Four Substance Formula by Honso

There is insufficient reliable information available about the effectiveness of cnidium.

(Read more about CNIDIUM)

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 extract 400 mg twice daily, in conjunction with irbesartan 150 mg daily, for 8 weeks decreases proteinuria by 36%, compared with a reduction of 28% with irbesartan alone (93662).

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about REHMANNIA)

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

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

(Read more about CNIDIUM)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Laboratory research shows that osthol, a constituent of cnidium, inhibits blood clotting and the activity of platelets (103851). Theoretically, cnidium might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Some anticoagulant or antiplatelet drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

(Read more about CNIDIUM)

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, cnidium has been reported to cause mild symptoms of bitter mouth, drowsiness, and stomach discomfort (103851).

Gastrointestinal ...Orally, cnidium has been reported to cause bitter mouth and stomach discomfort (103851).

Neurologic/CNS ...Orally, cnidium has been reported to cause drowsiness (103851).

(Read more about CNIDIUM)

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)