Radiance Boost + by Herbal Goodness

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dental caries. It is unclear if brushing the teeth with toothpaste containing bamboo salt can prevent dental carries. Details: A small clinical trial in dental students with good oral hygiene and a lack of dental carries shows that brushing with a specific toothpaste containing bamboo salt (Tiger Herb, LG) twice daily for 4 weeks reduces salivary counts of Streptococcus mutans and Lactobacillus when compared to baseline. These reductions were similar to those reported in students using a conventional toothpaste (Crest Complete) (109458). It is unclear whether this toothpaste is effective for preventing dental carries. More evidence is needed to rate bamboo for this use.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diarrhea. Clinical research in adults with acute diarrhea shows that taking guava leaf extract (QG-5) 500 mg every 8 hours for 3 days in addition to oral rehydration therapy (ORT) does not shorten the duration of diarrhea or improve stool consistency or pain intensity when compared with ORT alone. However, there was a reduction in the number of episodes of abdominal pain after the first day of treatment (70318).
• Dysmenorrhea. Clinical research in young women with dysmenorrhea shows that taking guava leaf extract 1 mg or 2 mg three times daily for 5 days starting 24 hours before menstruation for 3 cycles does not reduce pain when compared with placebo. However, pain was reduced by a small amount in the women with the best compliance (101782).
• Gingivitis. Clinical research in patients with moderate to severe chronic gingivitis shows that using a guava leaf extract 0.15% mouth rinse twice daily with brushing for 30 days is as effective as 0.2% chlorhexidine and more effective than water for reducing gingivitis severity and microbial counts. However, using the guava leaf extract mouth rinse does not appear to improve plaque (101754).
• Hypertension. Preliminary clinical research in patients with essential hypertension shows that eating guava fruit 500-1000 grams daily in place of other foods high in saturated fat and cholesterol for 12 weeks lowers systolic blood pressure by 9.0 mmHg and diastolic blood pressure by 8.0 mmHg compared to usual diet (95562).
• Knee pain. Preliminary clinical research in patients with knee pain shows that taking guava leaf extract 1 gram daily for 12 weeks reduces pain and stiffness by a small amount when compared to placebo. There is no effect on function (101758). This study was small and might not have been adequately powered to detect differences. More evidence is needed to rate guava for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there is interest in using oral fermented papaya for aging skin, there is insufficient reliable information about the clinical effects of papaya for this purpose.
• Androgenic alopecia. Papaya has only been evaluated in combination with other ingredients for androgenic alopecia; its effect when used alone is unclear. Details: A clinical study in adults with androgenic and diffuse alopecia shows that applying fermented papaya 2% hair lotion also containing fermented mangosteen and caffeine on the scalp daily plus fermented papaya 0.5% shampoo also containing fermented mangosteen on the scalp 3 times weekly for 14 weeks shows improvement in hair loss intensity and the quality of hair shaft compared to baseline (111719). It is unclear if the effect is due to the fermented papaya, other ingredients, or the combination.
• Colorectal cancer. It is unclear if oral papaya fruit prevents colorectal cancer. Details: One small observational study in adults living in Thailand has found that papaya fruit consumption is associated with a 42% lower odds of developing colorectal cancer (67941).
• Dengue fever. Small clinical studies suggest that oral papaya leaf extract might increase platelet counts in patients with dengue fever. Details: A meta-analysis of mostly small clinical studies in adults with dengue fever shows that taking papaya leaf extract reduces the duration of hospital stay by about 2 days and improves mean platelet count over the next five days by about 35 x 10⁹ when compared with standard treatment. The most common dosing ranged from 500 mg to 3300 mg daily for five days in divided doses (102799). This finding is limited by imprecision and high risk of bias. One additional small clinical study in patients with severe thrombocytopenia due to dengue fever shows that taking a papaya leaf extract (Caripill, Micro Labs) 1100 mg three times daily for 5 days increases platelet counts by a greater amount through day 3 when compared with placebo, and reduces the median time to platelet recovery by one day (102800).
• Diabetes. It is unclear if oral fermented papaya improves glycemic control in patients with diabetes. Details: A small clinical study in patients with type 2 diabetes shows that consuming fermented papaya fruit 3 grams once daily for 2 months reduces fasting and postprandial blood glucose levels by 13% and 10%, respectively, when compared to baseline (67902). The validity of this finding is limited by the lack of a comparator group.
• Gallbladder cancer. It is unclear if oral fermented papaya prevents gallbladder cancer. Details: One small observational study in adults living in Thailand has found that eating papaya fruit is associated with a 66% lower odds of developing gallbladder cancer (67871).
• Gingivitis. It is unclear if using toothpaste and/or mouthwash containing fermented papaya leaf extract improves symptoms of gingivitis. Details: Preliminary clinical research in adults with good oral hygiene shows that brushing teeth twice daily with a toothpaste containing papaya leaf extract for 4 weeks, with or without the use of a papaya leaf extract-containing mouthwash, decreases gingival bleeding when compared to baseline. However, using this toothpaste with or without the mouthwash is no better than using a sodium lauryl sulfate (SLS)-free, enzyme-containing toothpaste, with or without an essential oil mouthwash (99861).
• Human papillomavirus (HPV). It is unclear if oral papaya fruit prevents persistent HPV infection. Details: A small population study in females infected with HPV has found that consuming papaya fruit at least once weekly is associated with 70% lower odds of persistent HPV infection when compared with never eating papaya fruit (67881).
• Intestinal parasite infection. Although there is interest in using oral papaya for intestinal parasite infection, there is insufficient reliable information about the clinical effects of papaya for this condition.
• Periodontitis. It is unclear if applying fermented papaya gel into gingival pockets is beneficial for periodontitis. Details: One small open-label clinical study in adults with moderate to severe periodontitis shows that, when used in addition to standard treatment, applying fermented papaya gel (Carica Co.) 7 grams into intragingival pockets for 15 minutes daily for 10 days seems to improve bleeding, plaque, and gingivitis after 7-45 days when compared with standard treatment alone (93090). The validity of this finding is limited by the lack of blinding.
• Thrombocytopenia. Although there is interest in using oral papaya leaf extract for immune thrombocytopenic purpura (ITP), there is insufficient reliable information about the clinical effects of papaya for this condition.
• Wound healing. It is unclear if topical papaya fruit gel is beneficial for wound healing. Details: A small open-label clinical study in patients with post-caesarean section wound gape shows that applying a wound dressing containing partially ripe papaya fruit 200 grams to the edges of a gaped wound for 48 hours, and re-applying as needed, seems to modestly speed up the development of granulation tissue and reduce the duration of hospitalization when compared with using hydrogen peroxide dressings, changed daily (93091). The validity of this finding is limited because the control treatment with hydrogen peroxide may cause skin damage and slow wound healing. More evidence is needed to rate papaya for these uses.

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POSSIBLY EFFECTIVE

• Memory. Oral rosemary seems to improve memory in young adults. It is unclear if rosemary aromatherapy improves memory. Details: Clinical research in healthy adults shows that taking rosemary 500 mg orally twice daily for one month improves memory by approximately 14% when compared with placebo (98536). Other preliminary clinical research shows that applying four drops of pure rosemary essential oil (Tisserand Aromatherapy) to an aromatherapy diffuser pad 5 minutes before a single test period can improve the quality, but not the speed, of memory recall, and increase alertness and contentment more than lavender aromatherapy or no aroma (18323). Rosemary aromatherapy has also been evaluated for improving memory in adults with kidney failure. A small clinical study in patients (mean age 53 years) undergoing hemodialysis shows that aromatherapy with rosemary essential oil three times weekly for 1 month does not improve medication adherence or measures of prospective and retrospective memory when compared with a control group. In this study, five drops of rosemary essential oil were applied to gauze, which was then placed 10 cm from the patient's nose for 30 minutes starting 1 hour after hemodialysis (109559).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there has been interest in the use of oral rosemary as an abortifacient, there is insufficient reliable information about the clinical effects of rosemary for this purpose.
• Age-related cognitive decline. It is unclear if oral rosemary is beneficial for age-related cognitive decline. Details: A small clinical study in healthy individuals aged 65-90 years shows that a single 750 mg dose of powdered rosemary leaf in tomato juice may improve memory speed. However, higher single doses of 1500-6000 mg seem to have a deleterious effect on memory speed. For other measures of attention and memory, there were no clear benefits across the range of doses from 750-6000 mg (18246). Oral rosemary has also been evaluated in combination with other ingredients. A small clinical study in healthy adults aged 62 years or younger shows that taking a combination product containing equal parts rosemary, lemon balm, and sage twice daily for 2 weeks modestly improves word recall when compared with placebo. However, it does not appear to have benefit in adults aged 63 years and older (97277). It is unclear if any benefit is due to rosemary, other ingredients, or the combination.
• Alopecia areata. Topical rosemary oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rosemary oil 114 mg, in combination with lavender oil 108 mg, thyme oil 88 mg, and cedarwood oil 94 mg, mixed with jojoba oil 3 mL and grapeseed oil 20 mL and applied topically to the scalp, improves hair growth in 44% of patients, compared with 15% of those receiving placebo. This combination was massaged into the scalp for a minimum of 2 minutes, followed by wrapping the head in a warm towel, every night for 7 months (5177).
• Androgenic alopecia. It is unclear if topical rosemary is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying rosemary oil (Barij Essence Pharmaceutical Company) 1 mL to the scalp twice daily for 6 months is as effective as minoxidil 2% for increasing hair count in patients with androgenic alopecia (91729).
• Depression. It is unclear if oral rosemary is beneficial for major depressive disorder. Details: A small clinical trial among adults newly diagnosed with major depressive disorder and recent initiation of antidepressant medication shows that taking rosemary dried leaf extract 650 mg twice daily for 8 weeks might reduce some symptoms of depression and anxiety when compared with placebo (112141). However, the validity of these findings is limited by differences in baseline depression symptom scores between groups.
• Diabetes. It is unclear if oral rosemary is beneficial for improving glycemic control in patients with type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that taking rosemary tea daily for 90 days decreases glycated hemoglobin levels by 15% and waist and hip circumference by 6% and improves insulin resistance. However, there was no effect on fasting blood glucose, lipid profile, body weight, or body mass index (BMI). The tea was made by adding rosemary 2 grams to a liter of boiling water for 3 minutes and then passing through a sieve (105323). Other preliminary clinical research in adults with type 2 diabetes shows that taking rosemary powder 3 grams daily for 4 weeks does not reduce fasting blood glucose levels or improve lipid profile when compared with baseline. These endpoints were improved in a group of healthy adults (105327). The validity of the findings from these studies is limited by the lack a comparator group.
• Diabetic nephropathy. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Canephron N, Bionorica) containing 18 mg each of rosemary leaf, centaury herb, and lovage root per tablet, as two tablets three times daily for 6 months along with standard antidiabetes treatment and enalapril (Vasotec), decreases microalbuminuria by 73%, decreases albumin:creatinine ratio by 46%, increases high-density lipoprotein (HDL) cholesterol by 25%, and lowers triglyceride levels by 43%, but does not improve glomerular filtration rate, when compared to baseline. Improvements were greater in those taking the combination product than in those treated only with standard antidiabetes therapy and enalapril. However, the combination product does not appear to improve reductions in total cholesterol or low-density lipoprotein (LDL) cholesterol (91726).
• Dysmenorrhea. It is unclear if oral rosemary is beneficial for dysmenorrhea. Details: In patients with moderate primary dysmenorrhea, clinical research shows that taking rosemary extract 220 mg every 8 hours for the first three days of the menstrual cycle, repeated for two menstrual cycles, is as effective as mefenamic acid for reducing average pain and bleeding when compared with two baseline cycles (105328).
• Fatigue. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults with below-average energy levels shows that taking a single dose of a mixture of rosemary from Albania (Rosmarinus officinalis) and Morocco (Rosmarinus eriocalyx) 1.7 grams does not consistently improve sustained attention, motivation to perform cognitive tasks, mental energy, or mental fatigue when compared with placebo (91731).
• Fibromyalgia. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking an oral product containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (Meta050, Metagenics), at a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks, does not improve symptoms when compared to baseline (18327).
• Gingivitis. A mouth rinse containing rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with 10 mL of mouthwash containing 5% v/v of a combined alcoholic extract of rosemary, calendula, and ginger for 30 seconds twice daily after meals for 2 weeks decreases plaque formation, gingival inflammation, and gingival bleeding similarly to chlorhexidine gluconate 0.2% mouthwash and better than a placebo mouthwash (93555).
• Hypertension. Although there is interest in using oral rosemary for hypertension, there is insufficient reliable information about the clinical effects of rosemary for this condition.
• Hypotension. It is unclear if oral rosemary is beneficial for hypotension. Details: Preliminary clinical research in patients with primary hypotension shows that taking rosemary essential oil (Metapharmaceutical) 1 mL every 8 hours for 44 weeks increases systolic blood pressure by 13 mmHg and diastolic blood pressure by 7 mmHg when compared to baseline. However, blood pressure returned to near baseline values after treatment discontinuation (91730).
• Mental alertness. It is unclear if rosemary aromatherapy is beneficial for improving mental alertness. Details: Preliminary clinical research in nurses working on a night shift shows that placing one drop of rosemary oil on a surgical mask that is worn for 2 hours with a 10-minute on/15-minute off cycle modestly increases alertness and reduces sleepiness when compared with a water drop control (105324).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral rosemary leaf is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that taking rosemary leaf powder 2 grams twice daily for 8 weeks, in conjunction with diet and exercise recommendations, does not improve measures of liver function, glycemic control, cholesterol, or body weight when compared with placebo (109561).
• Opioid withdrawal. It is unclear if oral rosemary is beneficial for opioid withdrawal when used in combination with methadone. Details: Preliminary clinical research shows that taking rosemary leaf along with methadone for 2 weeks improves symptoms of opioid withdrawal and the ability to sleep when compared with methadone alone after 3 and 7 days of treatment, but not after 2 weeks. Rosemary leaf was provided in capsules containing 300 mg each (Barij Essence Pharmaceutical Company) at a dose of 16 capsules daily for the first 3 days, 12 capsules daily for the next 4 days, and eight capsules daily for the next 7 days, in divided doses (91727).
• Osteoarthritis. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective reductions in pain associated with osteoarthritis when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Raynaud syndrome. It is unclear if topical rosemary essential oil is beneficial in patients with Raynaud syndrome. Details: A very small, open-label study in patients with Raynaud syndrome caused by systemic scleroderma shows that applying 10 drops of rosemary 10% essential oil to the hands does not increase skin temperature or improve warmth perception when compared with olive oil (109560). However, this study may have been inadequately powered to detect a difference between groups.
• Rheumatoid arthritis (RA). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective decreases in pain associated with RA when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Stress. It is unclear if rosemary aromatherapy is beneficial for stress. Details: Preliminary clinical research on the use of rosemary aromatherapy for anxiety and stress is conflicting. In a group of graduate nursing students, perceived stress associated with taking a test was lower when inhalers containing rosemary or lavender oil were used. Three drops of rosemary essential oil were added to an inhaler and inhaled before and during the test. Pulse rates, but not blood pressure, were also reduced (18324). In contrast, a small clinical study in adults aged 18-30 years shows that the aroma from diluted rosemary essential oil applied to the wrist during timed crossword puzzle completion actually increases subjective feelings of anxiety and tension when compared with placebo (18325).
• Sunburn. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of rosemary and grapefruit extracts in a 1:1 ratio (NutroxSun, Monteloeder, Inc.), 250 mg orally once daily for 12 weeks, increases the amount of UV radiation needed to cause sunburn by 34% after 8 weeks and 56% after 12 weeks when compared to baseline (91728). The validity of these findings is limited by the lack of a comparator group.
• Upper respiratory tract infection (URTI). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among healthy adults shows that taking a combination product containing rosemary leaf extract, aloe gel powder, and poria mushroom extract daily for 8 weeks does not reduce the frequency, duration, or severity of URTI-related symptoms when compared with placebo. However, in patients receiving an influenza vaccine midway through the study, this product does seem to improve some immune response biomarkers when compared with placebo (111921). The amount of rosemary leaf extract in the supplement was not disclosed.
• Wound healing. It is unclear if topical rosemary cream is beneficial for wound healing. Details: A moderate-sized clinical trial among primiparous adults with medio-lateral episiotomy shows that applying a cream containing rosemary extract to the wound twice daily for 10 days improves episiotomy wound healing and reduces redness and discharge when compared with placebo cream (112143). More evidence is needed to rate rosemary for these uses.

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POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). Oral turmeric seems to improve symptoms in people with allergic rhinitis. Details: A large clinical study in people with allergic rhinitis shows that taking a specific curcumin product (Organika Health Products) 500 mg daily for 2 months reduces nasal symptoms, including sneezing, itching, runny nose, and congestion, when compared with placebo (96138).
• Depression. Most research shows that oral curcumin, a constituent of turmeric, 1 gram daily improves symptoms of depression after 6 weeks when taken along with an antidepressant. However, it is unclear whether curcumin is beneficial when used for greater than 8 weeks. Details: Curcumin appears to be most beneficial for depression in middle aged patients compared to older patients, when taken for at least 6 weeks, and when used at a dose of at least 1 gram daily. In adults with major depressive disorder, a meta-analysis of data from six clinical studies, as well as individual studies not included in this analysis, show that taking curcumin 1 gram daily along with an antidepressant moderately improves depression symptoms when compared with placebo (96131,96139). Another meta-analysis of 10 studies shows symptom reductions in patients with major depression when combined with conventional antidepressants, but not when used alone in patients with milder depressive symptoms. However, the quality of the evidence is low (104971). When used alone, one clinical study shows that curcumin 1 gram daily for 6 weeks may be similarly effective to fluoxetine 20 mg daily. Taking both products together seems to be more effective than either product alone, increasing the response rate from 65% to 78% (89728). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that curcumin extract at doses of 500-1000 mg daily is provisionally recommended for monotherapy or adjunctive use in mild to moderate depression (110318).
• Dyspepsia. Oral turmeric may be modestly beneficial for some patients with dyspepsia. In patients with functional dyspepsia, small clinical studies show that oral curcumin, a constituent of turmeric, is similarly effective when compared with the proton-pump inhibitor omeprazole. Details: Clinical research shows that taking turmeric 500 mg four times daily for 7 days can relieve overall symptoms of dyspepsia in 64% more patients than taking placebo (11144). A small, unblinded clinical study in patients with a type of dyspepsia called postprandial distress syndrome shows that taking turmeric 250 mg or 500 mg orally three times daily after meals for 4 weeks is associated with reductions in symptom scores which are similar to those seen with simethicone 60 mg three times daily for 4 weeks. However, the recurrence rate upon stopping therapy was about 14% with simethicone, compared with 43% to 46% with turmeric (104963). In patients with functional dyspepsia, taking the constituent curcumin appears similarly effective when compared with omeprazole, but might not provide further symptom reduction in those also taking famotidine or omeprazole (106063,106801,111599). One small clinical study in Iran shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing overall symptoms of dyspepsia, such as abdominal pain, heartburn, bloating, and nausea, when compared with famotidine alone (106063). Another small clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity and improving satisfaction when compared with an unspecified dose of omeprazole and more effective when compared with placebo (106801). Similarly, a moderate-size clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity when compared with omeprazole 20 mg daily. However, taking curcumin and omeprazole in combination did not provide further symptom reduction (111599). The validity of these results is limited by the high rate of study dropouts.
• Hyperlipidemia. Research is conflicting on whether oral turmeric, curcumin, or curcuminoids can reduce serum lipids. Any improvement in lipids is likely to be small. Reasons for the conflicting findings may relate to turmeric formulation, duration of treatment, and/or the baseline cholesterol status of the included patients. Details: Results from meta-analyses of clinical research show inconsistent and conflicting results. One large meta-analysis of over 50 clinical studies in healthy adults and those with a variety of conditions shows that supplementation with turmeric or curcumin 80-4000 mg daily for 4-24 weeks reduces total cholesterol by 4 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 7 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL when compared with placebo (112119). Two other meta-analyses of 27 clinical studies agree that taking turmeric, curcumin, or curcuminoids moderately reduce triglyceride levels but suggest that turmeric does not improve total cholesterol when compared with placebo. However, the meta-analyses contradict one another on whether turmeric and its constituents reduce LDL cholesterol or increase HDL cholesterol. (96128,96135). Additionally, a third meta-analysis of 10 clinical trials shows that taking up to 2400 mg daily of curcumin or curcuminoids, from turmeric or isolated sources, for up to 12 weeks, does not significantly improve triglycerides, LDL cholesterol, HDL cholesterol, or total cholesterol (110220).
• Nonalcoholic fatty liver disease (NAFLD). Oral curcumin, a constituent of turmeric, seems to attenuate fat deposition and improve some metabolic parameters in adults with NAFLD. Details: Clinical research shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared to 5% to 27.5% of patients receiving placebo. Curcumin also reduces the quantity of additional fat deposition in the liver to 0% to 4.5%, compared to 17.5% to 26% in those taking placebo. Most research shows that taking curcumin also reduces liver enzyme levels, body mass index (BMI), blood glucose levels, glycated hemoglobin (HbA1c), and total cholesterol when compared with placebo. Although some clinical research shows that taking curcumin improves levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, a meta-analysis of clinical research shows that these lipid levels are not improved in patients with NAFLD, specifically (97430,97431,100258,102350,106062,107120,109279,111349). However, another meta-analysis of 14 small, heterogeneous clinical studies in adults with NAFLD, that included some of these studies, shows that taking various doses and forms of turmeric or curcumin modestly reduces liver enzyme levels, improves measures of insulin resistance, reduces waist circumference, and improves LDL, HDL, and triglyceride levels when compared with placebo (111348). A small clinical trial in patients with NAFLD given specific lifestyle recommendations shows that taking curcumin modestly reduces the frequency of metabolic syndrome and fatty liver but does not have beneficial effects on fatty liver-associated indices, adiposity, or the atherogenic index, when compared with placebo (109285). Findings for specific endpoints are mixed between individual studies and may depend on the formulation of curcumin used or the duration of treatment. These studies have used various doses and formulations. In one study, 500 mg of a dispersion formulation equivalent to 70 mg of curcumin daily for 8 weeks was used (97430). Also, 250 mg once daily or 500 mg twice daily of a specific phytosomal formulation (Meriva, Indena) containing curcumin and soy phosphatidylcholine in a 1:2 ratio and standardized to an overall curcuminoid content of 20% was taken for 8 weeks (97431,106062). Another study used 1 gram of powdered turmeric rhizome taken three times daily with meals for 12 weeks (102350). One study used a curcumin-piperine complex (Curcumin C3 complex 500 mg plus Bioperine 5 mg) daily for 8 weeks (107120). One study used curcumin (Arjuna Natural Extract) 500 mg three times daily for 12 weeks (109285). Despite positive results with curcumin in several small clinical studies of patients with NAFLD, there is some concern that curcumin might cause hepatotoxicity in rare cases, especially when highly bioavailable formulations are used in high doses (103633). There is also evidence that the risk for hepatotoxicity with curcumin may be increased in individuals with the HLAB*35:01 allele (109288). Curcumin-induced hepatotoxicity has not been reported in clinical trials of patients with NAFLD, and its potential mechanism is unclear. However, patients seeking to take curcumin for NAFLD should be advised to monitor for symptoms of hepatotoxicity, including abdominal pain, dark urine, fatigue, jaundice, nausea, and pruritus.
• Oral mucositis. Oral curcumin or curcumin-containing mouthwash seem to reduce the development of severe oral mucositis, as well as reduce the severity and pain of oral mucositis, associated with cancer treatment. Details: Clinical research in patients receiving radiotherapy following recent radical surgery for oral cancer shows that taking turmeric (BCM-95, Arjuna Natural Pvt. Ltd., India) during radiotherapy reduces the incidence of severe oral mucositis to 25% or 20% in those taking turmeric 500 mg two or three times daily, respectively, compared with 65% in those taking placebo. The incidences of severe oral pain, dysphagia, and dermatitis were also reduced by at least 50% (105398). A small clinical study in patients receiving chemotherapy with or without head and neck radiotherapy shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 7 weeks improves severity of oral mucositis at weeks 1, 4, and 7 and reduces pain at week 7 when compared with placebo. Effects were more pronounced in those with chemotherapy-induced oral mucositis than radiotherapy-induced oral mucositis (106800). In patients with head and neck cancer receiving radiotherapy, preliminary clinical research shows that swishing with 10 mL of turmeric solution (prepared by dissolving turmeric 400 mg in 80 mL of water) six times daily for 6 weeks delays mucositis and reduces the number of cases of intolerable mucositis by 49% when compared to swishing with 10 mL of povidone-iodine solution twice daily for 6 weeks (89726). Another small clinical study shows that swishing with 10 mL of nanoparticulate curcumin 0.1% mouthwash three times daily for 6 weeks is associated with a 50% lower risk of developing oral mucositis, and a delay of 2 weeks in the onset of mucositis, when compared with benzydamine 0.15% mouthwash (104969). A small clinical study in patients with mucositis due to head and neck radiotherapy shows that taking curcumin nanoparticles (SinaCurcumin, ExirNanoSina) 40 mg daily or using 10 mL of a curcumin 0.1% mouthwash three times daily for up to 21 days improves scores related to pain, burning, ulceration, and erythema when compared with placebo. Results with either oral or topical curcumin were similar (111350).
• Osteoarthritis. Some oral turmeric extracts and combination products containing turmeric seem to improve certain symptoms of knee osteoarthritis. However, it is unclear how turmeric compares to the use of non-steroidal anti-inflammatory drugs (NSAIDs). Details: Several meta-analyses of clinical studies show that turmeric extracts and/or curcuminoid products reduce knee pain and stiffness, improve physical function, and reduce the need for rescue medication when compared with placebo (104970,106792,109280,110222). However, a reduced effect was noted in patients with increasing age or body mass index (104790). The studies evaluated in these meta-analyses are heterogeneous, of low- to moderate-quality, and utilized a variety of products and/or dosing strategies (104970,106792,109280,110222). Small to moderate-sized clinical studies show that specific products (Meriva, Indena; Theracurmin, Theravalues Corp) containing curcumin 90-100 mg twice daily for up to 6 months, or specific turmeric extracts (Turmacin, Natural Remedies Pvt. Ltd.; Curcugen, DolCas Biotech, LLC) 500 mg twice daily for 6-12 weeks, reduce pain and analgesic use and improve functionality when compared with placebo (17953,80988,89721,97424,104148,107118). A specific turmeric extract (CuraMed, EuroPharma USA) 1500 mg daily for 12 weeks improves functionality, but not pain, when compared with placebo (96127). Also, a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 40 mg twice daily for 6 weeks, improves pain, stiffness, and physical activity scores and reduces intake of rescue acetaminophen by about 60% when compared with placebo (102349). However, not all turmeric products seem to be effective for improving symptoms of osteoarthritis. One small clinical study shows that taking a specific turmeric extract (B-Turmactive, PLAMECA S.A.) 500 mg daily for one week does not reduce knee pain when compared with placebo (104147). Also, a meta-analysis of clinical research shows that benefits are limited to bio-optimized forms of curcuminoids, and benefits related to pure extracts are lacking (110222). Turmeric has also been compared with conventional treatments for knee osteoarthritis in small meta-analyses, a network meta-analysis, and individual clinical studies. However, the evidence is mixed as to whether turmeric is as effective or more effective than NSAIDs, such as ibuprofen 400 mg taken 2-3 times daily, diclofenac 25-100 mg daily, or chondroprotective drugs (17952,89720,89722,106792,109280,110222,113607). A network meta-analysis comparing 6 interventions in adults with knee osteoarthritis suggests that curcumin monotherapy, curcumin with chondroprotective agents, or curcumin with NSAIDs improves scores related to pain, function, and stiffness while reducing the need for rescue medication and the incidence of adverse events (113607). Individual studies are heterogenous with respect to comparator medication and dosing schedule. Doses included a non-commercial turmeric extract 500 mg 3-4 times daily for 4-6 weeks (17952,89720) or turmeric extract 500 mg twice daily for 3 months (89722). Topical turmeric has also been evaluated. One clinical study shows that applying curcumin topically as a 5% ointment in Vaseline twice daily for 6 weeks reduces pain associated with knee osteoarthritis by a mean of about 11 on a 100-point visual analog scale when compared with placebo (104964). Another clinical study in patients with knee osteoarthritis shows that applying curcumin in a self-nano-emulsifying polyethylene glycol organogel 1.5 grams to the knee twice daily for 8 weeks reduces pain, stiffness, and difficulty with physical function scores by 72%, 62%, and 46%, respectively, when compared to baseline, with improvements superior to placebo for all outcomes (113357). Research also shows that taking specific combination products containing turmeric and other ingredients can improve pain and functionality in patients with osteoarthritis. These combination products have combined turmeric with chondroitin sulfate and glucosamine hydrochloride (CartiJoint Forte, Fidia Farmaceutici SpA); boswellic acid (Curamin, EuroPharma USA; Rhulief); Boswellia serrata (Rhulief); ashwagandha, Boswellia serrata, and zinc (Articulin-F, Eisen Pharmaceutical Co. Pvt. Ltd.); devil's claw and bromelain (AINAT, Laboratoire de Rhumatologie Appliquée); Boswellia serrata, guggul, and valerian (Phytoproflex, OPTM Healthcare); Boswellia serrata and terminalia (LI73014F2, Laila Nutraceuticals); ashwagandha, Boswellia serrata, and ginger (Artrex, Mendar); or extracts of ginger rhizome, devil's claw tuber, Boswellia serrata resin, and celery seed (Tregocel, Max Biocare) (19276,51950,81466,89717,89719,96127,97419,97421,97428,106078)(109280).
• Pruritus. Oral turmeric has been evaluated for the management of pruritus of various etiologies, with promising results. Details: Clinical research in patients with kidney failure shows that taking turmeric 500 mg orally three times daily for 8 weeks decreases symptoms of uremic pruritus by 1.9-fold when compared with placebo (89724). Also, a small clinical study in patients with sulfur mustard-induced chronic pruritus shows that taking a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 1 gram plus extract from black pepper or long pepper (Bioperine) daily for 4 weeks reduces pruritus severity and improves quality of life when compared with placebo (81120,81176).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Neither oral turmeric nor its constituent curcumin appears to improve cognitive function or attenuate cognitive decline in adults with this condition. Details: A small clinical trial shows that taking the turmeric constituent, curcumin, 1-4 grams daily for 6 months does not improve mental state examination scores when compared with placebo (17096). Furthermore, a meta-analysis of this study and another small clinical study in patients with Alzheimer disease shows that the turmeric group experienced greater cognitive decline when compared with placebo (100261). While this research is limited by small study sizes and heterogeneous patient populations, the current evidence does not support the use of turmeric in patients with this condition.
• Peptic ulcers. Oral turmeric does not seem to improve the healing of peptic or gastric ulcers when compared with placebo or liquid antacids. Details: Some clinical research shows that taking turmeric 2 grams three times daily for 8 weeks does not improve the healing of peptic ulcers when compared with placebo in Vietnamese patients (81444). Also, taking powdered turmeric rhizome 250 mg four times daily for 6 weeks seems to be less effective than a liquid aluminum-magnesium-hydroxide antacid for promoting gastric ulcer healing (81284).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical turmeric for acne, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Age-related cognitive decline. Some small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve cognition in elderly patients experiencing cognitive decline. Details: A meta-analysis of three small clinical trials shows that curcumin modestly improves cognition in the elderly (100261). One of these clinical trials shows that taking a specific brand of curcumin (Theracurmin, Theravalues Corp.) 90 mg twice daily for 18 months improves long-term memory and attention when compared with placebo in middle-aged and older adults with or without mild cognitive impairment (96161).
• Amenorrhea. Although there has been interest in using oral turmeric for amenorrhea, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Ankylosing spondylitis. Although there has been interest in using oral turmeric for ankylosing spondylitis, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Aromatase inhibitor-induced arthralgia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for aromatase inhibitor-induced arthralgia. Details: A small clinical trial in patients experiencing aromatase inhibitor-induced arthralgia shows that taking curcuminoids as a nanoemulsion (Curcumin C3 Complex, Sabinsa Corporation) 200 mg daily for 3 months does not improve grip strength or joint symptoms when compared with placebo (113345). However, this study may have been underpowered to detect a difference between groups.
• Asthma. Some small clinical studies suggest that oral turmeric, as an adjunct to conventional asthma treatment, does not improve lung function or symptoms in adults and children with asthma. Details: One small clinical study in adults with mild to moderate asthma shows that adjuvant therapy with turmeric as curcumin 500 mg twice daily for 30 days does not improve lung function based on FEV1, or improve symptoms such as dyspnea, wheezing, cough, or tightness, when compared to standard treatment alone (99349). A small clinical trial in children 7-18 years of age with moderate to severe asthma shows that adding turmeric 500-1000 mg (containing 20-40 mg curcuminoids) daily for 6 months to standard therapy does not improve overall asthma symptoms when compared with placebo and standard therapy, although it may decrease the frequency of nighttime awakenings and the use of rescue inhalers (99348). Due to their small sizes and high drop-out rates, these studies may have been underpowered to detect a difference between groups.
• Athletic performance. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for athletic performance. Details: Preliminary clinical research in middle-aged male long-distance runners shows that taking a turmeric extract providing 2 grams of curcumin 95% and piperine 5% daily for 6 weeks does not improve aerobic capacity when compared with placebo (109286).
• Benign prostatic hyperplasia (BPH). It is unclear if oral curcumin, a constituent of turmeric, is beneficial in BPH. Details: A clinical study in patients with BPH shows that taking curcumin 2250 mg once daily along with tamsulosin and finasteride for 6 months improves lower urinary tract symptoms related to storage, but not overall symptoms or symptoms related to voiding, by about 35%, compared with 25% in those receiving tamsulosin and finasteride alone. Periprostatic fat thickness, quality of life, and erectile function also were improved (106799).
• Beta-thalassemia. It is unclear if oral turmeric is beneficial for iron overload in patients with beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia major and iron overload shows that taking turmeric extract containing curcumin 500 mg twice daily for 12 weeks modestly reduces non-transferrin bound iron (NTBI) by 0.6 micromol/L, but not hemoglobin, transferrin saturation, total iron binding capacity, ferritin, or hepcidin, when compared with placebo (99306). Another small clinical study in adult males with beta-thalassemia intermedia and iron overload shows that taking a higher dose of curcumin 500 mg three times daily for 12 weeks modestly reduces serum iron and ferritin turmeric levels and transferrin saturation when compared with placebo (108871).
• Bruises. Although there has been interest in using topical turmeric to alleviate bruising, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Cachexia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for cancer cachexia. Details: A small clinical trial in patients with cancer anorexia-cachexia syndrome shows that taking curcumin 800 mg twice daily for 8 weeks does not reduce weight loss or improve body composition or handgrip strength when compared with placebo (109283).
• Canker sores. Some preliminary research suggests that topical curcumin, a constituent of turmeric, is beneficial for minor canker sores. Details: Preliminary clinical research in young adults with minor canker sores shows that applying a 2% curcumin oral gel for 6 months reduces ulcer size, pain, and recurrence rate and increases healing rate similarly to 0.1% triamcinolone oral paste (104962). The validity of the study is limited by a lack of investigator blinding and the lack of an intention to treat analysis. Another small clinical study shows that applying a 1% curcumin nanomicelle gel (SinaCurcumin Pharmaceuticals) on lesions three times daily for one week is modestly more effective than applying a 2% curcumin gel for reducing pain and ulcer size (109282). The validity of this finding is limited by the lack of a non-curcumin comparator group.
• Carpal tunnel syndrome. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical curcumin, a constituent of turmeric, is beneficial for carpal tunnel syndrome. Details: A moderate-sized clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing turmeric, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and vitamins C, E, B1, B2, B6, and B12 twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to turmeric, other ingredients, or the combination. Topical turmeric has also been investigated. A small clinical study in patients with mild to moderate carpal tunnel syndrome shows that applying a 1% curcuminoid gel (Sinanomin) to the wrists twice daily for 8 weeks modestly decreases symptom severity and improves function when compared with a placebo gel. However, there was no change in electrodiagnostic testing of the injury. All patients also used a night splint (113356).
• Chemotherapy-induced acral erythema. It is unclear if oral or topical turmeric reduces the risk for acral erythema from capecitabine. Details: A small clinical trial in adults with cancer shows that taking turmeric 4 grams daily for 6 weeks starting at the beginning of treatment with capecitabine does not reduce the incidence of acral erythema overall; however, it does seem to reduce acral erythema grade 2 or higher when compared with expected incidence rates (99309). Topical turmeric has also been evaluated. A clinical study in patients with colorectal, gastric, pancreatic, or breast cancer receiving capecitabine shows that applying a specific ointment (Alpha) standardized to contain curcumin extract 0.5% and henna extract 10% to the soles and palms twice daily, beginning on day 1 of chemotherapy and continued for 4 cycles, does not prevent acral erythema or improve World Health Organization severity scores when compared with placebo. A post-hoc analysis suggests that there may have been a trend toward delayed onset and progression; however, this study was not structured to assess these outcomes (108874).
• Chemotherapy-induced constipation. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced constipation. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of constipation when compared with placebo (107111).
• Chemotherapy-induced diarrhea. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced diarrhea. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of diarrhea when compared with placebo (107111).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral curcumin reduces CINV. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of nausea, but not vomiting, in the second and third months after the start of treatment when compared with placebo (107111).
• Chemotherapy-induced peripheral neuropathy. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced peripheral neuropathy. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of chemotherapy-induced peripheral neuropathy over a three-month period when compared with placebo (107111).
• Chronic kidney disease (CKD). It is unclear if oral turmeric is beneficial for CKD. Details: A meta-analysis of four small clinical trials in patients with CKD related to diabetic nephropathy or lupus nephritis shows that taking curcumin or turmeric for 0.5-4 months moderately reduces proteinuria when compared with placebo (109276). Also, a small clinical trial in children and young adults ages 6-25 years with vascular dysfunction related to autosomal dominant polycystic disease (PKD) shows that curcumin powder 25 mg/kg daily for 12 months does not improve vascular function or kidney function when compared with placebo (107117).
• Colorectal adenoma. It is unclear if oral turmeric is beneficial for managing colorectal adenoma. Details: Preliminary clinical research in adults with familial adenomatous polyposis shows that taking curcumin 1500 mg twice daily for 12 months does not reduce the quantity or size of lower intestinal adenomatous polyps when compared with placebo (97427). A very small clinical trial in patients with familial adenomatous polyposis shows that taking 8 capsules daily of a turmeric extract, in a formulation also containing pepper fruit, spirulina, seaweed, and ginger root, for 6 months does not affect total polyp number or burden when compared with placebo. However, both number and burden were modestly reduced in the left colon. Each capsule provided curcuminoids 123.65 mg and turmerones 26.79 mg (110223).
• Colorectal cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of colorectal cancer. Details: A small clinical trial in patients undergoing chemotherapy following colorectal cancer surgery shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily for 8 weeks modestly improves some measures of quality of life when compared with placebo (107109). In addition, a small clinical study in people at high risk for colorectal cancer, such as those who smoke, shows that taking the turmeric constituent, curcumin, 4 grams daily for 30 days can reduce the number of precancerous rectal aberrant crypt foci (18204). It is not clear if this results in a reduced risk for colorectal cancer.
• Coronary artery bypass graft (CABG) surgery. One small study suggests that oral turmeric may reduce the risk for myocardial infarction after CABG surgery. Details: Preliminary clinical research shows that taking the turmeric constituent, curcuminoids, 4 grams daily in four divided doses, beginning 3 days prior to surgery and continuing for 5 days post-surgery, decreases the relative risk of myocardial infarction following CABG by approximately 56% when compared with placebo (81143).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing symptoms of COVID-19. Details: Small studies have evaluated curcumin as an adjunctive therapy in adults hospitalized with confirmed COVID-19. Patients in these studies also received treatments such as antimicrobials, anti-inflammatory medications, anticoagulants, antiretrovirals, and immunosuppressants (104966,105393,107119). One study shows that adding curcumin reduces the duration of shortness of breath by 6-9 days when compared with patients who received other treatments in combination with probiotics. However, there were no differences in the duration of other symptoms, including fever, cough, or sore throat. Subgroup analyses suggest that taking curcumin may improve oxygenation and reduce the need for supplemental oxygen or ventilation (105393). Another study shows that adding curcumin modestly reduces the time to resolution of COVID-19 symptoms, the length of supplemental oxygen use, and the likelihood for deterioration in the patients' condition when compared with patients who received other treatments alone (104966). A third study shows some benefit of curcumin on fever and cough when compared with baseline; however, it is unclear if any changes were significant when compared with placebo (107119). Doses of curcumin used in these studies include curcumin 525 mg with piperine 2.5 mg (C3 Complex, SamiDirect) twice daily, starting at admission and continuing for 14 days (105393), or a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 2 weeks or 240 mg daily in divided doses for 7 days (104966,107119). Limitations of these studies include the small number of patients with severe symptoms, the large number of outcomes evaluated, the inconsistencies in other treatments used, the lack of clarity related to presentation of some results, and, in most cases, a lack of blinding. Turmeric has also been evaluated in adults in the outpatient setting with suspected or confirmed mild to moderate COVID-19. One small clinical study shows that taking curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 14 days in addition to other COVID-19 treatments (mainly hydroxychloroquine and azithromycin) reduces the duration of cough, chills, myalgia, and smell and taste disturbance, but not dyspnea, fever, sore throat, or others, by 1-2 days when compared with placebo with other treatments (106802). The validity of this study is limited by the lack of confirmatory diagnosis at baseline and lack of consistency with other treatments, as well as the unclear reporting of symptom duration in relation to the initiation of treatment. Another small clinical study in outpatients confirmed to have COVID-19 shows that taking curcumin 1000 mg plus piperine 10 mg (Sami Labs Limited) daily for 14 days modestly improves weakness, but not cough, pain, headache, difficulty breathing, or biochemical indices, when compared with placebo (109278). Some research has also examined the effect of turmeric as part of a polyherbal combination. Clinical research in patients hospitalized for moderate COVID-19 symptoms shows that using an Ayurvedic formulation 1776 mg twice daily containing turmeric, ashwagandha, ginger, and Boswellia serrata (BV-4051) for 14 days modestly reduces the duration of illness and reduces the severity of fever, cough, and smell and taste dysfunction when compared to placebo. There was no beneficial effect on other symptoms, including nasal congestion, breathing difficulty, headache, and gastrointestinal symptoms. More than half of the patients were also treated with remdesivir which did not impact the majority of these findings (109899).
• Crohn disease. It is unclear if oral turmeric is beneficial for improving symptoms of active Crohn disease. Details: Some clinical research shows that taking the turmeric constituent, curcumin, 1.08 grams daily for one month, then 1.44 grams daily for one month, can reduce bowel movements, diarrhea, and abdominal pain when compared to baseline in patients with Crohn disease (79730). The validity of these findings is limited by the lack of a comparator group.
• Denture stomatitis. Topical turmeric may be beneficial for treating denture stomatitis. Details: A small clinical study in patients with denture stomatitis shows that applying topical curcumin gel (Curenext, Abbott Laboratories) three times daily for 2 weeks resolves denture stomatitis lesions similarly to clotrimazole ointment (106797).
• Diabetes. Low-quality clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve glycemic control in patients with diabetes. Details: A meta-analysis of small clinical trials in patients with diabetic kidney disease shows that curcumin reduces levels of fasting glucose by approximately 8.3 mg/dL when compared with placebo. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). Preliminary clinical research included in the analysis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL (104149). Other meta-analyses of low- to moderate-quality clinical studies in patients with a variety of conditions including type 2 diabetes show that taking turmeric extract, curcumin, or curcuminoids for 4-36 weeks improves glycated hemoglobin (HbA1c) by 0.4-0.7% and reduces fasting glucose by approximately 13 mg/dL when compared with placebo or conventional treatment (106806,108877,113604). The validity of these findings is limited by the heterogeneity of the included studies and broad curcuminoid doses ranging from 46-1500 mg daily. Conversely, other meta-analyses in patients with type 2 diabetes show that curcumin does not reduce HbA1c or insulin levels when compared with placebo (104965,108877,113604).
• Diabetic foot ulcers. It is unclear if oral curcumin is beneficial in patients with diabetic foot ulcers. Details: Preliminary clinical research in patients with grade 3 diabetic foot ulcers shows that taking nanocurcumin 80 mg orally daily for 12 weeks does not improve glycated hemoglobin (HbA1c) or change the rate of ulcer healing when compared with placebo. Taking turmeric did result in modest decreases in fasting blood glucose, insulin levels, and insulin resistance (104972).
• Diabetic nephropathy. It is unclear if oral curcumin is beneficial in patients with diabetic nephropathy. Details: Meta-analyses of two to four small clinical trials in patients with diabetic kidney disease show that curcumin modestly improves serum levels of creatinine, total cholesterol, and fasting glucose, and reduces systolic blood pressure by 4 mmHg, when compared with placebo. However, there was no effect on diastolic blood pressure, proteinuria, or serum levels of other plasma lipids or blood urea nitrogen. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). One small study included in this analysis, which evaluated patients receiving hemodialysis, shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL when compared with placebo (104149).
• Dysmenorrhea. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in university students aged 18 to 24 in Iran with mild to severe primary dysmenorrhea and premenstrual syndrome (PMS) shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805). Conversely, a small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing turmeric, Boswellia serrata, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). However, it is unclear if these effects are due to turmeric, other ingredients, or the combinations.
• Endometriosis. It is unclear if oral turmeric is beneficial for reducing pain due to endometriosis. Details: A small clinical study in adults with endometriosis shows that taking the turmeric constituent, curcumin, 500 mg twice daily for 8 weeks does not affect pain associated with endometriosis or quality of life when compared with placebo (113603).
• Erythema. Although there has been interest in using topical turmeric for reducing erythema, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Exercise-induced muscle soreness. It is unclear if oral turmeric is beneficial for reducing muscle soreness from exercise. Details: A small clinical study in healthy males shows that taking turmeric capsules containing curcumin 2.5 grams twice daily for 5 days, starting 2.5 days before exercise, slightly reduces pain from certain movements when compared with placebo (98998). Another small crossover clinical study in professional male soccer players shows that taking curcumin 500 mg (Elite Opti-Turmeric, Health Span) immediately, 12 hours, and 36 hours after a match accelerates muscle recovery and reduces delayed-onset muscle soreness when compared with medium chain triglyceride oil 1000 mg (111356). Turmeric has also been examined in combination with other ingredients. Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
• Gingivitis. Small clinical studies suggest that oral turmeric and turmeric mouthwash may reduce the severity of gingivitis. Turmeric mouthwash appears to be similarly effective to chlorhexidine mouthwash. Details: A meta-analysis of generally preliminary clinical research shows that rinsing with a mouthwash containing curcumin for 3-4 weeks is as effective as rinsing with chlorhexidine for reducing the severity of gingivitis or plaque (106059). Mouthwashes in these studies contained 0.05% to 20% curcumin and were usually used twice daily for 3-4 weeks (81127,89723,106059). One mouthwash contained 0.05% turmeric extract and 0.005% eugenol (89723). Another small clinical trial shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily by mouth after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo in patients with gingivitis and mild periodontitis (104146).
• Gout. Although there is interest in using oral turmeric for gout, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Gulf war syndrome. It is unclear if oral curcumin is beneficial in patients with Gulf war syndrome. Details: A small preliminary clinical trial in patients with Gulf war syndrome shows that taking curcumin (Meriva, Indena, S.p.A.) 500 mg twice daily for 30 days reduces overall symptoms, including pain, fatigue, gastrointestinal distress, and others, by 19% when compared with baseline. Taking a higher dose of 2000 mg twice daily for an additional 30 days appears to be no more effective than the lower dose (105395).
• Helicobacter pylori. Small clinical studies suggest that oral turmeric is not beneficial for eradicating H. pylori when used alone or in combination with standard triple therapy or famotidine. Details: One small clinical study in patients with H. pylori gastritis shows that taking turmeric 2.1 grams daily for 4 weeks is less effective for eradicating H. pylori than taking an omeprazole-based triple regimen for one week (80957). Another small study in adults with peptic ulcers shows that taking a specific curcumin product (C3 Complex, Sami Labs LTD) 500 mg daily for 7 days, in conjunction with standard triple therapy, does not improve H. pylori eradication rates when compared with standard triple therapy alone. The addition of curcumin increased the resolution of dyspepsia symptoms by an additional 21%, but the clinical significance of this outcome is unclear (97420). In patients with dyspepsia, most of whom tested positive for fecal H. pylori antigen, clinical research shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing fecal H. pylori antigen levels than taking famotidine alone (106063).
• Hypertension. It is unclear if oral curcumin is beneficial in patients with hypertension. Details: A meta-analysis of approximately 30 clinical studies in healthy adults or patients with a variety of conditions shows that taking turmeric, curcumin, curcuminoids, or nano-curcumin for 4 to 24 weeks reduces systolic blood pressure by about 2 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with placebo (113602). However, these blood pressure reductions may not be clinically meaningful. In addition, most of the included studies were small and utilized heterogeneous dosing regimens.
• Impaired glucose tolerance (prediabetes). Oral turmeric may modestly improve glucose control in some patients with prediabetes. Details: In overweight or obese individuals with prediabetes, clinical research shows that taking a turmeric extract (BCM95 or Cucugreen; M/s Arjuna Natural Pvt Ltd.) 500 mg daily, providing 95% curcuminoids and at least 65% curcumin, for 90 days, either alone or in combination with zinc 30 mg as zinc gluconate, results in a small reduction in fasting glucose and glycated hemoglobin (HbA1c) when compared with placebo. There was also a small benefit in insulin sensitivity (105391). Other preliminary clinical research in adults with prediabetes shows that taking 500 mg of a combination of turmeric extract and Indian gooseberry extract in a 1:2 ratio along with phosphatidylcholine (EmbliQur) twice daily for 6 months modestly reduces fasting glucose and improves insulin resistance, when compared with placebo. However, changes in most other endpoints were not significantly different from placebo. Each 500 mg capsule contained turmeric extracts 29.86% and turmeric oil 1.27% (113355). The effect of turmeric on progression to type 2 diabetes in patients with prediabetes has also been investigated. Preliminary clinical research shows that taking a turmeric extract containing curcumin 750 mg twice daily for 9 months reduces the percentage of patients with prediabetes who develop type 2 diabetes when compared with placebo (81163).
• Irritable bowel syndrome (IBS). It is unclear if oral turmeric is beneficial for improving symptoms of IBS. Details: Preliminary clinical research in otherwise healthy adults with IBS shows that taking a turmeric extract (Cynara Turmeric, Lichtwer Pharma) 72-144 mg daily for 8 weeks reduces IBS symptoms by about 40% to 60% when compared to baseline (79565). The validity of this finding is limited by the lack of a comparator group. Taking a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422). It is unclear if these effects are due to turmeric, fennel, or the combination. Observational research suggests that adding a supplement (Enterofytol PLUS) providing curcumin 42 mg and berberine 200 mg twice daily for 2 months to conventional IBS treatment is associated with improvements in symptoms, such as abdominal discomfort, distension, and stool status, by up to 48% when compared with conventional treatment alone. Use of the supplement was also associated with a 64% reduced need for conventional treatments (113354).
• Joint pain. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsulfonylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Juvenile idiopathic arthritis (JIA). Although there is interest in using oral turmeric for JIA, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Knee pain. It is unclear if oral turmeric is beneficial for knee pain. Details: Clinical research in individuals with knee pain not related to existing arthritis shows that taking turmeric extract (TurmXTRA 60N; Inventia Healthcare Ltd. and Laila Nutraceuticals) 250 mg, providing 60% curcuminoids, once daily for 90 days modestly reduces pain associated with walking 80 meters when compared with placebo. The time taken to walk 80 meters and to climb nine steps was reduced by 4-5 seconds (105396).
• Lichen planus. Evidence is conflicting on whether turmeric is beneficial for lichen planus. Details: A meta-analysis of several small, heterogeneous, mostly low-quality clinical and observational studies in adults with oral lichen planus shows that oral or topical curcumin with or without corticosteroids for 2-12 weeks does not improve erythema, lesion size, or pain when compared with control (113605). Similarly, a network meta-analysis of small clinical trials in patients with oral lichen planus shows that applying topical turmeric gel does not improve symptoms, clinical resolution, clinical scores, or reduce pain when compared with other available interventions (111640). However, small individual clinical studies have shown some benefit in using turmeric for lichen planus. A small clinical study shows that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) containing curcuminoids 6000 mg daily in three divided doses for 12 days can reduce erythema and ulceration associated with lichen planus when compared with placebo (81109). Another small clinical study shows that taking a nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg orally once daily for 1 month reduces oral lichen planus lesion size, pain, and burning similarly to prednisolone 10 mg taken orally once daily for 1 month (104961).
• Metabolic syndrome. It is unclear if oral turmeric is beneficial for metabolic syndrome. Details: Research is conflicting on how turmeric, curcumin, and other formulations affect various measures of metabolic syndrome. Some clinical research and a meta-analysis of 13 clinical studies in patients with metabolic syndrome show that taking turmeric or curcumin decreases low-density lipoprotein (LDL) cholesterol, waist circumference by 2 cm, fasting blood glucose by 9 mg/dL, and diastolic blood pressure by 3 mmHg and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared with placebo. However, other research shows that turmeric or curcumin have no effect on body weight, lipids, blood pressure, or blood glucose when compared with placebo (98999,99311,105400,109284,111347,112118). The validity of these effects is limited by high heterogeneity within the included studies and incomplete information about randomization and blinding. Studies have used turmeric, curcumin, and curcumin extract 80-2400 mg, in divided doses, daily for 4-12 weeks, nano-curcumin 80 mg daily for 12 weeks, or calebin A (CurCousin, Sabinsa), which is a constituent of turmeric, 25 mg twice daily for 3 months (98999,99311,105400,109284,111347,112118). Also, taking crude or phosphorylated curcuminoids 1 gram daily for 6 weeks does not improve sleep or reduce weight in these patients (105397).
• Migraine headache. It is unclear if oral curcumin is beneficial for migraine headache. Details: A small clinical trial in females with regular migraines shows that taking curcumin 500 mg twice daily for 8 weeks reduces the severity and duration, but not the frequency, of migraine headaches when compared with placebo. In individuals taking curcumin, the duration of headache per month was reduced by approximately 10.3 hours from baseline (107116).
• Myocardial infarction (MI). It is unclear if oral curcumin is beneficial for reducing myocardial injury following a MI. Details: Clinical research in patients with an acute MI shows that taking curcuminoids 500 mg plus piperine (Bioperine) 5 mg daily (Sami Labs) for 8 weeks does not improve ejection fraction, serum levels of cardiac troponin 1, blood pressure, levels of fasting blood glucose, or kidney function parameters when compared to placebo. However, there were some modest benefits on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycated hemoglobin, and certain liver enzymes such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) (107115). The validity of this study is limited by its short duration and relatively small sample size.
• Obesity. Oral turmeric might modestly improve weight loss, although any effect is unlikely to be clinically significant. Details: Multiple meta-analyses of small, mostly low-quality clinical studies in adults with a variety of comorbid conditions show that taking various forms and doses of turmeric or curcumin results in an average weight loss of about 0.6-1 kg, a decrease in body mass index (BMI) of about 0.2-0.5 kg/m2, and a decrease in waist circumference of about 1.3 cm when compared with control (102345,111351,111352). A sub-analysis of dose and duration shows that a reduction in waist circumference only occurs with curcumin daily doses above 1000 mg, and duration of treatment longer than 8 weeks (102345).
• Oral submucous fibrosis. Small studies suggest that topical or oral curcumin might be beneficial for oral submucous fibrosis. However, the research is heterogenous with respect to outcomes, comparators, and the turmeric preparations, doses, and routes of administration utilized. Details: A meta-analysis of 3 small clinical trials shows that turmeric modestly improves mouth opening when compared with control. In addition, a systematic review of 11 studies shows that turmeric improves overall symptoms, including mouth opening, tongue protrusion, burning sensation, and cheek flexibility. However, studies were small with short duration and used variable dosing strategies. Most trials have studied oral turmeric 300-400 mg, either alone or with black pepper 100 mg or piperine 5 mg, for 3-6 months. Less commonly, turmeric was provided in lozenge form (105399). Also, a network meta-analysis suggests that the turmeric constituent curcumin with or without piperine is most the effective for reducing tongue protrusion when compared indirectly with various medical and antioxidant therapies; however, this analysis suggests that curcumin does not rank among the most effective interventions for improving mouth opening, burning sensation, or cheek flexibility (113514). Other preliminary clinical research shows that taking a specific oral product containing curcumin 300 mg and piperine 5 mg (Turmix tablets, Sanat Products), three times daily for 12 weeks, improves mouth opening, burning sensation, and tongue protrusion when compared with baseline, but not when compared with an antioxidant product containing alpha-lipoic acid, beta-carotene, copper, lycopene, selenium, and zinc. Mouth opening is further improved by concurrent use of a mouthwash (Turmix mouthwash, Sanat Products), containing 0.1% w/v turmeric extract (standardized to 95% curcumin), with thymol, eucalyptol, clove oil, mentha oil, and tea tree oil, twice daily for 12 weeks (102347). A small clinical study shows that applying topical curcumin gel (Curenext, Abbott Laboratories) 5 mg daily in 3-4 divided doses for 6 weeks, in combination with oral physical therapy, improves mouth opening similarly to using an aloe vera gel in combination with oral physical therapy. However, decreases in burning sensation are greater with aloe gel than curcumin gel (104967). It is not clear whether the gels, oral physical therapy, or the combination of both is responsible for the outcome. Finally, clinical research shows that applying a paste providing turmeric and holy basil 10 grams each, mixed in 10 mL of honey, to the oral mucosa 4 times daily for 3 months modestly improves mouth opening, tongue protrusion, and burning sensation and reduces the presence of fibrous bands when compared with taking a vitamin B supplement. There was no effect on the shape of the uvula (113325).
• Pain (acute). Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
• Periodontitis. There is limited evidence on the oral or topical use of turmeric or its constituent curcumin in patients with periodontitis. Details: A meta-analysis of heterogenous clinical studies in patients with chronic periodontitis suggests that use of local delivery gel products, usually turmeric 2% or a specific product containing curcumin (Curenext), modestly reduces pocket depth when compared with routine products, such as chlorhexidine. However, limited research suggests that curcumin products do not affect plaque or gingivitis measures, and curcumin irrigation does not affect pocket depth based on limited research (107108). A small preliminary clinical study in patients with severe chronic periodontitis shows that placing curcumin gel 2 mg on one side of the mouth along with scaling and root planing (SRP) reduces plaque and probing pocket depth, but not gingival index, when compared with SRP alone (101339). The use of oral curcumin has also been investigated. A small clinical trial in patients with gingivitis and mild periodontitis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo (104146).
• Physical performance. It is unclear if oral turmeric may be beneficial for improving physical performance in older adults. Details: A very small clinical study in moderately functioning, sedentary adults over age 65 with low-grade chronic inflammation shows that that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) 500 mg twice daily for 12 weeks does not improve measures of physical function, walking speed, or muscle strength when compared with placebo (111357). However, this study may have been inadequately powered to detect any possible differences between groups.
• Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral curcumin may improve some metabolic parameters in patients with PCOS, but these improvements may not be considered clinically significant. Details: Clinical research in patients with PCOS shows that taking curcumin 500 mg one to three times daily for 6-12 weeks improves some metabolic parameters (104968,105394,106795). Conversely, a small clinical study in patients aged 18 to 45 with PCOS in Iran shows that taking curcumin 1000 mg daily for 12 weeks modestly reduces fasting glucose but does not improve other metabolic parameters when compared with placebo. Taking curcumin also did not improve testosterone levels or hirsutism scores (111355). Meta-analyses show that taking curcumin modestly decreases body mass index (BMI) and improves measures of glycemic control, including fasting glucose and insulin resistance, and levels of total cholesterol when compared with placebo or metformin alone. However, effects on high-density lipoprotein (HDL) cholesterol levels were mixed and there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels (105394,106795,110219). Other preliminary clinical research shows that taking curcumin decreases plasma dehydroepiandrosterone and fasting plasma glucose levels when compared with placebo (104968). Some clinical research also shows that taking nano-curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 3 months is beneficial in patients already taking metformin 1500 mg daily. Taking curcumin had modest beneficial effects on fasting insulin and insulin resistance, as well as levels of testosterone, LDL cholesterol, HDL cholesterol, and triglycerides, when compared with metformin alone. There was no effect of curcumin on body weight, fasting blood glucose, or other hormones (106060).
• Postoperative pain. Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly reduce pain in various postoperative recovery settings. Details: One small clinical study in patients undergoing laparoscopic cholecystectomy shows that taking curcumin 2 grams daily reduces postoperative pain, fatigue, and the need for analgesics by the second postoperative week when compared with placebo (81099). In patients undergoing surgery for inguinal hernia and/or hydrocele, taking curcumin 1.2 grams daily for 5 days reduces inflammation and tenderness by the sixth postoperative day when compared with placebo (81206). Curcumin was taken in 3-4 divided doses daily in these studies. Finally, taking a single dose of curcumin 200 mg after surgical removal of impacted third molars modestly reduces acute postoperative pain when compared with taking mefenamic acid 500 mg (99305).
• Premenstrual syndrome (PMS). It is unclear if oral turmeric may be beneficial for improving symptoms of PMS. Details: Some preliminary clinical research in patients with PMS shows that taking curcumin 100 mg twice daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation, improves physical, behavioral, and mood symptoms, as well as overall severity of symptoms, when compared with placebo (97433). Conversely, in university students aged 18 to 24 in Iran with mild to severe PMS and primary dysmenorrhea, a clinical study shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805).
• Prostate cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of prostate cancer. Details: One small clinical study shows that taking curcumin 1.8 grams orally three times daily for 7 days, starting 4 days prior to docetaxel and prednisone treatment and continuing for up to 6 cycles, reduces PSA levels by at least half in 59% of patients when compared to baseline. Also, all patients with measurable lesions showed at least stable disease after treatment, and 40% of patients showed partial response when compared with baseline (96132). It is unclear if the addition of turmeric is beneficial when compared with docetaxel and prednisone alone. In contrast, an additional small clinical trial shows that taking curcumin 6 grams daily for 7 days every 3 weeks, starting four days before docetaxel, does not improve PSA levels or progression-free or overall survival when compared with docetaxel alone (105392).
• Psoriasis. Evidence is limited to one small study of topical use in patients with scalp psoriasis. Details: Preliminary clinical research in adults with scalp psoriasis shows that applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves overall symptoms and quality of life when compared with a placebo tonic (97429).
• Quality of life. Some preliminary clinical research suggests that oral curcumin might improve quality of life in patients with various chronic conditions. Details: Small or low-quality clinical trials in various patient populations show that taking curcumin improves at least some measures of quality of life when compared with placebo. Research has been conducted in patients with cancer, sulfur mustard-induced chronic pruritus, benign prostatic hyperplasia (BPH), or irritable bowel syndrome (IBS). Studies have evaluated curcumin 2250 mg once daily for 6 months, a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 500-1000 mg plus piperine (Bioperine) daily for 4-9 weeks, or a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days (81120,81176,97422,106799,107109,107111). Also, in patients with scalp psoriasis, applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves quality of life when compared with a placebo tonic (97429).
• Radiation dermatitis. It is unclear if oral or topical turmeric is beneficial for reducing the severity of radiation dermatitis. Details: A meta-analysis of 4 clinical studies in patients with breast cancer shows that taking curcumin 500-2000 mg three times daily for 3-7 weeks or applying curcumin gel 500 mg three times daily for 7 weeks reduces the radiation dermatitis severity score by about 0.5 points (on a 4-point scale) when compared with placebo or other control (111354). The validity of this analysis is limited by the heterogeneity of the included studies. However, a small clinical study in patients with breast cancer shows that taking nanocurcumin 80 mg twice daily during and for up to 2 weeks after treatment does not reduce skin reaction severity overall, but does modestly reduce pain, when compared with taking placebo. Also, there was a small reduction in skin reaction severity near the end of the study. All patients also used aloe vera leaf as part of the hospital protocol (109281). Another small preliminary clinical study in head and neck cancer patients shows that a specific cream (Vicco turmeric cream, Vicco Laboratories) containing turmeric and sandalwood oil, applied 5 times daily during radiation therapy, seems to reduce frequency and severity of radiation dermatitis when compared with baby oil (99307).
• Radiation proctopathy. It is unclear if oral turmeric is beneficial for preventing proctitis or cystitis in patients receiving radiotherapy for prostate cancer. Details: A small clinical study in patients with prostate cancer shows that taking a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 120 mg daily, for 3 days before and also during a course of radiotherapy, does not reduce the occurrence of proctitis or cystitis when compared with placebo (100259). This study may have been underpowered to detect small treatment effects.
• Respiratory tract infections. Although there is interest in using oral turmeric for various respiratory tract infections, including bronchitis and the common cold, it has not been clinically evaluated.
• Rheumatoid arthritis (RA). Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve some symptoms of RA. Details: Meta-analyses of small clinical trials in patients with RA show that taking curcumin alone or with other treatments modestly reduces overall RA symptoms, pain, and markers of inflammation when compared with control groups, including placebo or other treatments. However, some research shows that there is no beneficial effect on tender or swollen joint count from the limited available clinical research (109280,111358), while other research shows that there is a benefit (112117). Clinical studies have evaluated curcumin 120-1200 mg daily for 2 weeks to 3 months (11149,18205,96129). The validity of these findings is limited by the small size of the studies, and in some cases, the lack of a comparator group.
• Sarcopenia. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with sarcopenia shows that taking a specific slow-release product containing turmeric, protein, carbohydrate, and fiber (Cureit, Aurea Biolabs), 500 mg orally daily for 3 months, increases handgrip strength by about 1% and distance walked before feeling tired by about 6% when compared with placebo. It also increases weightlifting capacity by about 6% from baseline, compared with a 5% decrease from baseline in those taking placebo (104973). It is unclear whether these small changes are clinically meaningful.
• Schizophrenia. Although there is interest in using oral turmeric for improving cognitive function in patients with schizophrenia, there is insufficient reliable information about the clinical effects of turmeric for this use.
• Sepsis. It is unclear if oral curcumin, a constituent of turmeric, is beneficial in patients with sepsis. Details: A small clinical trial in patients admitted to the intensive care unit (ICU) with sepsis shows that a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 80 mg dissolved in water and administered via gastric tube following lavage twice daily for 10 days does not affect length of ICU stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, blood pressure, or heart rate when compared with placebo (108873).
• Smoking cessation. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 50 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Stress. It is unclear if oral turmeric is beneficial for reducing occupational stress in healthy adults. Details: A small clinical trial in healthy adults with occupational stress-related anxiety and fatigue shows that taking a specific type of turmeric (CurQfen, Akay Flavours and Aromatics Pvt Ltd.) that contains fenugreek dietary fiber for improved bioavailability at a dose of 500 mg twice daily for 30 days reduces stress and fatigue and improves quality of life when compared with placebo, and also when compared with a standard curcumin supplement with lower bioavailability (99308).
• Stroke. It is unclear if oral turmeric is beneficial for stroke. Details: A small clinical study conducted in Iran in adults with a recent ischemic stroke shows that taking curcumin 500 mg and piperine, a pepper constituent, 5 mg (Sami Lans, India) daily for 12 weeks reduces carotid intima-media thickness, triglycerides, total cholesterol, and systolic and diastolic blood pressure, but does not improve low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or quality-of-life indicators when compared with placebo (113601). The validity of this study is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups.
• Systemic lupus erythematosus (SLE). There is limited evidence on the oral use of turmeric in adults with lupus nephritis. Details: Preliminary clinical research in adults with lupus nephritis shows that taking turmeric 1.5 grams daily in three divided doses for 3 months reduces systolic blood pressure and improves kidney function when compared to baseline (81104). The validity of this finding is limited by the lack of a comparator group.
• Tuberculosis. It is unclear if oral turmeric is beneficial in patients receiving treatment for tuberculosis. Details: A small clinical study in adults receiving antituberculosis treatment shows that taking a formulation containing turmeric 0.5 grams and Tinospora cordifolia 0.5 grams twice daily for 4 months can reduce levels of Mycobacterium tuberculosis in the sputum and improve lesion healing when compared with antituberculosis treatment alone. Also, liver toxicity associated with the antituberculosis treatment seems to be reduced when administered with this formulation (80424). It is unclear if these effects are due to turmeric, Tinospora cordifolia, or the combination.
• Ulcerative colitis. It is unclear if oral or rectal turmeric, or its constituent, curcumin, is beneficial in adults with ulcerative colitis. Details: Although two small clinical studies in adults with ulcerative colitis show that taking oral turmeric extract 2-3 grams daily for 1-6 months improves the rate of remission and reduces relapse rate (79966,97423), a meta-analysis of these studies and one additional clinical study shows that turmeric does not improve remission rates when compared with placebo (99000). A specific product (Cur-Cure, Bara Herbs Inc) was used in some of these studies. Reasons for the conflicting findings are unclear, but may be due to small patient populations, concerns about blinding, and the inclusion of patients who were also taking immunomodulating drugs. It may also be due to differences in how a study measures remission. A meta-analysis of small clinical studies in patients with mild to moderate ulcerative colitis shows that adding oral curcumin 0.5-3 grams daily to standard treatment for 1-6 months may improve clinical remission rates, but not endoscopic remission rates, when compared with placebo (108872). However, the validity of this finding is limited by the small number of studies that evaluated endoscopic remission. A small clinical study shows that administering an enema form of turmeric extract (NCB-02, Himalaya Drug Company) as 20 mL, containing turmeric extract 140 mg, daily for 8 weeks increases response rate from 50% to about 93% and increases remission rate from about 31% to 71% when compared with placebo in patients with active ulcerative colitis. However, patients using the turmeric extract enema for shorter durations did not improve when compared with placebo (89729). Turmeric has also been investigated in combination with the Mediterranean diet. A small clinical trial shows that taking curcumin (VeNatura Curcumin Supplement) 800 mg twice daily while following the Mediterranean diet for 8 weeks is no more effective for improving ulcerative colitis symptom severity than following the Mediterranean diet without supplemental curcumin (113339).
• Uveitis. It is unclear if oral curcumin is beneficial for uveitis. Details: Observational research in patients with acute non-infectious uveitic macular edema shows that taking a specific hydrophilic curcumin product (Cucrcuwin, Diabec, Alfa Intes) 60 mg twice daily for 6 months, in conjunction with standard corticosteroid treatment, and then alone for an additional 6 months, modestly improves best corrected visual acuity, but not macular thickness or intraocular pressure, when compared with standard treatment alone for 6 months (107110).
• Wound healing. Although there is interest in using topical turmeric for wound healing, there is insufficient reliable information about the clinical effects of turmeric for this condition. More evidence is needed to rate turmeric for these uses.

(Read more about TURMERIC)

LIKELY SAFE ...when properly prepared bamboo shoots are used orally in food amounts (96875).

POSSIBLY SAFE ...when bamboo salt-containing toothpaste is used topically during brushing twice daily for up to 4 weeks (109458). There is insufficient reliable information available about the safety of bamboo when taken by mouth in the amounts found in medicine or when used topically on areas of the body beyond the teeth and gums.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BAMBOO)

LIKELY SAFE ...when guava fruit is consumed as food. Guava fruit has Generally Recognized as Safe (GRAS) status (4912).

POSSIBLY SAFE ...when guava fruit or leaf extract is used orally for medicinal purposes, short-term. Guava fruit has been used with apparent safety at doses of 500-1000 grams daily for 12 weeks (95562). Guava leaf extract has been used with apparent safety at doses of 1 gram daily for 12 weeks or 1.5 grams daily for 3 days (101758,70318). ...when the leaf extract is used topically, short-term. Guava leaf extract has been used safely as a mouth rinse at a dose of 0.15% twice daily for 30 days (101754). Guava leaf extract has been safely used on the skin at a dose of 6% twice daily for 28 days (101757).

PREGNANCY AND LACTATION: LIKELY SAFE
when guava fruit is consumed as food. There is insufficient reliable information available about the safety of guava fruit or leaf when used for medicinal purposes during pregnancy and lactation.

(Read more about GUAVA)

LIKELY SAFE ...when the ripe fruit is used orally in amounts commonly found in foods. Papaya has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the leaf extract is used orally and appropriately in medicinal amounts, short term. The leaf extract has been used with apparent safety in doses of up to 3300 mg daily for up to 5 days (102799,102800). ...when the ripe fruit is used topically and appropriately, short term. The fruit has been applied with apparent safety to the gingiva or skin for up to 10 days (93090,93091).

POSSIBLY UNSAFE ...when the unripe fruit containing papaya latex and raw papain is used orally. Raw papain has been reported to cause esophageal perforation (6,93083). ...when papaya latex is used topically. Papaya latex, which contains raw papain, is a severe irritant and vesicant (6).

PREGNANCY: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods.

PREGNANCY: POSSIBLY UNSAFE
when the unripe fruit containing papaya latex is used orally; avoid using. There is some concern that crude papain, a constituent of papaya latex, is teratogenic and embryotoxic (6); however, this might be due to extraneous substances rather than papain (11). Some evidence also suggests that high doses of papaya seed extract have abortifacient activity and can adversely affect fetal development (67870). Theoretically, eating large amounts of papaya seeds may have similar effects.

LACTATION: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of using papaya medicinally; avoid using.

(Read more about PAPAYA)

LIKELY SAFE ...when used orally in amounts typically found in foods. Rosemary has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (18). Powdered rosemary leaf has been used with apparent safety as a single dose of up to 1.5 grams (18246,91731) or at a dose of 1-4 grams daily for up to 8 weeks (91727,98536,105327,109561). ...when the essential oil is used topically and appropriately for up to 7 months (5177,91729,109560). ...when the essential oil is used by inhalation as aromatherapy, short-term (7107,18323,105324,109559).

LIKELY UNSAFE ...when the essential oil or very large quantities of rosemary leaf are used orally. Ingestion of undiluted rosemary oil or very large quantities of rosemary leaf can cause serious adverse effects (18,515).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Rosemary might have uterine and menstrual flow stimulant effects (4,12,18), and might increase metabolism of estradiol and estrone (18331); avoid using. There is insufficient reliable information available about the safety of rosemary when used topically during pregnancy.

LACTATION:
There is insufficient reliable information available about the safety of using rosemary in medicinal amounts during lactation; avoid using.

(Read more about ROSEMARY)

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.

(Read more about TURMERIC)

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, long-term bamboo use might increase the effects and adverse effects of antithyroid drugs, possibly leading to hypothyroidism.  Details Animal research suggests that long-term consumption of bamboo shoot can decrease thyroid peroxidase activity, as well as levels of thyroxine (T4) and triiodothyronine (T3) (33538). This effect has not yet been reported in humans.

(Read more about BAMBOO)

(Read more about GUAVA)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.  Details Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70% (93093). This interaction has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.  Details A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose (67902).

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.  Details In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya (93087).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.  Details In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract (613).

(Read more about PAPAYA)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that rosemary inhibits platelet aggregation (18334,18335,18336,18337).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models (71821,71923). However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults (105327), no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs (105323,105327).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.  Details Rosemary is reported to contain salicylates (18330).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.  Details Rosemary is reported to contain salicylate (18330).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A1 substrates.  Details In vitro research shows that rosemary induces CYP1A1 enzymes (18332,18333). This effect has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that rosemary induces CYP1A2 enzymes (18332,18333). This effect has not been reported in humans.

SALSALATE (Disalcid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.  Details Rosemary is reported to contain salicylate (18330).

(Read more about ROSEMARY)

ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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.

AMLODIPINE (Norvasc) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D 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).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B 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.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B 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). 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).

ANTITUMOR ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.  Details Most in vitro and animal research suggests that the turmeric constituent, curcumin, INHIBITS CYP1A1, primarily in the liver (15823,21495,80876,81411). However, some evidence from in vitro research suggests that curcumin may INDUCE CYP1A1 in the intestines (21500).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.  Details In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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). Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

DOCETAXEL (Taxotere) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D 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.

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D 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).

GLYBURIDE (Diabeta, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B 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).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.  Details There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633,107122,109288,110221).

LOSARTAN (Cozaar) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D 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).

METHOTREXATE (Trexall, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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).

NORFLOXACIN (Noroxin) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D 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).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D 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.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.  Details In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484,111644).

PACLITAXEL (Abraxane, Onxol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D 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.

SULFASALAZINE (Azulfidine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B 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).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B 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.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B 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).

TOPOISOMERASE I INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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.

(Read more about TURMERIC)

General ...There is currently a limited amount of information on the adverse effects of bamboo.

Dermatologic ...Topically, bamboo shoots have been reported to cause contact dermatitis in a 44-year-old female (33540).

Gastrointestinal ...In one case report, melanosis coli, pigmentation of the colon wall, was reported following the ingestion of bamboo leaf extract (33547).

Other ...Bamboo shoots are a source of cyanide glycosides. However, the hydrogen cyanide produced by the plant is eliminated during boiling, fermentation, or superheated steam drying of the shoots (96875). During the rescue of a male who jumped into a well which was used for bamboo shoot pickling, cyanide poisoning occurred in 8 individuals. The poisoning caused high anion gap metabolic acidosis in all patients and resulted in two deaths due to cardiac arrest. Some patients also had pulmonary edema and/or infiltration (96874).

(Read more about BAMBOO)

General ...Orally, guava leaf extract may cause transient abdominal pain or nausea (101782). Topically, guava leaf extract may cause contact dermatitis (95560).

Dermatologic ...Topically, guava leaf extract may cause contact dermatitis and worsen atopic dermatitis. Exacerbation of atopic dermatitis has been reported for a 17-year-old male who added tea bags containing guava leaf 30 grams to his bath to help treat his condition. His eczema worsened after bathing with the guava tea bags and improved after discontinuation of use. Based on laboratory testing, the exacerbation of eczema was attributed to positive skin reactions of the patient to a protein and tannins found in guava leaf extract (95560).

Gastrointestinal ...Orally, transient abdominal pain or nausea has been reported in a clinical trial (101782).

(Read more about GUAVA)

General ...Orally, papaya fruit is well tolerated when consumed in food amounts. Papaya leaf extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Nausea and vomiting from papaya leaf extract.
Topically: Burning sensation from unripe papaya.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions.

Dermatologic ...Orally, high doses of papaya might cause yellow skin discoloration. A case of carotenemia has been reported for a 42-year-old female who consumed 1.5-2 papayas daily for 6 months. The condition resolved when she stopped eating papayas (67929).
Topically, unripe papaya fruit may cause occasional burning sensation when applied to skin ulcers (67856).

Gastrointestinal ...Orally, the leaf extract has been reported to cause nausea and vomiting in clinical research (102799). A case of esophageal perforation has been reported for a previously healthy 27-year-old female who used papain, a constituent of papaya latex, to digest a piece of meat stuck in her esophagus (93083).

Immunologic ...Orally, papain, a constituent of raw, unripe papaya, has been reported to cause allergic reactions in sensitive individuals, including itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea (6,967). Papaya may also cause hypersensitivity reactions such as systemic contact dermatitis, which occur more commonly in people who are allergic to latex (6197,7853,57635). A case of systemic contact dermatitis has been reported for a 55-year-old female with no prior history of atopic disease or drug allergy after ingesting a throat lozenge containing papaya juice (67942).

Other ...In regions with arsenic-contaminated soil, papaya fruits contain a higher mean concentration of arsenic compared with many other forms of vegetation grown in the regions. Eating papaya from these regions is thought to contribute to higher dietary levels of arsenic (32461,67879).

(Read more about PAPAYA)

General ...Orally, rosemary seems to be well tolerated when used in appropriate medicinal amounts. Undiluted rosemary oil or very large quantities of rosemary leaf should not be consumed. Topically and as aromatherapy, rosemary seems to be well tolerated.

Dermatologic ...Topically, rosemary use can lead to photosensitivity, erythema, dermatitis, and cheilitis in hypersensitive individuals (4,6).

Immunologic ...Topically, allergic reactions can occur. When used in the mouth, lip and gum edema have occurred (101173). When used on the skin, allergic contact dermatitis has occurred, likely due to the constituent carnosol (71715,71924,71926).
Rosemary might also cause occupational asthma. A case of occupational asthma caused by several aromatic herbs including thyme, rosemary, bay leaf, and garlic has been reported. The diagnosis was confirmed by inhalation challenges. Although all of the herbs caused immediate skin reactivity, a radioallergosorbent test (RAST) showed that garlic was the most potent allergen by weight, with rosemary and the other herbs showing less reactivity (783).

Neurologic/CNS ...Orally, the undiluted oil, as well as the camphor constituent of rosemary, might cause seizures (4,5,6,12868).

(Read more about ROSEMARY)

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).

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