BHI Hemorrhoid Relief by Heel, Inc. (formerly known as BHI)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if topical peony is beneficial in patients with aging skin. Details: Preliminary clinical research shows that using a cosmetic ingredient containing 0.5% paeoniflorin, a constituent of peony root, for 8 weeks can reduce facial wrinkles when compared with baseline (68356). The validity of this finding is limited by the lack of a comparator group.
• Anal fissures. Although there has been interest in using topical peony for anal fissures, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Ankylosing spondylitis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve disease symptoms in patients with ankylosing spondylitis. Details: A meta-analysis of 3 clinical trials in patients with ankylosing spondylitis (AS) shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves the AS disease activity score when compared with conventional treatment alone. TGP also improves inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, and interleukin-6 (112861). The reliability of these findings is limited by the low to very low quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Antipsychotic-induced hyperprolactinemia. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with risperidone-induced hyperprolactinemia shows that taking a specific combination of peony and licorice (Peony-Glycyrrhiza Decoction; PGD) 45 grams daily for 4 weeks is similarly effective to bromocriptine for reducing prolactin levels (59775). A similar trial in males with antipsychotic-induced hyperprolactinemia shows that taking an herbal extract containing peony and licorice (shakuyaku-kanzo-to), 2.5 grams three times daily, reduces prolactin levels after 4 weeks of treatment when compared with baseline. Prolactin levels returned to baseline 4 weeks after treatment cessation (59907). The validity of this study is limited by the lack of a comparator group. Subsequently, a higher quality clinical trial in females with antipsychotic-induced hyperprolactinemia shows that taking a peony and licorice decoction (PGD) 45 grams daily for 16 weeks does not improve prolactin levels or clinical symptoms when compared with placebo (97219). However, a small clinical trial in adults with schizophrenia and sexual dysfunction due to antipsychotic-induced hyperprolactinemia shows that taking a similar PGD formulation for 8 weeks improves sexual function scores and prevents further increases in prolactin levels when compared with a non-treated control group (112412). It is unclear if any effects are due to peony, licorice, or the combination.
• Atherosclerosis. Although there has been interest in using oral peony for atherosclerosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral peony for CFS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cirrhosis. Although there has been interest in using oral peony for cirrhosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cough. Although there has been interest in using oral peony for cough, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dysmenorrhea. Although there has been interest in using oral peony for dysmenorrhea, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dyspepsia. Although there has been interest in using oral peony for dyspepsia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Diabetic nephropathy. It is unclear if oral peony is beneficial in patients with diabetic nephropathy. Details: Preliminary clinical research in Chinese adults with diabetic nephropathy shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with losartan 100 mg daily for 6 months does not improve urinary albumin excretion rate when compared with losartan alone. Taking TGP in conjunction with losartan also did not affect serum creatinine, fasting glucose, glycated hemoglobin (HbA1c), triglycerides, or total cholesterol when compared with losartan alone (98466).
• Epilepsy. It is unclear if oral peony is beneficial in patients with epilepsy. Details: Preliminary clinical research in children 1-14 years of age with intractable epilepsy shows that taking peony root extract orally 20 mg/kg twice daily for 4 weeks reduces weekly seizure frequency and average seizure duration by 80% and 83%, respectively, when compared with baseline. Approximately 63% of subjects reported a reduction in seizure frequency of at least 50% when compared with baseline. The validity of this study is limited by the lack of a comparator group (106851).
• Gout. Although there has been interest in using oral peony for gout, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Hepatitis. Although there has been interest in using oral peony for hepatitis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Juvenile idiopathic arthritis (JIA). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with JIA. Details: A pooled analysis of low-quality clinical research in Chinese children 1.5-14 years of age with JIA shows that taking TGP 30-180 mg/kg daily or 600-1800 mg daily in conjunction with methotrexate for 9-26 weeks improves the odds of overall response rate by 1.5 to 2.5 times when compared with methotrexate alone. TGP also reduces erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels when compared with methotrexate alone. Preliminary subgroup analyses suggest that TGP is not effective for JIA if it is taken for 8 weeks or less (92785). Another meta-analysis of 7 small to moderate-sized clinical trials in children with JIA also shows that taking TGP 0.3 mg/kg, 30-60 mg/kg, or 1200 mg daily with conventional treatment for 12-24 weeks improves effectiveness rates when compared with conventional treatment alone. TGP also reduces ESR, CRP, and tumor necrosis factor alpha (TNF-α) (112861). The reliability of these findings is limited by the variability in the quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Mastalgia. Although there has been interest in using oral peony for mastalgia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Migraine headache. Although there has been interest in using oral peony for migraine, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Muscle cramps. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary, low-quality, clinical research shows that taking a specific combination of peony and licorice (shakuyaku-kanzo-to) orally, 2.5-6 grams daily for up to 4 weeks, relieves muscle cramps when compared to baseline in patients undergoing hemodialysis (13551,13552). The validity of these studies is limited by the lack of a comparator group. It is also unclear if this effect is due to peony, licorice, or the combination.
• Neuropathic pain. Although there has been interest in using oral peony for neuropathic pain, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Osteoarthritis. Some low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with osteoarthritis. Details: A meta-analysis of 4 moderate-sized clinical trials in adults with osteoarthritis shows that taking TGP 0.6 grams 2 or 3 times daily with conventional medical treatment for 4-12 weeks improves joint pain when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Pancreatitis. It is unclear if rectal peony is beneficial in patients with pancreatitis. Details: Preliminary clinical research in adults with moderate to severe acute pancreatitis shows that rectal administration of 150 mL water containing 15 grams of red peony root granules twice daily for 7 days in addition to standard care reduces the time to resolution of abdominal pain and normal bowel habits by 25% when compared with a placebo enema. Additionally, patients receiving red peony root had an average 2-day reduction in hospital stay and a greater improvement on the modified Balthazar CT score when compared with placebo (104283).
• Polycystic ovary syndrome (PCOS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking peony root extract 2250 mg daily, along with Ceylon cinnamon, levant berry, St. John's wort, Tribulus, and licorice, during the follicular phase of the menstrual cycle for 3 months reduces the rate of oligomenorrhea or amenorrhea by 33% and the time between menstrual cycles by 43 days when compared with lifestyle modification alone. Taking this combination also improves quality of life by about 30% and modestly reduces body weight and body mass index when compared with lifestyle intervention alone. Although taking this combination improved conception rate by 4-fold, live birth rate was similar to lifestyle intervention alone (97216). It is unclear if these effects are due to peony, the other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there has been interest in using oral peony for PMS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Psoriasis. It is unclear if oral peony is beneficial for plaque psoriasis. Details: Preliminary clinical research in Chinese adults with moderate to severe plaque psoriasis shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with acitretin for 12 weeks does not improve plaque size or severity when compared with acitretin alone. However, taking TGP in combination with acitretin might increase the number of patients achieving a 50% reduction in plaque size when compared with acitretin alone (97950).
• Psoriatic arthritis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve symptoms in patients with psoriatic arthritis. Details: A meta-analysis of 2 small clinical trials in adults with psoriatic arthritis shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves Psoriasis Area and Severity Index (PASI) scores and the inflammatory marker erythrocyte sedimentation rate when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Respiratory tract infections. Although there has been interest in using oral peony for respiratory tract infections, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Restless legs syndrome (RLS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 12 low-quality clinical studies in Chinese patients with RLS shows that taking peony-containing combination herbal preparations along with conventional therapy appears to improve sleep quality and decrease RLS symptoms when compared with conventional therapy alone. A few of the studies included in this analysis also suggest that taking peony-containing herbal products alone might be more effective than conventional therapy for RLS (100991). The peony-containing products included in this analysis contained between 4-15 other herbal ingredients. It is unclear whether the effects are due to peony, other ingredients, or the combination.
• Rheumatoid arthritis (RA). It is unclear if oral peony is beneficial in patients with RA; evidence is conflicting. Details: Although low-quality clinical research in patients with RA has shown that use of total glucosides of peony (TGP) in conjunction with standard treatment for 4-24 weeks reduces inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein when compared with standard treatment alone, effects on RA symptoms are conflicting (92786,101245,112861). A pooled analysis of clinical research in adults with RA shows that taking TGP in conjunction with leflunomide for 4-24 weeks is less effective for reducing RA symptom scores than taking leflunomide alone (92786). In contrast, another pooled analysis of clinical research in adults with RA shows that taking TGP for 12-24 weeks in combination with methotrexate improves swollen joint count, but not other symptoms such as morning stiffness and tender joint count, when compared with methotrexate alone. Preliminary subgroup analyses also suggest that taking TGP in conjunction with methotrexate might reduce overall adverse effects when compared with methotrexate alone (101245). Of note, the dose of TGP used is not reported in most trials included in these two analyses. Another meta-analysis of 10 mostly small to moderate-sized clinical trials in adults with RA shows that taking TGP 0.6 grams 1-3 times daily with conventional medical treatment for 12-48 weeks improves symptoms as evaluated with the Disease Activity of 28 joints (DAS28) scale when compared with conventional treatment alone (112861). However, these analyses are all limited by the low quality of the included studies. Additionally, all of the included studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Sjogren syndrome. It is unclear if oral peony is beneficial in patients with Sjogren syndrome. Details: Some clinical research in Chinese adults with Sjogren syndrome shows that taking total glucosides of peony (TGP) 600 mg three times daily for 24 weeks improves overall symptoms, with the greatest effects on symptoms of dry eye and fatigue, when compared with placebo (100992). An earlier and smaller clinical study from the same research group found that taking TGP at the same dose and duration improved symptoms of dry mouth, but did not reduce overall symptom scores or other markers of disease, when compared with placebo (97949). However, this study was not adequately powered to detect differences in overall symptom scores between TGP and placebo.
• Spasticity. Although there has been interest in using oral peony for spasticity, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Systemic lupus erythematosus (SLE). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve disease activity scores in patients with SLE. Details: A meta-analysis of 13 small to moderate-sized, low-quality clinical studies in patients with SLE shows that taking TGP 0.6 grams 2-3 times daily or 1.2 grams twice daily for 1-6 months in conjunction with conventional treatment modestly improves the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score when compared with conventional treatment alone. Analyses of secondary endpoints which were not available for all studies show that TGP also improves markers of SLE disease activity, including erythrocyte sedimentation rate (ESR) and C-reactive protein, reduces the average daily dose of glucocorticoids and the cumulative dose of cyclophosphamide, and decreases the rate of disease recurrence (110432). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies, which enrolled patients of varying age and disease severity. Additionally, a similar meta-analysis of 8 small to moderate-sized, low-quality clinical studies in adults with SLE shows that taking TGP 0.6 grams 2-3 times daily for 3-12 months in conjunction with conventional treatment of glucocorticoids and/or immunosuppressants improves SLEDAI scores when compared with conventional treatment alone. TGP also improves markers of inflammation such as ESR, levels of immunoglobulins A, G and M, and complement 3 and 4 (112862). The validity of these finding is also limited by substantial heterogeneity which may be due to differences in conventional therapies. In addition, all of the studies included in these meta-analyses were conducted in China; it is unclear if findings can be applied to other geographical regions and populations. More evidence is needed to rate peony for these uses.

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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.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.  Details In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might increase the levels and clinical effects of clozapine.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, peony might reduce the levels and clinical effects of phenytoin.  Details Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).

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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).

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