BHI Bleeding by Heel, Inc. (formerly known as BHI)

POSSIBLY EFFECTIVE

• Osteoarthritis. Topical arnica gel might reduce osteoarthritis pain. Details: One open-label clinical trial shows that applying arnica gel (A. Vogel Arnica Gel, Bioforce AG) twice daily for 3 weeks decreases total symptom scores, including pain, stiffness, and restriction-of-function, when compared to baseline (19112). A larger randomized clinical trial shows that applying the same gel is as effective as ibuprofen for reducing the intensity of pain and improving hand function (19108).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical arnica for acne, there is insufficient reliable information about the clinical effects of arnica for this purpose.
• Bleeding. It is unclear if oral arnica reduces bleeding after surgery. Details: A small clinical study in patients undergoing total mastectomy for breast cancer suggests that sublingual treatment with 5 drops of a homeopathic preparation of arnica extract (Arnica 1000 K) three times daily for 6 days might reduce the volume of blood and serum drainage by 95 mL over 5 days when compared with placebo (96769). However, because this product is a dilute homeopathic preparation, there is unlikely to be any arnica in the doses given. There is speculation that the slightly higher mean weight of the patients in the arnica group, rather than any effects of arnica itself, might have led to the statistically significant findings (96768).
• Breast cancer-related hot flashes. Oral homeopathic arnica has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in females with non-metastatic breast cancer treated with tamoxifen or an aromatase inhibitor shows that taking a specific homeopathic medicine (Actheane, Laboratories Boiron) daily for 3 months does not reduce hot flashes when compared with placebo. This product contains 4CH each of arnica, black cohosh, bloodroot, and nitroglycerin and 5CH of snake Lachesis muta (103004).
• Bruises. Most small clinical trials show that neither topical nor oral arnica reduces postoperative bruising. Details: Most clinical research shows that topical products containing arnica 10%, as well as homeopathic oral products such as tablets, globules, and capsules, are not effective for reducing postoperative bruising (19107,19119,19120,19121,19122,19123,19124,90611,96769,96772). However, some conflicting research shows benefit. One clinical study shows that applying arnica 20% ointment 0.25 grams twice daily for 2 weeks reduces laser-induced bruising when compared to white petrolatum ointment (19125). Another clinical study shows that applying a specific arnica cream (Arnica Krem 75 g, MediTech) four times daily reduces periorbital bruising in the first week after rhinoplasty when compared with no local treatment (96773). One small study has also evaluated oral homeopathic arnica. In females undergoing a face-lift, taking a specific homeopathic oral arnica product (SinEcch, Alpine Pharmaceuticals) may reduce bruising on postoperative days 1 and 7 when compared with placebo (19124).
• Diabetic retinopathy. Small clinical studies suggest that oral homeopathic arnica may reduce symptoms of diabetic retinopathy. Details: Two preliminary clinical trials in patients with diabetic retinopathy associated with both type 1 and type 2 diabetes shows that taking three pearls of homeopathic arnica 5C orally for 6 months might modestly improve measures of vision when compared with placebo (19110,19111).
• Dry eye. It is unclear if eye drops containing arnica extract can improve dry eye in children. Details: A small observational study in children aged 9-14 years with dry eye disease and allergic conjunctivitis suggests that applying eye drops containing hyaluronic acid 0.2% and arnica extract 0.1% three times daily for four weeks is associated with improvements in subjective and objective measures of dry eye severity when compared to baseline. Improvements in these outcomes were smaller and mostly non-significant in patients using eye drops containing hyaluronic acid only (111421). The validity of these findings is limited by a lack of between-group analysis and randomization.
• Exercise-induced muscle soreness. Small studies suggest that oral homeopathic arnica does not reduce muscle soreness after exercise. It is unclear if topical arnica is beneficial. Details: Despite some conflicting evidence (19135), most clinical research shows that taking homeopathic arnica formulations orally does not prevent delayed-onset muscle soreness (19129,19130,19131,19132,19133). Research on the use of topical arnica formulations is conflicting. One small study in trained athletes shows that using a gel containing 25 mg of dry arnica herb on muscles immediately after a run and then every 4 hours while awake for 5 days improves muscle tenderness and pain by a small amount after 3 days, but not at other time points, when compared with placebo (90612). However, another small study suggests that applying arnica 7% cream (Boiron Group) increases muscle pain following calf raises when compared with placebo (17113).
• Postoperative swelling. It is unclear if topical arnica reduces swelling after surgery. Details: One clinical study shows that applying arnica 10% ointment following blepharoplasty does not reduce postoperative swelling when compared with using a placebo ointment (96772). However, lower quality studies have yielded more promising results. One small clinical study shows that applying a specific arnica cream (Arnica Krem 75 g, MediTech) four times daily reduces swelling by a small amount in the first week after rhinoplasty when compared with no local treatment (96773). The validity of this finding is limited by the lack of a placebo control. A small retrospective study suggests that using a topical homeopathic preparation containing arnica 50M and marsh tea 50M (OcuMend, Cearna Inc.) is associated with reduced postoperative swelling after oculofacial surgery (96770); however, this study is limited by poor design (96771).
• Postoperative pain. Findings related to the use of oral homeopathic arnica are mixed; most studies utilizing a placebo control have yielded negative results. Details: Many small clinical studies show that taking homeopathic arnica preparations orally modestly reduces postoperative pain following tonsillectomy, knee surgery, and carpal tunnel release when compared with baseline or control. Most studies have used homeopathic arnica in dilutions of 30C, 30X, D6, or D4, for up to two weeks postoperatively (19102,19114,19115,19116). In one study, oral homeopathic arnica has been used along with arnica 5% ointment from 72 hours after surgery for up to 2 weeks (19116). The validity of these findings is limited by the lack of a placebo comparator. Studies utilizing a placebo or active control have not yielded positive results. Clinical research in patients recovering from carpal tunnel surgery shows that taking a homeopathic Arnica montana solution by mouth is no more effective than taking placebo for reducing postoperative pain and bruising (19107). Other clinical research shows that taking homeopathic arnica 30C for 5 days after total abdominal hysterectomy does not reduce postoperative pain when compared with placebo and usual treatment (19117). Also, homeopathic arnica D4 is inferior to diclofenac following bunion surgery (109102). Some clinical research in patients recovering from a knee ligament reconstruction shows that a homeopathic solution containing Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH, and Ruta graveolens 3 DH is no more effective than placebo for reducing analgesic use (32413).
• Postoperative recovery. It is unclear if oral homeopathic arnica is beneficial for postoperative recovery. Details: One meta-analysis of small- to moderate-sized clinical trials shows that taking homeopathic arnica does not improve postoperative recovery when compared with controls. Recovery endpoints were combined and included pain, swelling, bruising, wound healing, and others (109061).
• Stroke. A small study suggests that oral homeopathic arnica does not improve outcomes after stroke. Details: Preliminary clinical research shows that taking one tablet of arnica 30C sublingually every 2 hours for six doses doesn't benefit stroke patients (19126). Endpoints included level of consciousness, mobility, incontinence, social performance, and mental state.
• Tooth extraction. It is unclear if oral homeopathic arnica improves symptoms after tooth extraction in adults or children. Details: A small clinical trial in children aged 8-12 years undergoing two sessions of tooth extraction in different parts of the mouth shows that taking homeopathic arnica 30 minutes prior to the procedure, and then 3 times daily for 72 hours, is as effective as taking ibuprofen for reducing patient-reported and operator-assessed pain levels 24 hours after extraction. However, 48 hours after extraction, ibuprofen was more effective. Each child was provided with both arnica and weight-based doses of ibuprofen in a crossover manner while undergoing two sessions of tooth extraction in different parts of the mouth ten days apart (109224). A small observational study in adults undergoing third molar extractions suggests that taking homeopathic arnica 30X (Hyland's Inc.) 4 tablets before the procedure and then 4 tablets four times daily for 4 days after the procedure is associated with less pain, bleeding, and swelling when compared with standard treatment alone (105062). However, the validity of this study is limited by the lack of a placebo control. More evidence is needed to rate arnica for these uses.

(Read more about ARNICA)

There is insufficient reliable information available about the effectiveness of Canadian fleabane.

(Read more about CANADIAN FLEABANE)

POSSIBLY INEFFECTIVE

• Poisoning. Historically, ipecac syrup was commonly used to manage poisoning (15,56380,56387,56403,56415). However, the American Academy of Pediatrics, American Academy of Clinical Toxicologists, and European Association of Poisons Centres and Clinical Toxicologists state that ipecac should not be used routinely for poisoning due to a lack of evidence of improved outcomes over available alternatives and an increased risk for adverse consequences (11349,12394,56389). Research shows that inducing emesis with oral ipecac syrup within 10 minutes of poison ingestion can remove 28% to 54% of the poison dose from the patient (56408,56419,56455). However, as the interval between poison ingestion and ipecac-induced emesis is extended, the percentage of poison dose recovered declines, approaching zero after 90 minutes (56454,56466). Furthermore, ipecac syrup does not appear to be more effective than activated charcoal (103744). While some research shows that taking 30 mL of ipecac syrup within one hour of poison ingestion can reduce absorption of poisons by about the same amount as taking 50-60 grams of activated charcoal (56411), most research shows that ipecac syrup is less effective than activated charcoal (56427,56442,56444). Also, using ipecac followed by activated charcoal after cessation of vomiting does not provide any benefit over earlier administration of activated charcoal alone (56403,56451,103744), and may increase patient recovery times (56392). Finally, there are also adverse consequences of ipecac use, including an increased risk for aspiration pneumonia and the need to delay administration of activated charcoal, poison-specific oral antidotes, or fluids for whole bowel irrigation after ipecac administration in order to avoid emesis of these treatments (12394,56392,56406,56444,103744). There is insufficient reliable information available about the effectiveness of ipecac for its other uses.

(Read more about IPECAC)

POSSIBLY EFFECTIVE

• Alzheimer disease. Oral saffron might modestly improve cognition in patients with Alzheimer disease. Details: Two small clinical trials in patients with probable Alzheimer disease living in Iran shows that taking saffron extract (Green Plants of Life, Co., previously Impiran) 15 mg orally twice daily for 16-22 weeks improves cognitive ability and disease progression when compared with placebo, and is no different for improving cognition when compared with taking donepezil (Aricept) 10 mg daily (17401,93395). Another small clinical study in adults also living in Iran with moderate to severe Alzheimer disease shows that taking saffron extract 30 mg daily for 48 weeks seems to be no different for improving cognition when compared with taking memantine (Namenda) 20 mg (105617). It is unclear if these findings are generalizable to patients in other geographic locations.
• Chemotherapy-induced peripheral neuropathy. Oral saffron seems to improve symptoms of chemotherapy-induced peripheral neuropathy, although it is unclear how it compares with standard care. Details: A clinical crossover study in adults with mild to severe chemotherapy-induced peripheral neuropathy shows that taking the saffron constituent crocin 15 mg twice daily for 8 weeks progressively improves pain scores when compared with placebo, with significant improvements appearing after 5 weeks of treatment. During a 2-week washout period, pain scores in the treatment group returned to baseline, suggesting a loss of benefit after discontinuation. This study included patients who were actively receiving chemotherapy and those who had completed or discontinued treatment; however, a separate analysis for each subgroup was not conducted (108904).
• Depression. Oral saffron extract seems to improve symptoms of depression when used alone or as an adjunct to conventional antidepressants. Details: Meta-analyses and clinical trials in adults with mild to moderate major depressive disorder show that taking saffron extract 30 mg daily or dried saffron stigma 100 mg daily for 6-12 weeks improves symptoms of depression when compared with control (11024,13103,72434,93399,93404,100140,103928,103931). Saffron extract also seems to be comparable to imipramine 100 mg daily, fluoxetine 10 mg twice daily, citalopram 40 mg daily, or sertraline 100 mg daily (11024,17222,19032,93399,100140,100658,103927). Furthermore, some clinical research shows that taking a specific saffron extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 8 weeks or the saffron constituent, crocin, 15 mg twice daily for 4 weeks, as an adjunct to a selective serotonin reuptake inhibitor (SSRI) also modestly reduces depressive symptoms when compared with placebo (93410,103934). However, other research has produced mixed results, which may be due to the use of different depression scales. An umbrella meta-analysis consisting of 7 separate meta-analyses shows that taking saffron, either alone or with other treatments, improves symptoms of depression when compared with control in studies using the Beck depression inventory criteria, but not in those using the Hamilton depression rating scale, the depression anxiety stress scale, or mixed scales (108911). In general, the validity of the available research is limited by the variety of saffron doses and treatment durations, as well as the fact that most research has been conducted in Iran. It is unclear if saffron is beneficial for comorbid depression and anxiety. A small clinical trial in adults with this condition shows that taking saffron extract 15 mg twice daily for 8 weeks does not improve symptoms of depression, but does improve symptoms of anxiety, when compared with placebo (100137). This study may not have been adequately powered to detect smaller differences between groups. Saffron has also been studied in combination with other ingredients. One clinical trial in adults with major depressive disorder shows that taking saffron 15 mg twice daily in combination with curcumin 250 mg twice daily for 12 weeks does not reduce depressive symptoms when compared with placebo (97359). The validity of this finding may be limited by the large placebo response.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). Small studies suggest that oral saffron might slightly improve visual acuity in AMD. Details: Preliminary clinical research in adults 50 years and older with AMD shows that taking saffron extract 20 mg daily for 3 months has a modest effect on visual acuity and some other measurements of retinal health when compared with placebo. This improvement occurred in patients also taking Age-Related Eye Diseases Study (AREDS) supplements or equivalent. However, these small improvements are unlikely to be considered clinically significant (93398,100135).
• Antidepressant-induced sexual dysfunction. Small studies suggest that oral saffron may reduce some symptoms of fluoxetine-induced sexual dysfunction. Details: One small clinical study in females with major depression stabilized on fluoxetine 40 mg daily shows that taking saffron extract 30 mg daily for 4 weeks improves arousal, lubrication, and pain during sexual intercourse when compared with placebo (93401). A small clinical study in males with major depression stabilized on fluoxetine 40 mg daily shows that taking saffron extract 30 mg daily improves erectile dysfunction and intercourse satisfaction when compared with placebo (93407). However, taking saffron does not appear to significantly improve desire, overall satisfaction, or orgasm in patients taking fluoxetine (93401,93407).
• Antipsychotic-induced metabolic side effects. It is unclear if oral saffron reduces metabolic side effects from antipsychotic treatment. Details: A small clinical study in adults with schizophrenia who are taking olanzapine shows that taking saffron aqueous extract 30 mg daily for 12 weeks, or crocin, a constituent of saffron, 30 mg daily for 6 weeks, reduces fasting blood glucose and the risk of developing metabolic syndrome. At 6 weeks, metabolic syndrome occurred in 0% of patients taking saffron, about 9% of patients taking crocin, and about 27% of patients taking placebo. Levels of cholesterol, HBA1c, and insulin were unchanged (93397).
• Anxiety. Small clinical studies suggest that oral saffron might improve anxiety. Details: One preliminary clinical study in adults with type 2 diabetes and comorbid depression-anxiety (CDA) shows that taking saffron extract 15 mg twice daily for 8 weeks improves symptoms of anxiety by 34% when compared with placebo (100137). Other preliminary clinical research in adults with mild to moderate anxiety shows that taking saffron extract 50 mg twice daily for 12 weeks improves symptoms of anxiety by 81%, compared with an improvement of 53% with placebo (93404).
• Asthma. There is limited evidence on the oral use of saffron in patients with allergic asthma. Details: A small clinical study in patients with mild to moderate allergic asthma shows that taking saffron extract 100 mg daily for 8 weeks improves symptoms of asthma, but not asthma severity, when compared with placebo. The use of salbutamol was reduced by approximately 50% in patients taking saffron. Saffron also produced modest improvements in waking during the night due to asthma symptoms, shortness of breath during the night, and activity limitation (100141). However, due to the low rate of symptoms at baseline, it is difficult to determine if these improvements are clinically significant.
• Athletic performance. It is unclear if oral saffron is beneficial for athletic performance. Details: A small clinical study in healthy, untrained, young adult males shows that taking dried saffron stigma powder 300 mg every evening for 10 days improves muscular force by up to 10% and might improve reaction time when compared with placebo (93406). A very small clinical study in healthy adults suggests that taking crocetin, a constituent of saffron, 15 mg daily for 8 days might improve performance on a 3.5-hour physically exhausting task in males, but not in females, when compared with placebo (19058).
• Burning mouth syndrome. It is unclear if oral saffron reduces burning mouth syndrome. Details: A very small clinical study in patients with burning mouth syndrome shows that taking the saffron constituent crocin 15 mg daily for 11 weeks seems to reduce pain to a similar degree as citalopram 20 mg daily (103937).
• Cancer. Although there is interest in using oral saffron for cancer, there is insufficient reliable information about the clinical effects of saffron for this condition.
• Cough. Although there is interest in using oral saffron for cough, there is insufficient reliable information about the clinical effects of saffron for this purpose.
• Diabetes. Research evaluating oral saffron for glycemic control is conflicting. Details: Some clinical research in patients with type 2 diabetes shows that taking saffron extract 30 mg daily, saffron powder 100 mg daily, or drinking black tea stewed with saffron powder 1 gram three times daily, for 2-3 months, does not improve glycated hemoglobin (HbA1c), but might modestly reduce fasting blood glucose, when compared with placebo (99436,100138,103936,108905). The validity of these findings is limited due to differences in glycemic control at baseline and differences in the dose and form of saffron used. A meta-analysis of clinical trials shows that taking saffron, saffron extract, or the constituent crocin for up to 3 months does not improve levels of fasting blood glucose, blood lipids, or HbA1c when compared with placebo or control. However, this research included healthy individuals, as well as patients with type 2 diabetes, metabolic syndrome, coronary artery disease (CAD), schizophrenia, or depression (100139). Patients with type 2 diabetes were not analyzed separately, limiting the applicability of this finding.
• Dysmenorrhea. Oral saffron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in students with dysmenorrhea shows that taking a specific combination product containing saffron, celery seed, and anise extracts (SCA, Gol Daro Herbal Medicine Laboratory) 500 mg three times daily for 3 days reduces the severity and duration of menstrual pain when compared with placebo (17214).
• Erectile dysfunction (ED). It is unclear if oral or topical saffron improves ED; the available research is conflicting. Details: Preliminary clinical research in adults with diabetes and ED shows that applying a gel containing saffron 1% to the penis 30 minutes prior to intercourse for one month improves general symptoms when compared with placebo. ED, sexual desire, and orgasmic function improved by 37%, 14%, and 21%, respectively, for those using saffron gel compared to 2%, 2%, and 0%, respectively, for those in the placebo group (93408). A small, open-label study has also shown benefit with dried oral saffron 200 mg daily for 10 days (19057). However, in adults with ED who are naïve to treatment, one small clinical study shows that taking saffron extract 30 mg twice daily by mouth for 12 weeks does not improve symptoms when compared to baseline (93409). These conflicting results may be related to the cause of ED, as well as the route, dose, and form of saffron used.
• Exercise-induced muscle soreness. It is unclear if oral saffron reduces muscle soreness from exercise. Details: Preliminary clinical research in healthy but exercise-naïve young adult males shows that taking dried saffron powder 300 mg every evening for 10 days, starting one week before a leg press exercise, reduces delayed muscle soreness about 11-fold when compared with placebo. Saffron appears to be more effective than indomethacin for reducing pain and maintaining muscle force during the 72-hour period post-exercise (93405).
• Glaucoma. It is unclear if oral saffron reduces intraocular pressure in patients with glaucoma. Details: A small clinical study in patients with primary open-angle glaucoma shows that taking saffron extract 30 mg daily for 4 weeks, in conjunction with timolol and dorzolamide, reduces intraocular pressure by an additional 16.5% when compared with placebo. After a 4-week washout, intraocular pressure returned to baseline in the saffron group (93400).
• Hyperlipidemia. Small studies suggest that oral saffron does not affect lipid levels in most patients; the effect of saffron in adults with diagnosed hyperlipidemia is unclear. Details: A meta-analysis of clinical trials shows that taking saffron, saffron extract, or the constituent crocin for up to 3 months does not reduce levels of total cholesterol, low density lipoprotein (LDL) cholesterol, or triglycerides, or increase levels of high-density lipoprotein (HDL) cholesterol when compared with placebo or control. However, patients evaluated in the available clinical research include those with type 2 diabetes, metabolic syndrome, coronary artery disease (CAD), schizophrenia, and depression, as well as healthy or mildly overweight individuals (100139).
• Hypertension. It is unclear if oral saffron reduces blood pressure; the available research is conflicting. Details: Preliminary clinical research shows that drinking black tea containing saffron 1 gram three times daily for 8 weeks does not reduce blood pressure in patients with diabetes and elevated systolic blood pressure (96669). However, another small clinical study in males with hypertension shows that taking saffron stigma 200 mg daily for 12 weeks seems to reduce blood pressure when compared with no intervention (105618).
• Impaired glucose tolerance (prediabetes). It is unclear if oral saffron improves glycemic control in adults with prediabetes. Details: A small clinical study in patients with prediabetes and obesity shows that taking saffron extract 15 mg daily for 2 months modestly reduces fasting blood glucose and glycated hemoglobin (HbA1c) when compared with placebo (103933). It is unclear if this small improvement in glycemic control is maintained after 2 months.
• Insomnia. It is unclear if oral saffron is beneficial for reducing sleep problems and improving sleep quality in healthy adults or those with underlying medical conditions. Details: A small clinical study in patients with self-reported sleep problems shows that taking a specific saffron extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 4 weeks reduces insomnia, improves sleep quality, and increases restorative sleep when compared with placebo (103935). Another small clinical study in a similar population shows that taking this same product as 14 mg or 28 mg one hour before bedtime for 4 weeks reduces insomnia and improves sleep quality when compared with placebo, with no observed differences between dosage groups (108908). However, a small clinical study in adults with mild to moderate insomnia and anxiety shows that taking a different saffron extract (Saffr'activ SAF 3C PIM, Comercial Quimica Massó) 15.5 mg daily for 6 weeks improves most sleep quality parameters when compared with baseline, but not when compared with placebo (105624). All studies were funded by the supplement manufacturer, which may limit the validity of these findings. A meta-analysis of clinical research evaluating saffron for sleep in a variety of populations, including healthy patients, those with insomnia or type 2 diabetes, or individuals receiving methadone maintenance treatment, suggests that taking saffron or the constituent crocin improves sleep quality when compared with placebo (108912). Furthermore, a small clinical study in patients with type 2 diabetes with overweight or obesity shows that taking saffron 100 mg daily for 8 weeks improves global Pittsburgh Sleep Quality Index (PSQI) scores when compared with placebo (108905).
• Labor pain. Although there is interest in using oral saffron to reduce labor pain, there is insufficient reliable information about the clinical effects of saffron for this purpose.
• Male infertility. It is unclear if oral saffron is beneficial for improving sperm parameters in males with infertility. Details: Clinical research in males under 45 years of age with oligoasthenoteratozoospermia shows that taking a saffron extract 30 mg orally twice daily for 26 weeks does not increase sperm motility, density, or morphology when compared with placebo (18102). Other preliminary clinical research in males with idiopathic infertility shows that taking saffron 50 mg three times each week for 3 months improves sperm motility and morphology, but not sperm count, when compared to baseline (19033). These conflicting outcomes may be related to the cause of infertility, as well as the dose and form of saffron used.
• Menopausal symptoms. It is unclear if oral saffron reduces menopausal symptoms. Details: A small clinical study in patients with menopausal symptoms shows that taking a specific saffron stigma extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 12 weeks improves symptoms of depression and anxiety, but not vasomotor symptoms such as hot flashes, when compared with placebo (105622). Saffron has also been evaluated in combination with other ingredients. A small clinical study in patients with menopausal symptoms shows that taking a combination of saffron 60 mg, fennel 120 mg, and chamomile 1000 mg daily for 12 weeks modestly reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with either placebo or lower doses of this combination (103628). The validity of this study is limited by unclear reporting of results. Also, it is unclear if reported benefits are due to saffron, other ingredients, or the combination.
• Multiple sclerosis-related fatigue. It is unclear if oral saffron reduces symptoms of fatigue in patients with multiple sclerosis. Details: A small clinical study in patients with MS shows that taking one tablespoon of simple syrup containing saffron extract 0.5% every 8 hours for two months reduces fatigue when compared with baseline (103930). The validity of this finding is limited by the lack of a comparator group.
• Obsessive-compulsive disorder (OCD). It is unclear if oral saffron reduces symptoms of opioid withdrawal. Details: A small clinical study in adults with OCD shows that taking crocin, a constituent of saffron, 15 mg daily for 8 weeks reduces symptoms when compared with baseline, but is no better than fluoxetine 20 mg daily (105620). This finding is limited due to small study size and the subjectivity of outcome measures.
• Opioid withdrawal. It is unclear if oral saffron is beneficial for opioid withdrawal; the available research is conflicting. Details: A small clinical study in adults receiving treatment with methadone for opioid abuse shows that taking crocin, a constituent of saffron, 30 mg daily for 12 weeks modestly reduces cravings and withdrawal symptoms when compared with placebo (105616). Conversely, a small clinical study in patients with opioid dependence shows that taking a specific product (Krocina) containing crocin, a constituent of saffron, 15 mg twice daily for 6 weeks in addition to motivational counseling does not improve withdrawal symptoms, cravings, depression, anxiety, or stress during the detoxification or abstinence phase (108913). The reason for these conflicting findings is unclear but may be related to the differences in adjunctive treatments between studies.
• Postpartum depression. It is unclear if oral saffron is beneficial for speeding recovery from postpartum depression. Details: Preliminary clinical research in patients experiencing symptoms of depression less than 12 weeks after giving birth shows that taking saffron 30 mg daily for 6 weeks (SaffroMood, Green Plants of Life Co. Ltd) is as effective as fluoxetine for treating depression. Both treatment groups experienced similar remission and partial response rates (93402). Another preliminary study in breastfeeding Iranian patients with mild to moderate depression shows that taking saffron 15 mg twice daily for 8 weeks improves depressive symptoms by about 50% when compared to baseline (97361). However, it is not clear if the improvement in these studies was related to saffron or the natural resolution of postpartum depression.
• Premenstrual dysphoric disorder (PMDD). It is unclear if oral saffron improves PMDD symptoms. Details: A clinical study in patients with PMDD shows that taking saffron 15 mg twice daily for 14 days prior to menstruation improves patient-rated PMDD symptom severity when compared with placebo, but not when compared with taking fluoxetine 20 mg twice daily (105625).
• Premenstrual syndrome (PMS). It is unclear if oral saffron improves PMS symptoms. Details: A small clinical study in patients aged 20-45 years with PMS shows that taking a specific saffron extract 15 mg twice daily throughout two menstrual cycles improves symptom severity when compared with placebo (16555).
• Psoriasis. Although there is interest in using oral saffron for psoriasis, there is insufficient reliable information about the clinical effects of saffron for this condition.
• Rheumatoid arthritis (RA). It is unclear if oral saffron reduces RA symptoms. Details: A small clinical study in females with RA shows that taking saffron 100 mg daily for 3 months modestly reduces the number of tender and swollen joints and reduces pain when compared with placebo (103932). The validity of this study is limited by its small size and the fact that all clinical parameters were secondary, exploratory outcomes. In contrast, a small clinical study in patients with newly diagnosed RA shows that adding saffron 100 mg daily for 3 months to standard treatment with prednisolone 5 mg daily and methotrexate 7.5 mg once weekly does not improve disease activity or quality of life when compared with placebo and standard treatment (108907). The validity of this finding is limited due to low adherence to treatment protocols.
• Ulcerative colitis. It is unclear if oral saffron reduces ulcerative colitis symptoms. Details: A small clinical study in patients with ulcerative colitis shows that taking saffron extract 100 mg daily for 8 weeks reduces disease activity when compared with placebo (105626). More evidence is needed to rate saffron for these uses.

(Read more about SAFFRON)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using topical yarrow for atopic dermatitis, there is insufficient reliable information about the clinical effects of yarrow for this condition.
• Dysmenorrhea. It is unclear of oral yarrow tea is beneficial for improving symptoms of dysmenorrhea. Details: Preliminary clinical research in patients with moderate to severe dysmenorrhea shows that drinking a tea made with yarrow 4 grams three times daily for the first three days of two menstrual cycles modestly reduces dysmenorrhea pain when compared with a placebo tea (105361).
• Gingivitis. A mouthwash containing yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a mouthwash containing a combination of yarrow, juniper, and stinging nettle for 3 months does not improve dental plaque or gingivitis in patients with gingival inflammation when compared with a control group (76443).
• Irritable bowel syndrome (IBS). Oral yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate IBS shows that taking a capsule containing yarrow, ginger, and Boswellia serrata three times daily for 30 days improves pain by 46% and gastrointestinal symptoms by 60% when compared with placebo. Patients also experienced an improvement in overall mood when compared with placebo (96673). It is not clear if these effects are due to yarrow, the other ingredients, or the combination.
• Multiple sclerosis (MS). It is unclear if oral yarrow is beneficial for patients with MS. Details: A small clinical study in adults with relapsing-remitting MS shows that taking yarrow whole plant extract 250 mg or 500 mg daily in conjunction with conventional treatments for 12 months reduces the annual relapse rate and increases time to first relapse when compared with placebo. Taking yarrow 500 mg daily also reduced disability scores and improved functional scores when compared with either yarrow 250 mg daily or placebo (100346). However, most of the patients enrolled in the study were under 40 years of age, with undefined disease severity.
• Nipple fissures. It is unclear if topical yarrow is beneficial for patients with nipple fissures. Details: Preliminary clinical research in patients with inflamed nipples and/or nipple fissures shows that topical application with yarrow twice daily after breastfeeding for 7 days reduces redness and pain when compared with baseline. Yarrow 30 grams was boiled in 1 liter of water for 10 minutes. The benefits seen with yarrow were not significantly different from topical mountain honey or breast milk, both of which were also beneficial when compared with baseline (105359).
• Oral mucositis. It is unclear if gargling with yarrow is beneficial for oral mucositis. Details: Preliminary clinical research in patients with chemotherapy-induced oral mucositis shows that gargling with 15 mL of a routine solution containing yarrow distillate 50%, 4 times daily for 14 days, reduces symptom severity by 87%, compared with a worsening in severity in those using the routine solution alone. Of those using yarrow, all patients were able to eat solid foods at 14 days compared with about 40% of those using routine treatment alone. About 3.75 grams of yarrow flower was needed for each 7.5 mL of distillate and the solution was held for 3 minutes in the mouth before gargling (106664). It is unclear if the patients were adequately blinded, as the taste of the two solutions may have differed.
• Tonsillitis. Oral yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children 6-18 years of age with acute non-bacterial tonsillitis shows that taking a specific combination product (Imupret, Bionorica AG) containing yarrow and six other herbal ingredients along with standard care reduces the severity of tonsillitis symptoms when compared with standard care alone. Additionally, taking this combination product improved physician- and patient-rated assessments of general condition when compared with standard care alone (100347). It is not clear if these effects are due to yarrow, other ingredients, or the combination.
• Vaginal candidiasis. It is unclear if intravaginal yarrow is beneficial for vaginal candidiasis. Details: Clinical research in patients with vulvovaginal candidiasis shows that intravaginal application of 5 grams of a cream containing yarrow extract 2% for 7 days modestly reduces Candida growth and improves vulvar erythema and other general symptoms when compared with baseline. However, the cream was less effective overall than vaginal clotrimazole 1% cream (105360).
• Wound healing. It is unclear if topical yarrow is beneficial for wound healing. Details: Clinical research in postpartum adults who have had an episiotomy shows that applying approximately 1 cm of an ointment containing yarrow 5% over the clean and dried suture area twice daily for ten days reduces perineal pain, redness, and edema 1-2 weeks after the procedure when compared with placebo ointment or no treatment. However, using the yarrow ointment did not affect discharge time or reduce the occurrence of dehiscence (96910). More evidence is needed to rate yarrow for these uses.

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POSSIBLY SAFE ...when used orally in amounts commonly found in foods. Arnica has Generally Recognized As Safe (GRAS) status for use as a food flavoring in the US (4912). However, Canadian regulations do not allow its use as a food ingredient (12). ...when used orally in homeopathic dilutions of 30C and up to 5C (19110,19111,19117,19124,19126,96769). ...when used topically on unbroken skin, short-term (12).

LIKELY UNSAFE ...when used orally or when applied topically to broken skin. Arnica is considered poisonous and has caused severe or fatal poisonings (5). Arnica can cause gastroenteritis, muscle paralysis, bleeding, arrhythmia, hypertension, shortness of breath, nausea and vomiting, multi-organ failure, and death (4,5,17,104,19101,19102,19103,19104,19105,19106,19107,19108).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally or topically; avoid using (12).

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POSSIBLY SAFE ...when used orally and appropriately (12). There is insufficient reliable information available about the safety of Canadian fleabane when used topically.

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

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POSSIBLY SAFE ...when the rhizome or syrup of ipecac is used orally and appropriately, as a single dose. A single 15-30 mL dose of syrup containing 10-21 mg ipecac has been used with apparent safety in clinical research (12,56419,103744).

POSSIBLY UNSAFE ...when in contact with skin or when inhaled. The constituent emetine is a skin irritant, and ipecac powder is a respiratory irritant (6,18).

LIKELY UNSAFE ...when used orally long-term or in amounts greater than 30 mL. Misuse can lead to serious toxicity, including cardiomyopathy and death. Chronic ingestion of ipecac 30 mL (21 mg) 2-3 times daily for 5 months has been associated with cardiomyopathy. The acute lethal dose of ipecac is 850-1780 mL (600-1250 mg) (6,12,19,56412,56460,56467). ...when a total dose of more than 1 gram is injected, it can cause nervous system symptoms, blood in the urine, and circulatory collapse (6).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately as an emetic (272,11349).

CHILDREN: LIKELY UNSAFE
when used orally in large doses and in infants under 1 year old (12,19). Children are more sensitive to large doses and effects on the nervous system than adults (19).

PREGNANCY: LIKELY UNSAFE
when used orally; ipecac is a potential uterine stimulant (12,19).

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Saffron has Generally Recognized as Safe (GRAS) status in the US for use as a spice or food coloring agent (4912).

POSSIBLY SAFE ...when used orally and appropriately in larger amounts, short-term. Saffron extracts have been used with apparent safety in clinical trials at doses of up to 100 mg daily for up to 26 weeks (11024,13103,16555,17214,17401,18102,93395,93397,93400,93403)(93407,97359,99436,100135,100138,100140,100658,100659). The saffron constituent crocin has been used with apparent safety at a dose of up to 30 mg daily for up to 3 months (93410,100139,105616).

POSSIBLY UNSAFE ...when used orally in high doses or for longer than 26 weeks. Taking 5 grams or more of saffron can cause severe side effects. Doses of 12-20 grams can be lethal (12,18). There is insufficient reliable information available about the safety of saffron when used topically.

PREGNANCY: LIKELY UNSAFE
when used orally in amounts exceeding those commonly found in foods. Larger amounts of saffron have uterine stimulant and abortifacient effects (18); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Yarrow products that are thujone-free have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912); however, products containing thujone might not be safe. Thujone is a chemical that stimulates the central nervous system and is poisonous in large doses.

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (2,12,100346). Yarrow whole plant extract has been used with apparent safety at a dose of 250-500 mg daily for 12 months (100346). ...when used intravaginally as a cream containing yarrow extract 2% daily for 7 days (105360). There is insufficient reliable information available about the safety of yarrow when applied topically.

PREGNANCY: LIKELY UNSAFE
when used orally; yarrow is believed to be an abortifacient and affect the menstrual cycle (12).

LACTATION:
Insufficient reliable information available; avoid use.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, arnica might have additive effects with anticoagulant and antiplatelet drugs. Homeopathic arnica preparations are unlikely to have this interaction.  Details In vitro evidence shows that sesquiterpene lactones in arnica flowers can decrease platelet aggregation (104). However, this effect has not been reported in humans.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Canadian fleabane might cause additive effects and side effects when used with anticoagulant or antiplatelet drugs. Canadian fleabane has been shown to inhibit platelet aggregation in vitro (99708,99709).  Details Some anticoagulant/antiplatelet drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

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(Read more about IPECAC)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of saffron with antidiabetes drugs might increase the risk of hypoglycemia.  Details Some clinical research shows that taking saffron extract reduces fasting levels of glucose when used in addition to hypoglycemic agents (100138). However, saffron powder itself has not been shown to reduce fasting glucose levels (99436).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of saffron with antihypertensive drugs might have additive effects.  Details Animal and human research suggests that saffron extract can decrease blood pressure (72518,72365,72473,93409).

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, saffron might inhibit the metabolism of caffeine.  Details A small clinical study suggests that taking saffron powder 300 mg in 150 mL water daily for 5 days and then taking caffeine 200 mg seems to reduce caffeine metabolite levels in the saliva and urine in males, but not females. Theoretically, this may be due to the inhibition of cytochrome P450 1A2 by saffron (100130).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.  Details Clinical research shows that taking saffron extract 60 mg orally daily for 26 weeks can cause drowsiness and sedation (18102). Animal research suggests that adding saffron to hexobarbital further increases sleeping and slows motor activity (72544).

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LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking yarrow with lithium might increase the levels and adverse effects of lithium.  Details Animal research shows that yarrow has diuretic activity (106018). Theoretically, due to these potential diuretic effects, yarrow might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

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General ...Orally, arnica is unsafe and can cause toxicity. When used in homeopathic amounts, arnica seem to be generally well tolerated. Topically, arnica also seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Bleeding, gastroenteritis, hypertension, muscle paralysis, nausea and vomiting, shortness of breath.
Topically: Contact dermatitis and irritation.
Serious Adverse Effects (Rare):
Orally: Arrhythmia, coma, multi-organ failure, and death.

Cardiovascular ...Orally, arnica can cause tachycardia or a faster heart rate (11,17113,19101,19102). A 24-year-old female presented to the emergency department with palpitations and vomiting 24 hours after ingesting a cup of tea that reportedly contained arnica flowers picked from her local area of mountainous Southern California. The species was not specified in the article and there was no indication by the authors that any testing had been done to confirm the identity of the plant (90610).

Dermatologic ...Orally, arnica can cause irritation of mucous membranes (11,17113). Topically, arnica can cause contact itchiness, dry skin, and rash (17113). Oral lesions resulted in a woman who used a mouthwash incorrectly by not following dilution instructions. The mouthwash was 70% alcohol and contained arnica and oil of peppermint (19106).

Gastrointestinal ...Orally, arnica can cause stomach pain, nausea, vomiting, and diarrhea (11,17113,19101,19102). Homeopathic arnica has been reported to cause dry mouth (30C) and sore tongue (6C) (19107). A 24-year-old female presented to the emergency department with palpitations and vomiting 24 hours after ingesting a cup of tea that reportedly contained arnica flowers picked from her local area of mountainous Southern California. The species was not specified in the article and there was no indication by the authors that any testing had been done to confirm the identity of the plant (90610).

Musculoskeletal ...Adverse effects after ingesting arnica include muscle weakness (19101). Homeopathic arnica has been reported to result in the feeling of a "throbby" head or neck (19107).

Neurologic/CNS ...Orally, arnica may cause drowsiness, nervousness, and headache (11,17113,19101,19107).

Ocular/Otic ...In a case report, accidental intake of a large amount of a homeopathic Arnica-30 resulted in acute vision loss due to bilateral toxic optic neuropathy (19105).

Psychiatric ...Oral homeopathic arnica (6C) may cause depressed feelings, specifically a feeling of unhappiness (19107).

Pulmonary/Respiratory ...Orally, arnica can cause shortness of breath (11,17113).

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General ...Orally, Canadian fleabane seems to be well tolerated. It can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (19).

Immunologic ...Canadian fleabane can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (19). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

(Read more about CANADIAN FLEABANE)

General ...Orally, ipecac syrup can cause nausea, vomiting, diarrhea, GI irritation, dizziness, hypotension, dyspnea, and tachycardia. Rarely, it can also cause intracerebral hemorrhage, pneumomediastinum, retropneumoperitoneum, esophageal bleeding (3,6,11,13,15,18,56390,56440,56447,56448)(56449,56464). Chronic use is associated with myopathies and death (6,18,56391,56412,56413,56414,56416,56421,56422,56424)(56433,56441,56446,56459,56462,56467). Overdose is associated with erosion of GI tract mucous membranes, cardiac arrhythmias, disorders of respiratory function, convulsions, shock, and coma (18).
Topically, emetine is a skin irritant (6).
When inhaled, ipecac powder is a respiratory irritant and can result in allergic symptoms such as rhinitis, as well as aspiration pneumonitis (18,56406,56445).
Intravenously, emetine may cause inflammation of the muscle tissue at the injection site with chronic administration. In total doses over 1 gram, it can lead to gastrointestinal and nervous system symptoms, hematuria and circulatory collapse (6).

Cardiovascular ...Orally, ipecac can cause hypotension, dyspnea, and tachycardia (11,56440). Chronic use is associated with cardiac myopathy and death related to heart failure (6,18,56391,56409,56424,56467). Overdose is associated with shock and cardiac arrhythmias (18).
Intravenously, ipecac in total doses over 1 gram can lead to circulatory collapse (6).

Dermatologic ...Topically, emetine, a constituent of ipecac syrup, is a skin irritant (6).

Gastrointestinal ...Orally, ipecac causes nausea, vomiting, diarrhea, and GI irritation (3,6,11,13,15,18,56390,56464). In some cases, these adverse effects are severe. There is a case report of a pneumomediastinum (air in the membrane around the heart) and retropneumoperitoneum (air behind the chest cavity) indicative of esophageal rupture following administration of a therapeutic dose of ipecac (56448). There is also a case report of esophageal bleeding following therapeutic use of ipecac (56447). Overdose is associated with erosion of GI tract mucous membranes (18).
Intravenously, ipecac in total doses over 1 gram can lead to gastrointestinal symptoms (6).

Hematologic ...Orally, a case of intracerebral hemorrhage related to the use of ipecac syrup has been reported in an elderly patient (56449).

Immunologic ...When inhaled, ipecac powder has resulted in occupational allergy symptoms, such as rhinitis (56445).

Musculoskeletal ...Orally, progressive muscular weakness has occurred following ipecac abuse, in some cases resulting in death. Discontinuation of ipecac seems to reverse the myopathy (56391,56412,56413,56414,56416,56421,56422,56424,56433,56441)(56446,56459,56462).
Intravenously, emetine may cause inflammation of the muscle tissue at the injection site with chronic administration (6).

Neurologic/CNS ...Orally, ipecac may cause dizziness (11). Overdose is associated with convulsions and coma (18).
Intravenously, ipecac in total doses over 1 gram can lead to nervous system symptoms (6).

Pulmonary/Respiratory ...Orally, ipecac causes dyspnea (11). Overdose is associated with disorders of respiratory function (18).
When inhaled, ipecac powder is a respiratory irritant and can result in aspiration pneumonitis (18,56406).

Renal ...Intravenously, ipecac in total doses over 1 gram can lead to hematuria (6).

(Read more about IPECAC)

General ...Orally, saffron extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal complaints, nausea, sedation, vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...Orally, sweating and flushing have been reported in clinical research for patients taking saffron 30-60 mg daily (93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the skin (2,11).

Gastrointestinal ...Orally, saffron has been associated with changes in appetite, nausea, and vomiting when given at doses of 30 mg twice daily for 26 weeks, or when the saffron constituent crocin was given as 15 mg twice daily for 12 weeks (18102,105616). At lower doses of 30 mg daily, the occurrence rate of these and other adverse events such as dry mouth, dyspepsia, diarrhea, and constipation was rare or similar to placebo (13103,93395,93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the mucous membranes (mimicking icterus), vomiting, and bloody diarrhea (2,11).

Genitourinary ...One report of excessive uterine bleeding occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bleeding from the uterus (2,11).

Hematologic ...Orally, saffron extract has been reported to cause decreases in platelet, white blood cell, and red blood cell counts after 7 days to 12 weeks of use with doses of 60-200 mg daily. Many of these decreases were only significant when compared to baseline but did not maintain significance when compared to placebo. These reductions were not considered clinically significant (18102,72473,93403,93409).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bloody diarrhea, hematuria, bleeding from the nose, lips, eyelids or uterus, and thrombocytopenic purpura (2,11).

Immunologic ...Allergy to oral saffron has been reported in clinical trials (93404). Anaphylactic reactions can occur within minutes of eating food prepared with saffron (4107,72555). Occupational exposure to saffron has been associated with the development of rhinoconjunctivitis and allergy-induced asthma (4106).

Neurologic/CNS ...Orally, saffron has been reported to cause drowsiness, headache, agitation, and sedation when given at doses of 30 mg twice daily for up to 26 weeks or when crocin is given as 15 mg twice daily for 12 weeks (18102,105616). At doses of 30 mg daily for 6 weeks, the side effect occurrence rate was similar to placebo (13103). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include vertigo and numbness (2,11).

Ocular/Otic ...Orally, saffron poisoning with oral intake of doses of 5 grams or more can cause ocular symptoms such as yellow appearance of the sclera (2,11).

Psychiatric ...Orally, saffron has been reported to cause anxiety and hypomania when given at doses of 30 mg twice daily for 26 weeks (18102). At doses of 30 mg daily for 6 weeks, the occurrence rate was similar to placebo (13103,93395). One report of agitation occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).

Renal ...Orally, the saffron constituent crocin given as 15 mg twice daily for 12 week was associated with one case of urinary incontinence (105616). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include hematuria and uremic collapse (2,11).

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General ...Orally and intravaginally, yarrow seems to be well tolerated.
Most Common Adverse Effects:
Topically: Dermatitis.

Dermatologic ...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007). Yarrow has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385).
Intravaginally, aggravated facial acne was reported by 1 of 40 patients in a clinical trial (105360).

Endocrine ...Intravaginally, an early menses was reported by 1 of 40 patients in a clinical trial (105360).

Genitourinary ...Intravaginally, aggravated vaginal pruritus and dryness were reported by 1 of 40 patients in a clinical trial (105360).

Immunologic ...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007,96911). It has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385). In one 44-year-old female, handling yarrow flowers resulted in rhinitis and asthma (96911).

(Read more about YARROW)