Immunattack [Discontinued] by Herb Pharm

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 respiraA 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)

LIKELY INEFFECTIVE

• Schistosomiasis. Most research suggests that oral myrrh extract is not effective for treating schistosomiasis. Details: Although one manufacturer-sponsored study shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg once daily for 6 days cures schistosomiasis in about 90% of patients, multiple clinical studies show that taking this myrrh extract does not treat schistosomiasis in children or adults. In one study, only about 9% of adults and children treated with this myrrh extract at a dose of 600 mg every 3 weeks for 2 doses were cured compared to about 76% of patients treated with praziquantel (95541). A similar lack of benefit was shown in another clinical trial in which children were given a higher dose of 300 mg daily for 3 days or 600 mg daily for 6 days (95542,95545). A systematic review of the available literature concludes that praziquantel continues to be the treatment of choice for schistosomiasis, and that myrrh appears ineffective for parasitological cure (95544).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Back pain. It is unclear if oral myrrh is beneficial in patients with back pain, and topical myrrh has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with chronic low back pain shows that two 15-minute sessions of lumbar massage weekly with 5 mL of myrrh 2% and frankincense 2% essential oils for 3 weeks reduces measures of pain and disability when compared with placebo (111504). An observational study in adults with chronic lower back pain and sciatica suggests that taking a combination of myrrh 200 mg, palmitoylethanolamide 600 mg, and alpha-lipoic acid 800 mg daily for 30 days, along with periradicular infiltrations of oxygen-ozone, is associated with resolution of pain in 17% more patients when compared with periradicular steroid infiltrations at 60 days (111308). However, it is unclear if the effects in these studies are due to myrrh, other ingredients, or the combinations. Additionally, observational research in adults with chronic low back pain of varying intensity has found that taking a specific myrrh extract (MyrliMax, Sundyota Numandis Pharmaceuticals) 100 mg twice daily for 20 days is associated with reductions in pain and the need for rescue analgesics when compared to baseline (111112). The validity of these findings is limited by the lack of a control group.
• Cancer. Although there has been interest in using oral myrrh for cancer, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Canker sores. Although there has been interest in using topical myrrh for canker sores, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Common cold. Although there has been interest in using oral myrrh for the common cold, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Cough. Although there has been interest in using oral myrrh for cough, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Crohn disease. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 24-28 days in a small group of patients with active inflammatory bowel disease (50% ulcerative colitis and 50% Crohn disease) has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH) results in symptom resolution in 16-26 days. The probability of being free of symptoms did not differ between patients using other treatments, the myrrh combination product alone, or a combination of the myrrh product with other treatments. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Dental peri-implantitis. It is unclear if rinsing with myrrh mouthwash solution is effective for the prevention of dental peri-implantitis. Details: A small clinical study in adults undergoing dental implant placement shows that rinsing with myrrh 1% mouthwash solution twice daily for 2 weeks leads to similar rates of postoperative bleeding, pain, redness, and swelling when compared with chlorhexidine 0.12% mouthwash (111114).
• Diarrhea. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 7-14 days in a group of patients with active diarrhea related to an acute inflammatory disorder has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), alone or in combination with other therapies, improves overall symptoms of diarrhea. The median time to symptom resolution was 4 days. The probability of symptom resolution with use of the myrrh combination product was similar to that observed when other treatments were used. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Fasciolosis. It is unclear if oral myrrh extract is beneficial in patients with fasciolosis. Details: A small clinical study in adults and children with fasciolosis shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg daily for 6 days leads to a cure rate of about 94% at 3 months. However, the lack of standardized stool sample evaluation and absence of a control group limit the validity of this finding (95543). Furthermore, another small study in adults and children with fasciolosis shows that taking this same product, 600 mg daily for 6 days, leads to a 0% cure rate at both 1 and 2 months (95545).
• Gingivitis. Although there has been interest in using topical myrrh for gingivitis, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Herniated disc. Oral myrrh has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational study in adults with acute lumbosacral radiculopathy secondary to lumbar disc herniation suggests that taking a combination supplement containing myrrh 100 mg, alpha-lipoic acid 404 mg, and palmitoylethanolamide (PEA) 306 mg (Tiobec Dol, Uriach Italy Srl) twice daily for 4 weeks, along with steroids and as needed opioids, is associated with reduced pain and disability and improved physical but not mental health as it pertains to quality of life when compared with steroids and as needed opioids alone (111711). However, it is unclear if these effects are due to alpha-lipoic acid, other ingredients, or the combination.
• Intestinal parasite infection. It is unclear if oral myrrh extract is beneficial in children with intestinal parasite infections. Details: A small clinical study in immunocompetent children shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 10 mg/kg daily in combination with paromomycin 500 mg four times daily for 2 weeks improves symptoms such as abdominal pain, diarrhea, nausea, and vomiting when compared with paromomycin or myrrh extract alone. However, no differences in oocyst elimination were observed across groups (95546).
• Irritable bowel syndrome (IBS). Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research over a period of 24-28 days in a group of patients with IBS has found that taking a specific combination product containing myrrh 100 mg, coffee charcoal 50 mg, and chamomile extract 70 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), alone or in combination with other therapies, improves overall symptoms of diarrhea. The probability of being free of symptoms did not differ between patients using other treatments or when the myrrh combination product was used in combination with other treatments. Overall efficacy was rated as good to very good by patients and physicians (104593). The validity of these findings is limited by the observational nature of the study. Also, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Miscarriage. It is unclear if oral myrrh is beneficial in patients with incomplete miscarriage. Details: A small clinical study in adults with incomplete miscarriage (incomplete abortion) shows that taking myrrh 500 mg three times a day for 2 weeks increases the proportion of patients with successful complete abortion, defined as no retained products of conception, to 83%, compared to only 54% of those taking placebo (104840).
• Muscle cramps. Although there has been interest in using oral myrrh for muscle cramps, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Oral mucositis. Although there has been interest in using topical myrrh for oral mucositis, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Pain (acute). It is unclear if oral myrrh extract is beneficial in patients with acute pain. Details: A small clinical study shows that taking a specific, standardized myrrh extract (MyrLiq, Biosfered S.r.l.) 200-400 mg daily for 20 days can improve various types of acute pain, including headache, fever-associated pain, joint or muscle pain, lower back pain, and menstrual cramps, when compared with placebo (98224).
• Pain (chronic). It is unclear if oral myrrh extract is beneficial in patients with chronic pain. Details: A small clinical study shows that taking a specific, standardized myrrh extract (MyrLiq, Biosfered S.r.l.) 200-400 mg daily for 20 days can improve various types of chronic pain, including joint or muscle pain and lower back pain, when compared with placebo (98224).
• Peptic ulcers. Although there has been interest in using oral myrrh for peptic ulcers, there is insufficient reliable information about the clinical effects of myrrh for this purpose.
• Sciatica. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: Observational research in patients with sciatic pain due to herniated discs has found that taking a combination of myrrh extract 200 mg, alpha-lipoic acid 800 mg, and palmitoylethanolamide 600 mg daily for 20 days along with 3 sessions of oxygen-ozone therapy over 30 days is associated with slight improvements in pain when compared with oxygen-ozone therapy alone (111113). The validity of these findings is limited by the observational nature of the study. Additionally, it is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Tooth extraction. It is unclear if rinsing with myrrh extract solution is beneficial in patients undergoing tooth extraction. Details: A small clinical study in healthy, non-smoking adults shows that using a mouthwash containing myrrh extract 0.5% twice daily for 7 days following simple tooth extraction decreases the socket size in 90% of patients compared with 40% in the control group. Swelling and tenderness also decreased when compared with control (105846).
• Trichomoniasis. It is unclear if oral myrrh extract is beneficial in patients with trichomoniasis. Details: A small clinical study in patients with resistant Trichomonas vaginalis shows that taking a specific myrrh extract (Mirazid, Pharco Pharmaceuticals) 600 mg daily for 6-8 days cures infections in most patients. In this small study, 85% (11/13) of patients who did not respond to combination therapy with metronidazole and tinidazole were cured after receiving this myrrh extract (93652). A lack of control group limits the validity of these findings.
• Ulcerative colitis. Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: A small clinical study in patients with ulcerative colitis shows that taking a specific combination product containing myrrh 100 mg, chamomile extract 70 mg, and coffee charcoal 50 mg per tablet (MYRRHINIL-INTEST, Repha GmbH), four tablets three times daily for 12 months, is non-inferior to mesalamine therapy for maintaining remission (93653). In addition, observational research over a period of 24-28 days in a small group of patients with active inflammatory bowel disease (50% ulcerative colitis and 50% Crohn disease) has found that taking this same product results in symptom resolution in 16-26 days. The probability of being free of symptoms did not differ between patients using other treatments, the myrrh combination product alone, or the myrrh combination product with other treatments. Overall efficacy was rated as good to very good by physicians (104593). It is unclear if these findings are due to myrrh, other ingredients, or the combination.
• Urinary tract infections (UTIs). Oral myrrh has only been evaluated in combination with other ingredients, its effect when used alone is unclear. Details: A small clinical study in patients with at least 2 recurrent UTIs in the past 6 months or more than 3 UTIs in the past year shows that taking a combination of myrrh, hibiscus, and vegetable proteases (Aviur Retard ) for 6 months might reduce the risk of UTI recurrence. A UTI episode was not reported by 49% of females over the 6-month period, with an additional 35% reporting fewer than 2 UTIs (101115). The validity of these findings is limited by the lack of comparator group. Additionally, it unclear if this benefit is due to myrrh, other ingredients, or the combination.
• Wound healing. It is unclear if topical myrrh extract is beneficial for wound healing. Details: Two small clinical studies in patients requiring episiotomy during childbirth shows that using myrrh 1:5 tincture 10 mL or myrrh extract 20 mL, diluted in 5 L of water as a sitz bath, twice daily for 7 days, modestly improves ecchymosis, discharge, and wound healing scores when compared with either placebo, frankincense extract 20 mL, or betadine 10% solution 20 mL (104838,104839). It is unclear if these modest effects are clinically relevant. More evidence is needed to rate myrrh for these uses.

(Read more about MYRRH)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Common cold. Clinical research shows that taking three tablets of a specific combination product (Esberitox, Schaper & Brümmer GmbH & Co. KG) containing dry extracts of echinacea root, thuja leaf, and wild indigo root three times daily for 7-9 days improves the severity of cold symptoms, general well-being, and overall response rate when compared with placebo in patients experiencing moderate cold symptoms (6392). It is not clear if these effects are due to wild indigo, the other ingredients, or the combination. More evidence is needed to rate wild indigo for this use.

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

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

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

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

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when consumed in amounts commonly found in food. Myrrh is approved for use in foods as a flavoring agent in the US (11).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Myrrh 400 mg three times daily has been safely used for up to 12 months (93653,104593). Myrrh 500 mg three times daily has been used with apparent safety for 2 weeks (104840). ...when used topically and appropriately (2,4,5,11,18). As a diluted bath, myrrh has been used with apparent safety for up to 7 days (104838,104839).

POSSIBLY UNSAFE ...when used orally in excessive doses. Myrrh may cause kidney irritation and diarrhea when used in doses of 2-4 grams (12).

PREGNANCY: LIKELY UNSAFE
when used orally. Myrrh stimulates uterine tone and blood flow and may have an abortifacient effect (4,12,19,93645). There is insufficient reliable information available about the safety of the topical use of myrrh during pregnancy.

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY UNSAFE ...when used orally in large doses. Wild indigo is considered poisonous when consumed in doses of about 30 grams (12,19).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally or topically due to its toxic potential (12,19).

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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).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, myrrh might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details In vitro and animal research suggests that myrrh has hypoglycemic effects (4,104841).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, myrrh might decrease the effectiveness of warfarin.  Details In one case, a patient who was previously stable on warfarin had a significant decline in international normalized ratio (INR) following consumption of an aqueous extract of myrrh (14425).

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

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

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

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

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

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

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

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

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General ...Orally, myrrh seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Kidney impairment and heart rate changes at high doses.

Cardiovascular ...Orally, myrrh taken at doses of 2-4 grams may cause heart rate changes in some patients (12,19).

Dermatologic ...Topically, myrrh has been reported to cause dermatitis (6).

Gastrointestinal ...Orally, myrrh may cause diarrhea in some patients when taken at doses of 2-4 grams (12,19).

Genitourinary ...Severe lower abdominal pain has been reported in a pregnant woman drinking myrrh resin dissolved in 500 mL of water twice daily as prescribed by a traditional practitioner. This adverse effect resolved one day after discontinuing myrrh. The investigators suggest that this acute abdominal pain was related to myrrh's activity as a uterine stimulant (93645).

Immunologic ...Orally, myrrh has been reported to cause severe allergic skin reactions, with redness, swelling, and itching, in two case reports of individuals using oral traditional Chinese medicines containing myrrh (101114).

Renal ...Orally, myrrh may cause kidney impairment in some patients when taken at doses of 2-4 grams (12,19).

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General ...Orally, large doses of wild indigo are considered poisonous and can cause vomiting, diarrhea, gastrointestinal complaints, and spasms (12). Wild indigo has also been studied in combination with other herbal extracts.

Gastrointestinal ...Orally, large doses of wild indigo can cause vomiting, diarrhea, and gastrointestinal complaints (12).

Musculoskeletal ...Orally, large doses of wild indigo are considered poisonous and can cause spasms (12).

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