Proprietary Blend 1.90 g: Maca 4:1 root extract (Lepidium meyenii), Muira Puama 5:1 root extract (Ptychopetalum olacoides), Wild Oats 10:1 extract (Avena sativa), Kava Kava standardized root extract (Piper methsyticum), Dong Quai standardized extract (Angelica sinensis), Damiana 4:1 leaf extract (Turnera diffusa), Korean Ginseng (seed powder). Other Ingredients: Gelatin, Cellulose, Magnesium stearate, 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 StimuMax for Women. 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
Below is general information about the safety of the known ingredients contained in the product StimuMax for Women. 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 amounts commonly found in foods. Damiana has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12,46933,11866).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).
POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).
LACTATION:
Insufficient reliable information available; avoid use.
POSSIBLY SAFE ...when used orally, short-term. Kava extracts have been used safely in clinical trials under medical supervision for up to 6 months (2093,2094,2095,4032,7325,15046,15130,18314,18316,18318)(18320,29663,29671,98980,102086,112642). Historically, there has been some concern that kava preparations could induce hepatotoxicity and liver failure in patients taking relatively normal doses, short-term. At least 100 cases of liver toxicity following kava use have been reported. Although liver toxicity is more frequently associated with prolonged use of very high doses (6401,57346), in some cases the use of kava for as little as 1-3 months has been associated with the need for liver transplants, and even death (390,7024,7068,7086,7096,17086,57252)(57254,57297). However, some experts question the clinical validity of several of these cases (11369,11371).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
There is some concern that pyrone constituents in kava can cause loss of uterine tone (19); avoid using.
LACTATION: POSSIBLY UNSAFE
when used orally.
There is concern that the toxic pyrone constituents of kava can pass into breast milk (19); avoid using.
LIKELY SAFE ...when maca is consumed in food amounts (9926).
POSSIBLY SAFE ...when used orally and appropriately, short term. Maca appears to be safe in doses up to 3 grams daily for 4 months (9928,10218,18289,90278,108603).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Taking muira puama 500-1050 mg daily, as part of a combination product, has been used with apparent safety for 1 month (63920,103224). There is insufficient reliable information available about the safety of muira puama when used long-term.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately in food amounts (4960,4969,5792,5797). Oat bran has Generally Recognized as Safe (GRAS) status in the US (4912). Whole grain oats 50-100 grams daily have been used for up to 1 year without serious adverse effects (97520).
POSSIBLY SAFE ...when used topically and appropriately (12). Lotion containing colloidal oat 1% has been used topically without adverse effects for up to 6 weeks (97518,103340). There is insufficient reliable information available about the safety of oats when used orally in medicinal amounts.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (5792,5797).
LIKELY SAFE ...when used orally and appropriately, short-term. Panax ginseng seems to be safe when used for up to 6 months (8813,8814,17736,89741,89743,89745,89746,89747,89748,103044,103477).
POSSIBLY UNSAFE ...when used orally, long-term. There is some concern about the long-term safety due to potential hormone-like effects, which might cause adverse effects with prolonged use (12537). Tell patients to limit continuous use to less than 6 months. There is insufficient reliable information available about the safety of Panax ginseng when used topically.
CHILDREN: LIKELY UNSAFE
when used orally in infants.
Use of Panax ginseng in newborns is associated with intoxication that can lead to death (12). There is limited reliable information available about use in older children (24109,103049); avoid using.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Ginsenoside Rb1, an active constituent of Panax ginseng, has teratogenic effects in animal models (10447,24106,24107); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product StimuMax for Women. 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, damiana may lower blood glucose levels (4,25016). This might increase the risk of hypoglycemia in patients taking antidiabetes drugs.
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Some antidiabetes drugs include glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTabs, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), rosiglitazone (Avandia), and others.
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Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
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Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.
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Theoretically, dong quai may reduce the effects of estrogens.
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Dong quai may increase the risk of bleeding when used with warfarin.
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Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).
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Combining kava with alcohol may increase the risk of sedation and/or hepatotoxicity.
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Kava has CNS depressant effects (11373,18316). Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression (2093,2098). Additionally, kava has been associated with over 100 cases of hepatotoxicity. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs (7024,7068,7086,7096,17086,57346). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that alcohol not be used with kava (110318). |
Combining kava with CNS depressants can have additive sedative effects.
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Kava has CNS depressant effects (11373,18316). Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression (2093,2098). Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that CNS depressants, including alcohol and benzodiazepines, not be used with kava (110318).
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It is unclear if kava inhibits CYP1A2; research is conflicting.
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Although in vitro research and a case report suggest that kava inhibits CYP1A2 (8743,12479,88593), more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity (13536,98979).
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Theoretically, kava might increase levels of CYP2C19 substrates.
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Theoretically, kava might increase levels of CYP2C9 substrates.
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It is unclear if kava inhibits CYP1A2; research is conflicting.
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Kava might increase levels of CYP2E1 substrates.
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In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days inhibited the metabolism of CYP2E1 substrates (13536).
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It is unclear if kava inhibits CYP3AA; research is conflicting.
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Although in vitro research suggests that kava inhibits CYP3A4 (8743,12479), more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity (13536,98979).
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Combining kava and haloperidol might increase the risk of cardiovascular adverse effects and hypoxia.
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Atrial flutter and hypoxia has been reported for a patient who received intramuscular injections of haloperidol and lorazepam after using kava orally. The side effects were attributed to kava-induced inhibition of CYP2D6, but might also have been related to additive adverse effects with the concomitant use of haloperidol, lorazepam, and kava (88593).
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Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.
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It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.
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In vitro research shows that kava can inhibit P-gp efflux (15131). However, a clinical study in healthy volunteers shows that taking kava standardized to provide 225 mg kavalactones daily for 14 days does not affect the pharmacokinetics of digoxin, a P-gp substrate (15132,98979). It is possible that the use of other P-gp substrates or higher doses of kava might still inhibit P-gp.
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Taking kava with ropinirole might increase the risk for dopaminergic toxicity.
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A case of visual hallucinations and paranoid delusions has been reported for a patient who used kava in combination with ropinirole. The adverse effects were attributed to kava-induced inhibition of CYP1A2, which may have reduced the metabolism of ropinirole, resulting in excessive dopaminergic stimulation (88593).
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Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.
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Concomitant use of oats and insulin might increase the risk of hypoglycemia.
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In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).
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Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation (1522,11891). However, research in humans suggests that ginseng does not affect platelet aggregation (11890). Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research (11153). Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.
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Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
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Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Monitor blood glucose levels closely.
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Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
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Theoretically, Panax ginseng might decrease levels of drugs metabolized by CYP1A1.
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In vitro research shows that Panax ginseng can induce the CYP1A1 enzyme (24104).
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Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
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There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6% (1303,51331). In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount (103478). However, contradictory research suggests Panax ginseng might not inhibit CYP2D6 (10847). Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
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Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity (89764). In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4 (89734,103478). Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478). Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.
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Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
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Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
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Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein (24101).
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Theoretically, Panax ginseng might reduce the effects of furosemide.
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There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product (770).
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Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
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A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism (89764).
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Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
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Panax ginseng might have immune system stimulating properties (3122).
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Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
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Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.
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Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
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Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans (89734,89764). However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers (93578).
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Theoretically, Panax ginseng may increase the clearance of midazolam.
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Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478).
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Theoretically, Panax ginseng can interfere with MAOI therapy.
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Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
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Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers (22423). This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.
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Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
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Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
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A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels (23621).
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Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
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Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability (103053). More research is needed to confirm these effects.
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Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
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Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
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There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng (619). However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin (2531,11890,17204,24105). However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer (15176). More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.
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Below is general information about the adverse effects of the known ingredients contained in the product StimuMax for Women. 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, damiana is generally well tolerated. In a rare case, 200 grams of damiana extract has caused tetanus-like convulsions and paroxysms resulting in symptoms similar to rabies or strychnine poisoning (4).
Neurologic/CNS ...Orally, 200 grams of damiana extract has caused tetanus-like convulsions and paroxysms resulting in symptoms similar to rabies or strychnine poisoning (4).
General
...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.
Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).
Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).
Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).
Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).
Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.
Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).
Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).
Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).
General
...Orally, kava seems to be well tolerated.
Most Common Adverse Effects:
Orally: Drowsiness, dry mouth, dizziness, gastrointestinal upset, headache, memory problems, tremor.
Serious Adverse Effects (Rare):
Orally: There have been over 100 reported cases of hepatotoxicity and a few reported cases of rhabdomyolysis.
Cardiovascular ...Long-term use of very large amounts of kava, especially in high doses (400 mg kava pyrones daily), has been associated with overall poor health including symptoms of low body weight, reduced protein levels, puffy face, hematuria, increased red blood cell volume, decreased platelets and lymphocytes, and possibly pulmonary hypertension (4032,6402). Tachycardia and electrocardiogram (ECG) abnormalities (tall P waves) have been reported in heavy kava users (6402).
Dermatologic ...Orally, kava can cause allergic skin reactions, including sebotropic eruptions, delayed-type hypersensitivity, or urticarial eruption (4032,11370,28489,57277,57325,57343). Chronic use of high doses of kava has also been associated with kava dermopathy, which consists of reddened eyes; dry, scaly, flaky skin; and temporary yellow discoloration of the skin, hair, and nails (6240,6401,8414,8417,11370,28485,57342). This pellagra-like syndrome is unresponsive to niacinamide treatment (6240,7728,11370). The cause is unknown, but may relate to interference with cholesterol metabolism (6240). Kava's adverse effects on liver function might also contribute to kava dermopathy (6401,8417). Kava dermopathy usually occurs within three months to one year of regular kava use, and resolves when the kava dose is decreased or discontinued (6401,8414). Kava dose should be decreased or discontinued if kava dermopathy occurs (6401).
Gastrointestinal ...Orally, kava may cause gastrointestinal upset, nausea, or dry mouth (2093,2094,4032,11370,18316,57228,57343).
Hematologic ...Orally, chronic use of very high doses of kava has been associated with increased red blood cell volume, reduced platelet volume, reduced lymphocyte counts, and reduced serum albumin (6402,57258). Hematuria has also been reported anecdotally (6402).
Hepatic
...Since the early 2000's, hepatotoxicity has been a particular concern with kava.
Worldwide, there have been at least 100 reported cases of hepatotoxicity following use of kava products (7024,7068,7086,7096,11795,17086)(57252,57254,57297). However, some experts question the clinical validity of several of these cases (11369,11371). Some cases were reported multiple times and in some cases it was unlikely that kava was the causative agent (7068,57253).
In susceptible patients, symptoms can show up after as little as 3-4 weeks of kava use. Symptoms include yellowed skin (jaundice), fatigue, and dark urine (7024,7068). Liver function tests can be elevated after 3-8 weeks of use, possibly followed by hepatomegaly and onset of encephalopathy (7024). Kava has also been reported to exacerbate hepatitis in patients with a history of recurrent hepatitis (390). However, in many cases, symptoms seem to resolve spontaneously, and liver function tests usually normalize within eight weeks (390,7068).
Liver toxicity is more frequently associated with prolonged use of very high doses (6401,57346). But there is some concern that even short-term use of kava in typical doses might cause acute hepatitis in some patients, including severe hepatocellular necrosis. The use of kava for as little as 1-3 months has resulted in need for liver transplant and death, although these events are rare (7024,7068,7086,7096,17086).
There is some speculation that the type of extraction method could be responsible for these rare cases of hepatotoxicity (17086). The "Pacific kava paradox" holds that while the alcohol and acetone extracts of kava used for commercial products cause liver toxicity, the traditional kava rhizome preparation mixed with water might not be toxic (11794,17086). However, a more recent analysis reports cases of hepatotoxicity from the aqueous kava extract and suggests that kava's hepatotoxic effects may be due to contaminants such as mold (29676). Other suggested causes of hepatotoxicity include quality of the kava plant, concomitant medications, large doses and prolonged use, and toxic constituents and metabolites of kava (57300,88532).
Some commercial kava extracts contain parts of the stems and other aerial parts in addition to the rhizome, and it has been suggested that a constituent called pipermethysine, which is only found in these aerial parts, might be partly responsible for hepatotoxicity (17086). Other constituents of kava which might contribute to hepatotoxicity are kavalactones, which are metabolized by cytochrome P450 (CYP450) enzymes in the liver. Reactive metabolites are produced which conjugate with glutathione, and might deplete glutathione in a similar manner to acetaminophen (17086). Increased levels of gamma-glutamyl transferase, involved in the production of glutathione, have been reported in chronic kava users (17086). One of the enzymes involved in production of reactive metabolites from kavalactones is cytochrome P450 2E1 (CYP2E1), which is induced by chronic alcohol intake. Alcohol may also compete for other enzymes which clear kavalactone metabolites from the body. This might explain the observation that alcohol ingestion seems to increase the risk of hepatotoxicity with kava (7068,17086).
There is also speculation that "poor metabolizers" or those patients with deficiency in the cytochrome P450 2D6 (CYP2D6) isoenzyme, which occurs in up to 10% of people of European descent, may be at increased risk for hepatotoxic effects from kava (7068). This deficiency has not been found in Pacific Islanders. However, this theory has not been confirmed.
Due to the concerns regarding the potential hepatotoxicity of kava, kava supplements were withdrawn from European and Canadian markets in 2002 (7086). However, many of the market withdrawals of kava have been lifted after re-evaluation of kava suggested that the risk of hepatotoxicity was minimal (91593,91594,91615). Still, clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend exercising caution when using kava in patients with preexisting liver issues (110318). Until more is known, tell patients to use kava cautiously and recommend liver function tests for routine users or those with underlying liver disease.
Immunologic ...Sjögren syndrome has been associated with an herbal supplement containing kava, echinacea, and St. John's wort. Echinacea may have been the primary cause, because Sjögren syndrome is an autoimmune disorder. The role of kava in this syndrome is unclear (10319).
Musculoskeletal
...Kava has been linked with reports of rhabdomyolysis.
A 34-year-old man who consumed kava tea several times a week developed rhabdomyolysis with a peak creatine kinase level of 32,500 units/liter (18212). However, there is speculation that this might have been due to product impurities rather than kava itself. Another case report describes rhabdomyolysis with myoglobinuria and a creatine kinase level of 100,500 units/liter in a 29-year-old man who had taken kava in combination with guarana and ginkgo biloba (18213).
Cases of ataxia and tremors have been reported in patients taking single doses of kava powder 205 grams (11373).
Neurologic/CNS
...Orally, kava may cause headache, dizziness, and drowsiness (4032,6402,11370,11372,11373,18316,112642).
It might also cause extrapyramidal side effects such as involuntary oral and lingual reflexes, twisting movements of the head and trunk, tremors, and other parkinsonian-like symptoms possibly due to dopamine antagonism (534,4055,7727,8415,102086). In one clinical trial, patients taking a kava supplement providing 120 mg of kavalactones twice daily for 16 weeks had a 3.2-fold greater risk of experiencing tremors when compared with patients taking placebo (102086). Theoretically, kava may worsen symptoms in patients with Parkinson disease or precipitate Parkinson-like symptoms in certain patients (4055,7727). Unlike benzodiazepines, kava is not thought to be associated with impaired cognitive function (2097,2098,11373,57332,57333). However, one clinical trial shows that taking a kava supplement providing 120 mg of kavalactones twice daily for 16 weeks increases the risk for memory impairment by 55% when compared with placebo (102086).
Orally, kava may reduce alertness and impair motor coordination in a dose-dependent manner. Some preliminary reports have noted a decline in accuracy of visual attention and slower reaction times after kava ingestion, particularly at higher doses and in combination with alcohol (11373,95926). Population research has also found that ingesting large amounts of kava tea (typically 50 times higher than what is used medicinally in the US) within a 12-hour period before driving increases the odds of being involved in a serious motor vehicle crash resulting in death or serious injury by almost 5-fold when compared to not drinking kava tea (95927). Use of normal doses of kava may also affect the ability to drive or operate machinery, and driving under the influence (DUI) citations have been issued to individuals observed driving erratically after drinking large amounts of kava tea (535). However, in computer-based driving simulator tests, there are no reported adverse effects of kava on performance (95926). Additionally, other research shows that consuming over 4400 mg of kavalactones over a 6-hour kava session does not seem to impair alertness or attention when compared with non-kava drinkers (103867). Similar research using a specific psychometric tool (Brain Gauge) shows that consuming approximately 3680 mg of kavalactones in a 6-hour kava session seems to impair temporal order judgment, which is associated with the brain's ability to track the order of events, when compared with non-kava drinkers. However, it does not seem to impact cognitive domains related to focus, accuracy, timing perception, plasticity, or fatigue when compared with non-kava drinkers (110435).
Ocular/Otic ...Orally, high doses of kava may cause eye irritation (7728). There is one case report of impaired accommodation and convergence, increased pupil diameter, and oculomotor disturbance following a single dose of kava (9920).
Psychiatric ...Apathy has been associated with traditional use of kava at high doses (57313).
Pulmonary/Respiratory ...Orally, kava may cause shortness of breath, possibly due to pulmonary hypertension (6402).
Renal ...Orally, kava may cause acute urinary retention (57349).
General ...Orally, no adverse effects have been reported with the medicinal use of maca. However, a thorough evaluation of safety outcomes has not been conducted.
Gastrointestinal ...Consumption of fresh, uncooked maca may cause stomach pain (40231).
General ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, oats are well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, bloating, flatulence, and unpleasant taste.
Topically: Burning, contact dermatitis, itching, and redness.
Dermatologic ...Topically, oat-containing preparations can cause contact dermatitis (12515). Redness, burning, and itchiness have also been reported (103340).
Gastrointestinal
...When consumed orally, oats provide fiber.
Increasing fiber in the diet can cause flatulence, bloating, abdominal distention, and unpleasant taste. To minimize side effects, doses should be slowly titrated to the desired level. These adverse effects usually subside with continued use (12514).
In patients who have difficulty chewing food, or those with conditions that decrease small bowel motility, oat bran may cause bezoars (concretions) and intestinal obstruction. Oats and oat bran are unlikely to cause obstruction without other causative factors (4979,4985).
General
...Orally, Panax ginseng is generally well tolerated when used for up to 6 months.
There is some concern about the long-term safety due to potential hormone-like effects.
Topically, no adverse effects have been reported when ginseng is used as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Insomnia.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, arrhythmia, ischemia, Stevens-Johnson syndrome.
Cardiovascular ...Panax ginseng may cause hypertension, hypotension, and edema when used orally in high doses, long-term (3353). However, single doses of Panax ginseng up to 800 mg are not associated with changes in electrocardiogram (ECG) parameters or increases in heart rate or blood pressure (96218). There is a case report of menometrorrhagia and tachyarrhythmia in a 39-year-old female who took Panax ginseng 1000-1500 mg/day orally and also applied a facial cream topically that contained Panax ginseng. Upon evaluation for menometrorrhagia, the patient also reported a history of palpitations. It was discovered that she had sinus tachycardia on ECG. However, the patient was a habitual consumer of coffee 4-6 cups/day and at the time of evaluation was also mildly anemic. The patient was advised to discontinue taking Panax ginseng. During the 6 month period following discontinuation the patient did not have any more episodes of menometrorrhagia or tachyarrhythmia (13030). Also, a case of transient ischemic attack secondary to a hypertensive crisis has been reportedly related to oral use of Panax ginseng (89402).
Dermatologic
...Orally, Panax ginseng may cause itching or an allergic response consisting of systemic rash and pruritus (89743,89760,104953).
Skin eruptions have also been reported with use of Panax ginseng at high dosage, long-term (3353). Uncommon side effects with oral Panax ginseng include Stevens-Johnson syndrome (596).
In one case report, a 6-year-old male with a previous diagnosis of generalized pustular psoriasis, which had been in remission for 18 months, presented with recurrent pustular lesions after consuming an unspecified dose of Panax ginseng. The patient was diagnosed with pityriasis amiantacea caused by subcorneal pustular dermatosis. Treatment with oral dapsone 25 mg daily was initiated, and symptoms resolved after 4 weeks (107748).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, mild pain, local irritation, and burning have occurred (2537).
Endocrine
...The estrogenic effects of ginseng are controversial.
Some clinical evidence suggests it doesn't have estrogen-mediated effects (10981). However, case reports of ginseng side effects such as postmenopausal vaginal bleeding suggest estrogenic activity (590,591,592,10982,10983).
In a 12-year-old Korean-Japanese male, enlargement of both breasts with tenderness in the right breast (gynecomastia) occurred after taking red ginseng extract 500 mg daily orally for one month. Following cessation of the product, there was no further growth or pain (89733). Swollen and tender breasts also occurred in a 70-year-old female using Panax ginseng orally (590).
Gastrointestinal ...Orally, Panax ginseng can cause decreased appetite (3353), diarrhea (3353,89734,103477), abdominal pain (89734,87984), and nausea (589,87984). However, these effects are typically associated with long-term, high-dose usage (3353).
Genitourinary
...Amenorrhea has been reported with oral use of Panax ginseng (3353).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, sporadic erectile dysfunction and excessively delayed ejaculation have occurred (2537). Less commonly, patients can experience vaginal bleeding (591,592,3354,23630).
Hepatic ...Uncommon side effects can include cholestatic hepatitis (associated with a Panax ginseng-containing, multi-ingredient product, Prostata), such as that which occurred in a 65-year old male following oral use (598).
Immunologic ...A case of anaphylaxis, with symptoms of hypotension and rash, has been reported following ingestion of a small amount of Panax ginseng syrup (11971).
Neurologic/CNS ...Orally, one of the most common side effects to Panax ginseng is insomnia (589,89734). Headache (594,23638), vertigo, euphoria, and mania (594) have also been reported. Migraine and somnolence occurred in single subjects in a clinical trial (87984). In a case report of a 46-year-old female, orobuccolingual dyskinesia occurred following oral use of a preparation containing black cohosh 20 mg and Panax ginseng 50 mg twice daily for menopausal symptoms. The patient's condition improved once the product was stopped and treatment with baclofen 40 mg and clonazepam 20 mg daily was started (89735).