NervEase by Health King Enterprise and Balanceuticals Group, Inc.

There is insufficient reliable information available about the effectiveness of Albizia julibrissin.

(Read more about ALBIZIA JULIBRISSIN)

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.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amenorrhea. Although there has been interest in using oral German sarsaparilla for amenorrhea, there is insufficient reliable information about the clinical effects of German sarsaparilla for this purpose.
• Colic. Although there has been interest in using oral German sarsaparilla for colic, there is insufficient reliable information about the clinical effects of German sarsaparilla for this purpose.
• Flatulence. Although there has been interest in using oral German sarsaparilla for flatulence, there is insufficient reliable information about the clinical effects of German sarsaparilla for this purpose.
• Gout. Although there has been interest in using oral German sarsaparilla for gout, there is insufficient reliable information about the clinical effects of German sarsaparilla for this purpose. More evidence is needed to rate German sarsaparilla for these uses.

(Read more about GERMAN SARSAPARILLA)

POSSIBLY EFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral schisandra for aging, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Asthma. Although there is interest in using oral schisandra for asthma, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Athletic performance. Although there is interest in using oral schisandra for athletic performance, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Coronavirus disease 2019 (COVID-19). Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with a history of COVID-19 infection and current symptoms of long COVID-19 shows that taking 30 mL of a specific combination product (Chisan / ADAPT-232, Swedish Herbal Institute) containing schisandra extract 300 mg, rhodiola extract 90 mg, and eleuthero extract 78 mg twice daily for 2 weeks increases exercise capacity, but does not reduce the number of days with fatigue, headache, cough, respiratory problems, or other symptoms of long COVID-19, when compared with placebo (109635).
• Cough. Although there is interest in using oral schisandra for cough, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diarrhea. Although there is interest in using oral schisandra for diarrhea, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diabetes. Although there is interest in using oral schisandra for diabetes, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Familial Mediterranean fever. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a combination product (ImmunoGuard, Inspired Nutritionals) containing schisandra extract 100 mg, andrographis, Siberian ginseng, and licorice reduces symptom duration, frequency, and severity when compared with placebo (12382). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Hepatitis. Although there is interest in using oral schisandra for hepatitis, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Hypercholesterolemia. Although there is interest in using oral schisandra for hypercholesterolemia, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Menopausal symptoms. It is unclear if oral schisandra is beneficial for improving menopausal symptoms. Details: A small clinical trial in healthy patients with moderate or severe menopausal symptoms shows that taking schisandra extract (BMO-30, Biomix Inc) 784 mg in two divided doses daily for 6 weeks improves hot flushes and other menopausal symptoms when compared with placebo (96632).
• Muscle strength. It is unclear if oral schisandra is beneficial for improving muscle strength. Details: A small clinical study in healthy middle-aged females shows that taking schisandra powdered extract (Bioport Korea Inc.) 500 mg twice daily for 12 weeks seems to modestly increase quadriceps muscle strength and grip strength, but does not affect overall muscle mass, when compared with placebo (105563).
• Myopia. Although there is interest in using topical schisandra for myopia in children, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Physical performance. It is unclear if oral schisandra is beneficial for improving physical function in older adults. Details: A small clinical study in healthy adults over 50 years of age shows that taking schisandra 500 mg twice daily, 30 minutes after breakfast and dinner, for 12 months improves knee extension peak torque, but does not improve hand grip strength or body composition, when compared with placebo (105562).
• Pneumonia. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with acute, nonspecific pneumonia shows that taking 20 mL of a specific combination product (ADAPT-232 CHI San, Swedish Herbal Institute) containing schisandra berry extract 51%, rhodiola root extract 27.6%, and eleuthero root extract 24.4% twice daily for 10-15 days reduces the duration of antibiotic treatment and may improve quality of life when compared with standard treatment alone (71152). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Stress. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, fatigued females under experimental stress suggests that taking a single, 270 mg dose of a combination product (ADAPT-232, Swedish Herbal Institute) containing schisandra, rhodiola, and Siberian ginseng improves attention, as well as cognitive task speed and accuracy, when compared with placebo (19289). It is unclear if these effects are due to schisandra, other ingredients, or the combination. More evidence is needed to rate schisandra for these uses.

(Read more about SCHISANDRA)

There is insufficient reliable information available about the safety of Albizia julibrissin.

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

(Read more about ALBIZIA JULIBRISSIN)

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)

There is insufficient reliable information available about the safety of German sarsaparilla.

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

(Read more about GERMAN SARSAPARILLA)

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

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

(Read more about REHMANNIA)

POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Some evidence suggests schisandra fruit is a uterine stimulant (11).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about SCHISANDRA)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that certain constituents from Albizia julibrissin flowers can potentiate pentobarbital-induced sleeping time in mice (20022). Theoretically, Albizia julibrissin might enhance the therapeutic and adverse effects of CNS depressants.  Details Some CNS depressants include pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), clonazepam (Klonopin), lorazepam (Ativan), zolpidem (Ambien), and others.

(Read more about ALBIZIA JULIBRISSIN)

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.

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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).

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CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.  Details In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of cyclosporine.  Details A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.  Details In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.  Details In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of midazolam.  Details A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.  Details In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

SIROLIMUS (Rapamune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of sirolimus.  Details A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of tacrolimus.  Details Clinical research in healthy volunteers and transplant patients shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 48% to 73%. This effect is thought to be due to inhibition of CYP3A4 by schisandra, and possibly also inhibition of the P-glycoprotein drug transporter. It may also be related to the inhibition of CYP3A5 in people who are CYP3A5 expressors. Small clinical studies show that schisandra increases tacrolimus levels in both expressors and non-expressors of CYP3A5 (15570,17414,91387,96631,105623,109639,109641). However, some clinical and observational research shows that schisandra increases tacrolimus levels to a greater degree in CYP3A5 expressors when compared with CYP3A5 non-expressors (109638,109640). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of talinolol.  Details A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386). tly.

VORICONAZOLE (Vfend) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of voriconazole.  Details Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of warfarin.  Details Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.

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

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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).

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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).

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General ...There is limited reliable information available about the adverse effects of German sarsaparilla.

Gastrointestinal ...Orally and topically, the saponins contained in German sarsaparilla may cause local irritation (2).

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

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General ...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.

Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).

Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).

(Read more about SCHISANDRA)