Two caplets contain: Rudofil Proprietary Blend 1905 mg: Glucosamine Sulfate 2KCl, Boswellia resin standardized extract, Turmeric rhizome standardized extract, Trans-Resveratrol . Other Ingredients: Microcrystalline Cellulose, Croscarmellose Sodium, Stearic Acid, Magnesium Stearate, Silica, Film Coat (hypromellose, hydroxypropyl cellulose, polyethylene glycol, propylene glycol, titanium dioxide, FD&C yellow #6 lake, riboflavin, FD&C blue #2 lake). Caution: Contains Crab and Shrimp.
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 Rudofil. 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
Below is general information about the safety of the known ingredients contained in the product Rudofil. 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.
LIKELY SAFE ...when glucosamine sulfate is used orally and appropriately. Glucosamine sulfate has been used safely in multiple clinical trials at a dose of 1000-1500 mg daily for 4 weeks to 3 years (2604,7026,8942,11340,12461)(14305,16717,89558,89567,94380,94382,95785).
POSSIBLY SAFE ...when glucosamine hydrochloride is used orally and appropriately. Glucosamine hydrochloride has been used with apparent safety at a dose of 1400-1600 mg daily for up to 2 years (4237,13579,14809,18344,42477,89516,89519,95784). Glucosamine hydrochloride 2 grams daily has also been used with apparent safety for up to 3 weeks (103281). ...when N-acetyl glucosamine is used orally and appropriately. N-acetyl glucosamine 100 mg daily has been used with apparent safety for up to 24 weeks (95795). ...when N-acetyl glucosamine is applied topically and appropriately. A 2% N-acetyl glucosamine cream has been safely used for up to 10 weeks (92721). ...when N-acetyl glucosamine is used rectally and appropriately. N-acetyl glucosamine 3-4 grams daily in 2 divided doses has been safely used (10234). ...when glucosamine sulfate is used intramuscularly and appropriately, short-term. Intramuscular glucosamine sulfate seems to be well tolerated when given twice weekly for up to 6 weeks (2605).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used in amounts found in foods (2030).
POSSIBLY SAFE ...when taken orally in doses of up to 1500 mg daily for up to 3 months (71066,71097,91328,91331,95825,95833,98910,100695,105183,109163,109167). Higher doses of 2000-3000 mg daily have been well tolerated when taken for 2-6 months, but are more likely to cause gastrointestinal side effects (91327,98908). ...when used topically for up to 30 days (71064). ...when used as an intranasal spray for up to 4 weeks (97339).
CHILDREN: LIKELY SAFE
when used in amounts found in foods.
CHILDREN: POSSIBLY SAFE
when used as an intranasal spray for up to 2 months in children 4 years of age and older (91332).
There is insufficient reliable information available about the safety of resveratrol when used by mouth in larger amounts as medicine.
PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts found in foods (2030).
Resveratrol is found in grape skins, grape juice, wine, and other food sources. However, wine should not be used as a source of resveratrol during pregnancy and lactation.
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). ...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 Rudofil. 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 the levels of CYP3A4 substrates.
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In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes (21178).
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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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Acetaminophen might interfere with the activity of glucosamine sulfate by interacting with the sulfate portion.
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Anecdotal reports suggest that adding glucosamine to an acetaminophen regimen might decrease pain control in patients with osteoarthritis (14806). Some research suggests that the sulfate portion of glucosamine sulfate might contribute to its effect in osteoarthritis. Since acetaminophen metabolism requires sulfur and reduces serum sulfate concentrations, acetaminophen could theoretically interfere with the action of glucosamine sulfate. Conversely, the administration of sulfate could theoretically decrease the effectiveness of acetaminophen in sulfate-deficient people by increasing its clearance (10313).
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Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.
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In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production (371,372,3406,18342,18343). This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients (7026,7075,8942,10311,10317,15111).
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Theoretically glucosamine may induce resistance to topoisomerase II inhibitors.
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In vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells (7639). This effect has not been reported in humans.
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Glucosamine might increase the anticoagulant effects of warfarin and increase the risk of bruising and bleeding.
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In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in international normalized ratio (INR) in patients previously stabilized on warfarin (11389,16130). In one case, the increase in INR occurred only after tripling the dose of a glucosamine/chondroitin supplement from 500 mg/400 mg daily to 1500/1200 mg daily (16130). Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin (16130). There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin (16131). The mechanism of this interaction is unclear. Glucosamine is a small component of heparin, but is not thought to have anticoagulant activity; however, animal research suggests that it might have antiplatelet activity (16131).
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Resveratrol may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A1.
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Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A2.
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In vitro research shows that resveratrol can inhibit CYP1A2 enzymes (21733). However, this interaction has not been reported in humans.
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Theoretically, resveratrol might increase levels of drugs metabolized by CYP1B1.
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In vitro research shows that resveratrol can inhibit CYP1B1 enzymes (70834). However, this interaction has not been reported in humans.
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Theoretically, resveratrol might increase levels of drugs metabolized by CYP2C19.
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In vitro research shows that resveratrol can inhibit CYP2C19 enzymes (70896). However, this interaction has not been reported in humans.
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Resveratrol might increase levels of drugs metabolized by CYP2E1.
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In vitro research suggests that resveratrol inhibits CYP2E1 isoenzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.
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Theoretically, resveratrol might increase levels of drugs metabolized by CYP3A4.
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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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Theoretically, turmeric might increase levels of drugs metabolized by CYP3A4.
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In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499). 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 to 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 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 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 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 Rudofil. 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). 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, all forms of glucosamine seem to be well tolerated.
Topically and rectally, N-acetyl glucosamine also seems to be well tolerated. Intramuscularly, glucosamine sulfate seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted for non-oral routes of administration.
Most Common Adverse Effects:
Orally: Bloating, constipation, cramps, diarrhea, heartburn, nausea.
Serious Adverse Effects (Rare):
Orally: There have been rare reports of severe allergic reactions and hepatotoxicity.
Cardiovascular
...One case of mesenteric occlusion in a clinical trial was considered possibly related to use of oral glucosamine hydrochloride and chondroitin sulfate (89520).
Some observational research has found that glucosamine use in patients with osteoarthritis is associated with a higher risk of cardiovascular disease (CVD) events when compared with non-use (109642). However, glucosamine users tended to be older, have multiple comorbidities, and be on antihyperlipidemic or antiplatelet therapy. Furthermore, other observational research in healthy adults has found that glucosamine use is associated with a reduced risk of fatal and non-fatal CVD events (99682). Higher quality, prospective research is needed to clarify the relationship, if any, between glucosamine and CVD risk.
Dermatologic ...Orally, glucosamine might cause skin reactions, including itching, rash, and erythema (2608,20084,89567,110628). Also, fingernail and toenail toughening, with an increased rate of growth, has been reported (89572). Topically, N-acetyl glucosamine 2% with niacinamide 4% cream might cause rare skin reactions (92721). Photosensitization that was reproducible with re-challenge was reported in a case report of an individual using glucosamine (form unknown) and chondroitin (10408).
Endocrine ...Orally, glucosamine does not seem to impact blood glucose. Preliminary research and anecdotal reports have found that various forms of glucosamine might increase insulin resistance or decrease insulin production, increasing fasting plasma glucose levels (22,371,372,1203,3406,5059,7637,14810). This has raised concerns that taking glucosamine sulfate might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that various forms of glucosamine do not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, patients with type 2 diabetes or impaired glucose tolerance (7026,7075,7638,8942,10311,10317,12107,14808,15111,89563).
Gastrointestinal ...Orally, glucosamine has been associated with gastrointestinal problems, including epigastric and abdominal pain, cramps, heartburn, diarrhea, nausea, dyspepsia, vomiting, constipation, and flatulence (1520,2608,16717,20084,20104,20105,89561,89562,89567,89568)(108897,110628,111647). In older persons, use of glucosamine sulfate is associated with oral dryness (89564). In a clinical trial, a case of Helicobacter pylori gastritis was considered probably related to the use of glucosamine hydrochloride (89516).
Hepatic ...Although relatively uncommon, combinations of glucosamine and chondroitin sulfate have been associated with acute liver injury that mimics autoimmune hepatitis. Of 151 patients at an outpatient clinic for liver diseases, 23 acknowledged use of products containing glucosamine (form unspecified) and/or chondroitin. However, only 2 cases had an apparent relationship between transaminase elevation and the use of recommended doses of glucosamine and chondroitin sulfate. Aminotransferase levels, which were increased by four- to seven-fold, returned to normal following discontinuation of treatment (89515). In another case, a 65-year-old male presented to the hospital with signs and symptoms of drug-induced autoimmune hepatitis. The patient had used Condrosulf, containing chondroitin sulfate, for two years, followed by Vita Mobility Complex, containing chondroitin sulfate and glucosamine sulfate, for 8 weeks. The patient required maintenance treatment with azathioprine to remain in remission (89518). A case of acute cholestatic hepatitis due to Glucosamine Forte, which contains glucosamine hydrochloride, chondroitin sulfate, Devil's claw, and shark cartilage, has been reported (89522). It is unclear whether these adverse events were related to glucosamine, other ingredients, or the combination.
Immunologic ...There is some concern that glucosamine products might cause allergic reactions in sensitive individuals. One review of glucosamine-related adverse events in Australia found that 72% of all reports involved hypersensitivity reactions. Of these reactions, 35% were mild, including pruritis, urticaria, and lip edema, 49% were moderate, including dyspnea, and 16% were severe, including gait disturbance, somnolence, and hypotension. Anaphylaxis was reported in 1.5% of cases (102115). Also, in one clinical trial, a single patient developed allergic dermatitis considered to be likely due to glucosamine hydrochloride (89516). Glucosamine is derived from the exoskeletons of shrimp, lobster, and crabs. However, it is unclear if these adverse reactions were due to a shellfish sensitivity or general atopy. Additionally, shellfish allergies are caused by IgE antibodies to antigens in the meat of shellfish, not to antigens in the exoskeleton. Regardless, it is possible that some glucosamine products might be contaminated by this allergen during production (102115).
Neurologic/CNS ...Orally, glucosamine has been reported to cause drowsiness and headache (2608,89561). Glucosamine plus chondroitin combination products that also contain manganese (e.g., CosaminDS) should always be taken according to product directions. When taken at doses slightly higher than the recommended dose, these products can sometimes supply greater than the tolerable upper limit (UL) for manganese which is 11 mg/day. Ingestion of more than 11 mg/day of manganese might cause significant central nervous system toxicity (7135).
Ocular/Otic ...In older persons, use of glucosamine sulfate has been associated with ocular dryness (89564). Increased intraocular pressure has occurred with glucosamine sulfate supplementation (89573,112460). Data from the FDA MedWatch adverse event reporting system shows that 0.21% of subjects taking glucosamine reported glaucoma, which is significantly greater than the 0.08% of subjects who reported glaucoma while using any other drug (112460).
Pulmonary/Respiratory ...Cases of asthma exacerbations associated with the use of glucosamine (form unknown)-chondroitin products have been reported (10002).
Renal ...Anecdotal reports have associated glucosamine with nephrotoxicity signals such as modestly elevated creatine phosphokinase and 1+ to 2+ proteinuria, but changes in kidney function have not been reported in long-term studies (7026,8942,10408,10409). It was also noted that effects may have been due to other concurrent medications or impurities in glucosamine-chondroitin products. Cases of acute interstitial nephritis induced by glucosamine (form unknown) have also been reported (89523).
Other ...There has been concern that glucosamine might increase the risk of metabolic disturbances resulting in increased cholesterol levels and blood pressure. However, glucosamine does not appear to increase the risk of these adverse effects. Taking glucosamine sulfate for up to 3 years does not significantly increase blood glucose or lipid levels, or cause any other disturbances in metabolism (7026,7075,8942,10311,10317).
General
...In foods, resveratrol is well tolerated.
When used orally in higher doses, as well as topically or intranasally, resveratrol seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, and loose stools.
Dermatologic
...Orally, there is one case of a pruritic skin rash that occurred in a clinical trial.
The rash resolved two weeks after stopping resveratrol (109163).
Topically, a case of allergic contact dermatitis has been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing aqueous resveratrol 1% in combination with Baikal skullcap root extract 0.5%. Patch testing identified a positive reaction to both ingredients (110024).
Gastrointestinal ...Orally, mild gastrointestinal discomfort with increased diarrhea or loose stools has been reported, especially when resveratrol is taken in doses of 2. 5-5 grams daily (71042,71052,91327,95830,109163,109164,109167).
Hematologic ...In one clinical study, a patient developed severe febrile leukopenia and thrombocytopenia after taking oral resveratrol 500 mg three times daily for 10 days. Upon re-exposure to resveratrol, febrile leukopenia recurred (109163).
Musculoskeletal ...Orally, resveratrol has been associated with muscle cramps in patients on peritoneal dialysis. The causality of this adverse effect has not been established (95830).
Neurologic/CNS ...Orally, resveratrol has been associated with headache, fatigue, and memory loss in patients on peritoneal dialysis. The causality of these adverse effects has not been established (95830).
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). 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), 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).
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).
