Proprietary Blend of standardized extracts: Indian gooseberry , Catkins , Indian Gallnut , Long Pepper , Indian Pennywort , Cardamon , Nutmeg , Cinnamon , Bamboo Manna, Sandalwood , Asparagus , Bael fruit, Tribulus terrestris , Terminalia Chebula , Adhatoda vasica , Leptadenia reticulata , Aquilaria agallocha , Kush , Ashwagandha , Rotundus cyperus , Butterfly Pea , Thatch grass, Turmeric , Indian Trumpet flower, Caltrops , Gymnema Auranticum, Spreading Hogweed , Kudju , Uraria Picta , Cashmere bark, Arni , Phaseolus Trilobus , Desmodium , Gangeticum , Castor root, Indian Nightshade , Clarified Butter , Clarified Honey .
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 Amla Plus (Enhanced Chavanprash). 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
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 Amla Plus (Enhanced Chavanprash). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).
PREGNANCY: LIKELY UNSAFE
when used orally.
Ashwagandha has abortifacient effects (12).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used in amounts commonly found in foods. Asparagus seed and root extract have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). There is insufficient reliable information available about the safety of asparagus when used orally in medicinal amounts or when applied topically.
PREGNANCY: LIKELY SAFE
when used in amounts commonly found in foods (4912).
PREGNANCY: POSSIBLY UNSAFE
when used in larger amounts for medicinal purposes.
Asparagus extracts may have contraceptive effects (6); avoid using.
LACTATION: LIKELY SAFE
when used in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of asparagus when used in medicinal amounts during lactation.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
There is insufficient reliable information available about the safety of bael.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when properly prepared bamboo shoots are used orally in food amounts (96875).
POSSIBLY SAFE ...when bamboo salt-containing toothpaste is used topically during brushing twice daily for up to 4 weeks (109458). There is insufficient reliable information available about the safety of bamboo when taken by mouth in the amounts found in medicine or when used topically on areas of the body beyond the teeth and gums.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Cardamom has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Cardamom powder 3 grams daily in 2-3 divided doses has been used with apparent safety for up to 16 weeks (95308,95597,101885,107920). ...when the essential oil is used by inhalation for aromatherapy (77054,95307).
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Cardamom is thought to have abortifacient and emmenagogue effects (19,39884). Avoid using amounts greater than those used in food.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of cardamom when used in medicinal amounts. Avoid using amounts greater than those used in food.
POSSIBLY SAFE ...when used topically and appropriately. Gotu kola has been used safely in a cream or ointment for up to 10 weeks (11072,11073,67372,102792,105329,105335). An emulsion containing gotu kola extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571). ...when used orally and appropriately. Gotu kola extract has been used with apparent safety in doses of up to 180 mg daily for up to 12 months or 1000 mg daily for 60 days. Dried gotu kola has been used with apparent safety in doses of up to 2200 mg daily for 4 weeks (6887,11062,11063,11064,11065,11066,11067,11068,11069,11070)(11071,99756,99757,99758,105329,105332,105333). A specific gotu kola extract (Centellicum, Horphag Research Ltd) 450-675 mg daily has been used with apparent safety for up to 6 weeks (99756,99757).
PREGNANCY: POSSIBLY SAFE
when used topically and appropriately (11073,13559).
There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Gymnema leaf extract has been used safely in doses of 200 mg twice daily for up to 20 months or 300 mg twice daily for 12 weeks (45,46,42604,105346).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately (13160,14319). Concerns about botulism pertain only to children under 12 months of age and not to adults (13160). ...when used topically and appropriately. A specific commercially available wound dressing containing manuka honey (Medihoney) is approved as a medical device by the US Food and Drug Administration (FDA) (16353,16355,16357,16362,16369,16371). Some evidence suggests other honey preparations can also be used safely when applied to the skin or used to rinse the mouth (395,396,397,398,399,7847,7849,13133,14317)(16358,16372,97704,101034,108530).
POSSIBLY SAFE ...when properly diluted honey is used intranasally. Manuka honey 16.5% solution has been used with apparent safety as a nasal rinse twice daily for 14 days (103969). ...when specific, medical-grade honey products are used in eye drops. A specific product (Optimel Manuka Plus Eye Drops, Melcare Biomedical Pty Ltd) has been used safely 2-3 times daily for up to 4 weeks (105231,105234).
LIKELY UNSAFE ...when honey produced from the nectar of rhododendrons is used orally. This type of honey contains grayanotoxins, which may lead to cardiovascular symptoms, such as arrhythmias, hypotension, chest pain, bradycardia, syncope, asystole, various types of heart block, and myocardial infarction (12220,55119,55122,55125,55126,55129,55141,55142,55157)(55163,55170,55171,55180,55183,55190,55224,55233,55234,55239)(55248,55260,55261,55280,55281).
CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term in children at least 12 months of age (15910,17299,55210,55253,97693).
CHILDREN: POSSIBLY UNSAFE
when used orally in children less than 12 months of age.
Ingestion of raw honey contaminated with Clostridium botulinum spores can cause botulism poisoning in infants under 12 months of age (13160,55067,55290,91359). This is not a danger for older children or adults. Medical-grade, sterilized honey has been used with apparent safety in the formula of premature newborns at doses of up to 15 grams daily for up to 2 weeks (97697).
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in food amounts.
The concern about botulism pertains to children under 12 months of age and not to pregnant adults (13160). There is insufficient reliable information available about the safety of honey when used for medicinal purposes when pregnant or breast-feeding.
LIKELY SAFE ...when consumed in amounts commonly found in foods (6,2076).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Indian gooseberry fruit extract has been used safely in doses of up to 1000 mg daily for up to 6 months, 1500 mg daily for up to 8 weeks, or 2000 mg daily for up to 4 weeks (92515,99238,99240,99241,102855,102857,105352,105354,105356). Indian gooseberry leaf extract has been used with apparent safety at a dose of 750 mg daily for 10 days (99846). ...when used topically and appropriately. An emulsion containing Indian gooseberry extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571).
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.
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 used orally and appropriately in amounts commonly found in foods. Nutmeg is commonly used as a spice. Nutmeg and nutmeg oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of nutmeg when used orally in larger doses, up to 120 mg daily. These doses have not been adequately evaluated in clinical research. However, doses at or above 120 mg daily have been associated with serious adverse effects (19292).
POSSIBLY UNSAFE ...when used orally in doses of 120 mg or greater. Chronic use of nutmeg in these doses has been associated with psychotic episodes and hallucinations (19292,19296,19487). Acute intoxication from nutmeg has been described in several case reports in which subjects ingested a single dose of 5-80 grams (2563,19297,19300,19491,111750). Symptoms of toxicity ranged from nausea, dry mouth, and dizziness to palpitations, agitation, and hallucinations (2563,3494,19293,19294,19295,19297,19298,19299,19489,19490)(19491,103373,111750). Two deaths involving nutmeg intoxication have also been reported (19300,112016) . Symptoms generally start 0.5-8 hours after ingestion and last up to 24-48 hours (19298,19488,19491,103372,103373). There is insufficient reliable information available about the safety of nutmeg when used topically.
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Nutmeg might have abortifacient activity, and its safrole content might be mutagenic (12).
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
There is insufficient reliable information available about the safety of nutmeg when used in larger, medicinal amounts during lactation; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Several small studies have used Terminalia arjuna powdered bark or bark extract with apparent safely in doses up to 2000 mg or 400 mg daily, respectively, for 2 weeks to 3 months (2502,2503,2504,111012,111093); however, patients should avoid self-treatment with this product due to potentially significant cardiovascular effects. Further study is needed to determine the safety of Terminalia arjuna for long-term use.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY UNSAFE ...when the spine-covered fruit is used orally. There have been reports of bilateral pneumothorax and bronchial polyp after oral consumption of the spine-covered fruit (818).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Animal research suggests that tribulus might adversely affect fetal development (12674); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283,114899) and products providing up to 1500 mg of curcumin daily have been safely used for up to 12 months (114898). Additionally, turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357,114906). ...when used topically and appropriately (11148).
POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in food.
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food.
There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.
LIKELY SAFE ...when used orally in amounts commonly found in foods. White sandalwood oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY UNSAFE ...when used orally for longer than 6 weeks. Use for more than 6 weeks is associated with kidney damage (12,19). There is insufficient reliable information available about the safety of white sandalwood when inhaled or when used topically in amounts greater than those found in cosmetics.
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; sandalwood is reported to have abortifacient effects (19); avoid using.
LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in foods.
Below is general information about the interactions of the known ingredients contained in the product Amla Plus (Enhanced Chavanprash). 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, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
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Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
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Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
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There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.
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Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
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Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).
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Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
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In vitro research shows that ashwagandha extract induces CYP1A2 enzymes (111404).
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Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
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In vitro research shows that ashwagandha extract induces CYP3A4 enzymes (111404).
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Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
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Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
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Ashwagandha might increase the effects and adverse effects of thyroid hormone.
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Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).
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Theoretically, asparagus root might increase diuresis and electrolyte loss when used with diuretic drugs.
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Theoretically, asparagus root might cause diuresis, reducing lithium clearance.
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Theoretically, concurrent use might decrease the effectiveness of both agents.
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Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.
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Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
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In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.
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Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
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Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.
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Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
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In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
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Theoretically, bacopa might have additive effects when used with thyroid hormone.
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Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).
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Evidence from animal research suggests that extracts of bael seed and leaf can reduce blood glucose levels (33316,33325). Theoretically, bael might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia. Monitor blood glucose levels closely. Dose adjustments might be necessary.
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Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.
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Bael leaf extract shows acetylcholinesterase (AChE) inhibitory activity in vitro (99296). Theoretically, bael might have additive effects with cholinergic drugs and increase the risk of cholinergic side effects.
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Cholinergic drugs include bethanechol (Urecholine), donepezil (Aricept), echothiophate (Phospholine Iodide), edrophonium (Enlon, Reversol, Tensilon), neostigmine (Prostigmin), physostigmine (Antilirium), pyridostigmine (Mestinon, Regonol), succinylcholine (Anectine, Quelicin), and tacrine (Cognex).
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Bael extract and its constituent marmesinin inhibited cytochrome P450 1A2 (CYP1A2) activity in vitro (99300). So far, this interaction has not been reported in humans. Theoretically, bael might increase levels of drugs metabolized by CYP1A2.
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Some drugs metabolized by CYP1A2 include amitriptyline (Elavil), haloperidol (Haldol), ondansetron (Zofran), propranolol (Inderal), theophylline (Theo-Dur, others), verapamil (Calan, Isoptin, others), and others. Use bael cautiously or avoid in patients taking these drugs.
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Bael and its constituents marmelosin and marmesinin inhibited cytochrome P450 3A4 (CYP3A4) activity in vitro (99300). So far, this interaction has not been reported in humans. Theoretically, bael might increase levels of drugs metabolized by CYP3A4.
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Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and numerous others. Use bael cautiously or avoid in patients taking these drugs.
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Theoretically, long-term bamboo use might increase the effects and adverse effects of antithyroid drugs, possibly leading to hypothyroidism.
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Animal research suggests that long-term consumption of bamboo shoot can decrease thyroid peroxidase activity, as well as levels of thyroxine (T4) and triiodothyronine (T3) (33538). This effect has not yet been reported in humans.
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Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
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Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
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Theoretically, taking gymnema with antidiabetes drugs might increase the risk of hypoglycemia.
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Gymnema reduces blood glucose levels in some human and animal research. In human studies, it has been shown to enhance the blood glucose lowering effects of hypoglycemic drugs (45,46,92119,92121,92123). However, other research in adults with prediabetes or metabolic syndrome suggests that gymnema does not reduce fasting levels of blood glucose (96235,105346). Until more is known, monitor blood glucose levels closely.
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Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.
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Animal and in vitro research shows that gymnema can inhibit the CYP1A2 enzyme (96236,96237,96238). In one animal study, oral administration of gymnema for 7 days increased the plasma concentrations of phenacetin, a CYP1A2 substrate, by about 1.4-fold and reduced the clearance of phenacetin by about 29% (96237).
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Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.
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Theoretically, gymnema might increase levels of drugs metabolized by CYP3A4.
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One in vitro study using rat liver microsomes shows that gymnema can modestly inhibit the CYP3A4 enzyme (96238). However, other in vitro research using human liver microsomes shows that gymnema does not affect CYP3A4 activity (96236). Animal research also shows that gymnema does not alter the function of CYP3A4. In one study in rats, oral administration of gymnema for 7 days did not alter the clearance of amlodipine, a CYP3A4 substrate (96237).
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Theoretically, taking gymnema with phenacetin might increase the levels of phenacetin.
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Theoretically, taking gymnema with tolbutamide might the decrease levels of tolbutamide.
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Animal research shows that gymnema, administered orally for 7 days, increases the clearance of tolbutamide by 2.4-fold when compared to control (96237).
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Theoretically, honey may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
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In vitro, honey inhibits platelet aggregation and increases the time to clotting (55222). Furthermore, animal research suggests that feeding mice large doses of honey for 12 days increases bleeding time when compared with no intervention (103964). However, these effects have not been reported in humans.
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Theoretically, honey might decrease levels of drugs metabolized by CYP3A4, but research is conflicting.
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Theoretically, honey might increase levels of phenytoin.
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In an animal model, the rate and extent of absorption of phenytoin was increased by honey (20352). This effect has not been reported in humans.
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Theoretically, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.
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Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone (92514). Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.
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Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.
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Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone (92514).
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Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.
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Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone (92514).
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Theoretically, Indian long pepper might increase the effects and adverse effects of amoxicillin.
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Evidence from animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of amoxicillin when taken concomitantly (29269).
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Theoretically, Indian long pepper might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
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In vitro research shows that Indian long pepper extract inhibits platelet aggregation (101151).
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Theoretically, Indian long pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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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.
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Theoretically, Indian long pepper might increase blood levels of carbamazepine.
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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).
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Theoretically, Indian long pepper might increase the effects and adverse effects of cefotaxime.
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Animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of cefotaxime when taken concomitantly (29269).
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Theoretically, Indian long pepper might increase the effects and adverse effects of cyclosporine.
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In vitro research shows that piperine, a constituent of Indian long pepper, increases the bioavailability of cyclosporine (29282).
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Theoretically, Indian long pepper might increase the effects and adverse effects of CYP1A1 substrates.
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In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP1A1 (29213).
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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).
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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).
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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).
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Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
Details
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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).
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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).
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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).
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Theoretically, Indian long pepper might increase blood levels of rifampin.
Details
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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).
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Combining kava with alcohol may increase the risk of sedation and/or hepatotoxicity.
Details
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.
Details
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.
Details
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.
Details
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Theoretically, kava might increase levels of CYP2C9 substrates.
Details
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It is unclear if kava inhibits CYP1A2; research is conflicting.
Details
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Kava might increase levels of CYP2E1 substrates.
Details
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.
Details
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.
Details
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.
Details
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It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.
Details
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.
Details
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, concomitant use of nutmeg and anticholinergic drugs might decrease the effectiveness of either agent.
Details
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine levels (25549).
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Theoretically, concomitant use of nutmeg with other cholinergic drugs might have additive effects and increase the risk of cholinergic side effects.
Details
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine levels (25549).
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Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.
Details
Animal studies suggest that nutmeg extracts and several volatile oils in nutmeg, such as methyleugenol, isoeugenol, safrole, myristicin, trimyristin, 1,8-cineole, and geranyl acetate, have sedative effects (2563,25544,25545,25547,25548). One animal study shows that petroleum ether extracts of nutmeg can potentiate the effects of pentobarbital or phenobarbital (25547). However, evidence from other animal research suggests that the nutmeg constituent myristicin can actually reduce sleeping time in rats pretreated with phenobarbital (3492,3493).
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Theoretically, nutmeg might decrease the levels and clinical effects of drugs metabolized by CYP1A1.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A1 (3493).
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Theoretically, nutmeg might decrease levels of drugs metabolized by CYP1A2.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A2 (3493).
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Theoretically, nutmeg might decrease levels of drugs metabolized by CYP2B1.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP2B1 (3493).
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Theoretically, nutmeg might increase or decrease the effects and adverse effects of phenobarbital.
Details
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Theoretically, concomitant use of Terminalia arjuna with anticoagulant or antiplatelet drugs may increase the risk of bleeding in some patients.
Details
In vitro, Terminalia arjuna bark extract inhibits platelet aggregation, decreases platelet activation, and shows antithrombotic properties (92831).
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Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP2C9 substrates.
Details
In vitro research shows that Terminalia arjuna extract inhibits CYP2C9 enzymes and reduces CYP2C9 substrate metabolism (96729).
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Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP2D6 substrates.
Details
In vitro research shows that Terminalia arjuna extract inhibits CYP2D6 enzymes and reduces CYP2D6 substrate metabolism (96729).
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Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that Terminalia arjuna extract inhibits CYP3A4 enzymes and reduces CYP3A4 substrate metabolism (96729).
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Taking tribulus with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Clinical research shows that Tribulus can lower blood glucose levels in adults with type 2 diabetes who are taking antidiabetes medications (97327).
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Theoretically, taking tribulus with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, tribulus might increase the levels and clinical effects of lithium.
Details
Tribulus is thought to have diuretic properties (12681). Due to these potential diuretic effects, tribulus might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
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Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.
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Taking turmeric with amlodipine may increase levels of amlodipine.
Details
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).
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Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Details
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.
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Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo (104149,114898,114900).
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Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.
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Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.
Details
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Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
Details
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Turmeric might increase levels of drugs metabolized by CYP3A4.
Details
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544).
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Theoretically, turmeric might increase blood levels of oral docetaxel.
Details
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.
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Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
Details
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).
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Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Details
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).
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Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
Details
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Theoretically, turmeric might increase the effects of losartan.
Details
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).
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Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
Details
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).
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Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Details
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).
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Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
Details
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.
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Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
Details
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Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Details
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.
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Turmeric might increase the effects and adverse effects of sulfasalazine.
Details
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).
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Turmeric might increase the effects and adverse effects of tacrolimus.
Details
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).
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Turmeric may reduce the absorption of talinolol in some situations.
Details
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.
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Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
Details
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).
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Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.
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Turmeric might increase the risk of bleeding with warfarin.
Details
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.
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Theoretically, taking white sandalwood might reduce lithium excretion and increase serum levels of lithium.
Details
White sandalwood is thought to have diuretic properties, which may reduce lithium excretion. The dose of lithium might need to be decreased.
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Below is general information about the adverse effects of the known ingredients contained in the product Amla Plus (Enhanced Chavanprash). 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, ashwagandha seems to be well-tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute hepatitis, acute liver failure, hepatic encephalopathy, the need for liver transplantation, and death due to liver failure with ashwagandha treatment.
Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).
Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745). Additionally, an otherwise healthy adult who was taking ashwagandha extract orally for 2 months experienced clinical and laboratory-confirmed thyrotoxicosis. Thyrotoxicosis resolved 50 days after discontinuing ashwagandha, without other treatment (114111). Another case report describes a 37-year-old female who presented with moderate symptomatic hyponatremia secondary to adrenal insufficiency after chronic consumption of ashwagandha for 2 years. This subject was effectively managed with oral hydrocortisone (114790).
Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490,113609) and gastritis and flatulence (90651) have been reported.
Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).
Hepatic ...Orally, ashwagandha in doses of 154 mg to 20 grams daily has played a role in several case reports of cholestatic, hepatocellular, and mixed liver injuries. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain and distension, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111,113610,114113). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, serum bilirubin, and international normalized ratio (INR) (112111,113610,114113). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111,114113). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy, liver failure requiring liver transplantation, and acute-on-chronic liver failure resulting in death (110490,113610).
Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492,113609). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.
General
...Asparagus is usually well tolerated when used in food amounts.
Information on its use in medicinal amounts is limited.
Most Common Adverse Effects:
Orally: Urine odor.
Serious Adverse Effects (Rare):
All routes of administration: Allergic reactions.
Gastrointestinal ...Orally, a specific combination product (Asparagus-P, Grunwalder) containing asparagus root 6 grams and parsley leaf 6 grams caused constipation, abdominal distension and pain, nausea, dry mouth, and gallbladder complaints in up to 50% of the study population in one clinical trial (94940). It is not clear if these effects were due to asparagus root, parsley, or the combination.
Genitourinary
...Orally, asparagus can cause a strong urine odor in some people.
It is not produced in all individuals, nor are all individuals able to smell the odor (32581,32583,32584,94942).
Orally, a specific combination product (Asparagus-P, Grunwalder) containing asparagus root 6 grams and parsley leaf 6 grams caused dysuria in approximately 2.5% of patients in one clinical trial (94940). It is not clear if this effect was due to asparagus root, parsley, or the combination.
Immunologic ...Orally and topically, asparagus can cause allergic reactions. They can occur in individuals sensitive to other members of the Liliaceae family, including onions, garlic, leeks, and chives (15557,15561,15562). Ingestion of fresh or canned asparagus can cause itchy eyes, runny nose, coughing, urticaria, dysphagia, dyspnea, and anaphylaxis in sensitized people (15561,15562,15564,32536,32594). There are also reports of fixed food eruptions, with lesions occurring at the same skin locations after ingesting asparagus on three separate occasions (15557,94941). Topically, exposure to asparagus during harvesting, processing, or cooking has caused contact dermatitis, urticaria, asthma, rhinitis, and conjunctivitis (15557,15561,15562,15564,32587,94943).
Musculoskeletal ...Orally, a specific combination product (Asparagus- P, Grunwalder) containing asparagus root 6 grams and parsley leaf 6 grams caused gout in approximately 2% of patients in one clinical trial (94940). It is not clear if this effect was due to asparagus root, parsley, or the combination.
Renal ...Orally, a specific combination product (Asparagus-P, Grunwalder) containing asparagus root 6 grams and parsley leaf 6 grams caused kidney pain and peripheral edema in approximately 15% of patients in one clinical trial (94940). It is not clear if these effects were due to asparagus root, parsley, or the combination.
General
...Orally, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.
Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).
Gastrointestinal ...Orally, bacopa has been reported to cause abdominal cramps, abdominal pain, bloating, decreased appetite, diarrhea, dry mouth, excessive thirst, flatulence, indigestion, nausea, and increased stool frequency. Rates of adverse gastrointestinal events have ranged from 12% to 30% (10058,17946,33295,97605,109623,111520).
Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia, muscle fatigue, and myopathy (10058,109623,111522). In one case, a 21-year-old male experienced progressive proximal weakness, muscle atrophy, weight loss, dark urine, and elevated serum markers of myopathy, with muscle biopsy showing immune-mediated necrotizing myopathy, after taking a supplement containing bacopa for 5 years (111522).
Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).
Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605,111520).
General ...There is currently a limited amount of information on the adverse effects of bamboo.
Dermatologic ...Topically, bamboo shoots have been reported to cause contact dermatitis in a 44-year-old female (33540).
Gastrointestinal ...In one case report, melanosis coli, pigmentation of the colon wall, was reported following the ingestion of bamboo leaf extract (33547).
Other ...Bamboo shoots are a source of cyanide glycosides. However, the hydrogen cyanide produced by the plant is eliminated during boiling, fermentation, or superheated steam drying of the shoots (96875). During the rescue of a male who jumped into a well which was used for bamboo shoot pickling, cyanide poisoning occurred in 8 individuals. The poisoning caused high anion gap metabolic acidosis in all patients and resulted in two deaths due to cardiac arrest. Some patients also had pulmonary edema and/or infiltration (96874).
General ...Orally, cardamom seems to be well tolerated.
Dermatologic ...Orally, mild skin inflammation due to cardamom has been reported in one participant of a clinical trial (101887). Topically, a case report describes chronic hand dermatitis in a confectioner frequently exposed to cardamom. Skin patch tests were positive for cardamom, and for terpenoids present in the seeds (39875).
Genitourinary ...Orally, dysuria due to cardamom has been reported in one participant of a clinical trial (101887). Also, a case report describes a 5-year-old female who developed hematuria after eating ice cream flavored with cardamom. It resolved spontaneously and there was no re-challenge (95306). It is not clear if cardamom is the direct cause of hematuria in this case.
General
...Orally and topically, gotu kola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastric irritation and nausea.
Topically: Eczema.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.
Dermatologic ...Topically, gotu kola may cause eczema (10277,10278). Also, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina,Almirall, S. A.) has been reported to cause allergic contact dermatitis. However, not all patients with reactions to this product are sensitive to gotu kola; some patients are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).
Gastrointestinal ...In some patients, gotu kola can extract cause gastrointestinal upset and nausea (780,6887,52894).
Hepatic
...There is concern that gotu kola may cause liver toxicity in some patients.
There are at least four case reports of hepatotoxicity associated with gotu kola; however, hepatotoxic contaminants cannot be ruled out, as laboratory analysis was not conducted on the products used. Additionally, the doses of gotu kola used in these cases were not reported (13182,92506). In a clinical trial where liver function was monitored, taking gotu kola 120 mg daily for 6 months was not associated with changes in liver function (11065).
In one case of hepatotoxicity, a 61-year-old female developed elevated liver transaminase and total bilirubin levels after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis. Months later, the patient took gotu kola again and developed elevated liver transaminases after 2 weeks. In another case, a 52-year-old female developed symptoms of hepatitis and increased liver transaminases after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas, areas of necrosis, and cirrhotic transformation. Liver function normalized after discontinuation of gotu kola. In a third case, a 49-year-old female developed symptoms of hepatitis after taking gotu kola for 2 months. Biopsy revealed granulomatous hepatitis. Liver function normalized after discontinuation of gotu kola (13182). In a fourth case, a 15-year-old female taking an unknown dose of gotu kola and lymecycline for 6 weeks for acne experienced acute liver failure with abdominal pain and vomiting, as well as elevated liver transaminases, bilirubin, international normalized ratio (INR), and prothrombin. Liver function returned to normal after both products were discontinued (92506).
Immunologic ...Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina, Almirall, S. A.) has been reported to cause allergic contact dermatitis in some patients. However, not all patients who react to this product are sensitive to gotu kola; some are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).
Psychiatric ...A case of night eating syndrome has been reported for a 41-year-old female who had been taking a gotu kola tincture (dose not specified) for 2 years. Symptoms resolved after gotu kola use was discontinued (52878).
General ...Orally, gymnema seems to be well tolerated.
Hepatic ...A case of drug-induced hepatitis characterized by weakness, fatigue, jaundice, and elevated liver enzymes, has been reported for a patient who consumed gymnema tea three times daily for 10 days. The patient was administered prednisone 60 mg once daily and was eventually tapered off prednisone and discharged. Laboratory values normalized after 6 months (95005). A case of hepatitis-associated aplastic anemia characterized by jaundice, elevated liver function tests, and pancytopenia has been reported for a patient who consumed gymnema 2 grams twice daily for at least a month. Treatment with ursodeoxycholic acid for 8 weeks led to resolution of cholestatic hepatitis; however, the pancytopenia was not responsive to treatment with immunosuppressive drugs and the patient died 5 months after presentation (110021). The exact reason for these adverse effects is not clear; they may have been idiosyncratic.
General
...Orally and topically, honey is generally well tolerated in those at least 1 year of age.
When given intranasally or into the eyes, honey seems to be well tolerated. However, honey containing grayanotoxins, which are found in rhododendrons, is likely unsafe and should be avoided.
Most Common Adverse Effects:
Orally: Nausea, stomach pain, and vomiting.
Topically: Burning, pain, and stinging.
Intranasally: Burning and nausea.
Ocular: Stinging.
Serious Adverse Effects (Rare):
Orally: Case reports of botulism in infants have occurred. Anaphylaxis has been reported in sensitive individuals. Honey from the Black Sea coast of Turkey, which is derived from the nectar of rhododendrons, has caused respiratory depression, dizziness, sweating, weakness, bradycardia, atrioventricular (AV) block, hypotension, cardiac arrhythmias, and myocardial infarction within a few minutes to several hours after consumption.
Cardiovascular ...Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins from rhododendrons, which can cause bradycardia, atrioventricular (AV) block, cardiac arrhythmias, myocardial infarction, and hypotension within a few minutes to several hours after consumption (12220,55110,55126,55129,55238,55269,55270,55280). Fatalities have not been reported. Patients typically respond to fluids and reversal of cardiac conduction abnormalities with atropine.
Dermatologic ...Topically, the use of honey applied to wounds can cause local pain, stinging, and burning in about 5% of patients, some of whom stop treatment as a result (16356,16357,16358,16361,91362,97694,96595). Theoretically, honey may cause excessive drying of wounds, which could delay healing. This can be managed by application of saline packs as needed (7850).
Gastrointestinal ...Orally, honey may cause mild nausea, vomiting, and stomach ache (12220,55119,55190,55294,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins. These toxins can cause increased salivation, nausea, and vomiting within a few minutes to several hours after consumption (12220,55119,55190,55294). Intranasally, honey may cause nausea (55216).
Immunologic ...Orally, honey can cause allergic reactions, including anaphylaxis (6,11,108531,108532). These reactions may be due to various components of the honey, including the honey itself, pollen, or bee secretions (91370). When used topically, local allergic reactions have been reported in people with pre-existing atopy (16356,55118). Allergic contact dermatitis related to honey enriched with propolis has been reported (91365).
Neurologic/CNS ...Orally, honey may cause nervousness, insomnia, and hyperactivity in children (91366,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins, which can cause dizziness, sweating, and weakness within a few minutes to several hours after consumption (12220,55110,55119,55296).
Ocular/Otic ...When used in eye drops, transient stinging has been reported rarely (105231,105234).
Pulmonary/Respiratory ...When used intranasally, a burning sensation of the nasal passages has been reported (55216). Honey from the Black Sea coast of Turkey, which sometimes contains excessive concentrations of grayanotoxins, can cause respiratory depression within a few minutes to several hours after consumption (12220,55110,55119,55296).
Other ...Some honey is contaminated with Clostridium botulinum spores, which poses a risk to infants (6,11,13160,55067,55290,91359). Botulinum spores can proliferate in the intestines of infants and cause botulism poisoning (55112). However, this is not a concern for older children and adults.
General ...Orally, Indian gooseberry seems to be well tolerated.
Dermatologic ...Orally, itching has been reported by one individual in a clinical trial (105354).
Gastrointestinal ...Orally, epigastric discomfort or dyspepsia have been reported by up to four individuals in clinical trials (105354,105356).
Hepatic ...In clinical research, increased serum glutamic pyruvic transaminase (SGPT) levels, with otherwise normal liver function, occurred in patients taking Ayurvedic formulations containing ginger, Tinospora cordifolia, and Indian gooseberry, with or without Boswellia serrata. The SGPT levels normalized after discontinuing the treatments (89557). It is unclear if these hepatic effects were due to Indian gooseberry or other ingredients contained in the formulations.
Musculoskeletal ...Orally, musculoskeletal pain has been reported by three individuals in a clinical trial (105354).
Neurologic/CNS ...Orally, fatigue has been reported by one individual in a clinical trial (105354).
Pulmonary/Respiratory ...Orally, breathlessness has been reported by one individual in a clinical trial (105354).
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, 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 (4032,11370,28489,57277,57325,57343,114683). In one case of kava-associated urticarial eruption, biopsy revealed neutrophilic sebaceous glands with lymphocytic infiltrate (114683). 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). In addition to kava cessation, oral or topical corticosteroids have been described as treatment options in some cases of kava associated dermatitis (114683).
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 ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, nutmeg is generally well tolerated when used as a spice in foods.
Acute or chronic use of nutmeg at high doses is unsafe.
Most Common Adverse Effects:
Topically: Allergic contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Accidental or intentional overdose with nutmeg has been associated with several serious adverse cardiovascular, gastrointestinal, neurological, and psychiatric events. Death due to overdose has also been reported.
Cardiovascular ...Orally, in cases of nutmeg overdose, tachycardia, palpitations, weak pulse, hypotension, and nonspecific electrocardiographic changes have been reported (3494,19293,19295,19299,19300,19488,19489,25943,103372,103373)(111750).
Dermatologic ...Topically, allergic contact dermatitis to nutmeg has been reported (25945,25946).
Gastrointestinal ...Orally, nausea was reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). Vomiting was reported in a case of a 19-year-old female using high doses of nutmeg with a history of lysergic acid diethylamide (LSD) and cannabis use (19294). Burning epigastric pain, gastroenteritis, diarrhea, nausea, and increased thirst have been reported in other cases of intentional or unintentional nutmeg overdose (19293,19299,19300,19489,19490,103372,103373). Vomiting has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Hematologic ...Orally, hyponatremia and leukocytosis with neutrophilia associated with nutmeg overdose have been rarely reported (103372).
Hepatic ...Orally, elevated liver enzymes associated with nutmeg overdose have been reported rarely (103372).
Immunologic ...Topically, allergic contact dermatitis to nutmeg has been reported (25945,25946).
Musculoskeletal ...Orally, muscle weakness, numbness, and ataxia were reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). An ataxic gait has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Neurologic/CNS ...Orally, headache, dizziness, and drowsiness were reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). Adverse effects associated with high intake of nutmeg have included confusion, dizziness, drowsiness, hallucinations, headache, incoherent speech, hot and cold sensations, sensations of limb loss, convulsions, and coma (19294,19299,19300,19487,19489,19490,103372,103373,111750). Sweating and hypothermia have also been reported following intake of high doses of nutmeg (19293,19294). Lethargy has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Ocular/Otic ...Orally, a case of double, triple, and blurred vision has been reported for a 13-year-old female who consumed nutmeg capsules while smoking cannabis (2563). Pupil dilation and pupil constriction has been reported from exposure to nutmeg (25948). Involuntary eye movement has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Psychiatric ...Orally, visual, auditory, and tactile hallucinations, depression, suicidal ideation, insomnia, restlessness, and bizarre behavior have been reported following nutmeg intoxication in various reports (12,2563,19300,19492,103372,103373). Other adverse effects associated with high intake of nutmeg have included disorientation, stupor, euphoria, anxiety, and agitation (19300,19489,103373,103374). Chronic psychosis has been associated with rare cases of prolonged abuse of nutmeg (103372). However, some researchers suggest that nutmeg does not have significant psychological or behavioral effects, even when taken at high doses (25939,25947). Restlessness and anxiety have been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Other ...Orally, fatal poisoning associated with nutmeg is rare (19300,103372,103373).
General ...There is currently a limited amount of information available on the adverse effects of oral Terminalia arjuna. A thorough evaluation of safety outcomes has not been conducted.
General
...Orally, tribulus seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Cases of liver and kidney injury, seizures, and chronic painful erection with impaired sexual function have been reported. Pneumothorax and bronchial polyp after consuming the spine-covered tribulus fruit have been reported.
Gastrointestinal ...Orally, tribulus can cause abdominal pain, cramping, nausea, vomiting, diarrhea, and constipation (92022,92027). However, in one study, the rates of these gastrointestinal complaints were similar for patients taking tribulus and those receiving placebo (92022).
Genitourinary ...In one case report, a patient taking two tribulus tablets (unknown dose) daily for 15 days presented to the local emergency department with a painful erection lasting 72 hours. The priapism was resolved with medical management; however, post-episode sexual function was impaired (92023).
Hepatic ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).
Neurologic/CNS ...Orally, tribulus has been reported to cause general excitation and insomnia. These symptoms were reversed upon discontinuation of the drug or decreasing the dose (78867). In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).
Pulmonary/Respiratory ...In one case report, a patient developed a bilateral pneumothorax after consuming the spine-covered fruit of tribulus (818). In another case report, a patient developed a polyp in the lobar bronchus of the right interior lobe due to the presence of a tribulus fruit spine (78852).
Renal ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of the tribulus water (92069). In another case report, a healthy male taking one tribulus tablet (unknown dose) daily for a few months for bodybuilding purposes developed hyperbilirubinemia followed by acute kidney failure 2-3 weeks later. The patient was managed with intravenous fluids and a low-salt, low-protein diet (92025).
Other ...In one case report, gynecomastia was observed in a male weightlifter taking an herbal combination product containing tribulus. However, it is not clear if this adverse effect can be attributed to tribulus alone (78859).
General
...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.
Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).
Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148,114899). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).
Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118,114898,114899), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430,114898,114899), epigastric burning (81444), and tongue staining (89723).
Hepatic
...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury.
There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).
Neurologic/CNS ...Orally, turmeric has been associated with headache and vertigo (81163,114898).
Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).
Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).
Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).
General
...Orally, white sandalwood appears to be well tolerated when taken in food amounts.
There is currently a limited amount of information on the adverse effects of white sandalwood when taken in medicinal amounts. Topically and by inhalation, adverse effects to white sandalwood seem to be rare; however, a thorough safety evaluation has not been conducted.
Most Common Adverse Effects:
Orally: Itching, nausea.
Topically: Contact dermatitis.
Serious Adverse Effects (Rare):
Orally: Acute kidney injury.
Dermatologic ...Orally, white sandalwood may cause itching (18).
Gastrointestinal ...Orally, white sandalwood may cause nausea and gastrointestinal complaints (18).
Immunologic ...Topically or when inhaled, there are case reports of white sandalwood paste or oil causing contact and photoallergic contact dermatitis (73081,73082,99292).
Renal ...Orally, use of large doses of white sandalwood or for more than 6 weeks is associated with kidney damage, with blood in the urine (12,18,19).
