Candida Control [Discontinued] by BIOVEA

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Coronary heart disease (CHD). It is unclear if consuming black walnut as part of the diet can reduce the risk for CHD. Details: Epidemiological research has found that people who increase dietary consumption of nuts in general might have a lower risk of CHD and death due to coronary events. However, there is no available evidence showing that eating black walnut, specifically, reduces the risk of CHD (8478,13299). Still, in 2004, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming 1.5 ounces of walnuts per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD. The FDA has concluded that this claim is based on supporting, rather than conclusive, evidence (102335).
• Wound healing. Although there is interest in using topical black walnut hull and bark for wound healing, there is insufficient reliable information about the clinical effects of black walnut for this purpose. More evidence is needed to rate the effectiveness of black walnut for these uses.

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POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

(Read more about FENNEL)

POSSIBLY EFFECTIVE

• Sinusitis. Clinical research shows that taking gentian orally in a specific combination product (SinuComp; Sinupret) that also contains elderflower, verbena, cowslip flower, and sorrel improves the symptoms of acute or chronic sinusitis (374,379). In one cohort study, taking this specific combination product orally three times daily with mometasone furoate nasal spray 200 mcg twice daily for 7 days reduces symptoms related to acute sinusitis when compared with using mometasone nasal spray alone (95907).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Weight loss. Preliminary clinical research in healthy adults shows that consuming a pudding containing microencapsulated gentian root extract 1.25 g at breakfast modestly reduces caloric intake over 24 hours, but does not affect self-reported feelings of hunger or fullness, when compared with placebo pudding (96534). More evidence is needed to rate gentian for this use.

(Read more about GENTIAN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical oregano oil for acne, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Asthma. Although there has been interest in using oral oregano for asthma, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Bronchitis. Although there has been interest in using oral oregano for bronchitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Canker sores. Although there has been interest in using topical oregano oil for canker sores, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Cough. Although there has been interest in using oral oregano for cough, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dandruff. Although there has been interest in using topical oregano oil for dandruff, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Diabetes. Although there has been interest in using oral oregano for diabetes, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dysmenorrhea. Although there has been interest in using oral oregano for dysmenorrhea, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dyspepsia. Although there has been interest in using oral oregano for dyspepsia, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Gingivitis. Although there has been interest in using topical oregano oil for gingivitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Headache. Although there has been interest in using topical oregano oil for headache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Insect repellent. Although there has been interest in using topical oregano oil as an insect repellent, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Intestinal parasite infection. It is unclear if oral oregano is beneficial in patients with intestinal parasite infections. Details: In one small, uncontrolled study, taking a specific emulsified oregano leaf oil product (ADP, Biotics Research Corporation) 200 mg orally three times daily with meals for 6 weeks resulted in eradication of Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana from the stool in 10 of 13 patients (6878). The clinical significance of this is unclear since the Centers for Disease Control (CDC) considers Entamoeba hartmanni and Endolimax nana to be non-pathogenic, while blastocystosis caused by Blastocystis hominis is usually self-limiting and does not require treatment.
• Pain (acute). Although there has been interest in using topical oregano oil for the relief of acute pain, including joint and muscle pain, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Psoriasis. Although there has been interest in using topical oregano oil for psoriasis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Rhinosinusitis. Although there has been interest in using oral oregano for rhinosinusitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Seborrheic dermatitis. Although there has been interest in using topical oregano oil for seborrheic dermatitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea capitis. Although there has been interest in using topical oregano oil for tinea capitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea corporis. Although there has been interest in using topical oregano oil for tinea corporis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea pedis. Although there has been interest in using topical oregano oil for tinea pedis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Toothache. Although there has been interest in using topical oregano oil for toothache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral oregano for URTIs, such as the common cold and influenza, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral oregano for UTIs, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Varicose veins. Although there has been interest in using topical oregano oil for varicose veins, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Warts. Although there has been interest in using topical oregano oil for warts, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Wound healing. It is unclear if topical oregano is beneficial for improving healing or preventing infections in people with skin wounds. Details: One small clinical trial shows that applying an ointment containing a 3% concentration of the water-soluble fraction of the oregano plant twice daily for 10-14 days after minor dermatological surgery might reduce infection rates and improve scar formation when compared with petrolatum ointment (67348). More evidence is needed to rate oregano for these uses.

(Read more about OREGANO)

POSSIBLY EFFECTIVE

• Psoriasis. Clinical research shows that applying a specific 10% Oregon grape extract cream (Relieva, Apollo Pharmaceutical) modestly decreases the severity of psoriasis and improves quality of life in patients with psoriasis when compared with placebo (854,857,14000,14333). One small clinical study shows that this specific cream might be as effective as calcipotriene (Dovonex) cream for some patients (14000).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Preliminary clinical research shows that applying a specific Oregon grape extract cream (Relieva) for 12 weeks improves the severity and area of eczema when compared to baseline in adult patients with atopic dermatitis (67370). The validity of this finding is limited by the lack of a comparator group. In contrast, applying a combination of Oregon grape, heart's ease, and gotu kola extracts for 4 weeks does not improve eczema when compared with a base cream, although there appears to be improvement in eczema for skin exposed to cold weather (67372). More evidence is needed to rate Oregon grape for this use.

(Read more about OREGON GRAPE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there has been interest in using oral pau d'arco for cancer, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose.
• Peptic ulcers. Although there has been interest in using oral pau d'arco for peptic ulcers, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose.
• Wound healing. Although there has been interest in using oral and topical pau d'arco for wound healing, there is insufficient reliable information about the clinical effects of pau d'arco for this purpose. More evidence is needed to rate pau d'arco for these uses.

(Read more about PAU D'ARCO)

POSSIBLY EFFECTIVE

• Acne. Some clinical research shows that topical tea tree oil seems to improve symptoms of acne in adults and adolescents. Details: Some preliminary clinical research shows that applying a tea tree oil 5% gel is as effective as benzoyl peroxide 5% (Oxy-5, Benzac AC, and others) and more effective than placebo for treating acne. Tea tree oil might work more slowly than benzoyl peroxide, but it seems to be less irritating to facial skin (8573). Other clinical research shows that applying a tea tree oil 5% gel for 20 minutes twice daily for 45 days decreases acne lesions 3.6-fold, acne severity 5.7-fold, and comedone numbers, pustules, and papules when compared with placebo in patients with mild to moderate acne (19176). Another small clinical study in patients with mild to moderate acne shows that applying a topical tea tree oil nanoemulsion with adapalene gel 0.1% once daily for 12 weeks reduces acne lesions and improves acne severity scores when compared with adapelene gel alone. However, the tea tree oil product was associated with an increased occurrence of mild adverse effects (109945). Conversely, a small clinical trial shows that applying tea tree oil 5% cream twice daily for 8 weeks reduces inflammatory acne lesions by 38%, compared with a 65% reduction in patients using a product based on Lactobacillus-fermented Chamaecyparis obtuse 5% cream. Additionally, the time of onset was slower with tea tree oil (91447).
• Onychomycosis. Some clinical research suggests that topical pure tea tree oil seems to be beneficial for onychomycosis. It is unclear if the diluted oil is beneficial. Details: Topical application of pure tea tree oil twice daily for 6 months can produce a mycological cure in about 18% of patients with toenail infections. It can also improve nail appearance and symptoms in about 56% of patients after three months and 60% of patients after 6 months of treatment. It seems to be comparable to twice daily application of clotrimazole 1% solution (1538). However, preliminary clinical research shows that lower concentrations of tea tree oil do not seem to be as effective. For example, there is some evidence that a tea tree oil 5% cream applied three times daily for 2 months has no beneficial effect (7032).
• Tinea pedis. Some clinical research suggests that topical tea tree oil 25% or 50% seems to be beneficial for tinea pedis, although it does not seem to work as well as standard treatments. Details: Topical application of tea tree oil 25% or 50% solution twice daily appears to produce both clinical improvement and a mycological cure in 48% to 50% of patients after 4 weeks of treatment, compared with 13% of those using placebo (10033). However, tea tree oil 25% or 50% concentrations don't appear to be as effective for mycological cure as clotrimazole or terbinafine (13713). Also, although topical application of a tea tree oil 10% cream seems comparable to tolnaftate 1% cream for relieving symptoms of tinea pedis, including scaling, inflammation, itching, and burning, the tea tree oil cream appears no more effective than placebo in producing a mycological cure (4031).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Angular cheilitis. Although there is interest in using topical tea tree oil for angular cheilitis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Bacterial vaginosis. Although there is interest in using intravaginal tea tree oil for bacterial vaginosis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Blepharitis. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with seborrheic blepharitis shows that using a specific topical swab (TTO Thermal Swab, Jeomed Medicine and Health Production Company) containing tea tree oil and chamomile twice daily for 8 weeks improves blepharitis symptom scores, such as burning, itching, and dry eyes, when compared with using baby shampoo. Symptom improvements were maintained 4 weeks after treatment discontinuation (109944).
• Contact dermatitis. Preliminary clinical research suggests that topical tea tree oil is beneficial for nickel-induced contact dermatitis. Details: Preliminary clinical research shows that undiluted or diluted tea tree oil for 3-5 days may reduce the area and redness of acute contact dermatitis reactions in people with nickel hypersensitivity (16337,19191). Other preliminary clinical research in individuals with nickel allergy shows that applying 60-120 mcL of tea tree oil 20% or 50% (Australian bodycare tea tree oil, Maxmedica AB) once, immediately prior to nickel exposure, reduces nickel-induced contact dermatitis by 41% when compared with no treatment (19191).
• Dandruff. It is unclear if topical tea tree oil is beneficial for dandruff in adults and adolescents. Details: Preliminary clinical research shows that a tea tree oil 5% shampoo, used for three minutes daily prior to rinsing for 4 weeks, reduces the total area and severity of scalp lesions, as well as the severity of dandruff, itchiness, and greasiness, by 23% to 28% in patients aged 14 years and older. However, it does not improve scalp scaliness (19178).
• Dental plaque. It is unclear if brushing or rinsing with tea tree oil is beneficial for dental plaque; the available evidence is conflicting. Details: Preliminary clinical research shows that brushing with a tea tree oil 2.5% gel twice daily for 8 weeks reduces papillary bleeding, but does not improve gingival health or plaque, in patients with plaque-induced gingivitis (19179). Other preliminary clinical research also shows that using tea tree oil mouthwash does not reduce plaque formation following a professional tooth cleaning (19180). However, a small preliminary clinical trial shows that using a mouthwash made from 3-4 drops of pure tea tree oil in water 2-3 times daily after brushing for 14 days is as effective as using a mouthwash containing chlorhexidine 0.12% twice daily for reducing plaque (105241). Some preliminary clinical research has also evaluated tea tree oil in combination with other ingredients. A combination of tea tree oil 1.5% and xylitol 10% (Tebodont) for 3 months reduces plaque formation on tooth surfaces when compared with pretreatment (19181). Other research shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil 0.2% to 0.3% each, for 30 seconds twice daily for 21 days, reduces plaque formation by 64% when compared to baseline (91446). It is not clear if the effects in these studies are due to tea tree oil, other ingredients, or the combinations.
• Dry eye. It is unclear if topical tea tree oil is beneficial for improving symptoms of dry eye due to cataract surgery or meibomian gland dysfunction. Details: Clinical research in patients with dry eye due to cataract surgery also using artificial tears and topical steroid drops shows that eyelid scrubbing with eye shampoo containing an undisclosed amount of tea tree oil for one month improves symptoms of dry eye, such as sensitivity, pain, and blurred vision, and reduces demodex counts, when compared with using shampoo without tea tree oil. There was no benefit of the tea tree oil on visual acuity (101998). Clinical research in patients with meibomian gland dysfunction shows that applying a tea tree oil 1% shampoo around the eye once daily for 3 months improves gland function scores and dry eye symptom scores when compared with Johnson's baby shampoo (109943).
• Furuncles (boils). Although there is interest in using topical tea tree oil for boils, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Gingivitis. It is unclear if brushing or rinsing with tea tree oil is beneficial for gingivitis; the available evidence is conflicting. Details: A small preliminary clinical trial shows that using a mouthwash comprised of 3-4 drops of pure tea tree oil in water 2-3 times daily after brushing for 14 days is as effective as using a mouthwash containing chlorhexidine 0.12% twice daily for reducing plaque and bleeding and improving gum health (105241). Other preliminary clinical research in patients with severe gingivitis shows that brushing with a tea tree oil 2.5% gel twice daily for 8 weeks reduces papillary bleeding when compared with baseline. However, the gel does not appear to improve plaque or the severity of plaque-induced gingivitis (19179). Combination products containing tea tree oil have also been investigated. Preliminary clinical research shows that rinsing with a specific product containing a combination of tea tree oil 1.5% and xylitol 10% (Tebodont) for 3 months reduces gum inflammation by 26% to 32% when compared with pretreatment (19181). Also, clinical research shows that rinsing with 10 mL of a solution containing tea tree oil, clove, and holy basil 0.2% to 0.3% each, for 30 seconds twice daily for 21 days, reduces gum inflammation by 76% when compared to baseline (91446). It is not clear if the effects in these studies are due to tea tree oil, other ingredients, or the combinations.
• Halitosis. It is unclear if tea tree oil mouth rinses are beneficial for halitosis. Details: Preliminary clinical research in adults with halitosis shows that using a specific tea tree oil mouth rinse (100% Organic Tea Tree Oil, Dessert Essence) 10 mL twice daily for 7 days moderately improves halitosis severity scores and reduces salivary levels of Solobacterium moorei when compared with placebo. The improvements were similar to using chlorhexidine gluconate 0.2% mouth rinse (109941). Tea tree oil has also been studied as a combination treatment. One small clinical study suggests that applying an essential oil solution containing tea tree, peppermint, and lemon oils 0.125% as part of a single three-minute oral cleaning reduces the level of bad breath in patients from an intensive care unit when compared with baseline or benzydamine hydrochloride. 15 mL of the solution was applied to cotton sponges used to clean the teeth, tongue, and oral cavity (19177).
• Hemorrhoids. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children with hemorrhoids shows that application of a specific gel (Proctoial, BSD Pharma) containing tea tree oil, hyaluronic acid, and methylsulfonylmethane (MSM) daily for 14 days decreases symptoms of hemorrhoids, such as anal pain, defecation pain, irritation, inflammation, visible bleeding, and itching, when compared with placebo (19318).
• Herpes labialis (cold sores). It is unclear if topical tea tree oil is beneficial for herpes labialis. Details: One small clinical study in adults with cold sores shows that applying a tea tree oil 6% gel five times daily does not improve the rate of cold sore resolution when compared with a placebo gel (2035). However, this study may have been inadequately powered to detect a difference between groups.
• Hirsutism. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild idiopathic hirsutism shows that using a spray containing lavender and tea tree oils twice daily for 3 months on specific hirsutism-affected areas decreases hair diameter by 8% to 9% and total hirsutism score by 11% when compared with baseline. The spray provides lavender oil 48 mcg and tea tree oil 2 mcg per square cm of skin. These improvements were not observed in a placebo group (91448).
• Insect bite. Although there is interest in using topical tea tree oil for insect bites, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Lice. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: There is preliminary evidence that tea tree oil repels lice and reduces blood feeding (19187). When used in combination with lavender oil, tea tree oil has ovicidal effects on head lice and reduces the number of live lice. A pediculicide containing tea tree oil 10% weight per volume and lavender oil 1% weight per volume (NeutraLice Natural Lotion, Key Pharmaceuticals Pty Ltd) has been applied to the hair for 10 minutes, either as a single application or three times over 2 weeks, in children aged 4-12 years (19188,19189). It is unclear if any effects are due to tea tree oil, lavender, or the combination.
• Methicillin-resistant Staphylococcus aureus (MRSA). It is unclear if topical tea tree oil is beneficial for the prevention of MRSA colonization or the treatment of MRSA infection. Details: Preliminary clinical research shows that tea tree oil is not effective for preventing MRSA colonization. Using tea tree oil 5% body wash (Novabac 5% skin wash, Novasel Australia Pty Ltd.) is no more effective than a standard wash (Johnson's baby softwash, Johnson & Johnson) for preventing MRSA colonization in critically ill patients (91441). There is contradictory evidence on the effects of tea tree oil for the treatment of MRSA infection. In patients with MRSA-colonized wounds, use of a 3% water-miscible solution of tea tree oil during the wound cleansing routine for each dressing change does not improve MRSA clearance (19190). Also, in patients with MRSA colonization, tea tree oil given in various preparations along with standard treatment for 5 days does not appear to increase overall MRSA clearance when compared with standard treatment alone. These various preparations, which contain tea tree oil 5% or 10%, include a cream applied to the nostrils three times daily, a body wash used at least once daily, or a cream applied to lesions, ulcers, wounds, and axillae or groin areas once daily. Although these various preparations do not improve overall clearance, it seems that using a tea tree cream and body wash may be more effective for eradicating MRSA from specific sites such as wounds and superficial skin infections when compared with standard treatments alone (19163). Also, preliminary clinical research suggests that using tea tree oil 4% nasal ointment plus tea tree oil 5% body wash increases MRSA clearance when compared with a triclosan body wash and mupirocin 2% nasal ointment (19158,19159). Larger, high-quality studies are needed to confirm these results.
• Ocular demodicosis. It is unclear if topical tea tree oil is beneficial for ocular demodicosis; available evidence is conflicting. Details: Small clinical studies suggest that tea tree oil can eradicate Demodex infestation in the eyelids and reduce associated symptoms such as corneal and conjunctival inflammation, ocular irritation, and vision loss. In adults, treatments have included weekly scrubs of the eyelid using tea tree oil 50% and daily scrubs of the eyelid with tea tree shampoo, as well as eyelid massages with tea tree ointment 5% to 10%, for up to 12 weeks (19182,19183,19184,19185,91445,105243). In children aged 2.5-11 years, weekly scrubs of the eyelid using tea tree oil 50% and daily eyelid massages with tea tree oil 5% ointment for 4-6 weeks has been used (19184). However, conflicting evidence exists. One meta-analysis of two randomized controlled trials shows that although patients using tea tree oil for 4-6 weeks were 68% more likely to have an eradication of mites, while another meta-analysis of three randomized controlled trials shows that the use of tea tree oil products does not reduce the number of Demodex mites or reported symptoms. Also, a single study shows that receiving intense pulsed light over 12 weeks is more effective than tea tree oil. The certainty of evidence for these endpoints is very low and the majority of available research has an unclear or high risk of bias (105243).
• Oropharyngeal candidiasis. It is unclear if rinsing the mouth with tea tree oil is beneficial for the prevention of oropharyngeal candidiasis in various populations. Details: One very small clinical study in adults with HIV/AIDS who are refractory to fluconazole shows that swishing and expelling tea tree oil solution 15 mL four times daily for 2-4 weeks seems to improve oral candidiasis when compared to baseline (4445). Another small clinical study in adults with terminal cancer shows that using tea tree oil, as part of an essential oil mixture containing geranium, peppermint, and lavender twice daily for one week improves subjective measures of oral comfort and objective measures of oral health status and reduces Candida albicans count when compared with saline solution (19192). However, in patients with dentures, adding 1 mL of tea tree oil to a standard 5 mL dose of Coe-Comfort tissue conditioner treatment for 12 days does not reduce inflammation or Candida albicans growth when compared with Coe-Comfort alone (19193).
• Otitis externa. Although there is interest in using tea tree oil in the ear for otitis externa, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Otitis media. Although there is interest in using tea tree oil in the ear for otitis media, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Pharyngitis. Although there is interest in gargling with tea tree oil for pharyngitis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Rosacea. Topical tea tree oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild to moderate rosacea shows that applying permethrin 2.5% gel containing an undisclosed amount of tea tree oil to the affected area for one hour twice daily for 12 weeks reduces demodex mite counts by about 13% more than placebo. Furthermore, symptoms such as papules, burning, and redness were improved by moderate amounts when compared with placebo (101999). The effect of tea tree oil alone is unknown.
• Scabies. Although there is interest in using topical tea tree oil for scabies, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Seborrheic dermatitis. Although there is interest in using topical tea tree oil for seborrheic dermatitis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Tinea corporis. Although there is interest in using topical tea tree oil for tinea corporis, there is insufficient reliable information about the clinical effects of tea tree oil for this condition.
• Toothache. Although there is interest in rinsing the mouth with tea tree oil for toothache, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Vaginal candidiasis. Although there is interest in using intravaginal tea tree oil for vaginal candidiasis, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose.
• Water warts. It is unclear if topical tea tree oil is beneficial for water warts in children. Details: Preliminary clinical research in children with a mean age of 6.3 years with water warts shows that a 4 mcL drop of an oil containing iodine plus Australian tea tree oil 75%, standardized to 40.1% terpinene-4-ol, applied twice daily for up to 30 days, increases lesion resolution when compared with tea tree oil or iodine alone (19194).
• Wound healing. Although there is interest in topical tea tree oil for wound healing, there is insufficient reliable information about the clinical effects of tea tree oil for this purpose. More evidence is needed to rate tea tree oil for these uses.

(Read more about TEA TREE OIL)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cough. Although there has been interest in using oral usnea for cough, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Human papillomavirus (HPV). Topical usnic acid, a constituent of usnea, has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with HPV genital infection undergoing radiosurgical treatment of HPV lesions shows that vaginal application of a specific product containing zinc sulfate and the usnea constituent usnic acid (Zeta N, Bergamon Italia), before and after radiosurgical treatment of HPV lesions, improves wound healing and reduces the recurrence of infection for up to 6 months after surgical treatment when compared with radiosurgical treatment alone (81573). It is unclear if these effects are due to usnic acid, zinc sulfate, or the combination.
• Obesity. Although there has been interest in using oral usnea for weight loss, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Pain (acute). Although there has been interest in using oral usnea for acute pain, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Tinea pedis. Although there has been interest in using topical usnea for tinea pedis, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Wound healing. Although there has been interest in using topical usnea for wound healing, there is insufficient reliable information about the clinical effects of usnea for this purpose. More evidence is needed to rate usnea for these uses.

(Read more about USNEA)

LIKELY SAFE ...when the fruit (nut) is consumed in amounts normally found in food.

POSSIBLY UNSAFE ...when the bark is used orally or topically, due to its juglone content (2). When applied topically, juglone-containing bark can cause skin irritation. When used orally on a daily basis, the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12). There is insufficient reliable information available about the safety of the leaf or hull when used orally as a medicine or when applied topically.

PREGNANCY AND LACTATION: LIKELY SAFE
when the fruit (nut) is consumed in amounts normally found in foods.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the bark is used orally or topically (12); avoid using. There is insufficient reliable information available about the safety of black walnut leaf or hull when used orally in medicinal amounts during pregnancy or lactation; avoid using.

(Read more about BLACK WALNUT)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

(Read more about FENNEL)

LIKELY SAFE ...when the root preparations are used in amounts commonly found in foods. Gentian root is categorized by the FDA as a safe food additive flavoring in the US (4912).

POSSIBLY SAFE ...when gentian root is used orally in a specific combination that contains gentian root, elderflower, verbena, cowslip flower, and sorrel (SinuComp, Sinupret) (374,379,95907). There is insufficient reliable information available about the safety of the topical use of gentian.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of gentian in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about GENTIAN)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Oregano leaf and oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of oregano when used orally in amounts greater than those found in food. There is also insufficient reliable information available about the safety of oregano when used topically. Oregano oil in concentrations of greater than 1% may be irritating when applied to mucous membranes (67348,88188).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Oregano is thought to have abortifacient and emmenagogue effects (19,7122,19104).

LACTATION:
There is insufficient reliable information available about the safety of oregano when used in medicinal amounts; avoid amounts greater than those found in food.

(Read more about OREGANO)

LIKELY SAFE ...when used orally in amounts commonly found in food.

POSSIBLY SAFE ...when used topically and appropriately (854,856,857,14000,14333). A specific 10% Oregon grape cream (Relieva, Apollo Pharmaceutical) has been used with apparent safety in studies lasting up to 12 weeks (14000,14333). There is insufficient reliable information available about the safety of Oregon grape when used orally in medicinal amounts.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of Oregon grape can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589).

LACTATION: LIKELY UNSAFE
when used orally. Berberine and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about OREGON GRAPE)

POSSIBLY UNSAFE ...when used orally. The safety of pau d'arco in typical doses is unclear; however, serious toxicities have been found with high doses of the lapachol constituent (91939). In patients with cancer, doses of lapachol above 1.5 grams daily were associated with significant gastrointestinal toxicities and an increased risk of bleeding (91939). There is insufficient reliable information available about the safety of pau d'arco when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally in typical doses. Animal studies have found that lapachol, a constituent of pau d'arco, has teratogenic and abortifacient effects (68314,68315); avoid using. There is insufficient reliable information available about the safety of pau d'arco when used topically in pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PAU D'ARCO)

POSSIBLY SAFE ...when used topically and appropriately for up to 12 weeks (1538,4028,4031,4445,7032,8573,19157,19158,19159,19163)(19318,109944,109945).

LIKELY UNSAFE ...when used orally. Tea tree oil has been reported to cause significant toxicity when used orally (4028,10011,19166,19168,19170,109947).

CHILDREN: POSSIBLY SAFE
when used topically and appropriately. Tea tree oil 5% preparations have been used with apparent safety in children (8573).

CHILDREN: LIKELY UNSAFE
when used orally. Ingestion of tea tree oil can be toxic (4030,10010,10013,11799).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used topically and appropriately (512).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Ingestion of tea tree oil can be toxic (515).

(Read more about TEA TREE OIL)

POSSIBLY SAFE ...when used topically and appropriately (12).

POSSIBLY UNSAFE ...when used orally. There are case reports of hepatotoxicity associated with compounds containing usnic acid, a constituent of usnea (7091,81595,81600,81607,81612,81619).

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

(Read more about USNEA)

(Read more about BLACK WALNUT)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

(Read more about FENNEL)

(Read more about GENTIAN)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aristolochic acid isolated from oregano leaves has antithrombin activity (67164). It has also been reported that oregano oil inhibits arachidonic acid-induced, and ADP-induced, platelet aggregation (49445).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk for hypoglycemia when taken with antidiabetes drugs.  Details In vitro and animal research shows that oregano extracts might lower blood glucose levels (67191,67204,110122).

(Read more about OREGANO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation (33660,33694). Theoretically, Oregon grape might have additive effects when used with anticoagulant and antiplatelet drugs and increase the risk of bleeding.  Details Some anticoagulant and antiplatelet drugs include aspirin, cilostazol (Pletal), clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and others.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = A Clinical research suggests that berberine, a constituent of Oregon grape, can lower blood glucose levels (20579,34247,34265,34282). Theoretically, Oregon grape might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia.  Details Some antidiabetes drugs include glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that berberine, a constituent of Oregon grape, can have hypotensive effects (33692,34308). Also, an analysis of clinical evidence suggests that taking berberine in combination with amlodipine (Norvasc) can lower systolic and diastolic blood pressure when compared with taking amlodipine alone (91956). Theoretically, taking Oregon grape along with antihypertensive drugs might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.  Details Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects (13519,33650,33664,33692). Theoretically, use of Oregon grape along with CNS depressants might increase the risk of additive therapeutic and adverse effects.  Details Some CNS depressants are benzodiazepines, pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), thiopental (Pentothal), fentanyl (Duragesic, Sublimaze), morphine, propofol (Diprivan), and others.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9) (34279). Theoretically, taking Oregon grape with drugs metabolized by CYP2C9 might increase drug levels and potentially increase the risk of adverse effects.  Details Some drugs metabolized by CYP2C9 include celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), and S-warfarin (Coumadin).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6) (21117,34279,34297). Theoretically, taking Oregon grape with drugs metabolized by CYP2D6 might increase drug levels and potentially increase the risk of adverse effects.  Details Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4) (13524,21114,34279,34297). Theoretically, taking Oregon grape with drugs metabolized by CYP3A4 might increase drug levels and potentially increase the risk of adverse effects.  Details Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous others. Use European barberry cautiously or avoid in patients taking these drugs.

(Read more about OREGON GRAPE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, pau d'arco might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that pau d'arco reduces platelet aggregation and may interfere with vitamin K (18057,68319). One clinical study shows that taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily increases the risk of bleeding (91939). The effects of whole pau d'arco or pau d'arco extract in humans are unclear.

(Read more about PAU D'ARCO)

(Read more about TEA TREE OIL)

(Read more about USNEA)

General ...Orally, black walnut fruit (nut) is well tolerated. However, the leaf, bark, and hull of black walnut contain high quantities of tannins, which may cause adverse effects when used orally or topically.
Most Common Adverse Effects:
Orally: The leaf, bark, and hull can cause gastrointestinal upset.
Topically: Hull preparations may cause a temporary yellow or brown discoloration at the site of application. The leaf, bark, and hull can cause skin irritation.
Serious Adverse Effects (Rare):
Orally: The bark may increase the risk for tongue cancer or lip leukoplakia when used long-term.
All routes of administration: Allergic reactions, including anaphylaxis.

Dermatologic ...Topically, black walnut leaf, bark, or hull may have an irritating effect on the skin due to tannin content. Black walnut hull preparations might cause a temporary yellow or brown discoloration of the skin at the site of application (12).

Gastrointestinal ...Orally, black walnut leaf, bark, or hull may cause gastrointestinal upset due to tannin content (12). Also, daily use of the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12).

Hepatic ...Orally, black walnut leaf, bark, or hull may cause liver damage if taken for extended periods of time due to tannin content (12).

Immunologic ...Tree nuts, which include black walnuts, can cause allergic reactions in sensitive individuals. Due to the prevalence of this allergy in the general population, tree nuts are classified as a major food allergen in the United States (105410).

Renal ...Orally, black walnut leaf, bark, or hull may cause kidney damage if taken for extended periods of time due to tannin content (12).

(Read more about BLACK WALNUT)

General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

(Read more about FENNEL)

General ...Orally, gentian root, in combination with other herbs, seems to be generally well tolerated (95907). Side effects reported in clinical studies include gastrointestinal discomfort and allergic skin reactions (374,379). There is insufficient reliable information available about the adverse effects of gentian when taken as a medicine alone.

Gastrointestinal ...Orally, gentian root, in combination with other herbs, has been reported to cause gastrointestinal adverse effects (374,379). Gastrointestinal intolerance occurred in patients with cancer-associated anorexia who took gentian tincture 1 mL three times daily, in conjunction with turmeric 1 gram and ginger 1 gram twice daily, for 14 days. Six of 17 patients discontinued the regimen due to nausea, 3 due to vomiting, 2 due to diarrhea, and 2 due to bloating. It is unclear if this gastrointestinal intolerance was caused by gentian, the other herbs, or the patients' predisposing conditions (96263).

Immunologic ...Orally, gentian root, in combination with other herbs, has been reported to cause allergic skin reactions (374,379). It is unclear if these reactions were caused by gentian, the other herbs, or the combination.

(Read more about GENTIAN)

General ...Orally, oregano is well tolerated when used in amounts typically found in foods. There is currently a limited amount of information available about the safety of oregano when used in larger amounts as medicine.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Systemic allergic reactions, including anaphylaxis, in sensitive individuals.

Dermatologic ...Oregano has been reported to cause allergic contact dermatitis (46902). Topically, oregano oil in concentrations of greater than 1% has been reported to cause irritation when applied to mucous membranes (67348,88188).

Gastrointestinal ...Orally, large amounts of oregano can cause gastrointestinal upset. Concentrated, non-emulsified oil of oregano can cause localized irritation of the gastrointestinal tract (6878).

Immunologic ...Systemic allergic reactions have been reported with oregano. A 45-year-old male developed pruritus, respiratory difficulty, hypotension, swelling of the lips and tongue, and facial edema after ingesting pizza seasoned with oregano. He had 2 similar episodes after ingesting foods seasoned with thyme, another member of the Lamiaceae family. He did not react to similar foods without the seasoning, and he had positive skin tests to plants of the Lamiaceae family (3705).

(Read more about OREGANO)

General ...Orally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Topically, Oregon grape can cause itching, burning, skin irritation, and allergic reactions (854,14000).

Dermatologic ...Topically, Oregon grape can cause itching, burning, and skin irritation (854,14000).

Immunologic ...Topically, Oregon grape can cause allergic reactions (854,14000).

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General ...A thorough evaluation of safety outcomes with pau d'arco has not been conducted. However, taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily is regarded as unsafe.

Gastrointestinal ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause severe nausea, vomiting, and diarrhea (91939).

Hematologic ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause anemia and increased risk of bleeding (91939).

Immunologic ...Occupational exposure to sawdust from the pau d'arco tree and related species may cause asthma and dermatitis. The fresh sawdust can produce erythema and papules which progress to a severe weeping and crusting dermatitis (92184).

Neurologic/CNS ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause dizziness (91939).

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General ...Orally, tea tree oil can cause significant toxicity and should not be used. Topically, tea tree oil is generally well tolerated.
Most Common Adverse Effects:
Topically: Allergic reactions, burning, dryness, irritation, pruritus, redness, and stinging.

Dermatologic ...Ingestion of as little as 2. 5 mL of tea tree oil can cause petechial body rash. It can take up to a week for symptoms to resolve (10011).
Topically, tea tree oil is usually well tolerated. However, it can cause local irritation and inflammation in some patients. Treatment with topical corticosteroids may be needed in some cases (10033,13713,19176,91442,91443,109946,109947). Severe allergic contact dermatitis has also been reported (109948). Tea tree oil can cause skin dryness, and less frequently pruritus, stinging, burning, and redness in patients with acne (8573,91447,109947). It may also cause mild oral mucosal burning (4445).

Endocrine ...In one case, a prepubertal male who used a hair styling gel and shampoo product containing both tea tree oil and lavender oil developed gynecomastia. The gynecomastia resolved when the products were discontinued. It is possible that this effect was due to lavender oil, which has been associated with other cases of gynecomastia in prepubertal males (15254).

Gastrointestinal ...Orally, tea tree oil can cause eucalyptus-like odor on the breath. In young children, ingestion of 10 mL or less of tea tree oil can cause this effect (4030,10010,11799).

Hematologic ...Orally, as little as 2. 5 mL of tea tree oil can cause neutrophil leukocytosis. It can take up to a week for symptoms to resolve (10011).

Immunologic ...Orally, tea tree oil can cause or worsen systemic contact dermatitis (4028,19168). Topically, tea tree oil is usually well tolerated. However, it can cause allergic contact eczema and allergic contact dermatitis in some children and adults. Corticosteroids may be needed in some cases (658,4027,4028,4029,10015,10029,10030,10031,10032)(91443,105242,105244).
In young children, ingestion of 10 mL or less of tea tree oil can cause significant ataxia, drowsiness, disorientation, and coma (4030,10010,11799).

Neurologic/CNS ...Orally, tea tree oil can cause ataxia and CNS depression (109947).

Ocular/Otic ...There is some concern that topical use of tea tree oil in the middle ear for treatment of ear infections might cause ototoxicity. There is preliminary evidence from animal research that preparations of pure tea tree oil can cause ototoxicity and impaired hearing. However, so far there are no reports of ototoxicity in humans. Until more is known, tell patients to avoid pure or highly concentrated tea tree oil preparations. Concentrations of 2% seem less likely to have this effect (7025).

Pulmonary/Respiratory ...Orally, tea tree oil can cause dyspnea and pneumonitis (109947).

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General ...There is currently a limited amount of information about the adverse effects of usnea. Orally, usnea might be unsafe. The constituent usnic acid has been associated with hepatotoxicity. Topically, usnea is generally well tolerated.
Most Common Adverse Effects:
Topically: Usnic acid, a constituent of usnea, can cause conjunctivitis, contact dermatitis, and local irritation.
Serious Adverse Effects (Rare):
Orally: Usnic acid, a constituent of usnea, has been associated with reports of hepatotoxicity.

Dermatologic ...Topically, a compound containing zinc sulfate and usnic acid, a constituent of usnea, has been reported to cause local irritation and contact dermatitis (81573).

Hepatic ...Orally, usnic acid, a constituent of usnea, has been associated with reports of hepatotoxicity. From July to December 2000 there were at least seven cases of acute hepatotoxicity in patients taking LipoKinetix, a product containing usnic acid as sodium usniate. Symptoms including nausea, weakness and fatigue, abdominal pain, and yellowing of the skin usually developed from 2 weeks to 3 months after starting LipoKinetix and resolved upon discontinuation (7091). It is unclear if the sodium usniate ingredient is the cause of these adverse events. There are also individual case reports suggesting the development of hepatotoxicity related to the use of other weight loss products containing usnic acid (81595,81600,81607,81612,81619).

Immunologic ...Topically, usnea and its constituent, usnic acid, can cause allergic contact dermatitis with respiratory symptoms (11720,81580,81632).

Ocular/Otic ...Topically, usnic acid, a constituent of usnea, can cause conjunctivitis (11720).

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