Zhibai Dihuang Wan by Classical Remedia Ltd

There is insufficient reliable information available about the effectiveness of American dogwood.

(Read more about AMERICAN DOGWOOD)

There is insufficient reliable information available about the effectiveness of Asian water plantain.

(Read more about ASIAN WATER PLANTAIN)

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.

(Read more about PEONY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical phellodendron is beneficial in patients with acne. Details: A small clinical study in patients with mild to moderate acne shows that applying a facial mask containing an unknown dose of phellodendron for 15-20 minutes daily for 3 days, then every other day for 8 weeks, reduces the number of acne lesions when compared to baseline. About 33% of patients showed a moderate improvement and 11% showed an excellent improvement in overall lesions at week 8. However, no significant difference in the total number of lesions was seen (97317).
• Benign prostatic hyperplasia (BPH). Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with BPH shows that taking five tablets of a specific traditional Chinese medicine product containing phellodendron bark, gardenia fruit, licorice root, safflower, Indian long pepper, and other ingredients three times daily with conventional therapy for 6 months improves storage-related lower urinary tract symptoms, such as urinary frequency, urinary urgency, and nocturia, when compared with placebo plus conventional therapy. However, this product did not appear to improve voiding-related symptoms (109450).
• Diabetes. Although there has been interest in using oral phellodendron for diabetes, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Diabetic foot ulcers. Topical phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with diabetic foot ulcers shows that applying gauze soaked in a Traditional Chinese Medicine (TCM) solution containing phellodendron, forsythia, honeysuckle, dandelion, and Scolopendra once daily for 4 weeks is associated with a higher rate of clinical efficacy and greater reduction in wound area when compared with applying gauze soaked with a Kangfuxin control solution (106438). Kangfuxin is an herbal TCM solution commonly used in the treatment of diabetic foot ulcers. The validity of these findings is limited by the unclear reporting of outcomes and discrepancies in the data. Additionally, it is unclear how these findings would compare with the use of standard care. A small clinical study in adults undergoing negative pressure wound aspiration therapy (NPWT) for diabetic foot ulcers shows that the addition of liquid compound phellodendron TCM irrigation to NPWT for 30 days improves wound symptom scores and wound healing and bacterial cultures compared with saline control (112389). A moderate size clinical study in adults undergoing ultrasonic debridement for diabetic foot ulcers shows that rinsing the wound with a liquid compound phellodendron TCM for 4 weeks reduces wound area and bacterial cultures and improves healing rate and efficacy compared with a Kangfuxin control solution (112390). The lack of blinding and randomization limits the validity of these findings. Additionally, in all three trials the phellodendron solution contained other TCM ingredients such as forsythia, honeysuckle, dandelion, golden cypress, and centipede (106438,112389,112390). Thus, it is unclear if the effects are due to phellodendron, other ingredients, or the combination.
• Obesity. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in overweight individuals shows that taking a specific blend of phellodendron and sweet orange extracts (Citrofen, Next Pharmaceuticals) 740 mg twice daily for 8 weeks reduces body weight by 3.7% when compared with placebo (94902,94903). This blend also seems to reduce levels of low-density lipoprotein (LDL) cholesterol by about 30% and triglycerides by about 14% when compared with placebo. It also appears to reduce systolic and diastolic blood pressure and fasting glucose (94902). Another specific combination product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) has been evaluated for weight loss in females who have a tendency to eat during stressful situations. One small clinical study in overweight, postmenopausal individuals shows that taking this product 250 mg three times daily for 6 weeks prevents weight gain when compared with placebo (14349). However, another small clinical study in overweight, postmenopausal individuals shows that taking this product at the same dose for 6 weeks does not decrease appetite, caloric intake, body weight, or waist or hip circumference when compared with placebo (94901).
• Osteoarthritis. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with osteoarthritis of the knee shows that taking a specific blend of phellodendron and sweet orange extracts (Citrofen, Next Pharmaceuticals) 740 mg twice daily for 8 weeks improves functional measures of joint pain and movement by 16% to 41% when compared with placebo (94903).
• Peptic ulcers. Although there has been interest in using oral phellodendron for peptic ulcers, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Stress. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate stress shows that taking a specific product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) 250 mg twice daily for 4 weeks improves stress and mood by 11% when compared with placebo (94904).
• Tuberculosis. Although there has been interest in using oral phellodendron for tuberculosis, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Wound healing. Topical phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate sized clinical trial in adults recovering from anal fistulotomy shows that using 200 mL of compound phellodendron decoction in 1.8 liters of warm water for fumigation and sitting (sitz) bath for 7 days reduces pain, wound edema and exudation, and total wound healing time compared with fumigation and sitz bath with warm water alone (112391). Four other herbs were in the decoction, so it is unclear if the effects are due to phellodendron, other ingredients, or the combination. More evidence is needed to rate phellodendron for these uses.

(Read more about PHELLODENDRON)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there is interest in using oral poria mushroom for cancer, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral poria mushroom for CFS, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic kidney disease (CKD). Although there is interest in using oral poria mushroom for CKD, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral poria mushroom for COVID-19, there is insufficient reliable information about the clinical effects of poria mushroom for this purpose.
• Dementia. Although there is interest in using oral poria mushroom for dementia, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Diabetes. Oral poria mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of generally small clinical trials in patients with type 2 diabetes shows that taking Chinese herbal medicine combinations containing poria mushroom for 2-24 weeks along with hypoglycemic medications modestly reduces fasting blood glucose and glycated hemoglobin levels when compared with control groups taking hypoglycemic agents only. There were also modest improvements in levels of triglycerides and low-density lipoprotein (LDL) cholesterol and in insulin sensitivity (111920). Given the large number of other ingredients in the available formulations, it is unclear if any beneficial effects are related to poria mushroom, other ingredients in the formulation, or their combination.
• Diarrhea. Although there is interest in using oral poria mushroom for diarrhea, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Endometriosis. Although there is interest in using oral poria mushroom for endometriosis, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Influenza. Oral poria mushroom has only been evaluated for influenza vaccine enhancement in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking a product containing poria mushroom extract, rosemary extract, and aloe gel powder twice daily for 28 days prior to and following an influenza vaccination does not affect upper respiratory tract illness symptoms, severity, duration, or medication-related use when compared with taking placebo (111921). It is unclear if this study was large enough to detect differences between groups. Also, the effect of poria mushroom itself on influenza vaccine enhancement is unclear.
• Tinnitus. Although there is interest in using oral poria mushroom for tinnitus, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Urinary tract infections (UTIs). Although there is interest in using oral poria mushroom for UTIs, there is insufficient reliable information about the clinical effects of poria mushroom for this use. More evidence is needed to rate poria mushroom for these uses.

(Read more about PORIA MUSHROOM)

POSSIBLY EFFECTIVE

• Chronic kidney disease (CKD). Oral rehmannia acteosides might reduce proteinuria when used in conjunction with angiotensin II receptor blockers in patients with CKD. Details: A large clinical trial in adults with chronic glomerulonephritis shows that taking rehmannia acteosides extract 400 mg twice daily, in conjunction with irbesartan 150 mg daily, for 8 weeks decreases proteinuria by 36%, compared with a reduction of 28% with irbesartan alone (93662).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aplastic anemia. It is unclear if oral rehmannia is beneficial in patients with aplastic anemia. Details: A small clinical study in adults with aplastic anemia shows that taking rehmannia polysaccharide (dose unknown), in conjunction with stanozolol, increases the incidence of symptom remission by 45% when compared with stanozolol alone (70704).
• Atopic disease. Although there has been interest in using oral rehmannia for atopic disease, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetes. Although there has been interest in using oral rehmannia for diabetes, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetic nephropathy. Oral rehmannia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with chronic kidney disease due to type 2 diabetes receiving standard care with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker shows that taking a specific combination product (Rehmannia-6, PuraPharm) containing rehmannia, Japanese cornel dogwood, wild yam, poria mushroom, Asian water plantain, and peony root bark twice daily for 48 weeks modestly slows the decline in kidney function when compared with standard care alone (112821). It is unclear if this effect is due to rehmannia, other ingredients, or the combination.
• Metabolic syndrome. Although there has been interest in using oral rehmannia for metabolic syndrome, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Obesity. It is unclear if oral rehmannia root extract is beneficial in patients with obesity. Details: A very small clinical study in females with obesity shows that taking steamed rehmannia root extract 4 grams twice daily for 8 weeks decreases waist circumference by 2.6%, but does not affect body weight or body fat percentage, when compared to baseline (93660). The validity of these findings is limited by the lack of a control group.
• Osteoporosis. Although there has been interest in using oral rehmannia for osteoporosis, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral rehmannia for RA, there is insufficient reliable information about the clinical effects of rehmannia for this purpose. More evidence is needed to rate rehmannia for these uses.

(Read more about REHMANNIA)

POSSIBLY INEFFECTIVE

• Menopausal symptoms. Topical wild yam does not seem to improve menopausal symptoms. Details: Wild yam applied topically as a cream in menopausal patients for 3 months appears to be no better than placebo for relieving vasomotor symptoms, such as hot flashes and night sweats. It also does not appear to change serum follicle stimulating hormone (FSH), estradiol, or progesterone levels (10989).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if oral wild yam is beneficial for improving cognitive function in healthy adults. Details: Preliminary clinical research in healthy adults shows that taking a specific wild yam extract (Diopower 15, Anti-Aging Pro Corporation) orally, 50 mg (containing diosgenin 8 mg) daily for 12 weeks, modestly improves overall measures of cognitive function and semantic fluency when compared with placebo (96724).
• Dysmenorrhea. Although there is interest in using oral or topical wild yam for dysmenorrhea, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Gallbladder disease. Although there is interest in using oral wild yam for gallbladder disease, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Infertility. Although there is interest in using oral or topical wild yam for infertility, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Osteoporosis. Although there is interest in using oral wild yam for osteoporosis, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Postmenopausal conditions. Although there is interest in using oral wild yam for postmenopausal conditions, there is insufficient reliable information about the clinical effects of wild yam for these conditions.
• Premenstrual syndrome (PMS). Although there is interest in using oral wild yam for PMS, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral wild yam for RA, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Sexual dysfunction. Although there is interest in using oral wild yam for sexual dysfunction, there is insufficient reliable information about the clinical effects of wild yam for this condition. More evidence is needed to rate wild yam for these uses.

(Read more about WILD YAM)

There is insufficient reliable information available about the safety of American dogwood.

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

(Read more about AMERICAN DOGWOOD)

There is insufficient reliable information available about the safety of Asian water plantain.

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

(Read more about ASIAN WATER PLANTAIN)

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)

POSSIBLY SAFE ...when used orally and appropriately in combination with other ingredients, short-term. A specific product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) 250 mg 2-3 times daily has been used with apparent safety in clinical trials lasting up to 6 weeks (14349,94901,94904). Also, a specific product containing a combination of extracts of phellodendron plus sweet orange (Citrofen, Next Pharmaceuticals) 740 mg twice daily has been used with apparent safety for up to 8 weeks (94903). ...when used topically (97317). There is insufficient reliable information available about the safety of phellodendron when used orally as a single ingredient.

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

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

(Read more about PHELLODENDRON)

There is insufficient reliable information available about the safety of poria mushroom.

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

(Read more about PORIA MUSHROOM)

POSSIBLY SAFE ...when used orally and appropriately, short term. Rehmannia root extract 4 grams daily or rehmannia leaf extract 800 mg daily has been used with apparent safety for 8 weeks in clinical studies (93660,93662).

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

(Read more about REHMANNIA)

POSSIBLY SAFE ...when used orally. A dose of 50 mg (containing 8 mg diosgenin) has been used with apparent safety for 12 weeks (12,96724). ...when used topically. A wild yam cream has been used with apparent safety for 3 months (10989).

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

(Read more about WILD YAM)

(Read more about AMERICAN DOGWOOD)

(Read more about ASIAN WATER PLANTAIN)

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).

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

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

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase the sedative effects of CNS depressants.  Details Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects (13519,33650,33664,33692). Theoretically, phellodendron 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, phellodendron might increase blood levels of cyclosporine.  Details Phellodendron 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, phellodendron 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, phellodendron might increase serum levels of drugs metabolized by CYP2C9.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9 (34279). Theoretically, phellodendron 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, phellodendron might increase serum levels of drugs metabolized by CYP2D6.  Details Phellodendron contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6 (21117,34279,34297). Theoretically, phellodendron 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, phellodendron might increase serum levels of drugs metabolized by CYP3A4.  Details Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4 (13524,21114,34279,34297). Theoretically, phellodendron 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, phellodendron may increase serum levels of dextromethorphan.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279). Theoretically, phellodendron 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, phellodendron might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.  Details Phellodendron contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan (34279). Theoretically, phellodendron 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, phellodendron might increase the therapeutic and adverse effects of metformin.  Details Phellodendron 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 phellodendron might have this same effect.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam (34279). Theoretically, phellodendron 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, phellodendron might increase the sedative effect of pentobarbital.  Details Phellodendron contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time (13519). Theoretically, phellodendron 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, phellodendron might increase blood levels of tacrolimus.  Details Phellodendron 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 phellodendron might have this same effect.

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ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might decrease the clinical effects of anticholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might have additive effects when used with cholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking poria mushroom extract may enhance the therapeutic and adverse effects of sedatives.  Details Animal research shows that poria mushroom extract has sedative properties (111916). This interaction has not been shown in humans.

(Read more about PORIA MUSHROOM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research shows that rehmannia may have hypoglycemic effects (15061,93668).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research shows that rehmannia may have hypotensive effects. Laboratory research shows that formulations of dried and processed rehmannia root inhibit angiotensin-converting enzyme (ACE) (104272).

(Read more about REHMANNIA)

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, wild yam might increase or decrease the effects of estrogen.  Details Wild yam root shows estrogenic and anti-estrogenic effects in vitro (6180,70411,96723,96725). Theoretically, wild yam might interfere with hormone therapy.

(Read more about WILD YAM)

General ...Orally and topically, no adverse effects of American dogwood have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about AMERICAN DOGWOOD)

General ...There is limited information available about the potential adverse effects of Asian water plantain. Orally, it has been used as a part of Traditional Chinese Medicine (TCM) with apparent safety; there have been no reported adverse effects in most patients. However, one case of hepatotoxicity and nephrotoxicity has been reported with the use of a combination TCM product containing Asian water plantain (99434).

Hepatic ...One case report of drug-induced systemic toxicity, including hepatotoxicity, has occurred in a 59-year-old man with chronic hepatitis B who had taken six doses of a combination product containing Asian water plantain 3 weeks prior to admission. He presented with gum bleed and petechiae, and his admission lab values indicated fulminant liver failure. His condition progressed to include renal failure and eventual death after 4 weeks. It is not clear if Asian water plantain, the other ingredients, or the combination caused this toxicity. However, the authors identified Asian water plantain as the likely causative ingredient based on animal research (99434).

Renal ...One case report of drug-induced systemic toxicity, including nephrotoxicity, has occurred in a 59-year-old man with chronic hepatitis B who had taken six doses of a combination product containing Asian water plantain 3 weeks prior to admission. He initially presented with hepatic failure, which progressed to include renal failure and eventual death after 4 weeks. It is not clear if Asian water plantain, the other ingredients, or the combination caused this toxicity. However, the authors identified Asian water plantain as the likely causative ingredient based on animal research (99434).

(Read more about ASIAN WATER PLANTAIN)

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 ...Orally, phellodendron seems to be well tolerated.

Endocrine ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of thyroid dysfunction in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Gastrointestinal ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of heartburn in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Genitourinary ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of sexual dysfunction in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Neurologic/CNS ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with single reports of shaking hands, perilabial numbness, fatigue, and headache in clinical research (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

(Read more about PHELLODENDRON)

General ...Orally, poria mushroom seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.

Immunologic ...Allergic reactions have been reported rarely, including allergic rhinitis and allergic asthma (12).

(Read more about PORIA MUSHROOM)

General ...Orally, rehmannia seems to be well tolerated.

(Read more about REHMANNIA)

General ...Orally, wild yam is generally well tolerated.
Most Common Adverse Effects:
Orally: Fever, headache, upset stomach, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Gastrointestinal ...Orally, wild yam can cause upset stomach and vomiting, especially at higher doses (12,86450).

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 3 days after taking a combination phytoestrogen product containing wild yam 276 mg, dong quai 100 mg, red clover 250 mg, and black cohosh 250 mg (13155). It is unclear if wild yam contributed to this event.

Immunologic ...There are three case reports of anaphylaxis after ingestion of cooked wild yam (96722).

Neurologic/CNS ...Orally, wild yam can cause headache and fever, especially at higher doses (86450).

(Read more about WILD YAM)