Formule T 17 by Les Herbages Naturbec Ltee

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: A meta-analysis of three preliminary clinical trials in patients with breast cancer shows that topical calendula does not affect the development of radiation dermatitis or the incidence of moderate to severe symptoms when compared to control (110325). 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)

There is insufficient reliable information available about the effectiveness of lesser celandine.

(Read more about LESSER CELANDINE)

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)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Menorrhagia. Clinical research shows that taking shepherd's purse extract 640 mg twice daily with mefenamic acid 1000 mg three times daily up to 7 days during menstruation for two consecutive cycles decreases menstrual bleeding by 50% in the third cycle compared with a 45% reduction in women with heavy menstrual bleeding taking mefenamic acid only. The clinical significance of this small benefit is unclear (102404).
• Postpartum complications. Preliminary clinical research in postpartum women shows that taking shepherd's purse extract as ten sublingual drops, with an infusion of oxytocin, reduces postpartum bleeding by 32% in the first 3 hours after birth compared with oxytocin alone (102405). More evidence is needed to rate shepherd's purse for these uses.

(Read more about SHEPHERD'S PURSE)

There is insufficient reliable information available about the effectiveness of white oak bark.

(Read more about WHITE OAK)

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)

POSSIBLY SAFE ...when small amounts of fresh leaf sheaths are eaten in food amounts(18).

POSSIBLY UNSAFE ...when fresh parts of the plant are used topically (4,18). Extended contact with the fresh, bruised plant can cause blisters (18).

LIKELY UNSAFE ...when fresh parts of the plant are used orally (4,18). Freshly harvested lesser celandine contains protoanemonin-forming chemicals that can cause severe irritation to the lining of the gastrointestinal tract (18); avoid using. There is insufficient reliable information available about the safety of dried lesser celandine or lesser celandine extract when used orally or topically.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when fresh parts of the plant are used orally (4); avoid using.

(Read more about LESSER CELANDINE)

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 preparations of the above ground parts are used orally and appropriately (4,12). Doses of 1280 mg daily have been used safely for up to 7 days in a clinical trial (102404). ...when used topically (4).

POSSIBLY UNSAFE ...when large amounts of shepherd's purse are ingested, it can cause heart palpitations (12).

PREGNANCY: LIKELY UNSAFE
when used orally or topically, due to possible uterine stimulation, menstrual flow stimulation, and miscarriage (12).

LACTATION:
Insufficient reliable information available; avoid excessive use (4).

(Read more about SHEPHERD'S PURSE)

POSSIBLY SAFE ...when used orally for up to 3-4 days for treating diarrhea (2,12,7). ...when used topically up to 2-3 weeks on intact skin (2).

LIKELY UNSAFE ...when used topically on extensive areas of damaged skin or for longer than 2-3 weeks (2).

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

(Read more about WHITE OAK)

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)

(Read more about LESSER CELANDINE)

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.

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(Read more about SHEPHERD'S PURSE)

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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, lesser celandine may cause severe gastrointestinal irritation, colic, diarrhea, and irritation of the urinary tract (18). One report associates the use of lesser celandine with a case of recurrent, acute hepatitis (96287).
Topically, lesser celandine can cause mucous membrane and skin irritation (18). Extended contact with fresh, bruised plant can cause blisters (18). Some Ranunculus species also cause photodermatitis (19).

Dermatologic ...Topically, use of the plant can cause mucous membrane and skin irritation (18). Extended contact with fresh, bruised plant can cause blisters (18).

Gastrointestinal ...Orally, use of the plant is associated with severe gastrointestinal irritation, colic, and diarrhea (18).

Genitourinary ...Orally, use of the plant is associated with irritation of the urinary tract (18).

Hepatic ...There is a case of a 36-year old woman with acute hepatitis and jaundice probably related to use of lesser celandine. She consumed one cup per day as tea for 3 days. Alanine transaminase (ALT) levels were elevated by at least 174-fold and aspartate aminotransferase (AST) by at least 34-fold. Alkaline phosphatase and total bilirubin were also elevated. Elevated liver enzyme levels rapidly decreased following discontinuation of the product, returning to normal within 3 weeks (96287).

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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, shepherd's purse seems to be well tolerated when used in small amounts, short-term. Adverse effects traditionally thought to be associated with shepherd's purse have included sedation, hypertension, hypotension, abnormal thyroid function, abnormal menstruation (4), and palpitations (12).

Cardiovascular ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included hypertension, hypotension, (4), and palpitations (12).

Endocrine ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included abnormal thyroid function (4).

Genitourinary ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included abnormal menstruation (4).

Neurologic/CNS ...Orally, some adverse effects traditionally thought to be associated with shepherd's purse have included sedation (4).

(Read more about SHEPHERD'S PURSE)

General ...White oak bark seems to be well tolerated when used orally to topically on unbroken skin, short-term. White oak pollen may cause allergic reactions in some people (86395).

Immunologic ...White oak pollen may cause allergic reactions in some people (86395).

(Read more about WHITE OAK)