Cramp Bark Plus by Health Concerns

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Oral Corydalis yanhusuo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with functional constipation shows that taking a specific supplement (Motilitone, Dong-A ST) containing 30 mg of Corydalis yanhusuo and Pharbitis seed extracts three times daily before meals for 24 days improves colonic transit time, stool frequency, and symptoms of abdominal discomfort and pain when compared to baseline. At the start of the study, 63% of patients reported less than one stool per week. At the end of the study, 78% of patients were experiencing one or more stools per week, with 11% of patients reporting more than three stools per week (97159). The validity of these findings is limited by a lack of placebo control group.
• Depression. Although there has been interest in using oral Corydalis yanhusuo for depression, there is insufficient reliable information about the clinical effects of Corydalis yanhusuo for this purpose.
• Dysmenorrhea. Although there has been interest in using oral Corydalis yanhusuo for dysmenorrhea, there is insufficient reliable information about the clinical effects of Corydalis yanhusuo for this purpose.
• Dyspepsia. Oral Corydalis yanhusuo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in patients with functional dyspepsia shows that taking a specific supplement (Motilitone, Dong-A ST) containing 30 mg of Corydalis yanhusuo and Pharbitis seed extracts three times daily before meals for 4 weeks improves dyspepsia to a similar degree as pantoprazole 40 mg (97158).
• Gastroesophageal reflux disease (GERD). Oral Corydalis yanhusuo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with GERD shows that taking a specific supplement (Motilitone, Dong-A ST) containing 30 mg of Corydalis yanhusuo and Pharbitis seed extracts three times daily before meals for 4 weeks does not improve symptoms of dyspepsia or quality of life when compared with placebo (97160).
• Headache. Although there has been interest in using oral Corydalis yanhusuo for headache, there is insufficient reliable information about the clinical effects of Corydalis yanhusuo for this purpose.
• Helicobacter pylori. Although there has been interest in using oral Corydalis yanhusuo for Helicobacter pylori, there is insufficient reliable information about the clinical effects of Corydalis yanhusuo for this purpose. More evidence is needed to rate Corydalis yanhusuo for these uses.

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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.

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POSSIBLY EFFECTIVE

• Bleeding. Intramuscular motherwort injections, alone or in combination with standard treatment such as oxytocin, might reduce volume of blood loss and duration of bleeding after vaginal delivery, caesarian section, or induced abortion. Details: In females with postpartum bleeding after vaginal birth, most research shows that adding motherwort injection to oxytocin or carboprost treatment is more effective than those treatments alone. A meta-analysis of 29 low quality trials shows that injection with motherwort 40-140 mg, in addition to varying doses of oxytocin, is more effective than oxytocin alone for reducing blood loss after vaginal delivery (101890). This combination reduces the mean blood loss within 2 and 24 hours of delivery by 55 mL and 85 mL, respectively. Also, the risk of postpartum hemorrhage, defined as an estimated blood loss of at least 400 mL within 2 hours or at least 500 mL within 24 hours, is reduced by 71%, based on meta-analysis of 18 trials. Meta-analysis of 8 trials also shows motherwort alone to be more effective than oxytocin for reducing blood loss within 24 hours of delivery, but not within 2 hours of delivery. Meta-analysis of 4 trials shows that motherwort 40-200 mg is as effective as oxytocin for reducing the risk of postpartum hemorrhage (101890). Studies were all very low to low quality, with moderate to high risk of bias, and conducted in China, the latter of which limits generalizability to other geographic regions. In females with post-caesarian bleeding, adding motherwort injection to oxytocin reduces blood loss and the rate of post-partum hemorrhage when compared with using oxytocin alone. In a large clinical trial, motherwort 40 mg was injected into the uterus during the caesarian section, followed by 20 mg intramuscular injections every 12 hours over the next 36 hours. However, motherwort injection into the uterus does not seem to be more effective than oxytocin for reducing bleeding during the caesarian section (94203). However, a meta-analysis of 8 trials shows that prophylactic injection with motherwort 60-200 mg, in addition to carboprost 250 mcg, reduces the mean blood loss within 2 and 24 hours of delivery by 127 mL and 147 mL, respectively, with a 72% decrease in the incidence of postpartum hemorrhage over carboprost alone (101891). In 7 of the 8 trials the mode of delivery was caesarian section and 1 was a vaginal delivery. A large observational study suggests that intramuscular injection of motherwort into the uterus combined with intravenous oxytocin is associated with a lower risk of post-partum hemorrhage after caesarian section when compared with intravenous oxytocin plus intramuscular injection of oxytocin into the uterus (112291). A meta-analysis of 9 clinical trials among patients undergoing induced abortion shows that motherwort injection combined with oxytocin lowers the volume of blood loss both 2 hours and 24 hours after the procedure when compared with oxytocin alone (112292). However, motherwort alone is not more effective than oxytocin for blood loss post-abortion. Meta-analysis indicates that motherwort injected alone or with oxytocin reduces the duration of blood loss compared with oxytocin or no treatment. Studies were primarily of very low quality, and all studies were conducted in China, limiting generalizability to other populations and geographic locations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males experiencing alcohol withdrawal syndrome with disordered sleep, anxiety, and irritability shows that a single dose of a combination product containing motherwort 50 mg, valerian 170 mg, hops 50 mg, and lemon balm 50 mg, taken 1 hour before bedtime, improves sleep quality and decreases awakenings when compared with placebo (63884).
• Amenorrhea. Although there has been interest in using oral motherwort for amenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Anxiety. It is unclear if oral motherwort is beneficial in patients with anxiety. Details: Preliminary clinical research in adults with anxiety and hypertension shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces anxiety and depression scores when compared with baseline. A significant improvement occurred in 32% of subjects, and a moderate improvement occurred in 48% of subjects (94209). The validity of this finding is limited by the lack of a comparator group.
• Arrhythmia. Although there has been interest in using oral motherwort for arrhythmia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Asthma. Although there has been interest in using oral motherwort for asthma, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Cancer. Although there has been interest in using oral motherwort for cancer, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Dysmenorrhea. Although there has been interest in using oral motherwort for dysmenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Flatulence. Although there has been interest in using oral motherwort for flatulence, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Heart failure. Although there has been interest in using oral motherwort for heart failure, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Herpes zoster (shingles). Although there has been interest in using topical motherwort for herpes zoster, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Hypertension. It is unclear if oral motherwort is beneficial in patients with hypertension. Details: Preliminary clinical research in adults with hypertension and anxiety shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces blood pressure when compared with baseline. In subjects with mild hypertension, systolic and diastolic blood pressure decreased by 10% and 11%, respectively. In subjects with more severe hypertension, systolic and diastolic blood pressure decreased by 7% and 11%, respectively (94209). The validity of this finding is limited by the lack of a comparator group.
• Hyperthyroidism. Although there has been interest in using oral motherwort for hyperthyroidism, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Insomnia. Although there has been interest in using oral motherwort for insomnia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Menopausal symptoms. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with menopause shows that taking a combination of motherwort, burdock, dong quai, licorice root, and wild yam three times daily for 12 weeks reduces the number and severity of menopausal symptoms, such as hot flashes, sleep problems, mood changes, and vaginal dryness, in 71% of patients, compared with 17% of patients taking a placebo (48522).
• Pruritus. Although there has been interest in using topical motherwort for pruritus, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Wound healing. Although there has been interest in using topical motherwort for wound healing, there is insufficient reliable information about the clinical effects of motherwort for this purpose. More evidence is needed to rate motherwort for these uses.

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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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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Although there has been interest in using oral Viburnum opulus for diabetes, there is insufficient reliable information about the clinical effects of Viburnum opulus for this purpose.
• Dysmenorrhea. Although there has been interest in using oral Viburnum opulus for dysmenorrhea, there is insufficient reliable information about the clinical effects of Viburnum opulus for this purpose.
• Kidney stones (nephrolithiasis). It is unclear if oral Viburnum opulus extract is beneficial in patients with kidney stones. Details: One small observational study in patients with distal ureteral stones has found that taking Viburnum opulus extract 3000 mg twice daily for 4 weeks increases the relative rate of stone expulsion by 24%, reduces the time to stone expulsion by 5 days, and decreases the need for analgesics when compared with no treatment (103879). Clinical research has compared Viburnum opulus with tamsulosin. In patients with distal ureteral stones taking diclofenac as needed, taking Viburnum opulus 3000 mg twice daily for 4 weeks is at least as effective as taking tamsulosin 0.4 mg daily for the rate of stone expulsion and time to complete expulsion. Taking Viburnum opulus reduced the number of patients requiring diclofenac by 43% and emergency admission by 67% (110883).
• Muscle cramps. Although there has been interest in using oral Viburnum opulus for muscle cramps, there is insufficient reliable information about the clinical effects of Viburnum opulus for this purpose.
• Pregnancy-related leg cramps. Although there has been interest in using oral Viburnum opulus for pregnancy-related leg cramps, there is insufficient reliable information about the clinical effects of Viburnum opulus for this purpose. More evidence is needed to rate Viburnum opulus for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hypercholesterolemia. Taking 200 mL of tea prepared with 0.5 gram, 1 gram, or 1.5 grams of zedoary root powder twice daily between meals for 2 months reduces total cholesterol by 9%, 14% and 17% respectively in non-obese men aged 25-40 years with mild hypercholesterolemia. The highest dose also seems to increase high-density lipoprotein (HDL) cholesterol by 6.8% (99637).
• Rotaviral diarrhea. A meta-analysis of 5 Chinese studies in children with rotaviral diarrhea shows that giving zedoary turmeric oil injection (route unclear) 10 mg/kg daily for 3-7 days, in addition to standard rehydration therapy, has a higher clinical effectiveness rate than ribavirin combined with standard rehydration therapy. However, the times to defervescence are not significantly different. There is insufficient data to compare rates of disappearance of diarrhea and vomiting between the groups (112080). More information is needed to rate zedoary for these uses.

(Read more about ZEDOARY)

POSSIBLY SAFE ...when used orally, short-term. A specific supplement (Motilitone, Dong-A ST) containing Corydalis yanhusuo extract in combination with Pharbitis seed extract has been used with apparent safety in a dose of 90 mg daily for up to 4 weeks in clinical research (97158,97159,97160). There is insufficient reliable information available about the safety of Corydalis yanhusuo when used orally as a single ingredient.

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

PREGNANCY: LIKELY UNSAFE
when used orally. Corydalis yanhusuo might promote menstrual flow and stimulate uterine contractions (12). The berberine constituent of Corydalis yanhusuo is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589).

LACTATION: LIKELY UNSAFE
when used orally. The berberine constituent of Corydalis yanhusuo and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about CORYDALIS YANHUSUO)

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)

POSSIBLY SAFE ...when used orally and appropriately. A motherwort extract in soybean oil has been used with apparent safety at doses of 1200 mg daily for up to 28 days (94209) ...when administered intramuscularly, short-term. One or more intramuscular injections have been used with apparent safety in total combined doses of 40-200 mg over 48 hours or less to prevent and/or stop postpartum bleeding (94203,101890,101891,101892). Post-marketing surveillance of over 8000 females found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855) ...when administered by intrauterine injection, short-term. Post-marketing surveillance of over 1800 patients found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855).

PREGNANCY: LIKELY UNSAFE
when used orally or by injection. Alkaloids present in motherwort have uterine stimulant effects (4,12,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about MOTHERWORT)

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)

There is insufficient reliable information available about the safety of Viburnum opulus.

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

(Read more about VIBURNUM OPULUS)

There is insufficient reliable information available about the safety of zedoary.

PREGNANCY: LIKELY UNSAFE
when used orally. Zedoary is thought to have abortifacient effects (12,19); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ZEDOARY)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Corydalis yanhusuo contains berberine. In vitro and in vivo research suggest that berberine can inhibit platelet aggregation (33660,33694). Theoretically, Corydalis yanhusuo might also inhibit platelet aggregation.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo may increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Corydalis yanhusuo contains berberine. Clinical research shows that berberine may lower blood glucose levels (20579,34247,34265,34282). Theoretically, Corydalis yanhusuo might also lower blood glucose levels.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might have additive effects with antihypertensive drugs.  Details Corydalis yanhusuo contains berberine. Animal research suggests that berberine can have hypotensive effects (33692,34308). Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone (91956). Theoretically, Corydalis yanhusuo might also reduce blood pressure.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase the sedative effects of CNS depressants.  Details Corydalis yanhusuo contains berberine. Animal research suggests that berberine may have sedative effects (13519,33650,33664,33692). Theoretically, Corydalis yanhusuo might also have CNS depressants effects.

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase blood levels of cyclosporine.  Details Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can reduce metabolism of cyclosporine and increase serum levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524). Theoretically, Corydalis yanhusuo might also reduce the metabolism of cyclosporine.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2C9.  Details Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9 (34279). Theoretically, Corydalis yanhusuo might also inhibit CYP2C9.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2D6.  Details Corydalis yanhusuo contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6 (21117,34279,34297). Theoretically, Corydalis yanhusuo might also inhibit CYP2D6.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP3A4.  Details Corydalis yanhusuo contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4 (13524,21114,34279,34297). Theoretically, Corydalis yanhusuo might also inhibit CYP3A4.

DEXTROMETHORPHAN (Robitussin DM, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo may increase serum levels of dextromethorphan.  Details Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279). Theoretically, Corydalis yanhusuo may also inhibit the metabolism of dextromethorphan.

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.  Details Corydalis yanhusuo contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan (34279). Theoretically, Corydalis yanhusuo might also inhibit the metabolism of losartan.

METFORMIN (Glucophage) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase the therapeutic and adverse effects of metformin.  Details Corydalis yanhusuo contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin (103195). It is unclear if Corydalis yanhusuo might have this same effect.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.  Details Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam (34279). Theoretically, Corydalis yanhusuo might also inhibit the metabolism of midazolam.

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase the sedative effect of pentobarbital.  Details Corydalis yanhusuo contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time (13519). Theoretically, Corydalis yanhusuo might increase the sedative effects of pentobarbital.

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Corydalis yanhusuo might increase blood levels of tacrolimus.  Details Corydalis yanhusuo contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL (91954). It is unclear if Corydalis yanhusuo might have this same effect.

(Read more about CORYDALIS YANHUSUO)

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)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking motherwort concomitantly with other CNS depressants may increase the risk of sedation.  Details Motherwort has been reported to cause CNS depression and sedation (19,94205).

(Read more about MOTHERWORT)

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)

(Read more about VIBURNUM OPULUS)

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, zedoary might increase levels of drugs metabolized by CYP3A4.  Details In-vitro research shows that a methanol extract of zedoary strongly inhibits the CYP3A4 metabolism of the tyrosine kinase inhibitors lapatinib and sorafenib, and to a lesser extent, gefitinib (112079).

(Read more about ZEDOARY)

General ...Orally, Corydalis yanhusuo is generally well tolerated.
Serious Adverse Effects (Rare):
Orally: Clonic spasms and muscle tremors with high doses.

Musculoskeletal ...Orally, clonic spasms and muscle tremors may occur with overdoses of Corydalis yanhusuo (18).

(Read more about CORYDALIS YANHUSUO)

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).

(Read more about DONG QUAI)

General ...Orally or via intramuscular or intrauterine injection, motherwort appears to be generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, stomach irritation.
Topically: Contact dermatitis, photosensitivity.
Intramuscular / Intrauterine: Abdominal pain, erythema, eyelid edema, fever, nausea, pruritus, rash.

Dermatologic ...Motherwort leaves can cause contact dermatitis, and the oil may cause photosensitivity reactions (4). Intramuscularly and via intrauterine injection, mild erythema, rash, and pruritus have been reported (101892,104855).

Gastrointestinal ...Orally, use of motherwort in amounts greater than 3 grams can cause diarrhea and stomach irritation (12). Intramuscularly and via intrauterine injection, abdominal pain and nausea have been reported (104855).

Genitourinary ...Orally, use of motherwort in amounts greater than 3 grams can cause uterine bleeding (12).

Immunologic ...Motherwort can also cause allergic reactions in sensitive individuals (4). Intramuscularly and via intrauterine injection, transient fever and chills lasting less than 24 hours have been reported (104855).

Ocular/Otic ...Intramuscularly and via intrauterine injection, transient eyelid edema lasting less than 24 hours has been reported (104855).

(Read more about MOTHERWORT)

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).

(Read more about PEONY)

General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

(Read more about VIBURNUM OPULUS)

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

(Read more about ZEDOARY)