Fermented Aloe by New Chapter

POSSIBLY EFFECTIVE

• Acne. Topical aloe gel may reduce acne lesions when used with topical tretinoin in children and adults with acne. Details: One clinical trial in children and adults with acne shows that topical application of a gel containing aloe 50% in the morning and evening, in addition to topical application of tretinoin 0.025% cream and twice daily cleansing with a medical soap, improves acne lesions by approximately 35% more than using the same treatments without aloe (90124).
• Burns. Topical aloe gel or cream may reduce healing time in patients with superficial or partial thickness burns. Details: A meta-analysis of four small clinical trials in patients with second-degree burns shows that use of topical aloe vera reduces time to healing by about 4.4 days when compared to control groups treated with silvadene, silver sulfadiazine, or gauze containing 0.5% chlorhexidine acetate (110209). Most clinical research shows that applying aloe gel or cream topically up to twice daily reduces healing time when compared with silver sulfadiazine (19771,110210,110212), framycetin (19775), vaseline gauze (19773), or placebo (101,97320) in patients with superficial or partial thickness burns. Topical application of aloe cream up to twice daily might also decrease wound size when compared with silver sulfadiazine and framycetin (19771,19775). In addition, some clinical research in patients with burns caused by sulfur mustard shows that applying cream containing aloe and olive oil twice daily for 6 weeks improves pruritus similarly to betamethasone 0.1% cream and may lead to further reductions in excoriation and fissure (19768). However, some preliminary clinical research shows that applying fresh aloe mucilage or aloe extract daily is no more effective than silver sulfadiazine for reducing wound healing time in patients with superficial or partial thickness burns (19774,19776).
• Constipation. Oral aloe latex may improve symptoms in patients with constipation; however, the U.S. Food and Drug Administration (FDA) has banned the use of aloe latex as a laxative due to safety concerns. Details: Taking aloe latex 100-200 mg daily or aloe extract 50 mg as a stimulant laxative seems to relieve constipation due to the cathartic effects of the anthraquinones in the aloe (4,5,8). Taking 1-3 capsules of a formulation containing aloe 150 mg, celandine 300 mg, and psyllium 50 mg also seems to improve stool consistency and the mean number of stools in patients with chronic constipation when compared with placebo (19747). However, in 2002, the U.S. FDA banned the use of aloe latex for constipation due to safety concerns (8229,8443).
• Diabetes. Oral aloe may reduce blood glucose and glycated hemoglobin (HbA1c) in patients with diabetes. It may be most effective in patients with fasting blood glucose levels of 200 mg/dL or greater. Details: Most clinical research in adults with prediabetes and diabetes shows that taking aloe vera orally can reduce fasting blood glucose by 30-47 mg/dL and HbA1c by 0.41% to 1% (12164,17488,17489,19756,95943,95945,95946). One meta-analysis of 92 patients shows that aloe vera is associated with a larger overall reduction of fasting blood glucose in those with a baseline fasting blood glucose level greater than or equal to 200 mg/dL (95945). Another meta-analysis of 206 patients shows that aloe vera increases high-density lipoprotein (HDL) levels and reduces triglyceride, total cholesterol, and low-density lipoprotein (LDL) levels when compared with placebo in adults with prediabetes and untreated diabetes (95943). These analyses include studies that used multiple forms of aloe vera, including gel powder, extract, raw crushed leaves, and fresh extracted juice, as well as multiple doses ranging from 100-1000 mg of powder and 15-150 mL of juice taken for durations ranging from 4-14 weeks. Significant heterogeneity between studies, small sample sizes, and wide variability in the form and dose of aloe used limit the validity of these findings and the ability to identify an effective dose (95943,95945,95946). Additionally, some research has shown no benefit. This may be due to the different forms and doses of aloe used. One clinical study shows that taking aloe gel as 15 mL twice daily or taking aloe juice 15 mL twice daily does not decrease glucose levels in patients with type 2 diabetes (17420). Other clinical research shows that taking a specific aloe gel complex (Aloe QDM complex, Univera Inc.) containing processed aloe gel 147 mg twice daily for 8 weeks does not affect glycemic indices when compared with placebo in patients with diabetes or prediabetes (90121).
• Genital herpes. Topical aloe extract cream may improve healing of genital herpes lesions. Details: Clinical research in males with genital herpes shows that applying a cream containing aloe extract 0.5% three times daily, 5 days weekly, for up to 2 weeks increases healing rates when compared with aloe gel or placebo. The mean time to healing after application of the aloe extract was 5 days, compared with 12 days with placebo (12164,19745,19746).
• Lichen planus. Rinsing the mouth with aloe-containing mouthwash or applying aloe gel to the mouth or vulva may reduce pain and improve lesion healing in patients with lichen planus. Details: Clinical research in patients with oral lichen planus shows that using 0.4 mL of mouthwash containing aloe gel 70% three times daily for 12 weeks or applying a gel containing aloe mucilage 70% twice daily for 8 weeks is up to 6 times more likely to reduce pain when compared with placebo (19762,19763,19764). However, these findings are questionable due to poor study design. Other clinical research in patients with oral lichen planus shows that using 2 tablespoons of aloe-containing mouthwash four times daily for a month, or applying aloe gel three times daily for 8 weeks, reduces pain and improves lesion healing at least as much as triamcinolone acetonide paste (0.1% in one study) (19765,90130). However, aloe gel may not be as beneficial as laser therapy. A clinical study in patients with lichen planus show that applying a gel containing aloe powder 500 mg to the affected site three times daily for 2 months is less effective for improving pain and lesion healing than receiving low-level laser therapy twice weekly for 2 months. However, no between-group differences were maintained at 7 months after treatment completion (108722). A network meta-analysis of 2 small clinical trials shows that applying aloe trails only purslane of the herbal agents studied with regard to clinical improvement as measured by the Thongprasom scale. However, aloe does not seem to improve complete clinical resolution, clinical scores, or pain (111640). In patients with vulval lichen planus, clinical research shows that topical application with aloe gel twice daily for 8 weeks increases the number of patients who experience clinical improvement of at least 50% when compared with placebo (19766).
• Obesity. Oral aloe gel may modestly reduce body weight and fat mass in adults who are overweight or obese. Details: One clinical trial in overweight and obese adults with diabetes or prediabetes shows that taking a specific aloe gel complex (Aloe QDM complex, Univera Inc.) containing processed aloe gel 147 mg twice daily for 8 weeks reduces body weight by 0.6 kg and fat mass by 1 kg when compared with placebo (90121).
• Oral submucous fibrosis. Topical aloe may reduce burning sensations in patients with oral submucous fibrosis, but it may not improve mouth opening, tongue protrusion, or cheek flexibility in these patients. Details: A meta-analysis of five small clinical studies in patients with oral submucous fibrosis shows that topical application of aloe gel for 3 months reduces burning sensation, possibly for up to two months after treatment, when compared with placebo or active control. A network meta-analysis also found that aloe is most effective in reducing burning sensation, ranked only after treatment with corticosteroids, hyaluronidase, and antioxidants (113514). However, aloe does not seem to improve mouth opening, tongue protrusion, or cheek flexibility (100256). One of the studies included in the analysis used a specific aloe gel (Sheetal lab Surat) 5 mg applied topically on each side of the buccal mucosa three times daily for 3 months (90131). All of the studies included in the analysis were conducted in India, so it is unclear if the results are generalizable to other geographic locations. Limited research has also evaluated the use of topical and oral aloe vera in combination. A small clinical study shows that consuming pure aloe vera juice (Hamant Sai, Sun Vision Company) 30 mL twice daily and applying pure aloe vera gel (Hamant Sai, Sun Vision Company) three times daily for 3 months improves cheek flexibility and tongue protrusion when compared with a treatment regimen consisting of intralesional injections of hydrocortisone acetate 25 mg and hyaluronidase 1500 IU weekly for 6 weeks and supplementation with Cap SM Fibro (Indoco Remedies) twice daily for 3 months. Both treatment regimens show an improvement in mouth opening and burning sensation when compared to baseline, with the aloe vera treatment producing a more rapid improvement in burning sensation (95944). It is not clear how this combination of oral and topical aloe vera compares with topical aloe vera alone.
• Psoriasis. Topical aloe extract cream may reduce erythema and scaling and improve the resolution of psoriatic plaques in patients with psoriasis. Limited research suggests that topical aloe gel does not have the same effects. Details: Applying aloe extract 0.5% cream topically three times daily for 4 weeks significantly improves and increases the resolution of psoriatic plaques when compared with placebo (101,12096,12164). Aloe extract cream also seems to reduce desquamation, erythema, and infiltration (12096). Other preliminary clinical research shows that applying cream containing aloe mucilage 70% twice daily for 8 weeks improves psoriasis severity more effectively than triamcinolone 0.1% cream, although both treatments had similar effects on dermatology-specific quality of life (19741). Treatment with aloe gel does not seem to improve erythema, infiltration, and desquamation associated with psoriasis when compared with placebo (19748).
• Traumatic oral ulcers. Topical aloe gel may prevent oral ulcers after application of orthodontic appliances in adolescents and adults. Details: Clinical research in patients aged 12 years and older shows that applying a gel containing aloe 80% to the gums twice daily for one month after the cementation of orthodontic appliances prevents the development of mouth ulcers when compared with a chlorhexidine gel. Ulcers occurred in about 6% of patients using the aloe gel compared with 81% of those using the chlorhexidine gel. Bleeding and inflammation were also reduced (103305).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alveolar osteitis. It is unclear if topical aloe or the aloe constituent acemannan is beneficial in patients with alveolar osteitis. Details: One small clinical trial in patients with alveolar osteitis shows that applying a patch containing the aloe constituent acemannan (SaliCept patch) to the tooth socket, once after curettage and irrigation and again 3 days later, reduces pain intensity and improves clinical symptoms when compared with curettage and irrigation alone (19754).
• Amenorrhea. Although there has been interest in using oral aloe for amenorrhea, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Anal fissures. It is unclear if topical aloe is beneficial in patients with anal fissures. Details: One small clinical study in patients with chronic anal fissures shows that applying an aloe cream containing 0.5% powdered spray-dried inner aloe leaf juice (Zarban Phyto-Pharmaceutical Co) three times daily for at least 3 weeks, as an adjuvant to sitz baths three times daily, using a laxative, and eating a full fiber diet, improves pain, wound healing, and bleeding severity when compared with placebo (90129).
• Asthma. Although there has been interest in using oral aloe for asthma, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Atopic dermatitis (eczema). Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with atopic dermatitis shows that application of a specific combination cream (Olivederma, Kimi Daru Pharmaceutical Co.) containing aloe gel and virgin olive oil twice daily for 6 weeks improves disease severity and quality of life when compared with betamethasone cream (105020). It is unclear if this effect is due to aloe, olive oil, or the combination.
• Breast engorgement. It is unclear if topical aloe improves lactation-associated breast pain. Details: Meta-analyses of 4-5 clinical trials in lactating patients show that use of topical aloe modestly reduces nipple/breast pain and irritation when compared with no treatment, routine care with topical breast milk or breast massage, or treatment with lanolin (110213). However, studies included in this analysis were not specific to breast engorgement.
• Burning mouth syndrome. It is unclear if topical aloe is beneficial in patients with burning mouth syndrome. Details: One small clinical trial in patients with chronic burning mouth syndrome shows that applying 0.5 mL of aloe 70% gel to sore areas on the tongue three times daily prior to wearing a tongue protector for 12 weeks does not improve pain or symptoms when compared with placebo gel or using the tongue protector alone in patients with chronic burning mouth syndrome (90127). However, differences in baseline pain ratings between study groups limit the validity of these findings.
• Cancer. Oral aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with lung cancer shows that, when administered with standard chemotherapy, three daily doses of 10 mL of a mixture consisting of fresh aloe leaves 300 grams plus honey 500 grams dissolved in 40 mL of alcohol 40% increases the rate of complete response, partial response, or disease control when compared with chemotherapy alone (19752).
• Canker sores. Small clinical studies suggest that applying the aloe constituent acemannan to cancer sores may reduce ulcer size, but not pain. However, the effect of aloe is unclear. Details: Meta-analyses of clinical research show that topical aloe is no more effective than control interventions for reducing the size and pain of oral ulcers (110216). Control interventions have included carrier gel or triamcinolone acetonide 0.1% (19751,110216). However, a recent clinical trial shows that topical aloe gel (G.U.M Canker-X, Sunstar Americas, Schaumburg, USA) after meals and before bedtime for 5 days is more effective than amlexanox 5% paste and placebo for reducing pain and the size of canker sores in patients with recurrent symptoms (110215). Other small clinical trials have investigated the effects of fermented aloe or the aloe constituent acemannan. One small clinical trial in adults with recurrent canker sores shows that applying a fermented aloe gel to oral ulcers three times daily seems to accelerate healing time when compared with chitosan gel (104173). Another small clinical trial in patients with canker sores shows that using a wound dressing containing the aloe constituent acemannan (Carrisyn Gel Wound Dressing) shortens the average healing time of canker sores when compared with an oral analgesic (Orabase-Plain) (19750). Other clinical research shows that applying acemannan 0.5% in Carbopol 934P NF three times daily for 7 days reduces ulcer size, but not pain, when compared with Carbopol 934P NF alone in patients with canker sores (90123). However, applying triamcinolone acetonide 0.1% appears to be more effective in reducing pain and similarly effective in reducing ulcer size when compared with acemannan 0.5% (90123).
• Common cold. Although there has been interest in using oral aloe for the common cold, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Dental plaque. Using aloe-containing toothpaste may reduce dental plaque in adults; however, it is unclear if this is more effective than fluoride-containing toothpaste. Rinsing with an aloe-containing mouthwash may reduce dental plaque in children. Details: One small clinical trial in adults shows that brushing teeth with a dentifrice containing aloe gel (Forever Bright, Forever Living Products) three times daily for 30 days does not reduce the occurrence of plaque better than a fluoridated dentifrice (Sorriso Dentes Brancos, Kolynos do Brasil), although both treatments seem to show improvement when compared to baseline (19755). Another small clinical study in adults with gingivitis shows that using toothpaste containing aloe daily for 24 weeks reduces plaque more effectively than placebo or triclosan-containing toothpaste (19760). In children aged 8-14 years with mild plaque, using a mouth wash containing aloe vera 7% twice daily for 4 weeks reduced plaque by a large amount when compared with placebo. In addition, it was as effective as chlorhexidine 0.2% (103306).
• Depression. Although there has been interest in using oral aloe for depression, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Diabetic foot ulcers. It is unclear whether topical aloe is beneficial for patients with diabetic foot ulcers. Details: One small clinical trial in patients with a stage 1 or 2 diabetic foot ulcer who are receiving oral antibiotics shows that applying a topical product containing aloe and great plantain twice daily for 4 weeks reduces ulcer surface area and time to healing, but not ulcer depth, when compared with antibiotics alone (97323). The effect of applying aloe gel alone without concomitant oral antibiotic therapy is unknown.
• Diaper rash. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial shows that applying a cream containing aloe gel and olive oil three times daily for 5-10 days reduces diaper rash severity in children less than 3 years of age when compared to baseline; however, it does not seem to be as effective as calendula ointment (19779). The validity of this finding is limited by the lack of a placebo group.
• Dry mouth. It is unclear if rinsing with an aloe-containing mouthwash is beneficial for dry mouth. Details: In patients with dry mouth related to type 2 diabetes, clinical research shows that an aloe vera 50% mouthwash, as 20 mL swished and spit three times daily for 14 days, modestly reduces symptoms of dry mouth when compared with rinsing with a saline control mouthwash (106068). The validity of this study is limited due to unclear reporting.
• Dry skin. Topical aloe or oral aloe sterols may improve some measures of dry skin. However, findings are mixed due to the use of varied formulations and doses. Details: One small clinical trial shows that applying a cream containing freeze-dried aloe extract 0.1% to 0.5% to the skin for 2 weeks increases the amount of water in the stratum corneum, but does not reduce transepidermal water loss, when compared with placebo (19758). Another small clinical study in females with occupational dry skin shows that wearing gloves coated in aloe 8 hours daily for 30 days improves symptoms of dry skin when compared with no treatment (19759). However, it is not clear if the benefits resulted from applying aloe or wearing gloves. One small clinical trial in healthy females shows that consumption of a yogurt containing 500 mg of aloe vera gel powder (0.4 mg of aloe sterol) daily for 12 weeks increases skin hydration, skin elasticity, and collagen content of the dermis while reducing markers of skin fatigue and transepidermal water loss when compared with placebo (95942). However, another study in healthy females shows that taking aloe sterol-enriched aloe extract 0.5 grams daily for 12 weeks does not improve skin hydration when compared with placebo, although redness, itching, collagen content, and transepidermal water loss were improved (101577).
• Epilepsy. Although there has been interest in using oral aloe for epilepsy, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Frostbite. Although there has been interest in using topical aloe for frostbite, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Gingivitis. Using aloe-containing toothpaste may reduce gingivitis in adults, but it does not seem to be more effective than fluoride-containing toothpaste. Rinsing with an aloe-containing mouthwash may reduce gingivitis in children. Details: One small clinical trial in adults shows that brushing teeth with a dentifrice containing aloe gel (Forever Bright, Forever Living Products) three times daily for 30 days does not reduce the occurrence of gingivitis more effectively than a fluoridated dentifrice (Sorriso Dentes Brancos, Kolynos do Brasil), although both treatments seem to show improvement when compared to baseline (19755). Another small clinical study in adults with gingivitis shows that using aloe-containing toothpaste daily for 24 weeks reduces gingivitis more effectively than placebo, but not more than triclosan-containing toothpaste (19760). In children aged 8-14 years with mild gingivitis, using a mouthwash containing aloe vera 7% twice daily for 4 weeks reduced gingivitis by a large amount when compared with placebo. In addition, it was as effective as chlorhexidine 0.2% (103306).
• Heart failure. It is unclear if oral aloe is beneficial in patients with systolic heart failure. Details: A very small clinical study in adults with moderate to moderately severe chronic systolic heart failure shows that taking aloe vera gel capsules 150 mg twice daily for 8 weeks in addition to standard treatment decreases New York Heart Association (NYHA) functional class, improves Minnesota Living with Heart Failure Questionnaire (MLHFQ) total, physical, emotional, and social scores, and enhances sleep quality but does not reduce the severity of obstructive sleep apnea scores or improve six-minute walk test distance when compared with placebo (111663). The study may have been inadequately powered to detect a difference between groups. Additionally, the validity of these effects may be limited by the small sample size.
• Hematopoietic stem cell transplant (HSCT). Oral and topical aloe have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients undergoing hematopoietic stem cell transplantation shows that treatment with colostrum and aloe orally (Remargin Colostrum Gastro-Gel, Solimè srl, Cavriago, Reggio Emilia, Italy) and as a mouthwash (Remargin Colostrum OS, Solimè srl, Cavriago, Reggio Emilia, Italy) modestly reduces the risk and duration of severe oral mucositis and febrile neutropenia when compared with historical values. There was no effect on the duration of neutropenia, the length of hospital stay, pain, or duration of medications. All patients were also given standard care. The mouthwash was used after each oral hygiene, and the oral treatment was 3 to 5 times daily depending on symptoms (110211).
• Hepatitis. It is unclear if oral aloe is beneficial in patients with hepatitis. Details: One small clinical trial in patients with liver fibrosis primarily caused by hepatitis B or hepatitis C shows that taking a high molecular weight fraction of aloe 0.05 grams three times daily for 12 weeks reduces fibrosis, attenuates liver enzyme activity, and decreases hepatic glutathione content when compared with placebo (19780).
• HIV/AIDS. Small clinical studies suggest that oral aloe or the aloe constituent acemannan may not improve CD4 counts or viral load in patients with HIV. Details: One small clinical trial in patients with HIV shows that taking the aloe constituent, acemannan, 400 mg four times daily does not significantly improve CD4 counts, ratio of CD4 to CD8, or viral load when compared with placebo (19851). Another small clinical study in patients with HIV shows that taking aloe gruel 30-40 mL daily does not improve CD4 counts when compared with those treated with antiretroviral therapy, although both groups show similar increases in weight compared to baseline (19852).
• Hyperlipidemia. Although there has been interest in using oral aloe for hyperlipidemia, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Hypertrophic scars. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients undergoing median sternotomy shows that applying a silicone gel containing aloe extract and other herbal extracts (Bangkok Botanica) to postoperative hypertrophic scars for 6 months reduces the height of the scar and improves pliability by a moderate amount when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to aloe, other ingredients, or their combination.
• Influenza. Oral aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults shows that taking a combination supplement containing aloe vera gel, rosemary, and poria mushrooms twice daily 28 days before administering the influenza vaccine and 28 days after vaccination does not improve immunologic markers or reduce symptom severity, symptom duration, frequency of upper respiratory tract infection symptoms, or the use of cold and flu medications when compared with placebo (111921).
• Irritable bowel syndrome (IBS). Small clinical studies suggest that oral aloe extract or juice may not improve symptoms in patients with IBS. Details: Most research suggests that aloe is not effective for improving symptoms of IBS; however, the available evidence is of low-quality, with some studies having high dropout rates or inadequate power to detect significant differences. Two clinical trials show that taking a specific aloe extract (AVH200, Calmino Group AB) 250-500 mg twice daily for 4 weeks does not improve IBS-related symptoms or response rates when compared with placebo (101579,104169), although one of these studies did find a trend toward a higher response rate, defined as a 50% or greater improvement in symptom scores, with aloe over placebo (104169). Also, a pooled analysis of these two studies shows that taking this specific product improves IBS-related pain severity and frequency in patients with diarrhea-prominent IBS (IBS-D) when compared with placebo, but does not seem to improve stool consistency or frequency (108718). Clinical trials evaluating aloe juice 50 mL four times daily for 1 month or 60 mL twice daily for 5 months show no significant improvement in quality of life scores or IBS symptoms when compared with placebo (104170,104171), although one study did find a trend toward improved response in patients with IBS-D (104171). Despite a lack of significant findings in the individual studies, a pooled analysis of the two smallest studies above (104169,104171) shows that aloe extract or juice, taken for 4 weeks, may increase the rate of symptom response by almost 70% when compared with placebo (103307).
• Nipple Fissures. It is unclear if application of an aloe poultice improves nipple-related complications of breastfeeding, such as nipple fissures. Details: A clinical study in females who have just given birth and are breastfeeding for the first time shows that applying a poultice containing aloe gel to the nipples after breastfeeding six times daily for 5 days improves nipple eschar when compared with no treatment. Although there were modest improvements in other outcomes, such as redness, fissures, and epidermolysis, these differences were not significant (108721). Participants were instructed to clean with purified water before the next breastfeeding session.
• Multiple sclerosis (MS). Although there has been interest in using oral aloe for MS, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Oral mucositis. Small clinical studies suggest that oral aloe juice or application of aloe solution inside the mouth may prevent oral mucositis in patients receiving chemotherapy or radiation. Details: Some clinical research shows that drinking 15 mL of juice containing aloe 80% three times daily during radiation therapy decreases the risk of developing moderate or severe mucositis by approximately 39% when compared with placebo (19767,19964). In addition, in children aged 3-6 years undergoing chemotherapy for leukemia, application of a solution containing aloe 70% twice daily inside the mouth, starting three days before chemotherapy, reduces the severity of oral mucositis and delays its onset by 2 weeks when compared with sodium bicarbonate 5% (103304). Other clinical research in adults with head and neck cancer shows that rinsing and then swallowing 20 mL of a solution containing aloe juice 94.5% four times daily throughout the course of radiation therapy does not prevent mucositis when compared with placebo (19963). However, this study was not adequately powered to detect significant differences between study groups. Aloe has also been evaluated in combination with other ingredients for the treatment of oral mucositis. Preliminary clinical research in patients undergoing hematopoietic stem cell transplantation shows that treatment with colostrum and aloe orally (Remargin Colostrum Gastro-Gel, Solimè srl, Cavriago, Reggio Emilia, Italy) and as a mouthwash (Remargin Colostrum OS, Solimè srl, Cavriago, Reggio Emilia, Italy) modestly reduces the risk and duration of severe oral mucositis when compared with historical values. There was no effect on overall risk or time of onset of mucositis. All patients were also given standard care. The mouthwash was used after each oral hygiene, and the oral treatment was 3 to 5 times daily depending on symptoms (110211). Another small clinical study in adults with head and neck cancer receiving radiotherapy shows that rinsing with 5 mL of a mouthwash containing aloe, German chamomile, peppermint oil, and honey 3 times daily for 60 seconds for 6 weeks starting on the first day of radiotherapy reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine and placebo (111291). It is unclear if these findings are due to aloe, other ingredients, or the combination.
• Osteoarthritis. Although there has been interest in using oral and topical aloe for osteoarthritis, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Peptic ulcers. Although there has been interest in using oral aloe for peptic ulcers, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Periodontitis. It is unclear if application of aloe inside the mouth is beneficial for chronic periodontitis. Details: A meta-analysis of small clinical studies in patients with chronic periodontitis shows that using various aloe-containing gels, mouthwashes, and toothpastes improves plaque index when compared with placebo or other treatments (i.e., chlorhexidine rinse, metformin, and tea tree oil). The effect of these aloe products on gingival index could not be determined (108719). The validity of this finding is limited by the variety of aloe formulations and comparators used in the included studies.
• Pressure ulcers. It is unclear if topical aloe is beneficial for the prevention or treatment of pressure ulcers. Details: One small clinical study shows that applying a gel containing the aloe constituent acemannan to pressure ulcers daily for 10 weeks does not reduce the time to healing when compared with management with moist saline gauze (12160,19853). Another small clinical study conducted in Iran in patients with category II pressure ulcers shows that applying topical aloe vera gel after cleaning with normal saline and prior to dressing daily for 15 days reduces pain during dressing changes when compared with normal saline dressing (113672). Other clinical research shows that cleansing wounds with a saline spray containing aloe, silver chloride, and decyl glucoside for 2 weeks improves pressure ulcer healing when compared with isotonic saline spray (19854). It is unclear if this improvement is due to aloe, other ingredients, or the combination in the spray. Aloe has also been evaluated for the prevention of pressure ulcers. A small clinical study in hospitalized patients in an orthopedic ward shows that applying aloe vera gel to the hips, sacrum, and heels twice daily for 10 days reduces pressure ulcer occurrence to 3 of 39 patients, compared to 12 of 38 patients of those receiving placebo (98816). However, methodological limitations with this study, including differences in how the gels were applied, limit the reliability of these results. A clinical study in hospitalized patients receiving intensive care has evaluated either aloe gel 94%, olive oil 100%, or a compounded product containing aloe vera and olive oil in a 3:2 ratio, applied to pressure areas as 10-15 mL every 8 hours. At the end of 30 days, pressure ulcers occurred in 17% of patients receiving the combination product, 20% receiving olive oil, 33% receiving aloe gel, and 37% receiving standard care, suggesting that any benefit may be due to olive oil (108723).
• Radiation dermatitis. There is conflicting evidence about the effectiveness of topical aloe gel for preventing or delaying dermatitis in patients undergoing radiation therapy. These conflicting findings may be due to differences in study designs, products used, and application practices. Details: Two meta-analyses of clinical trials, some of which overlap, in patients with various types of cancer shows that topical aloe does not reduce the incidence or severity of radiation dermatitis (110325,113674) and does not reduce the incidence of erythema, pruritis, moist desquamation, or dry desquamation when compared with control (110325). However, the included studies are limited by a lack of blinding, questionable methodological quality, and a high risk of bias. In contrast, another meta-analysis of generally poor quality randomized controlled trials shows that topical pre-treatment application with aloe as gel, cream, lotion, or fresh plant reduces the risk of radiation dermatitis by 23%, especially mild to moderate radiation dermatitis, when compared with a control group not treated with aloe (110214). One U.S. study included in the analysis shows that applying aloe 98% gel twice daily starting within three days of radiation initiation does not reduce radiation dermatitis when compared with a placebo gel or no treatment (12163). Other research has focused on specific side effects. One clinical trial shows that applying aloe 98% gel three times daily throughout radiation treatment and after treatment does not seem to reduce symptoms of radiation dermatitis in patients being treated for breast cancer (12098). Some research shows that applying aloe 100% gel 6-8 times daily might prolong the time before radiation-related side effects occur, but only when the cumulative dose of radiation is high (>2,700 cGy) (12159). In addition, applying aloe-based gel once daily after radiation treatment is less effective than applying anionic phospholipid-based cream for reducing dryness, erythema, and peeling in children being treated for Hodgkin disease (19855). Aloe has also been evaluated in combination with other ingredients. A small cohort study in patients with head and neck cancer receiving radiation therapy shows that applying aloe 2% and radish 4% gel twice daily until ten days after the last radiotherapy session prevents radiation dermatitis as shown by fewer cases of radiation dermatitis in the 10th, 30th, and 35th radiation sessions when compared with placebo. Furthermore, after the 35th session, the subjects prophylactically treated with the aloe and radish gel had milder grades of radiation dermatitis when compared with control (111662). A preliminary clinical study shows that applying a specific cream product (Radioskin 2, Herbalab di Perazza Massimiliano Company), which contains aloe, ginkgo extract, and metal esculetina, along with another specific cream product (Radioskin 1, Herbalab di Perazza Massimiliano Company), which contains alga atlantica and ethylbisiminomethylguaicolo manganese cloruro, may improve skin hydration and reduce skin toxicity associated with radiation therapy in patients with breast cancer (89727). These creams were applied topically 2-3 times daily at least 3 hours before and after radiation treatment, from 15 days prior to radiation until one month after completion.
• Radiation proctopathy. It is unclear if topical aloe is beneficial for the prevention or treatment of radiation proctopathy. Details: One very small clinical study in females with radiation proctopathy shows that applying 1 gram of an ointment containing aloe vera 3% rectally twice daily in conjunction with taking sulfasalazine 500 mg four times daily for 4 weeks modestly reduces diarrhea, fecal urgency, radiation toxicity, and clinical symptoms when compared with sulfasalazine alone (95941). This same product, applied twice daily for 6 weeks starting on the first day of radiotherapy, has also been evaluated for the prevention of radiation proctopathy. One small clinical study in patients with pelvic cancer shows that applying this ointment prevents proctopathy-related diarrhea, rectal bleeding, and fecal urgency when compared with placebo. Proctopathy-related symptoms occurred in 5% of patients using aloe, compared with 65% of those using placebo. However, there was no difference in rectal pain, constipation, or symptoms of cystitis between groups (101578). A very small clinical study in patients with colorectal cancer shows that applying this ointment prevents proctopathy-related diarrhea and reduces proctopathy severity, but does not improve rectal bleeding, rectal pain, fecal urgency, or symptoms of cystitis, when compared with placebo (108717). Reasons for discrepancies are unclear but might relate to differences in cancer diagnosis and radiation regimens.
• Scabies. It is unclear if topical aloe is beneficial in patients with scabies. Details: One small open-label clinical study in children and adults with scabies shows that application of crude aloe gel for 3 consecutive days, repeated again after one week, may reduce itching and lesions similar to benzyl benzoate lotion in patients with scabies when compared to baseline (19769). The validity of this finding is limited by the lack of a placebo group.
• Seborrheic dermatitis. It is unclear if topical aloe is beneficial in patients with seborrheic dermatitis. Details: One small clinical study in adults with seborrheic dermatitis shows that applying aloe 30% emulsion twice daily for 4-6 weeks reduces scaling, itching, and the number of sites involved, but not erythema, when compared with placebo (19749).
• Stretch marks (striae gravidarum). It is unclear if topical aloe is effective for the prevention or treatment of stretch marks. Details: One small clinical trial in nulliparous patients shows that topical application of a cream containing aloe twice daily, starting at gestational week 16-18, reduces erythema and itching related to abdominal stretch marks, but does not seem to decrease the number of stretch marks, when compared with a base cream (97322). Aloe gel has also been evaluated in combination with fractional carbon dioxide (CO2) laser treatments. A small clinical trial shows that applying a gel containing aloe 87.4% twice daily for up to one month after each of three CO2 laser treatments improves the texture of the skin for up to 6 months after the last laser treatment when compared to baseline. This was as effective as topical recombinant human epidermal growth factor (rhEGF) and CO2 laser treatments. However, when specific sites were examined, only the texture of stretch marks on the buttocks were improved, and these improvements were less than those seen with rhEGF (101580). The effect of aloe for the prevention of stretch marks is unknown.
• Sunburn. Although there has been interest in using topical aloe for sunburn, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Tungiasis. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that applying a product containing coconut oil, jojoba oil, and aloe leaf extract (Zanzarin, Engelhard Arzneimittel GmbH & Co. KG) to the feet twice daily for one-week intervals seems to reduce the number of embedded sandfleas in individuals with tungiasis when compared with a control group (19778). It is not clear if this effect is due to aloe, the other ingredients, or the combination.
• Ulcerative colitis. It is unclear if oral aloe gel is beneficial in patients with ulcerative colitis. Details: One small clinical trial in patients with mild to moderate ulcerative colitis shows that taking aloe gel for 4 weeks, starting at 25-50 mL twice daily for the first 3 days and increasing to 100 mL twice daily thereafter, reduces symptoms when compared with placebo (11984).
• Vaginitis. It is unclear if topical aloe is beneficial for vaginitis. Details: One small clinical trial in postmenopausal patients with atrophic vaginitis shows that applying 5 mg of a vaginal cream containing aloe gel 2% nightly for 2 weeks, then 3 nights per week for 4 weeks, reduces vaginal dryness, burning, and pain during intercourse and improves measures of vaginal health and maturity when compared to baseline. These effects were similar to those seen with estrogen vaginal cream (104175).
• Varicose veins. Although there has been interest in using oral and topical aloe for varicose veins, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Wound healing. There is conflicting evidence about the effectiveness of topical aloe products for improving wound healing. These conflicting findings may be due to differences in study designs, products used, and application practices. Details: One small clinical study shows that applying aloe gel to a caesarean wound after surgery, followed by a dry gauze, improves wound healing over the first 24 hours when compared with the dry gauze alone (90128). However, other clinical research in a small number of patients undergoing gynecologic surgery or cesarean section shows that applying an aloe gel extract (Carrington Dermal Wound Gel) to surgical wounds may actually delay wound healing (11982). Another small clinical trial shows that applying a formulation of aloe gel 0.5% cream (Zarband, Phytopharmaceutical Co.) to hemorrhoidectomy wounds three times daily for 4 weeks improves healing rates and pain relief scores and decreases intake of narcotic analgesics when compared with placebo (17418). However, another clinical trial in patients with biopsy wounds shows that application of a hydrogel containing the aloe constituent, acemannan (Carrasyn, Carrington hydrogel), does not improve wound epithelialization, wound infections, or pain when compared with conventional therapy (19856). Additionally, there is contradictory evidence about the effectiveness of aloe for improving skin graft donor site healing. One small clinical study shows that applying aloe gel 87.4% daily to split-thickness skin graft donor sites reduces time to complete healing by about 2 days when compared with placebo (97320). However, another small clinical study shows that applying aloe cream three times daily to split-thickness skin graft donor sites does not improve healing time when compared with placebo (97321).
• Wrinkled skin. Although there has been interest in using topical aloe for wrinkled skin, there is insufficient reliable information about the clinical effects of aloe for this purpose. More evidence is needed to rate aloe for these uses.

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POSSIBLY EFFECTIVE

• Dyspepsia. Oral artichoke leaf extract may improve symptoms in patients with functional dyspepsia or dyspepsia associated with biliary disease. Details: Several clinical trials in patients with functional dyspepsia or dyspepsia associated with biliary disease show that taking artichoke leaf extract can reduce symptoms such as nausea, vomiting, flatulence, and abdominal pain. Improvement seems to occur after 2 to 8 weeks of treatment (2056,11429,12208). The validity of some of this evidence is limited by a small sample size (2056) or lack of a control group (11429). However, a higher-quality clinical trial in patients with mild dyspepsia shows that taking artichoke leaf extract 640 mg three times daily for 6 weeks improves overall symptom and quality of life scores. Specifically, patient ratings for flatulence, feelings of fullness, and early satiety were reduced when compared with placebo. Further, for every 12 patients treated with this extract over placebo, one additional patient reported markedly or completely improved symptoms (12208). Some studies have used a specific extract called ALE LI 220 (Hepar-SL forte, Serturner Arzneimittel GmbH) at doses ranging from 320-640 mg three times daily for up to 8 weeks (2056,12208). Another study has used a different artichoke leaf extract (Cynara SL, Lichtwer Pharma) at a dose of 320-640 mg daily for 2 months (11429). Some clinical research has also assessed artichoke extract in combination with ginger extract. Results show that taking 2 capsules of a specific product containing artichoke leaf extract 100 mg and ginger extract 20 mg (ProDigest, Indena) daily for 4 weeks markedly or completely improves symptoms such as nausea, fullness, pain, and bloating in about 1.5-fold more patients with functional dyspepsia when compared with placebo (91474).
• Hyperlipidemia. Most research shows that oral artichoke lowers cholesterol and triglyceride levels in patients with hyperlipidemia. However, frozen artichoke juice does not appear to have these effects. Details: Multiple meta-analyses and clinical studies in patients who are either healthy or have hyperlipidemia, nonalcoholic fatty liver disease, or pre-obesity show that taking artichoke leaf extract or concentrated artichoke juice capsules daily for 4-24 weeks reduces total cholesterol by 13-18 mg/dL, low-density lipoprotein (LDL) cholesterol by 15-17 mg/dL, and triglycerides by 9-18 mg/dL, but does not increase high-density lipoprotein (HDL) cholesterol, when compared with placebo (104132,108713,111560,111564). While the five studies including non-hyperlipidemic patients in one of these analyses reported mixed results, all four of the studies evaluating artichoke leaf extract in patients with hyperlipidemia showed significant reductions in total cholesterol and LDL cholesterol when compared with placebo (104132). Additionally, a dose-response analysis suggests that baseline cholesterol levels are a stronger predictor of benefit than dose and treatment duration (108713). The validity of these findings is limited due to the high heterogeneity of studies included in meta-analyses. Another clinical study in patients with mild hypercholesterolemia shows that taking artichoke extract 250 mg twice daily for 8 weeks decreases LDL cholesterol by about 11% and increases HDL cholesterol by about 10% when compared with placebo (91478). Other formulations have also been evaluated, including cynarin, a constituent of artichoke, and artichoke juice. Some older, small clinical studies suggest that taking cynarin 20 mg three times daily for 2-7 months reduces total cholesterol and triglyceride levels when compared to baseline in patients with hypercholesterolemia and/or hypertriglyceridemia (52222,52223,52236). However, cynarin does not appear to reduce cholesterol levels in patients with familial type II hyperlipoproteinemia (1424). In patients with hyperlipidemia, consuming frozen artichoke juice 20-30 mL daily for 6-12 weeks does not appear to reduce total or LDL cholesterol levels and may even increase triglyceride levels (52216,52234). Artichoke leaf extract has also been evaluated in combination with other ingredients. Clinical research shows that taking a product containing red yeast rice extract, artichoke leaf extract, and other ingredients (Limicol, Laboratoire Lescuyer) 3 or 6 tablets daily for 4-16 weeks decreases LDL cholesterol by 14% to 21% in patients with hyperlipidemia. However, the red yeast in this product contains monacolin K (lovastatin), which likely contributed to the cholesterol-lowering effect (89451,89452,89454). Another specific product (Vazguard; Indena SpA), containing artichoke leaf extract (Indena SpA) 100 mg and bergamot phytosome 600 mg, has also shown benefit in patients with mild hypercholesterolemia when taken twice daily for 2 months (108712). However, it is unclear if this effect is due to artichoke leaf, bergamot, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Biliary disorders. Although there has been interest in using oral artichoke for various biliary disorders, including for the treatment of cholestasis or prevention of gallstones, there is insufficient reliable information about the clinical effects of artichoke for these conditions.
• Diabetes. Several small clinical studies suggest that oral artichoke extract may slightly reduce fasting blood glucose, but may not improve glycated hemoglobin (HbA1c) or other measures of glycemic control, in patients with diabetes. Details: A meta-analysis of 9 small clinical trials shows that taking artichoke leaf extract for 8-12 weeks reduces fasting blood glucose by around 5 mg/dL, but does not improve HbA1c, insulin levels, or markers of insulin resistance, when compared with placebo (105768). The generalizability of these findings to patients with diabetes is limited; only 2 of the 9 studies specifically enrolled patients with diabetes. The other studies included patients who were overweight or with liver disease, hyperlipidemia, or metabolic syndrome. In contrast, a post-hoc analysis of clinical research in overweight adults at risk for developing diabetes shows that taking a specific artichoke leaf product (Altilix, Bionap S.r.l.) 50 mg daily for 6 months reduces HbA1c by around 0.9% and improves measures of insulin resistance and beta-cell function when compared with placebo (111564).
• Hangover. It is unclear if oral artichoke extract is beneficial for the prevention of hangover. Details: A small clinical study in healthy adults shows that taking artichoke extract 960 mg immediately before and after alcohol consumption does not prevent alcohol-induced hangover when compared with placebo (11774).
• Hepatitis C. It is unclear if oral artichoke is beneficial in patients with hepatitis C. Details: One small clinical study in patients with chronic hepatitis C shows that taking artichoke leaf extract 3200 mg daily for 12 weeks does not normalize liver enzyme levels or reduce viral load when compared to baseline. Although symptoms such as fatigue, abdominal discomfort, and joint problems appear to improve in the first 4 weeks, the improvement is not maintained over 12 weeks (91475). However, another small clinical study shows that drinking a tea infusion of wild artichoke three times daily for 3 months normalizes liver enzymes and serum virus levels in 12 of 15 patients with hepatitis C (97717). The validity of these findings is limited by the lack of a control group.
• Hypertension. Analyses of small clinical studies suggest that oral artichoke may slightly reduce blood pressure in patients with hypertension; however, individual study results are conflicting, and the improvements in blood pressure may not be clinically significant. Details: Evidence regarding an association between artichoke consumption and hypertension is conflicting (91477,104133,105767,111561). Two meta-analyses include many of the same studies yet reach contradictory conclusions. One meta-analysis of 8 small clinical trials shows that taking artichoke leaf extract, powder, or juice for 8-12 weeks does not reduce systolic blood pressure (SBP) or diastolic blood pressure (DBP). However, subgroup analysis in patients with documented hypertension shows that artichoke reduces SBP by around 3 mmHg and DBP by around 2 mmHg when compared with placebo (105767). In contrast, another meta-analysis of 7 small clinical trials shows that taking artichoke 50-2700 mg daily for 4-12 weeks reduces SBP by about 2 mmHg and DBP by about 1.5 mmHg. Subgroup analysis shows that the greatest reductions in SBP and DBP occur in doses of 500 mg daily or less, at durations longer than 8 weeks, and in patients under 50 years old (111561). Discrepancies between the results of the meta-analyses with overlapping studies may be due to the former meta-analysis including artichoke supplementation in combination with other ingredients, while the latter meta-analysis focused on artichoke supplementation alone.
• Irritable bowel syndrome (IBS). It is unclear if oral artichoke leaf extract is beneficial in patients with IBS. Details: Some observational research in patients with IBS has found that taking a specific artichoke leaf extract (Hepar-SL forte, Serturner Arzneimittel GmbH) 640 mg three times daily for 6 weeks is associated with reductions in abdominal pain, cramping, bloating, flatulence, and constipation when compared to baseline (2562). Also, a small clinical study in patients with IBS shows that taking a different specific artichoke leaf extract (Cynara SL, Lichtwer Pharma) 320-640 mg daily for 2 months reduces the incidence of IBS symptoms in patients with dyspepsia by about 26% when compared to baseline. Patients taking this extract also had improved quality of life (15204). The validity of these findings is limited by the lack of a control group.
• Metabolic syndrome. It is unclear if oral artichoke leaf extract is beneficial in patients with metabolic syndrome. Details: A small clinical trial in patients with metabolic syndrome shows that taking artichoke leaf extract 1800 mg daily for 12 weeks does not improve fasting blood glucose, insulin resistance, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or blood pressure when compared with placebo. However, taking artichoke extract does reduce triglycerides by around 27 mg/dL when compared with placebo (100935).
• Nausea and vomiting. Although there has been interest in using oral artichoke for nausea and vomiting, there is insufficient reliable information about the clinical effects of artichoke for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral artichoke leaf extract is beneficial in patients with NAFLD. Details: Meta-analyses of 12 clinical studies in adults with a variety of metabolic disorders, including NAFLD, show that taking artichoke 50-2700 mg daily for 4-24 weeks reduces alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when compared with placebo (111560,111563). These effects are greater for ALT in trials lasting 8 weeks or longer and for AST at doses over 500 mg daily (111563). The validity of these findings is limited by significant heterogeneity among the included studies. A small clinical trial in patients with NAFLD shows that taking a specific artichoke leaf extract (Cynarol, Niak Pharmaceuticals), standardized to contain cynarin 2%, as 200 mg three times daily for 2 months improves NAFLD severity, reduces liver size, and increases hepatic vein flow when compared with placebo. The severity of NAFLD improved in 82% of patients taking artichoke, compared with 5% taking placebo. NAFLD severity did not worsen in any patients taking artichoke, compared with 27.5% of those taking placebo. Serum levels of liver transaminases, total bilirubin, and lipids were also improved with artichoke when compared with placebo (100934). However, the validity of these findings is limited by inappropriate randomization, the use of a per-protocol analysis, and significant differences between groups at baseline. Artichoke leaf extract has also been evaluated in combination with conventional therapies. A clinical trial shows that taking metformin 500 mg twice daily and/or vitamin E 400 IU once daily along with a specific artichoke leaf extract (Tishoke; Goldaru Company) 400 mg twice daily, providing 40 mg chlorogenic acid daily, for 12 weeks improves NAFLD severity and reduces liver size when compared with baseline. However, these improvements were similar to those seen in patients taking metformin with vitamin E. After 12 weeks, the number of patients with no fat accumulation (steatosis grade 0) increased by 23% in the artichoke and metformin group, 17% in the artichoke and vitamin E group, and 10% in the metformin and vitamin E group (108714)
• Obesity. A meta-analysis of several small clinical studies suggests that oral artichoke extract may slightly reduce waist circumference, but not body weight or body mass index (BMI), in patients who are overweight or obese. Details: A meta-analysis of 10 small clinical trials shows that taking artichoke leaf extract, powder, or juice for 8-12 weeks reduces waist circumference by 1.11 cm, but does not improve body weight or BMI, when compared with placebo (105766). The generalizability of these findings to patients who are overweight or obese is limited by the fact that only 3 of the 10 trials specifically enrolled patients because they were overweight. Other studies evaluated patients with liver disease, metabolic syndrome, diabetes, hyperlipidemia, or hypertension. In contrast, a post-hoc analysis of clinical research in adults with overweight shows that taking an artichoke leaf supplement (Altilix, Bionap S.r.l.) 150 mg daily for 6 months reduces body weight by around 2.3 kg but does not improve waist circumference when compared with placebo (111564).
• Osteoarthritis. Although there has been interest in using oral artichoke for osteoarthritis, there is insufficient reliable information about the clinical effects of artichoke for this purpose. More evidence is needed to rate artichoke for these uses.

(Read more about ARTICHOKE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Small clinical studies suggest that oral cardamom may slightly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes, but it does not appear to improve blood glucose, blood pressure, or cholesterol levels in these patients. Details: A small clinical study in overweight or obese adults with type 2 diabetes who are taking antidiabetes medication shows that taking cardamom 1 gram three times daily for 10 weeks reduces HbA1c by 0.4% and improves insulin and triglyceride levels when compared with a rusk powder placebo (101887). However, other small clinical studies show that taking cardamom 1 gram three times daily does not reduce fasting blood glucose, blood pressure, or total cholesterol levels, or improve anthropometric measures in patients with type 2 diabetes (95597,99436,101887).
• Dyspepsia. Although there has been interest in using oral cardamom for dyspepsia, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Epilepsy. Although there has been interest in using oral cardamom essential oil for epilepsy, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Hyperlipidemia. Small clinical studies suggest that oral cardamom may modestly reduce triglyceride levels in patients with hyperlipidemia, but it does not seem to improve other lipid levels in these patients. Details: A meta-analysis of mostly small randomized controlled trials shows that taking cardamom 3 grams daily for 8-12 weeks does not improve total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol levels. However, it might modestly reduce triglyceride levels when compared with placebo (101886).
• Hypertension. It is unclear if oral cardamom powder is beneficial in patients with hypertension. Details: A small clinical study in adults with newly-diagnosed, untreated, stage 1 essential hypertension shows that taking cardamom powder 1.5 grams orally twice daily for 12 weeks reduces systolic blood pressure by about 19 mmHg and diastolic blood pressure by about 12 mmHg when compared to baseline (95308). The validity of these findings is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral cardamom for IBS, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Nausea and vomiting. Although there has been interest in using oral cardamom for nausea and vomiting, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral cardamom is beneficial in patients with NAFLD. Details: A small clinical study in overweight or obese patients with NAFLD shows that taking cardamom 1000 mg three times daily for 3 months improves some measures of cardiovascular and hepatic health when compared with placebo. Fatty liver grade, as measured by sonography, improved in 42% of patients taking cardamom, compared with 4.5% of those taking placebo. High-density lipoprotein (HDL) cholesterol levels, triglyceride levels, and insulin resistance also improved by a moderate amount. However, taking cardamom did not affect fasting blood glucose, body mass index (BMI), or low-density lipoprotein (LDL) cholesterol levels (101885).
• Obesity. It is unclear if oral cardamom is beneficial in patients with diabetes. Details: A small clinical study in overweight adults with diabetes shows that drinking black tea steeped with 3 grams of cardamom powder in three divided doses daily for 8 weeks does not affect weight, waist circumference, or blood pressure when compared with baseline or black tea only (95597).
• Polycystic ovary syndrome (PCOS). It is unclear if oral cardamom powder is beneficial in patients with PCOS. Details:A small clinical study in patients with PCOS shows that taking cardamom powder 1 gram three times daily for 16 weeks while following a low-calorie diet improves cyst size and number, reduces levels of testosterone and luteinizing hormone, increases levels of follicle stimulating hormone, and reduces levels of several inflammatory markers when compared with placebo plus a low-calorie diet (107920).
• Postoperative nausea and vomiting (PONV). Aromatherapy with cardamom essential oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that applying a mixture of essential oils from ginger, cardamom, and tarragon topically to the neck at the first sign of PONV can inhibit nausea and/or vomiting for 30 minutes in 50% to 88% of postoperative patients. The treatment effect appears to vary depending on the number of emetic drugs given during anesthesia or postoperatively, and whether the drugs were given during or after the operation (77054). Another small study shows that aromatherapy with a mixture of ginger, spearmint, peppermint, and cardamom, as 3 inhalations from a gauze pad, reduces nausea scores by 43% when compared with placebo. When compared with ginger aromatherapy alone, nausea scores were reduced by 15%. Using the combination aromatherapy also reduced the need for anti-nausea medications by 40% when compared with placebo and by 15% when compared with ginger aromatherapy (95307). It is unclear if these benefits are due to cardamom, other ingredients, or the combination.
• Pregnancy-induced nausea and vomiting. Although there has been interest in using oral cardamom for pregnancy-induced nausea and vomiting, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Respiratory tract infections. Although there has been interest in using oral cardamom for various respiratory tract infections, including bronchitis, influenza, and the common cold, there is insufficient reliable information about the clinical effects of cardamom for these conditions. More evidence is needed to rate cardamom for these uses.

(Read more about CARDAMOM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anorexia. Although there has been interest in using oral coriander to stimulate appetite in patients with anorexia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Anxiety. Although there has been interest in using oral coriander for anxiety, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Constipation. Oral coriander has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in nursing home residents with constipation shows that taking one cup of a specific tea (Smooth Move, Traditional Medicinals) containing senna leaf 1080 mg and 920 mg of a proprietary blend of coriander fruit, licorice root, fennel, orange peel, cassia cinnamon, and ginger daily for 28 days can increase the number of bowel movements when compared with placebo (46196). It is unclear if this effect is due to coriander, other ingredients, or the combination.
• Diabetes. Although there has been interest in using oral coriander for diabetes, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Diarrhea. Although there has been interest in using oral coriander for diarrhea, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Dyspepsia. Although there has been interest in using oral coriander for dyspepsia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Epilepsy. Although there has been interest in using oral coriander for epilepsy, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Flatulence. Although there has been interest in using oral coriander for flatulence, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Insomnia. Although there has been interest in using oral coriander for insomnia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Intestinal parasite infection. Although there has been interest in using oral coriander for intestinal parasite infection, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Irritable bowel syndrome (IBS). Oral coriander has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that taking 30 drops of a combination product containing total extracts of coriander, lemon balm, and spearmint (Carmint, Pour Sina) three times daily after meals for 8 weeks, in addition to standard treatment with loperamide or psyllium, reduces abdominal pain and discomfort when compared with standard treatment alone (19535). It is unclear if these effects are due to coriander, other ingredients, or the combination.
• Lactation. Although there has been interest in using oral coriander to stimulate lactation, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Osteoarthritis. Although there has been interest in using oral coriander for osteoarthritis, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral coriander for RA, there is insufficient reliable information about the clinical effects of coriander for this purpose.
• Skin irritation. It is unclear if oral coriander seed oil is beneficial in patients with skin irritation. Details: A small clinical study in Caucasian females aged 18-65 years with sensitive and reactive skin shows that taking a specific coriander seed oil product (Sepibliss, Seppic Inc.) 200 mg daily for 8 weeks reduces redness and itching after exposure to skin stress tests and improves patient-rated perceptions of skin sensitivity and reactivity when compared with placebo (111131).
• Tinea pedis. It is unclear if topical coriander oil is beneficial in patients with tinea pedis. Details: A small clinical study in adults with tinea pedis shows that applying coriander oil 6% ointment (Oleum Coriandri e Semine; Caesar & Loretz GmbH) twice daily to affected areas for 28 days is approximately 20% more effective for eliminating clinical signs of infection, as rated by patients and clinicians, when compared with applying the ointment alone (97874). More information is needed to rate coriander for these uses.

(Read more about CORIANDER)

LIKELY EFFECTIVE

• Irritable bowel syndrome (IBS). Oral enteric-coated peppermint oil is conditionally recommended by the American College of Gastroenterology (ACG) for the relief of global IBS symptoms, such as abdominal pain. Details: The ACG conditionally recommends the use of peppermint for the relief of global IBS symptoms. This recommendation is based on an available meta-analysis of generally low-quality clinical research (105124). Several clinical trials and meta-analyses show that taking enteric-coated peppermint oil 1-2 capsules orally two to four times daily reduces abdominal pain, distention, flatulence, and bowel movements in patients with IBS. Each capsule provides approximately 0.2 mL of peppermint oil or 180-225 mg peppermint oil. Most trials have used specific products (Colpermin, Tillotts Pharma; Mintoil, Cadigroup; Ibgard, IM HealthScience, Tempocol) (3802,3803,4469,11778,11779,17681,17682,68467,68515,68522)(68603,68604,68605,96360,99493,109980). The most recent meta-analysis to date shows that four patients would need to take peppermint oil to prevent one patient from having persistent IBS symptoms, and seven patients would need to take peppermint oil to prevent one patient from having abdominal pain. However, the individual studies included in the analysis lasted no more than 12 weeks (109980); any long-term effects are unclear. Although most studies have shown benefit for reducing symptoms, some older studies have found no significant effect (11777,11789) or only short-term benefits (68620). Also, a well-designed study shows that taking peppermint oil capsules designed for either small intestinal release (enteric-coated) or ileocolonic release does not increase the number of people with at least a 30% decrease in abdominal pain over a period of 4 weeks, although symptoms are modestly reduced when compared with placebo (102602). Another clinical trial in patients with moderate to severe IBS shows that taking a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) 180 mg three times daily for 6 weeks does not further improve symptom severity when compared with placebo. However, both groups experienced a large improvement on the IBS-Severity Scoring System (IBS-SSS) and the IBS Global Improvement Scale (107955). The validity of these findings is limited due to lost data and inconsistent follow-up; additionally, adverse effects occurred more frequently in the peppermint oil group. The reasons for these negative findings are unclear but may include short treatment durations and the use of different formulations; additionally, IBS is comprised of various subtypes and symptoms that can range in severity and presentation, which may alter treatment response. Some clinical research has also evaluated a specific combination product (Atrantil, KBS Research) containing peppermint leaf, red quebracho extract, and conker tree extract. Taking this product as needed for 2 weeks seems to reduce constipation and bloating when compared to baseline in patients with constipation-predominant IBS (95429,95430). It is unclear if the effects of this product are due to peppermint, the other ingredients, or the combination.

POSSIBLY EFFECTIVE

• Barium enema-related colonic spasm. Rectal peppermint, as part of barium enema preparations, seems to reduce colonic spasms during examination. Oral peppermint also seems to be beneficial. Details: Rectal use of peppermint oil, added as an ingredient in barium enema preparations, seems to relax the colon during barium enema examination and reduce the percentage of patients who experience colonic spasms by about 25% to 30% (6739,6749,12009). Adding peppermint oil to the barium enema seems to be at least as effective as using systemic scopolamine (Buscopan). Adding peppermint oil to the barium solution also does not seem to impair image quality (12009). Some clinical research also shows that taking peppermint oil orally before the start of a double-contrast barium enema examination decreases spasms and might also increase diagnostic quality (14467).
• Chemotherapy-induced nausea and vomiting (CINV). Oral and inhaled peppermint seem to reduce nausea and vomiting in patients with CINV. Details: Clinical research shows that adding peppermint oil, 40 drops in 20 mL water, every 8 hours following chemotherapy treatment to treatment with standard antiemetics reduces the severity of nausea, vomiting, and anorexia by moderate to large amounts over 48 hours when compared with a plain water placebo (105123). The use of peppermint oil aromatherapy has also been investigated. Clinical research shows that adding 2 drops of peppermint oil to a cool, damp washcloth for use on the neck as aromatherapy for about 30 minutes helps relieve chemotherapy-induced nausea by a small amount when compared with a washcloth without peppermint oil (102603). Additional clinical research in patients receiving standard antiemetics after chemotherapy shows that applying one drop of peppermint oil below the nose three times daily for 5 days reduces the severity of nausea and the frequency of nausea, vomiting, and retching by a moderate to large amount when compared with the antiemetics alone. These parameters were not improved following treatment with cisplatin (105122). A meta-analysis of 3 randomized controlled trials in adults receiving chemotherapy also shows that peppermint oil aromatherapy moderately improves nausea and vomiting when compared with control. However, the results of this analysis are limited by heterogenous application methods, doses, and durations of peppermint therapy (114761). In children with acute leukemia, a small clinical study shows that aromatherapy with 2 drops of peppermint oil and 3 drops of lemon oil in 80 mL of water diffused 30 minutes prior to and 2 and 4 hours after chemotherapy once weekly for 4 weeks decreases the severity of nausea, vomiting, and retching, and improves quality of life scores when compared with diffused water or no intervention (112015). The validity of these findings is limited by the use of patient-reported outcomes. Another small clinical trial in children receiving chemotherapy for acute leukemia shows that aromatherapy with peppermint oil 2%, 0.2 mL inhaled over 3 minutes immediately prior to 3 consecutive chemotherapy sessions, added to standard care (e.g. antiemetic medications), reduces overall incidence of nausea by 40%, and improves nausea and vomiting severity scores, when compared with no additional interventions. These results were similar to those receiving Swedish massage prior to chemotherapy sessions (114759).
• Dyspepsia. Oral peppermint, in combination with caraway and possibly other ingredients, seems to reduce symptoms of dyspepsia. It is unclear if oral peppermint alone is beneficial. Details: Some clinical research shows that taking specific products containing peppermint and caraway oil (Enteroplant, Dr Willmar Schwabe Pharmaceuticals; Menthacarin, Dr Willmar Schwabe GmbH & Co.) improves quality of life and reduces symptoms of dyspepsia, including feelings of fullness, pain, and mild gastrointestinal spasms (6740,6741,10075,96344,102600). A meta-analysis of three of these clinical studies shows that taking this combination product 2-3 times daily for 4 weeks modestly reduces abdominal pain when compared with placebo (110091). Taking this combination twice daily for 4 weeks also improves postprandial distress syndrome and epigastric pain syndrome, two subtypes of dyspepsia, when compared with placebo (96344). The combination of enteric-coated peppermint oil 90 mg and caraway oil 50 mg appears to be comparable to cisapride for relieving dyspepsia when taken 2-3 times daily for up to 4 weeks (6740,6741,10075). However, most trials investigating this combination are small and/or of overall low quality (102600). A specific combination product containing peppermint leaf (Iberogast, Steigerwald Arzneimittelwerk GmbH) also seems to improve symptoms of dyspepsia. The combination includes peppermint leaf plus clown's mustard plant, German chamomile, caraway, licorice, milk thistle, angelica, celandine, and lemon balm (7049). A meta-analysis of studies using this combination product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces the severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). A similar combination product containing extracts from peppermint leaf, clown's mustard plant, German chamomile flower, caraway, licorice root, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH) 1 mL taken three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more dyspepsia patients when compared with placebo (12724).
• Endoscopy-associated adverse effects. Intraluminal peppermint seems to reduce spasticity during an endoscopy. It is unclear if oral peppermint is beneficial for reducing adverse effects related to endoscopy. Details: A meta-analysis of four clinical trials show that peppermint oil, administered orally or intraluminally, reduces the incidence of spasticity by about 41% when compared with placebo in patients undergoing endoscopy, with severe spasticity occurring at about 30% the rate of those taking placebo. However, there was no effect on subjective pain (102604). Individual clinical studies show that intraluminal peppermint oil can reduce both pain and spams in patients undergoing endoscopy (18220,68371,68395,68445,68532). However, there are limitations with this form of administration, including cost and practicality, which has led to interest in the use of oral formulations (104221). Studies evaluating oral extended-release peppermint have been conflicting. While one study shows that a specific extended-release peppermint oil product (Colpermin) 187 mg or 0.2 mL taken orally 4 hours prior to a colonoscopy reduces procedure time, pain, and spasticity (68532), a study using another specific extended-release peppermint oil (IBGard) did not show an effect on colonic spasms, procedure time, or adenoma detection rate when compared with placebo (104221). These differing outcomes may be due to timing of administration. The study that showed benefit administered the treatment 4 hours prior to endoscopy, whereas the study showing no benefit administered the treatment only 1 hour prior. This suggests that extended-release peppermint may need to be administered at least 4 hours prior to the procedure to allow for adequate colonic release (68532,102604,104221).
• Nipple fissures. Topical peppermint seems to reduce cracked skin and pain in the nipples due to breastfeeding. Details: Clinical research shows that topical application of peppermint oil in gel or water reduces cracked skin and pain in the nipple area from breastfeeding when compared with using placebo, lanolin, or the expressed breast milk technique (68454,68462). Other research shows that applying peppermint oil in cream immediately after breastfeeding for 2 weeks decreases pain and trauma in the nipple area similarly to the topical application of dexpanthenol or lanolin (96365).
• Pressure ulcers. Topical peppermint seems to reduce the risk of pressure ulcers. Details: Clinical research in bedridden patients shows that prophylactic application of a topical gel containing peppermint oil 0.2% three times daily for up to 14 days results in pressure injuries in about 23% of patients compared with 77% of those given a placebo gel (102605).
• Tension headache. Topical peppermint seems to relieve tension headaches. Details: Clinical research shows that topical application of peppermint oil 10% relieves tension headaches when compared with placebo (3801,6190).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. Although there has been interest in using oral peppermint for abdominal pain, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety. Details: A clinical trial in patients presenting to the emergency department for an acute coronary syndrome event shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 1 hour improves anxiety and respiratory rate when compared with baseline or placebo (107958). Due to the single-dose nature of this study, the effects of repeated inhalation of peppermint oil are unclear.
• Athletic performance. It is unclear if oral peppermint oil is beneficial for athletic performance. Details: Preliminary clinical research in trained adult runners shows that taking peppermint essential oil, 0.05 mL diluted in 500 mL of water, orally once 30 minutes before exercise improves running time to exhaustion by 11% when compared with placebo (112742). Another very small clinical study in elite soccer athletes shows that use of a specific peppermint essential oil (doTERRA), 1 drop rubbed into hands and inhaled with 5 deep breaths, does not improve jump performance metrics when compared with placebo (114760).
• Breast cancer-related hot flashes. It is unclear if topical peppermint is beneficial for reducing hot flashes in patients with breast cancer. Details: Preliminary clinical research shows that using a spray containing a combination of peppermint and neroli hydrolat does not alleviate hot flashes in most patients receiving chemotherapy for breast cancer when compared with using a plain water spray (68481).
• Cognitive function. It is unclear if inhaled peppermint oil is beneficial for improving cognitive function. Details: Preliminary clinical research shows that inhalation of peppermint oil slightly improves memory and the performance of cognitive tasks such as typing, alphabetization, and ordering, but not attention and speed of task completion, when compared with control (56954,68416,68466).
• Common cold. Although there has been interest in using oral, topical, or inhaled peppermint for the common cold, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Dental plaque. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth for one minute with 10 mL of a specific combination product (HiOra, Himalaya Herbal Healthcare) containing peppermint oil and numerous other ingredients twice daily for two days reduces plaque index or plaque area when compared with placebo; however, it was not as effective as chlorhexidine 0.2% solution (68530). It is unclear if these effects are due to peppermint oil, other ingredients, or the combination.
• Diffuse esophageal spasm. It is unclear if oral peppermint oil is beneficial for diffuse esophageal spasm. Details: A small exploratory study in adults with diffuse esophageal spasm shows that drinking a solution of peppermint oil, 5 drops in 10 mL of water, can resolve esophageal contractions when compared with baseline (13415). The validity of this finding is limited by the lack of a comparator group.
• Dysmenorrhea. It is unclear if oral peppermint oil is beneficial for reducing menstrual pain. Details: Preliminary clinical research shows that taking three capsules of peppermint oil (Colpermin; Tillotts Company or Razak company) daily for 3 days, starting on the first day of menstruation, is as effective as mefenamic acid 250 mg three times daily for reducing pain, and more effective for reducing nausea and vomiting, associated with dysmenorrhea. However, mefenamic acid was more effective for reducing bleeding and analgesic use (105125).
• Fatigue. It is unclear if inhaled peppermint oil improves fatigue in patients with cardiac disease. Details: A clinical trial in hospitalized patients with various forms of cardiac disease shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores when compared with placebo. These improvements were similar to those seen with lavender oil inhalation. Fatigue scores decreased by 24 and 21 points in the peppermint and lavender groups, respectively, compared with a 2-point reduction in the placebo group (107959). The validity of these findings is limited due to the short duration of treatment.
• Halitosis. Peppermint has only been evaluated in combination with other ingredients as a mouthwash; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth with a specific combination of tea tree oil, peppermint, and lemon essential oil once for three minutes improves breath smell when compared with placebo or benzydamine hydrochloride (19177). Other preliminary clinical research in elderly adults with dementia who require oral care assistance shows that cleaning the mouth with a mixture of peppermint oil, tea tree oil, and lemon essential oils diluted to 0.5%, applied via gauze, twice daily for 7 days improves halitosis scores and oral condition scores when compared with placebo (112957).
• Insomnia. It is unclear if inhaled peppermint oil is beneficial for insomnia. Details: Preliminary clinical research in cancer patients shows that receiving aromatherapy as three drops of peppermint oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline. However, it seems to be no better than using lavender oil aromatherapy or using a control of lavender oil 1% (103063).
• Menopausal symptoms. It is unclear if inhaled peppermint oil is beneficial for menopausal symptoms. Details: Preliminary clinical research in adults with menopausal symptoms shows that receiving aromatherapy as 2 drops of peppermint oil with upper extremity massage and for 30 minutes twice weekly for 4 weeks moderately improves menopause symptom scores, including both somatic symptoms and urogenital symptoms, when compared with placebo (112745).
• Migraine headache. It is unclear if intranasal or inhaled peppermint oil is beneficial for migraine headache. Details: Preliminary clinical research shows that using 1-2 doses of intranasal peppermint oil 1.5% (Poursina Company) at the start of migraine pain is as effective as intranasal lidocaine 4%, and more effective than placebo, for reducing migraine headache intensity. Approximately 42% of those using peppermint oil indicated a high level of headache reduction, compared with 42% of those using lidocaine and 5% of those using placebo. Also, pain relief was felt within 5 minutes in more patients using peppermint than placebo (105126). However, it is unclear if participants were truly blinded to the use of peppermint oil. Other preliminary clinical research in pediatric patients with migraine or other chronic headaches shows that receiving aromatherapy with peppermint oil over 10 minutes during a footbath does not improve pain or anxiety scores when compared with control (112746).
• Mosquito repellent. Although there has been interest in using topical peppermint oil as a mosquito repellent, there is insufficient reliable information about the clinical effects of peppermint for this purpose.
• Myalgia. Although there has been interest in using topical peppermint oil for myalgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Oral mucositis. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults undergoing stem cell transplantation shows that using an oral rinse containing peppermint oil and German chamomile three times daily, in addition to standard treatment with sodium chloride and chlorhexidine, reduces the duration and severity of mucositis and the use of narcotic analgesics when compared with placebo and standard treatment. However, this oral rinse does not reduce or delay the occurrence of mucositis or affect the duration of hospitalization (96363). Another small clinical study in adults with head and neck cancers undergoing radiation shows that rinsing with 5 mL of a polyherbal mouthwash containing peppermint oil, German chamomile, aloe vera, and honey for 1 minute 3 times daily for 6 weeks reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine 0.2% and placebo (111291). Clinical research in adults receiving treatment with 5-fluorouracil shows that using an oral rinse containing peppermint, sage tea, and thyme in addition to basic oral care, starting on the first day of chemotherapy and continuing for 14 days, delays the onset of mucositis, but not the rate or severity of mucositis, when compared with basic oral care alone (96364). It is unclear if these effects are due to peppermint oil, other ingredients, or the combinations.
• Osteoarthritis. Although there has been interest in using topical peppermint oil for osteoarthritis, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Pain (acute). It is unclear if inhaled or topical peppermint oil is beneficial for acute pain. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy reduces pain associated with intravenous catheterization by a small amount when compared with a distilled water control (102601). Another small open-label study in adults undergoing venipuncture for dialysis shows that topical application of peppermint gel 5 mL reduces pain scores by approximately 50% when compared with no intervention. These results were similar to using a cold compress (114758). Additionally, a small open-label study in children undergoing a dental procedure, shows that topical application of peppermint oil 0.2% , moderately improves pain scores after a buccal injection when compared with lidocaine spray 15% (114757).
• Postherpetic neuralgia. Although there has been interest in using topical peppermint oil for postherpetic neuralgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Postoperative ileus. It is unclear if oral peppermint oil is beneficial for the prevention of postoperative ileus. Details: Clinical research shows that taking a specific peppermint oil product (Colpermin, Tillotts Pharma) as two capsules three times daily for 5 days after routine gynecological surgery does not prevent postoperative abdominal distension and dyspepsia when compared with placebo (68602). Conversely, a small clinical study in patients undergoing elective cesarean section shows that taking 20 drops of peppermint oil 4 hours after surgery and then hourly for a total of three doses reduces the time to first bowel sounds by around 3.3 hours, first flatulence by 4.4 hours, and first stool by 5 hours when compared with placebo (110092).
• Postoperative nausea and vomiting (PONV). Some preliminary clinical studies suggest that inhaled peppermint may be beneficial for PONV. However, it is unclear if the benefit is due to aromatherapy or improved breathing patterns. Details: Some preliminary clinical research shows that using peppermint aromatherapy helps relieve postoperative nausea (3804,13415,68524,104219,104220). Inhaling peppermint oil 10% and 30% as aromatherapy reduces the severity of nausea when compared with placebo, with no significant difference between concentrations (104220). Small clinical trials show improvement in PONV within the first 4 hours after surgery. However, this effect diminishes beyond 4 hours (104219). Other preliminary clinical research shows that peppermint oil aromatherapy is no more effective for reducing postoperative nausea than inhaling isopropyl alcohol or saline (13416,68529). It is possible that any relief of postoperative nausea observed with peppermint aromatherapy results from improved breathing patterns after surgery rather than peppermint oil itself (13416,90512). One small study shows that inhaling peppermint oil while practicing controlled breathing does not appear to relieve PONV better than practicing controlled breathing alone (90512). Some preliminary clinical research shows that inhaling vapors from a mixture of peppermint, ginger, spearmint, and cardamom essential oils reduces symptoms of postoperative nausea in approximately 15% more patients when compared with inhaling ginger essential oils alone, and in approximately 43% more patients when compared with inhaling saline (89888). However, it is not clear if the effect is due to peppermint, the other oils, or the combination. In contrast, a small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not reduce PONV rescue treatment when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses does not reduce overall PONV when compared with placebo (114622).
• Postoperative pain. It is unclear if inhaled peppermint oil is beneficial for postoperative pain. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses moderately improves pain scores when compared with placebo (112747). Other preliminary clinical research in adults undergoing lumbar discectomy surgery shows that receiving aromatherapy with peppermint oil 5 drops once postoperatively modestly improves pain scores and anxiety scores when compared with no intervention (112744). A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not improve pain scores or reduce opioid rescue treatment in the immediate post-operative period when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses modestly reduceses opioid consumption on postoperative day 2, but not day 1, 7, or 30, when compared with placebo (114622). However, these changes are unlikely to be clinically relevant. In addition, it is unclear if any potential effects are due to peppermint, lavender, or the combination.
• Postoperative recovery. Inhaled peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not shorten postoperative length of stay when compared with placebo (114623).
• Postoperative sleep disturbance. It is unclear if inhaled peppermint oil is beneficial for postoperative sleep disturbance. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses modestly improves sleep scores when compared with placebo (112747).
• Pre-procedural anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety prior to a medical procedure. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy does not reduce anxiety associated with intravenous catheterization when compared with a distilled water control (102601).
• Pregnancy-induced nausea and vomiting. Inhaled peppermint oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that aromatherapy with a mixture of 5% lemon and 5% peppermint essential oils modestly reduces the intensity of nausea and vomiting on days 2-4, but not day 1, when compared with placebo aromatherapy. When nauseated, patients placed three drops of the essential oil mixture (Barij Essence Co.) onto a cotton ball held 3 cm from the nose. This action could be repeated after 5 minutes if needed (105121).
• Pruritus. Some preliminary clinical studies suggest that topical peppermint oil improves itching of various etiologies. Details: Preliminary clinical research in adults with renal, hepatic, or diabetic pruritus shows that topical application of peppermint oil 5% in petrolatum twice daily for 2 weeks improves symptoms of pruritus when compared with petrolatum alone (96361). Preliminary clinical research in patients with severe or intractable pruritus secondary to burn scars shows that applying a specific product (Chongqing No.1, CQ-01, MJ Medical Gel Systems Ltd.) containing peppermint oil 3.6%, menthol 1.4%, and methyl salicylate 2.5%, covered with gauze for 24 hours, reduces the severity of pruritus for up to 7 days after application when compared with hydrogel covered with gauze or with gauze alone (96362). Preliminary clinical research in females experiencing itchy skin due to intrahepatic cholestasis of pregnancy also shows that applying peppermint oil 0.5% in sesame oil twice daily for 2 weeks reduces pruritus severity approximately 1.8-fold when compared with sesame oil alone (89478).
• Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral peppermint for SIBO, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Stress. It is unclear if inhaled peppermint oil is beneficial for stress. Details: Clinical research shows that peppermint aromatherapy decreases physical and perceived levels of stress when compared with baseline (68422,68517). A small clinical study in adults undergoing a virtual reality (VR) driving scenario to test road rage shows that exposure to peppermint oil (Pure Essential Oil of Peppermint, Tisserand Aromatherapy) 5 drops via fan diffuser improves aggressive driving behavior scores but does not seem to improve self-reported stress, aggression, alertness, happiness, or calmness when compared with controls that did not receive aromatherapy during the VR session (112017).
• Toothache. Although there has been interest in using topical peppermint oil for toothache, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Urticaria. Although there has been interest in using topical peppermint oil for urticaria, there is insufficient reliable information about the clinical effects of peppermint for this condition. More evidence is needed to rate peppermint for these uses.

(Read more about PEPPERMINT)

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 aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (101,11982,12096,12098,12159,12160,12163,12164,17418)(90123,90124,90127,90128,90129,90131,97320,98816,103305). When included in topical cosmetics, the Cosmetic Ingredient Review Expert Panel concluded that aloe-derived anthraquinone levels should not exceed 50 ppm (90122).

POSSIBLY SAFE ...when aloe gel is used orally and appropriately, short-term. Aloe gel has been safely used in a dose of 15 mL daily for up to 42 days or 100 mL of a 50% solution twice daily for up to 4 weeks (11984,12164). Also, a specific aloe gel complex (Aloe QDM complex, Univera Inc.) has been safely used at a dose of approximately 600 mg daily for up to 8 weeks (90121). ...when aloe extract is used orally and appropriately, short-term. Aloe extract has been used with apparent safety in a dose of 500 mg daily for one month (101579). Also, an aloe extract enriched in aloe sterols has been used with apparent safety in a dose of 500 mg daily for 12 weeks (101577).

POSSIBLY UNSAFE ...when aloe latex is used orally. There is some evidence that anthraquinones in aloe latex are carcinogenic or promote tumor growth, although data are conflicting (6138,16387,16388,91596,91597). In 2002, the US FDA banned the use of aloe latex in laxative products due to the lack of safety data (8229). ...when aloe whole-leaf extract is used orally. Aloe whole-leaf extract that has not been filtered over charcoal still contains anthraquinones. This type of aloe whole-leaf extract is referred to as being "nondecolorized". The International Agency for Research on Cancer has classified this type of aloe whole-leaf extract as a possible human carcinogen (91598,91908). Although filtering aloe whole-leaf extract over charcoal removes the anthraquinones, some animal research suggests that this filtered extract, which is referred to as being "decolorized", may still cause gene mutations (91598). This suggests that constituents besides anthraquinones may be responsible for the carcinogenicity of aloe whole-leaf extract. It should be noted that commercial products that contain aloe whole-leaf extract may be labeled as containing "whole leaf Aloe vera juice" or "aloe juice" (91908).

LIKELY UNSAFE ...when aloe latex is used orally in high doses. Ingesting aloe latex 1 gram daily for several days can cause nephritis, acute kidney failure, and death (8,8961).

CHILDREN: POSSIBLY SAFE
when aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (90124,90131).

CHILDREN: POSSIBLY UNSAFE
when aloe latex and aloe whole leaf extracts are used orally in children. Children younger than 12 years may experience abdominal pain, cramps, and diarrhea (4).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Anthraquinones present in aloe latex and aloe whole leaf extracts have irritant, cathartic, and possible mutagenic effects (4,16387,16388,90122). There are also anecdotal reports and evidence from animal research that anthraquinones or aloe whole leaf extracts might induce abortion and stimulate menstruation; avoid using (4,8,19,90122).

LACTATION: POSSIBLY UNSAFE
when aloe preparations are used orally. Cathartic and mutagenic anthraquinones present in aloe latex and aloe whole leaf extracts might pass into milk; avoid using (4,19).

(Read more about ALOE)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Artichoke has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Artichoke extract has been used with apparent safety at doses up to 3200 mg daily for up to 12 weeks (6282,15204,52235,91475,91478,100934). Artichoke leaf powder has been used with apparent safety at a dose of 1000 mg daily for up to 8 weeks (104133). Cynarin, a constituent in artichoke extract, has been used with apparent safety at daily doses of 750 mg daily for up to 3 months or 60 mg daily for up to 7 months (1423,1424,52222,52223,52236).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of artichoke when used in medicinal amounts during pregnancy or lactation; avoid amounts greater than those found in foods.

(Read more about ARTICHOKE)

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

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Cardamom powder 3 grams daily in 2-3 divided doses has been used with apparent safety for up to 16 weeks (95308,95597,101885,107920). ...when the essential oil is used by inhalation for aromatherapy (77054,95307).

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods.

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Cardamom is thought to have abortifacient and emmenagogue effects (19,39884). Avoid using amounts greater than those used in food.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of cardamom when used in medicinal amounts. Avoid using amounts greater than those used in food.

(Read more about CARDAMOM)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Coriander and coriander oil have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes (12). ...when used topically and appropriately. Coriander oil 6% ointment has been used with apparent safety twice daily for up to 28 days (97874).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid amounts in excess of those found in foods.

(Read more about CORIANDER)

LIKELY SAFE ...when peppermint oil is used orally, topically, or rectally in medicinal doses. Peppermint oil has been safely used in multiple clinical trials (3801,3804,6190,6740,6741,10075,12009,13413,14467,17681)(17682,68522,96344,96360,96361,96362,96363,96364,96365,99493).

POSSIBLY SAFE ...when peppermint leaf is used orally and appropriately, short-term. There is some clinical research showing that peppermint leaf can be used safely for up to 8 weeks (12724,13413). The long-term safety of peppermint leaf in medicinal doses is unknown. ...when peppermint oil is used by inhalation as aromatherapy (7107). There is insufficient reliable information available about the safety of using intranasal peppermint oil.

CHILDREN: POSSIBLY SAFE
when used orally for medicinal purposes. Enteric-coated peppermint oil capsules have been used with apparent safety under medical supervision in children 8 years of age and older (4469).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (96361). There is insufficient information available about the safety of using peppermint in medicinal amounts during pregnancy or lactation; avoid using.

(Read more about PEPPERMINT)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin (105501).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Preliminary clinical research suggests aloe gel might lower blood glucose levels (11983,12164,19756) and have additive effects when used with antidiabetes drugs. Monitor blood glucose levels closely.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that aloe extract induces CYP1A2 enzymes (111404).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.  Details Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity (19).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.  Details Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia (19).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.  Details Due to cathartic laxative effects of aloe latex, concomitant use with other stimulant laxatives might compound fluid and electrolyte loss (19,19742,19743,19744).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.  Details Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.

(Read more about ALOE)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, artichoke leaf extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details A meta-analysis of small clinical studies shows that taking artichoke leaf extract for 8-12 weeks can modestly reduce fasting plasma glucose when compared with placebo (105768).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, artichoke leaf extract may increase the risk of hypotension when taken with antihypertensive drugs.  Details A meta-analysis of small clinical studies in patients with hypertension shows that taking artichoke can reduce systolic blood pressure by around 3 mmHg and diastolic blood pressure by around 2 mmHg when compared with placebo (105767).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2B6.  Details In vitro research shows that artichoke leaf extract inhibits CYP2B6 activity (97717). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2C19.  Details In vitro research shows that artichoke leaf extract inhibits CYP2C19 activity (97717). However, this interaction has not been reported in humans.

(Read more about ARTICHOKE)

(Read more about CARDAMOM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, coriander might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Evidence from animal research suggests that coriander fruit and coriander extract can reduce blood glucose levels (14907,46153,46216). Monitor blood glucose levels closely. Dose adjustments might be necessary.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, coriander might increase the risk of hypotension when taken with antihypertensive drugs.  Details Evidence from animal research suggests that coriander fruit can lower blood pressure (46221).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, coriander might cause additive sedative effects when taken with CNS depressants.  Details Evidence from animal research suggests that coriander fruit extract has sedative effects (46184).

PHOTOSENSITIZING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, coriander might increase the risk of photosensitivity when taken with photosensitizing drugs.  Details Evidence from in vitro research suggests that coriandrin, a constituent of coriander, has photosensitizing effects (46228).

(Read more about CORIANDER)

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.  Details In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction (11784). An interaction between peppermint oil and cyclosporine has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP1A2 substrates.  Details In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2 (12479,12734). However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference (96359).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C19 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C9 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP3A4 substrates.  Details Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate (11783). However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations (12479).

(Read more about PEPPERMINT)

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.

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General ...Orally and topically, aloe products are generally well tolerated when used in typical doses. However, oral aloe latex is associated with a greater risk of adverse effects, especially when used in high doses or long-term.
Most Common Adverse Effects:
Orally: Aloe latex may cause abdominal pain, cramps, and diarrhea.
Topically: Burning, erythema, and itching. Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Aloe latex is associated with serious adverse effects when taken in high doses or long-term. Cases of acute hepatitis due to a hypersensitivity reaction to aloe leaf extract has been reported.

Dermatologic ...Topically, aloe gel has occasionally been associated with burning (12164,19741,30697,30706), itching (12164,19741,30697), eczema (90122), erythema (19748,30706,90123), contact dermatitis (12163,12164,30695,30736,30737,30738,30740), popular eruption (30732), and urticaria (30712). Also, a case of generalized nummular and popular dermatitis attributed to hypersensitivity has been reported for a 47-year-old male who used aloe leaf gel, both topically and orally, for 4 years (30740).

Endocrine ...A case of severe hypokalemia has been reported for a male breast cancer patient who was undergoing chemotherapy and using aloe vera 1 liter daily orally for 2 weeks. The hypokalemia was attributed to the cathartic effects of aloe and resolved once aloe use was discontinued (30704).

Gastrointestinal ...Orally, aloe latex can cause abdominal pain and cramps. Long-term use or abuse of aloe latex can cause diarrhea, sometimes with hypokalemia, albuminuria, hematuria, muscle weakness, weight loss, arrhythmia, and pseudomelanosis coli (pigment spots in intestinal mucosa). Pseudomelanosis coli is believed to be harmless, and usually reverses with discontinuation of aloe. It is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138). Orally, aloe gel may cause nausea, stomach cramps, and other gastrointestinal complaints in some patients (104174,111921,111663).
Topically, applying aloe gel in the mouth may cause nausea within 5 minutes of application in some patients (90124).

Hematologic ...A case of Henoch-Schonlein purpura, characterized by abdominal pain, purpura, and severe arthralgia, has been reported in a 52-year-old male who drank aloe juice prepared from four to five leaflets for 10 days prior to symptom development (91598).

Hepatic ...Cases of acute hepatitis have been reported after ingestion of aloe leaf extracts for between 3 weeks and 5 years. This is thought to be a hypersensitivity reaction (15567,15569,16386,17419,90126,91598). A case of acute hepatitis has also been reported for a 45-year-old female who drank two ounces of Euforia juice (Nuverus International), a product containing green tea, noni, goji, and aloe, daily for one month (90125). However, one small clinical trial in healthy individuals shows that taking aloe gel 2 ounces twice daily for 60 days does not impair liver function (104174).

Renal ...Orally, aloe latex can cause hemorrhagic gastritis, nephritis, and acute kidney failure following prolonged use of high doses (1 gram daily or more) (8961).

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General ...Orally, artichoke extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, flatulence, hunger, and nausea.
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to artichoke inulin has been reported in individuals sensitive to inulin.
Topically: Chest tightness, cough, and dyspnea after occupational exposure in sensitive individuals.

Dermatologic ...Artichoke can cause an allergic reaction in some patients. Patients sensitive to the Asteraceae/Compositae family may be at the greatest risk. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. Topically, allergic contact dermatitis can occur with the use of artichoke. This has been attributed to the constituent cynaropicrin (11,52206,52226,52230). Redness in the face (11774) and sweating (91475) have been reported rarely following oral use of artichoke extract.
Occupational or airborne exposure to artichoke may also cause allergic reactions. In one case, a 52-year-old male presented with severe spongiotic dermatitis in exposed areas that was recurrent over the past 8 years. A patch test confirmed allergies to artichokes and sesquiterpene lactones, a group of allergens from the Compositae family, and the patient confirmed occupational and airborne exposure to artichokes during the time of his symptoms. The patient improved considerably after treatment with dupilumab (111565).

Gastrointestinal ...Orally, artichoke extract might increase abdominal discomfort, flatulence, diarrhea, hunger, and nausea in some patients (2562,52238,91475). Abdominal pain and a bitter taste in the mouth were reported by a single person following oral use of a dietary supplement containing artichoke extract, as well as red yeast rice, pine bark extract, and garlic extract (89452). It is not clear if this adverse effect was due to artichoke, other ingredients, or the combination.
In one case report, the autopsy of an 84-year-old female revealed a colonic bezoar comprised of artichoke fiber and fragments. This bezoar caused complete intestinal obstruction, leading to fatal acute peritonitis. Although rare, patients who lack adequate teeth and/or who have a history of gastric surgery are at increased risk for fibrous bezoar formation (97716).

Pulmonary/Respiratory ...Following occupational exposure, allergic symptoms including dyspnea, cough, chest tightness, and asthma symptoms or exacerbation have been reported. The effects were attributed to sensitization to artichoke. Subsequent nasal challenge with artichoke extract caused reduced nasal patency in these patients (52210,52230).
Orally, severe anaphylactic shock in response to artichoke inulin as an ingredient in commercially available products has been reported (52217). Individuals with a noted sensitivity to artichokes should consume inulin with caution. While rare, individuals with a known inulin allergy should avoid artichoke and artichoke extract.

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General ...Orally, cardamom seems to be well tolerated.

Dermatologic ...Orally, mild skin inflammation due to cardamom has been reported in one participant of a clinical trial (101887). Topically, a case report describes chronic hand dermatitis in a confectioner frequently exposed to cardamom. Skin patch tests were positive for cardamom, and for terpenoids present in the seeds (39875).

Genitourinary ...Orally, dysuria due to cardamom has been reported in one participant of a clinical trial (101887). Also, a case report describes a 5-year-old female who developed hematuria after eating ice cream flavored with cardamom. It resolved spontaneously and there was no re-challenge (95306). It is not clear if cardamom is the direct cause of hematuria in this case.

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General ...Orally and topically, coriander seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Topically, coriander can cause pruritus and a burning sensation (97874).

Immunologic ...A case of anaphylactic reaction characterized by generalized urticaria, conjunctivitis, oropharyngeal angioedema, and bronchospasms has been reported in a 25-year-old spice worker who consumed food containing coriander fruit. The digestive spice allergy was attributed to sensitization to coriander caused by occupational exposure to coriander fruit, powder, and dust (46192). Also, cases of rhinitis and symptoms of asthma have been reported for patients exposed to dust from coriander spice, particularly people working with spices in the food industry (46226,46245). Like other members of the Apiaceae/Umbelliferae (carrot family), coriander can cause contact dermatitis (19). A case of occupational protein contact dermatitis has been reported for an individual exposed to coriander fruit (46168).

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General ...Orally, topically, or rectally, peppermint oil is generally well tolerated. Inhaled, peppermint oil seems to be well tolerated. Intranasally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Orally, peppermint leaf seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, anal burning, belching, diarrhea, dry mouth, heartburn, nausea, and vomiting.
Topically: Burning, dermatitis, irritation, and redness.

Dermatologic ...Topically, peppermint oil can cause skin irritation, burning, erythema, and contact dermatitis (3802,11781,31528,43338,68473,68457,68509,96361,96362). Also, a case of severe mucosal injury has been reported for a patient who misused an undiluted over the counter mouthwash that contained peppermint and arnica oil in 70% alcohol (19106).
In large amounts, peppermint oil may cause chemical burns when used topically or orally. A case of multiple burns in the oral cavity and pharynx, along with edema of the lips, tongue, uvula, and soft palate, has been reported for a 49-year-old female who ingested 40 drops of pure peppermint oil. Following treatment with intravenous steroids and antibiotics, the patient's symptoms resolved over the course of 2 weeks (68432). Also, a case of chemical burns on the skin and skin necrosis has been reported for a 35-year-old male who spilled undiluted peppermint oil on a previous skin graft (68572). Oral peppermint oil has also been associated with burning mouth syndrome and chronic mouth ulceration in people with contact sensitivity to peppermint (6743). Also, excessive consumption of mint candies containing peppermint oil has been linked to cases of stomatitis (13114).

Gastrointestinal ...Orally, peppermint oil can cause heartburn, nausea and vomiting, anal or perianal burning, abdominal pain, belching, dry mouth, diarrhea, and increased appetite (3803,6740,6741,6742,10075,11779,11789,17682,68497,68514)(68532,68544,96344,96360,102602,104219,107955). Enteric-coated capsules might help to reduce the incidence of heartburn (3802,4469,6740,11777). However, in one clinical study, a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) taken as 180 mg three times daily was associated with a higher rate of adverse effects when compared with placebo (48% versus 31%, respectively). Specifically, of the patients consuming this product, 11% experienced belching and 26% experienced heartburn, compared to 2% and 12%, respectively, in the placebo group (107955). A meta-analysis of eight small clinical studies in patients with irritable bowel syndrome shows that taking enteric-coated formulations of peppermint oil increases the risk of gastroesophageal reflux symptoms by 67% when compared with a control group (109980). Enteric-coated capsules can also cause anal burning in people with reduced bowel transit time (11782,11789).

Genitourinary ...Orally, a sensitive urethra has been reported rarely (102602).

Hepatic ...One case of hepatocellular liver injury has been reported following the oral use of peppermint. Symptoms included elevated liver enzymes, fatigue, jaundice, dark urine, and signs of hypersensitivity. Details on the dosage and type of peppermint consumed were unavailable (96358).

Immunologic ...One case of IgE-mediated anaphylaxis, characterized by sudden onset of lip and tongue swelling, tightness of throat, and shortness of breath, has been reported in a 69-year-old male who consumed peppermint candy (89479). An allergic reaction after use of peppermint oil in combination with caraway oil has been reported in a patient with a history of bronchial asthma (96344). It is not clear if this reaction occurred in response to the peppermint or caraway components.

Neurologic/CNS ...Orally, headache has been reported rarely (102602).

Ocular/Otic ...Orally, peppermint has been reported to cause blurry vision (3803).

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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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