Vinceel by Heel, Inc. (formerly known as BHI)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anal fissures. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax for 12 hours reduces pain, bleeding, and itching associated with anal fissures (34100). It is unclear if these effects are due to beeswax, the other ingredients, or the combination.
• Burns. Preliminary clinical research in individuals with second-degree burns shows that applying a dressing containing a mixture of beeswax, olive oil, and alkanna once daily reduces healing time by almost 4 days, decreases pain during dressing changes, and shortens the duration of hospitalization by about 6 days compared to using a dressing containing nitrofurazone and rifamycin, applied once every 2 days (96328). Other preliminary clinical research shows that using a topical product containing beeswax (Medilixir, Medilixir Pty Ltd) for 14 days decreases the severity of itching, lengthens the time until itch recurrence, and decreases the use of anti-itch medications compared to standard aqueous cream (Biotech Pharmaceuticals Pty Ltd) in individuals experiencing post-burn itch (96329). Poor study designs limit the reliability of the findings.
• Diaper rash. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax four times daily for 7 days reduces symptoms of diaper rash by more than 75% (34094). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Hemorrhoids. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax for 12 hours reduces pain, bleeding, and itching associated with hemorrhoids (34100). It is unclear if these effects are due to beeswax, the other ingredients, or the combination.
• Oral mucositis. Preliminary clinical research in children with severe chemotherapy-induced mucositis shows that applying of mixture of honey, olive oil-propolis extract, and beeswax topically three times daily until healing or for a maximum of 10 days, along with standard oral care, reduces recovery time by almost 3 days compared to using benzocaine 7.5% gel. However, the mixture does not appear to reduce recovery time compared to benzocaine in patients with moderate chemotherapy-induced mucositis. Additionally, applying honey alone 0.5 grams/kg (maximum 15 grams), appears to be more efficacious for both moderate and severe mucositis than either the honey mixture or benzocaine gel (55245).
• Radiation dermatitis. A small clinical study in patients undergoing radiotherapy shows that applying a topical ointment containing beeswax, olive oil, calendula oil extract, and St. John's wort oil extract to the treated area nightly during radiotherapy and for two weeks post-radiotherapy, while also applying a topical cream containing aloe vera gel, calendula oil extract, and St. John's wort oil extract to the treated area three to four times daily, reduces the intensity of dermatitis and improves quality of life scores when compared to baseline (105769). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if these findings are due to beeswax, other ingredients, or the combination.
• Tinea corporis. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 75% of patients with tinea corporis (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Tinea cruris. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 78% of patients with tinea cruris (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Tinea versicolor. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 86% of patients with tinea versicolor (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination. More evidence is needed to rate beeswax for these uses.

(Read more about BEESWAX)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there is interest in using oral belladonna for asthma, there is insufficient reliable information about the effects of belladonna for this condition.
• Common cold. Although there is interest in using oral belladonna for the common cold, there is insufficient reliable information about the effects of belladonna for this condition.
• Hemorrhoids. Although there is interest in using rectal belladonna for hemorrhoids, there is insufficient reliable information about the effects of belladonna for this condition.
• Irritable bowel syndrome (IBS). It is unclear if oral belladonna is beneficial in patients with IBS. Details: A prescription-only oral combination of belladonna and phenobarbital, first marketed prior to the passing of the Food, Drug, and Cosmetic Act of 1938, is considered an unapproved drug, but is allowed to remain on the market while the FDA evaluates its effectiveness and safety (106908). However, preliminary clinical research suggests that taking a combination of belladonna and phenobarbital orally for one month does not improve symptoms of IBS when compared with placebo (34156).
• Kidney stones (nephrolithiasis). It is unclear if rectal belladonna is beneficial in patients with ureteral spasm associated with kidney stones. Details: A prescription-only rectal combination of belladonna and opium, first marketed prior to the passing of the Food, Drug, and Cosmetic Act of 1938, is considered an unapproved drug, but is allowed to remain on the market while the FDA evaluates its effectiveness and safety (106909). Clinical trials for this indication have not been published, and clinical data are not included in the package insert.
• Parkinson disease. Although there is interest in using oral belladonna for Parkinson disease, there is insufficient reliable information about the effects of belladonna for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using topical belladonna for RA, there is insufficient reliable information about the effects of belladonna for this condition. More evidence is needed to rate belladonna for these uses.

(Read more about BELLADONNA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate acne associated with mask wearing shows that topical application of a combination of calendula 4%, licorice root extract 0.3%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to calendula, other ingredients, or the combination.
• Bacterial vaginosis. It is unclear if topical calendula is beneficial for improving bacterial vaginosis. Details: A small clinical study in patients with bacterial vaginosis shows that applying 5 grams of vaginal cream containing calendula flower extract before bed for one week improves vaginal burning, odor, painful urination, and painful intercourse when compared to baseline (96649). The validity of these findings is limited by the lack of a comparator group.
• Burns. It is unclear if oral calendula is beneficial for burn healing. Details: A small clinical trial in patients hospitalized for second-degree burns shows that taking calendula 2 grams daily for 2 weeks has a large beneficial effect on wound healing when compared with placebo (110323).
• Chronic obstructive pulmonary disease (COPD). Oral calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males aged 40-70 years with a history of smoking and stage 2 COPD shows that taking a specific combination of calendula flowers 165 mg, elderberry 165 mg, and heart's ease herb 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months, modestly improves symptoms, as measured on the breathlessness, cough, and sputum scale (BCSS), and mean forced expiratory volume in 1 second (FEV1) when compared to baseline. However, there was no improvement of COPD exacerbations or other pulmonary function tests (103629). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Furthermore, it is unclear if these effects are due to calendula, the other ingredients, or the combination.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Calendula in rectal suppositories has only been evaluated in combination with turmeric extract; its effect when used alone is unclear. Details: A small clinical study in patients with CP/CPPS shows that using a rectal suppository containing turmeric extract 350 mg and calendula extract 80 mg daily for one month improves pain, peak urine flow rate, and erectile function when compared with placebo (96648). It is unclear if these effects are due to calendula, turmeric, or the combination.
• Conjunctivitis. Although there is interest in using topical calendula for conjunctivitis, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Diabetic foot ulcers. It is unclear if topical calendula is beneficial for improving diabetic foot ulcers. Details: Observational research has found that applying a calendula hydroglycolic extract spray in addition to standard care and hygiene is associated with reduced bacterial colonization and improved odor in patients that have had a diabetic ulcer for over 3 months (93548).
• Diaper rash. It is unclear if topical calendula is beneficial for improving diaper rash. Details: One preliminary clinical study in children less than 3 years of age shows that topical application of calendula 1.5% ointment three times daily for 10 days improves diaper rash when compared with aloe gel (19779). However, other preliminary clinical research shows that applying calendula 1.5% cream every 4-6 hours for 3 days improves diaper rash in fewer infants when compared to treatment with bentonite 50% mineral solution (93545,93554).
• Dysmenorrhea. Although there is interest in using oral calendula for dysmenorrhea, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Gingivitis. It is unclear if using a mouth rinse with calendula is beneficial for improving gingivitis. Details: Preliminary clinical research in patients with mild gingivitis and bleeding gums shows that rinsing the mouth with a tincture containing calendula 25% (Dr. Willmar Schwabe Germany Home Pharmacy Pvt. Ltd.) twice daily for 6 months decreases plaque, gingivitis, and bleeding by 10% to 18% when compared to rinsing with water (93551). Other preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with a combination mouthwash containing a 5% extract of calendula, rosemary, and ginger for 30 seconds twice daily after food for 2 weeks decreases plaque, gingivitis, and bleeding when compared with a placebo mouthwash. The effects of this combination mouthwash appear to be similar to chlorhexidine 0.2% mouthwash (93555). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Hemorrhoids. Although there is interest in using topical calendula for hemorrhoids, there is insufficient reliable information about the clinical effects of calendula for this purpose.
• Liver disease. Although there is interest in using oral calendula for liver disease, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Mosquito repellent. It is unclear if topical calendula essential oil helps to repel mosquitos. Details: Preliminary clinical research shows that applying calendula 50% essential oil to the skin does not repel mosquitos as effectively as applying DEET. Mean repellency time was about 2 hours for patients applying calendula, which was shorter than the 6 hour repellency with DEET (93562).
• Oral leukoplakia. It is unclear if topical calendula is beneficial for improving oral leukoplakia. Details: Preliminary clinical research in patients with oral leukoplakia shows that applying a gel containing calendula flower extract 0.2% three times daily for one month reduces lesion size by about 2 cm when compared to baseline (96650). The validity of this finding is limited by the lack of a comparator group.
• Oral mucositis. Calendula as a mouth rinse has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with head and neck cancer receiving chemotherapy and radiotherapy shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing calendula powder extract 2%, propolis, aloe vera, and chamomile three times daily for 6 weeks does not prevent oral mucositis when compared with placebo (95879).
• Otitis media. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with otitis media shows that applying a specific combination product containing calendula, mullein, garlic, and St. John's wort in olive oil (Otikon Otic Solution, Healthy-On Ltd, Petach-Tikva, Israel), five drops into the affected ear three times daily for 3 days, may reduce ear pain when compared with baseline (39500,39552). It is unclear if this effect is due to calendula, other ingredients, or the combination. Furthermore, due to the lack of an adequate control group, it is unclear whether the pain reduction was due to the resolution of otitis media.
• Peptic ulcers. Although there is interest in using oral calendula for peptic ulcers, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Pressure ulcers. It is unclear if topical calendula is beneficial for improving pressure ulcers. Details: Observational research has found that the application of a specific calendula product (Plenusdermax) twice daily is associated with improved healing in patients with pressure ulcers that have not changed in size for at least 3 months (93549). Preliminary clinical research in hospice patients with symptomatic pressure ulcers and other wounds shows that applying a homeopathic powder (RGN107) containing calendula 0.1% and arnica 0.01% to wounds for 4 weeks is rated by the patients and caregivers to be acceptable for controlling pain, odor, and exudate when compared with baseline (96647). The validity of this finding is limited by the lack of a control group.
• Radiation dermatitis. It is unclear if topical calendula reduces radiation dermatitis symptoms. Details: Meta-analyses of three preliminary clinical trials in patients with breast cancer show that topical calendula does not affect the development of radiation dermatitis or the incidence of moderate to severe symptoms when compared to control (110325,113674). In addition, a meta-analysis of two studies (39503,93560) shows that topical calendula does not reduce the incidence of treatment interruptions due to severe symptoms of radiation dermatitis (110325). In one of the included studies, a specific calendula petroleum jelly ointment (Pommade au Calendula par Digestion, Boiron Ltd.) used twice daily during radiation therapy was found to reduce acute radiation dermatitis occurrence when compared with topical trolamine (Biafine) (39503). However, it is unclear if the benefit was due to calendula or petroleum jelly. Another clinical study used a specific calendula 10% cream in wool fat and sesame oil (Calendula Weleda, Weleda AG) twice daily during radiation therapy. This product was found to be no better than aqueous petroleum jelly cream (Essex, Schering-Plough) for reducing acute skin reactions and dermatitis symptoms of pain, burning, itching, pulling, and tenderness (93560).
• Vaginal atrophy. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in menopausal patients with vaginal atrophy shows that use of a specific vaginal gel containing calendula, Lactobacillus sporogenes, isoflavones, and lactic acid (Estromineral Gel, Rottapharm-Madaus) daily for 4 weeks reduces vaginal itching, burning, dryness, and painful intercourse when compared with no topical treatment. Both groups also received oral isoflavones (39534). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Vaginal candidiasis. One small clinical study suggest that topical calendula is not beneficial for the treatment of vaginal candidiasis. Details: Preliminary clinical research shows that applying 5 grams of calendula 1% cream intravaginally once daily for 7 days effectively treats vaginal candidiasis in 34% fewer patients when compared with using clotrimazole 1% cream (93559).
• Venous leg ulcers. It is unclear if topical calendula is beneficial for improving venous leg ulcers. Details: Preliminary clinical research shows that applying a calendula 7.5% ointment twice daily for 3 weeks to venous leg ulcers accelerates healing when compared with applying saline solution dressing (39509).
• Wound healing. It is unclear if topical calendula is beneficial for improving the healing of small wounds. Details: Two small clinical trials in postpartum patients show that applying calendula ointment (formulation unspecified) to the episiotomy wound every 8 hours for 5-10 days modestly reduces pain, and seems to speed up the resolution of redness, edema, and ecchymosis, when compared with standard care, such as application of betadine solution (93550,105087). Another small clinical study in adults with wounds smaller than 10 cm² on the hands and fingers shows that applying calendula flower extract 2% to the wound twice daily may modestly improve healing and epithelialization time when compared with mineral oil (107806). More evidence is needed to rate calendula for these uses.

(Read more about CALENDULA)

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 in healthy, recreationally active males. 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).
• 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.
• 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 patients with 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.
• 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)

There is insufficient reliable information available about the effectiveness of German ipecac.

(Read more about GERMAN IPECAC)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Burns. It is unclear if topical great plantain is beneficial for burns. Details: A very small clinical study in hospitalized adults with bilateral second degree burns shows that applying great plantain extract 10% ointment to burns on one side of the body is similarly effective to applying silver sulfadiazine 1% ointment daily to burns on the other side of the body in relation to healing time, pain intensity, and rate of wound infections (110088). Due to its small size, this study may have been inadequately powered to detect a difference between groups.
• Cough. Oral great plantain has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in children 3-6 years of age with acute cough shows that taking a specific syrup (KalobaTUSS, Schwabe Pharma Italia Srl) based on acacia honey with extracts of great plantain, elecampane, mallow, and sandy everlasting, as 5 mL four times daily for 8 days, produces rapid and sustained reductions in both nighttime and daytime cough scores when compared with placebo (105734). It is unclear if these findings are due to great plantain, other ingredients, or the combination.
• Diabetic foot ulcers. It is unclear if topical great plantain is beneficial for diabetic foot ulcers. Details: A small unblinded clinical study in hospitalized adults in Iran with Wagner's stage 1 or 2 diabetic foot ulcers or stage 2 or 3 pressure ulcers based on the National Pressure Injury Advisory Panel system shows that applying great plantain extract 10% gel for 14 days reduces wound size and erythema when compared to treatment with various standard wound dressings. Complete wound healing may also occur more frequently at 2 weeks with topical great plantain extract (110090). Poor study methodology and a lack of sub-analysis by ulcer type limits the reliability of these findings. Another small clinical study in patients with a Wagner's stage 1 or 2 diabetic foot ulcer receiving oral antibiotics shows that applying a topical product containing great plantain and aloe twice daily for 4 weeks reduces ulcer surface area and healing time when compared with antibiotics alone. However, the combination product has no effect on ulcer depth (97323). It is unclear if these findings are due to great plantain, aloe, or the combination.
• Menorrhagia. It is unclear if oral great plantain leaf extract is beneficial in patients with menorrhagia. Details: A small clinical trial in adults with abnormal uterine bleeding shows that taking a syrup containing great plantain leaf 12% extract 3 times a day for the first 5 days of menstruation and repeating over 3 cycles reduces bleeding severity, but not bleeding duration, similarly to mefenamic acid 250 mg taken every 8 hours (104214).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral great plantain seed is beneficial in patients with NAFLD. Details: One small clinical trial in patients with NAFLD shows that taking great plantain seed 1000 mg twice daily for 12 weeks improves fatty liver grade on ultrasound and reduces levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and triglycerides when compared with placebo (106645).
• Obesity. It is unclear if oral great plantain leaf is beneficial in patients with obesity. Details: One small clinical trial in females with obesity shows that taking powdered great plantain leaf 400 mg daily for 12 weeks does not reduce body weight or body mass index when compared with placebo (106642).
• Oral mucositis. Small clinical studies suggest that oral great plantain extract might reduce the severity of oral mucositis, but rinsing with great plantain solution does not seem to be superior to sodium bicarbonate or chlorhexidine for improving healing time. Details: A small clinical study in adults undergoing radiation therapy for head and neck cancer shows that taking a syrup containing great plantain extract 7.5 mL three times daily for 7 weeks reduces the severity of oral mucositis when compared with placebo. Patients taking great plantain syrup also reported lower pain scores as measured on a visual analogue scale when compared with those taking placebo (104213). However, a small clinical trial in cancer patients with oral mucositis shows that there is no difference in the healing time of lesions for patients rinsing with either sodium bicarbonate 5%, great plantain 5%, or chlorhexidine 0.12% solutions. All three solutions were used as a rinse for 2 minutes every 6 hours for up to 2 weeks (98209).
• Pressure ulcers. It is unclear if topical great plantain is beneficial in patients with pressure ulcers. Details: One small clinical trial in patients with pressure ulcers being treated with topical phenytoin cream shows that application of great plantain 10% cream 12 hours after application of phenytoin daily for 2 weeks improves healing rate when compared with phenytoin and placebo (106643). Another small, unblinded clinical study in hospitalized adults in Iran with stage 2 or 3 pressure ulcers based on the National Pressure Injury Advisory Panel system or Wagner's stage 1 or 2 diabetic foot ulcers shows that applying great plantain extract 10% gel for 14 days reduces wound size and erythema when compared to a treatment with various standard wound dressings. Complete wound healing may also occur more frequently at 2 weeks with topical great plantain extract (110090). Poor study methodology and a lack of sub-analysis by ulcer type limits the reliability of these findings.
• Ulcerative colitis. It is unclear if oral great plantain seed is beneficial in patients with ulcerative colitis. Details: One small clinical trial in patients with ulcerative colitis shows that taking roasted great plantain seed 1200 mg three times daily for 8 weeks reduces abdominal tenderness, gastroesophageal reflux, and gastric pain when compared with placebo (106644). More evidence is needed to rate great plantain for these uses.

(Read more about GREAT PLANTAIN)

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

(Read more about POKEWEED)

POSSIBLY EFFECTIVE

• Cognitive function. Oral sage seems to be beneficial for improving cognitive function in healthy adults. The benefits of sage aromatherapy are unclear. Details: Clinical research shows that taking a specific product providing common sage polyphenols and Spanish sage terpenoids (Cognivia), either as a single dose or daily for 29 days, modestly improves working memory and accuracy when compared with placebo. A single dose of this product contains common sage leaf extract 400 mg and Spanish sage essential oil 200 mg (105337). In addition, preliminary clinical research shows that Spanish sage essential oil 25-50 mcL orally as a single dose seems to dose-dependently enhance some measures of cognitive performance in young adults by a small amount (10811,72609,72616,72660). When used as aromatherapy, essential oils of common sage, but not Spanish sage, seem to improve quality of memory and secondary memory. Neither species improves speed of memory or working memory when used as aromatherapy. In this study, five drops of common sage essential oil and 5 mL water were placed on a warmed stone and allowed to diffuse for 5 minutes prior to exposure (72658).
• Hyperlipidemia. Oral sage seems to be beneficial for reducing low-density lipoprotein (LDL) cholesterol and triglyceride levels. Details: Clinical research in adults with mixed hyperlipidemia types shows that taking common sage leaf extract 500 mg, standardized to quercetin 2.16%, three times daily for 2 months reduces LDL cholesterol and triglyceride levels by about 20% and 23%, respectively, and increases high-density lipoprotein (HDL) cholesterol levels by 20%, when compared with placebo (72662). Also, preliminary clinical research in adults with type 2 diabetes and hypercholesterolemia shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers total cholesterol by 17%, LDL cholesterol by 36%, and triglycerides by 56%, and increases HDL cholesterol by 28%, when compared with placebo (91971).
• Menopausal symptoms. Oral sage seems to be beneficial for reducing menopausal symptoms. Details: Clinical research shows that taking a thujone-free common sage extract (Menosan, A.Vogel AG) 280 mg daily for 4 weeks reduces overall symptoms of menopause by 39% when compared with placebo. About 41% of patients taking common sage had at least a 50% reduction in symptoms, compared with 8% of those taking placebo. Hot flushes, sleep problems, joint and muscle discomfort, irritability, and physical and mental exhaustion were improved, whereas urogenital symptoms such as sexual desire and vaginal dryness were not (105338). Other clinical research shows that taking common sage extract 300 mg daily for 3 months moderately reduces overall symptoms of menopause after about 10 weeks when compared with placebo. However, there was no effect on vaginal dryness, physical and mental exhaustion, or urinary incontinence (103379). Another small clinical study shows that taking a specific thujone-free common sage extract (Sage Menopause, Bioforce AG) 280 mg daily for 56 days reduces daily hot flash frequency by 40% and reduces hot flash intensity when compared with baseline (17177). The validity of these findings is limited by the lack of a comparator group.

POSSIBLY INEFFECTIVE

• Postoperative pain. Using an oral rinse containing common sage does not seem to be beneficial for reducing postoperative pain. Details: A large open-label clinical trial in children and adults shows that using a common sage oral rinse 6 times daily in combination with ibuprofen or diclofenac is less effective than benzydamine hydrochloride, a local anesthetic, for reducing pain following tonsillectomy and/or adenoidectomy. Furthermore, treatment with common sage oral rinse is associated with an increased risk of postoperative infection in adults when compared with benzydamine hydrochloride (72700).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if a single oral dose of common sage is beneficial for age-related cognitive decline. Details: Clinical research in healthy, older adults shows that taking a single dose of common sage extract 333 mg improves accuracy of attention and some measures of memory when compared with placebo. However, not all doses were effective and some measures of cognitive function were not affected (72642).
• Alzheimer disease. It is unclear if oral sage is beneficial for Alzheimer disease. Details: Preliminary clinical research shows that taking extracts of common sage and Spanish sage orally seems to improve cognitive function in patients with mild to moderate Alzheimer disease when used for up to 4 months (10334,10810). In one study, a fixed dose of common sage hydroalcoholic extract, equivalent to 1 gram of sage per day, was used for 4 months (10810). In the other, an extract of Spanish sage titrated up to 2.5 mg three times daily for 6 weeks was used (10334). These studies are limited by their short duration and small numbers of participants.
• Androgen deprivation therapy (ADT)-associated hot flashes. It is unclear if oral sage is beneficial for ADT-associated hot flashes. Details: Preliminary clinical research in patients with prostate cancer receiving ADT shows that taking common sage extract 150 mg three times daily with meals for 4 weeks reduces hot flash severity by 48% and hot flash frequency by 42% when compared with baseline. These improvements were maintained with an additional 8 weeks of treatment (91970). The validity of these findings is limited by the lack of a comparator group.
• Athletic performance. It is unclear if oral sage is beneficial for improving athletic performance. Details: In young, healthy, physically active adults, taking a specific supplement (Cognivia, Nexira) containing 400 mg common sage leaf extract and 200 mg Spanish sage oil, orally 2 hours prior to a 40-minute stationary cycling session at 80% of maximum aerobic power, lowers perceived exertion scores and improves working memory and reaction times when compared with placebo (108961).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if topical sage is beneficial for the treatment or prevention of CINV. Details: A small clinical study in patients undergoing chemotherapy shows that using common sage oil 2 mL topically during 15-minute sessions of Swedish abdominal massage twice daily for 3 days modestly reduces nausea severity scores, but does not affect vomiting frequency, when compared with massage alone (107023).
• Dental plaque. It is unclear if rinsing the mouth with sage is beneficial for reducing plaque. Details: Preliminary clinical research shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), is as effective as normal saline for reducing dental plaque. However, there was no effect on tongue plaque. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Diabetes. It is unclear if oral sage is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers fasting blood glucose by 32% and glycated hemoglobin (HbA1c) by 23% when compared with placebo (91971). However, another small clinical study in patients with type 2 diabetes shows that taking common sage extract 150 mg three times daily for 3 months does not lower fasting blood glucose or HbA1c when compared with placebo, although there is a modest reduction in 2-hour postprandial blood glucose levels (105340). A meta-analysis of 3 small studies, including the 2 described above, shows that taking common sage, 150-500 mg three times daily for 2-3 months, modestly reduces fasting blood glucose and 2-hour postprandial blood glucose levels, as well as HbA1c, when compared with placebo (108962). These studies were all conducted in Iran; it is unclear if these findings are generalizable to other geographic locations.
• Dry mouth. It is unclear if rinsing the mouth with common sage is beneficial for dry mouth. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in conjunction with standard care involving brushing and an oral gel (Biotene), is as effective as normal saline for improving overall oral health and modestly more effective than normal saline for improving dry mouth. The rinse was made by steeping 2.5 grams dried sage leaf in 100 mL boiled water for two minutes (105339).
• Gingivitis. Sage has only been evaluated as a mouthwash in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly individuals shows that rinsing the mouth with a mouthwash containing sage, marshmallow, calendula, tormentil, horse chestnut, neem, and myrrh, once daily for 30 seconds for 6 weeks, is no more effective than placebo for improving plaque and gingival bleeding (105341).
• Herpes labialis (cold sores). It is unclear if topical sage is beneficial for herpes labialis. Details: Clinical research shows that topical application of a cream containing either sage alone or sage with rhubarb, starting within 1 day of the first symptoms and continuing for 10-14 days, heals herpes labialis legions in 7.6 days or 6.7 days, respectively, compared to a healing time of 6.3 days with acyclovir cream. The combination of sage and rhubarb also improves the time to healing and reduces pain when compared with sage alone. The cream provided 23 mg sage extract, with or without 23 mg rhubarb extract, per gram and was applied every 2-4 hours while awake (10437).
• Lung cancer. It is unclear if dietary sage is beneficial for lung cancer prevention. Details: Epidemiological research has found that regularly consuming sage is associated with a 54% lower risk of developing lung cancer when compared with those who do not use sage as a spice (72593).
• Oral mucositis. It is unclear if rinsing the mouth with sage is beneficial for oral mucositis. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a rinse containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve oral mucositis when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Pharyngitis. It is unclear if inhaling a spray containing sage, with or without other ingredients, is beneficial for pharyngitis. Details: Clinical research in patients with acute viral pharyngitis shows that inhaling three puffs (140 mcL) of a specific spray (Valverde Salvia Rachenspray) containing common sage extract 15%, six to nine times daily for 3 days, reduces throat pain intensity over 2 hours when compared with placebo. However, sprays containing common sage extract 5% or 30% do not seem to be more effective than placebo for reducing throat pain (72619). Other preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Polycystic ovary syndrome (PCOS). It is unclear if oral sage is beneficial for PCOS. Details: Clinical research shows that taking common sage extract 330 mg daily for 8 weeks modestly reduces body mass index (BMI), diastolic blood pressure, and fasting blood glucose, and modestly improves measures of insulin resistance, when compared with placebo in individuals with PCOS. However, there was no effect on waist to hip ratio or systolic blood pressure (103380).
• Sunburn. It is unclear if topical sage is beneficial for sunburn prevention. Details: Clinical research shows that a single application of a hydrophilic ointment containing common sage extract 2% to the skin immediately after exposure to ultraviolet light reduces the development of skin redness when compared with placebo (72638).
• Swallowing dysfunction. It is unclear if rinsing the mouth with sage is beneficial for swallowing dysfunction. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve swallowing when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Tonsillitis. Sage has only been evaluated in a spray in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Tonsillopharyngitis. It is unclear if oral sage is beneficial for treating tonsillopharyngitis. Details: A moderate-sized observational study in patients aged 12-75 years old with acute tonsillopharyngitis suggests that taking lozenges containing sage extract 378.5 mg and echinacea 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 findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to sage, echinacea, the combination, or natural resolution of the condition. More evidence is needed to rate sage for these uses.

(Read more about SAGE)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Beeswax has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used orally as a medicinal agent (11)....when used topically (11,55245,96328,96329).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of medicinal amounts of beeswax during pregnancy and lactation.

(Read more about BEESWAX)

POSSIBLY UNSAFE ...when used rectally. It is not known whether significant amounts of the toxic alkaloids are absorbed from the rectum (106909). ...when used topically. It is not known whether significant amounts of the toxic alkaloids are absorbed through the skin (106909).

LIKELY UNSAFE ...when used orally. Belladonna contains toxic alkaloids and has been linked to reports of serious adverse effects (12,553,34144).

CHILDREN: LIKELY UNSAFE
when used orally. Fatalities in children may occur at doses of belladonna providing atropine 0.2 mg/kg (34168). Two belladonna berries, which contain 2 mg atropine per fruit, may be lethal for a small child (34144). Severe adverse effects and fatalities have been reported in infants treated with topical homeopathic teething products containing belladonna (17493,34142,34146,93537).

PREGNANCY: LIKELY UNSAFE
when used orally. Belladonna contains toxic alkaloids and has been linked to reports of serious adverse effects (12,553,34144).

LACTATION: LIKELY UNSAFE
when used orally. Belladonna can reduce milk production and is secreted into breast milk (15).

(Read more about BELLADONNA)

LIKELY SAFE ...when the flower preparations are used orally or topically and appropriately (4,19779,36931,39503,93552,93557,96647,105088).

PREGNANCY: LIKELY UNSAFE
when used orally; contraindicated due to spermatocide, antiblastocyst, and abortifacient effects. There is insufficient reliable information available about the safety of calendula when used topically during pregnancy (4).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CALENDULA)

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.

(Read more about ECHINACEA)

POSSIBLY UNSAFE ...when used orally (18). There is insufficient reliable information available about the safety of German ipecac for its other uses.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally (18); avoid using.

(Read more about GERMAN IPECAC)

POSSIBLY SAFE ...when great plantain seed is used orally, short-term. Great plantain seed has been used with apparent safety at doses up to 3600 mg daily for up to 8 weeks and 2000 mg daily for up to 12 weeks (106644,106645). ...when used topically, short-term. Topical great plantain 10% has been used with apparent safety for up to 2 weeks (106643,110088,110090). There is insufficient reliable information available about the safety of great plantain leaf or leaf extract when used orally.

PREGNANCY: LIKELY UNSAFE
when used orally because it can increase uterine tone (4).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GREAT PLANTAIN)

LIKELY UNSAFE ...when pokeweed is used orally. All parts of the pokeweed plant, especially the root, are considered to be toxic (3477,3479). The Herb Trade Association recommends against selling pokeweed as an herbal beverage or food (3478). Severe poisoning has been reported from ingesting tea brewed from pokeweed root (3478) and pokeweed leaves (3480,69094). Poisoning also has resulted from ingestion of pokeberry wine and pokeberry pancakes (3479). Consuming just 10 berries can be toxic to an adult (6). Green berries are considered more toxic than mature, red berries (4). ...when applied topically to the skin. Skin contact can cause hematological changes (3477,3481,3482). Protective gloves should be used to handle the plant (3477).

CHILDREN: UNSAFE
when used orally. Children have died after ingesting pokeweed berries. Consumption of even one berry can be toxic (3479).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when pokeweed is used orally or applied topically; avoid using. Evidence suggests the pokeweed berry has uterine stimulant and abortifacient effects (4,19). Pokeweed is generally considered unsafe for any use.

(Read more about POKEWEED)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).

POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).

POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).

PREGNANCY: LIKELY UNSAFE
when used orally. The constituent thujone can have menstrual stimulant and abortifacient effects (19).

LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).

(Read more about SAGE)

(Read more about BEESWAX)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Belladonna may increase the risk of adverse effects when used concomitantly with anticholinergic drugs.  Details Belladonna has anticholinergic activity and increases the activity of anticholinergic drugs (2,12).

CISAPRIDE (Propulsid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, belladonna might reduce the effects of cisapride.  Details Belladonna contains atropine. In vivo evidence suggests that atropine can prevent cisapride from increasing motility in the gastrointestinal tract (25191).

(Read more about BELLADONNA)

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, calendula might have additive effects when used with CNS depressants, although this appears to be unlikely.  Details Although some animal research has suggested that a saponoside constituent in calendula may have sedative effects (39545,39547), calendula has been used for over 30 years without reports of sedation in humans (105088).

(Read more about CALENDULA)

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)

(Read more about GERMAN IPECAC)

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, consuming large amounts of great plantain leaves, which contain vitamin K, might decrease the clinical effects of warfarin.  Details Great plantain leaves contain relatively high concentrations of vitamin K (19,97741), which might interfere with the activity of warfarin.

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(Read more about POKEWEED)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the clinical effects of anticholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

ANTICONVULSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.  Details Some species of sage can cause convulsions when consumed in large quantities (10812).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.  Details In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase or decrease the effects of antihypertensive drugs.  Details Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.  Details In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might have additive effects when used with cholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.  Details Some constituents of sage have CNS depressant activity (10334).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6 (10848,19430). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.  Details Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4 (10848,72641). So far, this interaction has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with hormone therapy.  Details In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase levels of drugs transported by P-glycoprotein.  Details In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.

(Read more about SAGE)

General ...Orally, beeswax is well tolerated. Allergic reactions to beeswax are possible in some patients (11).
Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (55245,102517).

Dermatologic ...Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (55245,102517). While this reaction is thought to be rare in the general population, one cross-sectional study found that 18% of patients with a history of cheilitis or facial dermatitis experienced positive reactions to beeswax. While most of these patients also had a positive reaction to a propolis patch test, some did not, suggesting that a substance in beeswax itself may be involved in this sensitization (102517).

Immunologic ...Orally, beeswax may cause allergic reactions (11). Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (102517).

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General ...Orally, belladonna can cause anticholinergic side effects even at low doses, and is considered poisonous.
Most Common Adverse Effects:
Orally: Anticholinergic side effects, including blurred vision, constipation, delirium, dilated pupils, dizziness, dry mouth, fever, headache, hypertension, muscle rigidity and tremor, psychosis, respiratory failure, and slurred speech.

Cardiovascular ...Orally, belladonna can cause anticholinergic side effects such as hypertension, hypotension, tachycardia, and ventricular premature beats (553,34168,34180).

Dermatologic ...Orally, belladonna can cause anticholinergic side effects such as dry, red skin and decreased perspiration (553,34146,34152). One case of rash and another case of hives have been reported in patients taking belladonna with phenobarbital and ergotamine orally; it is unclear if the adverse effects were due to belladonna or the other ingredients (34154).
Topically, belladonna plaster (Cuxon Gerrard) can cause contact dermatitis (34152).

Gastrointestinal ...Orally, belladonna can cause anticholinergic side effects such as dry mouth and constipation (553,34162,34163,34176,34180,34181).

Genitourinary ...Orally, belladonna can cause anticholinergic side effects such as urinary retention (553,34145,34150,34163).

Neurologic/CNS ...Orally, belladonna can cause anticholinergic side effects such as memory and attention impairment, headache, and confusion (553,34163,34180).

Ocular/Otic ...Orally and topically, belladonna can cause anticholinergic side effects such as dilation of pupils and blurred vision (553,34157,34168,34169,34180). A case report describes anisocoria (unequal pupil sizes) in a 70-year-old female who used homeopathic pink eye relief drops (Similasan) containing belladonna, eyebright, and hepar sulphuris (calcium sulfide) in one eye for 3 days. The pupil dilation lasted more than 2 weeks and did not respond to bright light or pilocarpine (106907). Another report describes a case of acute angle closure glaucoma, requiring referral to an ophthalmologist, in a 55-year-old female who used these eye drops for 2 days (106906).

(Read more about BELLADONNA)

General ...Orally and topically, calendula is generally well tolerated.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions.

Dermatologic ...Topically, a preparation containing calendula powder 0. 1% resulted in inflammation around the wound to which it was applied (96647). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of calendula, licorice, and snail secretion filtrate to the face. The specific role of calendula is unclear (110322).

Immunologic ...Orally, calendula can cause allergic reactions. Topically, calendula can cause eczematous allergic reactions. Calendula-specific patch testing is recommended prior to usage to determine allergenic potential. Testing is particularly necessary in individuals sensitive to the Asteraceae/Compositae family (10691,11458,96647). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. A preparation containing calendula powder 0.1% resulted in hives in a patient with a ragweed allergy (96647). Despite the widespread use of calendula and the occurrence of allergies to other family members, there has been only one report of anaphylaxis (11152).

(Read more about CALENDULA)

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).

(Read more about ECHINACEA)

General ...Orally, high doses of German ipecac may cause vomiting, apnea, and cardiac arrest. Seed extracts may cause advancing paralysis of the central nervous system (18).

(Read more about GERMAN IPECAC)

General ...Orally and topically, great plantain seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.

Dermatologic ...Topically, application can cause allergic contact dermatitis in some individuals (4).

Gastrointestinal ...Theoretically, great plantain may have laxative effects when used orally in excessive amounts (4).

(Read more about GREAT PLANTAIN)

General ...Pokeweed is generally regarded as unsafe for use. Any benefits of therapy may not outweigh the risk of toxicity. Orally, all parts of the pokeweed plant can cause nausea, vomiting, cramping, abdominal pain, diarrhea, a burning sensation in the mouth and throat, weakness, hypotension, bloody emesis, bloody diarrhea, tachycardia, difficulty breathing, salivation, urinary incontinence, spasms, convulsions (3477,3478,3479), severe thirst, somnolence, transient blindness, respiratory failure (3477,3479), and death (3477).
Orally and topically, pokeweed has been reported to cause plasmacytosis, mitotic changes in peripheral blood cells, eosinophilia, thrombocytopenia, abnormal platelet morphology, and other hematologic abnormalities (3477,3478,3481,3482). Protective gloves should be used to handle the plant (3477).

Cardiovascular ...Orally, all parts of the pokeweed plant can cause hypotension and tachycardia (3477,3478,3479).

Gastrointestinal ...Orally, all parts of the pokeweed plant can cause nausea, vomiting, cramping, abdominal pain, diarrhea, a burning sensation in the mouth and throat, bloody emesis, and bloody diarrhea (3477,3478,3479).

Genitourinary ...Orally, all parts of the pokeweed plant can cause urinary incontinence (3477,3478,3479).

Hematologic ...Orally and topically, pokeweed has been reported to cause plasmacytosis, mitotic changes in peripheral blood cells, eosinophilia, thrombocytopenia, abnormal platelet morphology, and other hematologic abnormalities. When used topically, these effects are more likely to occur in individuals with cuts or abrasions on the skin (3477,3478,3481,3482). Protective gloves should be used to handle the plant (3477).

Neurologic/CNS ...Orally, all parts of the pokeweed plant can cause weakness, salivation, spasms, convulsions (3477,3478,3479), severe thirst, and somnolence (3477,3479).

Ocular/Otic ...Orally, all parts of the pokeweed plant can cause transient blindness (3477,3479),

Pulmonary/Respiratory ...Orally, all parts of the pokeweed plant can cause difficulty breathing (3477,3478,3479), respiratory failure (3477,3479), and death (3477).

(Read more about POKEWEED)

General ...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.

Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).

Dermatologic ...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).

Gastrointestinal ...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).

Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).

Pulmonary/Respiratory ...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).

(Read more about SAGE)