| Ingredients | Amount Per Serving |
|---|---|
|
(Curcuma longa )
(root)
|
1000 mg |
|
(Crocus sativus )
(flower)
|
89 mg |
|
(Elettaria cardamomum )
(seed)
|
50 mg |
|
(Cinnamomum verum )
(bark)
|
50 mg |
|
(Piper nigrum )
(fruit)
(Black Pepper extract)
|
10 mg |
Hypromellose capsule, Guar Gum, Magnesium Stearate
Below is general information about the effectiveness of the known ingredients contained in the product Turmeric Cinnamon Saffron + Cardamom. 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
Below is general information about the safety of the known ingredients contained in the product Turmeric Cinnamon Saffron + Cardamom. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Black pepper has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts.
Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
PREGNANCY: LIKELY UNSAFE
when used orally in large amounts.
Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.
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.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Ceylon cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Ceylon cinnamon 0.5-3 grams daily has been safely used in studies lasting up to 6 months (4,12,97248,97250,99874). ...when used as a mouth rinse for up to 15 days (92071). There is insufficient reliable information available about the safety of Ceylon cinnamon when used orally in greater amounts or for longer periods. Ceylon cinnamon contains trace amounts of coumarin (108260). In very high doses, coumarin can cause hepatotoxicity (15302). However, since the amount of coumarin in Ceylon cinnamon is negligible, it is unlikely to cause toxic effects (89652,92072,92073).
PREGNANCY: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in foods.
Fetal abnormalities have been reported in animals (4,12).
LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of Ceylon cinnamon in amounts greater than those found in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Saffron has Generally Recognized as Safe (GRAS) status in the US for use as a spice or food coloring agent (4912).
POSSIBLY SAFE ...when used orally and appropriately in larger amounts, short-term. Saffron extracts have been used with apparent safety in clinical trials at doses of up to 100 mg daily for up to 26 weeks (11024,13103,16555,17214,17401,18102,93395,93397,93400,93403)(93407,97359,99436,100135,100138,100140,100658,100659). The saffron constituent crocin has been used with apparent safety at a dose of up to 30 mg daily for up to 3 months (93410,100139,105616).
POSSIBLY UNSAFE ...when used orally in high doses or for longer than 26 weeks. Taking 5 grams or more of saffron can cause severe side effects. Doses of 12-20 grams can be lethal (12,18). There is insufficient reliable information available about the safety of saffron when used topically.
PREGNANCY: LIKELY UNSAFE
when used orally in amounts exceeding those commonly found in foods.
Larger amounts of saffron have uterine stimulant and abortifacient effects (18); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
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.
Below is general information about the interactions of the known ingredients contained in the product Turmeric Cinnamon Saffron + Cardamom. 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, black pepper might increase the effects and side effects of amoxicillin.
 Details
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
Details
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
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Theoretically, black pepper might increase blood levels of atorvastatin.
Details
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.
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Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
Details
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) 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). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).
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Theoretically, black pepper might increase the effects and side effects of cyclosporine.
Details
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.
Details
In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.
Details
In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
Details
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Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
Details
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Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Details
Black pepper is thought to have diuretic properties (11).
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Black pepper might increase blood levels of nevirapine.
Details
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).
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Theoretically, black pepper might increase levels of P-glycoprotein substrates.
Details
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Theoretically, black pepper might increase the sedative effects of pentobarbital.
Details
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).
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Black pepper might increase blood levels of phenytoin.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).
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Black pepper might increase blood levels of propranolol.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).
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Black pepper might increase blood levels of rifampin.
Details
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Black pepper might increase blood levels of theophylline.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).
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Theoretically, Ceylon cinnamon may have additive effects with antidiabetes drugs.
Details
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Theoretically, Ceylon cinnamon might have additive effects with antihypertensive drugs and increase the risk of hypotension.
Details
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Theoretically, concomitant use of saffron with antidiabetes drugs might increase the risk of hypoglycemia.
Details
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Theoretically, concomitant use of saffron with antihypertensive drugs might have additive effects.
Details
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Theoretically, saffron might inhibit the metabolism of caffeine.
Details
A small clinical study suggests that taking saffron powder 300 mg in 150 mL water daily for 5 days and then taking caffeine 200 mg seems to reduce caffeine metabolite levels in the saliva and urine in males, but not females. Theoretically, this may be due to the inhibition of cytochrome P450 1A2 by saffron (100130).
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Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.
Details
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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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Below is general information about the adverse effects of the known ingredients contained in the product Turmeric Cinnamon Saffron + Cardamom. 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, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose.
Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.
Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.
Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).
Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).
Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).
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, Ceylon cinnamon is generally well tolerated, and adverse reactions are uncommon.
Most Common Adverse Effects:
Orally: Bloating, dyspepsia, nausea.
Topically: Allergic dermatitis, irritation of mucous membranes and skin.
Dermatologic
...Orally, a case of systemic contact dermatitis has been reported in a patient who consumed cinnamon (type not specified) after being previously sensitized to cinnamyl alcohol via cutaneous exposure (95599).
In a small study of oral Ceylon cinnamon, two patients reported itching (104520). In another small study, two patients reported rashes (108263).
Topically, cinnamon oil can cause skin irritation and allergic dermatitis, probably due to cinnamaldehyde which makes up 60% to 80% of cinnamon oil (2537,12635,92071,95596,95599). In one case report, a 16-year-old female experienced worsening dermatitis after using a homemade facial scrub containing cinnamon powder (type not specified). Symptoms improved after discontinuation of the scrub (95596). Several cases of intraoral allergic contact dermatitis have been reported in patients consuming cinnamon (type not specified) or using products containing constituents of cinnamon (95598).
Gastrointestinal ...Orally, gastrointestinal side effects such as heartburn, nausea, bloating, and dyspepsia have been reported (97250).
Hematologic ...Orally, a case of postoperative hemorrhage is reported in a 49-year-old patient after taking Ceylon cinnamon 1 tablespoon daily for 10 months. One day post-colectomy, the patient had an INR of 1.59 and intraabdominal bleeding that required exploratory laparotomies, blood transfusion, and fresh frozen plasma. Ultimately, the patient was discharged (112421).
Hepatic ...While there is concern about the coumarin content in cassia cinnamon increasing the risk for hepatic adverse effects and bleeding, the amount of coumarin in Ceylon cinnamon is negligible and unlikely to cause toxic effects (89652,92072,92073). In one case report, a 73-year-old female taking rosuvastatin for several months developed elevated liver function tests (LFTs), abdominal pain, nausea, and vomiting after taking cinnamon (unknown dose and type) for 7 days. The acute hepatitis and elevated LFTs resolved after stopping both cinnamon and rosuvastatin. The patient was later able to resume rosuvastatin without recurrence (97249).
General
...Orally, saffron extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal complaints, nausea, sedation, vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Dermatologic ...Orally, sweating and flushing have been reported in clinical research for patients taking saffron 30-60 mg daily (93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the skin (2,11).
Gastrointestinal ...Orally, saffron has been associated with changes in appetite, nausea, and vomiting when given at doses of 30 mg twice daily for 26 weeks, or when the saffron constituent crocin was given as 15 mg twice daily for 12 weeks (18102,105616). At lower doses of 30 mg daily, the occurrence rate of these and other adverse events such as dry mouth, dyspepsia, diarrhea, and constipation was rare or similar to placebo (13103,93395,93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the mucous membranes (mimicking icterus), vomiting, and bloody diarrhea (2,11).
Genitourinary
...One report of excessive uterine bleeding occurred in a clinical trial.
The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bleeding from the uterus (2,11).
Hematologic
...Orally, saffron extract has been reported to cause decreases in platelet, white blood cell, and red blood cell counts after 7 days to 12 weeks of use with doses of 60-200 mg daily.
Many of these decreases were only significant when compared to baseline but did not maintain significance when compared to placebo. These reductions were not considered clinically significant (18102,72473,93403,93409).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bloody diarrhea, hematuria, bleeding from the nose, lips, eyelids or uterus, and thrombocytopenic purpura (2,11).
Immunologic ...Allergy to oral saffron has been reported in clinical trials (93404). Anaphylactic reactions can occur within minutes of eating food prepared with saffron (4107,72555). Occupational exposure to saffron has been associated with the development of rhinoconjunctivitis and allergy-induced asthma (4106).
Neurologic/CNS ...Orally, saffron has been reported to cause drowsiness, headache, agitation, and sedation when given at doses of 30 mg twice daily for up to 26 weeks or when crocin is given as 15 mg twice daily for 12 weeks (18102,105616). At doses of 30 mg daily for 6 weeks, the side effect occurrence rate was similar to placebo (13103). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include vertigo and numbness (2,11).
Ocular/Otic ...Orally, saffron poisoning with oral intake of doses of 5 grams or more can cause ocular symptoms such as yellow appearance of the sclera (2,11).
Psychiatric ...Orally, saffron has been reported to cause anxiety and hypomania when given at doses of 30 mg twice daily for 26 weeks (18102). At doses of 30 mg daily for 6 weeks, the occurrence rate was similar to placebo (13103,93395). One report of agitation occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Renal ...Orally, the saffron constituent crocin given as 15 mg twice daily for 12 week was associated with one case of urinary incontinence (105616). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include hematuria and uremic collapse (2,11).
General
...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).
