Super Suppositories by The Herbalist

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about BEESWAX)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate acne associated with mask wearing shows that topical application of a combination of calendula 4%, licorice root extract 0.3%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to calendula, other ingredients, or the combination.
• Bacterial vaginosis. It is unclear if topical calendula is beneficial for improving bacterial vaginosis. Details: A small clinical study in patients with bacterial vaginosis shows that applying 5 grams of vaginal cream containing calendula flower extract before bed for one week improves vaginal burning, odor, painful urination, and painful intercourse when compared to baseline (96649). The validity of these findings is limited by the lack of a comparator group.
• Burns. It is unclear if oral calendula is beneficial for burn healing. Details: A small clinical trial in patients hospitalized for second-degree burns shows that taking calendula 2 grams daily for 2 weeks has a large beneficial effect on wound healing when compared with placebo (110323).
• Chronic obstructive pulmonary disease (COPD). Oral calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males aged 40-70 years with a history of smoking and stage 2 COPD shows that taking a specific combination of calendula flowers 165 mg, elderberry 165 mg, and heart's ease herb 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months, modestly improves symptoms, as measured on the breathlessness, cough, and sputum scale (BCSS), and mean forced expiratory volume in 1 second (FEV1) when compared to baseline. However, there was no improvement of COPD exacerbations or other pulmonary function tests (103629). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Furthermore, it is unclear if these effects are due to calendula, the other ingredients, or the combination.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Calendula in rectal suppositories has only been evaluated in combination with turmeric extract; its effect when used alone is unclear. Details: A small clinical study in patients with CP/CPPS shows that using a rectal suppository containing turmeric extract 350 mg and calendula extract 80 mg daily for one month improves pain, peak urine flow rate, and erectile function when compared with placebo (96648). It is unclear if these effects are due to calendula, turmeric, or the combination.
• Conjunctivitis. Although there is interest in using topical calendula for conjunctivitis, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Diabetic foot ulcers. It is unclear if topical calendula is beneficial for improving diabetic foot ulcers. Details: Observational research has found that applying a calendula hydroglycolic extract spray in addition to standard care and hygiene is associated with reduced bacterial colonization and improved odor in patients that have had a diabetic ulcer for over 3 months (93548).
• Diaper rash. It is unclear if topical calendula is beneficial for improving diaper rash. Details: One preliminary clinical study in children less than 3 years of age shows that topical application of calendula 1.5% ointment three times daily for 10 days improves diaper rash when compared with aloe gel (19779). However, other preliminary clinical research shows that applying calendula 1.5% cream every 4-6 hours for 3 days improves diaper rash in fewer infants when compared to treatment with bentonite 50% mineral solution (93545,93554).
• Dysmenorrhea. Although there is interest in using oral calendula for dysmenorrhea, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Gingivitis. It is unclear if using a mouth rinse with calendula is beneficial for improving gingivitis. Details: Preliminary clinical research in patients with mild gingivitis and bleeding gums shows that rinsing the mouth with a tincture containing calendula 25% (Dr. Willmar Schwabe Germany Home Pharmacy Pvt. Ltd.) twice daily for 6 months decreases plaque, gingivitis, and bleeding by 10% to 18% when compared to rinsing with water (93551). Other preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with a combination mouthwash containing a 5% extract of calendula, rosemary, and ginger for 30 seconds twice daily after food for 2 weeks decreases plaque, gingivitis, and bleeding when compared with a placebo mouthwash. The effects of this combination mouthwash appear to be similar to chlorhexidine 0.2% mouthwash (93555). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Hemorrhoids. Although there is interest in using topical calendula for hemorrhoids, there is insufficient reliable information about the clinical effects of calendula for this purpose.
• Liver disease. Although there is interest in using oral calendula for liver disease, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Mosquito repellent. It is unclear if topical calendula essential oil helps to repel mosquitos. Details: Preliminary clinical research shows that applying calendula 50% essential oil to the skin does not repel mosquitos as effectively as applying DEET. Mean repellency time was about 2 hours for patients applying calendula, which was shorter than the 6 hour repellency with DEET (93562).
• Oral leukoplakia. It is unclear if topical calendula is beneficial for improving oral leukoplakia. Details: Preliminary clinical research in patients with oral leukoplakia shows that applying a gel containing calendula flower extract 0.2% three times daily for one month reduces lesion size by about 2 cm when compared to baseline (96650). The validity of this finding is limited by the lack of a comparator group.
• Oral mucositis. Calendula as a mouth rinse has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with head and neck cancer receiving chemotherapy and radiotherapy shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing calendula powder extract 2%, propolis, aloe vera, and chamomile three times daily for 6 weeks does not prevent oral mucositis when compared with placebo (95879).
• Otitis media. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with otitis media shows that applying a specific combination product containing calendula, mullein, garlic, and St. John's wort in olive oil (Otikon Otic Solution, Healthy-On Ltd, Petach-Tikva, Israel), five drops into the affected ear three times daily for 3 days, may reduce ear pain when compared with baseline (39500,39552). It is unclear if this effect is due to calendula, other ingredients, or the combination. Furthermore, due to the lack of an adequate control group, it is unclear whether the pain reduction was due to the resolution of otitis media.
• Peptic ulcers. Although there is interest in using oral calendula for peptic ulcers, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Pressure ulcers. It is unclear if topical calendula is beneficial for improving pressure ulcers. Details: Observational research has found that the application of a specific calendula product (Plenusdermax) twice daily is associated with improved healing in patients with pressure ulcers that have not changed in size for at least 3 months (93549). Preliminary clinical research in hospice patients with symptomatic pressure ulcers and other wounds shows that applying a homeopathic powder (RGN107) containing calendula 0.1% and arnica 0.01% to wounds for 4 weeks is rated by the patients and caregivers to be acceptable for controlling pain, odor, and exudate when compared with baseline (96647). The validity of this finding is limited by the lack of a control group.
• Radiation dermatitis. It is unclear if topical calendula reduces radiation dermatitis symptoms. Details: 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)

POSSIBLY EFFECTIVE

• Cardiovascular disease (CVD). Dietary cocoa seems to be beneficial for CVD prevention. Oral cocoa extract may reduce the risk of CVD-related death, but it is unclear if it can prevent other CVD-related outcomes like myocardial infarction (MI) or stroke. Details: A large clinical trial in adults without CVD shows that taking a specific cocoa extract daily for around 3.5 years reduces the risk of CVD-related death by 27%, but does not reduce the risk of cardiovascular events, including MI or stroke, or overall mortality when compared with placebo. This specific cocoa extract contained 500 mg of flavanols, including 80 mg of epicatechins (108898). In 2023, the US Food and Drug Administration (FDA) approved a qualified health claim stating that very limited scientific evidence suggests that the cocoa flavanols in high flavanol cocoa powder, for products containing at least 4% naturally conserved cocoa flavanols, may reduce the risk of cardiovascular disease (110017). Observational research in adults without CVD has also found that consuming a higher amount of cocoa is associated with a 10% lower risk of CVD and an up to 50% lower risk of CVD-related mortality when compared with consuming lower amounts of cocoa. Consuming more than 90 grams of cocoa per week did not add further benefit (14288,97192). Additional clinical research shows that taking cocoa flavanols 450 mg twice daily for one month improves cholesterol levels and blood pressure values, resulting in improved Framingham Risk Scores in healthy patients. These scores correspond to a 21% decrease in the 10-year risk for coronary heart disease, a 22% decrease in the risk for CVD, a 31% decrease in the risk for MI, and a 30% decrease in the risk for CVD-related mortality (92273). There is also evidence that consuming cocoa might improve flow-mediated dilatation, a measure of endothelial dysfunction. Meta-analyses of clinical research have found that increased cocoa or chocolate intake significantly improves flow-mediated dilatation. This is seen with intakes of 19-54 grams of cocoa daily, 46-100 grams of dark chocolate daily, or cocoa products containing 16.6-1080 mg of flavonoids daily (17187,42059,42137).
• Hypertension. Oral cocoa seems to be beneficial for modestly decreasing blood pressure in hypertensive patients. It is unclear if dietary cocoa is beneficial for preventing hypertension. Details: Overall, clinical research shows that chocolate or cocoa containing 25-1080 mg daily of flavonoids modestly reduces blood pressure in hypertensive patients (14306,15655,15752,42092,42107,42169,97190,103247). Meta-analyses of clinical research show that consuming commercially available dark chocolate or flavanol-enriched chocolate/cocoa products daily for 2-8 weeks reduces systolic blood pressure (SBP) by around 4 mmHg and diastolic blood pressure (DBP) by around 2 mmHg in patients with hypertension when compared to control products with low levels of flavanols or no flavanols (42169,97190). Additionally, a meta-analysis of clinical trials in middle-aged and elderly patients with or without hypertension shows that consuming cocoa products daily for 4-18 weeks reduces SBP and DBP by around 3 mmHg and 1.5 mmHg, respectively, when compared with control products (103249). Blood pressure lowering seems to occur more readily in hypertensive or pre-hypertensive individuals when compared with normotensive individuals (14306,15655,15752,42092,42107,42169,97190,103247). Consumption of cocoa might also reduce the risk of developing hypertension in normotensive patients. Observational research has found that long-term consumption of moderate amounts of cocoa (2.2 grams to 6.1 grams daily) is associated with a 7% lower risk of hypertension when compared with consumption of less than 0.61 grams daily. However, consumption of amounts greater than 6.1 grams daily does not seem to reduce hypertension risk. Also, this benefit seems to be limited to patients consuming cocoa from plain chocolate, as consumption of cocoa from desserts was linked with a 9% greater risk of hypertension (103248).

POSSIBLY INEFFECTIVE

• Hypercholesterolemia. Oral cocoa does not seem to be beneficial for reducing cholesterol levels in patients with hypercholesterolemia. Details: Some preliminary clinical research in healthy, normocholesterolemic males shows that diets high in stearic acid from cocoa butter result in lower cholesterol levels when compared with diets high in myristic acid from dairy butter. However, a diet high in stearic acid from cocoa butter does not significantly lower cholesterol when compared to baseline in this population (15063). A meta-analysis of 10 clinical studies shows that cocoa or dark chocolate can reduce total cholesterol and low-density lipoprotein (LDL) cholesterol in normocholesterolemic patients (42125). However, some preliminary clinical research in patients with hypercholesterolemia shows that drinking a high-flavanol cocoa beverage daily for 6 weeks does not reduce cholesterol when compared with a low-flavanol cocoa beverage (42013). Also, while some clinical research shows that taking cocoa powder 26 grams with sugar daily for 12 weeks can increase high-density lipoprotein (HDL) cholesterol levels when compared with sugar alone in normocholesterolemic and hypercholesterolemic patients (42026), taking cocoa or dark chocolate 13-41 grams daily does not seem to lower total cholesterol or LDL cholesterol in these patients (42026,42029,42225).
• Stretch marks (striae gravidarum). Topical cocoa butter does not seem to be beneficial for preventing stretch marks during pregnancy. Details: Clinical research shows that topical application with a cream containing cocoa butter 25% to the abdomen daily, starting during the second and third trimesters and continuing until delivery, does not prevent stretch marks when compared with a placebo cream (105261). Other clinical research shows that topical application with a cream containing cocoa butter and vitamin E as tocopheryl acetate to the abdomen, breasts, and thighs, daily, starting during the second trimester and continuing until delivery, does not reduce the prevalence or severity of stretch marks when compared to a cream not containing these ingredients (105262). More research is needed in individuals of all skin types.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral cocoa is beneficial for improving cognitive function in healthy older adults. Details: Some small clinical studies in healthy adults over the age of 60 with or without existing cognitive impairment show that sub-chronic intake of cocoa at doses of 45 mg, 520 mg, or 990 mg once daily for 8 weeks, or as a cocoa drink containing flavanols 609 mg daily for 30 days, modestly improves some measures of cognitive function, including task switching, visual attention, and verbal fluency (42184,92269). However, it does not improve performance on the mini mental state exam (92269). Also, one clinical study in healthy adults aged 60 years and older shows that consuming a dark chocolate bar containing 11 grams of cocoa and drinking 237 mL of an artificially sweetened drink containing 11 grams of cocoa daily for 6 weeks does not improve neuropsychological function when compared with placebo (42050). Additional preliminary clinical research in postmenopausal females aged 50-64 years shows that adding chocolate 10 grams daily, containing 99% cocoa, for 6 months does not improve most measures of cognitive function when compared with not taking cocoa (105259). Reasons for the discrepancies are unclear but may relate to the dose of cocoa, the duration of intake, or the specific cognitive testing procedures conducted.
• Age-related testosterone deficiency. Oral cocoa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy middle-aged adults shows that taking a combination product containing cocoa seed extract and pomegranate rind (Tesnor, Gencor) daily for 56 days increases serum testosterone levels and hand-grip strength and improves measures of sexual function and psychological well-being when compared with placebo (111527). It is unclear if these effects are due to cocoa, pomegranate, or the combination.
• Aging skin. It is unclear if oral cocoa is beneficial for aging skin. Details: Preliminary clinical research in adults with aging skin shows taking a specific product (GliSODin Skin Nutrients Advanced Anti-Aging Formula, Isocell North America Inc.) 780 mg three times daily, containing cocoa extract, as well as superoxide dismutase, krill oil, sea buckthorn, hyaluronic acid, and other nutrients, in combination with daily use of tazarotene cream 0.1%, for 90 days improves fine wrinkling, photodamage, and skin elasticity when compared with tazarotene cream and placebo (91778). Additional preliminary clinical research in patients with photoaged skin shows that drinking a cocoa drink containing 320 mg of flavanols daily for 24 weeks improves wrinkle depth and skin elasticity, but not skin hydration, when compared with placebo (92274).
• Asthma. Although there has been interest in using oral cocoa for asthma, there is insufficient reliable information about the clinical effects of cocoa for this condition.
• Athletic performance. Although there has been interest in using oral cocoa for improving athletic performance, there is insufficient reliable information about the clinical effects of cocoa for this use.
• Atrial fibrillation. It is unclear if dietary cocoa is beneficial for preventing atrial fibrillation. Details: Most population research has found that chocolate consumption is not associated with a reduced risk of atrial fibrillation (97188,97189).
• Chronic fatigue syndrome (CFS). It is unclear if oral cocoa is beneficial for CFS. Details: In patients with CFS, preliminary clinical research shows that consuming 45 grams of a polyphenol-rich chocolate in three divided doses daily for 8 weeks can reduce fatigue by 35%, anxiety by 37%, and depression by 45%, and can increase overall function by 30%, when compared with pretreatment (42116).
• Cirrhosis. It is unclear if oral cocoa is beneficial for cirrhosis. Details: Clinical research shows that consuming a liquid test meal (Ensure Plus) in addition to dark chocolate (Lindt Excellence 85% Cocoa, Lindt & Sprüngli) 0.55 grams/kg can reduce the postprandial increase in hepatic venous pressure gradient in patients with cirrhosis when compared with the test drink alone (42164).
• Cognitive function. Research on the use of oral cocoa for improving cognitive function in healthy adults is conflicting. Details: A large clinical trial in older adults shows that taking cocoa extract containing 500 mg of flavanols daily for 3 years does not improve measures of cognitive function including global cognition, episodic memory, and executive function when compared with placebo, even when taken with a multivitamin-mineral product (Centrum Silver) (111524). Also, in middle-aged participants, clinical research shows that taking 20 grams of a dark chocolate drink mix containing 250 mg or 500 mg of polyphenols as a single dose does not seem to improve measures of cognitive function (92272). In contrast, clinical research in healthy younger individuals shows that consuming a single dose of cocoa flavanols 520-994 mg as a specific powder (Cocoapro) improves some, but not all, measures of cognitive function when examined in a situation of sustained mental effort (42093). Additionally, consuming a single dose of cocoa flavanols 900 mg as a specific powder (Acticoa) seems to improve reaction time during cognitive testing when compared with placebo in healthy adults and patients with type 1 diabetes (103251). However, acute dosing with cocoa flavanols 374-747 mg as specific powders (Acticoa) or cocoa extract capsules (Naturex) does not seem to improve measures of cognitive function, visual working memory, or ability to focus during testing in young people (99984,99985,109448). Reasons for the discrepancies are unclear but may relate to the dose of cocoa, the duration of intake, the level of stress during cognitive testing, or the specific cognitive testing procedures conducted.
• Cognitive impairment. Oral cocoa flavanols have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A large clinical study in adults at least 55 years of age with subjective or mild cognitive impairment shows that consuming dark chocolate containing 500 mg cocoa flavanols and taking fish oil containing DHA 1.1 grams and EPA 0.4 grams daily for 12 months does not improve cognitive function scores when compared with placebo (111453).
• Constipation. Oral cocoa husk has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with chronic constipation shows that taking 2-4 sachets containing cocoa husk 8-16 grams and beta-fructosans 2-4 grams daily for 4 weeks can reduce hard stools by 45% and reduce transit time by 36 hours when compared with a placebo (42016).
• Diabetes. Several small clinical studies suggest that oral cocoa may cause small but clinically insignificant improvements in glycemic control in patients with diabetes. However, cocoa does not appear to be beneficial for the prevention of diabetes. Details: While some individual studies show conflicting results (97252,99982), two similar meta-analyses of 8-9 small clinical trials in patients with diabetes show that taking cocoa 1-54 grams daily for up to 52 weeks reduces fasting blood glucose by around 7-9 mg/dL and low-density lipoprotein (LDL) cholesterol by around 10-15 mg/dL, but does not improve glycated hemoglobin (HbA1c), insulin levels, blood pressure, total cholesterol, or high-density lipoprotein (HDL) cholesterol, when compared with control (109447,109449). This slight improvement in fasting blood glucose, along with a lack of effect on HbA1c, suggests that cocoa is unlikely to lead to clinically meaningful improvements in glycemic control. Population research has found that eating up to 60 grams of chocolate per week is associated with a lower risk of developing diabetes. Higher consumption was not found to affect diabetes risk (97192). However, secondary analysis of a large clinical study in adults aged 74 on average shows that taking an extract containing cocoa flavanols 500 mg daily, with or without a multivitamin, for about 3.5 years does not reduce the risk of developing self-reported type 2 diabetes when compared with placebo. Subgroup analysis based on body mass index, level of physical activity, or multivitamin consumption did not change results (111619).
• Exercise-induced muscle damage. It is unclear if oral cocoa flavanols are beneficial for preventing exercise-induced muscle damage. Details: Preliminary clinical research shows that taking a single dose of cocoa flavanols (Chococru Extraordinary Flavanol Cocoa) 830 mg or 1245 mg within 5 minutes of a strenuous exercise protocol does not reduce exercise-induced muscle damage over 72 hours when compared with a control providing no cocoa flavanols (105260).
• Fatigue. It is unclear if oral cocoa is beneficial for fatigue. Details: A moderate-size clinical study in otherwise healthy females aged 40-60 years with fatigue shows that consuming a beverage containing cocoa flavanols 240 mg daily for 8 weeks does not improve self-reported fatigue scores when compared with placebo (111620).
• Heart failure. It is unclear if dietary cocoa is beneficial for heart failure prevention. Details: Population research has found that consuming up to 250 grams of chocolate weekly is associated with reduced risk of heart failure. However, consuming 300 grams weekly or more does not appear to affect the risk of heart failure (97187,97191).
• HIV/AIDS-related dyslipidemia. It is unclear if oral cocoa is beneficial for HIV/AIDS-related dyslipidemia. Details: Preliminary clinical research in patients with HIV shows that consuming dark chocolate 65 grams containing cocoa 36 grams for 15 days does not affect low-density lipoprotein (LDL) cholesterol or total cholesterol levels when compared with a white chocolate placebo. However, it slightly increases levels of high-density lipoprotein (HDL) cholesterol (96472).
• Impaired glucose tolerance (prediabetes). It is unclear if oral cocoa is beneficial in patients with prediabetes. Details: A small clinical study in premenopausal adults with overweight or obesity and mild insulin resistance shows that drinking a cocoa drink high in flavanols twice daily for 4 weeks does not improve measures of insulin resistance or insulin-mediated glucose uptake when compared with a low-flavanol cocoa drink (111532).
• Influenza. Although there has been interest in using oral cocoa for influenza, there is insufficient reliable information about the clinical effects of cocoa for this condition.
• Insect repellent. It is unclear if topical cocoa oil is beneficial as an insect repellent. Details: Preliminary clinical research shows that topical application of cocoa oil, 1 mL on each leg and 0.5 mL on each forearm, reduces bites from black flies (Simulium damnosum) by 99% (41954).
• Isolated systolic hypertension. It is unclear if oral cocoa is beneficial for isolated systolic hypertension. Details: Preliminary clinical research shows that consuming 100 grams daily of cocoa polyphenol-rich dark chocolate might modestly reduce systolic and diastolic blood pressure in elderly patients with isolated systolic hypertension (13166).
• Menopausal symptoms. It is unclear if oral cocoa is beneficial for menopausal symptoms. Details: In postmenopausal individuals aged 50-64 years, preliminary clinical research shows that adding chocolate 10 grams daily, containing cocoa 99%, for 6 months reduces body fat mass by approximately 0.6 kg and body fat percentage by 0.8%, and modestly improves some measures of quality of life, when compared with no treatment (105255,105258). However, there was no effect on all measures of quality of life, general menopausal symptoms, weight, body mass index, or most measures of cognitive function (105255,105258,105259).
• Multiple sclerosis (MS). Although there has been interest in using oral cocoa for MS, there is insufficient reliable information about the clinical effects of cocoa for this condition.
• Muscle strength. Oral cocoa seed extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy males shows that taking a combination product containing cocoa seed extract and pomegranate rind extract 400 mg daily for 8 weeks increases testosterone levels, hand grip strength, and upper arm circumference when compared with placebo (108485).
• Nipple fissures. It is unclear if topical cocoa butter is beneficial for the treatment or prevention of nipple fissures. Details: A small clinical study in breastfeeding adults shows that applying topical cocoa butter to the nipple and areola after each breastfeeding session for 10 days immediately postpartum reduces nipple pain, rashes, and cracks when compared with the topical application of the mother's breastmilk (111525). The validity of this study is limited by a lack of blinding and a high dropout rate.
• Obesity. It is unclear if oral cocoa is beneficial for obesity. Details: Preliminary clinical research in overweight or obese premenopausal females shows that following a reduced-calorie diet in addition to consuming two squares of dark chocolate and drinking 8 ounces of a sugar-free cocoa beverage daily for 18 weeks does not increase weight loss when compared with the reduced-calorie diet plus a non-chocolate snack (42130,99983).
• Parkinson disease. It is unclear if oral cocoa is beneficial for Parkinson disease. Details: Preliminary clinical research shows that consuming a single dose of dark chocolate 200 grams containing approximately 80% cocoa does not improve motor function in patients with Parkinson disease when compared with a white chocolate control, although there seems to be some improvements after one hour when compared with baseline (42156).
• Peripheral arterial disease (PAD). It is unclear if oral cocoa is beneficial for PAD. Details: A small clinical study in patients with PAD shows that drinking a flavanol-rich cocoa beverage 15 grams daily for 6 months increases 6-minute walking distance by up to 43 meters when compared with placebo (103250). Cocoa has also been studied in adults with diabetes at risk for developing PAD, with conflicting results. A small clinical study in adults with and without diabetes shows that taking a single dose of cocoa flavanols 790 mg does not improve peripheral microvascular or macrovascular parameters compared with placebo (111529). However, another small clinical study in healthy adults and those with diabetes at risk for PAD shows that taking cocoa flavanols (CocoaVia, Mars Inc) 1350 mg improves endothelial function in the brachial and femoral arteries after 2 hours when compared with placebo, suggesting that cocoa flavanols might reduce the risk of developing PAD in both populations studied (111528). The validity of this study is limited by the small sample size and short study duration.
• Stroke. It is unclear if dietary cocoa is beneficial for stroke prevention. Details: Population research has found that the highest dietary intake of chocolate is associated with a 16% reduced risk of stroke when compared with the lowest intake (97192). More evidence is needed to rate cocoa for these uses.

(Read more about COCOA)

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

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

(Read more about BEESWAX)

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

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

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CALENDULA)

LIKELY SAFE ...when used orally and appropriately (13161,14306,14307,14308,15655,15752,17187,92271,92274,103247)(103250,108898). However, cocoa naturally contains caffeine, and caffeine may be unsafe when used orally in doses of more than 400 mg daily (11733,98806). While most cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), one cup of unsweetened, dry cocoa powder can contain up to 198 mg of caffeine (100515). To be on the safe side, cocoa should be used in amounts that provide less than 400 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine naturally found in ingredients such as cocoa does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Advise patients to consume cocoa in moderation. ...when used topically. Cocoa butter is used extensively as a base for ointments and suppositories and is generally considered safe (11).

CHILDREN: POSSIBLY UNSAFE
when dark chocolate is used orally. Cocoa and dark chocolate products worldwide contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Children are at increased risk of adverse effects from intake of lead and/or cadmium. There is insufficient reliable information available about the safety of other chocolate-based products that typically contain smaller quantities of cocoa.

PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts. However, due to the caffeine content of cocoa preparations, intake should be closely monitored during pregnancy to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Some research has found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, still birth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts. Caffeine found in cocoa crosses the placenta producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Additionally, high intake of caffeine during pregnancy have been associated with premature delivery, low birth weight, and loss of the fetus (6). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily (2708). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during pregnancy.

LACTATION: POSSIBLY SAFE
when used in moderate amounts or in amounts commonly found in foods. Due to the caffeine content of cocoa preparations, intake should be closely monitored while breastfeeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations. Moderate consumption of cocoa would likely result in very small amounts of caffeine exposure to a nursing infant (6). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

LACTATION: POSSIBLY UNSAFE
when used orally in large amounts. Consumption of excess chocolate (16 oz per day) may cause irritability and increased bowel activity in the infant (6026). Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during lactation.

(Read more about COCOA)

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 BEESWAX)

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

(Read more about CALENDULA)

ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.  Details Human research shows that dark chocolate can inhibit ACE (42112). Additionally, prolonged angioedema in an elderly patient on an ACE inhibitor was precipitated with intake of diabetic chocolate (42049).

ADENOSINE (Adenocard) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.  Details Cocoa contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might increase levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity (6085,17076,41928,41948,41957,41958,41995,42014,42070,42145)(111526) and increase aspirin-induced bleeding time (23800). For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation (111526).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research shows that cocoa can modestly decrease blood pressure in hypertensive and normotensive patients (13166,14306,15655,15752,17187,42059,42092,42107,42137,42143)(42169,103249,109446).

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.  Details Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15). A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported (42075).

CIMETIDINE (Tagamet) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine in cocoa.  Details Cocoa contains caffeine. Cimetidine decreases caffeine clearance by 30% to 50% (15,506).

CONTRACEPTIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in cocoa.  Details Cocoa contains caffeine. Oral contraceptives decrease the rate of caffeine clearance by 40% to 65% (2714,11737).

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from cocoa and increase caffeine levels.

DIPYRIDAMOLE (Persantine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.  Details Cocoa contains caffeine. Caffeine may inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, disulfiram might increase the risk of adverse effects from caffeine.  Details Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance (11840).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, using cocoa with diuretic drugs might increase the risk of hypokalemia.  Details Cocoa contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk for stimulant adverse effects.  Details Cocoa contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,10307).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, estrogens might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Estrogen inhibits caffeine metabolism (2714).

FLUCONAZOLE (Diflucan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, fluconazole might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).

FLUTAMIDE (Eulexin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa might increase the levels and adverse effects of flutamide.  Details Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553).

FLUVOXAMINE (Luvox) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.  Details Cocoa contains caffeine. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal (609,610).

METHOXSALEN (Oxsoralen) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).

METMORPHIN (Glucophage) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, metformin might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571).

MEXILETINE (Mexitil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, mexiletine might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741). Concomitant use might increase the effects and adverse effects of caffeine in cocoa.

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of a hypertensive crisis.  Details Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).

NICOTINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the risk of hypertension.  Details Cocoa contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, cocoa might decrease the effects of pentobarbital.  Details Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOBARBITAL (Luminal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa might reduce the effects of phenobarbital and increase the risk for convulsions.  Details Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital (23558,23559,23561). The exact mechanism of this interaction is unclear.

PHENOTHIAZINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574).

PHENYLPROPANOLAMINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.  Details Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin (23559,23561). The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Quinolones (also referred to as fluoroquinolones) decrease caffeine clearance (606,607,608).

RILUZOLE (Rilutek) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.  Details Cocoa contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use might increase stimulant adverse effects.  Details Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects (11832).

TERBINAFINE (Lamisil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, terbinafine might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Terbinafine decreases the rate of caffeine clearance (11740).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, cocoa might increase the levels and adverse effects of theophylline.  Details Cocoa contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741). Caffeine decreases theophylline clearance 23% to 29% (506).

TIAGABINE (Gabitril) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa tea might increase the levels and adverse effects of tiagabine.  Details Cocoa contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).

TICLOPIDINE (Ticlid) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.

VALPROATE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cocoa might reduce the effects of valproate and increase the risk for convulsions.  Details Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of valproate (23558,23559,23561,37882). However, the exact mechanism of this interaction is unclear.

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, verapamil might increase the levels and adverse effects of caffeine.  Details Cocoa contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

(Read more about COCOA)

(Read more about TEA TREE OIL)

(Read more about USNEA)

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

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

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

(Read more about BEESWAX)

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).

(Read more about CALENDULA)

General ...Orally and topically, cocoa is generally well tolerated.
Most Common Adverse Effects:
Orally: Borborygmi, constipation, diuresis, gastrointestinal discomfort, headaches, and nausea.
Serious Adverse Effects (Rare):
Orally: Tachycardia.

Cardiovascular ...Some cases of increased heart rate have been reported with oral cocoa use (13161,42132).

Dermatologic ...In some cases, when taken orally, cocoa can cause allergic skin reactions (13161). Topically, cocoa butter has occasionally caused a rash. In animals, it has been shown to block pores and cause acne; however, this has not been found in humans (11).

Gastrointestinal ...In human trials, chocolate consumption was associated with a higher incidence of flatulence, irritable bowel syndrome, upset stomach, gastric upset, borborygmi (a gurgling noise made by fluid or gas in the intestines), bloating, nausea, vomiting, and constipation or obstipation (41986,42221,41921,1374,42220,1373,42099,42097,42156,42123,18229,42169,42111). Chocolate consumption has been implicated as a provoking factor in gastroesophageal reflux disease (GERD) (41974,42005,41946,1374). Unpalatability has been reported (42079,42169). Consumption of chocolate and other sweet foods may lead to increased dental caries (42129,42030).

Genitourinary ...In some cases, when taken orally, cocoa can cause increased urination (13161).

Neurologic/CNS ...In some cases, when taken orally, cocoa can cause shakiness and might trigger migraine and other headaches (13161,42169,92271).

Other ...Due to the high sugar and caloric content of chocolate, there is concern about weight gain in people who consume large amounts of chocolate (17187).

(Read more about COCOA)

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).

(Read more about TEA TREE OIL)

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).

(Read more about USNEA)