Each capsule contains: Boswellia serrata (65% boswellic acid) 100 mg • Curcuma Longa 80:1 extract (95% curcumin, DHE: 400 mg) 5 mg • Harpagophytum procumbens DC burch pedaliaceae 2:1 extract (1% harpagosides, DHE: 150 mg) 75 mg • Juniperus communis 50 mg • Methylsulfonylmethane 250 mg • Zingiber officinale 8:1 extract (5% gingerois, DHE: 75 mg) 9.375 mg. Other Ingredients: Gelatin, Magnesium Stearate, Stearic Acid, Water.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
Below is general information about the effectiveness of the known ingredients contained in the product Joint +. 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
Below is general information about the safety of the known ingredients contained in the product Joint +. 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 and appropriately. Boswellia serrata extract in doses up to 1000 mg daily has been safely used in several clinical trials lasting up to 6 months (1708,1709,12432,12434,12438,17948,17949,17950,91379)(100699,100713,102089,109568). Boswellia serrata extract has been used with apparent safety at a dose of 2400 mg for up to 1 month (102092).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of using Boswellia serrata in medicinal amounts; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Devil's claw extract has been used with apparent safety in doses of up to 2400 mg daily for up 12 weeks (6472,8608,14332,14418,47112,47114,47116,47117,47155). There is insufficient reliable information available about the safety of devil's claw when used orally long-term or when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Anecdotal evidence suggests that devil's claw has oxytocic effects in humans. Also, in vitro research shows that moderate to high doses of devil's claw root extract induce contractions of isolated uterine muscle from pregnant and nonpregnant rats (94689); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).
POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).
CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).
PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods.
Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes.
Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).
LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods.
There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Juniper, juniper berry, and juniper extract have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used topically on limited areas of skin (12230). ...when the oil is used by inhalation and appropriately as aromatherapy (7107). There is insufficient reliable information available about the safety of juniper when used orally in doses of less than 10 grams of berries or 100 mg of oil daily, short-term. Juniper oil and berry have a long history of traditional use (12,103759).
LIKELY UNSAFE ...when used orally in excessive amounts or long-term. Use of daily doses greater than 10 grams of juniper berries (about 60 berries) or 100 mg of juniper essential oil, or prolonged oral use longer than 4 weeks, have been reported to increase the risk of severe adverse effects such as convulsions or kidney damage (8,19,103759).
PREGNANCY: UNSAFE
when used orally.
Juniper can increase uterine tone, interfere with fertility and implantation, and cause abortion (4,19).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short term. MSM in doses of 1.5-6 grams daily or 50 mg/kg daily has been used safely in studies lasting up to 6 months (8574,12469,14335,17127,19312,96446,96448,102555). One specific product (OptiMSM, Bergstrom Nutrition) is Generally Recognized As Safe (GRAS) by the United States Food and Drug Administration (FDA) (102555). ...when used topically. Topical cream containing MSM and silymarin, as well as topical gel containing MSM, hyaluronic acid, and tea tree oil, have been used with apparent safety for up to 20 days (19318,19319).
PREGNANCY AND 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). Turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357). ...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 Joint +. 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, Boswellia serrata might increase the levels of CYP1A2 substrates.
 Details
In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes (21178).
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Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates.
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In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes (21178).
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Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.
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In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes (21178).
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Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.
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In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes (21178).
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Theoretically, Boswellia serrata might increase or decrease the levels and clinical effects of CYP3A4 substrates.
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Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.
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Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity (12432,12435,12437,12438). However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways (21180).
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Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C19.
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In vitro research shows that devil's claw might inhibit CYP2C19, although this has not been reported in humans (12479).
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Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C9.
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In vitro research shows that devil's claw might inhibit CYP2C9, although this has not been reported in humans (12479).
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Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.
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In vitro research shows that devil's claw might inhibit CYP3A4, although this has not been reported in humans (12479).
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Theoretically, devil's claw might decrease the effectiveness of H2-blockers.
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Devil's claw has been reported to increase stomach acid, which might interfere with the effects of H2-blockers (19).
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Theoretically, devil's claw might increase levels of P-glycoprotein substrates.
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Theoretically, devil's claw might decrease the effectiveness of PPIs.
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Devil's claw has been reported to increase stomach acid, which might interfere with the effects of PPIs (19).
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Theoretically, Devil's claw might increase the activity of warfarin.
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In one case report, purpura occurred in a patient taking warfarin and devil's claw concurrently. This might indicate over-anticoagulation (613). It is unclear if this was due to Devil's claw or other contributing factors.
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Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
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Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
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Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
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Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).
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Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
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In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).
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Theoretically, ginger might increase the levels of CYP1A2 substrates.
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In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2B6 substrates.
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In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2C9 substrates.
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In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.
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Ginger might increase or decrease the levels of CYP3A4 substrates.
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In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans. |
Theoretically, ginger might increase levels of losartan and the risk of hypotension.
Details
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.
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Theoretically, ginger might increase levels of metronidazole.
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In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).
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Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
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Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).
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Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
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In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
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Ginger might increase the risk of bleeding with phenprocoumon.
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Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).
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Ginger might increase the risk of bleeding with warfarin.
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Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.
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Theoretically, taking juniper berry with antidiabetes medications might cause additive hypoglycemia.
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Theoretically, juniper berry might increase the risk of adverse effects from diuretic drugs.
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Theoretically, juniper berry might reduce lithium excretion and increase serum levels of lithium.
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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.
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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.
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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.
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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.
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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). Another clinical study in patients with diabetes on hemodialysis shows that taking curcumin 80 mg daily for 12 weeks can reduce blood glucose levels when compared with placebo (104149).
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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.
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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.
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Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
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Turmeric might increase levels of drugs metabolized by CYP3A4.
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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.
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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.
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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.
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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.
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Theoretically, turmeric might increase the effects of losartan.
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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.
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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.
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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.
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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.
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Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
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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.
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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.
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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.
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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.
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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.
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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.
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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 Joint +. 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, Boswellia serrata extract is generally well-tolerated.
For information on the safety of Boswellia serrata when applied topically or used as aromatherapy, see the Frankincense monograph.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, headache, heartburn, itching, nausea.
Serious Adverse Effects (Rare):
Orally: Large amounts of Boswellia serrata gum resin can cause bezoar formation.
Dermatologic ...Orally, Boswellia serrata extract (5-Loxin) has been associated with itching at doses of 100-250 mg daily (17948).
Gastrointestinal ...Orally, Boswellia serrata extract may cause diarrhea, nausea, abdominal pain, and heartburn (1708,12432,12438,17948,17949,17950,21149,109567,114685). A case of a large gastrointestinal bezoar has been reported in a 17-year-old female who chewed and swallowed large quantities of boswellia gum resin (Boswellia species not specified) for celiac disease (36914).
Musculoskeletal ...Orally, Boswellia serrata extract (5-Loxin) has been associated with one case of foot edema and four cases of generalized weakness in one clinical study (17948).
Neurologic/CNS ...Orally, Boswellia serrata extract may cause dizziness, headache, and vertigo. In one clinical study, nearly 11% of patients taking a specific Boswellia serrata extract (K-Vie) reported headache. Dizziness and vertigo were also reported, but at lower rates (109567). In another study, headache was reported in one patient taking a specific Boswellia serrata extract (5-Loxin) (17948).
Psychiatric ...Orally, one case of mania is reported in a 73-year-old male who took Boswellia powder mixed with honey for 3 days. The patient recovered after hospitalization and treatment with olanzapine (110526).
General
...Orally, Devil's claw seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin reactions, diarrhea, dyspepsia.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal bleeding.
Cardiovascular ...In one case report, a healthy patient with normal blood pressure presented with hypertension after taking devil's claw 250 mg twice daily for 2 weeks. It gradually resolved after discontinuation of devil's claw (92017). Some animal research shows that devil's claw might have negative chronotropic, as well as positive and negative inotropic, effects (8609). However, these effects have not been documented in humans.
Dermatologic ...Rarely, allergic skin reactions have been reported in patients taking devil's claw (8608,14418).
Endocrine ...In one case report, a 65-year-old female developed psychomotor agitation, nausea, and distress from euvolemic hyponatremia secondary to inappropriate secretion of antidiuretic hormone (SIADH) within 1 month of starting daily treatment with devil's claw. Within 5 days of discontinuing the product and receiving sodium replacement, the symptoms resolved. Two months later, the patient re-initiated devil's claw and again developed euvolemic hyponatremia (96747).
Gastrointestinal ...Gastrointestinal side effects, including mild gastrointestinal upset, diarrhea, anorexia, acid reflux, or loss of taste, have been reported in some individuals receiving devil's claw, especially at high doses (6472,8608,8613,14332,14418,47112,47116,47144,47169). Gastrointestinal complaints have been reported in 9% to 18% of patients taking a specific devil's claw extract (Doloteffin, Ardeypharm) (8608,47169), while diarrhea was reported in about 8% of patients taking devil's claw (Harpadol, Arkopharma) (6472). Several cases of gastrointestinal bleeding have been reported (104977).
Genitourinary ...Dysmenorrhea was reported in one patient taking a specific devil's claw extract (Doloteffin, Ardeypharm) for 8 weeks (8608).
Neurologic/CNS ...In a trial of devil's claw, one patient withdrew after 4 days of therapy due to a throbbing frontal headache, as well as tinnitus, anorexia, and loss of taste (8613). Rarely, dizziness, somnolence, and insomnia have been reported (47116,47169). It is unclear if these symptoms were caused by devil's claw.
Psychiatric ...Rarely, anxiety has been reported in patients taking devil's claw (8608).
General
...Orally, ginger is generally well tolerated.
However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.
Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).
Dermatologic
...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).
Gastrointestinal
...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076).
Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).
Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).
Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).
Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).
General
...Orally and topically, juniper seems to be generally well tolerated when used short-term in low doses.
However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Allergies, skin irritation.
Dermatologic ...Topically, juniper can cause skin irritation. Signs of topical poisoning include burning, erythema, inflammation with blisters, and edema (4). Repeated exposure to the juniper pollen can cause occupational allergies that affect the skin (6). In a case report, a 62-year-old woman developed burn-like blistering lesions after carrying juniper in close contact to her skin. Concurrent sun exposure was thought to worsen the skin irritation caused by juniper (103756).
Genitourinary ...Orally, large amounts of the juniper berry can cause purplish urine (4).
Pulmonary/Respiratory ...Repeated exposure to the juniper pollen can cause occupational allergies that affect the respiratory tract (6).
General
...Orally, MSM is generally well tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal discomfort, nausea.
Dermatologic ...In rare cases, MSM has caused pruritus when taken orally (8574).
Gastrointestinal ...Orally, MSM may cause mild gastrointestinal discomfort, nausea, bloating, and diarrhea (8574,12469).
Immunologic ...Orally, MSM may increase allergy symptoms (8574).
Neurologic/CNS ...Orally, MSM may cause headache, fatigue, insomnia, and difficulty concentrating (8574,14335).
Ocular/Otic ...In a case report, a 35-year-old female presented with bilateral acute angle closure glaucoma, which resolved 4 days after discontinuing a multi-ingredient product. Although the product contained over 35 vitamins, minerals, and other ingredients, only MSM contained sulfur, which the authors suggest acted like a sulfa-drug to cause acute angle closure glaucoma (90613).
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). 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), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430), 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, the turmeric constituent curcumin can cause vertigo, but this effect seems to be uncommon (81163).
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).
