WHITEE Patch by Wei Laboratories, Inc.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. Although there has been interest in using oral aconite for alopecia areata, there is insufficient reliable information about the clinical effects of aconite for this purpose.
• Amenorrhea. Although there has been interest in using oral aconite for amenorrhea, there is insufficient reliable information about the clinical effects of aconite for this purpose.
• Asthma. Although there has been interest in using oral aconite for asthma, there is insufficient reliable information about the clinical effects of aconite for this purpose.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using injectable aconite for COVID-19, there is insufficient reliable information about the clinical effects of aconite for this purpose.
• Diarrhea. Although there has been interest in using oral aconite for diarrhea, there is insufficient reliable information about the clinical effects of aconite for this purpose.
• Heart failure. It is unclear if oral aconite is beneficial in patients with left ventricular failure. Details: Preliminary clinical research in patients with left ventricular failure shows that taking heat processed aconite tuber 1000 mg daily for up to 7 months modestly improves heart and kidney function when compared with placebo (30314).
• Pneumonia. Injectable aconite has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Oral aconite has not been evaluated for this use. Details: A meta-analysis of 20 small, low-quality randomized and non-randomized studies in older Chinese adults with severe pneumonia shows that 77% of patients receiving an injection containing aconite extract 0.1 mg/mL and panax ginseng extract 0.8 mg/mL had improvement in symptoms such as fever, cough, and chest tightness when compared with 61% of those who received standard treatment. This combination injection may also modestly reduce disease severity and the risk of mortality when compared with standard treatment. However, these outcomes were not evaluated in all studies, and dosing regimens were heterogenous, with doses ranging from 60-100 mL daily or twice daily for 7-14 days (110472).
• Raynaud syndrome. Although there has been interest in using oral aconite for Raynaud syndrome, there is insufficient reliable information about the clinical effects of aconite for this purpose. More evidence is needed to rate aconite for these uses.

(Read more about ACONITE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amenorrhea. Although there has been interest in using oral cassia cinnamon for amenorrhea, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Angina. Although there has been interest in using oral cassia cinnamon for angina, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Common cold. Although there has been interest in using oral cassia cinnamon for the common cold, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Diabetes. Several clinical trials have evaluated oral cassia cinnamon for type 2 diabetes, but results are conflicting. Details: Some clinical studies and meta-analyses of cassia cinnamon have found significant benefits in patients with diabetes (11347,17011,21914,21918,89646,89649), while others have not (14344,16010,17689,21915,21916,89650). Results from meta-analyses are also mixed with respect to lowering fasting blood glucose and lipid levels (89647,108264). A meta-analysis including more than 500 adults with type 2 diabetes show that taking cassia cinnamon 120 mg To 14.4 grams daily for 4-18 weeks reduces fasting blood glucose by an average of 25 mg/dL, total cholesterol by 16 mg/dL, low-density lipoprotein (LDL) cholesterol by 9 mg/dL, and triglycerides by 30 mg/dL, and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL (89647). Analyses included studies examining either extract or powder, and two of the studies included used an unspecified type of cinnamon. In contrast, a more recent meta-analysis of studies limited to cassia cinnamon ground bark powder 1-2 grams daily for 40-90 days shows no benefit on fasting blood glucose or lipid levels (108264). Evidence regarding cassia cinnamon's effect on glycated hemoglobin (HbA1c) is mixed. In patients with type 2 diabetes, a meta-analysis of 18 low-quality clinical studies shows that cassia cinnamon lowers HbA1c by about 0.6% when compared with placebo (113675). However, other studies suggest that cassia cinnamon does not change HbA1c, although some of the studies were too short to detect a change (89647,108264). The individual studies included in the meta-analyses were also small, and very heterogenous in relation to dose, duration, use of conventional medications, and diabetes control at baseline (89647,108264). Cassia cinnamon has also been evaluated in combination with other ingredients. A study in treatment-naïve adults newly diagnosed with type 2 diabetes shows that taking a combination product containing cassia cinnamon extract 100 mg, black seed extract, and ficin extract (NW Low-Glu) 4-5 times daily for 12 weeks reduces HbA1c by 0.6-0.8% and 2-hour postprandial glucose by 25-35 mg/dl when compared to baseline, with similar findings when compared with metformin. However, there were no notable differences in fasting blood glucose, insulin resistance, and beta cell function (111710). It is unclear if these effects are due to cassia cinnamon, other ingredients, or the combination. In patients with type 1 diabetes, clinical research shows that taking cassia cinnamon daily does not improve fasting blood glucose, HbA1c, insulin sensitivity, or the rate of hypoglycemic episodes (16010,89648).
• Diarrhea. It is unclear if oral cassia cinnamon is beneficial for diarrhea. Details: A moderate-sized clinical study in adults with diarrhea shows that taking cinnamon water extract 1200 mg twice daily for 8 weeks increases colonic transit time by about 10 hours but does not improve other symptoms of diarrhea including percentage of bowel movements with diarrhea, Bristol stool scale score, abdominal pain, bowel urgency, or abdominal distension when compared with placebo (111712).
• Dyslipidemia. It is unclear if oral cassia cinnamon is beneficial for dyslipidemia. Details: A meta-analysis of 12 clinical studies in adults with metabolic syndrome, polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, prediabetes, and overweight or obesity shows that taking cassia cinnamon daily for 2-4 months reduces total cholesterol by 7 mg/dL, triglycerides by 9 mg/dL, and low-density lipoprotein (LDL) cholesterol by 6 mg/dL but does not increase high-density lipoprotein (HDL) cholesterol. Subgroup analysis suggests that cassia cinnamon improves lipid profiles of Asian patients but not European or American patients. Additionally, higher doses appear to regulate lipid profiles better, and cassia cinnamon doses above 1.5 grams daily increase high-density lipoprotein cholesterol by about 2.5 mg/dL. Subgroup analysis also shows that cassia cinnamon only reduces triglycerides for patients with metabolic syndrome and increases HDL cholesterol for patients with PCOS but does not impact total cholesterol for those with type 2 diabetes (111709).
• Erectile dysfunction (ED). Although there has been interest in using oral cassia cinnamon for ED, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Gastritis. It is unclear if oral cassia cinnamon is beneficial for gastritis. Details: A large clinical trial in adults in Korea with acute or chronic gastritis shows that taking cassia cinnamon 225 mg daily for up to 14 days improves the gastric erosion rate by approximately 1.4-fold when compared with control. A subgroup analysis indicates this effect was most pronounced in patients with chronic gastritis (115487).
• Hypertension. Although there has been interest in using oral cassia cinnamon for hypertension, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Impaired glucose tolerance (prediabetes). The effects of cassia cinnamon in patients with impaired glucose tolerance are unclear; results from clinical research are conflicting. Details: A small clinical study in patients with impaired glucose tolerance shows that taking cassia cinnamon powder 6 grams twice daily for 12 weeks does not improve fasting plasma glucose or insulin sensitivity when compared with placebo (96280). However, another clinical study in overweight or obese patients with impaired fasting blood glucose shows that taking a dried aqueous extract of cassia cinnamon 250 mg twice daily for 12 weeks reduces fasting blood glucose by about 12 mg/dL when compared with baseline, but does not affect fasting insulin levels (93118). Another preliminary clinical trial in overweight or obese patients with impaired glucose tolerance shows that taking two capsules of a specific combination product, (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months decreases fasting blood glucose by 6.5 mg/dL but has no effect on glycated hemoglobin (HbA1c), insulin sensitivity, or body weight, when compared with placebo (94234). It is unclear whether these effects are due to cassia cinnamon, ingredients, or the combination.
• Mosquito repellent. It is unclear if topical cassia cinnamon is beneficial as a mosquito repellent. Details: Preliminary clinical research suggests that applying a cream containing cassia cinnamon oil 5% to the skin provides protection from mosquito bites. However, the repellency of this cream appears to decrease more quickly over time compared to MeiMei cream (containing citronella and geranium oils) and Repellan S aerosol (containing 19% N,N-diethyl-m-toluamide (DEET)) (59580).
• Muscle cramps. Although there has been interest in using oral cassia cinnamon for muscle cramps, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Nausea and vomiting. Although there has been interest in using oral cassia cinnamon for nausea and vomiting, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Obesity. It is unclear if oral cassia cinnamon is beneficial for weight loss. Details: Preliminary clinical research in a small number of patients with overweight or obesity and impaired glucose tolerance shows that taking two capsules of a specific combination product (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months does not decrease body weight, BMI, fat mass, or lipid levels when compared with placebo (94234). A very small clinical study in healthy adults shows that drinking a single dose of cinnamon infusion containing 2 grams of powdered cinnamon served along with breakfast does not increase energy expenditure, diet-induced thermogenesis, respiratory quotient, or lipid and carbohydrate oxidation and does not affect appetite responses including hunger, fullness, desire to eat, macronutrient intake, and food intake throughout the day when compared with control. Furthermore, cassia cinnamon intake reduces feelings of satiety and increases energy intake in the first meal after the intervention when compared with control (111707). The validity of these findings is limited by a lack of blinding.
• Polycystic ovary syndrome (PCOS). It is unclear if oral cassia cinnamon is beneficial for patients with PCOS. Details: A small observational study in adults with PCOS suggests that taking cinnamon 500 mg three times daily for 8 weeks is associated with decreased body weight, body mass index, insulin resistance, and testosterone but does not appear to alter levels of luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone (DHEA), insulin, or lipids when compared with placebo (113514).
• Stroke. It is unclear if oral cassia cinnamon is beneficial for stroke prevention. Details: Preliminary clinical research in patients with a mild ischemic stroke or transient ischemic attack shows that taking cinnamon (Chinese herbal formula granules, Guangdong Yifang Pharmaceutical Co, Ltd) 5 grams with aspirin 100 mg daily for 90 days, starting within 24 hours of the ischemia, reduces the percentage of patients with a recurrent stroke to 3%, compared with 15% of those taking aspirin plus placebo. There were also modest improvements in levels of plasma lipids, glucose, and glycated hemoglobin, as well as a reduced likelihood of identifying unstable or severe plaques on carotid ultrasound (108265). The use of cassia cinnamon, specifically, was not confirmed; however, this species of cinnamon is commonly used in traditional Chinese medicine, as indicated in the study.
• Urinary incontinence. Although there has been interest in using oral cassia cinnamon for urinary incontinence, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose. More evidence is needed to rate cassia cinnamon for these uses.

(Read more about CASSIA CINNAMON)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using oral dong quai for atopic dermatitis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Chronic kidney disease (CKD). There is limited evidence on the use of dong quai in patients with CKD. Details: A large propensity score-matched observational study over 15 years in Taiwanese adults with CKD suggests that taking dong quai is associated with a 5.1% risk of end-stage renal disease (ESRD) and 38% risk of overall mortality when compared with 7% and 56%, respectively, in controls. Higher cumulative doses (i.e., 15 grams or more) and longer duration of exposure (i.e., > 60 days) are also associated with fewer ESRD events (112362). However, the interpretation of these findings is limited by the lack of exact dosage information and retrospective study design.
• Coronary heart disease (CHD). Intravenous dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with CHD shows that injecting 20 mL of an intravenous solution containing dong quai, ginseng, and astragalus (Yi-qi Huo-xue Injection) daily for 2 weeks reduces the frequency and severity of angina episodes when compared with placebo. It also seems to increase exercise tolerance and improve left ventricular function when compared with placebo (33046). It is unclear if these benefits are due to dong quai, other ingredients, or the combination.
• Dysmenorrhea. Although there is interest in using oral dong quai for dysmenorrhea, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Hypertension. Although there is interest in using oral dong quai for hypertension, there is insufficient reliable information about the clinical effects of dong quai for this purpose.
• Idiopathic interstitial pneumonia. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 17 studies conducted in China in patients with idiopathic interstitial pneumonia concludes that adding traditional Chinese medicine combinations containing dong quai root and astragalus root to treatment with conventional medicines improves pulmonary function index, six-minute walking distance, and the Borg scale of perceived exertion when compared with conventional treatment alone (103618). The included studies are of low quality, include a range of treatment durations from 1-12 months, and vary in the conventional medicines and Chinese herb combinations used. The doses of dong quai used were not stated.
• Infertility. Although there is interest in using oral dong quai for infertility, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Iron deficiency anemia. Although there is interest in using oral dong quai for iron deficiency anemia, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Menopausal symptoms. There is inconsistent and contradictory evidence about the effect of dong quai on menopausal symptoms. Benefits have only been seen when it is used in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking dong quai, 1.5 grams three times daily for 24 weeks, does not affect menopausal symptoms (738). Other clinical research shows that dong quai improves menopausal symptoms when used in combination with other constituents. In one clinical trial, taking five chewable tablets of a specific combination of dong quai and chamomile (Climex) daily for 12 weeks reduced the frequency and severity of hot flushes when compared with placebo (48445). In another trial, taking a combination providing dong quai 75 mg, along with American ginseng, black cohosh, milk thistle, red clover, and vitex agnus-castus (Phyto-Female Complex) twice daily for 3 months reduces menopausal symptoms, including the number and intensity of hot flushes, the number of night sweats, and sleep quality (19552). Taking another combination product containing dong quai, burdock root, licorice root, motherwort, and Mexican wild yam root, 500 mg three times daily for 3 months, also reduces menopausal symptoms when compared with placebo (48522). It is unclear if the beneficial effects in these studies were due to dong quai, other ingredients, or a combination of ingredients.
• Migraine headache. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with menstrual migraine shows that taking a combination of soy isoflavones 60 mg, dong quai 100 mg, and black cohosh 50 mg daily for 24 weeks reduces the frequency of attacks when compared with placebo (35797). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Osteoporosis. Although there is interest in using oral dong quai for osteoporosis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Peptic ulcers. Although there is interest in using oral dong quai for peptic ulcers, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Premature ejaculation. Topical dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In one preliminary clinical trial in patients with premature ejaculation, a multi-ingredient cream preparation (SS Cream) containing dong quai, Panax ginseng root, Cistanches deserticola, Zanthoxyl species, Torlidis seed, clove flower, Asiasari root, cinnamon bark, and toad venom was applied to the glans penis 1 hour prior to intercourse and washed off immediately before intercourse. Patients using the cream had significantly improved ejaculatory latency when compared with placebo cream (2537). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there is interest in using oral dong quai for PMS, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Psoriasis. Although there is interest in using oral dong quai for psoriasis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Pulmonary hypertension. Preliminary clinical research shows that intravenous dong quai may be effective in patients with pulmonary hypertension. Details: Some preliminary clinical research in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension shows that intravenous administration of 250 mL of a solution containing dong quai 25%, once daily for 5-10 days, reduces pulmonary arterial pressure and pulmonary vascular resistance when compared to baseline (48438,48442,48443). The validity of these findings is limited by the lack of comparator groups.
• Rheumatoid arthritis (RA). Although there is interest in using oral dong quai for RA, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Stroke. Preliminary evidence does not support the use of intravenous dong quai for acute ischemic stroke. Details: Preliminary clinical research in patients with acute ischemic stroke shows that administering 200 mL of a solution containing dong quai 25% intravenously daily for 20 days does not improve neurological symptoms when compared with dextran-40 (48483). More evidence is needed to rate dong quai for these uses.

(Read more about DONG QUAI)

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)

There is insufficient reliable information available about the effectiveness of ox-eye daisy.

(Read more about OX-EYE DAISY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if topical peony is beneficial in patients with aging skin. Details: Preliminary clinical research shows that using a cosmetic ingredient containing 0.5% paeoniflorin, a constituent of peony root, for 8 weeks can reduce facial wrinkles when compared with baseline (68356). The validity of this finding is limited by the lack of a comparator group.
• Anal fissures. Although there has been interest in using topical peony for anal fissures, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Ankylosing spondylitis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve disease symptoms in patients with ankylosing spondylitis. Details: A meta-analysis of 3 clinical trials in patients with ankylosing spondylitis (AS) shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves the AS disease activity score when compared with conventional treatment alone. TGP also improves inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, and interleukin-6 (112861). The reliability of these findings is limited by the low to very low quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Antipsychotic-induced hyperprolactinemia. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with risperidone-induced hyperprolactinemia shows that taking a specific combination of peony and licorice (Peony-Glycyrrhiza Decoction; PGD) 45 grams daily for 4 weeks is similarly effective to bromocriptine for reducing prolactin levels (59775). A similar trial in males with antipsychotic-induced hyperprolactinemia shows that taking an herbal extract containing peony and licorice (shakuyaku-kanzo-to), 2.5 grams three times daily, reduces prolactin levels after 4 weeks of treatment when compared with baseline. Prolactin levels returned to baseline 4 weeks after treatment cessation (59907). The validity of this study is limited by the lack of a comparator group. Subsequently, a higher quality clinical trial in females with antipsychotic-induced hyperprolactinemia shows that taking a peony and licorice decoction (PGD) 45 grams daily for 16 weeks does not improve prolactin levels or clinical symptoms when compared with placebo (97219). However, a small clinical trial in adults with schizophrenia and sexual dysfunction due to antipsychotic-induced hyperprolactinemia shows that taking a similar PGD formulation for 8 weeks improves sexual function scores and prevents further increases in prolactin levels when compared with a non-treated control group (112412). It is unclear if any effects are due to peony, licorice, or the combination.
• Atherosclerosis. Although there has been interest in using oral peony for atherosclerosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral peony for CFS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cirrhosis. Although there has been interest in using oral peony for cirrhosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cough. Although there has been interest in using oral peony for cough, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dysmenorrhea. Although there has been interest in using oral peony for dysmenorrhea, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dyspepsia. Although there has been interest in using oral peony for dyspepsia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Diabetic nephropathy. It is unclear if oral peony is beneficial in patients with diabetic nephropathy. Details: Preliminary clinical research in Chinese adults with diabetic nephropathy shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with losartan 100 mg daily for 6 months does not improve urinary albumin excretion rate when compared with losartan alone. Taking TGP in conjunction with losartan also did not affect serum creatinine, fasting glucose, glycated hemoglobin (HbA1c), triglycerides, or total cholesterol when compared with losartan alone (98466).
• Epilepsy. It is unclear if oral peony is beneficial in patients with epilepsy. Details: Preliminary clinical research in children 1-14 years of age with intractable epilepsy shows that taking peony root extract orally 20 mg/kg twice daily for 4 weeks reduces weekly seizure frequency and average seizure duration by 80% and 83%, respectively, when compared with baseline. Approximately 63% of subjects reported a reduction in seizure frequency of at least 50% when compared with baseline. The validity of this study is limited by the lack of a comparator group (106851).
• Gout. Although there has been interest in using oral peony for gout, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Hepatitis. Although there has been interest in using oral peony for hepatitis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Juvenile idiopathic arthritis (JIA). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with JIA. Details: A pooled analysis of low-quality clinical research in Chinese children 1.5-14 years of age with JIA shows that taking TGP 30-180 mg/kg daily or 600-1800 mg daily in conjunction with methotrexate for 9-26 weeks improves the odds of overall response rate by 1.5 to 2.5 times when compared with methotrexate alone. TGP also reduces erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels when compared with methotrexate alone. Preliminary subgroup analyses suggest that TGP is not effective for JIA if it is taken for 8 weeks or less (92785). Another meta-analysis of 7 small to moderate-sized clinical trials in children with JIA also shows that taking TGP 0.3 mg/kg, 30-60 mg/kg, or 1200 mg daily with conventional treatment for 12-24 weeks improves effectiveness rates when compared with conventional treatment alone. TGP also reduces ESR, CRP, and tumor necrosis factor alpha (TNF-α) (112861). The reliability of these findings is limited by the variability in the quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Mastalgia. Although there has been interest in using oral peony for mastalgia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Migraine headache. Although there has been interest in using oral peony for migraine, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Muscle cramps. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary, low-quality, clinical research shows that taking a specific combination of peony and licorice (shakuyaku-kanzo-to) orally, 2.5-6 grams daily for up to 4 weeks, relieves muscle cramps when compared to baseline in patients undergoing hemodialysis (13551,13552). The validity of these studies is limited by the lack of a comparator group. It is also unclear if this effect is due to peony, licorice, or the combination.
• Neuropathic pain. Although there has been interest in using oral peony for neuropathic pain, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Osteoarthritis. Some low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with osteoarthritis. Details: A meta-analysis of 4 moderate-sized clinical trials in adults with osteoarthritis shows that taking TGP 0.6 grams 2 or 3 times daily with conventional medical treatment for 4-12 weeks improves joint pain when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Pancreatitis. It is unclear if rectal peony is beneficial in patients with pancreatitis. Details: Preliminary clinical research in adults with moderate to severe acute pancreatitis shows that rectal administration of 150 mL water containing 15 grams of red peony root granules twice daily for 7 days in addition to standard care reduces the time to resolution of abdominal pain and normal bowel habits by 25% when compared with a placebo enema. Additionally, patients receiving red peony root had an average 2-day reduction in hospital stay and a greater improvement on the modified Balthazar CT score when compared with placebo (104283).
• Polycystic ovary syndrome (PCOS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking peony root extract 2250 mg daily, along with Ceylon cinnamon, levant berry, St. John's wort, Tribulus, and licorice, during the follicular phase of the menstrual cycle for 3 months reduces the rate of oligomenorrhea or amenorrhea by 33% and the time between menstrual cycles by 43 days when compared with lifestyle modification alone. Taking this combination also improves quality of life by about 30% and modestly reduces body weight and body mass index when compared with lifestyle intervention alone. Although taking this combination improved conception rate by 4-fold, live birth rate was similar to lifestyle intervention alone (97216). It is unclear if these effects are due to peony, the other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there has been interest in using oral peony for PMS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Psoriasis. It is unclear if oral peony is beneficial for plaque psoriasis. Details: Preliminary clinical research in Chinese adults with moderate to severe plaque psoriasis shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with acitretin for 12 weeks does not improve plaque size or severity when compared with acitretin alone. However, taking TGP in combination with acitretin might increase the number of patients achieving a 50% reduction in plaque size when compared with acitretin alone (97950).
• Psoriatic arthritis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve symptoms in patients with psoriatic arthritis. Details: A meta-analysis of 2 small clinical trials in adults with psoriatic arthritis shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves Psoriasis Area and Severity Index (PASI) scores and the inflammatory marker erythrocyte sedimentation rate when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Respiratory tract infections. Although there has been interest in using oral peony for respiratory tract infections, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Restless legs syndrome (RLS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 12 low-quality clinical studies in Chinese patients with RLS shows that taking peony-containing combination herbal preparations along with conventional therapy appears to improve sleep quality and decrease RLS symptoms when compared with conventional therapy alone. A few of the studies included in this analysis also suggest that taking peony-containing herbal products alone might be more effective than conventional therapy for RLS (100991). The peony-containing products included in this analysis contained between 4-15 other herbal ingredients. It is unclear whether the effects are due to peony, other ingredients, or the combination.
• Rheumatoid arthritis (RA). It is unclear if oral peony is beneficial in patients with RA; evidence is conflicting. Details: Although low-quality clinical research in patients with RA has shown that use of total glucosides of peony (TGP) in conjunction with standard treatment for 4-24 weeks reduces inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein when compared with standard treatment alone, effects on RA symptoms are conflicting (92786,101245,112861). A pooled analysis of clinical research in adults with RA shows that taking TGP in conjunction with leflunomide for 4-24 weeks is less effective for reducing RA symptom scores than taking leflunomide alone (92786). In contrast, another pooled analysis of clinical research in adults with RA shows that taking TGP for 12-24 weeks in combination with methotrexate improves swollen joint count, but not other symptoms such as morning stiffness and tender joint count, when compared with methotrexate alone. Preliminary subgroup analyses also suggest that taking TGP in conjunction with methotrexate might reduce overall adverse effects when compared with methotrexate alone (101245). Of note, the dose of TGP used is not reported in most trials included in these two analyses. Another meta-analysis of 10 mostly small to moderate-sized clinical trials in adults with RA shows that taking TGP 0.6 grams 1-3 times daily with conventional medical treatment for 12-48 weeks improves symptoms as evaluated with the Disease Activity of 28 joints (DAS28) scale when compared with conventional treatment alone (112861). However, these analyses are all limited by the low quality of the included studies. Additionally, all of the included studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Sjogren syndrome. It is unclear if oral peony is beneficial in patients with Sjogren syndrome. Details: Some clinical research in Chinese adults with Sjogren syndrome shows that taking total glucosides of peony (TGP) 600 mg three times daily for 24 weeks improves overall symptoms, with the greatest effects on symptoms of dry eye and fatigue, when compared with placebo (100992). An earlier and smaller clinical study from the same research group found that taking TGP at the same dose and duration improved symptoms of dry mouth, but did not reduce overall symptom scores or other markers of disease, when compared with placebo (97949). However, this study was not adequately powered to detect differences in overall symptom scores between TGP and placebo.
• Spasticity. Although there has been interest in using oral peony for spasticity, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Systemic lupus erythematosus (SLE). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve disease activity scores in patients with SLE. Details: A meta-analysis of 13 small to moderate-sized, low-quality clinical studies in patients with SLE shows that taking TGP 0.6 grams 2-3 times daily or 1.2 grams twice daily for 1-6 months in conjunction with conventional treatment modestly improves the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score when compared with conventional treatment alone. Analyses of secondary endpoints which were not available for all studies show that TGP also improves markers of SLE disease activity, including erythrocyte sedimentation rate (ESR) and C-reactive protein, reduces the average daily dose of glucocorticoids and the cumulative dose of cyclophosphamide, and decreases the rate of disease recurrence (110432). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies, which enrolled patients of varying age and disease severity. Additionally, a similar meta-analysis of 8 small to moderate-sized, low-quality clinical studies in adults with SLE shows that taking TGP 0.6 grams 2-3 times daily for 3-12 months in conjunction with conventional treatment of glucocorticoids and/or immunosuppressants improves SLEDAI scores when compared with conventional treatment alone. TGP also improves markers of inflammation such as ESR, levels of immunoglobulins A, G and M, and complement 3 and 4 (112862). The validity of these finding is also limited by substantial heterogeneity which may be due to differences in conventional therapies. In addition, all of the studies included in these meta-analyses were conducted in China; it is unclear if findings can be applied to other geographical regions and populations. More evidence is needed to rate peony for these uses.

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UNSAFE ...when used orally or topically. Aconite root contains toxic alkaloids that are strong, fast-acting poisons that affect the heart and central nervous system, causing severe arrhythmias, reduced consciousness, and death (15499,19669,30294,30300,30301,30303,30309,30334,30335,30336,92276,104514,106706). All species of this plant are dangerous. Severe poisoning has been reported after ingestion of 0.2-2 mg of aconitine, 1 gram of the raw plant, or 6 grams of processed and cured aconite (3490,104514). Even when a processed product is used, aconite can cause toxicity including nausea, vomiting, dizziness, muscle spasms, hypothermia, paralysis of the respiratory system, and heart rhythm disorders (15499). Aconite can also be absorbed through the skin and cause significant toxicity (12).

PREGNANCY AND LACTATION: UNSAFE
when used orally or topically (15499).

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LIKELY SAFE ...when consumed in amounts commonly found in foods. Cassia cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912) ...when used orally and appropriately, short-term. Cassia cinnamon up to 2 grams daily has been used safely for up to 3 months (17011,21914). Cassia cinnamon 3-6 grams daily has been used safely for up to 6 weeks (11347,14344). Cassia cinnamon extract corresponding to 3 grams daily of cassia cinnamon powder has also been used safely for up to 4 months (21916).

POSSIBLY SAFE ...when used topically, short-term. Cassia cinnamon oil 5% cream applied topically to the legs has been used safely in one clinical trial (59580).

POSSIBLY UNSAFE ...when used orally in high doses, long-term. Some cassia cinnamon products contain high levels of coumarin. Coumarin can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg daily can result in hepatotoxicity that resolves when coumarin use is discontinued (15302). In most cases, ingestion of cassia cinnamon will not provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Cassia cinnamon 1 gram daily has been used safely in adolescents 13-18 years of age for up to 3 months (89648).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of cassia cinnamon when used in medicinal amounts during pregnancy and breast-feeding. Stay on the safe side and stick to food amounts.

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POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).

POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).

LACTATION:
Insufficient reliable information available; avoid use.

(Read more about DONG QUAI)

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.

(Read more about MYRRH)

There is insufficient reliable information available about the safety of ox-eye daisy.

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

(Read more about OX-EYE DAISY)

POSSIBLY SAFE ...when used orally and appropriately, short term. Total glucosides of peony has been used with apparent safety in doses of up to 1800 mg daily for up to 12 months (92786,97949,97950,98466,100992,110432,112861,112862). Peony root extract has been used with apparent safety at a dose of 2250 mg daily for up to 3 months (97216). There is insufficient reliable information available about the safety of peony when used orally, topically, or rectally, long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Total glucosides of peony has been used with apparent safety in children 1.5-4 years of age at doses up to 180 mg/kg daily or 1.2 grams daily for up to 12 months (92785). Peony root extract 40 mg/kg daily has also been used with apparent safety in children 1-14 years of age for 4 weeks (106851).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Preliminary research suggests that peony can cause uterine contractions (13400). However, other preliminary research suggests a combination of peony and angelica with or without motherwort, banksias rose, and ligustica, might be safe (11015,48433). Until more is known, avoid use.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PEONY)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining aconite with other antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.  Details Higenamine, a constituent of aconite, is thought to have antiplatelet and antithrombotic effects. In an animal model of thrombosis, higenamine inhibited platelet aggregation and reduced the size of thrombus formation (92282).

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining aconite with other stimulant drugs might alter the effects of the stimulant drug or increase the risk of cardiovascular toxicity.  Details Aconite and its constituents have stimulant effects due to agonist activity at beta-2-adrenoreceptors. In cardiac muscle, aconite appears to have a positive inotropic effect and increases heart rate and blood pressure (2634,15499,30296,92282). However, some constituents of aconite can reduce heart rate and blood pressure (15499,30343).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.  Details Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents (11347,17011,21914,21918,89649). Dose adjustments to diabetes medications might be necessary.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.  Details There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued (15302,97249). Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

(Read more about CASSIA CINNAMON)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.  Details Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may reduce the effects of estrogens.  Details Dong quai has estrogenic effects (6180,7860,15108,15535,48459). Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Dong quai may increase the risk of bleeding when used with warfarin.  Details Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).

(Read more about DONG QUAI)

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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(Read more about OX-EYE DAISY)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.  Details In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might increase the levels and clinical effects of clozapine.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect 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, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, peony might reduce the levels and clinical effects of phenytoin.  Details Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).

(Read more about PEONY)

General ...Orally and topically, aconite is generally regarded as unsafe for use. Any benefits of therapy might not outweigh the risk of toxicity.
Most Common Adverse Effects:
All routes of administration: Serious neurologic, cardiovascular, gastrointestinal, and respiratory adverse effects have been reported.

Cardiovascular ...Orally and topically, aconite can cause hypotension, palpitations, chest tightness, pulmonary edema, arrhythmia, bradycardia, tachycardia, sustained or bidirectional ventricular tachycardia, ventricular fibrillation, and Torsade de pointes (558,559,561,562,563,3490,15499,15650,30294,30295)(30300,30305,30323,30336,92276,92277,92278,104514,106706,110473)(112901). Cardioversion has been reported to be ineffective for the reversal of aconite-induced dysrhythmia, but the use of agents such as amiodarone, lidocaine, and magnesium have been successful in some cases (2634,3490,106706,112901).

Gastrointestinal ...Orally, aconite can cause nausea, vomiting, diarrhea, and gastric pain (563,30297,30341,92277,92278). Topically, aconite can cause nausea and vomiting (92276).

Neurologic/CNS ...Orally, aconite can cause weakness, sweating, restlessness, dizziness, numbness, paresthesia, seizures, and reduced consciousness (558,559,561,562,563,3490,15499,15650,30335,30336,30341,92277,92278,104513). Topically, aconite can cause generalized paresthesia, fatigue, sweating, dizziness and tongue numbness (92276).

Ocular/Otic ...Orally, aconite has been reported to cause visual blurring and yellow-green vision with pupil dilation (30319).

Pulmonary/Respiratory ...Orally, aconite overdose can lead to respiratory failure (104513).

Renal ...Orally and topically, aconite can cause hypokalemia and metabolic and/or respiratory acidosis (558,559,561,562,563,3490,15499,15650).

Other ...Orally and topically, aconite has been reported to cause death in both adults and children (559,3490,3491,30301,30334,30341,92276,92278). In one case report, topical application of aconite to an infant led to cardiogenic shock with multi-organ failure and death (92276). Poisoning has been reported in 15 patients after consuming a homemade liquor containing aconite. Patients presented with tongue or extremity numbness, vomiting, dizziness, or heart palpitations, and 5 died (110471). Death has also been reported in individuals who cooked aconite tubers as vegetables or for health purposes (92278).
The first symptoms of aconite poisoning after oral ingestion of the leaves or root usually occur within 10-90 minutes, although toxicity may be delayed until a second or third dose (559,15499,104513,110471). Recovery time from aconite poisoning ranges from 1.5-2 days for mild intoxication to 7-9 days for patients with cardiovascular complications; fatalities in treated patients are about 5% (15499). Treatment of aconite toxicity is typically supportive, although charcoal hemoperfusion has aided in detoxification (15499,106706).

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General ...Orally, cassia cinnamon appears to be well-tolerated. Significant side effects have not been reported in most patients.
Most Common Adverse Effects:
Topically: Burning mouth, stomatitis.

Dermatologic ...In one clinical trial, a rash was reported in one patient taking cassia cinnamon 1 gram daily for 90 days (17011).
In one case, a 58-year-old female with a documented allergy to topically applied cinnamic alcohol presented with eyelid dermatitis, which was found to be a manifestation of systemic contact dermatitis to cinnamon in the diet. Symptoms improved in two days and completely cleared five days after discontinuing the addition of cinnamon to food products (95599). In other case reports, two adults presented with allergic contact cheilitis following the ingestion of chai tea with cinnamon and yogurt with cinnamon. Cinnamon components were confirmed as the causative allergic agents with patch tests, and both cases of allergic contact cheilitis completely resolved upon cessation of the cinnamon-containing products (113516,113515).
Topically, allergic skin reactions and stomatitis from toothpaste flavored with cassia cinnamon have been reported (11915,11920). Intraoral allergic reactions with symptoms of tenderness and burning sensations of the oral mucosa have also been reported in patients using breath fresheners, toothpaste, mouthwash, candy, or chewing gum containing cinnamon, cinnamic aldehyde or cinnamic alcohol as flavoring agents. Glossodynia, or burning mouth syndrome, has also been reported in a 62-year-old female who ate apples dipped in cinnamon nightly (95598), and allergic contact dermatitis has been reported in a teenage female using a homemade cinnamon sugar face scrub (95596).

Endocrine ...In one clinical trial, a hypoglycemic seizure was reported in one patient taking cassia cinnamon 1 gram daily for 3 months. The event occurred one day after enrolling in the study (89648). It is unclear if cassia cinnamon caused this event.

Hepatic ...There is some concern about the safety of ingesting large amounts of cassia cinnamon for extended durations due to its coumarin content. Coumarin can cause hepatotoxicity in animal models (15299). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin is discontinued (15302). In clinical trials, taking cassia cinnamon 360 mg to 12 grams daily for 3 months did not significantly increase levels of aspartate transaminase (AST) or alanine transaminase (ALT) (21918,96280,108259). However, in one case report, acute hepatitis with elevated AST and ALT occurred in a 73-year-old female who started taking a cinnamon supplement (dose unknown) one week prior to admission. The cinnamon supplement was added on to high-dose rosuvastatin, which may have led to additive adverse hepatic effects. After discontinuing both products, liver function returned to normal, and the patient was able to restart rosuvastati without further complications (97249). In most cases, ingestion of cassia cinnamon won't provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease or taking potentially hepatotoxic agents, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.

Immunologic ...An unspecified allergic reaction was reported in one patient taking cassia cinnamon 1 gram daily for 3 months (89648).

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General ...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.

Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).

Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).

Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).

Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).

Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.

Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).

Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).

Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).

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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 ...There is limited reliable information available about the adverse effects of ox-eye daisy.

Immunologic ...Ox-eye daisy can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

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General ...Orally, peony seems to be well tolerated when used alone and as part of Chinese herbal formulas.
Most Common Adverse Effects:
Orally: Abdominal distension, anorexia, diarrhea, gastrointestinal discomfort, nausea.
Topically: Dermatitis.

Dermatologic ...Topically, peony has been reported to cause contact dermatitis (13555).

Endocrine ...Orally, a specific traditional Chinese medicine preparation called DDT has been reported to lower follicle-stimulating hormone (FSH) levels and increase estradiol levels. It is not known if this effect is due to peony or the other ingredients (48404). Another specific traditional Chinese medicine preparation, Toki-shakuyaku-san, has been reported to increase plasma progesterone levels in some patients. It is not known if this effect is due to peony or the other ingredients (15294).

Gastrointestinal ...Orally, peony and total glucosides of peony (TGP) have been reported to cause gastrointestinal discomfort, including abdominal distension, anorexia, diarrhea, and nausea, in some patients (13538,92785,97949,98466,100992). In one clinical study, diarrhea was reported in 5% of patients taking TGP 600 mg three times daily for 24 weeks versus 1% of patients taking placebo (100992).

Hematologic ...Orally, there is one case report of easy gum bleeding, epistaxis, and skin bruising with an international normalized ratio (INR) above 6 in a 61-year-old male who was previously stable on warfarin therapy. This patient had switched from one brand of quilinggao, a popular Chinese herbal product, to another brand 5 days prior. This product contained Fritillaria spp. (beimu), Paeonia rubra, Chinese peony (chishao), Lonicera japonica (jinyinhua), and Poncirus trifoliata (jishi). The patient's INR decreased to 1.9 after temporary withdrawal of warfarin therapy. Upon re-initiation of quilinggao, his INR increased to 5.2. It is not known if the increased INR is due to peony or the other ingredients (68343).

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