the possibility that black cohosh and hepatitis might have been coincidental in some cases. Also, plant misidentification can occur, resulting in accidental substitution of a hepatotoxic plant (11910). Therefore, some experts argue that these cases do not provide conclusive evidence that black cohosh is responsible for liver disease (17085,35882,111634). Nonetheless, some countries require cautionary labeling on black cohosh products suggesting a risk of liver toxicity. The United States Pharmacopeia also recommends cautionary labeling on black cohosh products (16722). Until more is known about this potential risk, consider monitoring liver function in patients who take black cohosh.
Musculoskeletal
...One patient treated with black cohosh in a clinical trial discontinued treatment due to edema and arthralgia (35897).
Black cohosh has been linked to asthenia and muscle damage in one case. A 54-year-old female experienced asthenia with elevated creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels while taking black cohosh. The patient had taken a specific black cohosh extract (Remifemin) for 1 year, discontinued it for 2 months, restarted it, and then experienced symptoms 2 months later. Symptoms began to resolve 10 days after discontinuing black cohosh (14299).
Neurologic/CNS
...Orally, black cohosh may cause headache, dizziness, or tiredness (35852,35886).
There is one case report of seizures in a female who used black cohosh, evening primrose oil, and chasteberry (10988).
Also, there has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
In another case report, orobuccolingual dyskinesia, including tongue-biting, eating difficulties, and speech problems, was reported in a 46-year-old female who took two tablets containing black cohosh 20 mg and Panax ginseng 50 mg daily for 15 months. The patient's condition improved after stopping treatment with the herbs and taking clonazepam 2 mg daily with baclofen 40 mg daily (89735).
Ocular/Otic ...There is some concern that black cohosh might increase the risk of retinal vein thrombosis due to its estrogenic activity. In one case, a patient with protein S deficiency and systemic lupus erythematosus (SLE) experienced retinal vein thrombosis 3 days after taking a combination product containing black cohosh 250 mg, red clover 250 mg, dong quai 100 mg, and wild yam 276 mg (13155). It is unclear if this event was due to black cohosh, other ingredients, the combination, or another factor.
Oncologic ...There is some concern that black cohosh may affect hormone-sensitive cancers, such as some types of breast or uterine cancer, due to its potential estrogenic effects. However, evidence from a cohort study suggests that regular use of black cohosh is not associated with the risk of breast or endometrial cancer (17412,111634).
Psychiatric ...A 36-year-old female with a 15-year history of depression developed mania with psychotic and mixed features after taking a black cohosh extract 40 mg daily. The patient gradually recovered after stopping black cohosh and receiving treatment with antipsychotics (104517).
Pulmonary/Respiratory ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Renal ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Other ...While rare, weight gain has been reported in some patients taking black cohosh. However, in most cases the causality could not be established. A review of the literature, including published case reports, spontaneous reports to adverse event databases, and clinical trials, suggests that black cohosh does not cause weight gain (107907).
General
...Orally, flaxseed is usually well-tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal complaints.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions such as and anaphylaxis.
Gastrointestinal
...Integrating flaxseed in the diet can cause digestive symptoms similar to other sources of dietary fiber including bloating, fullness, flatulence, abdominal pain, diarrhea, constipation, dyspepsia, and nausea (12910,16761,16765,21198,21200,22176,22179,65866,101943).
Higher doses are likely to cause more gastrointestinal side effects. Flaxseed can significantly increase the number of bowel movements and the risk for diarrhea (6803,8021,16765). Doses greater than 45 grams per day may not be tolerated for this reason (6802). Metallic aftertaste and bowel habit deterioration have also been reported in a clinical trial (21198).
There is some concern that taking large amounts of flaxseed could result in bowel obstruction due to the bulk forming laxative effects of flaxseed. Bowel obstruction occurred in one patient in a clinical trial (65866). However, this is not likely to occur if flaxseed is consumed with an adequate amount of fluids.
Immunologic ...Occasionally, allergic and anaphylactic reactions have been reported after ingestion of flaxseed (16761). Handling and processing flaxseed products might increase the risk of developing a positive antigen test to flaxseed and hypersensitivity (6809,12911,26471,26482).
Oncologic ...Flaxseed contains alpha-linolenic acid (ALA). High dietary intake of ALA has been associated with increased risk for prostate cancer (1337,2558,7823,7147,12978). However, ALA from plant sources, such as flaxseed, does not seem to increase this risk (12909).
Other ...Orally, partially defatted flaxseed, which is flaxseed with less alpha-linolenic acid, might increase triglyceride levels (6808). Raw or unripe flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin). These chemicals can increase blood levels and urinary excretion of thiocyanate in humans. However, these glycosides have not been detected after flaxseed is baked (5899).
General
...Orally, hops extract and oil are generally well tolerated when used in food amounts.
Hops extract also seems to be well tolerated when used in supplemental amounts.
Most Common Adverse Effects:
Orally: Drowsiness, sedation.
Dermatologic ...Topically, allergic reactions have been reported after contact with the fresh hops plant and plant dust. Contact dermatitis is attributed to the pollen (4,12,105930).
Genitourinary ...Orally, supplements containing hops and soy have been associated with 4 cases of postmenopausal bleeding (55404). It is unclear if this effect is due to hops, soy, or the combination. Also, menstrual disturbances have been reported in female workers harvesting hops (10684,55405).
Neurologic/CNS ...Orally, hops might cause drowsiness and sedation. Historically, hops are thought to have sedative effects, since workers harvesting hops were observed to tire easily after oral contact with hop resin. The European Medicines Agency states that hops may have sedative effects; however, there is a lack of clinical research confirming that hops extract causes drowsiness and sedation (105930).
Pulmonary/Respiratory ...Occupational exposure to dust from hops, usually in combination with dust from other products, is associated with chronic respiratory symptoms such as dry cough, dyspnea, chronic bronchitis, and other occupational respiratory diseases (55333,55414).
General ...Orally, Indian long pepper is well tolerated when used in food (101151). No adverse effects have been reported when Indian long pepper is used as medicine. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, licorice is generally well tolerated when used in amounts commonly found in foods.
It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.
Cardiovascular
...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest.
These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).
Dermatologic
...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912).
There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).
Endocrine
...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234).
These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).
Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).
Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).
Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).
Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).
Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).
Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).
General
...Orally and topically, maritime pine bark extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal complaints, dizziness, and vertigo.
Cardiovascular ...A single case of chest pain has been reported for a patient treated with a standardized extract of maritime pine bark (Pycnogenol, Horphag Research). However, the patient had a history of myocardial infarction (50905). Another patient taking the same maritime pine bark extract experienced acute decompensation of heart failure. The patient previously has stable coronary artery disease (50929). It is not clear if either of these adverse effects were directly related to maritime pine bark extract.
Gastrointestinal ...Orally, a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) may cause gastrointestinal problems (15521,15522,17300,50891,50942). Also, mouth ulcer and bad breath have been reported in a single trial (15521).
Neurologic/CNS ...Orally, a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) may cause dizziness and severe vertigo (15521,15522,17300,50904,50933). Also, headache has been reported in a single trial (15521).
General
...Orally, neem extracts seem to be well tolerated in adults.
However, high-quality assessment of safety has not been conducted. In children, oral use of neem oil can cause serious adverse effects. Topically, neem seems to be well tolerated in children and adults.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Cardiac arrest, nephrotoxicity, and ventricular fibrillation with neem leaf in adults. Encephalopathy, hematologic abnormalities, hepatotoxicity, and nephrotoxicity with neem oil in infants and young children.
Cardiovascular ...Orally, neem leaf has been reported to cause ventricular fibrillation and cardiac arrest after ingestion in humans (64873,64870).
Dental ...Topically, use of neem twigs to brush teeth, which is a traditional dental hygiene practice in India, has been associated with vitiligo of the lips. The limonoid constituents in neem, which have been shown to inhibit melanogenesis and have cytotoxic effects, combined with repeated, local trauma from this dental hygiene practice are thought to cause this leucodermic reaction. In a case series of seven patients experiencing vitiligo of the lips from neem twigs, use of toothpaste and topical tacrolimus along with avoidance of neem stopped the progression of depigmentation in all patients. Repigmentation was reported in four of the seven patients 12 months after discontinuing neem-based dental hygiene practices (100958).
Dermatologic ...Topically, neem products have been associated with dermatologic reactions. Some case reports have associated the use of topical neem oil with contact dermatitis (64851,94568,102867). In one case series, the topical application of neem seed extract shampoo was associated with skin irritation, red spots, and a burning feeling of the scalp (64848). Use of neem twigs to brush teeth, which is a traditional dental hygiene practice in India, has been associated with vitiligo of the lips. The limonoid constituents in neem, which have been shown to inhibit melanogenesis and have cytotoxic effects, combined with repeated, local trauma from this dental hygiene practice are thought to cause this leucodermic reaction. In a case series of seven patients experiencing vitiligo of the lips from neem twigs, use of toothpaste and topical tacrolimus along with avoidance of neem stopped the progression of depigmentation in all patients. Repigmentation was reported in four of the seven patients 12 months after discontinuing neem-based dental hygiene practices (100958).
Gastrointestinal ...Orally, neem oil has been reported to cause vomiting and loose stools in infants and small children (3473,3474,3476,64865).
Genitourinary ...Orally, neem leaf has been reported to cause oliguria and anuria in adults (12833,12834). After a single intrauterine instillation, purified neem oil has been reported to cause endometritis in healthy, tubectomised females (64886).
Hematologic
...Orally, neem leaf has been reported to cause hemolysis in adults (12835).
In one case report, a 35-year-old male with diabetes and glucose-6-phosphate dehydrogenase (G6PD) deficiency developed hemolytic anemia and jaundice after drinking several liters of neem tea daily for 3 weeks. All symptoms resolved after discontinuation and supportive treatment (94571). Orally, neem oil has been reported to cause metabolic acidosis, anemia, and polymorphonuclear leukocytosis in infants and young children (3473,3474,3476,64865).
A single intrauterine instillation of purified neem oil has been reported to cause mild transient eosinophilia in healthy, tubectomised females (64886).
Hepatic ...Orally, neem oil has been associated with reports of hepatotoxicity in infants and children. These adverse effects occurred after single doses of neem oil ranging from a few drops to 60 mL. Pathologic findings on liver biopsy reports have been consistent with Reye-like syndrome (3473,3474,3475).
Immunologic ...Topically, a case of aggravated bullous pemphigoid requiring hospitalization is reported in a 47-year-old patient with this autoimmune condition after application of neem oil to blisters for an unknown duration (111715).
Neurologic/CNS ...Orally, single doses of neem oil ranging from a few drops to 60 mL have been associated with reports of encephalopathy in infants and small children. Symptoms include drowsiness, seizure, loss of consciousness, coma, cerebral edema, Reye-like syndrome, and death within hours of ingestion (3473,3474,3476,3476,64855,94750). There is also at least one case report of neurotoxicity in an adult after ingestion of a neem-based pesticide. A 35-year-old female experienced neurotoxicity requiring intensive medical care and ventilation after ingestion of a pesticide containing azadirachtin, a constituent of neem oil (64858).
Ocular/Otic ...In one case report, a 35-year-old female developed toxic optic neuropathy and vision loss in both eyes lasting for two days after consuming 150 mL of neem oil in a suicide attempt five days earlier (64856).
Renal ...Orally, neem leaf has been reported to cause oliguria, anuria, acute tubular necrosis, and nephrotoxicity in adults (12833,12834). There are some case reports of children developing Reye-like syndrome after ingestion of neem oil. Pathologic findings on renal biopsy reports have been consistent with Reye syndrome (3473,3474,3475).
General
...Orally, processed shilajit 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 has raised concerns about pseudohyperaldosteronism.
Cardiovascular ...Orally, a case of hypertension related to mineralocorticoid-excess syndrome or pseudohyperaldosteronism is reported in a 37-year-old female following the use of shilajit for 6 months during pregnancy. Electrocardiographic findings were normal. Product discontinuation and treatment with intravenous and oral potassium led to restoration of blood pressure and potassium levels (112622). The role of shilajit in this adverse effect cannot be confirmed. The presence of other ingredients or contaminants in the product was not ruled out.
Endocrine ...Orally, a case of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with edema, increased urinary potassium, calcium, and magnesium loss, hypokalemia, and metabolic alkalosis, is reported in a 37-year-old female following the use of shilajit for 6 months during pregnancy. Product discontinuation and treatment with intravenous and oral potassium led to restoration of potassium levels (112622). The role of shilajit in this adverse effect cannot be confirmed. The presence of other ingredients or contaminants in the product was not ruled out.
Immunologic ...Orally, a case of allergy to shilajit made worse by exercise is reported in a 43-year-old female. Although symptoms were lacking when shilajit 400 mg was taken daily with meals for 3 months, she developed hives within an hour of taking a single dose of shilajit 800 mg. With intramuscular corticosteroids, symptoms improved but did not resolve. The next day, following a meal and physical activity she developed anaphylaxis requiring adrenaline and intravenous corticosteroids (112620).
Neurologic/CNS ...Orally, headache is reported rarely following shilajit intake in clinical research (112616).
