Propolis Lozenges with Honey by Comvita

POSSIBLY EFFECTIVE

• Burns. Topical application of gauze containing honey seems to improve burn healing. Details: Honey applied directly in gauze applications seems to improve formation of granulation tissue and speed healing time in partial thickness burns. The benefits of honey appear to be comparable to topical antibiotics, including silver sulfadiazine and moisture permeable polyurethane dressing (OpSite) (395,396,397,398,399,14317,55175,55200,55204,55264)(91363,97696). In these studies, honey has been used under dressings or impregnated in gauze as needed for up to 12 weeks. The duration between changing of dressings or gauze has varied (395,396,397,398,399,55175,55200,55204,55264,91363). One small clinical study in adults with moderate burns shows that early surgical intervention with tangential excision and skin grafting appears to improve outcomes when compared with honey (7848). However, poor study design limits the reliability of these findings.
• Cough. Most studies show that oral honey reduces cough in children. It is unclear whether oral honey is beneficial for cough in adults. Details: Clinical research shows that taking honey 2.5-10 mL (0.5-2 teaspoons) at bedtime reduces nighttime cough frequency and severity and improves sleep when compared with placebo in children aged 2 years and older with upper respiratory tract infections (URTIs) (15910,55253,97693,103959). Honey also appears to be at least as effective as the cough suppressant dextromethorphan in typical over-the-counter doses (15910,17299,97693). The effects of honey on cough duration are not known (97693). One clinical study in children 1-5 years of age with URTIs and cough for up to 7 days shows that acacia honey is similarly effective to a honey-flavored placebo, given as 3 mL one hour before bedtime for 2 consecutive nights, for reducing cough frequency and severity and improving sleep (110003). However, this study may have been inadequately powered to detect a difference between groups. A meta-analysis of the available research suggests that honey does not improve cough in adults when compared with usual care (103959). However, due to the small number of available studies, the analysis might have been inadequately powered to detect a smaller magnitude of benefit. Some research in adults has also evaluated honey in combination with other ingredients. In adults with post-infectious cough of at least 3 weeks' duration, taking 25 grams of a paste in a warm water solution providing honey 20.8 grams and coffee 2.9 grams every 8 hours for one week reduces cough frequency by about 93% when compared with baseline. Those taking prednisolone experienced a cough reduction of 20% (91367). It is unclear if this effect is due to honey, coffee paste, or the combination.
• Diabetic foot ulcers. Topical honey seems to be beneficial for diabetic foot ulcers. Details: A meta-analysis of mainly lower quality clinical trials including 267-616 patients with diabetic foot ulcers shows that applying dressings impregnated with honey for 1-2 weeks shortens the wound debridement and healing time and increases the rate of wound healing by moderate to large amounts when compared with other dressings (101032). Individual clinical studies also show that using dressings impregnated with manuka honey (Medihoney Tulle Dressing) or beri honey decreases healing time for diabetic foot ulcers by 11-12 days and reduces the need for antibiotics when compared with saline-soaked gauze (19739,91364,97701).
• Dry eye. Specific manuka honey eyedrops seem to be modestly beneficial for improving symptoms of dry eye. Details: Most clinical research shows that specific honey products might be helpful for symptoms of dry eye (97694,97695,105231,105234). Preliminary clinical research shows that applying a specific manuka honey product (Optimel Manuka Plus Dry Eye Drops, Melcare Biomedical Pty Ltd) 2-3 times daily for 14 or 28 days reduces some, but not all, measures of eye discomfort (97694,105234). In patients with dry eye due to contact lenses, dry eye symptoms were reduced by about 18% when compared with baseline (97694). In patients with general mild dry eye symptoms, preliminary clinical research shows that symptoms were reduced by about 52% when compared with baseline (105234). These improvements were significant when compared with lubricant drops (97694,105234). Specific honey products also seem to be beneficial for dry eye associated with meibomian gland dysfunction. In these patients, preliminary clinical research shows that using Optimel Manuka Plus Eye Drops (Melcare, Biomedical Pty Ltd) or Optimel Antibacterial Manuka Eye Gel (Melcare Biomedical Pty Ltd) twice daily for 3 or 8 weeks along with warm compresses improves the function of the tear glands (97695,105231). In one study, 73% to 95% of participants using the honey products required less lubricant, compared with 48% of participants using warm compresses alone. However, the honey products did not improve bacterial counts, redness, or dryness (97695). In another study, eye dryness, lid margin, conjunctival redness, and meibomian gland function were modestly improved when compared with baseline. All improvements were statistically similar to the control group receiving a lubricant. However, patients using a lubricant did not experience an improvement in eye dryness when compared to baseline (105231).
• Herpes labialis (cold sores). Applying honey to cold sores may heal lesions 2-4 days faster than conventional therapies. Details: A meta-analysis of three clinical trials, including one relatively large study, in patients with herpes labialis shows that applying honey to lesions 4-5 times daily reduces lesion healing time by around 2 days, although it does not improve pain when compared with acyclovir 5% cream (108526). Also, a small crossover trial in patients with recurrent cold sores shows that applying medical grade honey three times daily to lesions at the onset of symptoms or blistering reduces lesion healing time by around 4 days and improves symptoms such as pain and itching when compared with conventional treatments, which ranged from prescription antivirals to herbal remedies and wound care products (108527).
• Herpetic gingivostomatitis. Slowly swallowing honey seems to be beneficial for herpetic gingivostomatitis treatment in children. Details: Clinical research in children aged 2-8 years with primary herpetic gingivostomatitis shows that use of a local honey 5 mL every 4 hours with slow swallowing, in combination with acyclovir 15 mg/kg five times daily for 7 days, results in the clearing of oral lesions 3 days faster when compared with acyclovir and a placebo syrup. Drooling and difficulties eating also improved faster, and pain and the need for analgesics were reduced. Fever and extra-oral lesions were not improved (101038).
• Oral mucositis. Rinsing the mouth with and then slowly swallowing honey seems to be beneficial for oral mucositis prevention or treatment, although most research is lower quality. Details: Although contradictory evidence exists (55219,91361), most research shows that honey may have some benefit in preventing or reducing symptoms of oral mucositis (16352,55133,55137,55202,55241,55245,55265,91368,97704,104562). A meta-analysis of eight trials shows that applying honey reduces the development of intolerable oral mucositis lesions by approximately 52%. Applying honey to lesions also appears to reduce pain associated with oral mucositis; however, the number of studies included in this latter analysis was small (101035). Another meta-analysis suggests that pure natural honey may be more effective than manuka honey or local honey for treating oral mucositis (101034). However, these analyses have significant quality issues. They included studies that did not fit inclusion criteria and omitted studies that did fit inclusion criteria (103967). The majority of these studies have had patients rinse with and then slowly swallow up to 20 mL honey three times or more daily, usually before radiation therapy, 15 minutes after radiation therapy, and 6 hours after radiation therapy or at bedtime. Some studies have used honey topically or as ice chips or lozenges (16352,55133,55137,55202,55219,55241,55265,91361,97704,101034)(101035,104562). Also, rinsing the mouth and swallowing a paste of honey or honey and coffee 10 mL every 3 hours for one week has been used (91368). Preliminary clinical research in patients undergoing chemoradiation and using conventional treatments shows that a combination of licorice powder 5 grams mixed in honey and applied twice daily along with oral licorice powder 500 mg twice daily for 6 weeks also seems to reduce the risk of oral mucositis and severe symptoms when compared with conventional treatments alone (104562). However, it is not clear whether any benefit in this study is due to honey, licorice, or the combination. In pediatric intensive care patients aged 2-16 years, preliminary clinical research shows that applying a local honey, 1-1.5 grams/kg in two divided doses, with a spoon to the inside of the mouth, teeth, lips, and tongue, reduces the severity and development of oral mucositis when compared with using chlorhexidine. However, honey was not as effective as topical vitamin E (101036).
• Rosacea. Topical honey seems to be beneficial for rosacea. Details: Clinical research in adults shows that applying a 90% medical-grade kanuka honey (Honevo) with glycerin to affected areas twice daily for 8 weeks and washed off after 30-60 minutes is more effective than Cetomacrogol, an emollient, for improving symptoms of rosacea. Approximately twice as many patients responded to the honey product when compared with Cetomacrogol cream (97699).
• Wound healing. Topical honey seems to improve the healing of various types of wounds, although the optimal formulation and application regimen remains unclear. Details: Several small clinical trials and case reports describe the use of honey or honey-impregnated dressings for various types of wounds, including post-surgical wounds, chronic leg ulcers, abscesses, burns, abrasions, lacerations, and skin graft donor sites. Honey seems to improve granulation and epithelialization, reduce odors and purulent exudate, help clean the wound, increase eradication of infection, reduce pain, and decrease time to healing (7847,7849,14317,16354,16355,16357,16358,16360,16362,16369)(16372,16374,55109,55130,55144). Meta-analyses of clinical research show that applying honey reduces healing time of partial thickness burns by 4.7 days when compared with conventional dressing and about 5 days when compared with silver sulfadiazine. Honey also appears to improve healing time for postoperative wounds when compared with antiseptic washes followed by gauze (55264). In some reports, wounds healed with honey after failing previous treatments (16369,16371). Honey applied directly to wounds appears to be comparable to hydrogels such as carboxymethylcellulose, povidone iodine, and hypochlorite solutions (16355,16358,16360,16376,55235). Honey dressings also appear to be comparable to hydrocolloid dressings, paraffin gauze, nanocrystalline silver, and saline-soaked gauze (16358,16360,16372,55101). However, poor study design limits the reliability of some of these findings. Trials cannot be directly compared due to variation in wound type and severity, patient characteristics, honey type and processing, dressing techniques, treatment duration, and concomitant use of antibiotics. Adequate blinding is also difficult to achieve due to the distinctive properties and smell of honey (16360). Many of the clinical trials used manuka honey, which is derived from the nectar of Leptospermum scoparium and is gamma irradiated to inactivate bacterial spores (16355,16357,16362,16369,16371). Other trials used unprocessed honey (16358,16372). Honey dressings are typically changed every 24-48 hours, although in some cases dressings are changed only twice weekly (16355,16362,16372,16374,55101,55130,55235). In children aged 2 months to 14 years, honey soaked gauze has been packed into wounds twice daily until closure (16376). When used directly, unprocessed honey or manuka honey 15-30 mL has been applied and covered with sterile gauze and bandages or a polyurethane dressing. When applied directly, honey is typically used every 12-48 hours, although in some cases it has been used only once weekly (16354,16358,16369,16372,16376,55144).

POSSIBLY INEFFECTIVE

• Acne. Topical honey does not seem to be beneficial for acne. Details: Clinical research in adolescents and adults 16 years of age and older shows that applying a 90% medical-grade kanuka honey (Honevo) with glycerine to the face twice daily after using an antibacterial soap does not improve facial acne when compared with antibacterial soap alone (97700).
• Hyperlipidemia. Oral honey does not seem to improve lipid levels in patients with hyperlipidemia. Details: A meta-analysis of 15 small clinical studies in patients with hyperlipidemia shows that taking honey 20-75 grams daily for up to 4 months does not reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride levels when compared with control (108533).
• Rhinosinusitis. Intranasal honey does not seem to be beneficial for improving symptoms of chronic rhinosinusitis. Details: A small clinical study in adults who have undergone maximal medical and surgical treatment for allergic fungal rhinosinusitis shows that using 2 mL of an intranasal spray containing honey 50% in saline once daily at night for 30 days does not reduce symptoms when compared with usual treatment (55216). Manuka honey nasal spray also does not seem to work better than saline spray in adults with chronic rhinosinusitis. A small clinical study shows that manuka honey 10% (Medihoney, Derma Sciences) in saline sinus irrigation twice daily for 30 days is no more effective than saline irrigation for reducing overall symptoms (97705). Additionally, a small clinical study in patients with recalcitrant chronic rhinosinusitis shows that using manuka honey 16.5% twice daily augmented with 1.3 mg/mL methylglyoxal sinonasal rinses for 14 days is no better than taking targeted oral antibiotics and performing normal saline rinses twice daily (103969). However, this study was not adequately powered to detect a difference between treatment groups. Additional research is needed to determine if honey-containing nasal sprays are beneficial in circumstances with limited access to antibiotics or nasal steroids, or in patients with high immunoglobulin E (IgE) levels (55216,97705). Intranasal honey has also been evaluated in patients recovering from surgery for rhinosinusitis. A small clinical study in adults with chronic rhinosinusitis who have undergone endoscopic sinus surgery shows that applying 2 mL of Tualang honey to the nasal dressing, which remains in place for one week, results in similar improvements in symptoms when compared with a triamcinolone-containing dressing at 7, 14, and 28 days after surgery. However, at 3 months after surgery, triamcinolone seems to provide further improvement in rhinosinusitis symptoms and surgical recovery when compared with honey (108529).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral honey is beneficial for hay fever. Details: Preliminary clinical research shows that consuming honey one tablespoon (20 grams) daily, in addition to standard treatment, does not improve allergy symptoms (14319). Other preliminary clinical research shows that ingesting honey 1 gram/kg daily for 4 weeks, in addition to taking loratadine 10 mg daily, may improve allergic symptoms during treatment and for up to 4 weeks following cessation of treatment. However, it's not clear if this improvement is significant when compared with loratadine alone (91360).
• Alveolar osteitis. It is unclear if oral honey is beneficial for alveolar osteitis. Details: A small, low-quality clinical study in patients with alveolar osteitis after dental surgery shows that applying gauze soaked in 2 mL of honey, 3 times over 10 days, improves healing, pain, and formation of granulation tissue when compared with baseline (103961).
• Asthma. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking a combination of honey and black seed modestly improves measures of lung function when compared with baseline in patients with moderate to severe asthma. However, another preliminary clinical study using this combination did not show improvement on all measures. Both studies were small and may not have been adequately powered to detect a difference in outcomes (105228). Other preliminary clinical research shows that taking a combination of honey and celery seed modestly improves some measures of lung function when compared with baseline (105228). It is unclear whether any benefit is due to honey, the other ingredient, or the combinations. Additionally, the validity of these studies is limited by the lack of a comparator group.
• Athletic performance. Although there is interest in using oral honey to improve athletic performance, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Atopic dermatitis (eczema). It is unclear if topical honey is beneficial for atopic dermatitis. Details:In patients with bilateral atopic dermatitis, a small preliminary clinical trial shows that topical application of manuka honey to one site overnight for 7 days improves lesions when compared to baseline (105239). The validity of this finding is limited by the lack of a placebo comparator group.
• Blepharitis. It is unclear if topical honey is beneficial for blepharitis. Details: A small clinical study in patients with blepharitis shows that applying MGO Manuka Honey microemulsion (Manuka Health New Zealand Ltd) eye cream to closed eyelids nightly for 3 months improves symptoms of dry eye and reduces ocular mites and bacterial load when compared with no intervention (103962). The validity of this finding is limited by the lack of a placebo comparator group.
• Cataracts. Although there is interest in using topical honey for cataracts, there is insufficient reliable information about the clinical effects of honey for this condition.
• Catheter-related infections. It is unclear if topical medical honey is beneficial for preventing catheter-related infections in patients on hemodialysis or in those with diabetes. Details: Preliminary clinical research shows that manuka honey (Medihoney, Medihoney Pty Ltd) applied three times weekly to the exit sites of tunneled, cuffed central venous hemodialysis catheters is as effective as mupirocin ointment in reducing the incidence of catheter-associated infection and bacteremia. It may also be associated with a lower rate of bacterial resistance than mupirocin (16361). A retrospective analysis also found that use of povidone iodine for dialysis catheter site care is associated with a 58% increased cumulative incidence rate of exit-site infections or peritonitis when compared with use of medical honey. Patients were followed from catheter insertion until catheter removal, transplant, death, or end of treatment (101039). However, well-designed clinical research shows that application of antibacterial honey (Medihoney Antibacterial Wound Gel, Comvita) 10 mg at the exit site along with standard care is no more effective than standard care alone for reducing dialysis-related infections (91362). It is unclear if honey reduces the risk of catheter-related infection in patients with diabetes. Some evidence shows that applying an antibacterial honey product approximately doubles the risk of infection and peritonitis in patients with diabetes when compared with no honey (91362). However, a large retrospective analysis found that exit-site application of honey was associated with a lower chance of peritoneal dialysis-related infection when compared with povidone iodine, even in patients with diabetes (101039).
• Chemotherapy-related fatigue. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with breast cancer and chemotherapy-related fatigue shows that taking a specific product (Jollab tonic beverage) containing honey, saffron, and rose water, as 20 mL three times daily for 4 weeks, reduces scores on a cancer fatigue scale when compared with placebo. Scores on a visual analog fatigue scale and on a fatigue severity scale were only improved when compared with baseline, not placebo (110001).
• Corneal opacity. Although there is interest in using topical honey for corneal opacity, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Corneal ulceration. It is unclear if honey-containing ophthalmic drops are beneficial for corneal ulceration. Details: A small clinical study in patients with foreign body-induced corneal ulceration shows that applying ophthalmic drops containing honey into the affected eye every 6 hours for 14 days might speed up healing of corneal epithelial defect, but does not improve corneal infiltration, when compared with using ciprofloxacin eye drops. The honey in these drops was produced from the nectar of various ziziphus species (103968). The validity of this study is limited by its small size and short duration.
• Diabetes. It is unclear if oral honey is beneficial for diabetes. Details: In patients with type 2 diabetes, small clinical trials show that taking honey 50 grams or 1-2.5 grams/kg daily for 8 weeks increases glycated hemoglobin (HbA1c) levels by a small amount (55182,105235). However, lower doses of 5-25 grams daily for 16 weeks or 0.5 grams/kg daily for 12 weeks seem to have no effect on HbA1c and may modestly reduce levels when compared to baseline or no treatment (105230,105236). Also, although some research disagrees, taking honey does not seem to affect fasting levels of insulin or glucose, or measures of insulin resistance (105230,105235,105236). There is conflicting evidence regarding the effects of honey on lipid levels in patients with diabetes. Some preliminary clinical research shows that consuming honey 0.5-2.5 grams/kg daily modestly decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and modestly increases high-density lipoprotein (HDL) cholesterol (55182,105230), while other research does not show any effect on plasma lipids (105236). In patients with type 1 diabetes, one clinical study shows that taking honey 0.5 mL/kg daily for 12 weeks decreases fasting blood glucose, total cholesterol, triglycerides, and LDL cholesterol when compared with control (55263).
• Diabetic neuropathy. It is unclear if oral honey is beneficial for diabetic neuropathy. Details: In patients with mild to moderate diabetic neuropathy who are taking antidiabetes medications and gabapentin, preliminary clinical research shows that taking honey 0.5 gram/kg daily in water for 3 months modestly reduces nerve pain and improves quality of life when compared with baseline. Nerve conduction was generally not affected (105230). The validity of this study is limited by the lack of an appropriate control group.
• Diarrhea. Small clinical studies suggest that oral honey is beneficial in children and infants with diarrhea. Details: One small clinical study in children and infants with gastroenteritis shows that adding honey to oral rehydration solution (ORS) at a concentration of 50 mL per liter ORS decreases the frequency of vomiting and diarrhea, and reduces recovery time when compared with ORS alone (55194). Other clinical research shows that adding honey to ORS at the same concentration reduces the duration of diarrhea by about 1.4 days when compared with standard ORS in infants and children with bacterial gastroenteritis, but not when all types of gastroenteritis are considered (55273). Another small clinical study in children hospitalized with acute diarrhea shows that taking 1.5-2 mL of honey every 6 hours for 5 days plus 5 mL of zinc gluconate syrup, providing 5 mg of elemental zinc, every 6 hours for 10 days reduces the duration of diarrhea by 6.5 hours and the duration of hospitalization by 24 hours when compared with zinc gluconate alone (108534).
• Dry mouth. It is unclear if oral honey is beneficial for dry mouth associated with intubation. Details: Preliminary clinical research in a small group of intubated adults in an intensive care unit shows that applying Indonesian honey 20 mL to all areas of the mouth with a brush and gauze swab twice daily for 3 days, in addition to standard oral care with 20 mL chlorhexidine gluconate 0.2%, improves overall oral health scores on a modified Beck Oral Assessment Scale when compared with chlorhexidine alone (110002).
• Dysmenorrhea. It is unclear if oral honey is beneficial for dysmenorrhea. Details: Preliminary clinical research shows that taking honey 1.2 mg/kg daily, starting on the 15th day of the menstrual cycle and continuing until the onset of menstruation, is comparable to mefenamic acid 250 mg every 6 hours for reducing pain associated with dysmenorrhea (97702).
• Gingivitis. It is unclear if chewing "leather" made from manuka honey is beneficial for gingivitis. Details: Preliminary clinical research shows that chewing "leather" made from manuka honey after meals for 21 days reduces plaque severity and the number of bleeding sites when compared to baseline in patients with gingivitis and plaque (55091).
• Hemorrhoids. Topical honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a spoonful of a mixture containing equal volumes of honey, olive oil, and beeswax to the skin twice daily for up to 4 weeks reduces bleeding and itching when compared to baseline in patients with hemorrhoids (34100). It is not clear if these effects are due to honey, the other ingredients, or the combination.
• Genital herpes. It is unclear if topical honey is beneficial for genital herpes. Details: Preliminary clinical research shows that applying a gauze soaked with honey four times daily to the lesion until healing does not improves symptoms or healing time (55095).
• Impaired glucose tolerance (prediabetes). It is unclear if oral honey is beneficial for prediabetes. Details: Preliminary clinical research shows that taking honey does not improve glycemic control or lipid levels in patients with prediabetes. In one study, taking honey (Dutch Gold Honey) providing 50 grams of carbohydrates daily for 2 weeks does not improve these measures when compared with sucrose or corn syrup providing similar amounts of carbohydrates (105238). In another study, taking Malaysian Kelulut honey (Bayu Kelulut) 30 grams daily for 30 days was not beneficial (105237). The validity of these studies is limited by the lack of an appropriate control group.
• Leishmania lesions. It is unclear if topical honey is beneficial for leishmania lesions. Details: Some research shows that honey might prevent the healing of leishmania lesions. One preliminary clinical study shows that applying honey-soaked gauze onto leishmania lesions twice daily for 6 weeks in addition to receiving a glucantime injection reduces the proportion of patients with healed wounds by about 28% when compared with glucantime injection alone (55118).
• Male infertility. Intravaginal honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying 10 mL of a combination mixture containing various bee products intravaginally immediately before or after each coital act, beginning one day after the last menstruation and continuing for three menstrual cycles or until pregnancy, increases pregnancy rate from 3% to 8% when compared to standard intrauterine insemination in couples having difficulty getting pregnant due to male asthenozoospermia. However, since all unsuccessful couples were crossed over to the alternative treatment after 2 months, the causality of successful pregnancy is unclear. The mixture consisted of Egyptian bee honey 100 grams, royal jelly 3 grams, and bee bread 1 teaspoon, which was diluted in saline in a 1:1 ratio prior to application (55131).
• Malnutrition. It is unclear if oral honey is beneficial for malnutrition in children. Details: Preliminary clinical research in infants and children with a mean age of 11-13 months with protein-energy malnutrition (PEM) shows that honey improves weight and other biomarkers when compared to control. Honey 2 mL/kg diluted in water was used daily for 2 weeks in combination with conventional nutritional rehabilitation (55196,55210).
• Menopausal symptoms. It is unclear if oral honey is beneficial for metabolic control in postmenopausal individuals. Details: In postmenopausal individuals, preliminary clinical research shows that taking Tualang honey 20 grams daily for 4 months results in a slight increase in low-density lipoprotein (LDL) cholesterol and fasting blood sugar when compared with baseline. However, there were no statistically significant differences in lipid profile, glycemic control, or bone density when compared with low-dose hormone replacement therapy (105241). The validity of this study is limited by its short duration and lack of blinding.
• Necrotizing fasciitis. It is unclear if topical honey is beneficial for necrotizing fasciitis. Details: Preliminary clinical research has shown conflicting results with the use of honey, applied directly and covered with a dressing or applied as a honey-soaked gauze, given as an adjunct to antibiotics, for the treatment of Fournier's gangrene, a type of necrotizing fasciitis (55106,55293,55295,55315,91363).
• Obesity. It is unclear if oral honey is beneficial for metabolic control in adolescents with obesity. Details: Preliminary clinical research in obese prepubertal females on a calorie-reduced diet shows that consuming a wild flower and thyme honey product (Attiki) 15 grams daily for 6 months does not improve levels of glucose, insulin, or blood lipids when compared with a marmalade control (101037).
• Osteoarthritis. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults 40-85 years of age with knee osteoarthritis shows that taking a specific product (G-rup syrup, Yas Daru Pharmaceutical Co.) containing honey 150 mg/mL and ginger extract 100 mg/mL in a dose of 30 mL twice daily for 12 weeks reduces pain scores on a visual analog scale and improves scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) when compared with baseline. Total WOMAC scores decreased by about 7 in the active group and by 4 in the placebo group (110000). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Additionally, it is unclear whether these changes would be considered clinically significant.
• Peptic ulcers. Although there is interest in using oral honey for peptic ulcers, there is insufficient reliable information about the clinical effects of honey for this condition.
• Postoperative pain. Several small clinical studies suggest that topical honey may reduce pain after tonsillectomy in children and adults. Details: A meta-analysis of low-quality clinical research in children 3 years and older immediately post-tonsillectomy shows that honey might reduce pain, analgesic use, and night-time awakening by a small to moderate amount in the week after surgery when compared with placebo or control. In these studies, honey was used in doses ranging from 4-15 mL every hour or once daily for 1-7 days (97703). A small observational cohort in adults post-tonsillectomy has found that applying honey 20 grams to the oral cavity for 5 minutes, 8 times daily for the first 5 days after surgery, is associated with reduced pain and bleeding when compared with usual treatment (103963). Another small clinical trial in adults post-tonsillectomy shows that gargling and then swallowing a solution containing 15 mL of honey mixed with 5 mL of water for two minutes every 6 hours for 10 days reduces pain and analgesic use when compared with placebo or no treatment (108530).
• Pressure ulcers. It is unclear if topical honey is beneficial for pressure ulcers in children. Details: Preliminary clinical research in critically ill children aged 2 months to 17 years shows that use of a manuka honey dressing reduces the median time to complete healing of pressure ulcers by approximately 2 days when compared with standard wound care. In addition, complete healing was about 1.9 times more likely in children given the honey dressing. However, there were no differences in the proportion of children with complete healing or treatment failure, or in the duration of stay in the ICU or hospital (105229).
• Pruritus. It is unclear if topical honey is beneficial for pruritus due to intertrigo. Details: Preliminary clinical research shows in adults with intertrigo that applying a honey cream (Medihoney Barrier Cream, Derma Sciences, Inc.) topically twice daily for 21 days reduces pruritus complaints when compared with zinc oxide ointment (55258).
• Radiation dermatitis. It is unclear if topical honey is beneficial for treating radiation dermatitis. Details: Clinical research shows that applying honey gauze (HoneySoft) once daily to radiation-induced skin wounds does not increase the speed of wound healing when compared with paraffin gauze in patients with severe radiation-induced dermatitis (55105).
• Radiation-induced esophagitis. It is unclear if topical honey is beneficial for radiation-induced esophagitis. Details: In patients with radiation esophagitis, preliminary clinical research shows that taking liquid manuka honey 10 mL or honey lozenges providing 10 mL of dehydrated manuka honey four times daily for 4 weeks does not improve pain on swallowing when compared with standard supportive care. However, only 14% of patients using liquid honey reported opioid use, compared with 37% of those given only supportive care (97698).
• Sinonasal polyposis. It is unclear if intranasal honey is beneficial in patients recovering from surgery for sinonasal polyposis. Details: A small clinical study in patients recovering from sinus surgery for nasal polyposis shows that intranasal irrigation with a diluted processed honey spray four times daily starting the day after surgery does not improve healing or reduce polyp recurrence when compared with normal saline irrigation (108528).
• Sunburn. Although there is interest in using topical honey for sunburn, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Tooth extraction. It is unclear if topical honey is beneficial for wound healing after tooth extraction. Details: A small clinical study in children that had a tooth extraction shows that applying a thin layer of Iranian Kurdistan Mountains honey with a cotton swab and keeping the swab in place for 45 minutes seems to reduce wound size more rapidly when compared with using normal saline (103966). The validity of this finding is limited because a large percentage of study participants were excluded from the final analysis.
• Vaginal candidiasis. It is unclear if intravaginal honey is beneficial for vaginal candidiasis. Details: In patients with vulvovaginal candidiasis, preliminary clinical research shows that applying 5 grams of a vaginal gel containing honey 50% nightly for 8 days is as effective as the same amount of clotrimazole 1% cream for reducing burning and sensitivity and improving culture results. Honey also reduces vaginal discharge in almost twice as many patients as those using clotrimazole (105227). More evidence is needed to rate honey for these uses.

(Read more about HONEY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Lemon has only been evaluated in combination with quince in a nasal spray for hay fever; its effect when used alone is unclear. Details: A small clinical study in patients with grass pollen allergy shows that using a specific nasal spray (Gencydo, Weleda AG) containing lemon and quince three times daily for 7 days does not improve the symptoms of allergic rhinitis when compared with placebo. In this study, using the nasal spray reduced airway resistance during inspiration at 10 and 20 minutes after pollen exposure, and reduced airway resistance during expiration at 20 minutes after pollen exposure (98826).
• Anxiety. It is unclear if aromatherapy with lemon essential oil reduces test anxiety. Details: A small clinical study in first year nursing students in Turkey shows that administering aromatherapy with lemon essential oil for 15 minutes prior to an exam reduces test anxiety scores when compared with control students (110779). However, it is unclear whether any improvements are clinically significant or lead to improved test scores.
• Halitosis. Lemon essential oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Preliminary research in males with dementia in a long-term care facility shows that cleaning the tongue, gums, and teeth with a solution of lemon, peppermint, and tea tree essential oils twice daily for 7 days improves oral condition, measured on the Korean Oral Assessment Guide scale, increases salivary pH into the normal range, and decreases halitosis score when compared with saline control. On a scale of 0 to 5, the essential oil mixture reduced the halitosis score by 1.24 points, compared with 0.2 points for the control (112957).
• Hypertension. It is unclear if oral lemon is beneficial in patients with high blood pressure. Details: A small, prospective, population study in middle-aged Japanese women has found that increased lemon intake is associated with a modest reduction in systolic, but not diastolic, blood pressure (93471).
• Kidney stones (nephrolithiasis). It is unclear if oral lemon juice is beneficial for recurrent idiopathic calcium oxalate nephrolithiasis. Details: A randomized, controlled trial in patients with recurrent idiopathic calcium oxalate nephrolithiasis shows that taking fresh lemon juice 60 mL orally twice daily for 2 years with a standard diet does not improve the time to stone recurrence when compared with no supplementation. The validity of these findings is limited due to poor patient adherence, which declined from 79% at 6 months, to 68% at 1 year, and 48% at 2 years. When restricted to a 1-year follow-up, stone recurrence occurred in 10% of patients taking lemon juice, compared with 21% of patients in the control group; this difference was statistically significant (107489).
• Meniere disease. Although there is interest in using lemon orally for Meniere disease, there is insufficient reliable information about the clinical effects of lemon for this condition.
• Myocardial infarction (MI). It is unclear if aromatherapy with lemon essential oil is beneficial in patients with acute MI. Details: A small clinical study in hospitalized patients with acute MI shows that administering aromatherapy with lemon essential oil over 3 days moderately reduces systolic blood pressure, but not diastolic blood pressure, when compared with a paraffin control. Heart rate and anxiety were reduced by a small amount the day following the completion of lemon aromatherapy (103455).
• Nausea and vomiting. It is unclear if aromatherapy with lemon oil is beneficial in palliative care patients with nausea and vomiting. Details: A small observational study in hospitalized palliative care patients with advanced cancer has found that administering aromatherapy with lemon oil pads relieves nausea and vomiting in 73% of applications (110778). The interpretation of these findings is limited by the use of a retrospective chart review and the lack of a comparator group.
• Obesity. Although there is interest in using lemon orally for obesity, there is insufficient reliable information about the clinical effects of lemon for this condition.
• Oral mucositis. Lemon has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A randomized, controlled trial in patients with head and neck cancer receiving external beam radiotherapy 5 days weekly shows that using a 2:1 oral honey-lemon throat spray four to eight times daily, beginning 1 day prior to radiotherapy initiation and continuing for 5 weeks, does not improve severity of mucositis when compared with oral benzydamine hydrochloride throat spray applied four to eight times daily. The actual rate of oral mucositis occurrence is 65% in those receiving the honey-lemon spray, compared with 35% with the benzydamine hydrochloride spray; however, this difference was not statistically significant (107487). This study may have been inadequately powered to detect a difference between groups. Also, the validity of these findings is limited due to the lack of objective outcome measures.
• Postoperative nausea and vomiting (PONV). It is unclear if aromatherapy with lemon essential oil is beneficial in patients with PONV. Details: Preliminary research in patients undergoing lower extremity fracture surgery shows that aromatherapy with lemon essential oil started the morning of surgery, then every 2 hours to the end of surgery, in the recovery room, and 16 hours after surgery reduces the frequency, severity, and amount of PONV, and the frequency of anti-emetic drug administration after surgery, when compared with control. The intensity of pain is also reduced, but not the amount of post-operative opioid needed (112956).
• Pregnancy-induced nausea and vomiting. It is unclear if aromatherapy with lemon essential oil is beneficial in patients with nausea and vomiting due to pregnancy. Details: A small clinical study in pregnant patients shows that practicing aromatherapy with 2 drops of lemon essential oil placed on a cotton ball as needed modestly reduces pregnancy-induced nausea and vomiting on 2 of 4 days of the study when compared with placebo (93475).
• Radiation-induced sialadenitis. Aromatherapy with lemon essential oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: A small clinical study in patients with thyroid cancer shows that receiving 10-minute aromatherapy baths with lemon and ginger essential oils prior to meals for 2 weeks before treatment with radioactive iodine therapy attenuates damage to the salivary gland when compared with distilled water baths (98129).
• Respiratory tract infections. Although there is interest in using lemon orally for respiratory tract infections such as cold and flu, there is insufficient reliable information about the clinical effects of lemon for these conditions. More evidence is needed to rate lemon for these uses.

(Read more about LEMON)

LIKELY EFFECTIVE

• Irritable bowel syndrome (IBS). Oral enteric-coated peppermint oil is conditionally recommended by the American College of Gastroenterology (ACG) for the relief of global IBS symptoms, such as abdominal pain. Details: The ACG conditionally recommends the use of peppermint for the relief of global IBS symptoms. This recommendation is based on an available meta-analysis of generally low-quality clinical research (105124). Several clinical trials and meta-analyses show that taking enteric-coated peppermint oil 1-2 capsules orally two to four times daily reduces abdominal pain, distention, flatulence, and bowel movements in patients with IBS. Each capsule provides approximately 0.2 mL of peppermint oil or 180-225 mg peppermint oil. Most trials have used specific products (Colpermin, Tillotts Pharma; Mintoil, Cadigroup; Ibgard, IM HealthScience, Tempocol) (3802,3803,4469,11778,11779,17681,17682,68467,68515,68522)(68603,68604,68605,96360,99493,109980). The most recent meta-analysis to date shows that four patients would need to take peppermint oil to prevent one patient from having persistent IBS symptoms, and seven patients would need to take peppermint oil to prevent one patient from having abdominal pain. However, the individual studies included in the analysis lasted no more than 12 weeks (109980); any long-term effects are unclear. Although most studies have shown benefit for reducing symptoms, some older studies have found no significant effect (11777,11789) or only short-term benefits (68620). Also, a well-designed study shows that taking peppermint oil capsules designed for either small intestinal release (enteric-coated) or ileocolonic release does not increase the number of people with at least a 30% decrease in abdominal pain over a period of 4 weeks, although symptoms are modestly reduced when compared with placebo (102602). Another clinical trial in patients with moderate to severe IBS shows that taking a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) 180 mg three times daily for 6 weeks does not further improve symptom severity when compared with placebo. However, both groups experienced a large improvement on the IBS-Severity Scoring System (IBS-SSS) and the IBS Global Improvement Scale (107955). The validity of these findings is limited due to lost data and inconsistent follow-up; additionally, adverse effects occurred more frequently in the peppermint oil group. The reasons for these negative findings are unclear but may include short treatment durations and the use of different formulations; additionally, IBS is comprised of various subtypes and symptoms that can range in severity and presentation, which may alter treatment response. Some clinical research has also evaluated a specific combination product (Atrantil, KBS Research) containing peppermint leaf, red quebracho extract, and conker tree extract. Taking this product as needed for 2 weeks seems to reduce constipation and bloating when compared to baseline in patients with constipation-predominant IBS (95429,95430). It is unclear if the effects of this product are due to peppermint, the other ingredients, or the combination.

POSSIBLY EFFECTIVE

• Barium enema-related colonic spasm. Rectal peppermint, as part of barium enema preparations, seems to reduce colonic spasms during examination. Oral peppermint also seems to be beneficial. Details: Rectal use of peppermint oil, added as an ingredient in barium enema preparations, seems to relax the colon during barium enema examination and reduce the percentage of patients who experience colonic spasms by about 25% to 30% (6739,6749,12009). Adding peppermint oil to the barium enema seems to be at least as effective as using systemic scopolamine (Buscopan). Adding peppermint oil to the barium solution also does not seem to impair image quality (12009). Some clinical research also shows that taking peppermint oil orally before the start of a double-contrast barium enema examination decreases spasms and might also increase diagnostic quality (14467).
• Chemotherapy-induced nausea and vomiting (CINV). Oral and inhaled peppermint seem to reduce nausea and vomiting in patients with CINV. Details: Clinical research shows that adding peppermint oil, 40 drops in 20 mL water, every 8 hours following chemotherapy treatment to treatment with standard antiemetics reduces the severity of nausea, vomiting, and anorexia by moderate to large amounts over 48 hours when compared with a plain water placebo (105123). The use of peppermint oil aromatherapy has also been investigated. Clinical research shows that adding 2 drops of peppermint oil to a cool, damp washcloth for use on the neck as aromatherapy for about 30 minutes helps relieve chemotherapy-induced nausea by a small amount when compared with a washcloth without peppermint oil (102603). Additional clinical research in patients receiving standard antiemetics after chemotherapy shows that applying one drop of peppermint oil below the nose three times daily for 5 days reduces the severity of nausea and the frequency of nausea, vomiting, and retching by a moderate to large amount when compared with the antiemetics alone. These parameters were not improved following treatment with cisplatin (105122). In children with acute leukemia, a small clinical study shows that aromatherapy with 2 drops of peppermint oil and 3 drops of lemon oil in 80 mL of water diffused 30 minutes prior to and 2 and 4 hours after chemotherapy once weekly for 4 weeks decreases the severity of nausea, vomiting, and retching, and improves quality of life scores when compared with diffused water or no intervention (112015). The validity of these findings is limited by the use of patient-reported outcomes.
• Dyspepsia. Oral peppermint, in combination with caraway and possibly other ingredients, seems to reduce symptoms of dyspepsia. It is unclear if oral peppermint alone is beneficial. Details: Some clinical research shows that taking specific products containing peppermint and caraway oil (Enteroplant, Dr Willmar Schwabe Pharmaceuticals; Menthacarin, Dr Willmar Schwabe GmbH & Co.) improves quality of life and reduces symptoms of dyspepsia, including feelings of fullness, pain, and mild gastrointestinal spasms (6740,6741,10075,96344,102600). A meta-analysis of three of these clinical studies shows that taking this combination product 2-3 times daily for 4 weeks modestly reduces abdominal pain when compared with placebo (110091). Taking this combination twice daily for 4 weeks also improves postprandial distress syndrome and epigastric pain syndrome, two subtypes of dyspepsia, when compared with placebo (96344). The combination of enteric-coated peppermint oil 90 mg and caraway oil 50 mg appears to be comparable to cisapride for relieving dyspepsia when taken 2-3 times daily for up to 4 weeks (6740,6741,10075). However, most trials investigating this combination are small and/or of overall low quality (102600). A specific combination product containing peppermint leaf (Iberogast, Steigerwald Arzneimittelwerk GmbH) also seems to improve symptoms of dyspepsia. The combination includes peppermint leaf plus clown's mustard plant, German chamomile, caraway, licorice, milk thistle, angelica, celandine, and lemon balm (7049). A meta-analysis of studies using this combination product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces the severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). A similar combination product containing extracts from peppermint leaf, clown's mustard plant, German chamomile flower, caraway, licorice root, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH) 1 mL taken three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more dyspepsia patients when compared with placebo (12724).
• Endoscopy-associated adverse effects. Intraluminal peppermint seems to reduce spasticity during an endoscopy. It is unclear if oral peppermint is beneficial for reducing adverse effects related to endoscopy. Details: A meta-analysis of four clinical trials show that peppermint oil, administered orally or intraluminally, reduces the incidence of spasticity by about 41% when compared with placebo in patients undergoing endoscopy, with severe spasticity occurring at about 30% the rate of those taking placebo. However, there was no effect on subjective pain (102604). Individual clinical studies show that intraluminal peppermint oil can reduce both pain and spams in patients undergoing endoscopy (18220,68371,68395,68445,68532). However, there are limitations with this form of administration, including cost and practicality, which has led to interest in the use of oral formulations (104221). Studies evaluating oral extended-release peppermint have been conflicting. While one study shows that a specific extended-release peppermint oil product (Colpermin) 187 mg or 0.2 mL taken orally 4 hours prior to a colonoscopy reduces procedure time, pain, and spasticity (68532), a study using another specific extended-release peppermint oil (IBGard) did not show an effect on colonic spasms, procedure time, or adenoma detection rate when compared with placebo (104221). These differing outcomes may be due to timing of administration. The study that showed benefit administered the treatment 4 hours prior to endoscopy, whereas the study showing no benefit administered the treatment only 1 hour prior. This suggests that extended-release peppermint may need to be administered at least 4 hours prior to the procedure to allow for adequate colonic release (68532,102604,104221).
• Nipple fissures. Topical peppermint seems to reduce cracked skin and pain in the nipples due to breastfeeding. Details: Clinical research shows that topical application of peppermint oil in gel or water reduces cracked skin and pain in the nipple area from breastfeeding when compared with using placebo, lanolin, or the expressed breast milk technique (68454,68462). Other research shows that applying peppermint oil in cream immediately after breastfeeding for 2 weeks decreases pain and trauma in the nipple area similarly to the topical application of dexpanthenol or lanolin (96365).
• Pressure ulcers. Topical peppermint seems to reduce the risk of pressure ulcers. Details: Clinical research in bedridden patients shows that prophylactic application of a topical gel containing peppermint oil 0.2% three times daily for up to 14 days results in pressure injuries in about 23% of patients compared with 77% of those given a placebo gel (102605).
• Tension headache. Topical peppermint seems to relieve tension headaches. Details: Clinical research shows that topical application of peppermint oil 10% relieves tension headaches when compared with placebo (3801,6190).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. Although there has been interest in using oral peppermint for abdominal pain, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety. Details: A clinical trial in patients presenting to the emergency department for an acute coronary syndrome event shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 1 hour improves anxiety and respiratory rate when compared with baseline or placebo (107958). Due to the single-dose nature of this study, the effects of repeated inhalation of peppermint oil are unclear.
• Breast cancer-related hot flashes. It is unclear if topical peppermint is beneficial for reducing hot flashes in patients with breast cancer. Details: Preliminary clinical research shows that using a spray containing a combination of peppermint and neroli hydrolat does not alleviate hot flashes in most patients receiving chemotherapy for breast cancer when compared with using a plain water spray (68481).
• Cognitive function. It is unclear if inhaled peppermint oil is beneficial for improving cognitive function. Details: Preliminary clinical research shows that inhalation of peppermint oil slightly improves memory and the performance of cognitive tasks such as typing, alphabetization, and ordering, but not attention and speed of task completion, when compared with control (56954,68416,68466).
• Common cold. Although there has been interest in using oral, topical, or inhaled peppermint for the common cold, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Dental plaque. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth for one minute with 10 mL of a specific combination product (HiOra, Himalaya Herbal Healthcare) containing peppermint oil and numerous other ingredients twice daily for two days reduces plaque index or plaque area when compared with placebo; however, it was not as effective as chlorhexidine 0.2% solution (68530). It is unclear if these effects are due to peppermint oil, other ingredients, or the combination.
• Diffuse esophageal spasm. It is unclear if oral peppermint oil is beneficial for diffuse esophageal spasm. Details: A small exploratory study in adults with diffuse esophageal spasm shows that drinking a solution of peppermint oil, 5 drops in 10 mL of water, can resolve esophageal contractions when compared with baseline (13415). The validity of this finding is limited by the lack of a comparator group.
• Dysmenorrhea. It is unclear if oral peppermint oil is beneficial for reducing menstrual pain. Details: Preliminary clinical research shows that taking three capsules of peppermint oil (Colpermin; Tillotts Company or Razak company) daily for 3 days, starting on the first day of menstruation, is as effective as mefenamic acid 250 mg three times daily for reducing pain, and more effective for reducing nausea and vomiting, associated with dysmenorrhea. However, mefenamic acid was more effective for reducing bleeding and analgesic use (105125).
• Fatigue. It is unclear if inhaled peppermint oil improves fatigue in patients with cardiac disease. Details: A clinical trial in hospitalized patients with various forms of cardiac disease shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores when compared with placebo. These improvements were similar to those seen with lavender oil inhalation. Fatigue scores decreased by 24 and 21 points in the peppermint and lavender groups, respectively, compared with a 2-point reduction in the placebo group (107959). The validity of these findings is limited due to the short duration of treatment.
• Halitosis. Peppermint has only been evaluated in combination with other ingredients as a mouthwash; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth with a specific combination of tea tree oil, peppermint, and lemon essential oil once for three minutes improves breath smell when compared with placebo or benzydamine hydrochloride (19177).
• Insomnia. It is unclear if inhaled peppermint oil is beneficial for insomnia. Details: Preliminary clinical research in cancer patients shows that receiving aromatherapy as three drops of peppermint oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline. However, it seems to be no better than using lavender oil aromatherapy or using a control of lavender oil 1% (103063).
• Menopausal symptoms. Although there has been interest in using inhaled peppermint oil for menopausal symptoms, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Migraine headache. It is unclear if intranasal peppermint oil is beneficial for migraine headache. Details: Preliminary clinical research shows that using 1-2 doses of intranasal peppermint oil 1.5% (Poursina Company) at the start of migraine pain is as effective as intranasal lidocaine 4%, and more effective than placebo, for reducing migraine headache intensity. Approximately 42% of those using peppermint oil indicated a high level of headache reduction, compared with 42% of those using lidocaine and 5% of those using placebo. Also, pain relief was felt within 5 minutes in more patients using peppermint than placebo (105126). However, it is unclear if participants were truly blinded to the use of peppermint oil.
• Mosquito repellent. Although there has been interest in using topical peppermint oil as a mosquito repellent, there is insufficient reliable information about the clinical effects of peppermint for this purpose.
• Myalgia. Although there has been interest in using topical peppermint oil for myalgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Oral mucositis. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults undergoing stem cell transplantation shows that using an oral rinse containing peppermint oil and German chamomile three times daily, in addition to standard treatment with sodium chloride and chlorhexidine, reduces the duration and severity of mucositis and the use of narcotic analgesics when compared with placebo and standard treatment. However, this oral rinse does not reduce or delay the occurrence of mucositis or affect the duration of hospitalization (96363). Another small clinical study in adults with head and neck cancers undergoing radiation shows that rinsing with 5 mL of a polyherbal mouthwash containing peppermint oil, German chamomile, aloe vera, and honey for 1 minute 3 times daily for 6 weeks reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine 0.2% and placebo (111291). Clinical research in adults receiving treatment with 5-fluorouracil shows that using an oral rinse containing peppermint, sage tea, and thyme in addition to basic oral care, starting on the first day of chemotherapy and continuing for 14 days, delays the onset of mucositis, but not the rate or severity of mucositis, when compared with basic oral care alone (96364). It is unclear if these effects are due to peppermint oil, other ingredients, or the combinations.
• Osteoarthritis. Although there has been interest in using topical peppermint oil for osteoarthritis, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Pain (acute). It is unclear if inhaled peppermint oil is beneficial for acute pain. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy reduces pain associated with intravenous catheterization by a small amount when compared with a distilled water control (102601).
• Postherpetic neuralgia. Although there has been interest in using topical peppermint oil for postherpetic neuralgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Postoperative ileus. It is unclear if oral peppermint oil is beneficial for the prevention of postoperative ileus. Details: Clinical research shows that taking a specific peppermint oil product (Colpermin, Tillotts Pharma) as two capsules three times daily for 5 days after routine gynecological surgery does not prevent postoperative abdominal distension and dyspepsia when compared with placebo (68602). Conversely, a small clinical study in patients undergoing elective cesarean section shows that taking 20 drops of peppermint oil 4 hours after surgery and then hourly for a total of three doses reduces the time to first bowel sounds by around 3.3 hours, first flatulence by 4.4 hours, and first stool by 5 hours when compared with placebo (110092).
• Postoperative nausea and vomiting (PONV). Some preliminary clinical studies suggest that inhaled peppermint may be beneficial for PONV. However, it is unclear if the benefit is due to aromatherapy or improved breathing patterns. Details: Some preliminary clinical research shows that using peppermint aromatherapy helps relieve postoperative nausea (3804,13415,68524,104219,104220). Inhaling peppermint oil 10% and 30% as aromatherapy reduces the severity of nausea when compared with placebo, with no significant difference between concentrations (104220). Small clinical trials show improvement in PONV within the first 4 hours after surgery. However, this effect diminishes beyond 4 hours (104219). Other preliminary clinical research shows that peppermint oil aromatherapy is no more effective for reducing postoperative nausea than inhaling isopropyl alcohol or saline (13416,68529). It is possible that any relief of postoperative nausea observed with peppermint aromatherapy results from improved breathing patterns after surgery rather than peppermint oil itself (13416,90512). One small study shows that inhaling peppermint oil while practicing controlled breathing does not appear to relieve PONV better than practicing controlled breathing alone (90512). Some preliminary clinical research shows that inhaling vapors from a mixture of peppermint, ginger, spearmint, and cardamom essential oils reduces symptoms of postoperative nausea in approximately 15% more patients when compared with inhaling ginger essential oils alone, and in approximately 43% more patients when compared with inhaling saline (89888). However, it is not clear if the effect is due to peppermint, the other oils, or the combination.
• Pre-procedural anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety prior to a medical procedure. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy does not reduce anxiety associated with intravenous catheterization when compared with a distilled water control (102601).
• Pregnancy-induced nausea and vomiting. Inhaled peppermint oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that aromatherapy with a mixture of 5% lemon and 5% peppermint essential oils modestly reduces the intensity of nausea and vomiting on days 2-4, but not day 1, when compared with placebo aromatherapy. When nauseated, patients placed three drops of the essential oil mixture (Barij Essence Co.) onto a cotton ball held 3 cm from the nose. This action could be repeated after 5 minutes if needed (105121).
• Pruritus. Some preliminary clinical studies suggest that topical peppermint oil improves itching of various etiologies. Details: Preliminary clinical research in adults with renal, hepatic, or diabetic pruritus shows that topical application of peppermint oil 5% in petrolatum twice daily for 2 weeks improves symptoms of pruritus when compared with petrolatum alone (96361). Preliminary clinical research in patients with severe or intractable pruritus secondary to burn scars shows that applying a specific product (Chongqing No.1, CQ-01, MJ Medical Gel Systems Ltd.) containing peppermint oil 3.6%, menthol 1.4%, and methyl salicylate 2.5%, covered with gauze for 24 hours, reduces the severity of pruritus for up to 7 days after application when compared with hydrogel covered with gauze or with gauze alone (96362). Preliminary clinical research in females experiencing itchy skin due to intrahepatic cholestasis of pregnancy also shows that applying peppermint oil 0.5% in sesame oil twice daily for 2 weeks reduces pruritus severity approximately 1.8-fold when compared with sesame oil alone (89478).
• Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral peppermint for SIBO, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Stress. It is unclear if inhaled peppermint oil is beneficial for stress. Details: Clinical research shows that peppermint aromatherapy decreases physical and perceived levels of stress when compared with baseline (68422,68517). A small clinical study in adults undergoing a virtual reality (VR) driving scenario to test road rage shows that exposure to peppermint oil (Pure Essential Oil of Peppermint, Tisserand Aromatherapy) 5 drops via fan diffuser improves aggressive driving behavior scores but does not seem to improve self-reported stress, aggression, alertness, happiness, or calmness when compared with controls that did not receive aromatherapy during the VR session (112017).
• Toothache. Although there has been interest in using topical peppermint oil for toothache, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Urticaria. Although there has been interest in using topical peppermint oil for urticaria, there is insufficient reliable information about the clinical effects of peppermint for this condition. More evidence is needed to rate peppermint for these uses.

(Read more about PEPPERMINT)

POSSIBLY EFFECTIVE

• Diabetes. Oral propolis seems to improve glycemic control in patients with type 2 diabetes; however, some conflicting evidence exists. Details: A meta-analysis of six clinical trials including 374 patients with type 2 diabetes shows that taking propolis for 8 weeks to 6 months reduces glycated hemoglobin (HbA1c) by 0.5% and fasting plasma glucose by 14 mg/dL when compared with placebo. However, significant improvements in insulin levels or measures of insulin resistance were lacking (102520). While this pooled analysis suggests that propolis is modestly effective for improving glycemic control, individual study results are mixed. Three of the trials in the analysis failed to demonstrate significant improvements in HbA1c or glucose levels; however, all of these studies were small and likely underpowered to detect meaningful improvements in glycemic control (102523,102524,102525). Other studies showed positive results, with reductions in HbA1c ranging from 0.9% to 1.1% and reductions in fasting plasma glucose ranging from 21 mg/dL to 26 mg/dL. The doses and durations of propolis therapy in these studies included 400 mg daily for 6 months (99173), 900 mg daily for 12 weeks (95883), and 500 mg three times daily for 8 weeks (102521).
• Herpes labialis (cold sores). Topical propolis ointment or cream, applied five times daily, may improve lesion healing and reduce symptoms in patients with cold sores. Details: One small clinical study in patients with cold sores shows that applying a specific propolis 3% ointment (Herstat or ColdSore-FX by Afexa), five times daily at the start of symptoms, reduces cold sore duration by about 3-4 days and may reduce cold sore-related pain when compared with placebo (17664,17665). Larger clinical studies in patients with cold sores in the papular or vesicular stages show that applying a lip cream containing a specific propolis extract (GH2002) 0.5% five times daily for 5-10 days reduces the time to complete encrustation/epithelialization by about 1 day and improves symptoms of pain, burning, itching, tension, and swelling when compared with acyclovir 5% cream (95875,102519).
• Oral mucositis. Most clinical research shows that oral propolis or propolis-containing mouthwash can reduce the risk for severe, chemotherapy-induced oral mucositis. Details: A meta-analysis of five clinical trials including 209 patients shows that using mouthwash containing propolis reduces the odds of severe chemotherapy-induced oral mucositis by 65% when compared with placebo in cancer patients (99171). Rinsing with 5-10 mL of a propolis mouth rinse for 1 minute three times daily, alone or in addition to chlorhexidine mouthwash and fluconazole for 7-14 days, improves mucositis and redness when compared to control in patients receiving chemotherapy (92793,95877). A small clinical study in patients receiving chemotherapy for breast cancer also shows that taking tablets of propolis (Natur Farma S.A.S.) 80 mg two or three times daily for 3 weeks, in addition to rinsing with sodium bicarbonate solution, decreases the development of mucositis when compared with only rinsing with sodium bicarbonate solution (95882). However, at least one high quality clinical study shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing propolis extract 6% and other ingredients three times daily for 6 weeks does not prevent the development of mucositis due to chemotherapy when compared with placebo in patients with head and neck cancer (95879).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral propolis is beneficial for improving athletic performance. Details: A small clinical study in healthy male military cadets shows that taking propolis 450 mg twice daily for 4 weeks does not improve measures of aerobic or anaerobic performance during exercise testing when compared with placebo (108519).
• Atopic disease. It is unclear if oral propolis can prevent atopic disease in lactating adults or their infants. Details: A small clinical study in lactating adults shows that taking propolis 300 mg daily for 4-10 months does not appear to reduce the risk for developing atopic disease in either the mothers or their infants when compared with placebo (102518). However, due to the small sample size, this study may have been inadequately powered to detect a difference between groups.
• Breast cancer. It is unclear if oral propolis is beneficial in patients with breast cancer. Details: A small clinical study in patients with stage II or III breast cancer receiving chemotherapy shows that taking propolis 250 mg twice daily for 3 months improves quality of life and nutritional status when compared with placebo (108518). It is unknown if propolis can increase the likelihood of survival or remission in patients with breast cancer.
• Burns. It is unclear if topical propolis is beneficial in patients with minor burns. Details: One small clinical study in patients with minor burns shows that application of propolis cream to burn wounds every 3 days improves healing and reduces inflammation when compared with silver sulfadiazine. Propolis cream seems to be as effective for preventing infection as silver sulfadiazine in these patients (8663).
• Canker sores. It is unclear if oral propolis is beneficial in patients with canker sores. Details: A very small clinical study in patients with recurrent canker sores shows that taking propolis 500 mg daily for 6-13 months significantly reduces canker sore outbreaks and improves quality of life when compared with placebo. A 50% or greater reduction in cold sore outbreaks was reported in 60% and 11% of patients taking propolis or placebo, respectively (17629).
• Catheter-related infections. It is unclear if topical propolis is beneficial for the prevention of catheter-related infections. Details: One small clinical study in patients with peritoneal dialysis catheters shows that cleaning the exit site after dialysis with a normal saline wash and propolis 10% ointment for 6 months does not reduce the rate of catheter site infections when compared with using normal saline wash plus mupirocin 2% ointment or normal saline wash alone (109985).
• Chronic kidney disease (CKD). It is unclear if oral propolis is beneficial in patients with CKD. Details: A small clinical study in patients with CKD shows that taking Brazilian green propolis extract (EPP-AF) 250 mg twice daily for 12 months reduces proteinuria, but does not increase estimated glomerular filtration rate (eGFR), when compared with placebo (105785).
• Chronic obstructive pulmonary disease (COPD). Oral propolis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with frequent exacerbations of COPD shows that taking a combination of N-acetylcysteine (NAC) 1200 mg and propolis 160 mg orally once daily for 3 months reduces the incidence of acute exacerbations during 1 year of follow-up when compared with placebo or a lower dose combination of NAC 600mg and propolis 80 mg (109984). Further research shows that using the higher dose combination for 6 months reduces acute exacerbations, cough, and overall COPD severity, and increases dyspnea-free walking distance, when compared with placebo or the lower dose combination (109986).
• Common cold. It is unclear if oral propolis is beneficial in patients with the common cold. Details: One small clinical study in patients with rhinovirus infection shows that taking propolis (dose and duration unknown) might decrease the duration of cold symptoms 2.5-fold when compared with placebo (6602).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral propolis is beneficial for the prevention or treatment of COVID-19. Details: A small observational study in healthcare professionals working in an emergency department shows that taking a 30% Anatolian propolis solution as 20 drops twice daily for one month reduces the occurrence of COVID-19 positivity to 2 of 102 subjects, compared with 14 of 102 in an untreated control group (109983). The validity of this study is limited by the lack of blinding and randomization. A small, open-label clinical study in hospitalized adults with COVID-19 shows that taking a standardized green propolis extract (EPP-AF) 100 mg or 200 mg four times daily for 7 days, along with conventional therapy, reduces length of hospital stay by around 5-6 days, but does not affect the need for supplemental oxygen, odds of intubation, or admission to the intensive care unit, when compared with conventional therapy alone (108514).
• Dengue fever. It is unclear if oral propolis is beneficial in patients with dengue fever. Details: A small clinical study in patients with dengue hemorrhagic fever shows that taking propolis extract (Propoelix) 400 mg three times daily for 7 days reduces the length of hospital stay by about 18 hours when compared with placebo. This was based on being deemed technically fit for discharge because of a recovery of platelet counts. The effect of propolis on other symptoms of dengue fever was not investigated in this study (99168).
• Dental caries. It is unclear if topical propolis, used either as a chewing gum or mouthwash, can prevent dental caries in children. Details: One small clinical trial in children 6-8 years of age at high risk of dental caries shows that chewing propolis gum twice daily for 20 minutes or rinsing with 10 mL of propolis 2% mouthwash for 1 minute twice daily for 2 weeks reduces plaque and Streptococcus mutans count when compared to baseline. There were no differences between the two propolis formulations; however, children preferred the chewing gum over the mouthwash (105790). The validity of these findings is limited by a lack of control group.
• Denture stomatitis. Small clinical studies suggest that topical propolis may speed recovery in patients with denture stomatitis. Details: One very small clinical study in denture-bearing patients with prosthesis stomatitis candidiasis shows that applying Brazilian green propolis 20% ethanol extract topically four times daily for 7 days can cause regression of candidiasis lesions. After 7 days, 58% of patients treated with propolis and 67% of patients treated with nystatin had total lesion remission. After 15 days, all patients in both groups saw total lesion remission (70070). Also, two small clinical studies in patients with denture-induced oral mucositis show that applying propolis 2% to 3% gel (EPP-AF) to dentures three to four times daily for 7-14 days improves the cure rate and reduces erythema. In these studies, propolis appeared to be comparable to applying miconazole to dentures (95881,95884).
• Depression. It is unclear if oral propolis is beneficial as adjunct therapy in patients with depression. Details: A small clinical study in patients with moderate to severe depression inadequately managed with selective serotonin reuptake inhibitors (SSRIs) shows that taking propolis 1000 mg daily for 6 weeks, in addition to SSRI therapy, reduces symptoms of depression, as measured on the 17-item Hamilton Depression Scale (HAMD-17) and Beck Depression Inventory (BDI), when compared with placebo (108523).
• Diabetic foot ulcers. It is unclear if topical propolis is beneficial in patients with diabetic foot ulcers. Details: A small clinical study in patients with diabetic foot ulcers shows that topical application of propolis 5% ointment in addition to routine care for 4 weeks reduces ulcer size about 2.5-fold more than routine care alone (99172).
• Genital herpes. It is unclear if topical propolis is beneficial in patients with genital herpes. Details: A small clinical study in patients with recurrent genital herpes caused by herpes simplex virus type 2 (HSV-2) shows that applying propolis 3% ointment (Herstat or ColdSore-FX by Afexa) four times daily for 10 days reduces healing time and increases the relative rate of complete healing by 1.7- and 2-fold when compared with acyclovir 5% ointment and placebo, respectively (1926).
• Gingivitis. Small clinical studies suggest that topical propolis may modestly improve symptoms in patients with gingivitis. Details: A small clinical study shows that rinsing with a propolis 2% solution 20 mL twice daily for 21 days is as effective as a rinse containing sodium fluoride 0.05% plus cetylpyridinium chloride 0.05% for the prevention of induced gingival redness and bleeding (99169). Another small clinical study in patients with gingivitis shows that rinsing with a propolis solution twice daily for 4 weeks reduces gingival bleeding, but does not improve plaque index, when compared with placebo (108513). Propolis has also been evaluated in combination with other ingredients. One small clinical study in patients with plaque-induced gingivitis shows that adjuvant therapy with a topical gel containing propolis and other ingredients (Oralsan NBF gel, IDS SpA) for 15 days following scaling and root planing is as effective as a chlorhexidine-based gel for improving bleeding, plaque, and probing depth (99170). Another small clinical study in patients with generalized or localized gingivitis or stage I periodontitis shows that taking 194 mg of a product containing propolis and mangosteen improves the modified gingival index by 31% or 40% at weeks 4 or 8, respectively, compared with 16% or 25% in those receiving placebo. No changes in probing depth, clinical attachment, plaque index, bleeding, or gingival recession were observed (106789).
• Helicobacter pylori. It is unclear if oral propolis is beneficial in patients with H. pylori infection. Details: One very small, uncontrolled clinical study in patients with H. pylori infection shows that taking 60 drops of an alcoholic preparation of Brazilian green propolis daily for 7 days does not reduce H. pylori infection when compared to baseline (70107).
• HIV/AIDS. Although there has been interest in using oral propolis as an adjunct to antiretroviral therapy for HIV/AIDS, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Intestinal parasite infection. It is unclear if oral propolis is beneficial in patients with giardiasis. Details: One small clinical study in adults with giardia infection shows that taking a specific propolis 30% extract (Propolisina, Apis Flora) for 5 days increases cure rates when compared with tinidazole. The cure rate was 60% with propolis extract, compared to only 40% with tinidazole. In children with giardiasis, taking propolis 10% extract showed a 52% cure rate; however, the rate of cure with tinidazole was not available (70121).
• Malnutrition. It is unclear if oral red propolis is beneficial in malnourished children with frequent respiratory tract infections. Details: A small clinical study in children aged 1-5 years with frequent respiratory tract infections and growth failure associated with malnutrition shows that giving 3% red propolis in 8 mL (10 grams) of honey once daily in addition to adequate nutrition does not improve weight gain or reduce the frequency of respiratory infections when compared with honey plus adequate nutrition (109987).
• Muscle fatigue. It is unclear if oral propolis is beneficial for speeding recovery from muscle fatigue. Details: One small study in young, healthy males shows that taking Brazilian green propolis 1575 mg before meals three times daily for one week, followed by exercise to induce muscle fatigue, reduces the time to regain maximal contraction torque after stopping when compared with placebo or a 100-mg dose of propolis. There was no difference in average peak power between the groups (109989).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral propolis is beneficial in patients with NAFLD. Details: One small clinical study in patients with NAFLD shows that taking propolis extract 250 mg twice daily for 4 months improves markers of hepatic steatosis and fibrosis, but does not improve liver function, when compared with placebo (105786). Another small study in adults with obesity and NAFLD shows that taking propolis 510 mg daily for 8 weeks with a calorie-restricted diet reduces liver fibrosis, fasting blood glucose levels, serum insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) when compared with placebo. However, it does not affect the severity of fatty liver, anthropometric measurements, lipid profile, or levels of inflammatory markers (109988).
• Peptic ulcers. Although there has been interest in using oral propolis for peptic ulcers, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Periodontitis. It is unclear if oral propolis or propolis extract rinse is beneficial in patients with periodontitis. Details: One small clinical study in patients with type 2 diabetes and chronic periodontitis also receiving scaling and root planing shows that taking propolis 400 mg daily for 6 months reduces probing depth and improves clinical attachment by a small amount when compared with scaling and planing alone. There was no additional benefit with propolis on measures of gingivitis, plaque, or bleeding when compared with scaling and planing alone (99173). Another very small clinical study in patients with chronic periodontitis shows that irrigation of the gums with an ethanol solution containing propolis extract 20% twice weekly for 2 weeks reduces gum bleeding when compared with irrigation with ethanol 14% solution (95876). Propolis has also been evaluated in combination with other ingredients. A small clinical study in patients with generalized or localized gingivitis or stage I periodontitis shows that taking 194 mg of a product containing propolis and mangosteen improves the modified gingival index by 31% or 40% at weeks 4 or 8, respectively, compared with 16% or 25% in those receiving placebo. No changes in probing depth, clinical attachment, plaque index, bleeding, or gingival recession were observed (106789).
• Rheumatoid arthritis (RA). It is unclear if oral propolis is beneficial in patients with RA. Details: A small clinical study in females with RA shows that taking Brazilian propolis 508.5 mg daily for 24 weeks does not improve measures of disease activity, quality of life, or activities of daily living when compared with placebo (108515).
• Sepsis. It is unclear if oral propolis is beneficial in patients with sepsis. Details: A small clinical study in patients with pneumosepsis shows that taking propolis 1000 mg daily along with conventional therapy does not improve survival rates or disease severity, as measured using APACHE II and SOFA scores, when compared with placebo. The combination of propolis 1000 mg plus melatonin 20 mg daily did improve disease severity scores but had no effect on survival (108524).
• Tinea pedis. It is unclear if topical propolis is beneficial in patients with tinea pedis. Details: A case series involving students with athlete's foot found that topical treatment with a 100 mg/mL ethanolic extract of Brazilian green propolis results in less skin itching, peeling, and redness when compared with petroleum jelly placebo, but not when compared with miconazole (95880).
• Tuberculosis. Although there has been interest in using oral propolis for tuberculosis, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Upper respiratory tract infection (URTI). It is unclear if oral propolis spray is beneficial in patients with URTI. Details: One small clinical study in patients reporting mild URTI symptoms shows that use of a propolis oral spray (M.E.D. Propolis, B Natural srl), 2-4 sprays daily, providing 6 mg of polyphenols per spray, for 5 days reduces the time to complete resolution of symptoms by 2 days when compared with placebo (105787). Propolis has also been evaluated in combination with other ingredients. A large clinical study in children 1-5 years of age shows that taking 5-7.5 mL of a specific combination product (Chizukit, Hadas Corp Ltd.) containing propolis 50 mg/mL, echinacea extract 50 mg/mL, and vitamin C 10 mg/mL for 12 weeks reduces the number of children who experience one or more upper respiratory tract illnesses, as well as the number and duration of illnesses, when compared with placebo (48551). It is unclear if these findings are due to propolis, other ingredients, or the combination.
• Urinary tract infections (UTIs). Oral propolis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 3 small clinical studies in adults with uncomplicated UTIs shows that taking combination products containing propolis, Hibiscus sabdariffa, and gelatin or xyloglucan daily for 5-10 days, then daily for two weeks each month for two months, reduces the odds of UTI recurrence by 87% when compared with control (108520). One of these studies used a specific product (Utipro Plus, Noventure) containing propolis 100 mg, xyloglucan extract 100 mg, Hibiscus sabdariffa extract 100 mg, and gelatin 50 mg once daily for 15 consecutive days each month for 6 months (101734). A small clinical study in females with recurrent UTIs shows that taking two capsules of a specific combination product (DUAB, Nutrivercell) containing propolis, cranberry, and zinc daily for 6 months reduces the number of recurrent UTIs by around 0.8 and delays the time to first recurrent UTI by around 26 days when compared with placebo (102522).
• Vaginitis. It is unclear if topical propolis is beneficial in patients with vaginitis. Details: A small clinical study in patients with chronic vaginitis shows that applying 50 mL of a specific aqueous solution containing propolis 5% (Melprotect, Melbrosin International) to the vagina for 7 days can reduce symptoms and improve quality of life when compared to baseline (70068). The validity of these findings is limited by a lack of control group.
• Warts. It is unclear if oral propolis is beneficial in patients with warts. Details: One small clinical study in adults and children with common and plane warts shows that taking propolis (Bee Propolis, Pollen) 500 mg orally daily for up to 3 months increases wart cure rates when compared with echinacea or placebo. Common warts were cured in 73% of patients taking propolis, compared to 20% taking echinacea and 8% taking placebo. Plane warts were cured in 75% of patients taking propolis, compared with 36% taking echinacea and 21% taking placebo. Neither propolis nor echinacea were effective for treating plantar warts (92800).
• Wound healing. It is unclear if topical propolis or propolis mouth rinse improves wound healing. Details: One small clinical study shows that using an aqueous alcohol mouth rinse containing propolis 5% five times daily for 1 week following sulcoplasty improves healing and reduces pain and inflammation (799). Another small clinical study in males recovering from surgery for sacrococcygeal pilonidal disease shows that using 1 mL of propolis 15% solution on the wound dressing daily for 28 days accelerates wound healing when compared with normal saline (108516) However, another small clinical trial in patients undergoing dental surgery shows that using a propolis 20% solution in a dressing is no more effective than the dressing alone for improving wound healing and reducing pain associated with the wound (99167). More evidence is needed to rate propolis for these uses.

(Read more about PROPOLIS)

LIKELY SAFE ...when used orally and appropriately (13160,14319). Concerns about botulism pertain only to children under 12 months of age and not to adults (13160). ...when used topically and appropriately. A specific commercially available wound dressing containing manuka honey (Medihoney) is approved as a medical device by the US Food and Drug Administration (FDA) (16353,16355,16357,16362,16369,16371). Some evidence suggests other honey preparations can also be used safely when applied to the skin or used to rinse the mouth (395,396,397,398,399,7847,7849,13133,14317)(16358,16372,97704,101034,108530).

POSSIBLY SAFE ...when properly diluted honey is used intranasally. Manuka honey 16.5% solution has been used with apparent safety as a nasal rinse twice daily for 14 days (103969). ...when specific, medical-grade honey products are used in eye drops. A specific product (Optimel Manuka Plus Eye Drops, Melcare Biomedical Pty Ltd) has been used safely 2-3 times daily for up to 4 weeks (105231,105234).

LIKELY UNSAFE ...when honey produced from the nectar of rhododendrons is used orally. This type of honey contains grayanotoxins, which may lead to cardiovascular symptoms, such as arrhythmias, hypotension, chest pain, bradycardia, syncope, asystole, various types of heart block, and myocardial infarction (12220,55119,55122,55125,55126,55129,55141,55142,55157)(55163,55170,55171,55180,55183,55190,55224,55233,55234,55239)(55248,55260,55261,55280,55281).

CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term in children at least 12 months of age (15910,17299,55210,55253,97693).

CHILDREN: POSSIBLY UNSAFE
when used orally in children less than 12 months of age. Ingestion of raw honey contaminated with Clostridium botulinum spores can cause botulism poisoning in infants under 12 months of age (13160,55067,55290,91359). This is not a danger for older children or adults. Medical-grade, sterilized honey has been used with apparent safety in the formula of premature newborns at doses of up to 15 grams daily for up to 2 weeks (97697).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in food amounts. The concern about botulism pertains to children under 12 months of age and not to pregnant adults (13160). There is insufficient reliable information available about the safety of honey when used for medicinal purposes when pregnant or breast-feeding.

(Read more about HONEY)

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

POSSIBLY SAFE ...when inhaled in amounts used for aromatherapy, short-term. Lemon essential oil has been used with apparent safety as aromatherapy for up to 2 weeks in clinical research (93475,98128,98129). There is insufficient reliable information available about the safety of lemon when used topically, or when used orally or intranasally in medicinal amounts.

PREGNANCY AND LACTATION:
Insufficient reliable information available. Avoid using in amounts greater than those typically found in foods.

(Read more about LEMON)

LIKELY SAFE ...when peppermint oil is used orally, topically, or rectally in medicinal doses. Peppermint oil has been safely used in multiple clinical trials (3801,3804,6190,6740,6741,10075,12009,13413,14467,17681)(17682,68522,96344,96360,96361,96362,96363,96364,96365,99493).

POSSIBLY SAFE ...when peppermint leaf is used orally and appropriately, short-term. There is some clinical research showing that peppermint leaf can be used safely for up to 8 weeks (12724,13413). The long-term safety of peppermint leaf in medicinal doses is unknown. ...when peppermint oil is used by inhalation as aromatherapy (7107). There is insufficient reliable information available about the safety of using intranasal peppermint oil.

CHILDREN: POSSIBLY SAFE
when used orally for medicinal purposes. Enteric-coated peppermint oil capsules have been used with apparent safety under medical supervision in children 8 years of age and older (4469).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (96361). There is insufficient information available about the safety of using peppermint in medicinal amounts during pregnancy or lactation; avoid using.

(Read more about PEPPERMINT)

POSSIBLY SAFE ...when used orally and appropriately. Propolis has been used with apparent safety in clinical research at doses of up to 1500 mg daily (95883,99173,102520,102521). ...when used topically. Propolis as a 3% or 10% ointment, 0.5% cream, 30% mouth rinse, or 15% solution has been used with apparent safety in small clinical studies (799,1926,6602,8663,17629,17664,17665,92793,92800,95882)(99171,99173,102519,102521,105785,105786,108516,108523,109985).

PREGNANCY:
Insufficient reliable information available; avoid using.

LACTATION: POSSIBLY SAFE
when used orally and appropriately during lactation. Propolis 300 mg daily has been used for 4-10 months in one clinical study with no apparent adverse effects to nursing infants (102518).

(Read more about PROPOLIS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, honey may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details In vitro, honey inhibits platelet aggregation and increases the time to clotting (55222). Furthermore, animal research suggests that feeding mice large doses of honey for 12 days increases bleeding time when compared with no intervention (103964). However, these effects have not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, honey might decrease levels of drugs metabolized by CYP3A4, but research is conflicting.  Details Some clinical research shows that honey induces CYP3A4 (55116). However, other clinical studies found no effect on CYP3A4 activity (55208). Different honey preparations may have different effects on CYP3A4.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, honey might increase levels of phenytoin.  Details In an animal model, the rate and extent of absorption of phenytoin was increased by honey (20352). This effect has not been reported in humans.

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ITRACONAZOLE (Sporanox) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.  Details In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage (110781).

(Read more about LEMON)

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.  Details In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction (11784). An interaction between peppermint oil and cyclosporine has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP1A2 substrates.  Details In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2 (12479,12734). However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference (96359).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C19 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C9 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP3A4 substrates.  Details Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate (11783). However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations (12479).

(Read more about PEPPERMINT)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.  Details In vitro research shows that propolis water extract and the propolis constituent, caffeic acid phenethyl ester, can inhibit platelet aggregation (50794,95885). Additionally, evidence from an animal model shows that taking propolis in addition to warfarin decreases INR, suggesting that propolis can decrease the effectiveness of warfarin (95874).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP1A2.  Details In vitro research shows that propolis extract can inhibit CYP1A2 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP1A2 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP1A2 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2C19.  Details In vitro research shows that propolis extract can inhibit CYP2C19 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2C19 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2C19 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2C9.  Details In vitro research shows that propolis extract can inhibit CYP2C9 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2C9 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2C9 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2D6.  Details In vitro research shows that propolis extract can inhibit CYP2D6 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2D6 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2D6 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might increase levels of drugs metabolized by CYP2E1.  Details In vitro research shows that propolis can inhibit CYP2E1 (92799). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP3A4.  Details Some in vitro research shows that propolis extract can inhibit CYP3A4 (92797); however, other in vitro research shows that propolis has no effect on CYP3A4 activity (92799). Furthermore, animal research shows that propolis extract does not significantly affect CYP3A4 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that might in inhibit CYP3A4 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might decrease the effectiveness of warfarin.  Details Animal research shows that taking propolis in addition to warfarin decreases the international normalized ratio (INR) (95874). This effect has not been reported in humans.

(Read more about PROPOLIS)

General ...Orally and topically, honey is generally well tolerated in those at least 1 year of age. When given intranasally or into the eyes, honey seems to be well tolerated. However, honey containing grayanotoxins, which are found in rhododendrons, is likely unsafe and should be avoided.
Most Common Adverse Effects:
Orally: Nausea, stomach pain, and vomiting.
Topically: Burning, pain, and stinging.
Intranasally: Burning and nausea.
Ocular: Stinging.
Serious Adverse Effects (Rare):
Orally: Case reports of botulism in infants have occurred. Anaphylaxis has been reported in sensitive individuals. Honey from the Black Sea coast of Turkey, which is derived from the nectar of rhododendrons, has caused respiratory depression, dizziness, sweating, weakness, bradycardia, atrioventricular (AV) block, hypotension, cardiac arrhythmias, and myocardial infarction within a few minutes to several hours after consumption.

Cardiovascular ...Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins from rhododendrons, which can cause bradycardia, atrioventricular (AV) block, cardiac arrhythmias, myocardial infarction, and hypotension within a few minutes to several hours after consumption (12220,55110,55126,55129,55238,55269,55270,55280). Fatalities have not been reported. Patients typically respond to fluids and reversal of cardiac conduction abnormalities with atropine.

Dermatologic ...Topically, the use of honey applied to wounds can cause local pain, stinging, and burning in about 5% of patients, some of whom stop treatment as a result (16356,16357,16358,16361,91362,97694,96595). Theoretically, honey may cause excessive drying of wounds, which could delay healing. This can be managed by application of saline packs as needed (7850).

Gastrointestinal ...Orally, honey may cause mild nausea, vomiting, and stomach ache (12220,55119,55190,55294,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins. These toxins can cause increased salivation, nausea, and vomiting within a few minutes to several hours after consumption (12220,55119,55190,55294). Intranasally, honey may cause nausea (55216).

Immunologic ...Orally, honey can cause allergic reactions, including anaphylaxis (6,11,108531,108532). These reactions may be due to various components of the honey, including the honey itself, pollen, or bee secretions (91370). When used topically, local allergic reactions have been reported in people with pre-existing atopy (16356,55118). Allergic contact dermatitis related to honey enriched with propolis has been reported (91365).

Neurologic/CNS ...Orally, honey may cause nervousness, insomnia, and hyperactivity in children (91366,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins, which can cause dizziness, sweating, and weakness within a few minutes to several hours after consumption (12220,55110,55119,55296).

Ocular/Otic ...When used in eye drops, transient stinging has been reported rarely (105231,105234).

Pulmonary/Respiratory ...When used intranasally, a burning sensation of the nasal passages has been reported (55216). Honey from the Black Sea coast of Turkey, which sometimes contains excessive concentrations of grayanotoxins, can cause respiratory depression within a few minutes to several hours after consumption (12220,55110,55119,55296).

Other ...Some honey is contaminated with Clostridium botulinum spores, which poses a risk to infants (6,11,13160,55067,55290,91359). Botulinum spores can proliferate in the intestines of infants and cause botulism poisoning (55112). However, this is not a concern for older children and adults.

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General ...Orally, lemon is well tolerated in amounts commonly found in foods. A thorough evaluation of safety outcomes has not been conducted on the use of larger amounts.
Most Common Adverse Effects:
Orally: Epigastralgia and heartburn with the regular consumption of fresh lemon juice.

Dermatologic ...Topically, the application of lemon oil might cause photosensitivity, due to furocoumarin derivative content. This occurs most often in fair-skinned people (11019).

Gastrointestinal ...Orally, fresh lemon juice, taken as 60 mL twice daily, has been reported to cause gastrointestinal disturbances in 37% of patients in one clinical trial, compared with 8% of patients in the placebo group. Specifically, of the patients consuming lemon juice, 21% experienced heartburn and 8% experienced epigastralgia, compared to 1% and 3%, respectively, in the placebo group (107489).

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General ...Orally, topically, or rectally, peppermint oil is generally well tolerated. Inhaled, peppermint oil seems to be well tolerated. Intranasally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Orally, peppermint leaf seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, anal burning, belching, diarrhea, dry mouth, heartburn, nausea, and vomiting.
Topically: Burning, dermatitis, irritation, and redness.

Dermatologic ...Topically, peppermint oil can cause skin irritation, burning, erythema, and contact dermatitis (3802,11781,31528,43338,68473,68457,68509,96361,96362). Also, a case of severe mucosal injury has been reported for a patient who misused an undiluted over the counter mouthwash that contained peppermint and arnica oil in 70% alcohol (19106).
In large amounts, peppermint oil may cause chemical burns when used topically or orally. A case of multiple burns in the oral cavity and pharynx, along with edema of the lips, tongue, uvula, and soft palate, has been reported for a 49-year-old female who ingested 40 drops of pure peppermint oil. Following treatment with intravenous steroids and antibiotics, the patient's symptoms resolved over the course of 2 weeks (68432). Also, a case of chemical burns on the skin and skin necrosis has been reported for a 35-year-old male who spilled undiluted peppermint oil on a previous skin graft (68572). Oral peppermint oil has also been associated with burning mouth syndrome and chronic mouth ulceration in people with contact sensitivity to peppermint (6743). Also, excessive consumption of mint candies containing peppermint oil has been linked to cases of stomatitis (13114).

Gastrointestinal ...Orally, peppermint oil can cause heartburn, nausea and vomiting, anal or perianal burning, abdominal pain, belching, dry mouth, diarrhea, and increased appetite (3803,6740,6741,6742,10075,11779,11789,17682,68497,68514)(68532,68544,96344,96360,102602,104219,107955). Enteric-coated capsules might help to reduce the incidence of heartburn (3802,4469,6740,11777). However, in one clinical study, a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) taken as 180 mg three times daily was associated with a higher rate of adverse effects when compared with placebo (48% versus 31%, respectively). Specifically, of the patients consuming this product, 11% experienced belching and 26% experienced heartburn, compared to 2% and 12%, respectively, in the placebo group (107955). A meta-analysis of eight small clinical studies in patients with irritable bowel syndrome shows that taking enteric-coated formulations of peppermint oil increases the risk of gastroesophageal reflux symptoms by 67% when compared with a control group (109980). Enteric-coated capsules can also cause anal burning in people with reduced bowel transit time (11782,11789).

Genitourinary ...Orally, a sensitive urethra has been reported rarely (102602).

Hepatic ...One case of hepatocellular liver injury has been reported following the oral use of peppermint. Symptoms included elevated liver enzymes, fatigue, jaundice, dark urine, and signs of hypersensitivity. Details on the dosage and type of peppermint consumed were unavailable (96358).

Immunologic ...One case of IgE-mediated anaphylaxis, characterized by sudden onset of lip and tongue swelling, tightness of throat, and shortness of breath, has been reported in a 69-year-old male who consumed peppermint candy (89479). An allergic reaction after use of peppermint oil in combination with caraway oil has been reported in a patient with a history of bronchial asthma (96344). It is not clear if this reaction occurred in response to the peppermint or caraway components.

Neurologic/CNS ...Orally, headache has been reported rarely (102602).

Ocular/Otic ...Orally, peppermint has been reported to cause blurry vision (3803).

(Read more about PEPPERMINT)

General ...Orally and topically, propolis seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache.
Topically: Contact cheilitis and contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions in sensitive individuals.

Dermatologic ...Propolis can cause allergic reactions and acute oral mucositis with ulceration from the use of the propolis-containing lozenges (2632).
Topically, propolis-containing products, including some cosmetics, can cause eczematous contact dermatitis, erythema multiforme-like contact dermatitis, or allergic contact cheilitis (2632,15647,92796,92798,95878,95882,102517).
Patients allergic to bees or bee products may be more likely to experience allergic reactions to propolis.

Genitourinary ...Vulvar eczema caused by propolis sensitization after topical therapy has been reported (70067).

Hepatic ...Orally, propolis may cause an increase in liver enzymes when used long-term at high doses. In one case, a 30-year-old male presented with persistent abnormal liver enzymes for six months. With other causes ruled out, the patient disclosed using more than 10 propolis lozenges per day for several months to treat a sore throat. Upon discontinuation of the propolis lozenges, liver enzymes returned to normal (105788). Despite concerns presented in this case, analyses of small clinical studies suggest that propolis may have hepatoprotective effects when used at doses of 500-1000 mg daily for up to one year (108521,108522).

Immunologic ...In one case report, a 36-year-old female developed severe erythematous papules and patches with edema of the face, neck, arms, abdomen, and thighs after consuming propolis solution for a few weeks. After symptom resolution, a patch test showed an extreme positive reaction to propolis (106443). In another case, laryngeal edema and severe anaphylactic reaction has been reported in a patient who used topical propolis for the treatment of acute pharyngitis. The patient died due to complications of hypoxia that resulted from the allergic reaction (70063).
Topically, propolis-containing products can cause allergic contact dermatitis, including cheilitis, when used on or near the lips or mouth (15647,92796,92798,102517). Propolis-containing lozenges can cause allergic reactions as well as acute oral mucositis with ulceration (2632).
Patients allergic to bees or bee products may be more likely to experience allergic reactions to propolis.

Neurologic/CNS ...Orally, propolis may cause headache in some patients. In one clinical trial, around 7% of patients taking propolis 250 mg twice daily for 4 months reported mild headache (105786).

Renal ...In one case report, a 59-year-old male with cholangiocarcinoma developed acute kidney failure requiring hemodialysis after taking a Brazilian preparation of propolis 5 mL three times daily for 2 weeks. Renal function improved when propolis was discontinued. The patient restarted taking propolis and symptoms developed again and the patient again required hemodialysis. Symptoms of renal failure improved when propolis was finally discontinued. This product was not screened for contaminants; however, family members of this patient used the same product without apparent adverse effects (14300).

(Read more about PROPOLIS)