Tong Jing Wan

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amenorrhea. Although there has been interest in using oral cassia cinnamon for amenorrhea, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Angina. Although there has been interest in using oral cassia cinnamon for angina, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Common cold. Although there has been interest in using oral cassia cinnamon for the common cold, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Diabetes. Several clinical trials have evaluated oral cassia cinnamon for type 2 diabetes, but results are conflicting. Details: Some clinical studies and meta-analyses of cassia cinnamon have found significant benefits in patients with diabetes (11347,17011,21914,21918,89646,89649,111692), while others have not (14344,16010,17689,21915,21916,89650). Results from meta-analyses are also mixed with respect to lowering fasting blood glucose and lipid levels (89647,108264). Meta-analyses including more than 1500 adults with type 2 diabetes show that taking cassia cinnamon 120 mg To 14.4 grams daily for 4-18 weeks reduces fasting blood glucose by an average of 25 mg/dL, total cholesterol by 16 mg/dL, low-density lipoprotein (LDL) cholesterol by 9 mg/dL, and triglycerides by 30 mg/dL, and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL (89647,111692). Analyses included studies examining either extract or powder, and two of the studies included used an unspecified type of cinnamon. In contrast, a more recent meta-analysis of studies limited to cassia cinnamon ground bark powder 1-2 grams daily for 40-90 days shows no benefit on fasting blood glucose or lipid levels (108264). Evidence regarding cassia cinnamon's effect on glycated hemoglobin (HbA1c) is mixed, with one meta-analysis of 15 clinical studies suggesting that it moderately lowers HbA1c, while other studies suggest that it does not, although some of the studies were too short to detect a change (89647,108264,111692). One meta-analysis found that cassia cinnamon was most beneficial for adults with HbA1c of 8% or higher (111692). The individual studies included in the meta-analyses were also small, and very heterogenous in relation to dose, duration, use of conventional medications, and diabetes control at baseline (89647,108264). Cassia cinnamon has also been evaluated in combination with other ingredients. A study in treatment-naïve adults newly diagnosed with type 2 diabetes shows that taking a combination product containing cassia cinnamon extract 100 mg, black seed extract, and ficin extract (NW Low-Glu) 4-5 times daily for 12 weeks reduces HbA1c by 0.6-0.8% and 2-hour postprandial glucose by 25-35 mg/dl when compared to baseline, with similar findings when compared with metformin. However, there were no notable differences in fasting blood glucose, insulin resistance, and beta cell function (111710). It is unclear if these effects are due to cassia cinnamon, other ingredients, or the combination. In patients with type 1 diabetes, clinical research shows that taking cassia cinnamon daily does not improve fasting blood glucose, HbA1c, insulin sensitivity, or the rate of hypoglycemic episodes (16010,89648).
• Diarrhea. It is unclear if oral cassia cinnamon is beneficial for diarrhea. Details: A moderate-sized clinical study in adults with diarrhea shows that taking cinnamon water extract 1200 mg twice daily for 8 weeks increases colonic transit time by about 10 hours but does not improve other symptoms of diarrhea including percentage of bowel movements with diarrhea, Bristol stool scale score, abdominal pain, bowel urgency, or abdominal distension when compared with placebo (111712).
• Dyslipidemia. It is unclear if oral cassia cinnamon is beneficial for dyslipidemia. Details: A meta-analysis of 12 clinical studies in adults with metabolic syndrome, polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, prediabetes, and overweight or obesity shows that taking cassia cinnamon daily for 2-4 months reduces total cholesterol by 7 mg/dL, triglycerides by 9 mg/dL, and low-density lipoprotein (LDL) cholesterol by 6 mg/dL but does not increase high-density lipoprotein (HDL) cholesterol. Subgroup analysis suggests that cassia cinnamon improves lipid profiles of Asian patients but not European or American patients. Additionally, higher doses appear to regulate lipid profiles better, and cassia cinnamon doses above 1.5 grams daily increase high-density lipoprotein cholesterol by about 2.5 mg/dL. Subgroup analysis also shows that cassia cinnamon only reduces triglycerides for patients with metabolic syndrome and increases HDL cholesterol for patients with PCOS but does not impact total cholesterol for those with type 2 diabetes (111709).
• Erectile dysfunction (ED). Although there has been interest in using oral cassia cinnamon for ED, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Hypertension. Although there has been interest in using oral cassia cinnamon for hypertension, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Impaired glucose tolerance (prediabetes). The effects of cassia cinnamon in patients with impaired glucose tolerance are unclear; results from clinical research are conflicting. Details: A small clinical study in patients with impaired glucose tolerance shows that taking cassia cinnamon powder 6 grams twice daily for 12 weeks does not improve fasting plasma glucose or insulin sensitivity when compared with placebo (96280). However, another clinical study in overweight or obese patients with impaired fasting blood glucose shows that taking a dried aqueous extract of cassia cinnamon 250 mg twice daily for 12 weeks reduces fasting blood glucose by about 12 mg/dL when compared with baseline, but does not affect fasting insulin levels (93118). Another preliminary clinical trial in overweight or obese patients with impaired glucose tolerance shows that taking two capsules of a specific combination product, (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months decreases fasting blood glucose by 6.5 mg/dL but has no effect on glycated hemoglobin (HbA1c), insulin sensitivity, or body weight, when compared with placebo (94234). It is unclear whether these effects are due to cassia cinnamon, ingredients, or the combination.
• Mosquito repellent. It is unclear if topical cassia cinnamon is beneficial as a mosquito repellent. Details: Preliminary clinical research suggests that applying a cream containing cassia cinnamon oil 5% to the skin provides protection from mosquito bites. However, the repellency of this cream appears to decrease more quickly over time compared to MeiMei cream (containing citronella and geranium oils) and Repellan S aerosol (containing 19% N,N-diethyl-m-toluamide (DEET)) (59580).
• Muscle cramps. Although there has been interest in using oral cassia cinnamon for muscle cramps, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Nausea and vomiting. Although there has been interest in using oral cassia cinnamon for nausea and vomiting, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
• Obesity. It is unclear if oral cassia cinnamon is beneficial for weight loss. Details: A meta-analysis of 7 clinical studies shows that cassia cinnamon reduces body mass index (BMI) when compared with placebo (111692). However, preliminary clinical research in a small number of patients with overweight or obesity and impaired glucose tolerance shows that taking two capsules of a specific combination product (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months does not decrease body weight, BMI, fat mass, or lipid levels when compared with placebo (94234). A very small clinical study in healthy adults shows that drinking a single dose of cinnamon infusion containing 2 grams of powdered cinnamon served along with breakfast does not increase energy expenditure, diet-induced thermogenesis, respiratory quotient, or lipid and carbohydrate oxidation and does not affect appetite responses including hunger, fullness, desire to eat, macronutrient intake, and food intake throughout the day when compared with control. Furthermore, cassia cinnamon intake reduces feelings of satiety and increases energy intake in the first meal after the intervention when compared with control (111707). The validity of these findings is limited by a lack of blinding.
• Polycystic ovary syndrome (PCOS). It is unclear if oral cassia cinnamon is beneficial for patients with PCOS. Details: A small observational study in adults with PCOS suggests that taking cinnamon 500 mg three times daily for 8 weeks is associated with decreased body weight, body mass index, insulin resistance, and testosterone but does not appear to alter levels of luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone (DHEA), insulin, or lipids when compared with placebo (113514).
• Stroke. It is unclear if oral cassia cinnamon is beneficial for stroke prevention. Details: Preliminary clinical research in patients with a mild ischemic stroke or transient ischemic attack shows that taking cinnamon (Chinese herbal formula granules, Guangdong Yifang Pharmaceutical Co, Ltd) 5 grams with aspirin 100 mg daily for 90 days, starting within 24 hours of the ischemia, reduces the percentage of patients with a recurrent stroke to 3%, compared with 15% of those taking aspirin plus placebo. There were also modest improvements in levels of plasma lipids, glucose, and glycated hemoglobin, as well as a reduced likelihood of identifying unstable or severe plaques on carotid ultrasound (108265). The use of cassia cinnamon, specifically, was not confirmed; however, this species of cinnamon is commonly used in traditional Chinese medicine, as indicated in the study.
• Urinary incontinence. Although there has been interest in using oral cassia cinnamon for urinary incontinence, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose. More evidence is needed to rate cassia cinnamon for these uses.

(Read more about CASSIA CINNAMON)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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.

(Read more about CORYDALIS YANHUSUO)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Intestinal parasite infection. It is unclear if oral costus root is beneficial in children with intestinal parasite infections. Details: Preliminary clinical research in children shows that taking a single dose of costus root 50 mg/kg reduces the number of nematode eggs per gram of feces similarly to treatment with pyrantel pamoate (1516). More evidence is needed to rate costus for this use.

(Read more about COSTUS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral danshen for acne, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Angina. Preliminary clinical research suggests that compound danshen dripping pill, containing danshen extract, Panax notoginseng, and borneol, reduces symptoms and improves electrocardiogram (ECG) parameters in adults with angina. The effect of danshen alone is unclear. Details: Analyses of preliminary clinical research, as well as individual lower-quality clinical studies, have shown that danshen dripping pill is effective in reducing symptoms of angina, although the extent of this effect and place in therapy is unclear (47021,47025,96442,96443,96445). Analyses of the available clinical research, involving up to 109 studies with 11,973 patients, show that compound danshen dripping pill, 216-270 mg, taken as 8-10 pills, three times daily for 1-6 months, is more effective than isosorbide dinitrate taken as 5-20 mg three times daily in improving the symptoms and ECG parameters associated with angina (96442,96445). Another analysis involving 17 studies with 1,433 patients found that danshen injection as an adjunct to standard treatment options was more effective in improving symptoms of angina and ECG parameters when compared with standard treatment alone. However, details on the dose of danshen injection and the standard treatments used in the reviewed studies were not provided (96443). The low quality and high heterogeneity of the reviewed studies limit the validity of these findings. Also, the optimal dose and optimal form of danshen for treating angina has not been identified. Additionally, the effects of danshen alone are unclear. Salvianolate, a component of danshen, has been evaluated for the treatment of angina. A review of the available research shows that giving salvianolate as an intravenous infusion 250 mg in 250 mL dextrose daily for 10-14 days reduces angina severity and nitroglycerin tablet use in about 28% of people with stable angina. The patients most likely to respond are overweight, hypertensive, or experience at least 3 angina episodes per week (99069).
• Atopic dermatitis (eczema). Although there is interest in using oral danshen for eczema, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Cancer. It is unclear if oral danshen is beneficial for cancer treatment. Details: A meta-analysis of 13 small, heterogenous clinical trials shows that taking various formulas containing danshen in combination with chemotherapy increases the odds of response and survival over 1-5 years when compared with chemotherapy alone. In patients with various types of cancer, including leukemia, and lung, liver, breast, colon, and gastric cancer, the odds of survival were increased by at least 1.7-fold (101976). It is unclear what other treatments these patients were receiving.
• Cirrhosis. It is unclear if oral or intravenous danshen are beneficial for cirrhosis. Details: A meta-analysis of results from low-quality clinical research, including 11 studies involving 1,086 patients, suggests that compound danshen injection or danshen injection 16-30 mL in conjunction with astragalus injection 10-30 mL daily for up to 90 days is superior to control in reducing liver function enzyme levels, increasing albumin levels, and reducing markers of fibrosis in adults with cirrhosis. However, the variability of treatments used as control, the wide range of outcomes assessed, and the significant heterogeneity between trials limits the validity of these findings (90622). Additionally, the effect of danshen injection alone is unclear.
• Coronary heart disease (CHD). Preliminary clinical research suggests that taking compound danshen dripping pills containing danshen extract, Panax notoginseng, and borneol may improve some cardiac symptoms, surrogate markers of cardiac function, and metabolic indices in patients with CHD. The effect of danshen alone is unclear. Details: A meta-analysis of the results of low-quality clinical research, including 10 studies involving 1,367 patients, shows that taking compound danshen dripping pills 240-270 mg as 10 tablets three times daily in combination with aspirin 25-100 mg daily for 4 weeks to 2 years reduces symptoms of CHD and pain when compared with aspirin alone in adults with CHD (96439). Also, meta-analyses of low-quality clinical research, including up to 19 studies, show that taking compound danshen dripping pills in combination with aspirin reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, as well as plasma viscosity and platelet aggregation, and increases high-density lipoprotein (HDL) cholesterol levels, when compared with aspirin alone in adults with CHD (96439,109369). The low quality and high heterogeneity of the reviewed studies limit the validity of these findings. A meta-analysis of randomized clinical trials in adults with CHD that require percutaneous coronary intervention (PCI) shows that taking compound danshen dripping pills three times daily for 1-6 months reduces the risk of recurrent angina by 80%, coronary restenosis by 71%, heart failure by 55%, and malignant arrhythmia by 47% when compared with usual treatment, although there was no reduction in the risk for acute myocardial infarction or sudden cardiac death. Taking compound danshen dripping pills also improved LDL cholesterol levels, but not HDL cholesterol or triglyceride levels (105516). The validity of this study is limited by an unreported dose of compound danshen dripping pills, unclear use of antiplatelet and other adjunctive therapies in the control group, and possible publication bias. A more recent large clinical trial in adults with CHD complicated with anxiety and depression who recently underwent PCI shows that taking compound danshen dripping pills 400 mg three times daily for three months improves quality of life, anxiety, angina symptoms, and surrogate biomarkers such as endothelin and high-sensitivity C-reactive protein compared with placebo (112398).
• Diabetes. Although there is interest in using oral danshen for diabetes, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Diabetic foot ulcers. Although there is interest in using oral danshen for diabetic foot ulcers, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Diabetic nephropathy. It is unclear if oral or intravenous danshen are beneficial for diabetic nephropathy. Details: A meta-analysis of up to 13 preliminary clinical trials in patients with early diabetic kidney disease shows that intravenous administration of danshen and Ligusticum striatum extract for 2-4 weeks, in combination with conventional medications such as angiotensin receptor blockers, alprostadil, benazepril, and others, modestly reduces urinary albumin and serum creatinine levels when compared with conventional medications alone (109380). The effects of oral danshen or intravenous danshen alone in patients with diabetic nephropathy are unclear.
• Diabetic retinopathy. Preliminary clinical research suggests that taking compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, may improve visual acuity and the severity of diabetic retinopathy. The effect of danshen alone is unclear. Details: Meta-analyses of available preliminary clinical research in adults with diabetic retinopathy, including up to 13 studies, show that taking compound danshen dripping pill at doses of 270-540 mg or ten pills three times daily improves retinal and choroid circulation, visual field, and visual acuity, and reduces the occurrence of microaneurysm and retinal hemorrhage when compared with placebo, control, or conventional treatment alone. However, the low quality and high heterogeneity of the reviewed studies limit the validity of these findings (96437,109376). Some clinical research shows that taking compound danshen dripping pill 5 mg three times daily for 6 months may be more effective than taking captopril 12.5 mg two or three times daily for reducing macular edema and the severity of retinopathy and improving vision (109372). Additional clinical research shows that higher doses of compound danshen dripping pill of 540-810 mg three times daily may be most effective in improving symptoms of diabetic retinopathy when compared with placebo (96444).
• Endometriosis. Preliminary clinical research suggests that taking danshen-containing herbal products with gonadotropin-releasing hormone agonist (GnRH-a) may improve postoperative management of endometriosis. The effect of danshen alone is unclear. Details: A meta-analysis of eight preliminary clinical trials shows that taking danshen-containing herbal products along with GnRH-a following surgery for endometriosis reduces the recurrence of endometriosis by 74% when compared with GnRH-a alone. Some research also suggests that danshen-containing products reduce symptoms such as abnormal vaginal bleeding and hot flashes and increase the pregnancy rate (109381).
• Heart failure. Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of small clinical trials in adults with heart failure shows taking a danshen decoction 400 to 1600 mL daily for 2 to 8 weeks in combination with conventional therapy improves some markers of cardiac function such as left ventricular ejection fraction, left ventricular end-diastolic dimension, left ventricular end-systolic diameter, and serological indicators such as brain natriuretic peptide, N-terminal pro-B type natriuretic peptide, and C-reactive protein when compared with conventional therapy alone (112397). Danshen comprised 75% of the herbs in the decoction and Tanxiang and Sha ren equally comprised the other 25%. It is unclear if these findings are due to danshen, other ingredients, or the combination. The moderate to low quality of the evidence limits the validity of these findings. All studies in this analysis were conducted in China which may limit generalizability to other geographic regions.
• Hepatitis. Although there is interest in using oral danshen for chronic hepatitis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Hyperlipidemia. It is unclear if oral or intravenous danshen are beneficial for hyperlipidemia. Details: Preliminary clinical research in adults with hyperlipidemia shows that taking lipid-lowering medication and injecting 1 mL of danshen into two of four possible acupuncture points daily for 30 days decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increases high-density lipoprotein (HDL) cholesterol. Improvements appear to occur in 90% of patients using danshen plus lipid-lowering medication, compared with only 44% of patients using lipid-lowering medication alone (47072). However, other preliminary clinical research shows that taking danshen extract 3 grams three times daily for 28 days leads to increases in total cholesterol and LDL cholesterol levels, with no change in HDL cholesterol levels, when compared with placebo in adults with hyperlipidemia and hypertension (96441).
• Hypertension. It is unclear if oral danshen is beneficial for hypertension. Details: Clinical research in adults with uncontrolled hypertension shows that taking a mixture of extracts of danshen 450 mg, rhodiola 40 mg, chrysanthemum 200 mg, and kudzu 200 mg twice daily for 12 weeks along with antihypertensive drugs does not increase response to treatment, defined as a sitting systolic blood pressure (SBP) less than 140 mmHg and/or sitting diastolic blood pressure (DBP) less than 90 mmHg OR achieving a reduction of more than 10 mmHg in SBP or more than 5 mmHg in DBP. However, taking this combination along with antihypertensive drugs increases the percentage of patients with a sitting SBP less than 140 mmHg and/or sitting DBP less than 90 mmHg by about 3.5-fold when compared with antihypertensive drugs alone (94396). However, other preliminary clinical research shows that taking danshen extract 3 grams three times daily for 28 days does not lower SBP or DBP when compared with placebo in adults with hyperlipidemia and hypertension (96441).
• Hypoparathyroidism. Intravenous danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. The effect of oral danshen is unclear. Details: Preliminary clinical research in patients with postoperative hypoparathyroidism after a total thyroidectomy shows that intravenous danshen and the rhizome of Ligusticum chuanxiong 10 mL daily for one week reduces the time to recovery of parathyroid function by about 2 weeks, and results in increased serum parathyroid hormone and calcium levels over 6 months, when compared with conventional treatment including calcitriol and calcium gluconate. Also, there was a reduction in the number of patients with permanent hypoparathyroidism (109379).
• Intrauterine Adhesions. Intrauterine danshen has only been evaluated in combination with various oral ingredients; its effect when used alone is unclear. The effect of oral danshen is unclear. Details: Preliminary clinical research in patients with moderate to severe intrauterine adhesions shows that use of intrauterine danshen (Harbin Pharm Group Sanjing Pharmaceutical Co, Ltd.) 5 mL, along with oral Chinese medications for 6 months after adhesion resection and balloon uterine stent placement, may improve clinical efficacy when compared with a control group receiving hyaluronic acid and an intrauterine device (IUD). Clinical efficacy, defined as normal menstruation with at least a near normal intrauterine lining and normal or slightly reduced blood volume, was 89% after treatment with danshen, compared with 69% in the control group. Uterine re-adhesion after 3 months was also reduced. However, there was no difference in the 6-month follow-up pregnancy rate (109374).
• Kidney transplant. It is unclear if oral or intravenous danshen are beneficial following kidney transplantation. Details: Preliminary clinical research shows that injection with danshen 60 mL daily for 10 days in addition to conventional treatment improves urinary volume and creatinine clearance and reduces the incidence of renal function recovery after kidney transplantation when compared with conventional treatment alone. However, the risk of acute rejection does not seem to be affected (47019).
• Obesity. Although there is interest in using oral danshen for obesity, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Oral submucous fibrosis. It is unclear if oral or intravenous danshen are beneficial for oral submucous fibroids. Details: A meta-analysis of 13 generally low-quality randomized controlled trials shows that danshen injection with corticosteroids, usually triamcinolone acetonide, improves symptoms of oral submucous fibrosis better than conventional corticosteroid treatment alone. Danshen modestly improved maximal mouth opening and moderately improved the oral mucosal lesion area and sensation of burning (101975). The effect of oral danshen is unclear.
• Pancreatitis. Although there is interest in using oral danshen for pancreatitis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Polycystic ovary syndrome (PCOS). It is unclear if oral danshen is beneficial for PCOS. Details: A meta-analysis of two preliminary clinical trials in patients with PCOS shows that taking danshen along with medication does not increase the pregnancy rate when compared with medication alone. However, these studies differed in their findings, with a 2.6-fold increase in pregnancy rate when compared with letrozole alone in one study and no increase when compared with cyproterone acetate in the other. Taking danshen may decrease fasting levels of glucose and insulin and improve levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and reproductive hormones when compared with placebo or medications alone (109378). However, the number of clinical trials in each meta-analysis was small.
• Pre-eclampsia. It is unclear if intravenous or oral danshen is beneficial for pre-eclampsia. Details: Preliminary clinical research in patients with severe pre-eclampsia on bed rest shows that intravenous danshen 16 mL in combination with magnesium sulfate up to 30 grams daily for 7 days results in clinical improvements when compared with magnesium sulfate alone. Blood pressure reductions to below 150/100 mmHg and improvement in clinical symptoms occurred in 93% of patients, compared with 77% of those in the control group. There were also modest improvements in liver and kidney function indices (109382). The effect of oral danshen is unclear.
• Pregnancy-induced hypertension. It is unclear if intravenous or oral danshen is beneficial for pregnancy-induced hypertension. Details: Preliminary clinical research in patients with pregnancy-induced hypertension shows that intravenous danshen 10-20 mL in combination with magnesium sulfate 4-10 mL once daily for 10 days modestly reduces systolic and diastolic blood pressure, as well as 24-hour urinary protein levels, when compared with magnesium sulfate alone. Also, the number of patients with a reduction or elimination of clinical symptoms was increased (109373).
• Psoriasis. Although there is interest in using oral danshen for psoriasis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Stroke. Preliminary clinical research suggests that oral or intravenous danshen may be beneficial for reducing symptoms following a stroke. Details: Preliminary clinical research shows that taking danshen orally or intravenously, usually as composite products, or administering the constituent salvianolic acid intravenously, might produce some improvement in neurological deficits, sleep quality, and blood flow indices after acute ischemic stroke (15538,47002,47017,101978,109371,109377). In one study, compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen, 270 mg (10 pills) three times daily for 28 days was used (15538). Compound danshen 16 mL or 20 mL and danshen 30 mL injection have been used for up to 28 days, occasionally in combination with snake venom (15538,96436). Other research shows that danshen injection is not as effective as danhong injection, an extract of danshen and safflower, in improving neurological deficits after acute ischemic stroke; however, the clinical relevance of this finding in the context of standard treatments is unclear (96436).
• Unstable angina. Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with unstable angina shows that taking danshen dripping pill 0.4 grams three times daily, alone or in combination with andrographis 0.2 grams three times daily, for 4 weeks modestly improves symptoms, although the combination of andrographis with danshen dripping pill was more effective than danshen dripping pill alone (109370).
• Venous Thromboembolism (VTE). Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with multiple myeloma receiving treatment with thalidomide shows that taking compound danshen dripping pill, containing danshen extract, Panax notoginseng, and borneol, 108 mg (4 tablets) three times daily for 8 months is as effective as warfarin for preventing VTE. Compound danshen dripping pills and warfarin demonstrate equal efficacy in preventing thalidomide-induced elevations in D-dimer and fibrinogen levels after 3 months of prophylaxis (96440). The effects of danshen alone are unclear.
• Wound healing. Although there is interest in using oral danshen for wound healing, there is insufficient reliable information about the clinical effects of danshen for this purpose. More evidence is needed to rate danshen for these uses.

(Read more about DANSHEN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Preliminary clinical research in adults with moderate to severe atopic dermatitis shows that taking a combination of whey powder 30 grams daily and dodder seed extract 2 grams daily for 15 days improves symptoms, including pruritus, skin moisture, and skin elasticity, when compared with placebo. These improvements persisted a few weeks after the supplement was discontinued (99156). It is not clear if these effects are due to dodder seed extract, whey powder, or the combination.
• Depression. A small clinical study shows that taking dodder aerial part powder 2 grams daily in combination with conventional antidepressant medications for 8 weeks improves overall symptoms of depression by 71% to 76% compared to 41% to 45% in patients using conventional medications alone (99157). More evidence is needed to rate dodder for these uses.

(Read more about DODDER)

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about DONG QUAI)

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)

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 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.
• 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)

LIKELY SAFE ...when consumed in amounts commonly found in foods. Cassia cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912) ...when used orally and appropriately, short-term. Cassia cinnamon 1-2 grams daily has been used safely for up to 3 months (17011,21914). Cassia cinnamon 3-6 grams daily has been used safely for up to 6 weeks (11347,14344). Cassia cinnamon extract corresponding to 3 grams daily of cassia cinnamon powder has also been used safely for up to 4 months (21916).

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

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

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

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

(Read more about CASSIA CINNAMON)

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)

LIKELY SAFE ...when used in amounts commonly found in foods. Costus oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

UNSAFE ...when aristolochic acid-contaminated costus products are used orally. Costus root is commonly contaminated with aristolochic acid, which is nephrotoxic and carcinogenic. The US Food and Drug Administration (FDA) considers all products containing aristolochic acid to be unsafe and adulterated. Only products analytically verified to be aristolochic acid-free should be used (6118). There is insufficient reliable information available about the safety of non-contaminated costus when used orally or topically in medicinal amounts.

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

(Read more about COSTUS)

POSSIBLY SAFE ...when used orally and appropriately (12,94396,96441,96444). There is insufficient reliable information available about the safety of danshen when used by intravenous injection.

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

(Read more about DANSHEN)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Dodder seed extract has been used safely at doses of up to 2 grams daily for up to 15 days (99156). The powder of dodder aerial parts has been used safely at doses of up to 2 grams daily for up to 8 weeks (99157). There is insufficient reliable information available about the safety of dodder when used in higher doses or for longer time periods.

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

(Read more about DODDER)

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, 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, 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)

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

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

(Read more about CASSIA CINNAMON)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = 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)

(Read more about COSTUS)

AMLODIPINE (Norvasc) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking danshen in combination with amlodipine may decrease the clinical effects of amlodipine.  Details In animal research, taking danshen orally in combination with amlodipine reduced blood levels of amlodipine by about 52%. This may have been due to induction of cytochrome P450 3A4 (CYP3A4) by danshen, which has been demonstrated in vitro (101977). So far, this interaction has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, danshen may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Danshen has been reported to have antithrombotic effects (6048,96440). Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone (112399).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking danshen with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that danshen can produce dose-dependent hypotensive effects. Furthermore, concomitant use with captopril appears to potentiate this effect (47071).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, danshen may increase the levels of aspirin and the risk of bleeding.  Details Research in healthy adult males shows that taking a combination of danshen and kudzu with aspirin increases plasma aspirin area under the curve by approximately 3.4-fold (105517). Animal research also shows that taking a combination of danshen and kudzu (danshen-gegen formula) with aspirin increases maximal blood levels of aspirin and salicylic acid by approximately 4-fold and 3.7-fold, respectively, without impacting blood loss (94399). Taking danshen increases the antiplatelet activity of aspirin and might increase the side effects of aspirin (105517).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the risk of bleeding if taken with clopidogrel.  Details Clopidogrel is an antiplatelet prodrug that is metabolized by carboxyl esterase 1 (CES1) to an inactive metabolite. Animal research shows that a danshen combination formula decreases the activity of CES1, decreasing levels of the inactive metabolite in the blood and possibly increasing levels of the active metabolite (94389). Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone (112399).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research shows that danshen tincture and various constituents of danshen inhibit the activity of CYP1A2 (94393,94394). However, this activity has not been shown in humans when theophylline, a CYP1A2 substrate, was used as a target drug (94398).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro research shows that various constituents of danshen inhibit the activity of CYP2C9 (94393). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2E1.  Details In vitro research shows that various constituents of danshen inhibit the activity of CYP2E1 (94393). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Danshen might alter the levels and clinical effects of drugs metabolized by CYP3A4.  Details Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases the clearance of midazolam, a CYP3A4 substrate. The maximum concentration of midazolam was decreased by 31% to 67%, and drug levels were decreased by 27% to 80% (17404,94390). However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87% (94390).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, using danshen with digoxin might increase the risk of adverse effects.  Details Danshen has structural and pharmacological similarities to cardiac glycosides (5884,6048,7311).

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Danshen might increase the levels and clinical effects of fexofenadine.  Details Pharmacokinetic research in healthy volunteers shows that taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2% (94391).

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen might affect the levels and clinical effects of drugs requiring glucuronidation.  Details In vitro research shows that danshen induces the expression of glucuronosyltransferases. However, it also inhibits the activity of glucuronosyltransferases, including various members of the 1A and 2B families. The extent of inhibition of a specific glucuronosyltransferase seems to be dependent on whether or not the danshen is processed via 'sweating'. This type of processing may affect the levels of constituents in danshen that alter glucuronosyltransferase activity (109375). So far, this interaction has not been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Danshen might alter the levels and clinical effects of midazolam.  Details Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases midazolam clearance. The maximum concentration was decreased by 31% to 67%, and drug levels were decreased by 27% to 80% (17404,94390). However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87% (94390).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Danshen might alter the levels of drugs cleared by p-glycoprotein.  Details Pharmacokinetic research in healthy volunteers suggests that danshen might affect p-glycoprotein activity. Taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2% (94391).

ROSUVASTATIN (Crestor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen might increase the levels and clinical effects of rosuvastatin.  Details Animal research shows that a single dose of danshen increases levels of rosuvastatin at least 2-fold, possibly by increasing absorption and/or decreasing elimination (94395). So far, this interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, danshen may increase the risk of bleeding if used with warfarin.  Details There have been several case reports of increased international normalized ratio (INR) after concomitant use of danshen and warfarin. Elevations in INR have occurred as early as 3-5 days after start of danshen (611,612,2237,5883,5884). However, a clinical trial in adults taking warfarin with stable INR found that the addition of compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, 270 mg three times daily for 4 weeks did not alter INR levels or the average required warfarin dose when compared to baseline (96438). These findings are consistent with animal research, which found no change in warfarin pharmacokinetics with the use of danshen (94388,94397,94399). Other research in healthy adult males also shows that taking a combination of danshen and kudzu with warfarin does not increases plasma warfarin area under the curve, but may reduce plasma soluble thrombomodulin levels (105517). However, other research shows that danshen might increase the rate of absorption and decrease the elimination rate of warfarin (5884,6048,94398). Also, research in healthy adult males shows that taking a combination of danshen and kudzu with warfarin increases plasma area under the curve of danshensu, a constituent of danshen, by approximately 29.5-fold (105517). Danshen should be used cautiously in patients taking warfarin.

(Read more about DANSHEN)

(Read more about DODDER)

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)

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)

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)

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

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

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

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

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

(Read more about CASSIA CINNAMON)

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 ...There is limited reliable information available about the adverse effects of costus when used orally or topically.

Immunologic ...Orally and topically, costus might cause allergic reactions, including contact dermatitis (11,73140,73155,73281,73284,73288).

Oncologic ...Costus root is commonly contaminated with aristolochic acid, which is carcinogenic (6118).

Renal ...Costus root is commonly contaminated with aristolochic acid, which is nephrotoxic (6118).

(Read more about COSTUS)

General ...Orally, danshen seems to be well tolerated. There is limited reliable information available about the adverse effects of danshen when used intravenously.
Most Common Adverse Effects:
Orally or intravenously: Upset stomach, pruritus, and reduced appetite.

Cardiovascular ...Orally, in clinical trials, side effects of danshen preparations include palpitations; however, it is not known if these effects were due to danshen or other drugs (109370).

Dermatologic ...Orally or intravenously, danshen can cause pruritus (12,96440).

Gastrointestinal ...Orally or intravenously, danshen can cause upset stomach and reduced appetite (12). In clinical trials, side effects of danshen preparations include loose stools; however, it is not known if these effects were due to danshen or other drugs (109370).

Hematologic ...Orally or intravenously, side effects of danshen preparations reported in clinical trials include thrombocytopenia; however, it is not known if this effect was due to danshen or other drugs (15538).

Neurologic/CNS ...Orally or intravenously, in clinical trials, side effects of danshen preparations include drowsiness, dizziness, or headache; however, it is not known if these effects were due to danshen or other drugs (15538,109370).

(Read more about DANSHEN)

General ...Orally, dodder is generally well tolerated. High doses may cause intestinal colic and diarrhea (18,99156).

Gastrointestinal ...Orally, a combination of whey and dodder seed extract has been reported to cause anorexia, mild dyspepsia, and feelings of stomach heaviness. It is not known if these symptoms are related to whey, dodder, or the combination (99156). Intestinal colic and diarrhea have been reported as possible symptoms of dodder overdose (99156). Traditional sources suggest a maximum daily dose of 8 grams of dodder aerial parts (99157).

(Read more about DODDER)

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, 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, rehmannia seems to be well tolerated.

(Read more about REHMANNIA)