7 Herb Cream by Bioforce USA

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.

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POSSIBLY EFFECTIVE

• Hypercholesterolemia. Consuming a diet rich in avocados seems to improve serum lipid levels. Details: Consuming a diet rich in avocados (e.g., 0.5-2 avocados daily or a diet in which avocados account for 75% of total daily fat intake) for 1-4 weeks seems to lower total serum cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B. It may also increase high-density lipoprotein (HDL) serum cholesterol levels (668,669,670,671,33256). In contrast, a meta-analysis of 8 clinical studies in adults with various metabolic conditions shows that consuming avocado 99-330 grams daily for 3-24 weeks reduces total cholesterol by 5 mg/dL but does not reduce LDL cholesterol or triglycerides or increase HDL cholesterol when compared with diets containing no or low amounts of avocado. However, subgroup analysis in patients with hypercholesterolemia suggests that consuming avocado reduces LDL cholesterol by 9 mg/dL and total cholesterol by 7.5 mg/dL (112435).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if consuming avocado is beneficial for aging skin. Details: A small study in females with overweight or obesity shows that consuming one avocado daily for 8 weeks improves forehead skin firmness, but not elasticity or tiring, when compared with no avocado consumption. No improvements in under eye skin firmness, elasticity, or tiring were observed (108010).
• Cardiovascular disease (CVD). It is unclear if consuming avocado is beneficial for reducing the risk of CVD. Details: Observational research has found that consumption of at least one avocado weekly is associated with a 16% lower risk of CVD and a 21% lower risk of coronary heart disease (CHD) when compared with no avocado consumption. However, there was no association between avocado consumption and the risk of stroke. Additionally, replacement of half a serving daily of certain fat-containing foods (i.e., margarine, butter, egg, yogurt, cheese, processed meats) with an equivalent amount of avocado is associated with a 16% to 22% lower risk of CVD (108007).
• Cognitive function. It is unclear if consuming avocados is beneficial for improving cognitive function. Details: Preliminary clinical research in adults with overweight or obesity shows that consuming one avocado daily as part of a test meal for 12 weeks improves attentional inhibition, but not response inhibition, during cognitive testing when compared with baseline. Improvements on these tests were not reported in patients receiving an isocaloric control meal (103895). A cross-sectional study in older adults has also found that avocado consumption is associated with improvements in memory performance on immediate learning and delayed recall tests as well as global cognitive scores when compared with no avocado consumption (108013).
• Metabolic syndrome. It is unclear if consuming avocados is beneficial for metabolic syndrome. Details: A very large clinical study in adults with an elevated waist circumference shows that consuming a large avocado daily for 6 months reduces total cholesterol by 3 mg/dL and low-density lipoprotein cholesterol by 2.5 mg/dL but does not change any other measures of metabolic syndrome including visceral adiposity, waist circumference, body weight, body mass index (BMI), systolic and diastolic blood pressure, glucose, insulin, triglycerides, very low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol when compared with a standard diet without avocados (112436). Additionally, a small clinical study in adults with overweight, obesity, and insulin resistance shows that consuming an avocado daily for 12 weeks does not change BMI, body composition, blood pressure, fasting glycemic indices, glucose levels, plasma lipid profiles, insulin sensitivity, or markers of inflammation or endothelial function when compared with control (112438).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if consuming avocados is beneficial for NAFLD. Details: A secondary analysis of a previous clinical study in adults with overweight and obesity shows that consuming 14 avocados per week per family for 6 months does not improve NAFLD fibrosis score or biomarkers of hepatic function including alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl-transferase (GGT), or high-sensitivity c-reactive protein (hsCRP) when compared with low avocado consumption, defined as 3 avocados per week per family (112437).
• Obesity. It is unclear if consuming avocados is beneficial for weight loss or prevention of weight gain. Details: A meta-analysis of clinical trials and a very large clinical study in adults with overweight, obesity, and elevated waist circumference shows that consuming one avocado daily or 136-200 grams daily for 6 weeks to 6 months does not reduce body weight, body mass index (BMI), percent fat mass, or visceral adipose tissue when compared with control (112433,112436). However, a small study in adults with overweight or obesity shows that consuming one avocado daily for 12 weeks changes abdominal adiposity distribution among females, but not males, when compared with no avocado consumption. No significant effects were observed for glucose or insulin outcomes (108008). Preliminary clinical research in adults with overweight or obesity shows that eating half of an avocado with lunch increases satisfaction by 23% to 26% and decreases desire to eat by 28% to 40% when compared with a control lunch with no avocado (93109). A large observational study in the same population has found that habitual consumption of avocado at an average intake of 32 grams or more daily is not associated with reductions in body weight or body mass index (BMI) over 5 years when compared with no avocado consumption. Additionally, this study suggests that while habitual avocado consumption in patients with normal weight may slightly attenuate increases in body weight and BMI, it does not seem to reduce the odds of these patients becoming overweight or developing obesity over time when compared with no avocado intake (100936).
• Psoriasis. Topical avocado has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with psoriasis shows that applying a specific cream containing avocado oil and vitamin B12 (Regividerm, Regeneratio Pharma AG) 0.7 mg/gram to the affected area for 12 weeks reduces symptoms to a similar extent when compared with calcipotriol ointment (Psorcutan). The avocado combination cream also causes significantly less irritation than calcipotriol (14909). It is unclear if these effects are due to avocado, vitamin B12, or the combination. More evidence is needed to rate avocado for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anal fissures. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax for 12 hours reduces pain, bleeding, and itching associated with anal fissures (34100). It is unclear if these effects are due to beeswax, the other ingredients, or the combination.
• Burns. Preliminary clinical research in individuals with second-degree burns shows that applying a dressing containing a mixture of beeswax, olive oil, and alkanna once daily reduces healing time by almost 4 days, decreases pain during dressing changes, and shortens the duration of hospitalization by about 6 days compared to using a dressing containing nitrofurazone and rifamycin, applied once every 2 days (96328). Other preliminary clinical research shows that using a topical product containing beeswax (Medilixir, Medilixir Pty Ltd) for 14 days decreases the severity of itching, lengthens the time until itch recurrence, and decreases the use of anti-itch medications compared to standard aqueous cream (Biotech Pharmaceuticals Pty Ltd) in individuals experiencing post-burn itch (96329). Poor study designs limit the reliability of the findings.
• Diaper rash. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax four times daily for 7 days reduces symptoms of diaper rash by more than 75% (34094). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Hemorrhoids. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax for 12 hours reduces pain, bleeding, and itching associated with hemorrhoids (34100). It is unclear if these effects are due to beeswax, the other ingredients, or the combination.
• Oral mucositis. Preliminary clinical research in children with severe chemotherapy-induced mucositis shows that applying of mixture of honey, olive oil-propolis extract, and beeswax topically three times daily until healing or for a maximum of 10 days, along with standard oral care, reduces recovery time by almost 3 days compared to using benzocaine 7.5% gel. However, the mixture does not appear to reduce recovery time compared to benzocaine in patients with moderate chemotherapy-induced mucositis. Additionally, applying honey alone 0.5 grams/kg (maximum 15 grams), appears to be more efficacious for both moderate and severe mucositis than either the honey mixture or benzocaine gel (55245).
• Radiation dermatitis. A small clinical study in patients undergoing radiotherapy shows that applying a topical ointment containing beeswax, olive oil, calendula oil extract, and St. John's wort oil extract to the treated area nightly during radiotherapy and for two weeks post-radiotherapy, while also applying a topical cream containing aloe vera gel, calendula oil extract, and St. John's wort oil extract to the treated area three to four times daily, reduces the intensity of dermatitis and improves quality of life scores when compared to baseline (105769). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if these findings are due to beeswax, other ingredients, or the combination.
• Tinea corporis. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 75% of patients with tinea corporis (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Tinea cruris. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 78% of patients with tinea cruris (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination.
• Tinea versicolor. Preliminary clinical research shows that topical use of a mixture of honey, olive oil, and beeswax three times daily for 4 weeks achieves clinical response in 86% of patients with tinea versicolor (34092). It is unclear if this effect is due to beeswax, the other ingredients, or the combination. More evidence is needed to rate beeswax for these uses.

(Read more about BEESWAX)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical calendula 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 acne associated with mask wearing shows that topical application of a combination of calendula 4%, licorice root extract 0.3%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to calendula, other ingredients, or the combination.
• Bacterial vaginosis. It is unclear if topical calendula is beneficial for improving bacterial vaginosis. Details: A small clinical study in patients with bacterial vaginosis shows that applying 5 grams of vaginal cream containing calendula flower extract before bed for one week improves vaginal burning, odor, painful urination, and painful intercourse when compared to baseline (96649). The validity of these findings is limited by the lack of a comparator group.
• Burns. It is unclear if oral calendula is beneficial for burn healing. Details: A small clinical trial in patients hospitalized for second-degree burns shows that taking calendula 2 grams daily for 2 weeks has a large beneficial effect on wound healing when compared with placebo (110323).
• Chronic obstructive pulmonary disease (COPD). Oral calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males aged 40-70 years with a history of smoking and stage 2 COPD shows that taking a specific combination of calendula flowers 165 mg, elderberry 165 mg, and heart's ease herb 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months, modestly improves symptoms, as measured on the breathlessness, cough, and sputum scale (BCSS), and mean forced expiratory volume in 1 second (FEV1) when compared to baseline. However, there was no improvement of COPD exacerbations or other pulmonary function tests (103629). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Furthermore, it is unclear if these effects are due to calendula, the other ingredients, or the combination.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Calendula in rectal suppositories has only been evaluated in combination with turmeric extract; its effect when used alone is unclear. Details: A small clinical study in patients with CP/CPPS shows that using a rectal suppository containing turmeric extract 350 mg and calendula extract 80 mg daily for one month improves pain, peak urine flow rate, and erectile function when compared with placebo (96648). It is unclear if these effects are due to calendula, turmeric, or the combination.
• Conjunctivitis. Although there is interest in using topical calendula for conjunctivitis, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Diabetic foot ulcers. It is unclear if topical calendula is beneficial for improving diabetic foot ulcers. Details: Observational research has found that applying a calendula hydroglycolic extract spray in addition to standard care and hygiene is associated with reduced bacterial colonization and improved odor in patients that have had a diabetic ulcer for over 3 months (93548).
• Diaper rash. It is unclear if topical calendula is beneficial for improving diaper rash. Details: One preliminary clinical study in children less than 3 years of age shows that topical application of calendula 1.5% ointment three times daily for 10 days improves diaper rash when compared with aloe gel (19779). However, other preliminary clinical research shows that applying calendula 1.5% cream every 4-6 hours for 3 days improves diaper rash in fewer infants when compared to treatment with bentonite 50% mineral solution (93545,93554).
• Dysmenorrhea. Although there is interest in using oral calendula for dysmenorrhea, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Gingivitis. It is unclear if using a mouth rinse with calendula is beneficial for improving gingivitis. Details: Preliminary clinical research in patients with mild gingivitis and bleeding gums shows that rinsing the mouth with a tincture containing calendula 25% (Dr. Willmar Schwabe Germany Home Pharmacy Pvt. Ltd.) twice daily for 6 months decreases plaque, gingivitis, and bleeding by 10% to 18% when compared to rinsing with water (93551). Other preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with a combination mouthwash containing a 5% extract of calendula, rosemary, and ginger for 30 seconds twice daily after food for 2 weeks decreases plaque, gingivitis, and bleeding when compared with a placebo mouthwash. The effects of this combination mouthwash appear to be similar to chlorhexidine 0.2% mouthwash (93555). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Hemorrhoids. Although there is interest in using topical calendula for hemorrhoids, there is insufficient reliable information about the clinical effects of calendula for this purpose.
• Liver disease. Although there is interest in using oral calendula for liver disease, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Mosquito repellent. It is unclear if topical calendula essential oil helps to repel mosquitos. Details: Preliminary clinical research shows that applying calendula 50% essential oil to the skin does not repel mosquitos as effectively as applying DEET. Mean repellency time was about 2 hours for patients applying calendula, which was shorter than the 6 hour repellency with DEET (93562).
• Oral leukoplakia. It is unclear if topical calendula is beneficial for improving oral leukoplakia. Details: Preliminary clinical research in patients with oral leukoplakia shows that applying a gel containing calendula flower extract 0.2% three times daily for one month reduces lesion size by about 2 cm when compared to baseline (96650). The validity of this finding is limited by the lack of a comparator group.
• Oral mucositis. Calendula as a mouth rinse has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with head and neck cancer receiving chemotherapy and radiotherapy shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing calendula powder extract 2%, propolis, aloe vera, and chamomile three times daily for 6 weeks does not prevent oral mucositis when compared with placebo (95879).
• Otitis media. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with otitis media shows that applying a specific combination product containing calendula, mullein, garlic, and St. John's wort in olive oil (Otikon Otic Solution, Healthy-On Ltd, Petach-Tikva, Israel), five drops into the affected ear three times daily for 3 days, may reduce ear pain when compared with baseline (39500,39552). It is unclear if this effect is due to calendula, other ingredients, or the combination. Furthermore, due to the lack of an adequate control group, it is unclear whether the pain reduction was due to the resolution of otitis media.
• Peptic ulcers. Although there is interest in using oral calendula for peptic ulcers, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Pressure ulcers. It is unclear if topical calendula is beneficial for improving pressure ulcers. Details: Observational research has found that the application of a specific calendula product (Plenusdermax) twice daily is associated with improved healing in patients with pressure ulcers that have not changed in size for at least 3 months (93549). Preliminary clinical research in hospice patients with symptomatic pressure ulcers and other wounds shows that applying a homeopathic powder (RGN107) containing calendula 0.1% and arnica 0.01% to wounds for 4 weeks is rated by the patients and caregivers to be acceptable for controlling pain, odor, and exudate when compared with baseline (96647). The validity of this finding is limited by the lack of a control group.
• Radiation dermatitis. It is unclear if topical calendula reduces radiation dermatitis symptoms. Details: Meta-analyses of three preliminary clinical trials in patients with breast cancer show that topical calendula does not affect the development of radiation dermatitis or the incidence of moderate to severe symptoms when compared to control (110325,113674). In addition, a meta-analysis of two studies (39503,93560) shows that topical calendula does not reduce the incidence of treatment interruptions due to severe symptoms of radiation dermatitis (110325). In one of the included studies, a specific calendula petroleum jelly ointment (Pommade au Calendula par Digestion, Boiron Ltd.) used twice daily during radiation therapy was found to reduce acute radiation dermatitis occurrence when compared with topical trolamine (Biafine) (39503). However, it is unclear if the benefit was due to calendula or petroleum jelly. Another clinical study used a specific calendula 10% cream in wool fat and sesame oil (Calendula Weleda, Weleda AG) twice daily during radiation therapy. This product was found to be no better than aqueous petroleum jelly cream (Essex, Schering-Plough) for reducing acute skin reactions and dermatitis symptoms of pain, burning, itching, pulling, and tenderness (93560).
• Vaginal atrophy. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in menopausal patients with vaginal atrophy shows that use of a specific vaginal gel containing calendula, Lactobacillus sporogenes, isoflavones, and lactic acid (Estromineral Gel, Rottapharm-Madaus) daily for 4 weeks reduces vaginal itching, burning, dryness, and painful intercourse when compared with no topical treatment. Both groups also received oral isoflavones (39534). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Vaginal candidiasis. One small clinical study suggest that topical calendula is not beneficial for the treatment of vaginal candidiasis. Details: Preliminary clinical research shows that applying 5 grams of calendula 1% cream intravaginally once daily for 7 days effectively treats vaginal candidiasis in 34% fewer patients when compared with using clotrimazole 1% cream (93559).
• Venous leg ulcers. It is unclear if topical calendula is beneficial for improving venous leg ulcers. Details: Preliminary clinical research shows that applying a calendula 7.5% ointment twice daily for 3 weeks to venous leg ulcers accelerates healing when compared with applying saline solution dressing (39509).
• Wound healing. It is unclear if topical calendula is beneficial for improving the healing of small wounds. Details: Two small clinical trials in postpartum patients show that applying calendula ointment (formulation unspecified) to the episiotomy wound every 8 hours for 5-10 days modestly reduces pain, and seems to speed up the resolution of redness, edema, and ecchymosis, when compared with standard care, such as application of betadine solution (93550,105087). Another small clinical study in adults with wounds smaller than 10 cm² on the hands and fingers shows that applying calendula flower extract 2% to the wound twice daily may modestly improve healing and epithelialization time when compared with mineral oil (107806). More evidence is needed to rate calendula for these uses.

(Read more about CALENDULA)

POSSIBLY EFFECTIVE

• Cognitive function. Oral sage seems to be beneficial for improving cognitive function in healthy adults. The benefits of sage aromatherapy are unclear. Details: Clinical research shows that taking a specific product providing common sage polyphenols and Spanish sage terpenoids (Cognivia), either as a single dose or daily for 29 days, modestly improves working memory and accuracy when compared with placebo. A single dose of this product contains common sage leaf extract 400 mg and Spanish sage essential oil 200 mg (105337). In addition, preliminary clinical research shows that Spanish sage essential oil 25-50 mcL orally as a single dose seems to dose-dependently enhance some measures of cognitive performance in young adults by a small amount (10811,72609,72616,72660). When used as aromatherapy, essential oils of common sage, but not Spanish sage, seem to improve quality of memory and secondary memory. Neither species improves speed of memory or working memory when used as aromatherapy. In this study, five drops of common sage essential oil and 5 mL water were placed on a warmed stone and allowed to diffuse for 5 minutes prior to exposure (72658).
• Hyperlipidemia. Oral sage seems to be beneficial for reducing low-density lipoprotein (LDL) cholesterol and triglyceride levels. Details: Clinical research in adults with mixed hyperlipidemia types shows that taking common sage leaf extract 500 mg, standardized to quercetin 2.16%, three times daily for 2 months reduces LDL cholesterol and triglyceride levels by about 20% and 23%, respectively, and increases high-density lipoprotein (HDL) cholesterol levels by 20%, when compared with placebo (72662). Also, preliminary clinical research in adults with type 2 diabetes and hypercholesterolemia shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers total cholesterol by 17%, LDL cholesterol by 36%, and triglycerides by 56%, and increases HDL cholesterol by 28%, when compared with placebo (91971).
• Menopausal symptoms. Oral sage seems to be beneficial for reducing menopausal symptoms. Details: Clinical research shows that taking a thujone-free common sage extract (Menosan, A.Vogel AG) 280 mg daily for 4 weeks reduces overall symptoms of menopause by 39% when compared with placebo. About 41% of patients taking common sage had at least a 50% reduction in symptoms, compared with 8% of those taking placebo. Hot flushes, sleep problems, joint and muscle discomfort, irritability, and physical and mental exhaustion were improved, whereas urogenital symptoms such as sexual desire and vaginal dryness were not (105338). Other clinical research shows that taking common sage extract 300 mg daily for 3 months moderately reduces overall symptoms of menopause after about 10 weeks when compared with placebo. However, there was no effect on vaginal dryness, physical and mental exhaustion, or urinary incontinence (103379). Another small clinical study shows that taking a specific thujone-free common sage extract (Sage Menopause, Bioforce AG) 280 mg daily for 56 days reduces daily hot flash frequency by 40% and reduces hot flash intensity when compared with baseline (17177). The validity of these findings is limited by the lack of a comparator group.

POSSIBLY INEFFECTIVE

• Postoperative pain. Using an oral rinse containing common sage does not seem to be beneficial for reducing postoperative pain. Details: A large open-label clinical trial in children and adults shows that using a common sage oral rinse 6 times daily in combination with ibuprofen or diclofenac is less effective than benzydamine hydrochloride, a local anesthetic, for reducing pain following tonsillectomy and/or adenoidectomy. Furthermore, treatment with common sage oral rinse is associated with an increased risk of postoperative infection in adults when compared with benzydamine hydrochloride (72700).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if a single oral dose of common sage is beneficial for age-related cognitive decline. Details: Clinical research in healthy, older adults shows that taking a single dose of common sage extract 333 mg improves accuracy of attention and some measures of memory when compared with placebo. However, not all doses were effective and some measures of cognitive function were not affected (72642).
• Alzheimer disease. It is unclear if oral sage is beneficial for Alzheimer disease. Details: Preliminary clinical research shows that taking extracts of common sage and Spanish sage orally seems to improve cognitive function in patients with mild to moderate Alzheimer disease when used for up to 4 months (10334,10810). In one study, a fixed dose of common sage hydroalcoholic extract, equivalent to 1 gram of sage per day, was used for 4 months (10810). In the other, an extract of Spanish sage titrated up to 2.5 mg three times daily for 6 weeks was used (10334). These studies are limited by their short duration and small numbers of participants.
• Androgen deprivation therapy (ADT)-associated hot flashes. It is unclear if oral sage is beneficial for ADT-associated hot flashes. Details: Preliminary clinical research in patients with prostate cancer receiving ADT shows that taking common sage extract 150 mg three times daily with meals for 4 weeks reduces hot flash severity by 48% and hot flash frequency by 42% when compared with baseline. These improvements were maintained with an additional 8 weeks of treatment (91970). The validity of these findings is limited by the lack of a comparator group.
• Athletic performance. It is unclear if oral sage is beneficial for improving athletic performance. Details: In young, healthy, physically active adults, taking a specific supplement (Cognivia, Nexira) containing 400 mg common sage leaf extract and 200 mg Spanish sage oil, orally 2 hours prior to a 40-minute stationary cycling session at 80% of maximum aerobic power, lowers perceived exertion scores and improves working memory and reaction times when compared with placebo (108961).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if topical sage is beneficial for the treatment or prevention of CINV. Details: A small clinical study in patients undergoing chemotherapy shows that using common sage oil 2 mL topically during 15-minute sessions of Swedish abdominal massage twice daily for 3 days modestly reduces nausea severity scores, but does not affect vomiting frequency, when compared with massage alone (107023).
• Dental plaque. It is unclear if rinsing the mouth with sage is beneficial for reducing plaque. Details: Preliminary clinical research shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), is as effective as normal saline for reducing dental plaque. However, there was no effect on tongue plaque. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Diabetes. It is unclear if oral sage is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers fasting blood glucose by 32% and glycated hemoglobin (HbA1c) by 23% when compared with placebo (91971). However, another small clinical study in patients with type 2 diabetes shows that taking common sage extract 150 mg three times daily for 3 months does not lower fasting blood glucose or HbA1c when compared with placebo, although there is a modest reduction in 2-hour postprandial blood glucose levels (105340). A meta-analysis of 3 small studies, including the 2 described above, shows that taking common sage, 150-500 mg three times daily for 2-3 months, modestly reduces fasting blood glucose and 2-hour postprandial blood glucose levels, as well as HbA1c, when compared with placebo (108962). These studies were all conducted in Iran; it is unclear if these findings are generalizable to other geographic locations.
• Dry mouth. It is unclear if rinsing the mouth with common sage is beneficial for dry mouth. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in conjunction with standard care involving brushing and an oral gel (Biotene), is as effective as normal saline for improving overall oral health and modestly more effective than normal saline for improving dry mouth. The rinse was made by steeping 2.5 grams dried sage leaf in 100 mL boiled water for two minutes (105339).
• Gingivitis. Sage has only been evaluated as a mouthwash in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly individuals shows that rinsing the mouth with a mouthwash containing sage, marshmallow, calendula, tormentil, horse chestnut, neem, and myrrh, once daily for 30 seconds for 6 weeks, is no more effective than placebo for improving plaque and gingival bleeding (105341).
• Herpes labialis (cold sores). It is unclear if topical sage is beneficial for herpes labialis. Details: Clinical research shows that topical application of a cream containing either sage alone or sage with rhubarb, starting within 1 day of the first symptoms and continuing for 10-14 days, heals herpes labialis legions in 7.6 days or 6.7 days, respectively, compared to a healing time of 6.3 days with acyclovir cream. The combination of sage and rhubarb also improves the time to healing and reduces pain when compared with sage alone. The cream provided 23 mg sage extract, with or without 23 mg rhubarb extract, per gram and was applied every 2-4 hours while awake (10437).
• Lung cancer. It is unclear if dietary sage is beneficial for lung cancer prevention. Details: Epidemiological research has found that regularly consuming sage is associated with a 54% lower risk of developing lung cancer when compared with those who do not use sage as a spice (72593).
• Oral mucositis. It is unclear if rinsing the mouth with sage is beneficial for oral mucositis. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a rinse containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve oral mucositis when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Pharyngitis. It is unclear if inhaling a spray containing sage, with or without other ingredients, is beneficial for pharyngitis. Details: Clinical research in patients with acute viral pharyngitis shows that inhaling three puffs (140 mcL) of a specific spray (Valverde Salvia Rachenspray) containing common sage extract 15%, six to nine times daily for 3 days, reduces throat pain intensity over 2 hours when compared with placebo. However, sprays containing common sage extract 5% or 30% do not seem to be more effective than placebo for reducing throat pain (72619). Other preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Polycystic ovary syndrome (PCOS). It is unclear if oral sage is beneficial for PCOS. Details: Clinical research shows that taking common sage extract 330 mg daily for 8 weeks modestly reduces body mass index (BMI), diastolic blood pressure, and fasting blood glucose, and modestly improves measures of insulin resistance, when compared with placebo in individuals with PCOS. However, there was no effect on waist to hip ratio or systolic blood pressure (103380).
• Sunburn. It is unclear if topical sage is beneficial for sunburn prevention. Details: Clinical research shows that a single application of a hydrophilic ointment containing common sage extract 2% to the skin immediately after exposure to ultraviolet light reduces the development of skin redness when compared with placebo (72638).
• Swallowing dysfunction. It is unclear if rinsing the mouth with sage is beneficial for swallowing dysfunction. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve swallowing when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Tonsillitis. Sage has only been evaluated in a spray in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Tonsillopharyngitis. It is unclear if oral sage is beneficial for treating tonsillopharyngitis. Details: A moderate-sized observational study in patients aged 12-75 years old with acute tonsillopharyngitis suggests that taking lozenges containing sage extract 378.5 mg and echinacea extract 5 times daily for 4 days reduces throat pain and tonsillopharyngitis symptoms when compared to baseline, both acutely within 90 minutes and after 4 days of treatment (111530). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to sage, echinacea, the combination, or natural resolution of the condition. More evidence is needed to rate sage for these uses.

(Read more about SAGE)

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

(Read more about SANICLE)

LIKELY EFFECTIVE

• Depression. Specific formulations of oral St. John's wort are effective for mild or moderate major depressive disorder. St. John's wort may also cause fewer side effects than certain conventional antidepressants. Details: Moderate quality meta-analyses and individual clinical trials show that St. John's wort extracts are more effective than placebo (76057,76140,76143,76271,89669,104036), and likely as effective as low-dose tricyclic antidepressants (6434,76143), tetracyclic antidepressants (76174), and selective serotonin reuptake inhibitors (SSRIs) (76143,76144,96551), including fluoxetine (Prozac) (3550,4897), sertraline (Zoloft) (6400), and paroxetine (Paxil) (13021) for treating depression. However, some of these studies have been critiqued for using lower doses of SSRIs than typical dosing in comparative studies (104037). St. John's wort also seems to have better tolerability and less gastrointestinal, neurologic, and sexual adverse effects than certain conventional antidepressants (104036). Taking St. John's wort extract improves mood and decreases anxiety, somatic symptoms, and insomnia related to mild to severe major depression (3550,4897,6400,13021,13157,76143,104036). Short-term response rates to St. John's wort appear to be between 65% and 100%; however, long-term, the response rates appear to range from 60% to 69% (13156). Most studies have evaluated St. John's wort in adults; however, there is also some evidence that taking St. John's wort 300-1800 mg daily might be effective for depression in children less than 17 years old (4538,10844,76110). There is some concern that St. John's wort may not be effective for severe major depressive disorder necessitating psychiatric care. Two studies in psychiatric care settings showed no benefit of using St. John's wort (5096,10843). Clinical guidelines from the American College of Physicians state that St. John's wort may be as effective and better tolerated than conventional antidepressants for mild to moderate depression (104037). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that St. John's wort is recommended as monotherapy for mild to moderate forms of major depressive disorder (110318). There is no guarantee that people living in the United States can obtain St. John's wort preparations of similar potency and effectiveness as those used in clinical research (104037). The CANMAT Taskforce recommendation is for specific formulations of 3:1 to 7:1 extracts, standardized to approximately 0.2-0.3% hypericin and/or 5-6% hyperforin, in single or divided doses of 600 mg to 1800 mg daily (110318). Most studies have used St. John's wort extracts standardized to hypericin content, usually 0.3%, but extracts standardized to 1% to 4% hyperforin also seem to be effective. Extracts containing hypericin 0.2% to 0.3%, including LI 160 (Lichtwer Pharma) and Remotiv (Zeller) have most often been studied in doses of 300 mg three times daily for up to 6 weeks, or 250 mg twice daily for up to 6 weeks. Extracts containing 3% to 6% hyperforin, including Movana (Pharmaton) and WS 5570 (Schwabe Pharmaceuticals) have most often been studied in doses of 300-600 mg three times daily for 6-26 weeks (761,4538,4630,104036).

POSSIBLY EFFECTIVE

• Menopausal symptoms. Oral St. John's wort seems to be beneficial for patients with menopausal symptoms. Details: Most clinical research shows that taking St. John's wort as a single supplement can reduce menopausal symptoms. A meta-analysis of small clinical trials in menopausal adults shows that taking St. John's wort up to 900 mg daily for up to 16 weeks, alone or in combination with other herbs, reduces frequency and severity of hot flashes when compared with placebo (95510). Some research also suggests that St. John's wort might improve quality of life and psychological symptoms when compared with placebo (76043,76146,89666,95510). St. John's wort has also shown benefit when used in combination with black cohosh (Remifemin Plus, Schaper & Brummer GmbH & Co. KG; Gynoplus, Jin-Yang Pharm; Feramin Q, Dongkook Pharm) (15037,15893,35853,95510), and with Vitex agnus-castus (41482).
• Somatic symptom disorder. Oral St. John's wort seems to be beneficial for patients with somatoform disorder. Details: Two clinical trials in patients with somatoform disorders shows that taking a specific standardized St. John's wort extract (LI 160, Lichtwer Pharma) 600 mg daily seems to reduce symptoms of somatization disorder by 45% after 6 weeks of treatment when compared with placebo (9476,76089).

POSSIBLY INEFFECTIVE

• Burning mouth syndrome. Oral St. John's wort does not appear to reduce pain from burning mouth syndrome. Details: A small clinical study in patients with burning mouth syndrome shows that taking St. John's wort 300 mg (standardized to hypericin 0.3% and hyperforin 3.0%) three times daily for 12 weeks does not alleviate pain when compared to placebo (76133).
• Hepatitis C. St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral drug for hepatitis C. Details: A small clinical study in patients with chronic hepatitis C virus (HCV) infection shows that giving synthetic hypericin 0.05-0.1 mg/kg orally daily does not seem to be effective for reducing viral load and may be unsafe due to the risk for phototoxic reactions (4631).
• HIV/AIDS. St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral and intravenous drug for HIV. Details: A small clinical study in adults infected with HIV shows that giving synthetic hypericin 0.25-0.5 mg/kg, either intravenously 2-3 times weekly or orally every day, as an antiretroviral agent does not seem to be effective and may be unsafe due to the risk for phototoxic reactions, which occurred in about 50% of patients (206).
• Irritable bowel syndrome (IBS). Oral St. John's wort does not seem to improve symptoms in patients with IBS. Details: A small clinical study shows that taking a specific St. John's wort extract (St. John's Wort Extract Extra Strength, Enzymatic Therapy) 450 mg twice daily is no more effective than placebo for reducing symptoms of IBS after 12 weeks of treatment. In fact, patients taking placebo had improved symptoms compared to St. John's wort (16893).
• Peripheral neuropathy. Oral St. John's wort does not seem to relieve pain in patients with peripheral neuropathy. Details: A small clinical study in diabetic and non-diabetic patients with polyneuropathy shows that taking St. John's wort containing 0.9 mg hypericin orally daily for 5 weeks does not seem to relieve most measures of pain when compared with placebo (7047).
• Social anxiety disorder. Oral St. John's wort does not seem to be beneficial for patients with social anxiety disorder. Details: A small clinical study shows that taking St. John's wort 600-1800 mg daily for 12 weeks does not improve social phobia or social anxiety disorder when compared with placebo (76101).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical St. John's wort is beneficial for acne. Details: A small clinical trial in patients with mild to moderate acne treated with photodynamic therapy shows that topical application with 1.5 mL of a St. John's wort 0.5% extract (DR-Light complex; Genicos Co., Ltd, Cheongju, Korea) for 10 minutes for four weekly sessions reduces acne lesion count as effectively as treatment with indole-3-acetic acid (110327).
• Anxiety. Although there is interest in using oral St. John's wort for anxiety, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral St. John's wort is beneficial for improving symptoms in children with ADHD. Details: A small clinical study in children ages 6-17 years with ADHD shows that taking a specific St. John's wort extract standardized to 0.3% hypericin, 300 mg three times daily for 8 weeks, does not improve symptoms such as inattentiveness when compared with placebo (17986).
• Brain tumor. St. John's wort contains hypericin. Synthetic hypericin has been studied as an oral drug for malignant brain tumors, with unclear benefit. Details: A small clinical study in patients with malignant gliomas shows that taking synthetic hypericin 0.05-0.5 mg/kg daily orally for up to 3 months was associated with stable disease in 7 of 42 patients and partial response in 2 of 42 patients (76160). However, it is unclear how these outcomes would compare with historical controls or a prospectively enrolled control group.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral St. John's wort for CFS, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Crigler-Najjar syndrome type 2. It is unclear if oral St. John's wort is beneficial for patients with this condition. Details: Crigler-Najjar syndrome type 2 is a rare genetic disorder characterized by the accumulation of bilirubin in the body. One case report of a 24 year-old female with this condition shows that taking St. John's wort (Jarsin LI160, Vifor SA) 300 mg three times daily by mouth for two 8-week periods 18 months apart decreases bilirubin levels by 34%, reduces jaundice, and improves fatigue (95509).
• Fibromyalgia. Although there is interest in using oral St. John's wort for fibromyalgia, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
• Genital herpes. Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear. Details: A clinical study in patients with herpes simplex virus 1 (HSV-1) or 2 (HSV-2) shows that applying a single dose of a specific topical product (Dynamiclear, Global Herbal Supplies Pty Ltd), which contains St. John's wort 0.1% and copper sulfate pentahydrate 5%, helps reduce symptoms such as stinging, burning, erythema, and pain. In fact, the combination product appears to reduce erythema, itching, and pain more than applying acyclovir 5% (Zovirax, Glaxo Smith Kline) five times daily for 7 days (76164).
• Herpes labialis (cold sores). Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear. Details: A clinical study in patients with herpes simplex virus 1 (HSV-1) or 2 (HSV-2) shows that applying a single dose of a specific topical product (Dynamiclear, Global Herbal Supplies Pty Ltd), which contains St. John's wort 0.1% and copper sulfate pentahydrate 5%, helps reduce symptoms such as stinging, burning, erythema, and pain. In fact, the combination product appears to reduce erythema, itching, and pain more than applying acyclovir 5% (Zovirax, Glaxo Smith Kline) five times daily for 7 days (76164).
• Mastitis. It is unclear if topical St. John's wort is beneficial for granulomatous mastitis. Details: In patients with idiopathic granulomatous mastitis, persistent or intractable skin lesions may remain after treatment with oral steroids and antibiotics. Preliminary clinical research shows that topical application with St. John's wort oil for two minutes twice daily for 6 weeks reduces the severity of skin lesions in patients with persistent lesions following treatment. After treatment, the success rate, based on clearance or remaining mild symptoms, was 94.1% (110326).
• Memory. It is unclear if oral St. John's wort is beneficial for improving memory in healthy people. Details: A small clinical study in healthy adults shows that taking a specific supplement (Remotiv, Zeller) containing St. John's wort 250 mg, standardized to 0.5 mg of hypericin, by mouth as a single dose, seems to improve short-term memory when compared with baseline. In contrast, the same product containing a higher dose of St. John's wort, 500 mg, seems to worsen memory when compared with baseline (100245). The validity of this finding is limited by the lack of a control group.
• Migraine headache. It is unclear if oral St. John's wort is beneficial for reducing migraine headache. Details: A small low quality clinical study in patients with migraines suggests that adding a specific St. John's wort product (Perforan, Godaru) 160 mg three times daily to sodium valproate 400 mg daily might modestly improve migraine intensity, but not migraine frequency, when compared with sodium valproate alone (89667).
• Obsessive-compulsive disorder (OCD). It is unclear if oral St. John's wort is beneficial for reducing OCD symptoms. Details: There is conflicting evidence about the effectiveness of St. John's wort for OCD. A small open-label study suggests that taking a specific St. John's wort extract standardized to 0.3% hypericin (Alterra, Upsher-Smith Laboratories) 450 mg twice daily for 12 weeks might improve symptoms of OCD when compared to baseline (5075). The validity of this finding is limited by the lack of a control group. A small, higher quality clinical study using a different St. John's wort extract (LI 160, Lichtwer Pharma AG) 600-1800 mg daily for 12 weeks shows that it does not improve symptoms of OCD when compared with placebo (14417). However, this study excluded patients with concomitant depression, so it's unclear if St. John's wort might improve OCD symptoms in patients with depression.
• Osteoarthritis. It is unclear if topical St. John's wort is beneficial for osteoarthritis. Oral St. John's wort is not studied for this use. Details: A moderate-sized clinical study in adults with knee osteoarthritis shows that applying St. John's wort oil (concentration unknown) to the knees three times a day for 21 days improves patient-reported pain, stiffness, and function scores when compared with placebo (olive oil) (113093). However, participants were aware of which treatment they received and were allowed to continue use of analgesics as needed, which limits the validity of this study.
• Polycystic ovary syndrome (PCOS). Oral St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking three tablets containing St. John's wort, licorice root, Ceylon cinnamon, levant berry, peony, and Tribulus daily for 3 months, in addition to lifestyle changes, improves oligomenorrhea by 33% and quality of life by 30% when compared with lifestyle changes alone in adults with PCOS (97216). It is unclear if these effects are due to St. John's wort, other ingredients, or the combination.
• Premenstrual syndrome (PMS). It is unclear if oral St. John's wort is beneficial for patients with PMS. Details: There is conflicting evidence on the effects of St. John's wort for treating PMS, although most evidence suggests benefit. A small clinical study shows that taking a specific St. John's wort extract standardized to contain 0.18% hypericin and 3.38% hyperforin (LI 160, Lichtwer Pharma AG) 450 mg twice daily for two menstrual cycles reduces physical and behavioral PMS symptoms, but not mood or pain, when compared with placebo (76150). Another clinical study shows that taking St. John's wort extract containing hypericin 1.36 mg daily for two menstrual cycles can reduce symptoms of PMS, including anxiety, depression, forgetfulness, crying, headache, and fatigue, when compared with placebo (76159). However, one clinical study shows that taking St. John's wort 600 mg (standardized to contain 1.8 mg of hypericin) does not reduce anxiety or other PMS symptoms when compared with placebo (76104). The conflicting results may be due to differences in St. John's wort formulations and dosages.
• Psoriasis. It is unclear if topical St. John's wort improves symptoms in patients with plaque psoriasis. Details: A small clinical study in patients with mild or moderate plaque psoriasis shows that applying an ointment containing St. John's wort extract 5% twice daily to one side of the body for 4 weeks modestly decreases the severity, thickness, and degree of erythema of psoriasis plaques when compared with applying placebo ointment to the other side of the body (95940).
• Seasonal affective disorder (SAD). It is unclear if oral St. John's wort is beneficial for patients with SAD. Details: Preliminary clinical research shows that St. John's wort extract improves symptoms associated with SAD, including anxiety, decreased libido, and sleep disturbances, when compared with baseline. It may be beneficial when used alone or in combination with light therapy (9686,76175). However, the validity of these findings is limited by the lack of a comparator group.
• Scleroderma. Topical St. John's wort has only been evaluated in combination with neem oil; its effect when used alone is unclear. Details: A small observational study in patients with systemic sclerosis has found that topical application of a specific cream (Holoil, RI.MOS. SRL) containing St. John's wort and neem oil is associated with improved healing, decreased pain, and reduced need for surgical interventions and antibiotics when compared with a control group (102867). It is unknown if these effects are due to St. John's wort, neem, or the combination. Additionally, the validity of these results is limited by a lack of randomization, blinding, and placebo-control.
• Smoking cessation. It is unclear if oral St. John's wort is beneficial for patients trying to quit smoking. Details: A small clinical study in cigarette smokers shows that taking a specific St. John's wort extract (LI-160, Lichtwer Pharma US) 300 mg once or twice daily, starting 1 week before and continuing for 3 months after quitting smoking, is associated with a continuous abstinence rate of 18% at 3 months and 0% at 12 months, suggesting a lack of benefit (14481).
• Wound healing. Topical St. John's wort seems to improve wound healing and wound-related pain for certain types of surgery. Details: A clinical study in patients who have had a Cesarean section shows that applying ointment containing St. John's wort extract 20% three times a day for 16 days improves wound healing and reduces scar formation when compared with placebo ointment (17225). Preliminary clinical research in patients who have had impacted third molars removed shows that using a mouthwash, prepared by macerating the above ground parts of St. John's wort in virgin olive oil, for 60 days is as effective as chlorhexidine gluconate plus benzydamine hydrochloride mouthwash for improving periodontal healing, and reducing swelling, pain, and infectious complications. However, it was also as effective as plain virgin olive oil, suggesting that St. John's wort did not provide additional benefit. 15 mL of each mouthwash was swished for 30 seconds 3 times daily for 7 days (104957). St. John's wort has also been evaluated in combination with other ingredients. A moderate-sized clinical study in adults with dehisced post-surgical wounds shows that applying a specific aerosol product (1PWD, Kerecis AG) containing St. John's wort and neem oil to wounds during dressing changes does not improve wound healing scores at day 28 but may reduce pain scores when compared with silver-based dressings (alginates or polyurethane foam) (111592). However, this study may have been inadequately powered to detect a difference between groups. It is also unclear if these effects are due to St. John's wort, neem oil, or the combination.
• Tinnitus. St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in adults with tinnitus shows that taking St. John's wort 600 mg and ginkgo biloba daily for 12 weeks does not suppress tinnitus or improve tinnitus-related handicap when compared with ginkgo biloba monotherapy (111513). More evidence is needed to rate St. John's wort for these uses.

(Read more about ST. JOHN'S WORT)

POSSIBLY EFFECTIVE

• Coronary heart disease (CHD). The U.S. Food and Drug Administration (FDA) allows a qualified health claim stating that using high-oleic acid sunflower oil as a replacement for other dietary fats and oils higher in saturated fat may reduce the risk of CHD. Details: A meta-analysis of clinical studies shows that replacing 7.5% of energy from partially hydrogenated vegetable oils with high-oleic acid sunflower oil can reduce CHD risk by about 9% to 19%. Furthermore, analysis of results from observational studies found that replacing partially hydrogenated oil with high-oleic acid sunflower oil is associated with a 16% to 35% reduction in the risk of CHD events (95745). The FDA allows for a qualified health claim that replacing dietary fats and oils higher in saturated fat with high-oleic acid sunflower oil may reduce the risk of CHD. To achieve this benefit, the use of high-oleic acid sunflower oil should not increase total daily energy intake. The suggested daily dietary intake is about 20 grams (1.5 tbsp) of high-oleic sunflower oil in place of other fats and oils (98563). Sunflower oil that contains high amounts of linoleic acid rather than oleic acid does not appear to improve cholesterol levels or reduce the risk of cardiovascular events in patients with CHD (96205).
• Hypercholesterolemia. Consuming sunflower oil in the diet may reduce low-density lipoprotein (LDL) cholesterol levels in some patients. Details: There is evidence that using sunflower oil in the diet as 45-50 grams daily for up to 12 weeks is more effective than olive oil for decreasing LDL cholesterol and apolipoprotein B levels in healthy individuals (9780). Also, clinical research in patients with mild hyperlipidemia or moderate hypercholesterolemia shows that consuming specific brands of mid-oleic acid (NuSun) or high-oleic acid (Sunola, Meadow Lea Foods) sunflower oils as 15% to 20% of dietary calories for up to 5 weeks is more effective than olive oil or saturated fat for decreasing total cholesterol, LDL cholesterol, and apolipoprotein B levels (76697,76698). Also, consuming a high-oleic sunflower oil-rich diet for 3 weeks decreases total cholesterol levels to a greater extent than diets enriched with palm oil or medium-chain triglycerides in patients with mild hypercholesterolemia (67569). Other preliminary clinical research in patients with moderate hypercholesterolemia shows that consuming a diet rich in sunflower oil for 3 weeks decreases total cholesterol and LDL cholesterol levels when compared with baseline. However, levels of high-density lipoprotein (HDL) cholesterol appear to be lowered as well (76714). Despite these beneficial effects, sunflower oil might be less effective than some other dietary oils. Taking sunflower oil for 3 months appears to be less effective than rice bran oil for lowering cholesterol in patients with hypercholesterolemia (76699). Also, while consuming sunflower oil 45 grams daily, as part of the diet and as a supplement, for 12 weeks reduces levels of total cholesterol and LDL cholesterol when compared to baseline, it appears to be less effective at reducing total cholesterol levels than flaxseed oil in certain patients at risk for atherosclerosis (76696). In addition, taking sunflower oil 15.1 grams daily for 4 months does not appear to reduce levels of total or LDL cholesterol in patients with peripheral vascular disease (76691).

POSSIBLY INEFFECTIVE

• Hypertension. Oral sunflower oil does not seem to lower blood pressure. Details: Preliminary clinical research in adults with hypertension shows that taking sunflower oil 30-40 grams daily for one year is less effective than extra-virgin olive oil for reducing blood pressure (5091). Also, clinical research in elderly adults with hypertension shows that taking 60 grams of sunflower oil daily for 4 weeks is less effective than virgin olive oil for reducing systolic blood pressure (76692).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. It is unclear if oral sunflower oil is beneficial for atherosclerosis; some clinical research suggests that it may provide less benefit than other dietary oils. Details: Some preliminary clinical research in individuals with overweight and obesity shows that taking sunflower oil 30 mL (about 27 grams) daily for 90 days decreases carotid intima-media thickness (CIMT) by 3.5% when compared to baseline, but not when compared with olive oil or flaxseed oil. Sunflower oil also improves flow-mediated vasodilation by 73% when compared to baseline, compared with no improvement in those taking flaxseed oil or olive oil (99303). Other preliminary clinical research in individuals waiting for carotid endarterectomy shows that taking sunflower oil 6 grams daily for up to 189 days is less effective than the same dose of fish oil, and equivalent to control oil, for improving the status of atherosclerotic plaques (76688).
• Atopic dermatitis (eczema). Although there is interest in using topical sunflower oil for atopic dermatitis, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Child growth. It is unclear if topical sunflower oil is beneficial for early child growth. Details: A large preliminary clinical trial in newborn infants in India shows that exclusive topical application of 10 mL of high-linoleic acid sunflower oil, an average of 2.7 times daily for about one month, increases weight gain by 1.3 gram/kg daily when compared with a control group exclusively given traditional vigorous massage with mustard oil an average of 2.4 times daily. The increase in weight gain was highest for infants weighing less than 1500-2000 grams at birth (108141). However, it is unclear if any beneficial effects are due to the sunflower oil, the massage, their combination, or the lack of mustard oil.
• Dry mouth. It is unclear if rinsing the mouth with sunflower oil is beneficial for dry mouth. Details: Preliminary clinical research in adults with moderate dry mouth associated with medication use shows that using a sunflower oil mouth rinse and gargling for 5-8 minutes before spitting it out twice daily for 7 days improves dry mouth scores by 23% when compared to baseline. Sunflower oil also improves the ability to swallow and sleep with dry mouth, but not other dry mouth symptoms or saliva flow rate, when compared with control (105523). This study may have been inadequately powered to detect a difference between groups.
• Dry skin. It is unclear if topical sunflower oil is beneficial for dry skin in infants. Details: Preliminary clinical research in full-term, newborn infants shows that topical application of 4 drops of sunflower oil to each of three parts of the body twice daily for 4 weeks improves skin hydration, but not skin barrier function or the presence of redness or rash, when compared with not using topical oil. Furthermore, use of sunflower oil may impede the normal development of skin barrier function that occurs during the first four weeks of life (96144).
• Fetal and premature infant mortality. It is unclear if topical sunflower oil is beneficial for preventing early mortality in premature infants. Details: A large clinical trial in newborn infants in India shows that exclusive topical application of 10 mL of high-linoleic acid sunflower oil, an average of 2.7 times daily for about one month, reduces infant mortality by 58% when compared to a control group exclusively given traditional vigorous massage with mustard oil an average of 2.4 times daily. A subgroup analysis of premature infants also shows a 52% reduction in mortality with the use of high-linoleic acid sunflower oil when compared with control (108143). However, it is unclear if any beneficial effects are due to the sunflower oil, the massage, their combination, or the lack of mustard oil.
• Prematurity. Small to moderate-sized clinical studies suggest that topical sunflower oil might increase body weight, reduce length of hospital stay, and improve skin hydration and skin integrity in preterm neonates. Details: Preliminary clinical research in preterm infants with low birth weight shows that massaging for 5-10 minutes using sunflower oil 10 mL/kg three times daily for 2 weeks increases weight gain by approximately 35% over 2 months when compared with massage using no oil. Sunflower oil massage does not appear to increase length or head circumference (96145). A small clinical study in premature infants in the intensive care unit (ICU) shows that a similar massage with sunflower oil three times daily for 5 days shortens ICU stay by about 5 days when compared with no massage. Furthermore, over the ICU stay, infants in the sunflower oil massage group gained an average of 15 grams, whereas infants in the control group experienced weight loss (98479). The effect of sunflower oil on skin hydration and integrity in preterm infants has also been assessed. A clinical trial of 90 preterm infants in a Turkish neonatal ICU shows that whole body skin treatment (not massage) with either sunflower oil or almond oil 4 mL/kg four times daily for 5 days improves measures of skin hydration and skin integrity when compared with control infants that did not receive oil treatment. The sunflower and almond oil treatments are equally effective (105524). Another clinical study in 90 infants (42% preterm) in a Turkish neonatal ICU shows that whole body skin treatment (not massage) with sunflower oil or liquid Vaseline 3-4 mL for preterm and 5-6 mL for full-term infants daily for 16 days improves measures of skin integrity when compared with control infants that did not receive any oil treatment. Skin integrity scores were better in the sunflower oil group than liquid Vaseline at some time points (111726).
• Psoriasis. Although there is interest in using topical sunflower oil for psoriasis, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral sunflower oil for RA, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Tinea pedis. It is unclear if topical sunflower oil is beneficial for tinea pedis. Details: Preliminary clinical research shows that topical application of a specific brand of ozonized sunflower oil (Oleozon) twice daily for 6 weeks is as effective as ketoconazole for curing athlete's foot (76687). More evidence is needed to rate sunflower oil for these uses.

(Read more about SUNFLOWER OIL)

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).

(Read more about ARNICA)

LIKELY SAFE ...when the fruit is consumed in amounts commonly found in foods (668,669,670,671).

POSSIBLY SAFE ...when the oil is applied to the skin topically and appropriately, short-term. Avocado oil in combination with vitamin B12 appears to be safe when used for up to 12 weeks (14909). There is insufficient reliable information available about the safety of avocado for its other uses.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts exceeding those commonly found in foods.

(Read more about AVOCADO)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Beeswax has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used orally as a medicinal agent (11)....when used topically (11,55245,96328,96329).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of medicinal amounts of beeswax during pregnancy and lactation.

(Read more about BEESWAX)

LIKELY SAFE ...when the flower preparations are used orally or topically and appropriately (4,19779,36931,39503,93552,93557,96647,105088).

PREGNANCY: LIKELY UNSAFE
when used orally; contraindicated due to spermatocide, antiblastocyst, and abortifacient effects. There is insufficient reliable information available about the safety of calendula when used topically during pregnancy (4).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CALENDULA)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).

POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).

POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).

PREGNANCY: LIKELY UNSAFE
when used orally. The constituent thujone can have menstrual stimulant and abortifacient effects (19).

LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).

(Read more about SAGE)

POSSIBLY SAFE ...when used orally and appropriately (2,12).

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

(Read more about SANICLE)

LIKELY SAFE ...when used orally and appropriately. St. John's wort extracts in doses up to 900 mg daily seem to be safe when used for up to 12 weeks (3547,3550,4835,5096,6400,6434,7047,13021,13156,13157)(14417,76143,76144,89666,89669,95510). Some evidence also shows that St. John's wort can be safely used for over one year (13156,13157,76140), and may have better tolerability than selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) (4897,76153,76143,104036).

POSSIBLY SAFE ...when used topically and appropriately. St. John's wort 0.5% extract seems to be safe when used once weekly for 4 weeks (110327). St. John's wort oil has been used with apparent safely twice daily for 6 weeks (110326). However, topical use of St. John's wort can cause photodermatitis with sun exposure (110318).

POSSIBLY UNSAFE ...when used orally in large doses. St. John's wort extract can be unsafe due to the risk of severe phototoxic skin reactions. Taking 2-4 grams of St. John's wort extract (containing hypericin 5-10 mg) daily appears to increase the risk of photosensitivity (758,4631,7808).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neural tube, urinary, and cardiovascular malformations. Subgroup analyses suggest that these risks may be higher when taking St. John's wort during the first trimester when compared with the second or third trimester. However, more research is needed to confirm these findings (106052). Animal-model research also shows that constituents of St. John's wort might have teratogenic effects (9687,15122). Until more is known, St. John's wort should not be taken during pregnancy.

LACTATION: POSSIBLY UNSAFE
when used orally. Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy (1377,15122,22418); avoid using.

CHILDREN: POSSIBLY SAFE
when used orally, and appropriately, short-term. St. John's wort extracts in doses up to 300 mg three times daily seem to be safe when used for up to 8 weeks in children aged 6-17 years (4538,17986,76110).

(Read more about ST. JOHN'S WORT)

LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. When used as a substitute for other dietary oils, the recommended intake of high-oleic acid sunflower oil is 20 grams (1.5 tablespoons) daily (9780,98563). ...when used topically and appropriately, short-term. Sunflower oil has been applied to the skin twice daily for up to 6 weeks (76687). There is insufficient reliable information available about the safety of sunflower oil when used as an oral rinse.

CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.

CHILDREN: POSSIBLY SAFE
when applied topically and appropriately, short-term. Sunflower oil has been applied to the skin of infants daily for up to 2 months (96144,96145,105524,108143). There is insufficient reliable information available about the safety of sunflower oil when used orally in larger amounts as medicine.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods. There is insufficient reliable information available about the safety of sunflower oil when used in amounts greater than those found in food.

(Read more about SUNFLOWER OIL)

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.

(Read more about ARNICA)

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Avocado may antagonize the anticoagulant effects of warfarin.  Details Avocado may antagonize the anticoagulant effects of warfarin; however, there has been only one case report of this interaction (667).

(Read more about AVOCADO)

(Read more about BEESWAX)

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, calendula might have additive effects when used with CNS depressants, although this appears to be unlikely.  Details Although some animal research has suggested that a saponoside constituent in calendula may have sedative effects (39545,39547), calendula has been used for over 30 years without reports of sedation in humans (105088).

(Read more about CALENDULA)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the clinical effects of anticholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

ANTICONVULSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.  Details Some species of sage can cause convulsions when consumed in large quantities (10812).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.  Details In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase or decrease the effects of antihypertensive drugs.  Details Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.  Details In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might have additive effects when used with cholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.  Details Some constituents of sage have CNS depressant activity (10334).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6 (10848,19430). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.  Details Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4 (10848,72641). So far, this interaction has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with hormone therapy.  Details In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase levels of drugs transported by P-glycoprotein.  Details In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.

(Read more about SAGE)

(Read more about SANICLE)

ALPRAZOLAM (Xanax) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort increases the clearance of alprazolam and decreases its effects.  Details Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours (10830).

AMBRISENTAN (Letairis) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the clearance of ambristentan and decrease its effects.  Details Clinical research in healthy volunteers shows that taking St. John's wort 900 mg daily decreases the area under the concentration-time curve of ambrisentan 5 mg by 17% to 26%. Ambrisentan clearance was increased by 20% to 35% depending on CYP2C19 genotype. However, these small changes are unlikely to be clinically significant (99511).

AMINOLEVULINIC ACID Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might have additive phototoxic effects with aminolevulinic acid.  Details Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort (9474).

BOCEPREVIR (Victrelis) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of boceprevir.  Details Boceprevir increases the maximum concentration and concentration at 8 hours of the St. John's wort constituent, hypericin, by approximately 30%. However, St. John's wort does not significantly change the area under the concentration-time curve or maximum plasma concentration of boceprevir 800 mg three times daily in healthy adults (95507,96552).

BUPROPION (Wellbutrin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might reduce the levels and effects of bupropion.  Details Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort (89662).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B St. John's wort might increase the levels and effects of clopidogrel.  Details Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity (13038,89671,96552). Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D St. John's wort might decrease the levels and clinical effects of clozapine.  Details A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort (96552).

CONTRACEPTIVE DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.  Details Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy (11886,11887,13099). Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract (9880). St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives (1292,7809,9204).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of cyclosporine.  Details Concomitant use can decrease plasma cyclosporine levels by 30% to 70% (1234,4826,4831,4834,7808,9596,10628,96552). Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection (1234,1293,1301,6112,6435,7808,9596). This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day (6435,10628). Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels (1234,4513,4826,4831,4834). St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance (1293,1340,9204,9596).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.  Details Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4 (9204,10848,76163,111404).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.  Details Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20% (89662).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2C19 substrates.  Details Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces CYP2C19 and increases metabolism of mephenytoin (Mesantoin). In patients with wild-type 2C19 (2C19*1/*1) metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405). Theoretically, St. John's wort might increase metabolism of other CYP2C19 substrates.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the levels of CYP2C9 substrates.  Details There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4 (9204,10848,11889). St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate (11890). Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate (15546). Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.  Details St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates (9204,10830,10847,10848,11889,22423,22424,22425,22427,48603,111404,111644,113094). Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more (97171).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of digoxin.  Details St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs (382,6473,7808,7810,9204,96552,97171). St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels (97171).

DOCETAXEL (Taxotere) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of docetaxel.  Details Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89661).

FENTANYL Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, St. John's wort may reduce the levels and clinical effects of fentanyl.  Details Given that St. John's wort induces cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, it is possible that concomitant use of St. John's wort with fentanyl will reduce plasma levels and analgesic activity of fentanyl (96552). However, some clinical research in healthy adults shows that taking St. John's wort (LI-160, Lichtwer Pharma) 300 mg daily for 21 days does not alter the pharmacokinetics or clinical effects of intravenous fentanyl (102868). It is unclear if these findings can be generalized to oral, intranasal, or transdermal fentanyl.

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the levels and clinical effects of fexofenadine.  Details A single dose of St. John's wort decreases the clearance of fexofenadine and increases its plasma levels. However, the effect of St. John's wort on plasma levels of fexofenadine seems to be lost if dosing is continued for more than 2 weeks (9685). Patients taking fexofenadine and St. John's wort concurrently should be monitored for possible fexofenadine toxicity.

FINASTERIDE (Proscar, Propecia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D St. John's wort may reduce the levels and clinical effects of finasteride.  Details St. John's wort reduces plasma levels of finasteride in healthy male volunteers due to induction of finasteride metabolism via cytochrome P450 3A4 (CYP3A4). The clinical significance of this interaction is not known (96552).

GLICLAZIDE (Diamicron, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort may reduce the levels and clinical effects of gliclazide.  Details Taking St. John's wort decreases the half-life and increases clearance of gliclazide in healthy people (22431).

HMG-CoA REDUCTASE INHIBITORS ("Statins") Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort may increase the metabolism and reduce the effectiveness of atorvastatin, lovastatin, and rosuvastatin. However, it does not seem to affect pravastatin, pitavastatin, or fluvastatin.  Details Concomitant use of St. John's wort can reduce plasma concentrations of the active simvastatin metabolite, simvastatin hydroxy acid, by 28%. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter. This increases simvastatin clearance. It also increases the clearance of atorvastatin (Lipitor), lovastatin (Mevacor), and rosuvastatin (Crestor). St. John's wort does not seem to affect the plasma concentrations of pravastatin (Pravachol), pitavastatin (Livalo) or fluvastatin (Lescol), which are not substrates of CYP3A4 or P-glycoprotein (10627,96552,97171).

IMATINIB (Gleevec) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = A St. John's wort reduces the levels and clinical effects of imatinib.  Details Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib (11888,96552).

INDINAVIR (Crixivan) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort may reduce the levels and clinical effects of indinavir.  Details In healthy volunteers, taking St. John's wort concurrently with indinavir reduces plasma concentrations of indinavir by inducing metabolism via cytochrome P450 3A4 (CYP3A4) (96552). Theoretically, this could result in treatment failure and viral resistance.

IRINOTECAN (Camptosar) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = A St. John's wort reduces the levels and clinical effects of irinotecan.  Details St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve (9206,97171). This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (7092,96552).

IVABRADINE (Corlanor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might reduce the levels and clinical effects of ivabradine.  Details Taking St. John's wort 900 mg containing 7.5 mg of hyperforin daily for 14 days with a single dose of ivabradine causes a 62% reduction in plasma levels of ivabradine. This interaction is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, increasing the metabolism of ivabradine (96552,97171).

KETAMINE (Ketalar) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of ketamine.  Details Taking St. John's wort 300 mg three times daily for 14 days can decrease maximum serum levels of ketamine by around 66% and area under the concentration-time curve of ketamine by 58%. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89663).

MEPHENYTOIN (Mesantoin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of mephenytoin.  Details Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405).

METHADONE (Dolophine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might reduce the levels and clinical effects of methadone.  Details St. John's wort might decrease the effectiveness of methadone by reducing its blood concentrations. In one report, two out of four patients on methadone maintenance therapy for addiction experienced methadone withdrawal symptoms after taking St. John's wort 900 mg daily for a median of 31 days. There was a median decrease in blood methadone concentration of 47% (range: 19% to 60%) when compared to baseline (22419).

METHYLPHENIDATE (Concerta, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D St. John's wort might reduce the levels and clinical effects of methylphenidate.  Details St. John's wort might decrease the effectiveness of methylphenidate. In one report, an adult male, stabilized on methylphenidate for attention deficit-hyperactivity disorder (ADHD), experienced increased attention problems and ADHD symptoms after taking St. John's wort 600 mg daily for 4 months. ADHD symptoms improved when St. John's wort was discontinued (15544). The mechanism of this interaction is unknown.

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of NNRTIs.  Details St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter (1290,1340,4837,96552).

OMEPRAZOLE (Prilosec) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of omeprazole.  Details Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers (22440,96552).

OXYCODONE (Oxycontin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of oxycodone.  Details St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity (96552).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.  Details St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action (382,1340,7810,11722).

PHENOBARBITAL (Luminal) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenobarbital.  Details St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped (9204).

PHENPROCOUMON (Marcoumar, others) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenprocoumon.  Details St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR) (9204).

PHENYTOIN (Dilantin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of phenytoin.  Details St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped (9204).

PHOTOSENSITIZING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.  Details St. John's wort might increase photosensitivity reactions due to its hypericin content (166,111644). However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans (3900,4542,76266).

PROCAINAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might decrease the levels and clinical effects of procainamide.  Details Animal research shows that taking St. John's wort extract increases the bioavailability of procainamide, but does not increase its metabolism (14865). Whether this interaction is clinically significant in humans is not known.

PROTEASE INHIBITORS (PIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort reduces the levels and clinical effects of PIs.  Details In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance (1290,7808,96552). St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination (9204).

RESERPINE (Raudixin, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might decrease the effectiveness of reserpine.  Details Animal research shows that St. John's wort can antagonize the effects of reserpine (758).

RIVAROXABAN (Xarelto) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of rivaroxaban.  Details A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20% (104038).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.  Details Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction disorders (166,542,3569,8056,110318).

TACROLIMUS (Prograf) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of tacrolimus.  Details Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes (7095,10329). A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively (113094).

THEOPHYLLINE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D St. John's wort might decrease the levels of theophylline, although this effect might not be clinically relevant.  Details St. John's wort does not seem to significantly affect theophylline pharmacokinetics (11802). There is a single case report of a possible interaction with theophylline. A patient who smoked and was taking 11 other drugs experienced an increase in theophylline levels after discontinuation of St. John's wort. This increase has been attributed to a rebounding of theophylline serum levels after St. John's wort was no longer present to induce metabolism via cytochrome P450 1A2 (CYP1A2) (3556,7808,9204). However, studies in healthy volunteers show that St. John's wort is unlikely to affect theophylline to any clinically significant degree (11802).

TRAMADOL (Ultram) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D St. John's wort might decrease the levels and clinical effects of tramadol.  Details St. John's wort can increase tramadol metabolism via induction of cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity (96552). Theoretically, concurrent use of St. John's wort with tramadol might also cause additive serotonergic effects (763,6427,8056,8936).

VORICONAZOLE (Vfend) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of voriconazole.  Details Clinical research shows that taking St. John's wort with voriconazole reduces voriconazole exposure and increases voriconazole metabolism by approximately 107%. Voriconazole is primarily metabolized by cytochrome P450 (CYP) 2C19, with CYP3A4 and CYP2C9 also involved (89660). St. John's wort induces CYP2C19, CYP3A4, and CYP2C9 (9204,10830,10847,10848,11889,11890,17405,22423,22424,22425)(22427,48603).

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = B St. John's wort decreases the levels and clinical effects of warfarin.  Details Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers (11890,15176). This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4 (11890). St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin (1292). In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption (10448).

ZOLPIDEM (Ambien) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B St. John's wort might decrease the levels and clinical effects of zolpidem.  Details In clinical research, concomitant use of zolpidem with St. John's wort decreased zolpidem plasma levels due to induction of its metabolism by cytochrome P450 3A4 (22441,96552). Whether this interaction is clinically significant is not known.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, sunflower oil might decrease the effectiveness of antidiabetes medications.  Details A diet using sunflower oil as a fat source can cause increased fasting blood glucose levels in patients with type 2 diabetes (8132). Dose adjustments to diabetes medications might be necessary.

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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).

(Read more about ARNICA)

General ...Orally, avocado has been generally well tolerated in clinical research.
Most Common Adverse Effects:
Topically: A cream containing avocado oil in combination with vitamin B12 can cause itching.
Serious Adverse Effects (Rare):
Orally: Avocado may lead to allergic cross-sensitivity in latex sensitive patients. While rare, avocado can cause acute food protein-induced enterocolitis syndrome (FPIES), a food hypersensitivity reaction characterized by excessive vomiting and diarrhea.

Dermatologic ...Topically, a cream containing avocado oil in combination with vitamin B12 can cause itching when applied initially, but itching appears to diminish with continued use (14909). Orally, avocado may cause skin rash (112436).

Gastrointestinal ...Orally, avocado can cause acute food protein-induced enterocolitis syndrome (FPIES). This is a rare, delayed, non-IgE-mediated gastrointestinal food hypersensitivity reaction most often reported in infants and young children. Symptoms of FPIES include excessive vomiting within 1-4 hours of avocado consumption and diarrhea. Treatment is generally supportive in nature, including oral or intravenous rehydration, along with avoidance of avocado (100938). There have also been reports of gastrointestinal upset including gas, bloating, and diarrhea due to daily avocado consumption, though it is possible that these symptoms were due to E. coli infection (112436).

Immunologic ...Orally, avocado may lead to type I hypersensitivity reactions in people who are allergic to latex (6197,7853,25216,33248,33253,33254). While rare, avocado can also cause acute food protein-induced enterocolitis syndrome (FPIES). This is a delayed, non-IgE-mediated gastrointestinal food hypersensitivity reaction most often reported in infants and young children. Symptoms of FPIES include excessive vomiting within 1-4 hours of avocado consumption and diarrhea. Many infants and children who experience FPIES after eating avocado will have the same reaction to other foods, such as milk, oat, and rice (100938).

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General ...Orally, beeswax is well tolerated. Allergic reactions to beeswax are possible in some patients (11).
Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (55245,102517).

Dermatologic ...Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (55245,102517). While this reaction is thought to be rare in the general population, one cross-sectional study found that 18% of patients with a history of cheilitis or facial dermatitis experienced positive reactions to beeswax. While most of these patients also had a positive reaction to a propolis patch test, some did not, suggesting that a substance in beeswax itself may be involved in this sensitization (102517).

Immunologic ...Orally, beeswax may cause allergic reactions (11). Topically, beeswax may cause allergic contact dermatitis. In most cases, this reaction is likely caused by the propolis component of beeswax (102517).

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General ...Orally and topically, calendula is generally well tolerated.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions.

Dermatologic ...Topically, a preparation containing calendula powder 0. 1% resulted in inflammation around the wound to which it was applied (96647). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of calendula, licorice, and snail secretion filtrate to the face. The specific role of calendula is unclear (110322).

Immunologic ...Orally, calendula can cause allergic reactions. Topically, calendula can cause eczematous allergic reactions. Calendula-specific patch testing is recommended prior to usage to determine allergenic potential. Testing is particularly necessary in individuals sensitive to the Asteraceae/Compositae family (10691,11458,96647). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. A preparation containing calendula powder 0.1% resulted in hives in a patient with a ragweed allergy (96647). Despite the widespread use of calendula and the occurrence of allergies to other family members, there has been only one report of anaphylaxis (11152).

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General ...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.

Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).

Dermatologic ...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).

Gastrointestinal ...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).

Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).

Pulmonary/Respiratory ...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).

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General ...Orally, sanicle seems to be well tolerated (2,12). Large amounts of sanicle may cause upset stomach, nausea, and vomiting due to its saponin content (7).

Gastrointestinal ...Orally, large amounts of sanicle may cause upset stomach, nausea, and vomiting due to its saponin content (7).

(Read more about SANICLE)

General ...Orally, St. John's wort is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dizziness, dry mouth, gastrointestinal discomfort (mild), fatigue, headache, insomnia, restlessness, and sedation.
Topically: Skin rash and photodermatitis.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of suicidal ideation and psychosis after taking St. John's wort.

Cardiovascular ...In clinical research, palpitations have been reported for patients taking St. John's wort orally, although the number of these events was higher for the patients taking sertraline (76070). In one case report, an adult female developed recurrent palpitations and supraventricular tachycardia (SVT) within 3 weeks of initiating St. John's wort 300 mg daily. SVT and related symptoms responded to Valsalva maneuvers and did not recur after discontinuing therapy (106051).
Edema has also been reported in clinical research for some patients treated with St. John's wort 900-1500 mg daily for 8 weeks (10843). Cardiovascular collapse following induction of anesthesia has been reported in an otherwise healthy patient who had been taking St. John's wort for 6 months (8931). A case of St. John's wort-induced hypertension has been reported for a 56-year-old patient who used St. John's wort extract 250 mg twice daily for 5 weeks. Blood pressure normalized after discontinuation of treatment (76073). A case of new-onset orthostatic hypotension and light-headedness has been reported for a 70 year-old homebound patient who was taking multiple prescription medications and herbal products, including St. John's wort (76128). When all herbal products were discontinued, these symptoms improved, and the patient experienced improvement in pain control.

Dermatologic ...Both topical and chronic oral use of St. John's wort can cause photodermatitis (206,620,758,4628,4631,6477,13156,17986,76072,76148)(95506,110318). The average threshold dose range for an increased risk of photosensitivity appears to be 1.8-4 grams St. John's wort extract or 5-10 mg hypericin, daily. Lower doses might not cause this effect (4542,7808). For example, a single dose of St. John's wort extract 1800 mg (5.4 mg hypericin) followed by 900 mg (2.7 mg hypericin) daily does not seem to produce skin hypericin concentrations thought to be high enough to cause phototoxicity (3900,4542,76266). Females appear to have a higher risk of dose-related photosensitivity. In a dose-ranging, small clinical trial, almost all of the female participants experienced mild to moderate photosensitivity with paresthesia in sun-exposed skin areas after administration of St. John's wort (Jarsin, Casella Med) 1800 mg daily for 3-6 days. Symptoms resolved about 12-16 days after discontinuation (95506). Male participants reported no adverse effects at this dose, and both genders reported no adverse effects at lower doses. Light or fair-skinned people should employ protective measures against direct sunlight when using St. John's wort either topically or orally (628).
Total body erythroderma without exposure to sunlight, accompanied by burning sensation of the skin, has also been reported (8930). Orally, St. John's wort may cause pruritus or skin rash, although these events seem to occur infrequently (76140,76148,76245). A case of persistent scalp and eyebrow hair loss has been reported for a 24-year-old schizophrenic female who was taking olanzapine plus St. John's wort 900 mg/day orally (7811). Also, a case of surgical site irritation has been reported for a patient who applied ointment containing St. John's wort (17225).

Endocrine ...A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 67-year-old male with depression has been reported. During a 3-month period, the patient was taking St. John's wort 300 mg daily then increased to 600-900 mg daily with no adverse effects despite a low serum sodium level of 122mEq/L, elevated levels of urine sodium, and urine osmolality suggestive of SIADH. St. John's wort appeared to be the only contributing factor. The patient's sodium level normalized 3 weeks after discontinuation of St. John's wort (95508).

Gastrointestinal ...Orally, St. John's wort may cause dyspepsia, anorexia, diarrhea, nausea, vomiting, and constipation, although these events seems to occur infrequently (4897,13021,17986,76070,76071,76113,76146,76150,76271).

Genitourinary ...Orally, St. John's wort can cause intermenstrual or abnormal menstrual bleeding (1292,76056). However, this effect has occurred in patients who were also taking an oral contraceptive. Changes in menstrual bleeding might be the result of a drug interaction (1292,76056). Also, St. John's wort has been associated with anorgasmia and frequent urination when used orally (10843,76070).
Sexual dysfunction can occur with St. John's wort, but less frequently than with SSRIs (10843). A case of erectile dysfunction and orgasmic delay has been reported for a 49-year-old male after taking St. John's wort orally for one week. Co-administration of sildenafil 25-50 mg prior to sexual activity reversed the sexual dysfunction. Previously, the patient had experienced orgasmic delay, erectile dysfunction, and inhibited sexual desire when taking a selective serotonin reuptake inhibitor (sertraline) (4836).

Hepatic ...A case of acute hepatitis with prolonged cholestasis and features of vanishing bile duct syndrome has been reported for a patient who used tibolone and St. John's wort orally for 10 weeks (76135). A case of jaundice with transaminitis and hyperbilirubinemia has been reported for a 79 year-old female who used St. John's wort and copaiba (95505). Laboratory values normalized 7 weeks after discontinuation of both products.

Musculoskeletal ...Orally, St. John's wort may cause muscle or joint stiffness, tremor, muscle spasms, or pain, although these events appear to occur rarely (76070).

Neurologic/CNS ...St. John's wort may cause headache, dizziness, fatigue, lethargy, or insomnia (5096,13021,76070,76071,76113,76132,76133,76150,89666). Isolated cases of paresthesia have been reported for patients taking St. John's wort (5073). A case of subacute toxic neuropathy has been reported for a 35-year-old female who took St. John's wort 500 mg daily orally for 4 weeks (621).

Ocular/Otic ...There is concern that taking St. John's wort might increase the risk of cataracts. The hypericin constituent of St. John's wort is photoactive and, in the presence of light, may damage lens proteins, leading to cataracts (1296,17088). In population research, people with cataracts were significantly more likely to have used St. John's wort compared to people without cataracts (17088). Ear and labyrinth disorders have been possibly attributed to use of St. John's wort in clinical research, although these events rarely occur (76120).

Psychiatric ...St. John's wort can induce hypomania in depressed patients and mania in depressed patients with occult bipolar disorder (325,3524,3555,3568,10845,76047,76064,76137,110318). Cases of first-episode psychosis have been reported for females who used St. John's wort orally. In both cases, symptoms resolved following discontinuation of St. John's wort and treatment with antipsychotics for several weeks (13015,89664). Also, psychosis and delirium have been reported for a 76-year-old female patient who used St. John's wort for 3 weeks. The patient may have been predisposed to this effect due to undiagnosed dementia (76270). Restlessness, insomnia, panic, and anxiety have been noted for some patients taking St. John's wort orally (5073,13156,76070,76132,76268,76269,89665).
In isolated cases, St. John's wort has been associated with a syndrome consisting of extreme anxiety, confusion, nausea, hypertension, and tachycardia. These symptoms may occur within 2-3 weeks after it is started, in patients with no other predisposing factors. This syndrome has been diagnosed as the serotonin syndrome (6201,7811,110318). In one case, the symptoms began after consuming tyramine-containing foods, including aged cheese and red wine (7812). In an isolated case, a 51-year-old female reported having had suicidal and homicidal thoughts for 9 months while taking vitamin C and a St. John's wort extract. Symptoms disappeared within 3 weeks of discontinuing treatment (76111). A case of decreased libido has been reported for a 42-year-old male with mood and anxiety disorders who had taken St. John's wort orally for 9 months (7312).
St. John's wort has been associated with withdrawal effects similar to those found with conventional antidepressants. Headache, nausea, anorexia, dry mouth, thirst, cold chills, weight loss, dizziness, insomnia, paresthesia, confusion, and fatigue have been reported. Withdrawal effects are most likely to occur within two days after discontinuation but can occur one week or more after stopping treatment in some people. Occurrence of withdrawal symptoms may not be related to dose or duration of use (3569,11801).

Pulmonary/Respiratory ...Orally, St. John's wort may cause sore throat, swollen glands, laryngitis, sinus ache, sweating, and hot flashes, although the frequency of these events appears to be similar to placebo (76150).

Renal ...Orally, St. John's wort has been associated with a case report of acute kidney failure in a 46-year-old female after one dose of homemade St. John's wort tea. Three sessions of hemodialysis were required before there was full recovery (106741). However, causality is unclear since the patient had also been taking diclofenac intermittently for a month prior to developing kidney failure.

Other ...Sjogren's syndrome has been reported in a patient taking herbal supplements including St. John's wort, echinacea, and kava. Echinacea may have been the primary cause, because Sjogren's syndrome is an autoimmune disorder. The role of St. John's wort in causing this syndrome is unclear (10319).

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General ...Orally and topically, sunflower oil is well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions in sensitive individuals have been reported.

Immunologic ...Orally, sunflower oil can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. However, the protein content of sunflower oil is very low. In one case report, an allergic response to sunflower oil did not occur despite presenting with severe allergy and anaphylaxis to sunflower seed (108140).

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