Reishi Extract by Wild Rose

POSSIBLY EFFECTIVE

• Common cold. Taking echinacea orally while still healthy may help prevent the common cold, but the benefit is probably modest. Echinacea does not seem to have a significant benefit for treating colds that have already developed. Details: Three meta-analyses show a 10% to 58% reduction in the risk of developing a cold when taking various forms of echinacea (17520,17522,95652). A large clinical study shows that adults who use a specific echinacea extract (Echinaforce, A. Vogel Bioforce AG) 0.9 mL three times daily (2400 mg echinacea daily) for 4 months, with an increase to 0.9 mL five times daily (4000 mg echinacea daily) at the first sign of a cold, have 59% fewer cold episodes and 26% fewer days with cold symptoms than those taking placebo (18225). Many smaller studies have shown a non-significant trend toward a prophylactic benefit, but they were likely underpowered to detect a statistically significant difference (3282,6386,17521,95652). Research in adults who are deliberately infected with cold viruses shows that taking echinacea products either does not reduce the incidence of colds, or has a limited effect which is not statistically significant. Products used include E. angustifolia root extract 300 mg three times daily for 7 days before and 5 days after experimental infection (13419), an alcoholic extract of E. purpurea above-ground parts (EchinaGuard, Madaus AG) 2.5 mL three times daily for 7 days before and 7 days after experimental infection (12354), or echinacea 300 mg three times daily for 14 days before and 5 days after experimental infection (8228). These studies are small and have methodological problems. Some small clinical studies have suggested that taking E. purpurea extracts as a tincture or tea to treat the common cold modestly reduces symptom severity and reduces cold duration by a couple of days (6384,10320,10802,12355,14419,20062,111530). Specific products used in these studies include Echinilin by Inovobiologic Inc., and Echinacin and EchinaGuard by Madaus AG (10320,10802,12355,20062). In contrast, higher quality clinical research shows that taking E. purpurea alone or with E. angustifolia does not reduce duration or severity of cold symptoms when compared with placebo (10800,11970,17519,20059). Echinacea has also been evaluated in children. Preliminary clinical research in healthy children 4-12 years old shows that taking a specific E. purpurea product (Echinaforce Junior, A. Vogel) 400 mg three times daily for 4 months reduces the occurrence of cold symptoms, respiratory complications (such as pneumonia and otitis media), and antibiotic prescriptions by 30%, 52%, and 62%, respectively, when compared with vitamin C 50 mg three times daily. Taking echinacea also reduces the average duration of symptoms during respiratory illness by an average of 1.4 days when compared with vitamin C (105719). However, other clinical research in children has found no benefit with a specific E. purpurea product (Echinacin, Madaus AG) (4989,95653).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. It is unclear if oral echinacea reduces anxiety. Details: Preliminary clinical research shows that taking a specific E. angustifolia extract (ExtractumPharma ZRT) 40 mg once or twice daily for 7 days reduces anxiety scores on the State-Trait Anxiety Inventory scale when compared with placebo (20064,103233). This extract seems to be more effective in patients with high baseline anxiety scores (103233). A lower dose of 20 mg daily appears to be ineffective (20064). Conversely, a small clinical study in physically healthy adults with mild to moderate anxiety shows that taking the same E. angustifolia extract at doses of 20 or 40 mg twice daily for 6 weeks does not reduce anxiety when compared with placebo (106626).
• Athletic performance. It is unclear if oral echinacea improves athletic performance. Details: Preliminary clinical research in healthy, recreationally active males shows that taking echinacea (Puritan's Pride) 2 grams four times daily for 28 days increases serum erythropoietin levels and maximal oxygen consumption (VO2max) during exercise tests (20066). However, two small clinical studies in endurance trained athletes and in non-athletes with high aerobic fitness show that taking E. purpurea 8 or 16 grams once daily for 35 days in combination with other ingredients (Biomedical Research Lab), or taking E. purpurea (Puritan's Pride) 8 grams daily for 42 days, has no effect on erythropoietin levels, VO2max, or aerobic capacity (95651,101593). A meta-analysis of these and other small clinical trials in trained and recreational athletes shows that taking echinacea 8 grams orally daily for 28-42 days does not improve VO2max, hemoglobin, or erythropoietin levels when compared with placebo (114569). However, this analysis may have been inadequately powered to detect a difference between groups.
• Atopic dermatitis (eczema). Some evidence shows that an echinacea cream may be effective in mild disease, but it has not been compared to conventional treatments such as corticosteroids. Details: Preliminary clinical research in patients with mild atopic dermatitis shows that applying a cream containing echinacea (Linola Plus Cream, Dr. August Wolff GmbH & Co) 2-3 times daily for 12 weeks reduces symptoms such as erythema, edema, pruritus, and dryness when compared with a cream containing birch bark extract (Imlan Crème Pur, Birken AG). However, the echinacea product was no different to the comparator cream at the 4- and 8-week assessments, indicating that it might take up to 12 weeks to show benefit (97499).
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral echinacea for ADHD, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Burns. Although there has been interest in using topical echinacea for burns, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral echinacea for CFS, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral echinacea is beneficial for preventing or treating COVID-19. Details: A moderate-size open-label clinical study tested the effects of echinacea to prevent or treat respiratory viruses. This study of otherwise healthy adults in Bulgaria shows that taking echinacea extract (Echinaforce, A. Vogel AG) 2400 mg daily for cycles of 2, 2, and 1 months, with a 1-week break between each cycle, does not reduce symptomatic respiratory tract infections, including SARS-CoV-2, or respiratory virus detection overall when compared with usual care. However, echinacea extract does reduce the risk of a positive test for coronaviruses or SARS-CoV-2 by 48% and 63%, respectively. In patients who develop a symptomatic respiratory tract infection, this study also shows that taking the same echinacea extract 4000 mg daily for up to 10 days speeds viral clearance compared with usual care when all virus types were analyzed; however, clearance of SARS-CoV-2 was not improved. Echinacea may also reduce the number of days with a fever, but not other symptoms (111174). The validity of this study is limited by lack of blinding. Further, most patients were unvaccinated against COVID-19; it is unclear whether these results can be extrapolated to vaccinated patients. Echinacea has also been studied for long COVID. A moderate-size clinical trial in adults with recent COVID -19 infection shows that taking a combination product containing echinacea 30 mg, rose hips, zinc, and other ingredients orally daily for 2 months moderately improves fatigue scores when compared with placebo (114570).
• Genital herpes. It is unclear if oral echinacea is beneficial for genital herpes in patients with herpes simplex virus (HSV) type 1 or 2. Details: Some clinical research shows that a specific E. purpurea extract (Echinaforce, A. Vogel Bioforce AG) 800 mg orally twice daily for 6 months does not seem to prevent or reduce the frequency or duration of recurrent genital herpes in patients with herpes simplex virus (HSV) type 1 or 2 (7087).
• Gingivitis. Echinacea, in a mouth rinse or periodontal patch, has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a mouth rinse containing echinacea, gotu kola, and elderberry (HM-302, Izun Pharmaceuticals) 15 mL three times daily for 14 days might prevent worsening of gingivitis when compared with a placebo rinse, but it produces only minimal improvement in symptoms (20069). Applying a periodontal patch containing echinacea, gotu kola, and elderberry (PerioPatch, Izun Pharmaceuticals) either as a single dose, or three times daily for 1 day then once daily for 2 days seems to reduce some measures of inflammation and gingivitis at some time points, but effects lack consistency (20068,20070).
• Herpes labialis (cold sores). Although there has been interest in using topical echinacea for herpes labialis, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• HIV/AIDS. Although there has been interest in using oral echinacea for HIV/AIDS, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Human papillomavirus (HPV). Oral echinacea has only been studied in combination with other ingredients; its benefit when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product containing echinacea, andrographis, grapefruit, papaya, pau d'arco, and cat's claw (Immune Act, Erba Vita SpA) three tablets daily for one month reduces the recurrence of anal condylomata in patients following surgical removal. After one month, the recurrence rate was about 4% in the echinacea group compared with 18% in the control group; after 6 months the recurrence rates were about 7% and 27%, respectively (20073). However, poor study methodology limits the validity of these findings.
• Influenza. Limited data suggest that oral echinacea may improve the response to influenza vaccine, and that a combination product containing echinacea may improve rates of recovery from influenza. Details: Preliminary clinical research shows that a taking a specific echinacea product (Monoselect Echinacea, PharmExtracta) 200 mg orally daily for 15 days, then 100 mg daily for 15 days, followed by 100 mg every other day for 60 days, might improve the response to influenza vaccine in people with chronic bronchitis or asthma (18226). Higher quality research is needed to confirm these results. Taking a specific combination product (Echinaforce Hot Drink, A. Vogel Bioforce AG), containing elderberry juice and extracts of E. purpurea above-ground parts and roots, 5 mL five times daily for 3 days, then three times daily for 7 days, improves rates of recovery and influenza-related respiratory complications similarly to oseltamivir 75 mg twice daily for 5 days (95650). However, due to the lack of a placebo group, it is unclear if both treatments were beneficial or if the outcomes represent the natural progression of influenza.
• Insect bite. It is unclear if topical homeopathy with a gel containing echinacea is beneficial for insect bite treatment. Oral echinacea has not been evaluated for this use. Details: Preliminary clinical research shows that using a homeopathic after-bite gel, containing echinacea, marsh Labrador tea, and stinging nettle, on affected areas does not reduce erythema or itching after a mosquito bite when compared with placebo (89235).
• Lichen planus. It is unclear if oral echinacea is beneficial for patients with this condition. Details: A small clinical study in adults with erosive oral lichen planus in Iran shows that taking a specific echinacea extract tablet (Immustim, Goldaru Corp.) 114 mg three times daily for 35 days decreases pain scores, number of lesions, and symptom severity when compared with placebo. However, all patients also used a mouthwash containing betamethasone, diphenhydramine, nystatin, and aluminum-magnesium suspension three times daily (111173).
• Malaria. Although there has been interest in using oral echinacea for malaria, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Migraine headache. Although there has been interest in using oral echinacea for migraine headache, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Otitis media. Oral echinacea does not seem to reduce the rate of recurrence of otitis media in young children, and may actually increase it. Details: Preliminary clinical research shows that taking a specific liquid extract of echinacea fresh roots and dried mature seeds, 0.5 mL three times daily for 3 days at the first sign of a common cold, followed by 0.25 mL three times daily for 7 days, does not prevent otitis media in children 1-5 years of age with a history of recurrent otitis media. In fact, the risk of an episode of otitis media during the 6 month follow-up seemed to increase by 59% in those taking echinacea when compared with placebo (20063).
• Psoriasis. Although there has been interest in using topical echinacea for psoriasis, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Respiratory tract infections. It is unclear if oral echinacea is beneficial for preventing or treating respiratory tract infections. Details: A large clinical study in adults with respiratory tract infections shows that using echinacea spray or taking echinacea lozenges 16,800 mg daily during days 1-3 and 2240-3360 mg daily afterward for up to 10 days does not improve time to recovery, symptom relief, or number of sick days when compared with echinacea tablets or drops at a prophylactic dose of 2400 mg daily for 10 days. However, the higher dose from days 1-3 is associated with faster viral clearance than the prophylactic dose (111540). The validity of these effects is limited by insufficient blinding and a lack of a placebo group. Additionally, echinacea has been studied for prevention of respiratory tract infections. A meta-analysis of many clinical trials shows that taking echinacea up to 16,800 mg daily, alone or in combination with other products, for up to 17 weeks reduces the risk of respiratory infection and antibiotic prescriptions when compared with control (114568). The validity of this study is limited by heterogenous methods between clinical trials, including population, dose, and outcome definitions and measurements.
• Rheumatoid arthritis (RA). Although there has been interest in using oral echinacea for RA, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Tonsillitis. Oral echinacea has been used with azithromycin to reduce relapses of recurrent tonsillitis in children. A throat spray containing echinacea has also been evaluated for tonsillitis-associated sore throat. It is unclear if echinacea is beneficial for either purpose. Details: Preliminary clinical research in children with recurrent tonsillitis shows that adding echinacea suspension, 250 mg root powder per 5 mL, orally 3 times daily for 10 consecutive days per month for 6 months, to azithromycin 10 mg/kg/day for 6 consecutive days per month for 6 months reduces the number of tonsillitis attacks when compared with azithromycin alone (104127). However, the study was not blinded and the number of tonsillitis episodes in both groups was very low. Other preliminary clinical research shows that applying a throat spray containing sage and echinacea whole plant extract every 2 hours up to 10 times daily for up to 5 consecutive days is as effective as a chlorhexidine-lidocaine spray in patients with sore throat due to acute pharyngitis or tonsillitis (20077).
• Tonsillopharyngitis. Oral echinacea has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized study in patients aged 12-75 years with acute tonsillopharyngitis shows that taking lozenges containing echinacea extract 800 mg and sage extract 5 times daily for 4 days reduces throat pain and tonsillopharyngitis symptoms when compared to baseline, both acutely within 90 minutes and after 4 days of treatment (111530). The validity of these effects is limited by a lack of a comparator group. It is unclear if these effects are due to echinacea, sage, or the combination.
• Upper respiratory tract infection (URTI). It is unclear if oral echinacea is beneficial for preventing or treating URTIs. Details: A moderate-size open-label clinical study tested the effects of echinacea to prevent or treat respiratory viruses. This study of otherwise healthy adults in Bulgaria shows that taking echinacea extract (Echinaforce, A. Vogel AG) 2400 mg daily for cycles of 2, 2, and 1 months, with a 1-week break between each cycle, does not reduce symptomatic respiratory tract infections, including SARS-CoV-2, or respiratory virus detection overall when compared with usual care. However, echinacea extract does reduce the risk of a positive test for coronaviruses or SARS-CoV-2 by 48% and 63%, respectively. In patients who develop a symptomatic respiratory tract infection, this study also shows that taking the same echinacea extract 4000 mg daily for up to 10 days speeds viral clearance compared with usual care when all virus types were analyzed; however, clearance of SARS-CoV-2 was not improved. Echinacea may also reduce the number of days with a fever, but not other symptoms (111174). The validity of this study is limited by lack of blinding. Further, most patients were unvaccinated against COVID-19; it is unclear whether these results can be extrapolated to vaccinated patients. Another large study in adults with URTIs shows that taking a combination product containing echinacea 1100-2200 mg, zinc, and vitamin C (EZC Pak) daily for 5 days reduces time to recovery by 1.4 days but does not reduce symptom severity when compared with placebo (111512). The validity of these effects is severely limited by multiple instances of selection bias. Additionally, it is unclear if these effects are due to echinacea, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there has been interest in using oral echinacea for UTIs, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Vaginal candidiasis. Although there has been interest in using oral echinacea for vaginal candidiasis, there is insufficient reliable information about the clinical effects of echinacea for this purpose.
• Warts. It is unclear if oral echinacea is beneficial for warts when used alone or in combination with other ingredients. Details: Preliminary clinical research shows that taking echinacea 600 mg orally once daily for up to 3 months does not clear common, plantar, or plain cutaneous warts any more effectively than placebo (20080). Other preliminary clinical research shows that taking an oral supplement containing echinacea with methionine, zinc, probiotics, antioxidants and immunostimulants for 6 months, in addition to using conventional topical therapy to treat cutaneous warts, seems to increase the rate of complete remission from 54% to 86% when compared with conventional therapy alone (20071). It is unclear if these effects are due to echinacea, other ingredients, or the combination.
• Water warts. It is unclear if oral echinacea is beneficial for water warts (molluscum contagiosum). Details: In children who have been successfully treated with curettage for molluscum contagiosum, taking a combination of E. angustifolia and E. purpurea orally daily for 2 months is associated with a relapse rate of about 39%, compared with a rate of 68% in a control group that received no oral treatment (104128). The validity of this finding is limited by the lack of a placebo control. E. angustifolia and E. purpurea were taken in doses of 200 mg each in children under 20 kg and 400 mg each in children over 20 kg. More evidence is needed to rate echinacea for these uses.

(Read more about ECHINACEA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral European barberry fruit is beneficial for acne. Details: Preliminary clinical research in adolescents 12-17 years of age with moderate or severe acne shows that taking European barberry aqueous extract 200 mg three times daily for 4 weeks reduces acne severity and decreases the number of acne lesions when compared with placebo (94824).
• Bacterial vaginosis. It is unclear if topical European barberry is beneficial for bacterial vaginosis. Details: A small clinical study in adults with bacterial vaginosis shows that applying 5 grams of a cream containing European barberry 5% with metronidazole 0.75% vaginally nightly for 7 days modestly reduces infection recurrence rate over the following three weeks when compared with metronidazole cream alone (94826).
• Breast cancer. Although there is interest in using oral European barberry for breast cancer prevention, there is insufficient reliable information about the clinical effects of European barberry for this condition.
• Dental plaque. It is unclear if brushing the teeth with a gel containing European barberry is beneficial for dental plaque. Details: Preliminary clinical research in males 11-12 years of age shows that brushing with a European barberry extract gel containing berberine 1%, three times daily for 3 weeks reduces plaque index when compared with placebo. This effect was similar to that seen with a commercial antiplaque toothpaste (Colgate) (33695).
• Diabetes. It is unclear if oral European barberry is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking European barberry juice 200 mL daily for 8 weeks, in conjunction with standard treatment, reduces fasting blood glucose levels by 7.5%, compared with an increase of 20% in those receiving standard treatment alone. Patients taking European barberry also had improvements in body weight, systolic and diastolic blood pressure, and total cholesterol when compared with standard treatment alone (98575).
• Gingivitis. It is unclear if brushing the teeth with a gel containing European barberry is beneficial for gingivitis. Details: Preliminary clinical research in males 11-12 years of age shows that brushing with a European barberry extract gel containing berberine 1%, three times daily for 3 weeks, reduces gingival inflammation when compared with placebo. This effect was similar to that seen with a commercial antiplaque toothpaste (Colgate) (33695).
• Hyperlipidemia. It is unclear if oral European barberry is beneficial for hyperlipidemia. Details: Meta-analyses of five small clinical trials shows that taking European barberry decreases total cholesterol by 24 mg/dL, low-density lipoprotein (LDL) cholesterol by 14 mg/dL, and triglycerides by 29 mg/dL, without significantly affecting high-density lipoprotein (HDL) cholesterol, when compared with a control intervention (102055,105756). However, because the studies included in these analyses enrolled patients with diabetes, metabolic syndrome, or nonalcoholic fatty liver disease (NAFLD), the effects of European barberry on lipid levels in patients with hyperlipidemia are unclear.
• Opioid withdrawal. It is unclear if oral European barberry is beneficial for opioid withdrawal. Details: Clinical research in patients using methadone during opioid withdrawal shows that taking European barberry root extract 500 mg twice daily for 4 weeks reduces overall symptoms of withdrawal by a large amount, but does not improve depression, anxiety, stress, or sleep quality, when compared with placebo (108156). More evidence is needed to rate European barberry for these uses.

(Read more about EUROPEAN BARBERRY)

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.

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POSSIBLY INEFFECTIVE

• Hyperlipidemia. Preliminary clinical studies show that oral reishi mushroom does not improve lipid levels in patients with hyperlipidemia or type 2 diabetes. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not significantly improve the lipid profile in patients with hyperlipidemia (70776). Also, a meta-analysis shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce total cholesterol or low-density lipoprotein (LDL) cholesterol in patients with type 2 diabetes (91435).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral reishi mushroom for aging, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Altitude sickness. Although there has been interest in using oral reishi mushroom for altitude sickness, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Alzheimer disease. A small clinical study suggests that oral reishi mushroom does not improve Alzheimer disease symptoms. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking reishi mushroom powder 1000 mg three times daily for 6 weeks does not improve memory, language skills, or quality of life when compared with placebo (97942).
• Asthma. Although there has been interest in using oral reishi mushroom for asthma, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral reishi mushroom extract can help reduce some lower urinary tract symptoms in patients with BPH. Details: Clinical research in patients with mild to moderate lower urinary tract symptoms (LUTS) associated with BPH, urinary incontinence, overactive bladder, or other conditions, shows that taking reishi mushroom extract 6 mg orally once daily for up to 12 weeks moderately improves total symptom severity measured on the International Prostate Symptom Score (IPSS) scale, when compared with placebo (91436,91437). A higher dose of 60 mg daily is not more effective than the 6 mg dose, and a lower dose of 0.6 mg daily is not more effective than placebo (91437). Reishi mushroom extract does not improve peak urine flow rate, residual urine volume, prostate volume, or quality of life when compared with placebo (91436,91437). The relevance of these results is unclear since not all of the patients with LUTS had BPH.
• Bronchitis. Although there has been interest in using oral reishi mushroom for bronchitis, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Cancer. It is unclear if oral reishi mushroom is beneficial when used in conjunction with chemotherapy. Details: A meta-analysis of 9 clinical trials using various reishi mushroom products in combination with chemotherapy found that complete and partial responses increased by 30% with combination therapy when compared with chemotherapy alone. However, there was no difference in overall survival (102915). The reliability and applicability of these results are unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy, and were all conducted in China or other Asian countries.
• Cancer-related fatigue. It is unclear if oral reishi mushroom is beneficial in patients with breast cancer and fatigue. Details: Results from a small clinical study in breast cancer patients show that taking reishi mushroom powder 1000 mg orally three times daily for 4 weeks can improve cancer-related fatigue when compared with placebo (91438). However, it is not clear if the improvement is clinically meaningful.
• Cardiovascular disease (CVD). It is unclear if oral reishi mushroom is beneficial for reducing CVD risk factors. Details: A meta-analysis of 5 low-quality studies in adults with diabetes shows that taking reishi mushroom 1400-3000 mg daily for 12-16 weeks does not reduce CVD risk factors, including total and low-density lipoprotein (LDL) cholesterol, triglycerides, blood pressure, and body mass index, when compared with placebo (91435).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral reishi mushroom for CFS, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Chronic kidney disease (CKD). Although there has been interest in using oral reishi mushroom for CKD, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Colorectal adenoma. Limited clinical research suggests that oral reishi mushroom extract may be beneficial for reducing colorectal adenoma size. Details: Preliminary clinical research in patients with colorectal adenomas shows that taking reishi mushroom extract 1500 mg orally in two divided doses daily for 12 months reduces the number and size of adenomas when compared with no treatment (70774).
• Coronary heart disease (CHD). It is unclear if oral reishi mushroom is beneficial for CHD. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces symptoms of CHD, such as chest pain, palpitations, and shortness of breath, in a greater percentage of patients when compared with placebo (70800).
• Diabetes. Evidence on the use of oral reishi mushroom in patients with type 2 diabetes is conflicting. Details: A meta-analysis of clinical research in patients with type 2 diabetes shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce glycated hemoglobin (HbA1c) or plasma lipids (91435). However, one preliminary clinical study in patients with type 2 diabetes shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg three times daily for 12 weeks reduces HbA1c, but not fasting blood glucose, when compared with placebo (70801).
• Fibromyalgia. It is unclear if oral reishi mushroom is beneficial for fibromyalgia. Details: A small clinical trial in patients with fibromyalgia shows that taking reishi mushroom (MundoReishi Salud S.L.) powder 3 grams twice daily for 6 weeks does not improve mood, quality of life, anthropometric measures, blood pressure, or glycemic or lipid parameters when compared with placebo (108309,108310). However, the study may have been underpowered to detect any differences between groups.
• Genital herpes. Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent genital herpes shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by 6 days when compared with previous outbreaks (91434).
• Gulf war syndrome. It is unclear if oral reishi mushroom is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in adults with Gulf war syndrome shows that taking reishi mushroom extract (JHS Natural Products, Mushroom Science) 1600 mg in two divided doses daily for 30 days does not improve symptoms when compared with placebo. Also, symptoms modestly worsened after an additional 30 days of treatment at a dose of 3200 mg daily (108311).
• Hepatitis B. One small clinical study suggests that a specific reishi mushroom extract may reduce hepatitis B activity and improve liver function. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces levels of hepatitis B viral DNA and hepatitis B surface antigen, which are markers of hepatitis B activity, and normalizes aminotransferase levels in a greater percentage of patients when compared with placebo (70799).
• Herpes labialis (cold sores). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent herpes labialis shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by almost 4 days when compared with previous outbreaks (91434).
• Herpes zoster (shingles). Although there has been interest in using oral reishi mushroom for herpes zoster, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Human papillomavirus (HPV). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oral HPV shows that taking a combination of reishi and coriolus mushroom powders, 400 mg orally daily for 2 months, clears HPV in 88% of patients when compared with baseline (91433). The validity of this finding is limited by the lack of a comparator group.
• Hypertension. Limited research suggests that oral reishi mushroom may be beneficial in some types of hypertension. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not lower blood pressure in patients with hypertension (70776). However, in other clinical research, taking reishi mushroom extract 330-1440 mg daily for 1-6 months reduces blood pressure in patients with stage II or essential hypertension, but not in those with mild hypertension or diabetes (70786,70802,91435).
• Influenza. Although there has been interest in using reishi mushroom for influenza, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Insomnia. Although there has been interest in using reishi mushroom for insomnia, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Lung cancer. Small clinical studies suggest that oral reishi mushroom does not reduce the size of lung tumors. Details: A meta-analysis of preliminary clinical research shows that taking reishi mushroom does not reduce the size of lung tumors. However, it may stimulate immune function and improve quality of life in lung cancer patients when compared with control (70779).
• Peptic ulcers. Although there has been interest in using oral reishi mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Rheumatoid arthritis (RA). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with active RA who are taking disease-modifying antirheumatic drugs shows that taking reishi mushroom extract 4 grams in combination with San Miao San (containing 2.4 grams each of atractylodes, phellodendron, and Achyranthes bidentata) daily for 24 weeks does not increase the percentage of patients achieving a 20% response based on the American College of Rheumatology (ACR) criteria or modify blood markers of disease and inflammation when compared with placebo (70767).
• Stress. Although there has been interest in using oral reishi mushroom for stress, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose. More evidence is needed to rate reishi mushroom for these uses.

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LIKELY SAFE ...when used orally and appropriately, short-term. Various liquid extracts of Echinacea purpurea have been used safely for up to 10 days, including EchinaGuard (Madaus AG) 20 drops every 2 hours for 1 day, then three times daily (10320), or Echinilin (Inovobiologic Inc.) 40 mL in divided doses for 1 day, then 15 mL in divided doses daily thereafter (12355,20062). Other liquid extracts have been used safely for relatively longer periods, including Echinaforce (A. Vogel Bioforce AG) 2.4 grams daily for 4 months or 1.6 grams daily for 6 months (7087,18225), and Echinacin (Madaus AG) 5 mL twice daily for 10 days, or 4 mL twice daily for 8 weeks (3282,10802). Specific solid dosage forms of echinacea that have been used safely for up to 10 days include Echinacea purpurea above-ground parts (EchinaFresh, Enzymatic Therapy) 300 mg daily (11970), and mixtures of Echinacea purpurea and Echinacea angustifolia herb in divided doses of 6 grams to 10.5 grams for 1 day then 3 grams to 5.1 grams daily (10800,17519,20059). A specific Echinacea angustifolia extract (ExtractumPharma ZRT) has also been used with apparent safety at a dose of 40 mg once or twice daily for up to 7 days (20064,103233). An Echinacea purpurea product (Natures Resource) has been used safely at a dose of 1.8 grams daily for 8 weeks (17521), and echinacea (Puritan's Pride) has been used safely at 8 grams daily for 28 days (20066).

POSSIBLY SAFE ...when used topically, short-term. A specific cream (Linola Plus Cream, Dr. August Wolff GmbH & Co.) containing echinacea extract (WO 3260) has been applied to the skin safely 2-3 times daily for up to 12 weeks (97499). There is insufficient reliable evidence about the safety of echinacea when used parenterally.

CHILDREN: POSSIBLY SAFE
when used orally, short-term. Some clinical research shows that an extract of the above-ground parts of Echinacea purpurea (EC31J2, Echinacin Saft, Madaus AG) in a dose of 3.75 mL twice daily (for ages 2 years to 5 years) or 7.5 mL twice daily (for ages 6 years to 11 years) is safe when used for up to 10 days (4989). However, about 7% of children experienced a rash after taking echinacea, which might have been caused by an allergic reaction (4989). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). In contrast, another clinical study in children 4-12 years old shows that a specific Echinacea purpurea product (Echinaforce Junior, A. Vogel) does not cause allergic or urticarial reactions more frequently than vitamin C (105719).

PREGNANCY: POSSIBLY SAFE
when used orally, short-term. There is preliminary evidence that mothers can safely use echinacea in the form of E. purpurea or E. angustifolia solid dosage forms, 250-1000 mg daily, or tinctures, up to 30 drops daily, for 5 days to 7 days during the first trimester without adversely affecting the fetus (7056,13418,15123). There is insufficient reliable information available about the safety of echinacea when used for longer than 7 days.

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when the fruit is consumed orally in food amounts (13527). There is insufficient reliable information available about the safety of European barberry when used orally in medicinal amounts or when used topically.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of European barberry can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589). There is insufficient reliable information available about the safety of European barberry when used orally in older children.

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).

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

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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)

POSSIBLY SAFE ...when an extract of reishi mushroom is used orally and appropriately for up to one year (12,5485,70767,70774,70786,70799,70800,70801,70802). ...when whole powdered reishi mushroom is used orally and appropriately for up to 16 weeks (70776,70799,70800,70801,91433,91435,91436,91437,108309).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using

(Read more about REISHI MUSHROOM)

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.  Details Echinacea seems to increase plasma concentrations of caffeine by around 30% (12155). This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.  Details Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30% (12155). Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.  Details Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir (13712,48618,88164,88165). However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4 (48618). The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4 (12155). In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate (6450,11026,88162,88167).

DARUNAVIR (Prezista) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.  Details Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients (88163,93578).

DOCETAXEL (Taxotere) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.  Details Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study (88164).

ETOPOSIDE (VePesid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Echinacea may increase levels of etoposide.  Details In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism (20082). Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme (6450,11026,12155,88162,88167).

ETRAVIRINE (Intelence) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.  Details Etravirine is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg three times daily for 14 days did not alter the pharmacokinetics of etravirine in HIV-infected patients (88165,93578).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.  Details Theoretically, echinacea may interfere with immunosuppressant therapy because of its immunostimulant activity (3279,6388,6389,12639).

LOPINAVIR/RITONAVIR (Kaletra) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.  Details Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers (48618,93578).

MIDAZOLAM (Versed) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Theoretically, echinacea may increase the metabolism of intravenous midazolam.  Details Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam (12155). Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.

WARFARIN (Coumadin) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.  Details Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR (20083).

(Read more about ECHINACEA)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with anticholinergic drugs might cause additive effects.  Details In vitro evidence suggests that European barberry might have anticholinergic properties (13527).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, European barberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal evidence suggest that berberine, a constituent of European barberry, might inhibit platelet aggregation (33591,33660,33661,33694). Theoretically, European barberry might have a similar effect.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking European barberry with antidiabetes drugs might increase the risk of hypoglycemia.  Details Preliminary clinical evidence suggests that European barberry juice reduces fasting glucose levels in patients with type 2 diabetes who are also taking antidiabetes drugs (98575). Additionally, some animal studies show that berberine, a constituent of European barberry, has antiglycemic potential (33622,33667). Monitor blood glucose levels closely.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with antihypertensive drugs might increase the risk of hypotension.  Details Animal and human research suggests that European barberry extracts can have hypotensive effects (13528,33604,98575).

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with cholinergic drugs might decrease the effects of cholinergic drugs.  Details In vitro evidence suggests that European barberry might have anticholinergic properties (13527).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.  Details Animal research suggests that berberine, a constituent of European barberry, might have sedative effects (33650,33692). Theoretically, European barberry might have a similar effect.

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with cyclosporine may cause additive effects.  Details Berberine, a constituent of European barberry, can reduce the metabolism and increase serum levels of cyclosporine. This effect is attributed to the ability of berberine to inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524). Theoretically, European barberry might have a similar effect.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, European barberry might increase the levels and clinical effects of CYP3A4 substrates.  Details There is very preliminary evidence suggesting that berberine, a constituent of European barberry, might inhibit the CYP3A4 enzyme (13524). Theoretically, European barberry might have a similar effect.

(Read more about EUROPEAN BARBERRY)

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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of reishi mushroom might increase the risk of bleeding.  Details A dose of 1.5 grams daily of reishi mushroom does not seem to decrease platelet aggregation, but a higher dose of 3 grams daily does (5476,13235).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, reishi mushroom might have additive effects with antidiabetes drugs.  Details Animal research suggests that reishi mushroom decreases blood sugar (70769). However, in patients with type 2 diabetes, taking reishi mushroom does not reduce fasting glucose levels, and its effects on glycated hemoglobin are inconsistent (70801,91435).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of reishi mushroom with antihypertensive drugs might increase the risk of hypotension.  Details Reishi mushroom has shown hypotensive activity in animal research (5488,70784). Clinical evidence suggests that reishi mushroom reduces blood pressure in some, but not all, patients with hypertension (70786,70802).

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General ...Orally, echinacea is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, heartburn, nausea and vomiting, rashes, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions and hepatitis have been reported.

Dermatologic ...Itching, urticaria, tingling, and allergic rashes have been reported with various echinacea preparations (8225,12355,17519,20059,20077,101592,111530,111540). In a study of children aged 2-11 years, rash occurred in about 7% of children treated with an extract of the above-ground parts of E. purpurea (EC31J2, Echinacin Saft, Madaus AG), compared with about 3% of those treated with placebo (4989,95652). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). However, another study in children 4-12 years old shows that a specific E. purpurea product (Echinaforce Junior, A. Vogel) did not cause allergic or urticarial reactions more frequently than vitamin C (105719).

Gastrointestinal ...Gastrointestinal adverse effects include nausea and vomiting, abdominal pain, stomach upset, heartburn, diarrhea, and constipation (10802,11970,12355,13419,17519,20059,48680,105719,106626). An unpleasant taste, dry mouth, and burning, tingling or numbness of the tongue also occur (11970,12355,17519,20059,20070,20077).

Hematologic ...A 51-year-old female presented with leukopenia after taking echinacea 450 mg three times daily for 2 months, along with ginkgo biloba, multivitamins, and calcium. Her leukocyte count recovered upon stopping these supplements, but dropped again when she restarted echinacea alone about a year later. The problem resolved when echinacea was stopped permanently (48533). A 32-year-old male presented with severe thrombotic thrombocytopenic purpura (TTP) about 2 weeks after using an extract of E. pallida to treat a cold. He required admission to an intensive care unit and extensive plasmapheresis. The authors speculate that immunostimulant effects of echinacea induced or exacerbated the TTP (48572).

Hepatic ...Although uncommon, cases of echinacea-induced hepatitis have been reported. One case report describes acute cholestatic autoimmune hepatitis in a 45-year-old male who had been taking an echinacea root extract 1500 mg daily for about 2 weeks. He presented with significantly elevated liver function tests (LFTs), elevated immunoglobulin G (IgG) levels, and a positive test for anti-smooth muscle antibodies, indicating an autoimmune process. Elevated LFTs and IgG levels returned to normal within one month of stopping echinacea (17518). Another case report describes acute cholestatic hepatitis in a 44-year-old male who had taken echinacea root tablets 600 mg daily for 5 days to treat flu-like symptoms. He presented with elevated LFTs, prothrombin time, and international normalized ratio (INR). His condition gradually improved after stopping echinacea, and his LFTs normalized within 3 months (91528).
Seven cases of hepatitis associated with echinacea use were reported to the Australian Adverse Drug Reactions Advisory Committee between 1979 and 2000, but specific details are lacking (8225).
One case report describes acute liver failure in a 2 year-old child who had been given about 100 mg of echinacea daily for 2 weeks. The patient presented with jaundice, diarrhea, lethargy, anorexia, and significantly elevated LFTs. A liver biopsy showed hepatocyte swelling, spotty necrosis, and inflammatory infiltrate with eosinophils. A full recovery was made over a 2-week period (88166).

Immunologic ...Allergic reactions, including urticaria, runny nose, dyspnea, bronchospasm, acute asthma, angioedema, and anaphylaxis, have been reported with various echinacea preparations (638,1358,8225). Atopic individuals and those sensitive to other members of the Asteraceae family (ragweed, chrysanthemums, marigolds, daisies) seem to be at higher risk for these reactions (1358,8225).
A case report describes a 36-year-old female who presented with muscle weakness, electrolyte abnormalities, renal tubular acidosis, fatigue, and dry mouth and eyes after taking echinacea, kava, and St. John's Wort for 2 weeks., She also had a positive antinuclear antibody (ANA) test, with elevated anti-dsDNA antibodies SSA and SSB. Sjogren syndrome was diagnosed; the authors hypothesize that it may have been triggered by the immunostimulant effects of echinacea (10319). A 55-year-old male with a history of pemphigus vulgaris in remission for about a year experienced a flare of the disease after taking an echinacea supplement for one week. After stopping echinacea, medical treatment resulted in partial control of the disease (12171). Another case report describes a 58-year-old male who presented with marked eosinophilia and elevated immunoglobulin E (IgE) levels while taking an echinacea supplement. He required prednisone therapy until he stopped taking echinacea 3 years later, at which time his eosinophils and IgE normalized (48623). A 41-year-old male experienced four episodes of erythema nodosum, each occurring after he had taken echinacea for early symptoms of influenza. After stopping echinacea, he had no further exacerbations of erythema nodosum, suggesting that it had been triggered by the immunostimulant effects of echinacea (7057).

Musculoskeletal ...Reports of arthralgia and myalgia have been associated with echinacea (13418).

Neurologic/CNS ...Headache has been reported in people taking various echinacea preparations orally (3282,11970,17519,20059,20064). Dizziness has also been reported (3282,8225,11970). In one study using an alcoholic extract of the above-ground parts of E. purpurea (EC31J0, Echinacin, Madaus AG), somnolence and a tendency to aggressiveness were reported (3282).

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General ...European barberry is generally well tolerated when consumed in amounts commonly found in food. A thorough evaluation of safety outcomes has not been conducted for the use of larger, medicinal amounts. Topically, European barberry seems to be well tolerated.

Hepatic ...Orally, a case of hepatitis-associated aplastic anemia is reported in an adult male after consuming European barberry 15 drops and nannari root 15 drops twice a day for 2 weeks. The patient presented with lethargy, loss of appetite, and jaundice that progressed to high-grade fevers, chills, rigors, severe pancytopenia, and abnormal liver function tests. Liver biopsy was suggestive of drug-induced liver injury. The patient was hospitalized for multiple infections and symptomatic thrombocytopenia. Despite receiving supportive care, blood transfusions, and corticosteroids, the patient died 7 weeks after diagnosis (110021). The exact reason for this adverse effect is not clear.

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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).

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General ...Orally, reishi mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, dry mouth, itching, nausea, rash, and stomach upset.

Dermatologic ...Orally, reishi mushroom can cause itching, rash, and other skin reactions (12,5479).

Gastrointestinal ...Orally, reishi mushroom can cause dryness of the mouth, throat, or nasal cavity, nausea, stomach upset, and, more rarely, diarrhea (12,70779,91438,108309).

Hematologic ...Orally, reishi mushroom can cause nosebleed and bloody stools (12,91438).

Hepatic ...One case of hepatotoxicity and one case of fatal fulminant hepatitis have been reported in patients who had used reishi mushroom powder for 1-2 months (70766). There is a case report of a 61-year-old male with hypereosinophilia associated with hepatic nodules following the use of reishi mushroom powder for about 2 months. Symptoms resolved after discontinuation of the product. Although these side effects were thought to be associated with the use of reishi mushroom powder, it is unclear if other factors played a role. The patient had been taking tegafur, gimeracil, and oteracil potassium for about 4 months following anterior resection for rectal adenocarcinoma but discontinued these agents and initiated reishi mushroom due to liver injury (108312).

Neurologic/CNS ...Orally, reishi mushroom can cause dizziness (91438). Other rare symptoms include insomnia and headache (70776,70779).

Pulmonary/Respiratory ...Respiratory allergy to reishi spores can occur (12,5479). Sore throat and runny nose have also been reported (70776,91438).

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