Black Walnut Coptis Supreme Alcohol Free Liquid Extract [Discontinued] by Gaia Herbs

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral Baikal skullcap for allergic rhinitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Anxiety. Although there has been interest in using oral Baikal skullcap for anxiety, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Atherosclerosis. Although there has been interest in using oral Baikal skullcap for atherosclerosis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Baikal skullcap for ADHD, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Bronchiolitis. Intravenous Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a combination of Baikal skullcap, forsythia, and honeysuckle, known as Shuang Huang Lian in traditional Chinese medicine, given intravenously, with or without antibiotics, decreases the duration of cough by about 1.5-2 days, the duration of wheezing by about 2 days, and the duration of hospitalization by about 2-3 days when compared with antibiotics alone in children with respiratory syncytial virus (RSV) infection. Baikal skullcap injection was administered as a 20 mL dose for patients under 6 months, a 40 mL dose for patients 7-36 months, or a 60 mL dose for patients older than 36 months (12613).
• Cancer. Although there has been interest in using oral Baikal skullcap for cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Diabetes. It is unclear if oral Baikal skullcap is beneficial in patients with diabetes. Details: A very small clinical trial in patients with uncontrolled diabetes taking metformin 500 mg daily shows that taking Baikal skullcap extract 3.52 grams in three divided doses daily for 8 weeks does not decrease levels of fasting glucose or insulin or improve levels of glycated hemoglobin (HbA1c) when compared with placebo. However, taking Baikal skullcap reduces blood glucose levels during an oral glucose tolerance test (OGTT) at 60 minutes, but not 120 minutes, when compared with placebo (101738). This study may have been inadequately powered to detect a difference between groups.
• Epilepsy. Although there has been interest in using oral Baikal skullcap for epilepsy, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hand, foot, and mouth disease. It is unclear if intravenous Baikal skullcap is beneficial in patients with hand, foot, and mouth disease. Details: Low-quality observational research in children hospitalized with severe hand, foot, and mouth disease has found that children who are given Baikal skullcap intravenously as a Tanreqing injection 0.3-0.5 mL/kg once daily have a shorter duration of fever, oral ulcers, and rash, as well as reduced viral load, when compared with those given ribavirin 10 mg/kg once daily (96281). The validity of these findings is limited by the retrospective nature of the study.
• Headache. Although there has been interest in using oral Baikal skullcap for headache, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hemorrhoids. Although there has been interest in using oral Baikal skullcap for hemorrhoids, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hepatitis. Although there has been interest in using oral Baikal skullcap for hepatitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• HIV/AIDS. Although there has been interest in using oral Baikal skullcap for HIV/AIDS, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Insomnia. Although there has been interest in using oral Baikal skullcap for insomnia, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Osteoarthritis. Oral Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific product (Limbrel, Primus Pharmaceuticals) that contains flavocoxid, a blend of Baikal skullcap extract and catechu flavonoid extract, 500 mg once or twice daily for up to 12 weeks reduces symptoms of osteoarthritis of the knee when compared with baseline. These studies found no significant difference between this combination product and naproxen 440 mg once daily to 500 mg twice daily for reducing symptoms (17030,18012,92776). However, in 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). See the Adverse Effects section for more information.
• Peyronie disease. It is unclear if oral Baikal skullcap is beneficial in patients with Peyronie disease. Details: Observational research has found that taking oral Baikal skullcap root extract 150 mL twice daily for 6 months is associated with reduced time to disease stabilization, with an average reduction of 5 months, when compared with no treatment. In addition, 17% of patients taking Baikal skullcap had pain resolution and only 33% required surgical correction, compared with 0% and 58%, respectively, of control patients. In patients requiring surgery, taking Baikal skullcap did not appear to affect resolution; however, the study may have been inadequately powered to detect a difference between groups (105867).
• Prostate cancer. Although there has been interest in using oral Baikal skullcap for prostate cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Psoriasis. Although there has been interest in using oral Baikal skullcap for psoriasis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Seizures. Although there has been interest in using oral Baikal skullcap for seizures, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral and intravenous Baikal skullcap for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose. More evidence is needed to rate Baikal skullcap for these uses.

(Read more about BAIKAL SKULLCAP)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Coronary heart disease (CHD). It is unclear if consuming black walnut as part of the diet can reduce the risk for CHD. Details: Epidemiological research has found that people who increase dietary consumption of nuts in general might have a lower risk of CHD and death due to coronary events. However, there is no available evidence showing that eating black walnut, specifically, reduces the risk of CHD (8478,13299). Still, in 2004, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming 1.5 ounces of walnuts per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD. The FDA has concluded that this claim is based on supporting, rather than conclusive, evidence (102335).
• Wound healing. Although there is interest in using topical black walnut hull and bark for wound healing, there is insufficient reliable information about the clinical effects of black walnut for this purpose. More evidence is needed to rate the effectiveness of black walnut for these uses.

(Read more about BLACK WALNUT)

POSSIBLY EFFECTIVE

• Dysmenorrhea. In people with dysmenorrhea, taking oral ginger seems to reduce pain. Clinical research shows that ginger might be comparable to ibuprofen or mefenamic acid. In addition, taking ginger seems to be beneficial when used as an adjunct to mefenamic acid 250 mg twice daily. Details: Clinical research in individuals at least 15 years of age shows that ginger can reduce pain from dysmenorrhea. Clinical studies show that taking ginger powder 500-2000 mg daily usually for the first 3-4 days of a menstrual cycle modestly decreases pain severity by an average of 2.3-2.7 points on a 10-point scale when compared to control groups (89889,89899,91139,91892,96255,106077). However, a meta-analysis of clinical research shows that taking ginger does not reduce pain duration when compared with placebo (106077). Clinical research also shows that ginger might be as effective as some anti-inflammatory agents. Taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily for 3 days at the beginning of the menstrual period or until pain relief improves symptoms similarly to ibuprofen or mefenamic acid (17931,96259,106077). Also, taking a ginger extract 200 mg four times daily for 3-4 days at the beginning of pain is equally effective to taking Novafen, a combination of acetaminophen, caffeine, and ibuprofen (99444). Ginger also seems to improve pain when given as an adjunct to anti-inflammatory agents. A small clinical study in young females with dysmenorrhea shows that adding ginger (Vomigone, Dineh Co.) 500 mg daily to mefenamic acid 250 mg twice daily for 5 days further reduces pain when compared with taking mefenamic acid alone (102464).
• Osteoarthritis. Most clinical research shows that taking ginger extract by mouth improves pain in some patients with osteoarthritis. Topical ginger, on the other hand, has not shown benefit for knee osteoarthritis in low quality research. Details: Meta-analyses of clinical research show that taking ginger extract 500-1000 mg daily for 3-12 weeks can modestly improve pain when compared with placebo in some patients with osteoarthritis of the knee or hip (96253,103357). However, a meta-analysis of two clinical studies shows that taking ginger extract about 500 mg daily for 6 weeks does not have an effect on function (103357). One small clinical trial in patients with mild osteoarthritis of the knee also shows that taking steamed golden ginger extract 480 mg daily for 12 weeks moderately improves pain and functional scores when compared with placebo (114784). Some clinical research has also compared ginger to conventional drug treatment. In one clinical trial, there was no significant difference between ginger extract 30 mg daily and ibuprofen 400 mg three times daily for one month in patients with osteoarthritis of the hip or knee (17930). However, taking a specific ginger extract (Eurovita Extract 33; EV ext-33) orally 170 mg three times daily for 3 weeks was significantly less effective than ibuprofen 400 mg three times daily for reducing pain (7048). Since ginger is thought to take several weeks for significant benefit, this trial might not have lasted long enough. Ginger has also been compared with diclofenac. When used orally as 1500 mg daily in two divided doses, ginger is less effective than oral diclofenac 100 mg daily in two divided doses, or the combination of ginger and diclofenac, for 12 weeks (89898). Various studies have evaluated formulations containing ginger with other ingredients. These combinations have all been shown to improve osteoarthritis pain, and in some cases, functionality. Studied formulations include ginger (Eurovita Extract 35; EV ext-35) 340 mg with glucosamine (Zinaxin glucosamine, Ferrosan AS) 1000 mg daily for 4 weeks, a ginger extract with an alpinia (Alpinia galanga) extract (Eurovita Extract 77; EV ext-77) 255 mg twice daily for 6 weeks, a ginger extract with curcuminoids, and extracts of devil's claw, Boswellia serrata, and celery (Tregocel) for 36 weeks, or Ayurvedic shunthi-guduchi formulations containing ginger, Indian gooseberry, and Tinospora cordifolia, either with or without Boswellia serrata (7084,18210,89557,106078). However, it's too early to know if the effects of these combination agents are associated with ginger or other ingredients in the formulations. Topical ginger, alone or in combination with other ingredients, has also been studied for knee osteoarthritis. Although a meta-analysis of two randomized clinical trials shows no evidence of benefit of topical ginger for pain and disability when compared with placebo or standard therapy (103357), some benefits have been shown in individual preliminary studies (20340,20341,89897,96668,97537,97542). These trials have used a specific gel containing ginger and plai 4% by weight (Plygersic gel, Thailand Institute of Scientific and Technological Research) 4 grams/day in four divided doses for 6 weeks (89897), an ointment composed of ginger, cinnamon, mastic (Saghez), and sesame oil twice daily for 6 weeks (20340), or one gram of ginger extract 5% (standardized to 11.18% of 6-gingerol) in a nanostructure lipid carrier three times daily for up to 12 weeks to the affected knee (96668,97537). Some studies have used ginger essential oil in a massage oil, alone or with sweet orange essential oil or standard therapy, twice weekly for 3 or 6 weeks (20341,97542).
• Pregnancy-induced nausea and vomiting. Oral ginger seems to reduce the severity of nausea and vomiting in some people during pregnancy. Ginger seems to be more effective than placebo, comparable to vitamin B6 or dimenhydrinate, and less effective than metoclopramide. Details: Although most clinical studies are small and have methodological limitations, the available research shows that ginger is more effective than placebo, and comparable to vitamin B6 or dimenhydrinate (721,1922,5343,11346,13071,16306,20312,20315,90103,91201,102462). Although ginger is comparable to dimenhydrinate for reducing symptoms of morning sickness, it seems to take about 3 days to reduce vomiting episodes compared to 1 day with dimenhydrinate (16305). In addition, clinical research shows that ginger is less effective than metoclopramide at relieving nausea and vomiting associated with pregnancy (20315). Ginger doses of 500 to 2500 mg daily, divided into two to four daily doses for 3 days to 3 weeks, have been used in clinical research (721,5343,16305,16306,20312,20315,90103,91201). The American College of Obstetrics and Gynecology (ACOG) considers ginger capsules 250 mg 4 times daily a first-line nonpharmacological treatment option for pregnancy-induced nausea based on limited evidence. However, there is no evidence that ginger reduces vomiting (111601).

POSSIBLY INEFFECTIVE

• Chemotherapy-induced nausea and vomiting (CINV). Most clinical research shows that oral ginger does not reduce acute or delayed CINV. The effect of ginger might depend on the dose, the other antiemetics used, or the specific chemotherapy regimen. Details: Most clinical research shows that taking ginger as adjunct to adequate antiemetic therapy does not reduce DELAYED CINV when compared with antiemetic therapy alone (20316,96260,89891,96675,97538,97541,101760,102461,113616). Clinical research from meta-analyses and most individual clinical studies also show that taking ginger 0.5-3.5 grams as an adjunct to standard antiemetic therapy does not reduce the incidence or severity of ACUTE CINV when compared with antiemetic therapy alone (89891,96675,101760,102461,102466,113616). However, conflicting results exist from some individual clinical studies (20316,102466). These individual studies evaluated powdered ginger root or liquid extract of ginger root 0.5-2 grams taken in two to four divided doses daily, starting on either the day of or 3 days before chemotherapy and continuing for 3-5 days after chemotherapy initiation (20316,102466). Also, one small study shows that ginger in doses of 1 gram or less for more than 3 days reduces the likelihood of acute vomiting by 60% (101760). More research is needed to confirm the efficacy of this lower dose. Reasons for the conflicting results are unclear, but several theories have been postulated. One theory is that ginger might help reduce CINV associated with some, but not all, chemotherapy regimens. One preliminary clinical study shows that ginger 500 mg twice daily for 3 days reduces vomiting in patients receiving cyclophosphamide and doxorubicin, but not in patients also receiving 5-fluorouracil or docetaxel (96251). However, since there is limited evidence supporting this theory, additional research is needed to confirm. Another theory is that ginger helps when used with certain antiemetic drugs, but not others. For example, ginger seems to help in cases when optimal antiemetic therapy, such as 5-HT3 receptor antagonists, is not available. Small clinical studies show that ginger reduces the severity of acute nausea when compared with prochlorperazine or metoclopramide, both of which are suboptimal antiemetic therapy for CINV (89891). Another small study shows that ginger is comparable to metoclopramide for improving delayed chemotherapy-induced nausea (13244). On the other hand, several studies show that taking ginger 0.5-2 grams daily along with antiemetic therapy that includes aprepitant does NOT improve acute or delayed CINV (20318,89891,96251,96675). In fact, one study found an association between concomitant use of ginger 2 grams daily with aprepitant and worsened severity of delayed nausea. Ginger is hypothesized to decrease the absorption of aprepitant and reduce its effectiveness for delayed nausea (20318,96675). However, this effect has not been replicated, and aprepitant serum levels were not measured to confirm this hypothesis. Finally, many of the studies showing a benefit of ginger for CINV when used as an adjunct to standard antiemetic therapy are considered to be methodologically flawed (20317,96252,96677). For instance, one study using powdered ginger root 1-2 grams daily during the first three days of chemotherapy in children and adults (20317) has been criticized for inaccurately representing data (89891). Other studies of ginger 500 mg twice daily for up to 10 days used questionable methods to measure outcomes and usually did not differentiate between acute and delayed CINV (96252,96677). Ginger essential oil aromatherapy has also been evaluated. One small study shows that using two drops of ginger essential oil on an aromatherapy necklace for 2 minutes daily for 5 days, starting on the first day of chemotherapy, reduces acute nausea, but not vomiting or delayed nausea, when compared with placebo in females with breast cancer taking standard antiemetics including granisetron, dexamethasone, and metoclopramide (96256).
• Exercise-induced muscle soreness. Most research shows that oral ginger in single or multiple doses does not prevent or treat exercise-induced muscle soreness. Details: Two small studies in healthy adults show that single doses of ginger supplements do not seem to reduce muscle soreness from exercise. Taking capsules of ground ginger 2 grams, 30 minutes before a 30-minute cycling bout, or 24-48 hours after eccentric exercise, does not reduce muscle pain during exercise or within one hour of ingestion when compared with placebo (17932,17934). Taking multiple doses also does not seem to help. One small study in healthy adults shows that taking capsules with ginger powder 4 grams daily for 5 days before high-intensity eccentric exercise does not reduce muscle soreness over 4 days when compared with placebo (96258). Another small study in healthy adults shows that taking capsules of heated or raw ground ginger 2 grams daily for 8 days prior to eccentric exercise, and continuing supplementation for 3 more days, might modestly reduce muscle soreness 24 hours post-exercise, but not at later time points, when compared with placebo (17933,96258). Ginger has also been tested in combination with other ingredients. One small study in healthy adults shows that taking a specific combination product (ReWin(d), Natural Origins) containing a 4:3 ratio of ginger and annatto powder, 2 grams in divided doses daily for 4 weeks before eccentric exercise and continuing for 3 days after exercise, may modestly reduce muscle pain 48 hours after exercise but not at other time points (105057). This study was funded by the supplement manufacturer.
• Motion sickness. Most research shows that oral ginger does not prevent or treat motion sickness. Details: Most clinical research shows that taking ginger 500-1000 mg up to 4 hours prior to travel does not prevent motion sickness (7624,7625,20330,20331). Some patients report subjective feelings of improvement, but in many studies objective measures did not significantly improve (7400). However, one clinical trial suggests that ginger is more effective than dimenhydrinate at reducing gastrointestinal distress associated with motion sickness (20332). Another clinical study seems to show that taking ginger 1-2 grams as a single dose reduces nausea severity and increases the latency before the onset of nausea caused by simulated motion sickness when compared to baseline (20333). The validity of this finding is limited by the lack of a comparator group.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). Some small clinical studies show that giving ginger with tube feeds to hospitalized patients might reduce the duration of serious sequelae from ARDS. Details: A small clinical trial in adults with ARDS shows that administering ginger extract 120 mg in three divided doses daily via nasogastric tubing for 21 days increases the number of ventilator-free days and the amount of feeding tolerated and decreases the number of intensive care unit (ICU) days when compared with placebo. However, it does not seem to improve overall mortality (20343). Also, another small clinical study shows that adding ginger extract 120 mg to tube feeds in three divided doses daily for 8-21 days improves blood oxygen levels by 13% to 20%, as well as the ability of the lungs to expand by 17%, when compared with a coconut oil placebo. The duration of mechanical ventilation and stay in the ICU also improved. However, ginger does not affect other measurements of lung function or physical organ damage in these patients (89886).
• Allergic rhinitis (hay fever). It is unclear if oral ginger is beneficial in allergic rhinitis. Details: A small clinical trial shows that taking ginger extract 500 mg daily for 6 weeks is as effective as loratadine 10 mg daily for reducing nasal symptoms of allergic rhinitis (103359).
• Antiretroviral-induced nausea and vomiting. Oral ginger seems to improve nausea and vomiting in patients using antiretroviral agents. Details: A small clinical study in patients with HIV shows that taking ginger 0.5 grams twice daily, 30 minutes prior to each dose of antiretroviral for 14 days, reduces the relative likelihood of nausea and vomiting by about 63% and 79%, respectively, when compared with placebo (89887).
• Asthma. Although there has been interest in using oral ginger for asthma, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Atopic dermatitis (eczema). Topical ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical trial in adults and children with eczema shows that applying a combination topical product containing ginger and cannabidiol twice daily for 5 days moderately improves eczema scores, including erythema, dryness, itching, and scaling, when compared to baseline. It is unclear if this effect is due to ginger, other ingredients, or the combination. The validity of this study is limited by the lack of a comparator group (114783).
• Back pain. Although there has been interest in using oral ginger for back pain, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Burns. Although there has been interest in using topical ginger for burns, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Cancer-related anorexia. It is unclear if oral ginger improves appetite in people with cancer-related anorexia. Details: A small clinical study in patients with cancer-related anorexia and cachexia shows that taking a capsule containing ginger 1650 mg daily for 14 days improves nausea, appetite, reflux, dysmotility, and other gastrointestinal symptoms when compared to baseline (102460). The validity of these findings is limited by the lack of comparator group.
• Chronic obstructive pulmonary disease (COPD). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules of a specific combination product (AKL1, AKL International Ltd.) containing ginkgo extract, ginger, and Picrorhiza kurroa twice daily for 8 weeks does not improve respiratory symptoms when compared with placebo in patients with COPD (89702). Another moderate-sized clinical study in adults with COPD shows that taking a combination product containing extracts of ginger, alpinia, cardamom, cinnamon, and saffron in honey 3 times daily for 8 weeks improves confidence in leaving home and the ratio of forced exploratory volume per second to forced vital capacity of the lungs (FEV1/FVC) when compared with placebo. However, the combination product does not improve most measures of respiratory function or symptoms such as cough, phlegm, chest tightness, dyspnea, reduced energy levels, sleeping disorders, or activity limitations when compared with placebo (111542). It is unclear if these effects are due to ginger, other ingredients, or the combination.
• Colic. Although there has been interest in using oral ginger for colic, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Constipation. Although there has been interest in using oral ginger for constipation, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Coronavirus disease 2019 (COVID-19). It is unclear whether oral ginger is beneficial for patients with COVID-19. Details: Clinical research in adults hospitalized with asymptomatic COVID-19 infection shows that taking ginger 1.5 grams twice daily orally until hospital discharge reduces length of stay from around 8.5 days to 6 days, when compared with placebo. The strongest effect is seen in males over 60 years of age (110005). The relevance of these results is reduced by a lack of blinding, and the fact that the subjects were initially asymptomatic. Another small study in adults with COVID-19 treated in the community shows that taking ginger 1000 mg three times a day for 7 days does not improve viral clearance, oxygen saturation, or respiratory rate when compared with placebo. Taking ginger also did not reduce the risk of hospitalization (114779). The efficacy of ginger for treating COVID-19 has also been evaluated in combination with other ingredients. In adults with uncomplicated, moderate COVID-19, taking a combination of ginger, turmeric, ashwagandha, and boswellia (BV-4051, Artovid-20), 1776 mg twice daily orally for 14 days in addition to standard care and starting 48-96 hours after symptom onset, reduces the mean duration of symptoms from about 8 days to 7 days, when compared with placebo (109899). A small open-label study in adults with confirmed mild to moderate COVID-19 shows that taking ginger 1000 mg and ashwagandha 500 mg twice daily for 15 days, along with conventional therapy, leads to a 13.8-fold and 2.6-fold increase in the relative rate of clinical cure at 7 days and 15 days, respectively, when compared with conventional therapy alone. Taking this combination also appears to reduce time to recovery by around 6 days but does not improve the rate of negative COVID-19 tests, chest imaging findings, viral clearance, serum antibodies, or other measures of disease progression when compared with conventional therapy alone (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Additionally, it is unclear if these effects are due to ginger, ashwagandha, or the combination.
• Diabetes. Some preliminary clinical studies suggest that oral ginger might have a small beneficial effect on glycemic control in patients with type 2 diabetes or gestational diabetes. Details: Meta-analyses of several small clinical trials in adults with type 2 diabetes show that taking ginger 1200-3000 mg daily for 8-13 weeks reduces glycated hemoglobin (HbA1c) by around 0.6% to 1% and fasting blood glucose by 19-21 mg/dL when compared with placebo (96680,107898). However, a recent meta-analysis of randomized clinical trials in adults with type 2 diabetes shows that taking ginger 1200-2000 mg daily for 4-12 weeks does not improve HbA1c or fasting blood glucose when compared with placebo (114780). The reasons for these discordant results are not entirely clear, but they are likely related to heterogeneity of the included populations, treatment dose, and duration of follow up. Additionally, a small clinical study in adults with diabetes on hemodialysis for end stage renal disease shows that taking ginger powder 2000 mg daily for 8 weeks reduces fasting blood glucose and measures of insulin resistance, but not serum insulin levels, when compared with placebo (111543). In patients with gestational diabetes at weeks 24-28 of pregnancy, clinical research shows that taking ginger 1500 mg daily in three divided doses for 6 weeks reduces fasting blood glucose, insulin levels, and measures of insulin resistance by a small amount when compared with placebo, with no effect on postprandial glucose levels (103358).
• Diabetic neuropathy. Topical ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults treated with gabapentin for diabetic neuropathy of the foot shows that applying a combination balm containing ginger, menthol, camphor, and other ingredients three times a day for 4 weeks moderately improves pain scores when compared with a placebo balm without ginger but containing menthol, camphor, and other ingredients.(114781). It is unclear if this effect is due to ginger, other ingredients, or the combination.
• Diarrhea. Although there has been interest in using oral ginger for various types of diarrhea, including cholera and acute bacterial dysentery, there is insufficient reliable information about the clinical effects of ginger for these conditions.
• Dry mouth. It is unclear if rinsing the mouth with ginger extract is beneficial for dry mouth. Details: In patients with dry mouth related to type 2 diabetes, clinical research shows that use of a ginger extract 25% mouthwash 20 mL three times daily for 14 days modestly reduces symptoms of dry mouth when compared with rinsing with a saline control mouthwash (106068). Although this study was indicated as being triple-blind, it is unclear how the taste of ginger was masked.
• Dyspepsia. It is unclear if oral ginger is beneficial for dyspepsia. Details: In patients with dyspepsia, a small clinical trial shows that a single dose of ginger root powder 1.2 grams, taken 1 hour prior to eating, does not reduce abdominal discomfort when compared with placebo. However, it increases the rate of gastric emptying (20325).
• Erectile dysfunction (ED). It is unclear if oral ginger is beneficial for erectile dysfunction. Details: Preliminary clinical research in middle-aged males with ED shows that taking two capsules of a specific combination product (Revactin, MD Concepts LLC) containing ginger root 250 mg, muira puama 250 mg, guarana 250 mg, and L-citrulline 800 mg twice daily for 3 months improves scores related to erectile function and intercourse satisfaction, but does not improve sexual desire or orgasmic function scores, when compared to baseline (103224). This study is limited by the lack of a placebo control, the use of per-protocol analysis, and a high dropout rate. In fact, 44% of patients withdrew in order to resume use of phosphodiesterase type 5 (PDE5) inhibitors. Further, it is unclear if these effects are due to ginger, other ingredients, or the combination.
• Gastroenteritis-associated nausea and vomiting. It is unclear if oral ginger is beneficial for children with gastroenteritis-associated vomiting. Details: In children aged 1-10 years with acute gastroenteritis-associated vomiting, clinical research shows that taking a single dose of ginger reduces the risk of vomiting at least once in the subsequent 8 hours by 20% when compared with placebo. The incidence of vomiting over the next 24 and 48 hours was also modestly reduced. The children were given 20 drops of ginger equivalent to 10 mg immediately, followed by every 8 hours until cessation of vomiting. All children were offered hypotonic oral rehydration solution (ORS) 30 minutes after the first dose (106076). The number of children accepting ORS, and the quantity of ORS consumed, was less in the group receiving placebo. It is unclear if this affected the outcomes of this study. Also, the incidence or severity of nausea was not investigated.
• Hangover. It is unclear if oral ginger is beneficial for managing symptoms of hangover. Details: Preliminary clinical research shows that use of a decoction containing a combination of ginger 6 grams, pith of Citrus tangerine 3 grams, and brown sugar decreases symptoms of alcohol hangovers, including nausea, vomiting, and diarrhea, when compared with placebo. The decoction was taken once 5 hours prior to drinking alcohol or four times after drinking alcohol (20320).
• Hyperlipidemia. Oral ginger may be modestly beneficial for some patients with hyperlipidemia. Details: A meta-analysis of preliminary clinical research in adults with and without hyperlipidemia shows that taking ginger 200-3000 mg orally daily for 2-24 weeks reduces triglyceride and low-density lipoprotein cholesterol levels by 12 mg/dL and 5 mg/dL, respectively, and increases high-density lipoprotein cholesterol levels by 1 mg/dL when compared with placebo (109521). However, the validity of this study is limited by high heterogeneity. A clinical study in adults with hyperlipidemia shows that taking ginger powder 1 gram three times daily for 45 days reduces triglyceride and cholesterol levels by an additional 36% and 90%, respectively, when compared with placebo (20327).
• Hypertension. It is unclear if oral ginger is beneficial for lowering blood pressure. Details: A preliminary clinical study in patients with diabetes and elevated systolic blood pressure shows that drinking black tea containing ginger 3 grams three times daily for 8 weeks does not reduce blood pressure by a clinically significant amount when compared with plain black tea (96669).
• Hypothyroidism. It is unclear if oral ginger is beneficial in patients with hypothyroidism. Details: A small clinical study in patients with primary hypothyroidism who are stabilized on thyroid hormone therapy shows that taking ginger powder 500 mg twice daily for 30 days improves symptoms associated with hypothyroidism, including cold intolerance, constipation, dizziness, dry skin, weight gain, and concentration and memory issues, when compared with placebo. However, ginger supplementation does not seem to improve hair loss, hearing, nail fragility, speech, or feelings of depression in these patients (107903).
• Insect bite. It is unclear if topical ginger is beneficial for reducing the size of insect bites. Details: Preliminary clinical research shows that a topical application of Trikatu, which contains ginger, long pepper, and black pepper extracts with 0.074% piperine and 0.046% gingerol, does not reduce the papule size associated with mosquito bites when compared with a control compound containing the same base ingredients of camphor 2%, menthol 2%, and eucalyptus oil 4% (89893).
• Intraoperative nausea and vomiting (IONV). It is unclear if oral ginger is beneficial for preventing IONV. Details: Clinical research in individuals undergoing elective C-section and receiving cimetidine and metoclopramide, shows that taking ginger 1 gram orally 30 minutes prior to anesthesia reduces the number of episodes of intraoperative nausea, but not vomiting, when compared with placebo (89890). In other clinical research in adults undergoing elective surgical procedures, adding ginger to a high calorie drink consumed pre-operatively reduces the incidence of nausea from 40% to 10%, and the incidence of vomiting from 25% to 10% when compared with the high calorie drink alone (110007). The validity of these results is unclear as only patients were blinded to the treatment group.
• Irritable bowel syndrome (IBS). Oral ginger might reduce symptoms of IBS when used in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking ginger 1-2 grams daily for 28 days does not improve symptoms or the number of responders when compared with placebo (90102). However, some research shows that ginger might be beneficial in some patients when used along with other herbal ingredients. Taking a capsule containing ginger, boswellia, and yarrow three times daily for 30 days reduces the frequency and severity of abdominal pain, as well as the severity of bloating, when compared with placebo in females, but not males, with mild to moderate IBS (96673). Another clinical study shows that taking an herbal mixture containing ginger, English horsemint, and purple nut sedge tuber three times daily for 8 weeks improves IBS symptoms including abdominal pain, stool frequency, stool consistency, incomplete evacuation, and urgency, when compared to baseline; these improvements are similar to those achieved by taking mebeverine 135 mg three times daily (89900). However, it is unclear if these effects are due to ginger, other ingredients, or the combination.
• Joint pain. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsufonlylmethane 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 ginger, other ingredients, or the combination.
• Menorrhagia. It is unclear if oral ginger is beneficial for menorrhagia. Details: Preliminary clinical research in healthy adults experiencing heavy menstrual bleeding shows that taking ginger 250 mg three times daily for 4 days, starting the day prior to menstruation, and repeating for three menstrual cycles, reduces the amount of menstrual bleeding when compared with placebo (96672).
• Menopausal symptoms. Although there has been interest in using oral ginger for menopausal symptoms such as insomnia, there is insufficient reliable information about the clinical effects of ginger for this purpose.
• Migraine headache. Small clinical studies suggest that oral ginger may modestly reduce migraine pain severity and duration. However, taking ginger doesn't seem to PREVENT migraines. Details: Ginger does not seem to be effective for the prevention of migraines. Clinical research in patients with episodic migraine shows that taking ginger extract 200 mg three times daily for 3 months does not reduce the number of migraine attacks, the use of analgesics, or the number of days with pain, any more than taking placebo (101761). However, ginger may be beneficial for the treatment of migraine. Clinical research shows that taking ginger extract 400 mg orally in the emergency room along with intravenous ketoprofen 100 mg reduces pain over the next 2 hours when compared with ketoprofen and placebo. This combination also resulted in an overall better response with a higher likelihood of having no or mild pain with treatment (101762). Taking ginger 250 mg at the onset of a common migraine headache seems to be as effective as taking sumatriptan 50 mg for reducing headache severity within two hours of treatment (89894). Furthermore, a combination of ginger and feverfew (GelStat Migraine, GelStat Corporation; LipiGesic M, PuraMed BioScience), administered sublingually at the onset of a migraine attack, decreases the duration and intensity of migraine pain when compared with placebo (19357,22602). It is unclear if these effects are due to ginger, feverfew, or the combination. Feverfew alone has demonstrated some benefit in treating migraines.
• Multiple sclerosis (MS). It is unclear if oral ginger is beneficial for MS. Details: A small clinical study in adults with MS shows that taking ginger 500 mg three times daily for 12 weeks reduces disability scores and improves physical and psychological quality of life scores when compared with placebo (111541). Another small clinical study in adults with relapsing-remitting MS shows that taking ginger 500 mg three times daily for 12 weeks reduces the frequency and severity of nausea and constipation and the severity but not frequency of bloating when compared with placebo. However, no improvement was noted in other gastrointestinal symptoms of MS including abdominal pain, anorexia, diarrhea, dysphagia, gas, or heartburn (113614).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral ginger is beneficial for NAFLD. Details: A small clinical study in patients with NAFLD shows that taking ginger 1000 mg twice daily for 12 weeks improves liver steatosis scores but not liver fibrosis scores when compared with placebo. Ginger also modestly improves levels of alanine aminotransferase and gamma-glutamyl transferase but not aspartate aminotransferase (113615). However, it is unclear whether any improvements are clinically significant. Another small clinical study in patients with NAFLD shows that taking ginger root 1500 mg daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol and fasting blood glucose levels, but does not affect triglycerides, high-density lipoprotein (HDL) cholesterol, insulin resistance, blood pressure, or fatty liver index, when compared with placebo (102465).
• Obesity. Oral ginger has primarily been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Although some individual research disagrees (40802), a meta-analysis and most individual clinical trials show that taking ginger alone or with other ingredients does not reduce weight by a clinically significant amount when compared with placebo in overweight or obese individuals (20346,20347,96676,109521). Ginger has been taken alone or in combination with green tea and capsaicin; rhubarb, astragalus, red sage, turmeric, and gallic acid (Number Ten); or raspberry ketone (Razberi K, Integrity Nutraceuticals), caffeine, capsicum extract (Capsimax, OmniActive Health Technologies), bitter orange fruit (Advantra Z, Nutratech Inc), L-theanine, and black pepper fruit extract (Biperine, Sabinsa Corporation) (Prograde Metabolism) (20346,20347,40802,96676). Due to the various other ingredients contained in available formulations, any effect from ginger is unclear.
• Parturition. It is unclear if bathing in a ginger bath is beneficial for shortening the duration of labor. Details: Preliminary clinical research shows that bathing in 228 liters of water containing 4 drops of ginger essential oil does not shorten the duration of labor when compared with a regular bath (20345).
• Polycystic ovary syndrome (PCOS). It is unclear if oral ginger is beneficial for females with PCOS. Details: Preliminary clinical research in females with PCOS shows that taking ginger 500 mg three times daily orally for 8 weeks decreases body weight, body mass index, and levels of follicle stimulating hormone and luteinizing hormone, when compared with placebo. It does not affect testosterone levels (110006).
• Postoperative nausea and vomiting (PONV). Evidence for the use of oral ginger for preventing PONV is inconclusive and conflicting. Reasons for the conflicting findings may relate to the ginger formulation used and the outcomes measured. It is unclear if ginger aromatherapy is beneficial for PONV. Details: Some individual clinical studies, as well as a large, recent meta-analysis of the available clinical research, show that taking ginger by mouth 1 hour prior to surgery does not reduce the incidence of 24-hour PONV (3452,3453,17369,99445). Also, the meta-analysis found that, although ginger reduces the severity of PONV when measured on a visual analogue scale (VAS), it does not reduce the severity of PONV when measured on a verbal descriptive scale (VDS). Furthermore, ginger does not reduce the use of rescue antiemetic medications (99445). However, some small, individual clinical studies and a meta-analysis of older clinical research show that taking ginger by mouth prior to surgery reduces the incidence of 24-hour PONV by up to 16% to 38% (722,723,1919,13237,20336,20338,20339). In addition, large clinical trials show that the frequency and severity of PONV 2-6 hours after surgery are similar when ginger 1 gram is given orally or when medications such as metoclopramide or dexmedetomidine are given intravenously prior to undergoing anesthesia (103356,103360). However, taking ginger prior to general anesthesia, in combination with other antiemetics like dexamethasone or cimetidine and metoclopramide, does not seem to reduce nausea and vomiting when compared with the other medications alone (20337,89890). In contrast, other research shows that powdered ginger 1-2 grams 30-60 minutes before induction of anesthesia has been used in most studies showing benefit, occasionally followed by 1 gram of ginger administered two hours after surgery (722,723,13237,20336,20338,103356,103360). Ginger aromatherapy has also been evaluated for the prevention of PONV. Application of 5% ginger essential oil to the wrists of patients prior to the induction of general anesthesia seems to prevent PONV in approximately 80% of treated patients (20334). Also, use of ginger essential oil aromatherapy on a gauze pad results in nausea relief in approximately 67% of patients compared with 40% in the placebo group; however, a blend of essential oils including ginger, spearmint, peppermint, and cardamom, results in nausea relief in 82% of patients (89888).These conflicting findings may be due to differences in outcome measures and the chemical compositions of ginger preparations used in the various clinical studies. Some evidence suggests that the efficacy of ginger for preventing PONV differs based on the formulation used. A network meta-analysis of 18 studies evaluating various ginger preparations, including ginger oil, ginger powder, ginger extract, and a combination of ginger powder and antiemetics, for the prevention of PONV suggests that ginger powder and ginger oil are the most effective formulations for preventing nausea and vomiting, respectively. The analysis also shows that while no ginger formulation is superior to another for the prevention of nausea, ginger powder and ginger oil have a lower risk of postoperative vomiting when compared with ginger extract. A subgroup analysis suggests that ginger seems to be most effective in adults over 30 years of age, when administered preoperatively, and when used for gastrointestinal, hepatobiliary, obstetric, or ophthalmic surgeries (112108).
• Postoperative recovery. It is unclear if oral ginger is beneficial for postoperative recovery. Details: One preliminary clinical study in adults who had a tonsillectomy shows that taking a specific ginger supplement (Solgar, Leonia) 500 mg twice daily for 7 days along with acetaminophen and antibiotics modestly improves pain and wound healing when compared with acetaminophen and antibiotics alone (96674).
• Postpartum complications. It is unclear if oral ginger is beneficial in patients with postpartum pain. Details: A small clinical study in patients recovering from vaginal delivery shows that taking ginger powder 500 mg 8-hours post-delivery, followed by 250 mg every 8 hours thereafter for 24 hours, reduces postpartum pain by nearly 1 point on a 10-point rating scale when compared with placebo (107904). It is unclear if this improvement would be considered clinically relevant.
• Radiation-induced nausea and vomiting. It is unclear if oral ginger is beneficial in patients with radiation-induced nausea and vomiting. Details: A very small study in adults with cervical cancer undergoing treatment with cisplatin and radiotherapy shows that taking ginger 250-500 mg twice daily for 6 weeks in addition to standard antiemetic therapy does not reduce acute or delayed nausea and vomiting when compared with antiemetic therapy alone (113616).
• Rheumatoid arthritis (RA). One small clinical study suggests that oral ginger may improve some symptoms of RA. Details: Preliminary clinical research in adults with RA shows that taking ginger powder 1500 mg daily for 12 weeks improves disease activity on the Disease Activity Score-28 when compared with placebo (100697). Another small study in adults with RA shows that taking a combination product containing ginger, ashwagandha, black pepper, and colchicum luteum twice daily for 4 weeks does not improve RA disease scores when compared with celecoxib 100 mg orally twice daily (114785). However, the interpretation of these results is limited by. poor methodology, and the study may have been inadequately powered to detect a difference between groups.
• Smoking cessation. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults in India with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ginger 50 mg, ashwagandha, cowhage, turmeric and other herbal extracts (Smotect, Smotect India) twice 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 also unclear if these effects are due to ginger, other ingredients, or the combination.
• Swallowing dysfunction. The effects of oral ginger for treating swallowing dysfunction are inconclusive. Reasons for the conflicting findings may relate to the route of administration or the number of treatments provided. Details: Clinical research shows that applying a spray containing ginger and clematix root (Tongyan) to the oropharynx for 28 days is more effective than placebo at treating grade 2 or 3 dysphagia in stroke victims. However, there does not seem to be a beneficial effect in patients with grade 1 dysphagia (20342). Other clinical research in elderly patients with dysphagia shows that taking a single dose of ginger 2 mg orally does not improve swallowing but increases saliva (96671). It is possible that a single dose of ginger is not enough to improve swallowing function.
• Toxin-induced liver damage. Oral ginger might help to prevent liver damage in patients using antimycobacterial drugs. Details: Preliminary clinical research shows that a specific ginger supplement (Zintoma, Goldaru) 500 mg taken 30 minutes prior to antimycobacterial drugs daily for 4 weeks reduces the percentage of patients experiencing an increase in liver function enzymes to greater than five times the upper limit of normal by 54% when compared with placebo. Antimycobacterial drugs used for tuberculosis in the study included isoniazid 5 mg/kg, rifampin 10 mg/kg, ethambutol 15 mg/kg, and pyrazinamide 25 mg/kg daily (96670).
• Traumatic brain injury (TBI). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary research in young adults with subjective memory dysfunction associated with mild TBI, shows that taking a combination of ginger 36 mg and boswellia 360 mg (Memoral) every 8 hours orally for one month improves scores for some, but not all, parameters on an auditory-visual learning test performed at one and three months, when compared with placebo. Total learning scores increased by about 7.5 points with the ginger combination product, compared with 4 points for placebo (110132). It is unclear if these effects are due to ginger, boswellia, or the combination.
• Ulcerative colitis. It is unclear if oral ginger is beneficial for improving symptoms of ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking ginger powder 1000 mg twice daily for 12 weeks improves disease activity as measured by the Simple Clinical Colitis Activity Index Questionnaire when compared with taking placebo. However, taking ginger did not improve quality of life, stool frequency, bowel distress, or flatulence when compared with placebo (100694). It is possible that this study was not adequately powered to detect a difference in these secondary outcomes.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral ginger for various upper respiratory tract infections, there is insufficient reliable information about the clinical effects of ginger for this condition.
• Vertigo. It is unclear if oral ginger is beneficial for improving symptoms of vertigo. Details: A small clinical study shows that taking 1 gram of ginger orally as a single dose prior to stimulated vertigo seems to reduce symptoms of vertigo, including nausea, when compared with placebo. However, it does not seem to reduce nystagmus (7623). More evidence is needed to rate ginger for these uses.

(Read more about GINGER)

There is insufficient reliable information available about the effectiveness of goldthread.

(Read more about GOLDTHREAD)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical oregano oil for acne, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Asthma. Although there has been interest in using oral oregano for asthma, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Bronchitis. Although there has been interest in using oral oregano for bronchitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Canker sores. Although there has been interest in using topical oregano oil for canker sores, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Cough. Although there has been interest in using oral oregano for cough, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dandruff. Although there has been interest in using topical oregano oil for dandruff, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Diabetes. Although there has been interest in using oral oregano for diabetes, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dysmenorrhea. Although there has been interest in using oral oregano for dysmenorrhea, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dyspepsia. Although there has been interest in using oral oregano for dyspepsia, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Gingivitis. Although there has been interest in using topical oregano oil for gingivitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Headache. Although there has been interest in using topical oregano oil for headache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Insect repellent. Although there has been interest in using topical oregano oil as an insect repellent, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Intestinal parasite infection. It is unclear if oral oregano is beneficial in patients with intestinal parasite infections. Details: In one small, uncontrolled study, taking a specific emulsified oregano leaf oil product (ADP, Biotics Research Corporation) 200 mg orally three times daily with meals for 6 weeks resulted in eradication of Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana from the stool in 10 of 13 patients (6878). The clinical significance of this is unclear since the Centers for Disease Control (CDC) considers Entamoeba hartmanni and Endolimax nana to be non-pathogenic, while blastocystosis caused by Blastocystis hominis is usually self-limiting and does not require treatment.
• Pain (acute). Although there has been interest in using topical oregano oil for the relief of acute pain, including joint and muscle pain, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Psoriasis. Although there has been interest in using topical oregano oil for psoriasis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Rhinosinusitis. Although there has been interest in using oral oregano for rhinosinusitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Seborrheic dermatitis. Although there has been interest in using topical oregano oil for seborrheic dermatitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea capitis. Although there has been interest in using topical oregano oil for tinea capitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea corporis. Although there has been interest in using topical oregano oil for tinea corporis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea pedis. Although there has been interest in using topical oregano oil for tinea pedis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Toothache. Although there has been interest in using topical oregano oil for toothache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral oregano for URTIs, such as the common cold and influenza, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral oregano for UTIs, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Varicose veins. Although there has been interest in using topical oregano oil for varicose veins, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Warts. Although there has been interest in using topical oregano oil for warts, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Wound healing. It is unclear if topical oregano is beneficial for improving healing or preventing infections in people with skin wounds. Details: One small clinical trial shows that applying an ointment containing a 3% concentration of the water-soluble fraction of the oregano plant twice daily for 10-14 days after minor dermatological surgery might reduce infection rates and improve scar formation when compared with petrolatum ointment (67348). More evidence is needed to rate oregano for these uses.

(Read more about OREGANO)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there has been interest in using oral pau d'arco for cancer, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose.
• Dysmenorrhea. Oral pau d'arco has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open-label study in adults with dysmenorrhea shows that taking pau d'arco 1050 mg plus rutin 75 mg daily for up to 8 weeks may reduce pain intensity scores by 41% when compared to baseline (114012). The validity of this finding is limited by the lack of a comparator group and common use of other pain medications, such as NSAIDs.
• Peptic ulcers. Although there has been interest in using oral pau d'arco for peptic ulcers, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose.
• Wound healing. Although there has been interest in using oral and topical pau d'arco for wound healing, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose. More evidence is needed to rate pau d'arco for these uses.

(Read more about PAU D'ARCO)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Topical red clover has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in individuals with androgenic alopecia shows that topical application of a combination of red clover flower extract and acetyl tetrapeptide-3 increases the growth phase of hair production by 13% and decreases the resting phase of hair production by 29% when compared to baseline (19540). The validity of these findings is limited by the lack of a comparator group.
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral red clover for BPH, there is insufficient reliable information about the clinical effects of red clover for this condition.
• Breast cancer-related hot flashes. It is unclear if oral red clover is beneficial for reducing hot flashes in patients who have had breast cancer. Details: A small clinical study in breast cancer patients with menopausal symptoms due to tamoxifen therapy shows that taking red clover extract (Promensil Forte) 80 mg daily for 24 months does not reduce menopausal symptoms, including hot flashes, sleep disturbance, and fatigue, any more than placebo (102901).
• Hyperlipidemia. It is unclear if oral red clover is beneficial in patients with hyperlipidemia; research is conflicting. Details: Most clinical trials in adult females with or without elevated cholesterol levels show that taking red clover extracts providing isoflavones 40-120 mg daily for 3 months to 1 year does not reduce total or low-density lipoprotein (LDL) cholesterol, or increase high-density lipoprotein (HDL) cholesterol, when compared with control (3375,8502,11089,11091,17091,19450,19543). However, a meta-analysis of 10 clinical trials in perimenopausal and postmenopausal patients with or without hyperlipidemia shows that red clover decreases total cholesterol by around 11 mg/dL, but does not affect LDL cholesterol, triglyceride, or HDL cholesterol levels, when compared with placebo (102840). This finding is limited by imprecision and inconsistency of the results and the fact that the benefit seems to be mostly attributed to two trials with a high risk of detection and performance bias. When this meta-analysis was repeated without those two trials, red clover supplementation for at least three months still shows a significant, albeit smaller, reduction in total cholesterol of around 4 mg/dL when compared with placebo among post-menopausal individuals. The meta-analysis also shows a small but statistically significant increase in HDL by approximately 1.5 mg/dL and no change in LDL or triglyceride levels (112145). Included studies were of moderate to high quality and lacked heterogeneity.
• Mastalgia. It is unclear if oral red clover is beneficial in patients with mastalgia. Details: One very small study in patients with cyclic mastalgia shows that taking red clover isoflavones (Promensil, Novogen) 40-80 mg daily reduces subjective ratings of breast pain and tenderness. Reductions in pain were 44% with 40 mg and 31% with 80 mg, compared with 13% for placebo (9552).
• Menopausal symptoms. It is unclear if oral red clover is beneficial for menopausal symptoms; research is conflicting and has notable methodological issues. Details: The most recent meta-analysis of 8 small clinical trials in patients with menopausal symptoms suggests that red clover reduces hot flash frequency by an average of 1.7 times when compared with control. The benefit tends to be greater in those with a higher frequency of hot flashes at baseline (5 or more) and when higher doses of red clover isoflavones are used (80 mg or more daily) (105694). However, this finding is limited by imprecision and inconsistency, as well as selective reporting bias in some of the included trials. An older meta-analysis of small, low-quality clinical studies in menopausal patients also suggests that red clover might improve psychological symptoms such as anxiety and depression when compared with control (91525). The most extensively studied product is a specific red clover supplement (Promensil or Melbrosin, Novogen). A meta-analysis of 5 small clinical studies assessing only Promensil shows that taking 80 mg daily for 12 weeks reduces hot flash frequency by 30% to 50%, or by about 3-4 hot flashes per day, when compared with placebo (96731). The validity of these findings is limited by imprecision, inconsistency, and publication bias. Notably, this meta-analysis and all included studies were funded by the supplement manufacturer (8925,10976,10991,17103,19545,96731). In contrast, studies with independent funding sources have not found a benefit with red clover isoflavones 40-120 mg daily for up to 12 months when compared with placebo (10975,17091,19549). Some research has also found benefit for menopausal symptoms when red clover is used in combination with other ingredients. Red clover has been used in combination with black cohosh, dong quai, milk thistle, American ginseng, and Vitex agnus-castus (Phyto-Female Complex) twice daily for 3 months (19552). Red clover isoflavones 37.1 mg have also been used in combination with a probiotic-rich liquid daily for 12 weeks (96730).
• Osteoarthritis. It is unclear if topical red clover is beneficial in patients with osteoarthritis. Details: Preliminary clinical research shows that applying 20 drops of a standardized extract of red clover aerial parts to the knee twice daily for 4 weeks, in addition to taking meloxicam orally, improves subjective measures of pain and function more than using meloxicam plus placebo. However, radiological and laboratory changes were not evaluated (102839).
• Osteoporosis. It is unclear if oral red clover is beneficial in patients with osteoporosis; research is conflicting. Details: One small clinical study in healthy postmenopausal patients shows that taking red clover providing isoflavones 57-85.5 mg daily for 6 months increases bone mineral density (BMD) of the proximal radius and ulna by 3% to 4% (10948). Another clinical study in females ages 49-65 years shows that taking a specific red clover extract (Promensil, Novogen) providing isoflavones 40 mg daily for one year does not increase BMD or bone mineral content (BMC) of the hip, but seems to slightly reduce the loss of lumbar spine BMD and BMC when compared with placebo (6127). However, other research has found no benefit. One clinical study in patients who are at least one year post-menopause and not taking bone preserving medications shows that taking a specific product containing enriched red clover isoflavones (Rimostil [formononetin enriched], Novagen) 50 mg daily for 2 years does not improve BMD of the spine, femoral neck, distal radius, or proximal radius when compared with placebo. However, this study may have been underpowered due to a high drop-out rate (91524). Another small clinical study in perimenopausal and postmenopausal adults shows that taking red clover flowering tops providing isoflavones 120 mg daily for one year does not seem to slow the loss of hip, femoral neck, or lumbar spine BMD when compared with placebo (17091). More evidence is needed to rate red clover for these uses.

(Read more about RED CLOVER)

POSSIBLY EFFECTIVE

• Acne. Some clinical research shows that topical tea tree oil seems to improve symptoms of acne in adults and adolescents. Details: Some preliminary clinical research shows that applying a tea tree oil 5% gel is as effective as benzoyl peroxide 5% (Oxy-5, Benzac AC, and others) and more effective than placebo for treating acne. Tea tree oil might work more slowly than benzoyl peroxide, but it seems to be less irritating to facial skin (8573). Other clinical research shows that applying a tea tree oil 5% gel for 20 minutes twice daily for 45 days decreases acne lesions 3.6-fold, acne severity 5.7-fold, and comedone numbers, pustules, and papules when compared with placebo in patients with mild to moderate acne (19176). Another small clinical study in patients with mild to moderate acne shows that applying a topical tea tree oil nanoemulsion with adapalene gel 0.1% once daily for 12 weeks reduces acne lesions and improves acne severity scores when compared with adapelene gel alone. However, the tea tree oil product was associated with an increased occurrence of mild adverse effects (109945). Conversely, a small clinical trial shows that applying tea tree oil 5% cream twice daily for 8 weeks reduces inflammatory acne lesions by 38%, compared with a 65% reduction in patients using a product based on Lactobacillus-fermented Chamaecyparis obtuse 5% cream. Additionally, the time of onset was slower with tea tree oil (91447).
• Onychomycosis. Some clinical research suggests that topical pure tea tree oil seems to be beneficial for onychomycosis. It is unclear if the diluted oil is beneficial. Details: Topical application of pure tea tree oil twice daily for 6 months can produce a mycological cure in about 18% of patients with toenail infections. It can also improve nail appearance and symptoms in about 56% of patients after three months and 60% of patients after 6 months of treatment. It seems to be comparable to twice daily application of clotrimazole 1% solution (1538). However, preliminary clinical research shows that lower concentrations of tea tree oil do not seem to be as effective. For example, there is some evidence that a tea tree oil 5% cream applied three times daily for 2 months has no beneficial effect (7032).
• Tinea pedis. Some clinical research suggests that topical tea tree oil 25% or 50% seems to be beneficial for tinea pedis, although it does not seem to work as well as standard treatments. Details: Topical application of tea tree oil 25% or 50% solution twice daily appears to produce both clinical improvement and a mycological cure in 48% to 50% of patients after 4 weeks of treatment, compared with 13% of those using placebo (10033). However, tea tree oil 25% or 50% concentrations don't appear to be as effective for mycological cure as clotrimazole or terbinafine (13713). Also, although topical application of a tea tree oil 10% cream seems comparable to tolnaftate 1% cream for relieving symptoms of tinea pedis, including scaling, inflammation, itching, and burning, the tea tree oil cream appears no more effective than placebo in producing a mycological cure (4031).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bacterial vaginosis. Although there is interest in using intravaginal tea tree oil for bacterial vaginosis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Blepharitis. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with seborrheic blepharitis shows that using a specific topical swab (TTO Thermal Swab, Jeomed Medicine and Health Production Company) containing tea tree oil and chamomile twice daily for 8 weeks improves blepharitis symptom scores, such as burning, itching, and dry eyes, when compared with using baby shampoo. Symptom improvements were maintained 4 weeks after treatment discontinuation (109944). A small open-label clinical trial in adults with mild-to-moderate anterior blepharitis shows that applying an eye gel containing tea tree oil 2%, hyaluronic acid, and other ingredients (Blephamed eye gel, Saya Teb Mana Co, Tehran, Iran) to the eyelid and roots of the eyelashes twice daily for 2 weeks improves symptoms of eyelid debris, but not eyelid erythema or edema, when compared with standard treatment including topical erythromycin ointment and fluorometholone eye drops(113000). It is unclear if this effect is due to tea tree oil, hyaluronic acid, or the combination.
• Cheilitis. Although there is interest in using topical tea tree oil for cheilitis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Contact dermatitis. Preliminary clinical research suggests that topical tea tree oil is beneficial for nickel-induced contact dermatitis. Details: Preliminary clinical research shows that undiluted or diluted tea tree oil for 3-5 days may reduce the area and redness of acute contact dermatitis reactions in people with nickel hypersensitivity (16337,19191). Other preliminary clinical research in individuals with nickel allergy shows that applying 60-120 mcL of tea tree oil 20% or 50% (Australian bodycare tea tree oil, Maxmedica AB) once, immediately prior to nickel exposure, reduces nickel-induced contact dermatitis by 41% when compared with no treatment (19191).
• Dandruff. It is unclear if topical tea tree oil is beneficial for dandruff in adults and adolescents. Details: Preliminary clinical research shows that a tea tree oil 5% shampoo, used for three minutes daily prior to rinsing for 4 weeks, reduces the total area and severity of scalp lesions, as well as the severity of dandruff, itchiness, and greasiness, by 23% to 28% in patients aged 14 years and older. However, it does not improve scalp scaliness (19178).
• Dental plaque. It is unclear if brushing or rinsing with tea tree oil is beneficial for dental plaque; the available evidence is conflicting. Details: Preliminary clinical research shows that brushing with a tea tree oil 2.5% gel twice daily for 8 weeks reduces papillary bleeding, but does not improve gingival health or plaque, in patients with plaque-induced gingivitis (19179). Other preliminary clinical research also shows that using tea tree oil mouthwash does not reduce plaque formation following a professional tooth cleaning (19180). However, a small preliminary clinical trial shows that using a mouthwash made from 3-4 drops of pure tea tree oil in water 2-3 times daily after brushing for 14 days is as effective as using a mouthwash containing chlorhexidine 0.12% twice daily for reducing plaque (105241). Some preliminary clinical research has also evaluated tea tree oil in combination with other ingredients. A combination of tea tree oil 1.5% and xylitol 10% (Tebodont) for 3 months reduces plaque formation on tooth surfaces when compared with pretreatment (19181). Other research shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil 0.2% to 0.3% each, for 30 seconds twice daily for 21 days, reduces plaque formation by 64% when compared to baseline (91446). It is not clear if the effects in these studies are due to tea tree oil, other ingredients, or the combinations.
• Dry eye. It is unclear if topical tea tree oil is beneficial for improving symptoms of dry eye due to cataract surgery or meibomian gland dysfunction. Details: Clinical research in patients with dry eye due to cataract surgery also using artificial tears and topical steroid drops shows that eyelid scrubbing with eye shampoo containing an undisclosed amount of tea tree oil for one month improves symptoms of dry eye, such as sensitivity, pain, and blurred vision, and reduces demodex counts, when compared with using shampoo without tea tree oil. There was no benefit of the tea tree oil on visual acuity (101998). Clinical research in patients with meibomian gland dysfunction shows that applying a tea tree oil 1% shampoo around the eye once daily for 3 months improves gland function scores and dry eye symptom scores when compared with Johnson's baby shampoo (109943).
• Furuncles (boils). Although there is interest in using topical tea tree oil for boils, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Gingivitis. It is unclear if brushing or rinsing with tea tree oil is beneficial for gingivitis; the available evidence is conflicting. Details: A small preliminary clinical trial shows that using a mouthwash comprised of 3-4 drops of pure tea tree oil in water 2-3 times daily after brushing for 14 days is as effective as using a mouthwash containing chlorhexidine 0.12% twice daily for reducing plaque and bleeding and improving gum health (105241). Other preliminary clinical research in patients with severe gingivitis shows that brushing with a tea tree oil 2.5% gel twice daily for 8 weeks reduces papillary bleeding when compared with baseline. However, the gel does not appear to improve plaque or the severity of plaque-induced gingivitis (19179). Combination products containing tea tree oil have also been investigated. Preliminary clinical research shows that rinsing with a specific product containing a combination of tea tree oil 1.5% and xylitol 10% (Tebodont) for 3 months reduces gum inflammation by 26% to 32% when compared with pretreatment (19181). Also, clinical research shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil 0.2% to 0.3% each, for 30 seconds twice daily for 21 days, reduces gum inflammation by 76% when compared to baseline (91446). It is not clear if the effects in these studies are due to tea tree oil, other ingredients, or the combinations.
• Halitosis. It is unclear if tea tree oil mouth rinses are beneficial for halitosis. Details: Preliminary clinical research in adults with halitosis shows that using a specific tea tree oil mouth rinse (100% Organic Tea Tree Oil, Dessert Essence) 10 mL twice daily for 7 days moderately improves halitosis severity scores and reduces salivary levels of Solobacterium moorei when compared with placebo. The improvements were similar to using chlorhexidine gluconate 0.2% mouth rinse (109941). Tea tree oil has also been studied as a combination treatment. One small clinical study suggests that applying an essential oil solution containing tea tree, peppermint, and lemon oils 0.125% as part of a single three-minute oral cleaning reduces the level of bad breath in patients from an intensive care unit when compared with baseline or benzydamine hydrochloride. 15 mL of the solution was applied to cotton sponges used to clean the teeth, tongue, and oral cavity (19177). Similarly, a small clinical trial in adults shows that cleaning the teeth, oral mucosa and tongue with gauze soaked in solution containing a tea tree oil, lemon and peppermint essential oil blend in a 1:1:0.2 ratio diluted with distilled water to 0.5% twice daily for 7 days improves halitosis when compared with gauze soaked with saline solution (112957). It is unclear if this effect is due to the tea tree oil, other ingredients, or the combination.
• Hemorrhoids. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children with hemorrhoids shows that application of a specific gel (Proctoial, BSD Pharma) containing tea tree oil, hyaluronic acid, and methylsulfonylmethane (MSM) daily for 14 days decreases symptoms of hemorrhoids, such as anal pain, defecation pain, irritation, inflammation, visible bleeding, and itching, when compared with placebo (19318).
• Herpes labialis (cold sores). It is unclear if topical tea tree oil is beneficial for herpes labialis. Details: One small clinical study in adults with cold sores shows that applying a tea tree oil 6% gel five times daily does not improve the rate of cold sore resolution when compared with a placebo gel (2035). However, this study may have been inadequately powered to detect a difference between groups.
• Hirsutism. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild idiopathic hirsutism shows that using a spray containing lavender and tea tree oils twice daily for 3 months on specific hirsutism-affected areas decreases hair diameter by 8% to 9% and total hirsutism score by 11% when compared with baseline. The spray provides lavender oil 48 mcg and tea tree oil 2 mcg per square cm of skin. These improvements were not observed in a placebo group (91448).
• Insect bite. Although there is interest in using topical tea tree oil for insect bites, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Lice. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: There is preliminary evidence that tea tree oil repels lice and reduces blood feeding (19187). When used in combination with lavender oil, tea tree oil has ovicidal effects on head lice and reduces the number of live lice. A pediculicide containing tea tree oil 10% weight per volume and lavender oil 1% weight per volume (NeutraLice Natural Lotion, Key Pharmaceuticals Pty Ltd) has been applied to the hair for 10 minutes, either as a single application or three times over 2 weeks, in children aged 4-12 years (19188,19189). It is unclear if any effects are due to tea tree oil, lavender, or the combination.
• Methicillin-resistant Staphylococcus aureus (MRSA). It is unclear if topical tea tree oil is beneficial for the prevention of MRSA colonization or the treatment of MRSA infection. Details: Preliminary clinical research shows that tea tree oil is not effective for preventing MRSA colonization. Using tea tree oil 5% body wash (Novabac 5% skin wash, Novasel Australia Pty Ltd.) is no more effective than a standard wash (Johnson's baby softwash, Johnson & Johnson) for preventing MRSA colonization in critically ill patients (91441). There is contradictory evidence on the effects of tea tree oil for the treatment of MRSA infection. In patients with MRSA-colonized wounds, use of a 3% water-miscible solution of tea tree oil during the wound cleansing routine for each dressing change does not improve MRSA clearance (19190). Also, in patients with MRSA colonization, tea tree oil given in various preparations along with standard treatment for 5 days does not appear to increase overall MRSA clearance when compared with standard treatment alone. These various preparations, which contain tea tree oil 5% or 10%, include a cream applied to the nostrils three times daily, a body wash used at least once daily, or a cream applied to lesions, ulcers, wounds, and axillae or groin areas once daily. Although these various preparations do not improve overall clearance, it seems that using a tea tree cream and body wash may be more effective for eradicating MRSA from specific sites such as wounds and superficial skin infections when compared with standard treatments alone (19163). Also, preliminary clinical research suggests that using tea tree oil 4% nasal ointment plus tea tree oil 5% body wash increases MRSA clearance when compared with a triclosan body wash and mupirocin 2% nasal ointment (19158,19159). Larger, high-quality studies are needed to confirm these results.
• Nipple Fissures. It is unclear if topical tea tree oil improves nipple-related complications of breastfeeding, such as nipple fissures and pain. Details: A small clinical study in breastfeeding adults in Turkey shows that applying either tea tree oil or coconut oil to the nipples immediately after breastfeeding on the 3rd, 7th and 10th day postpartum reduces the incidence of nipple fissures when compared with a control group receiving no treatment (113002).
• Ocular demodicosis. It is unclear if topical tea tree oil is beneficial for ocular demodicosis; available evidence is conflicting. Details: Small clinical studies suggest that tea tree oil can eradicate Demodex infestation in the eyelids and reduce associated symptoms such as corneal and conjunctival inflammation, ocular irritation, and vision loss. In adults, treatments have included weekly scrubs of the eyelid using tea tree oil 50% and daily scrubs of the eyelid with tea tree shampoo, as well as eyelid massages with tea tree ointment 5% to 10%, for up to 12 weeks (19182,19183,19184,19185,91445,105243). In children aged 2.5-11 years, weekly scrubs of the eyelid using tea tree oil 50% and daily eyelid massages with tea tree oil 5% ointment for 4-6 weeks has been used (19184). However, conflicting evidence exists. One meta-analysis of two randomized controlled trials shows that although patients using tea tree oil for 4-6 weeks were 68% more likely to have an eradication of mites, while another meta-analysis of three randomized controlled trials shows that the use of tea tree oil products does not reduce the number of Demodex mites or reported symptoms. Also, a single study shows that receiving intense pulsed light over 12 weeks is more effective than tea tree oil. The certainty of evidence for these endpoints is very low and the majority of available research has an unclear or high risk of bias (105243).
• Oropharyngeal candidiasis. It is unclear if rinsing the mouth with tea tree oil is beneficial for the prevention of oropharyngeal candidiasis in various populations. Details: One very small clinical study in adults with HIV/AIDS who are refractory to fluconazole shows that swishing and expelling tea tree oil solution 15 mL four times daily for 2-4 weeks seems to improve oral candidiasis when compared to baseline (4445). Another small clinical study in adults with terminal cancer shows that using tea tree oil, as part of an essential oil mixture containing geranium, peppermint, and lavender twice daily for one week improves subjective measures of oral comfort and objective measures of oral health status and reduces Candida albicans count when compared with saline solution (19192). However, in patients with dentures, adding 1 mL of tea tree oil to a standard 5 mL dose of Coe-Comfort tissue conditioner treatment for 12 days does not reduce inflammation or Candida albicans growth when compared with Coe-Comfort alone (19193).
• Otitis externa. Although there is interest in using tea tree oil in the ear for otitis externa, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Otitis media. Although there is interest in using tea tree oil in the ear for otitis media, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Pharyngitis. Although there is interest in gargling with tea tree oil for pharyngitis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Rosacea. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild to moderate rosacea shows that applying permethrin 2.5% gel containing an undisclosed amount of tea tree oil to the affected area for one hour twice daily for 12 weeks reduces demodex mite counts by about 13% more than placebo. Furthermore, symptoms such as papules, burning, and redness were improved by moderate amounts when compared with placebo (101999). The effect of tea tree oil alone is unknown.
• Scabies. Although there is interest in using topical tea tree oil for scabies, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Seborrheic dermatitis. Although there is interest in using topical tea tree oil for seborrheic dermatitis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Tinea corporis. Although there is interest in using topical tea tree oil for tinea corporis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Toothache. Although there is interest in rinsing the mouth with tea tree oil for toothache, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Vaccine reaction. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in adults shows that applying tea tree oil, in combination with inhaling aromatherapy with eucalyptus oil, immediately after a COVID-19 vaccination and every 2 waking hours over the next 48 hours reduces self-reported pain, swelling, and lump at the injection site, but not erythema, in the first 24 hours when compared with control. However, after 48 hours, only lump at the injection site was reduced compared to control (113141). It is unclear if these effects are due to tea tree oil, eucalyptus oil, or the combination. Additionally, the interpretation of these results is limited by the lack of a placebo in the control group.
• Vaginal candidiasis. Although there is interest in using intravaginal tea tree oil for vaginal candidiasis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Water warts. It is unclear if topical tea tree oil is beneficial for water warts in children. Details: Preliminary clinical research in children with a mean age of 6.3 years with water warts shows that a 4 mcL drop of an oil containing iodine plus Australian tea tree oil 75%, standardized to 40.1% terpinene-4-ol, applied twice daily for up to 30 days, increases lesion resolution when compared with tea tree oil or iodine alone (19194).
• Wound healing. Although there is interest in topical tea tree oil for wound healing, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose. More evidence is needed to rate tea tree oil for these uses.

(Read more about TEA TREE OIL)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if a topical thyme flower and leaf extract reduces wrinkles. Details: A small clinical trial in healthy females aged 40-60 years with wrinkles shows that applying a specific gel preparation (ThymLec 2%, PhytoPharmaTech) containing thyme flower and leaf 1-3% extract in lecithin on the face twice daily for 60 days reduces facial wrinkles when compared with inactive control gel, but not when compared with an active comparator gel containing propanediol, ornithine, phospholipids, and glycolipids (105909).
• Alopecia areata. Topical thyme 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 combination of the essential oils from thyme, rosemary, lavender, and cedarwood improves hair growth in up to 44% of patients after 7 months of treatment when compared with baseline (5177). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to thyme, other ingredients, or the combination.
• Bronchitis. Oral thyme has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some research has evaluated thyme in combination with cowslip. One observational study in adults and children has found that taking a specific product (Bronchipret) containing thyme and cowslip relieves symptoms of bronchitis and increases production of sputum (13557). A clinical study in patients with acute bronchitis shows that taking a similar combination extract (Bronchicum Tropfen) containing thyme and cowslip root 1 mL five times daily for 7-9 days seems to reduce severity and duration of coughing when compared with placebo (49219). Other thyme and cowslip preparations such as Bronchicum Elixir S and Bronchcium Tropfen seem to be similarly beneficial for bronchitis (49223). Thyme has also been studied in combination with other ingredients. A large clinical study in patients with acute bronchitis shows that taking a specific syrup (Bronchipret Saft, Bionorica AG) containing thyme and English ivy leaf 5.4 mL three times daily for 11 days reduces the frequency and duration of cough when compared with placebo (78152). Additionally, an observational study in children with acute bronchitis has found that taking this combination product in an age-specific dosing schema is associated with reduced bronchitis severity and coughing fits when compared to baseline (78181). However, due to the lack of a comparator group, it is unclear if these changes are due to the product or to the natural resolution of the condition.
• Colic. Although there is interest in using oral thyme for colic, there is insufficient reliable information about the clinical effects of thyme for this condition.
• Cough. Oral thyme has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large open-label, uncontrolled study in adults with acute cough due to an upper respiratory tract infection who purchased a specific syrup (Bronchipret drops, Bionorica AG) containing thyme and English ivy leaf extracts suggests that taking this product as 2.6 mL three times daily for at least 4 days may improve patient-reported bronchitis symptom severity, cough severity, and quality of life, with over 90% of patients reporting overall satisfaction and product tolerability (110401). However, due to the lack of a comparator group, it is unclear if these changes are due to the product or the natural resolution of the condition. Additionally, the validity of these findings is limited by poor study methodology.
• Common cold. Although there is interest in using oral thyme for the common cold, there is insufficient reliable information about the clinical effects of thyme for this condition.
• Dementia. It is unclear if aromatherapy with thyme oil is beneficial in patients with dementia. Details: One very small clinical study in patients with advanced dementia shows that attaching a pad containing thyme oil to the collar area of the shirt does not reduce agitation when compared with lavender oil or unscented grapeseed oil (12213).
• Developmental coordination disorder (DCD). Oral thyme oil has only been evaluated in combination with other oils; its effect when used alone is unclear. Details: One very small clinical study in children with DCD shows that taking thyme oil, in combination with evening primrose oil, fish oil, and vitamin E (Efalex, Efamol Ltd.), seems to modestly improve movement disorders when compared with baseline (5708). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to thyme, other ingredients, or the combination.
• Dyspepsia. Although there is interest in using oral thyme for dyspepsia, there is insufficient reliable information about the clinical effects of thyme for this condition.
• Dysmenorrhea. It is unclear if drinking thyme tea is beneficial for the prevention of dysmenorrhea. Details: One small observational study in adolescents living in Ethiopia has found that drinking thyme tea is associated with a lower occurrence of primary dysmenorrhea when compared with those who did not drink thyme tea (105910).
• Halitosis. It is unclear whether oral thyme is beneficial for halitosis. Details: One small retrospective study in adults with gingival halitosis who received periodontal treatment and oral hygiene instructions suggests that drinking thyme tea twice daily for 1 week is associated with a reduction in volatile sulfur compounds, which is a marker for halitosis, when compared with chlorhexidine or oral hygiene alone (111716). However, the interpretation of this finding is limited by the lack of thyme dosing information and the narrow focus on intraoral halitosis, excluding most extraoral halitosis-associated conditions.
• Laryngitis. Although there is interest in using oral and topical thyme for laryngitis, there is insufficient reliable information about the clinical effects of thyme for this condition.
• Oral mucositis. Although there is interest in using oral and topical thyme for oral mucositis, there is insufficient reliable information about the clinical effects of thyme for this condition.
• Tonsillitis. Although there is interest in using oral and topical thyme for tonsillitis, there is insufficient reliable information about the clinical effects of thyme for this condition. More evidence is needed to rate thyme for these uses.

(Read more about THYME)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.

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

(Read more about BAIKAL SKULLCAP)

LIKELY SAFE ...when the fruit (nut) is consumed in amounts normally found in food.

POSSIBLY UNSAFE ...when the bark is used orally or topically, due to its juglone content (2). When applied topically, juglone-containing bark can cause skin irritation. When used orally on a daily basis, the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12). There is insufficient reliable information available about the safety of the leaf or hull when used orally as a medicine or when applied topically.

PREGNANCY AND LACTATION: LIKELY SAFE
when the fruit (nut) is consumed in amounts normally found in foods.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the bark is used orally or topically (12); avoid using. There is insufficient reliable information available about the safety of black walnut leaf or hull when used orally in medicinal amounts during pregnancy or lactation; avoid using.

(Read more about BLACK WALNUT)

LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).

POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).

CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).

PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods. Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.

PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes. Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).

LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods. There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.

(Read more about GINGER)

There is insufficient reliable information available about the safety of goldthread when used in adults in medicinal amounts.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of goldthread can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589). Preliminary evidence suggests that maternal intake of goldthread during the first trimester increases the risk of congenital malformations of the central nervous system (15129).

LACTATION: LIKELY UNSAFE
when used orally. Berberine and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about GOLDTHREAD)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Oregano leaf and oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of oregano when used orally in amounts greater than those found in food. There is also insufficient reliable information available about the safety of oregano when used topically. Oregano oil in concentrations of greater than 1% may be irritating when applied to mucous membranes (67348,88188).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Oregano is thought to have abortifacient and emmenagogue effects (19,7122,19104).

LACTATION:
There is insufficient reliable information available about the safety of oregano when used in medicinal amounts; avoid amounts greater than those found in food.

(Read more about OREGANO)

POSSIBLY UNSAFE ...when used orally. The safety of pau d'arco in typical doses is unclear. Serious toxicities have been found with high doses of the lapachol constituent (91939). In patients with cancer, doses of lapachol above 1.5 grams daily were associated with significant gastrointestinal toxicities and an increased risk of bleeding (91939). However, in patients with dysmenorrhea, doses of pau d'arco 1050 mg plus rutin 75 mg daily for up to 8 weeks did not lead to serious adverse effects (114012). There is insufficient reliable information available about the safety of pau d'arco when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally in typical doses. Animal studies have found that lapachol, a constituent of pau d'arco, has teratogenic and abortifacient effects (68314,68315); avoid using. There is insufficient reliable information available about the safety of pau d'arco when used topically in pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PAU D'ARCO)

LIKELY SAFE ...when used orally in amounts commonly used in foods. Red clover has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912,10372).

POSSIBLY SAFE ...when used orally and appropriately in supplemental amounts. Red clover extracts containing up to 80 mg isoflavones have been used with apparent safety in clinical studies lasting up to 2 years (3375,6127,8925,11089,11091,17091,19540,19556,91524,102901,102840). ...when used topically and appropriately. Red clover extracts have been used topically with apparent safety for up to 4 weeks (102839).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts. Red clover has estrogenic activity (19555); avoid using. There is insufficient reliable information available about the safety of the topical use of red clover during pregnancy and lactation.

(Read more about RED CLOVER)

POSSIBLY SAFE ...when used topically and appropriately for up to 12 weeks (1538,4028,4031,4445,7032,8573,19157,19158,19159,19163)(19318,109944,109945,113000).

LIKELY UNSAFE ...when used orally. Tea tree oil has been reported to cause significant toxicity when used orally (4028,10011,19166,19168,19170,109947).

CHILDREN: POSSIBLY SAFE
when used topically and appropriately. Tea tree oil 5% preparations have been used with apparent safety in children (8573).

CHILDREN: LIKELY UNSAFE
when used orally. Ingestion of tea tree oil can be toxic (4030,10010,10013,11799).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used topically and appropriately (512).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Ingestion of tea tree oil can be toxic (515).

(Read more about TEA TREE OIL)

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

POSSIBLY SAFE ...when thyme is used orally and appropriately in supplemental amounts. Orally, thyme, in combination with other herbs, has been used safely for up to 23 days (13557,49219,49223,78133). ...when diluted thyme oil is used topically, short-term. Diluted thyme oil has been used with apparent safety for up to 7 months (5177). There is insufficient reliable information available about the safety of thyme oil when used orally or when inhaled.

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

CHILDREN: POSSIBLY SAFE
when thyme is used orally in medicinal amounts in combination with English ivy. Thyme has been used with apparent safety in combination with English ivy for up to 10 days (78181). There is insufficient reliable information available about the safety of thyme oil when used orally or topically in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts commonly found in foods. Thyme has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of thyme when used in medicinal amounts during pregnancy and breast-feeding; avoid using.

(Read more about THYME)

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.  Details Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.  Details Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.  Details Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.  Details In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.  Details In vitro evidence suggests that constituents of Baikal skullcap inhibit the activity of CYP1A2 (33346,33484). This effect 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, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.  Details In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.  Details In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.  Details Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.  Details Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.  Details In vitro and animal research suggests that baicalein, oroxylin A, and wogonin, constituents of Baikal skullcap, can inhibit P-glycoprotein (33372,33395,33440,33462). This effect has not been reported in humans.

(Read more about BAIKAL SKULLCAP)

(Read more about BLACK WALNUT)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.  Details Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels (12636,20402,20403,20404,20405,89895,89896,107898).

CALCIUM CHANNEL BLOCKERS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.  Details Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.  Details In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP1A2 substrates.  Details In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP2B6 substrates.  Details In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase the levels of CYP2C9 substrates.  Details In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, 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 = D Ginger might increase or decrease the levels of CYP3A4 substrates.  Details In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644). Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase levels of losartan and the risk of hypotension.  Details In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

METRONIDAZOLE (Flagyl) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ginger might increase levels of metronidazole.  Details In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.  Details Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.  Details In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).

PHENPROCOUMON (Marcoumar, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Ginger might increase the risk of bleeding with phenprocoumon.  Details Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Ginger might increase the risk of bleeding with warfarin.  Details Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.

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(Read more about GOLDTHREAD)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aristolochic acid isolated from oregano leaves has antithrombin activity (67164). It has also been reported that oregano oil inhibits arachidonic acid-induced, and ADP-induced, platelet aggregation (49445).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk for hypoglycemia when taken with antidiabetes drugs.  Details In vitro and animal research shows that oregano extracts might lower blood glucose levels (67191,67204,110122).

(Read more about OREGANO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, pau d'arco might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that pau d'arco reduces platelet aggregation and may interfere with vitamin K (18057,68319). One clinical study shows that taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily increases the risk of bleeding (91939). The effects of whole pau d'arco or pau d'arco extract in humans are unclear.

(Read more about PAU D'ARCO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.  Details In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low (17091,19557,19558,19559). Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years (17091,91524).

CAFFEINE Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, soy might reduce the clearance of caffeine; however, a small clinical study found no effect.  Details Red clover contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females (23582). However, this effect does not seem to occur with the lower amounts of genistein found in red clover. A clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine (105693).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.  Details In vitro evidence shows that red clover inhibits CYP1A2 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate (105693).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details In vitro evidence suggests that red clover weakly inhibits CYP2C19 (12479). This interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.  Details In vitro evidence suggests that red clover might inhibit CYP2C9 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate (105693).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.  Details In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes (6450,12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate (105693).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.  Details Red clover contains phytoestrogens which might have estrogenic activity in some people. Theoretically, red clover might compete for estrogen receptors and interfere with estrogen-containing drug therapy (4743,19560,19729).

METHOTREXATE (Trexall, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, red clover might increase the risk of methotrexate toxicity.  Details In a case report, a 52-year-old female receiving weekly methotrexate injections for psoriasis developed symptoms of methotrexate toxicity, including severe vomiting and epigastric pain, after three days of taking red clover 430 mg daily. Toxicity resolved after red clover was discontinued. However, no liver function tests or methotrexate levels were reported (91522).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, the phytoestrogens in red clover might interfere with tamoxifen.  Details In vitro and animal research suggests that genistein, a constituent of red clover, might antagonize the antitumor effects of tamoxifen (8192). However, there is some evidence from an animal study that red clover does not reduce the efficacy of tamoxifen (102901). Until more is known, tell patients taking tamoxifen to avoid red clover.

(Read more about RED CLOVER)

(Read more about TEA TREE OIL)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of anticholinergic drugs and thyme essential oil might reduce the effects of anticholinergic drugs.  Details In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, thyme leaf extract might have additive effects with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that thyme leaf extract has antiplatelet effects (13457,18335,49445). However, this effect has not been observed in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of cholinergic drugs and thyme essential oil might cause additive cholinergic effects.  Details In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, thyme might competitively inhibit the effects of estrogen replacement therapy.  Details In vitro research shows that thyme has estrogen receptor-binding activity and phytoestrogen content (3701). However, this effect has not been observed in humans.

(Read more about THYME)

General ...Orally, Baikal skullcap seems to be well-tolerated. There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.

Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).

Dermatologic ...Orally, taking Baikal skullcap may cause erythema and pruritus (105867). Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).

Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).

Hepatic ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage. There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).

Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.

Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).

(Read more about BAIKAL SKULLCAP)

General ...Orally, black walnut fruit (nut) is well tolerated. However, the leaf, bark, and hull of black walnut contain high quantities of tannins, which may cause adverse effects when used orally or topically.
Most Common Adverse Effects:
Orally: The leaf, bark, and hull can cause gastrointestinal upset.
Topically: Hull preparations may cause a temporary yellow or brown discoloration at the site of application. The leaf, bark, and hull can cause skin irritation.
Serious Adverse Effects (Rare):
Orally: The bark may increase the risk for tongue cancer or lip leukoplakia when used long-term.
All routes of administration: Allergic reactions, including anaphylaxis.

Dermatologic ...Topically, black walnut leaf, bark, or hull may have an irritating effect on the skin due to tannin content. Black walnut hull preparations might cause a temporary yellow or brown discoloration of the skin at the site of application (12).

Gastrointestinal ...Orally, black walnut leaf, bark, or hull may cause gastrointestinal upset due to tannin content (12). Also, daily use of the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12).

Hepatic ...Orally, black walnut leaf, bark, or hull may cause liver damage if taken for extended periods of time due to tannin content (12).

Immunologic ...Tree nuts, which include black walnuts, can cause allergic reactions in sensitive individuals. Due to the prevalence of this allergy in the general population, tree nuts are classified as a major food allergen in the United States (105410).

Renal ...Orally, black walnut leaf, bark, or hull may cause kidney damage if taken for extended periods of time due to tannin content (12).

(Read more about BLACK WALNUT)

General ...Orally, ginger is generally well tolerated. However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).

Dermatologic ...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).

Gastrointestinal ...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076). Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).

Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).

Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).

Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).

(Read more about GINGER)

General ...No adverse effects have been reported in adults. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, oregano is well tolerated when used in amounts typically found in foods. There is currently a limited amount of information available about the safety of oregano when used in larger amounts as medicine.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Systemic allergic reactions, including anaphylaxis, in sensitive individuals.

Dermatologic ...Oregano has been reported to cause allergic contact dermatitis (46902). Topically, oregano oil in concentrations of greater than 1% has been reported to cause irritation when applied to mucous membranes (67348,88188).

Gastrointestinal ...Orally, large amounts of oregano can cause gastrointestinal upset. Concentrated, non-emulsified oil of oregano can cause localized irritation of the gastrointestinal tract (6878).

Immunologic ...Systemic allergic reactions have been reported with oregano. A 45-year-old male developed pruritus, respiratory difficulty, hypotension, swelling of the lips and tongue, and facial edema after ingesting pizza seasoned with oregano. He had 2 similar episodes after ingesting foods seasoned with thyme, another member of the Lamiaceae family. He did not react to similar foods without the seasoning, and he had positive skin tests to plants of the Lamiaceae family (3705).

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General ...A thorough evaluation of safety outcomes with pau d'arco has not been conducted. However, taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily is regarded as unsafe.

Gastrointestinal ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause severe nausea, vomiting, and diarrhea (91939).

Hematologic ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause anemia and increased risk of bleeding (91939).

Immunologic ...Occupational exposure to sawdust from the pau d'arco tree and related species may cause asthma and dermatitis. The fresh sawdust can produce erythema and papules which progress to a severe weeping and crusting dermatitis (92184).

Neurologic/CNS ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause dizziness (91939).

(Read more about PAU D'ARCO)

General ...Orally and topically, red clover seems to be well tolerated.
Most Common Adverse Effects:
Orally: Myalgia, nausea, and vaginal spotting.

Dermatologic ...Orally, a specific red clover isoflavone product (Promensil) has been associated with mild cases of psoriasis and thrush, although a direct causal link has not been established (9552).

Gastrointestinal ...Orally, red clover has been reported to cause nausea (8194).

Genitourinary ...In human research, 80 mg, but not 40 mg, of a specific red clover isoflavone product (Promensil) increased the duration of menstrual cycles in patients with mastalgia (9552). Red clover has also been reported to cause vaginal spotting (8194).

Hematologic ...In one case report, a 53-year-old female had a spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero. It is not clear if this was due to red clover, another ingredient, the combination of ingredients, or other factors (70419). In another case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis 3 days after taking a combination phytoestrogen product containing red clover 250 mg, wild yam 276 mg, dong quai 100 mg, and black cohosh 250 mg (13155). It is unclear if red clover contributed to this event.

Musculoskeletal ...Orally, red clover has been reported to cause myalgia (8194).

Neurologic/CNS ...Orally, a specific red clover isoflavone product (Medoflavon) has been associated with headache, although with a similar frequency to placebo (19545).

Oncologic ...Due to potential estrogenic effects of red clover isoflavones, there has been some concern that red clover might increase the risk of estrogen-sensitive cancers such as breast cancer or uterine cancer. A meta-analysis of 8 clinical trials suggests that increased intake of red clover- and soy-derived isoflavones may modestly increase mammographic breast density in premenopausal, but not postmenopausal, adults when compared with placebo. However, in a sub-group analysis assessing only isolated red clover isoflavones, there was no change in breast density (70428). Furthermore, a 2015 review by the European Food Safety Authority (EFSA) reported no increase in risk of breast cancer in females taking isoflavone-containing supplements (91725). Similarly, no effect was found on endometrial thickness and histopathological changes in the uterus after up to 36 months of supplementation with 40-120 mg daily of isoflavones from red clover extract (91725).

(Read more about RED CLOVER)

General ...Orally, tea tree oil can cause significant toxicity and should not be used. Topically, tea tree oil is generally well tolerated.
Most Common Adverse Effects:
Topically: Allergic reactions, burning, dryness, irritation, pruritus, redness, and stinging.

Dermatologic ...Ingestion of as little as 2. 5 mL of tea tree oil can cause petechial body rash. It can take up to a week for symptoms to resolve (10011).
Topically, tea tree oil is usually well tolerated. However, it can cause local irritation and inflammation in some patients. Treatment with topical corticosteroids may be needed in some cases (10033,13713,19176,91442,91443,109946,109947). Severe allergic contact dermatitis has also been reported (109947,109948,112999). Tea tree oil can cause skin dryness, and less frequently pruritus, stinging, burning, and redness in patients with acne (8573,91447,109947). It may also cause mild oral mucosal burning (4445).

Endocrine ...In one case, a prepubertal male who used a hair styling gel and shampoo product containing both tea tree oil and lavender oil developed gynecomastia. The gynecomastia resolved when the products were discontinued. It is possible that this effect was due to lavender oil, which has been associated with other cases of gynecomastia in prepubertal males (15254).

Gastrointestinal ...Orally, tea tree oil can cause eucalyptus-like odor on the breath. In young children, ingestion of 10 mL or less of tea tree oil can cause this effect (4030,10010,11799).

Hematologic ...Orally, as little as 2. 5 mL of tea tree oil can cause neutrophil leukocytosis. It can take up to a week for symptoms to resolve (10011).

Immunologic ...Orally, tea tree oil can cause or worsen systemic contact dermatitis (4028,19168). Topically, tea tree oil is usually well tolerated. However, it can cause allergic contact eczema and allergic contact dermatitis in some children and adults. Corticosteroids may be needed in some cases (658,4027,4028,4029,10015,10029,10030,10031,10032,91443)(105242,105244,109947,109948,112999).
In young children, ingestion of 10 mL or less of tea tree oil can cause significant ataxia, drowsiness, disorientation, and coma (4030,10010,11799).

Neurologic/CNS ...Orally, tea tree oil can cause ataxia and CNS depression (109947).

Ocular/Otic ...There is some concern that topical use of tea tree oil in the middle ear for treatment of ear infections might cause ototoxicity. There is preliminary evidence from animal research that preparations of pure tea tree oil can cause ototoxicity and impaired hearing. However, so far there are no reports of ototoxicity in humans. Until more is known, tell patients to avoid pure or highly concentrated tea tree oil preparations. Concentrations of 2% seem less likely to have this effect (7025).

Pulmonary/Respiratory ...Orally, tea tree oil can cause dyspnea and pneumonitis (109947).

(Read more about TEA TREE OIL)

General ...Orally, thyme is well tolerated when used in food and seems to be well tolerated when used medicinally. Topically, thyme seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic reactions, diarrhea, dizziness, headache, heartburn, nausea, or vomiting.
Topically: Contact dermatitis and skin irritation.

Dermatologic ...Topically, thyme, thyme oil, or the constituent thymol can cause contact dermatitis and skin irritation (13463,78252,78362,78384,77982,78154,78310,78313,78384). In one study of 100 patients with contact allergies, 5% were attributed to thyme oil as an allergen contained in wound dressings (78362). Toothpastes containing thymol have been associated with cheilitis and glossitis (13463).

Gastrointestinal ...Orally, thyme and thyme oil may cause heartburn, nausea, vomiting, stomach upset, or diarrhea (13557,94033). In a clinical study, two patients using extracts of thyme herb and ivy leaves experienced temporary stomach ache and mild nausea (78181).
Intravaginally, cream containing thyme and garlic has been associated with reports of nausea and vomiting in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.

Genitourinary ...Intravaginally, cream containing thyme and garlic has been associated with reports of vaginal dryness and vaginal irritation in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.

Immunologic ...Orally, thyme can cause allergic reactions; however, this is uncommon (13463). Allergic reactions to thyme might be more common in people who are also allergic to oregano and other Lamiaceae species (3808).

Neurologic/CNS ...Orally, thyme may case headache or dizziness (94033).

Pulmonary/Respiratory ...By inhalation, occupational exposure to thyme dust can cause acute airway obstruction (783,13463,13464,77982,78098).

(Read more about THYME)