Aconitum napellus 6X • Actaea racemosa 6X • Aletris Farinosa 6X • Arnica montana 6X • Caulophyllum thalictroides 6X • Chamomilla 6X • Crocus sativus 6X • Mercurius Corrosivus 10X • Sabina 6X • Secale cornutum 6X • Silicea 10X • Thlaspi Bursa-Pastoris 4X • Viburnum Opulus 6X • Viburnum Prunifolium 6X. Other Ingredients: Aqua, Ethanol.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
This is a homeopathic preparation. Homeopathy is a system of medicine established in the 19th century by a German physician named Samuel Hahnemann. Its basic principles are that "like treats like" and "potentiation through dilution." For example, in homeopathy, diarrhea would be treated with an extreme dilution of a substance that normally causes diarrhea when taken in high doses.
Practitioners of homeopathy believe that more dilute preparations are more potent. Many homeopathic preparations are so diluted that they contain little or no active ingredient. Therefore, most homeopathic products are not expected to have any pharmacological effects, drug interactions, or other harmful effects. Any beneficial effects are controversial and cannot be explained by current scientific methods.
Dilutions of 1 to 10 are designated by an "X." So a 1X dilution = 1:10, 3X=1:1000; 6X=1:1,000,000. Dilutions of 1 to 100 are designated by a "C." So a 1C dilution = 1:100; 3C = 1:1,000,000. Dilutions of 24X or 12C or more contain zero molecules of the original active ingredient.
Homeopathic products are permitted for sale in the US due to legislation passed in 1938 sponsored by a homeopathic physician who was also a Senator. The law still requires that the FDA allow the sale of products listed in the Homeopathic Pharmacopeia of the United States. However, homeopathic preparations are not held to the same safety and effectiveness standards as conventional medicines. For more information, see the Homeopathy monograph.
Below is general information about the effectiveness of the known ingredients contained in the product A Complex Drops. 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
There is insufficient reliable information available about the effectiveness of aletris.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of blue cohosh.
There is insufficient reliable information available about the effectiveness of ergot.
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of savin tops.
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 A Complex Drops. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
UNSAFE ...when used orally or topically. Aconite root contains toxic alkaloids that are strong, fast-acting poisons that affect the heart and central nervous system, causing severe arrhythmias, reduced consciousness, and death (15499,19669,30294,30300,30301,30303,30309,30334,30335,30336,92276,104514,106706). All species of this plant are dangerous. Severe poisoning has been reported after ingestion of 0.2-2 mg of aconitine, 1 gram of the raw plant, or 6 grams of processed and cured aconite (3490,104514). Even when a processed product is used, aconite can cause toxicity including nausea, vomiting, dizziness, muscle spasms, hypothermia, paralysis of the respiratory system, and heart rhythm disorders (15499). Aconite can also be absorbed through the skin and cause significant toxicity (12).
PREGNANCY AND LACTATION: UNSAFE
when used orally or topically (15499).
There is insufficient reliable information available about the safety of aletris.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally due to the possibility that aletris contains components that cause estrogenic activity (11) and oxytocin (Pitocin) antagonism (12); avoid using.
POSSIBLY SAFE ...when used orally in amounts commonly found in foods. Arnica has Generally Recognized As Safe (GRAS) status for use as a food flavoring in the US (4912). However, Canadian regulations do not allow its use as a food ingredient (12). ...when used orally in homeopathic dilutions of 30C and up to 5C (19110,19111,19117,19124,19126,96769). ...when used topically on unbroken skin, short-term (12).
LIKELY UNSAFE ...when used orally or when applied topically to broken skin. Arnica is considered poisonous and has caused severe or fatal poisonings (5). Arnica can cause gastroenteritis, muscle paralysis, bleeding, arrhythmia, hypertension, shortness of breath, nausea and vomiting, multi-organ failure, and death (4,5,17,104,19101,19102,19103,19104,19105,19106,19107,19108).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally or topically; avoid using (12).
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 UNSAFE ...when used orally (4,12). Poisonings have occurred after ingestion of blue cohosh leaf or seeds (4).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally.
Blue cohosh is a uterine stimulant and can induce labor (12047). Several blue cohosh constituents, such as anagyrine and N-methylcytisine, are potentially teratogenic and might cause congenital malformations in newborns (1122,7110,36718,94534). Use of blue cohosh near term can cause life-threatening toxicity in the infant (1207,9492,9493,12047,36725), as well as severe toxicity in the mother (36720). Many midwives still use blue cohosh to facilitate delivery. This dangerous practice should be avoided (1122,1207).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Saffron has Generally Recognized as Safe (GRAS) status in the US for use as a spice or food coloring agent (4912).
POSSIBLY SAFE ...when used orally and appropriately in larger amounts, short-term. Saffron extracts have been used with apparent safety in clinical trials at doses of up to 100 mg daily for up to 26 weeks (11024,13103,16555,17214,17401,18102,93395,93397,93400,93403)(93407,97359,99436,100135,100138,100140,100658,100659). The saffron constituent crocin has been used with apparent safety at a dose of up to 30 mg daily for up to 3 months (93410,100139,105616).
POSSIBLY UNSAFE ...when used orally in high doses or for longer than 26 weeks. Taking 5 grams or more of saffron can cause severe side effects. Doses of 12-20 grams can be lethal (12,18). There is insufficient reliable information available about the safety of saffron when used topically.
PREGNANCY: LIKELY UNSAFE
when used orally in amounts exceeding those commonly found in foods.
Larger amounts of saffron have uterine stimulant and abortifacient effects (18); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE ...when used topically. The essential oil from savin tops can cause severe irritation of skin and mucous membranes (18).
UNSAFE ...when used orally. Fatal poisonings have occurred with as little as 6 drops of the essential oil (18).
PREGNANCY AND LACTATION: UNSAFE
when used orally or topically.
Savin tops are contraindicated in pregnancy because they can induce abortion, and fatal poisoning has occurred with as little as 6 drops of the essential oil (18,19).
POSSIBLY SAFE ...when preparations of the above ground parts are used orally and appropriately (4,12). Doses of 1280 mg daily have been used safely for up to 7 days in a clinical trial (102404). ...when used topically (4).
POSSIBLY UNSAFE ...when large amounts of shepherd's purse are ingested, it can cause heart palpitations (12).
PREGNANCY: LIKELY UNSAFE
when used orally or topically, due to possible uterine stimulation, menstrual flow stimulation, and miscarriage (12).
LACTATION:
Insufficient reliable information available; avoid excessive use (4).
There is insufficient reliable information available about the safety of Viburnum opulus.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product A Complex Drops. 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, combining aconite with other antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
Details
Higenamine, a constituent of aconite, is thought to have antiplatelet and antithrombotic effects. In an animal model of thrombosis, higenamine inhibited platelet aggregation and reduced the size of thrombus formation (92282).
|
Theoretically, combining aconite with other stimulant drugs might alter the effects of the stimulant drug or increase the risk of cardiovascular toxicity.
Details
Aconite and its constituents have stimulant effects due to agonist activity at beta-2-adrenoreceptors. In cardiac muscle, aconite appears to have a positive inotropic effect and increases heart rate and blood pressure (2634,15499,30296,92282). However, some constituents of aconite can reduce heart rate and blood pressure (15499,30343).
|
Theoretically, due to reports that aletris increases stomach acid, aletris might decrease the effectiveness of antacids (19).
|
Aletris might have estrogenic effects (6). Theoretically, use of aletris with estrogens might increase the risk for additive adverse effects.
|
Theoretically, due to reports that aletris increases stomach acid, aletris might decrease the effectiveness of H2-blockers (19). The H2 blockers include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid).
|
Theoretically, due to reports that aletris increases stomach acid, aletris might decrease the effectiveness of PPIs (19). PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium).
|
Theoretically, arnica might have additive effects with anticoagulant and antiplatelet drugs. Homeopathic arnica preparations are unlikely to have this interaction.
Details
In vitro evidence shows that sesquiterpene lactones in arnica flowers can decrease platelet aggregation (104). However, this effect has not been reported in humans.
|
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.
|
There is some concern that blue cohosh might increase blood glucose levels (6002,36724). Theoretically, it might decrease the effectiveness of medicines used for diabetes. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
|
Constituents in blue cohosh might increase blood pressure by causing coronary vasoconstriction (6002). Theoretically, concomitant use might decrease the effectiveness of drugs used for angina and high blood pressure; use with caution. Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
|
Blue cohosh can increase the effects of nicotine (6002).
|
Ergotamine, a constituent of ergot, is a substrate of cytochrome P450 3A4 (CYP3A4) (11163). Theoretically, drugs that inhibit CYP3A4 might increase the risk of ergot toxicity. Some of these drugs include amiodarone (Cordarone), clarithromycin (Biaxin), diltiazem (Cardizem), erythromycin (E-mycin, Erythrocin), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Fortovase, Invirase), and many others.
|
Concomitant use of ergot with ergot alkaloids or derivatives may increase the risk of adverse effects (11163). Some of these include bromocriptine (Parlodel), dihydroergotamine (Migranal, DHE-45), ergotamine (Cafergot), and pergolide (Permax).
|
Certain ergot alkaloids, such as dihydroergotamine, act as serotonin agonists. Theoretically, combining serotonergic drugs with ergot might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders (8056,11163). Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using ergot with serotonergic drugs.
Details
Serotonergic drugs include the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft); tricyclic and atypical antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), and imipramine (Tofranil); triptans such as sumatriptan (Imitrex), zolmitriptan (Zomig), and rizatriptan (Maxalt); opioids such as methadone (Dolophine) and tramadol (Ultram); and many other medications.
|
Co-administration of stimulant drugs with ergot may increase the risk of vasoconstriction (11163).
Details
Some stimulant drugs include albuterol (Proventil, Ventolin), diethylpropion (Tenuate), dopamine, epinephrine, phentermine (Ionamin), pseudoephedrine (Sudafed), and many others.
|
Theoretically, concomitant use of saffron with antidiabetes drugs might increase the risk of hypoglycemia.
Details
|
Theoretically, concomitant use of saffron with antihypertensive drugs might have additive effects.
Details
|
Theoretically, saffron might inhibit the metabolism of caffeine.
Details
A small clinical study suggests that taking saffron powder 300 mg in 150 mL water daily for 5 days and then taking caffeine 200 mg seems to reduce caffeine metabolite levels in the saliva and urine in males, but not females. Theoretically, this may be due to the inhibition of cytochrome P450 1A2 by saffron (100130).
|
Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.
Details
|
Theoretically, concomitant use with drugs with sedative properties may cause additive effects and side effects (4).
|
Theoretically, concomitant use may interfere with thyroid dysfunction therapy (4).
|
Below is general information about the adverse effects of the known ingredients contained in the product A Complex Drops. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally and topically, aconite is generally regarded as unsafe for use.
Any benefits of therapy might not outweigh the risk of toxicity.
Most Common Adverse Effects:
All routes of administration: Serious neurologic, cardiovascular, gastrointestinal, and respiratory adverse effects have been reported.
Cardiovascular ...Orally and topically, aconite can cause hypotension, palpitations, chest tightness, pulmonary edema, arrhythmia, bradycardia, tachycardia, sustained or bidirectional ventricular tachycardia, ventricular fibrillation, and Torsade de pointes (558,559,561,562,563,3490,15499,15650,30294,30295)(30300,30305,30323,30336,92276,92277,92278,104514,106706,110473)(112901). Cardioversion has been reported to be ineffective for the reversal of aconite-induced dysrhythmia, but the use of agents such as amiodarone, lidocaine, and magnesium have been successful in some cases (2634,3490,106706,112901).
Gastrointestinal ...Orally, aconite can cause nausea, vomiting, diarrhea, and gastric pain (563,30297,30341,92277,92278). Topically, aconite can cause nausea and vomiting (92276).
Neurologic/CNS ...Orally, aconite can cause weakness, sweating, restlessness, dizziness, numbness, paresthesia, seizures, and reduced consciousness (558,559,561,562,563,3490,15499,15650,30335,30336,30341,92277,92278,104513). Topically, aconite can cause generalized paresthesia, fatigue, sweating, dizziness and tongue numbness (92276).
Ocular/Otic ...Orally, aconite has been reported to cause visual blurring and yellow-green vision with pupil dilation (30319).
Pulmonary/Respiratory ...Orally, aconite overdose can lead to respiratory failure (104513).
Renal ...Orally and topically, aconite can cause hypokalemia and metabolic and/or respiratory acidosis (558,559,561,562,563,3490,15499,15650).
Other
...Orally and topically, aconite has been reported to cause death in both adults and children (559,3490,3491,30301,30334,30341,92276,92278).
In one case report, topical application of aconite to an infant led to cardiogenic shock with multi-organ failure and death (92276). Poisoning has been reported in 15 patients after consuming a homemade liquor containing aconite. Patients presented with tongue or extremity numbness, vomiting, dizziness, or heart palpitations, and 5 died (110471). Death has also been reported in individuals who cooked aconite tubers as vegetables or for health purposes (92278).
The first symptoms of aconite poisoning after oral ingestion of the leaves or root usually occur within 10-90 minutes, although toxicity may be delayed until a second or third dose (559,15499,104513,110471). Recovery time from aconite poisoning ranges from 1.5-2 days for mild intoxication to 7-9 days for patients with cardiovascular complications; fatalities in treated patients are about 5% (15499). Treatment of aconite toxicity is typically supportive, although charcoal hemoperfusion has aided in detoxification (15499,106706).
General ...There is currently a limited amount of information available about the adverse effects of aletris. Orally, aletris has been reported to cause colic, stupefaction, and vertigo (6).
Gastrointestinal ...Orally, small doses of aletris have been reported to cause colic (6).
Neurologic/CNS ...Orally, small doses of aletris have been reported to cause stupefaction and vertigo (6).
General
...Orally, arnica is unsafe and can cause toxicity.
When used in homeopathic amounts, arnica seem to be generally well tolerated. Topically, arnica also seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Bleeding, gastroenteritis, hypertension, muscle paralysis, nausea and vomiting, shortness of breath.
Topically: Contact dermatitis and irritation.
Serious Adverse Effects (Rare):
Orally: Arrhythmia, coma, multi-organ failure, and death.
Cardiovascular ...Orally, arnica can cause tachycardia or a faster heart rate (11,17113,19101,19102). A 24-year-old female presented to the emergency department with palpitations and vomiting 24 hours after ingesting a cup of tea that reportedly contained arnica flowers picked from her local area of mountainous Southern California. The species was not specified in the article and there was no indication by the authors that any testing had been done to confirm the identity of the plant (90610).
Dermatologic ...Orally, arnica can cause irritation of mucous membranes (11,17113). Topically, arnica can cause contact itchiness, dry skin, and rash (17113). Oral lesions resulted in a woman who used a mouthwash incorrectly by not following dilution instructions. The mouthwash was 70% alcohol and contained arnica and oil of peppermint (19106).
Gastrointestinal ...Orally, arnica can cause stomach pain, nausea, vomiting, and diarrhea (11,17113,19101,19102). Homeopathic arnica has been reported to cause dry mouth (30C) and sore tongue (6C) (19107). A 24-year-old female presented to the emergency department with palpitations and vomiting 24 hours after ingesting a cup of tea that reportedly contained arnica flowers picked from her local area of mountainous Southern California. The species was not specified in the article and there was no indication by the authors that any testing had been done to confirm the identity of the plant (90610).
Musculoskeletal ...Adverse effects after ingesting arnica include muscle weakness (19101). Homeopathic arnica has been reported to result in the feeling of a "throbby" head or neck (19107).
Neurologic/CNS ...Orally, arnica may cause drowsiness, nervousness, and headache (11,17113,19101,19107).
Ocular/Otic ...In a case report, accidental intake of a large amount of a homeopathic Arnica-30 resulted in acute vision loss due to bilateral toxic optic neuropathy (19105).
Psychiatric ...Oral homeopathic arnica (6C) may cause depressed feelings, specifically a feeling of unhappiness (19107).
Pulmonary/Respiratory ...Orally, arnica can cause shortness of breath (11,17113).
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, blue cohosh can cause significant adverse effects including mucous membrane irritation, stomach upset including diarrhea and cramping, chest pain (angina), hypertension, and hyperglycemia (6002).
Neonatal acute myocardial infarction (MI), congestive heart failure (CHF), and shock has occurred following maternal use of a blue cohosh combination product one month before delivery (566,3383,94534). There is also 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 and blue cohosh at 42 weeks gestation to induce labor (1122,9492,94534). In another case, a mother was advised to drink a blue cohosh tea to induce labor. The infant experienced a seizure during delivery, and 2 days later it was discovered that the infant was experiencing an evolving ischemic stroke (12047,94534). In another case, nicotinic toxicity characterized by tachycardia, sweating, abdominal pain, vomiting, and muscle twitching and weakness was reported for a woman taking blue cohosh to induce abortion (36720,94534).
Due to these life-threatening side effects pregnant women should be advised not to ingest any blue cohosh product during pregnancy.
Cardiovascular ...Orally, blue cohosh can cause tachycardia, hypertension, and chest pain (angina) (36720,36724,94934). Neonatal acute myocardial infarction (MI), congestive heart failure (CHF), myocardial toxicity, and shock has occurred following maternal use of a blue cohosh combination product one month before delivery (566,3383,12047,36722,36725).
Gastrointestinal ...Orally, blue cohosh can cause mucous membrane irritation, stomach upset including diarrhea and cramping, nausea, vomiting, and abdominal pain (36720).
Musculoskeletal ...Orally, blue cohosh can cause muscle weakness and involuntary muscle contractions (36720).
Neurologic/CNS ...In one case, a mother was advised to drink a blue cohosh tea to induce labor. The infant experienced a seizure during delivery and 2 days later it was discovered that the infant was experiencing an evolving ischemic stroke (12047,94534). There is also another case report of severe complications, including seizures, in an infant whose mother was given an unknown dose of black and blue cohosh at 42 weeks gestation to induce labor (1122,9492,94934).
Renal ...There is a case report of severe complications, including renal failure, in an infant whose mother was given an unknown dose of black and blue cohosh at 42 weeks gestation to induce labor (1122,9492,94934).
General
...Orally, ergot can cause gastrointestinal symptoms such as nausea and abdominal pain.
Weakness, muscle pain of the extremities, and numbness and tingling of the fingers and toes may also occur (9). Symptoms of acute overdose include nausea, vomiting, diarrhea, extreme thirst, coldness, tingling and itching of the skin, a rapid and weak pulse, hypotension, shock, confusion, seizures, unconsciousness, and death (9).
Chronic toxicity, or ergotism, rarely occurs after a single oral dose. It usually results from cumulative doses over a short period of time (11163). Ergotism from food is rare today. It is more common from overdoses of prescription ergot alkaloids (11164). Symptoms of ergotism are related to circulatory disturbances. Numbness, coldness, and tingling of the extremities, particularly the feet and legs occur along with paleness or cyanosis. There may be no pulse in the affected area, which may develop into gangrene, especially in the toes (9,11163). A convulsive form of ergotism may also occur. Symptoms include muscle spasms in the trunk and limbs, painful involuntary flexion of the fingers and wrists, and either flexion or extension of the ankles. Neurologic adverse effects such as drowsiness, delirium, lethargy, mental changes, and visual disturbances can also occur. Sweating, fever, muscle stiffness, twitching and seizures have also been reported (9,11163).
Cardiovascular ...Orally, chronic toxicity with ergot, or ergotism, results from cumulative doses over a short period of time. Symptoms are often related to circulatory disturbances. Numbness, coldness, and tingling of the extremities, particularly the feet and legs occur along with paleness or cyanosis. There may be no pulse in the affected area, which may develop into gangrene, especially in the toes (9,11163)
Gastrointestinal ...Orally, ergot can cause gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain (9).
Musculoskeletal ...Orally, chronic toxicity from cumulative ergot doses over a short period of time can present as a convulsive form of ergotism. Symptoms include muscle spasms in the trunk and limbs, painful involuntary flexion of the fingers and wrists, and either flexion or extension of the ankles. Sweating, fever, muscle stiffness, twitching and seizures have also been reported (9,11163).
Neurologic/CNS ...Orally, ergot can cause drowsiness, delirium, lethargy, mental changes, and visual disturbances (9,11163).
Other ...Symptoms of acute ergot oral overdose include nausea, vomiting, diarrhea, extreme thirst, coldness, tingling and itching of the skin, a rapid and weak pulse, hypotension, shock, confusion, seizures, unconsciousness, and death (9).
General
...Orally, saffron extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal complaints, nausea, sedation, vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Dermatologic ...Orally, sweating and flushing have been reported in clinical research for patients taking saffron 30-60 mg daily (93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the skin (2,11).
Gastrointestinal ...Orally, saffron has been associated with changes in appetite, nausea, and vomiting when given at doses of 30 mg twice daily for 26 weeks, or when the saffron constituent crocin was given as 15 mg twice daily for 12 weeks (18102,105616). At lower doses of 30 mg daily, the occurrence rate of these and other adverse events such as dry mouth, dyspepsia, diarrhea, and constipation was rare or similar to placebo (13103,93395,93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the mucous membranes (mimicking icterus), vomiting, and bloody diarrhea (2,11).
Genitourinary
...One report of excessive uterine bleeding occurred in a clinical trial.
The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bleeding from the uterus (2,11).
Hematologic
...Orally, saffron extract has been reported to cause decreases in platelet, white blood cell, and red blood cell counts after 7 days to 12 weeks of use with doses of 60-200 mg daily.
Many of these decreases were only significant when compared to baseline but did not maintain significance when compared to placebo. These reductions were not considered clinically significant (18102,72473,93403,93409).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bloody diarrhea, hematuria, bleeding from the nose, lips, eyelids or uterus, and thrombocytopenic purpura (2,11).
Immunologic ...Allergy to oral saffron has been reported in clinical trials (93404). Anaphylactic reactions can occur within minutes of eating food prepared with saffron (4107,72555). Occupational exposure to saffron has been associated with the development of rhinoconjunctivitis and allergy-induced asthma (4106).
Neurologic/CNS ...Orally, saffron has been reported to cause drowsiness, headache, agitation, and sedation when given at doses of 30 mg twice daily for up to 26 weeks or when crocin is given as 15 mg twice daily for 12 weeks (18102,105616). At doses of 30 mg daily for 6 weeks, the side effect occurrence rate was similar to placebo (13103). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include vertigo and numbness (2,11).
Ocular/Otic ...Orally, saffron poisoning with oral intake of doses of 5 grams or more can cause ocular symptoms such as yellow appearance of the sclera (2,11).
Psychiatric ...Orally, saffron has been reported to cause anxiety and hypomania when given at doses of 30 mg twice daily for 26 weeks (18102). At doses of 30 mg daily for 6 weeks, the occurrence rate was similar to placebo (13103,93395). One report of agitation occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Renal ...Orally, the saffron constituent crocin given as 15 mg twice daily for 12 week was associated with one case of urinary incontinence (105616). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include hematuria and uremic collapse (2,11).
General
...Savin tops are generally regarded as unsafe for use.
Any benefits of therapy may not outweigh the risk of toxicity. Orally, symptoms of savin tops poisoning include nausea, nervousness, cardiac rhythm disorders, spasm, kidney damage, hematuria, central paralysis, unconsciousness, and death (18). Ingestion can also cause irritation of mucous membranes resulting in gastroenteritis, hepatitis, pneumonitis, and nephritis (19).
Topically, savin tops oil can cause skin irritation, blisters, and necrosis (18).
Cardiovascular ...Orally, savin tops can cause toxicity. Cardiovascular symptoms of savin tops toxicity include cardiac rhythm disturbances (18).
Dermatologic ...Topically, the volatile oil from savin tops can cause skin irritation, blisters, and necrosis. It can also cause severe irritation to mucous membranes (18,19).
Gastrointestinal ...Orally, savin tops can cause toxicity. Gastrointestinal symptoms of savin tops toxicity include nausea and gastroenteritis (18,19).
Hepatic ...Orally, savin tops can cause toxicity. Hepatic symptoms of savin tops toxicity include hepatitis (19).
Neurologic/CNS ...Orally, savin tops can cause toxicity. Neurologic symptoms of savin tops toxicity include nervousness, spasm, central paralysis, unconsciouness, and death (18).
Pulmonary/Respiratory ...Orally, savin tops can cause toxicity. Pulmonary symptoms of savin tops toxicity include pneumonitis (19).
Renal ...Orally, savin tops can cause toxicity. Renal symptoms of savin tops toxicity include kidney damage, hematuria, and nephritis (18,19).
General ...Orally, shepherd's purse seems to be well tolerated when used in small amounts, short-term. Adverse effects traditionally thought to be associated with shepherd's purse have included sedation, hypertension, hypotension, abnormal thyroid function, abnormal menstruation (4), and palpitations (12).
Cardiovascular ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included hypertension, hypotension, (4), and palpitations (12).
Endocrine ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included abnormal thyroid function (4).
Genitourinary ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included abnormal menstruation (4).
Neurologic/CNS ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included sedation (4).
General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.