Super Bee + by Wonder Laboratories

POSSIBLY INEFFECTIVE

• Athletic performance. Small clinical studies suggest that oral bee pollen may not improve athletic performance. Details: Clinical research in athletes shows that taking bee pollen supplements orally does not seem to improve athletic performance or stamina (7062,7063,33973).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral bee pollen for aging, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Allergic rhinitis (hay fever). Although there has been interest in using oral bee pollen for allergic rhinitis (hay fever), there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Amenorrhea. Although there has been interest in using oral bee pollen for amenorrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Atopic dermatitis (eczema). Although there has been interest in using topical bee pollen for atopic dermatitis (eczema), there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Benign prostatic hyperplasia (BPH). Although there has been interest in using oral bee pollen for BPH, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Bleeding. Although there has been interest in using oral bee pollen for bleeding, including intracranial hemorrhage, there is insufficient reliable information about the clinical effects of bee pollen for these conditions.
• Breast cancer-related hot flashes. It is unclear if oral bee pollen is beneficial for the treatment of menopause-like symptoms in breast cancer patients. Details: Preliminary clinical research in breast cancer patients suggests that taking a combination of bee pollen and honey does not reduce hot flashes or other menopause-like symptoms when compared with honey alone (91983).
• Constipation. Although there has been interest in using oral bee pollen for constipation, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Diarrhea. Although there has been interest in using oral bee pollen for diarrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Diaper rash. Although there has been interest in using topical bee pollen for diaper rash, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Dysmenorrhea. Although there has been interest in using oral bee pollen for dysmenorrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Obesity. Although there has been interest in using oral bee pollen for obesity, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Oral mucositis. Although there has been interest in using oral bee pollen for oral mucositis, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Premenstrual syndrome (PMS). Oral bee pollen has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking two tablets twice daily of a specific combination product (Female, Natumin Pharma) containing royal jelly 6 mg, bee pollen extract 36 mg, and bee pollen with pistil extract 120 mg per tablet over a period of 2 menstrual cycles seems to decrease some symptoms of PMS, including irritability, weight gain, and edema, when compared with placebo (12008). More evidence is needed to rate bee pollen for these uses.

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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)

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)

POSSIBLY EFFECTIVE

• Menopausal symptoms. Several clinical studies suggest that oral royal jelly, taken alone or in combination with other ingredients, modestly improves menopausal symptoms. It is unclear if topical royal jelly is beneficial for this use. Details: One clinical study in postmenopausal patients shows that taking royal jelly 1000 mg daily for 8 weeks reduces menopausal symptom scores by around 30% when compared with placebo (102527). Other small clinical studies show that taking one to two capsules of a specific combination product containing royal jelly and flower pollen (Melbrosia) daily for 12 weeks reduces menopausal symptoms and improves feelings of well-being when compared with baseline or placebo (18064,71956,72005). Another clinical trial in postmenopausal patients shows that taking two capsules of a specific combination product containing royal jelly, evening primrose oil, damiana, and ginseng (Lady 4) daily for 4 weeks decreases self-rated menopausal symptoms when compared with placebo (21003). Topical royal jelly has also been evaluated. A small clinical study in postmenopausal adults shows that applying vaginal cream containing royal jelly 15% daily for 12 weeks improves quality of life, sexual problems, and urinary problems similarly to vaginal estrogen cream 0.625 mg. However, estrogen cream improves vaginal atrophy better than royal jelly (92884).

POSSIBLY INEFFECTIVE

• Allergic rhinitis (hay fever). Oral royal jelly does not appear to prevent or treat symptoms of allergic rhinitis in children. Details: A clinical trial in children 5-16 years of age with allergic rhinitis shows that taking a specific royal jelly product (Bidro) 150 mg twice daily for 3-6 months before and during pollen season does not prevent or treat nasal congestion, sneezing, or eye discomfort when compared with placebo (71968).
• Diabetes. Oral royal jelly does not appear to improve glycemic control in patients with type 2 diabetes. Details: Most clinical research in patients with type 2 diabetes, along with a meta-analysis of five small clinical trials including patients with or without type 2 diabetes, shows that taking royal jelly 0.5-6 grams daily for 4-8 weeks does not improve markers of glycemic control such as fasting plasma glucose and glycated hemoglobin (HbA1c) (92879,92880,92881,102529).
• Physical performance. Oral royal jelly does not appear to improve physical performance in elderly nursing home residents. Details: A clinical trial in elderly nursing home residents shows that taking royal jelly 1.2 grams or 4.8 grams daily for one year does not improve hand grip strength, walking, or ability to stand on one leg when compared with placebo (95870).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Although there has been interest in using topical royal jelly for androgenic alopecia, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Atherosclerosis. Although there has been interest in using oral royal jelly for atherosclerosis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Athletic performance. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small clinical trials in elite male swimmers and runners show that taking royal jelly 400 mg and coenzyme Q10 60 mg daily for 10 days does not improve high-intensity interval training performance when compared with placebo (109992,109993). These studies were small and may not have been adequately powered to detect a difference between groups.
• Cancer-related fatigue. It is unclear if oral royal jelly is beneficial for improving cancer-related fatigue. Details: A small clinical study in patients with solid (nonhematologic) malignancies shows that taking 5 mL of processed honey and royal jelly twice daily for 4 weeks reduces fatigue when compared with 5 mL of honey alone (92877).
• Chemotherapy-induced acral erythema. It is unclear if oral royal jelly is beneficial for preventing acral erythema from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of acral erythema when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced hepatotoxicity. It is unclear if oral royal jelly is beneficial for preventing hepatotoxicity from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of hepatotoxicity when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced nephrotoxicity. It is unclear if oral royal jelly is beneficial for preventing chemotherapy-induced nephrotoxicity. Details: A small clinical study in patients receiving two cycles of cisplatin therapy shows that taking royal jelly capsules daily may attenuate increases in serum creatinine and urea levels when compared with placebo. However, it is unclear if this effect is clinically significant; the increased levels that occurred in the placebo group were still within normal limits (95871). The validity of these results is also limited by the short study duration and lack of statistical comparison between groups. Another small clinical trial in patients receiving tyrosine kinase inhibitor therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of kidney dysfunction when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-related fatigue. It is unclear if oral royal jelly is beneficial for preventing fatigue from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces the frequency of chemotherapy-related fatigue when compared with placebo (105773,105774).
• Cognitive impairment. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly patients with mild cognitive impairment shows that taking a specific combination product (Memo, Pharco Pharmaceuticals), which contains natural lyophilized royal jelly 750 mg, ginkgo leaf extract 120 mg, and Panax ginseng root extract 150 mg, daily for 4 weeks improves cognitive ability when compared with placebo (89712).
• Coronavirus disease 2019 (COVID-19). Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults without diabetes in Iran hospitalized with moderately severe COVID-19 receiving corticosteroids shows that taking a specific combination supplement (Tang Forte, HealthAid) containing royal jelly extract 350 mg and vitamin E 2 mg daily for 7 days does not improve markers of the clinical course of COVID-19, such as oxygen saturation or length of hospital stay, when compared with placebo (114535). However, this study may not have been adequately powered to detect a difference between groups. It is unclear if this effect is due to royal jelly, other ingredients, or the combination.
• Diabetic foot ulcers. Small clinical studies suggest that topical application of royal jelly plus panthenol may improve healing of diabetic foot ulcers. It is unclear if topical royal jelly alone is beneficial for this use. Details: One small clinical study shows that applying royal jelly 5% to a wound after conventional cleansing and debriding three times weekly for 3 months does not improve the healing of diabetic foot ulcers when compared with placebo (92882). However, other small clinical studies show that applying 1-3 grams of a specific combination ointment (Pedyphar) containing royal jelly and panthenol after conventional cleansing and debriding procedures twice weekly for up to 6 months may improve the healing of diabetic foot ulcers (71980,102526). In one of these studies, the rate of complete healing of life-threatening ulcers was 2.7-fold greater with this combination ointment when compared with panthenol alone (102526). Possible reasons for these discrepancies include the use of combination versus single ingredient ointments and the duration of treatment.
• Dry eye. It is unclear if oral royal jelly is beneficial in patients with dry eye. Details: A small clinical trial in Japanese patients with dry eye shows that taking enzyme-treated royal jelly 2.4 grams daily for 8 weeks does not improve tear stability or dry eye symptoms when compared with placebo (95869).
• Fractures. Although there has been interest in using oral royal jelly for healing of fractures, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Hepatitis. Although there has been interest in using oral royal jelly for hepatitis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Male infertility. Intravaginal application of royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in couples experiencing infertility due to asthenozoospermia shows that applying a saline solution containing royal jelly 3 grams, Egyptian bee honey 100 grams, and bee bread 1 teaspoon intravaginally before or after intercourse, starting one day after menstruation and continuing for 2 weeks, can increase the rate of pregnancy when compared with intrauterine insemination (55131). It is unclear if this effect is due to royal jelly, other ingredients, or the combination.
• Obesity. It is unclear if oral royal jelly is beneficial for reducing body weight in patients who are overweight or obese. Details: One small clinical study in overweight patients with type 2 diabetes shows that taking fresh royal jelly 1 gram daily for 8 weeks reduces body weight by around 2 kg and body mass index (BMI) by around 0.7 kg/m², as well as carbohydrate and total energy intake, when compared with placebo. However, the improvement is modest and may not be clinically significant (92878). Another small clinical study in overweight adults shows that taking royal jelly 1000 mg daily for 8 weeks does not reduce body weight, BMI, or appetite when compared with placebo (102528). However, this study may have been inadequately powered to detect a difference in these outcomes.
• Oral mucositis. It is unclear if oral royal jelly is beneficial for preventing or treating oral mucositis in patients receiving radiotherapy and/or chemotherapy. Details: One small clinical trial in patients receiving chemotherapy and radiotherapy shows that swishing and swallowing royal jelly 1 gram in two divided doses daily, in addition to standard rinses with benzydamine and nystatin, improves healing time of mild or moderate oral mucositis when compared with standard rinses alone (95867).
• Osteoporosis. It is unclear if oral royal jelly is beneficial in patients with osteoporosis. Details: A small clinical trial in postmenopausal adults shows that taking royal jelly powder 1000 mg, equivalent to 3000 mg of fresh royal jelly, daily for 6 months maintains bone mineral density (BMD) in the proximal femur and lumbar spine, while patients taking placebo saw significant reductions in lumbar spine BMD. Also, markers of bone turnover were significantly reduced with placebo, while significant changes in these markers were lacking in patients taking royal jelly (105775). It is unclear whether these findings can be generalized to patients with documented osteoporosis.
• Peptic ulcers. Although there has been interest in using oral royal jelly for peptic ulcers, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Premenstrual syndrome (PMS). It is unclear if oral royal jelly, taken alone or in combination with other ingredients, is beneficial in patients with PMS. Details: A small clinical study in healthy college students shows that taking royal jelly 1 gram daily starting on the first day of menstruation and continuing for two consecutive menstrual cycles improves PMS symptoms when compared with placebo (95873). However, methodological flaws associated with the study limit the validity of these results. A small clinical study shows that taking a specific combination product (Femal, Natumin Pharma), providing royal jelly 12 mg, bee pollen extract 72 mg, and bee pollen plus pistil extract 240 mg, twice daily over 2 menstrual cycles seems to decrease some symptoms of PMS including irritability, weight increases, and edema (12008). It is unclear if these effects are due to royal jelly, other ingredients, or the combination.
• Renal cell carcinoma. It is unclear if oral royal jelly is beneficial in patients with renal cell carcinoma. Details: One small clinical trial in patients receiving tyrosine kinase inhibitor (TKI) therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces tumor size, improves chemotherapy-related fatigue and anorexia, and reduces the need for dose reduction or the discontinuation of therapy when compared with placebo (105773,105774). Royal jelly does not seem to reduce other TKI-related adverse effects, including gastrointestinal symptoms, oral mucositis, acral erythema, anemia, hepatotoxicity, or nephrotoxicity, when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference in these outcomes. More evidence is needed to rate royal jelly for these uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Bee pollen has been safely used in clinical trials lasting up to 30 days (7062,7063,12008,33973). There is also preliminary evidence that taking 2 tablets twice daily of a specific combination product containing royal jelly 6 mg, bee pollen extract 36 mg, and bee pollen plus pistil extract 120 mg (Femal, Natumin Pharma) per tablet for up to 2 months seems to be safe (12008).

PREGNANCY: POSSIBLY UNSAFE
when used orally. There is some concern that bee pollen might have uterine stimulant effects (5,6,11); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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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.

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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).

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Royal jelly 1-4.8 grams daily for up to 1 year has been used in clinical research without reported adverse effects (95869,95870,102527,102528,105773,105774)....when used topically and appropriately for up to 6 months (71980,102526).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 6 months. A specific royal jelly product (Bidro) 150 mg twice daily has been used with apparent safety for 3-6 months in children 5-16 years of age (71968).

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

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WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that bee pollen might interact with warfarin and increase the risk of bleeding.  Details In one case report, a patient on warfarin had a stable international normalized ratio (INR) of 1.9-3.3 for 9 months. The patient's INR was found to be 7.1 after starting bee pollen granules one teaspoon twice daily for approximately one month. The patient's warfarin dose was decreased by approximately 11% in order to return the INR to the therapeutic range while continuing the bee pollen supplement (18063).

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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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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.

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, royal jelly might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that royal jelly might lower blood pressure (71982,71963).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Royal jelly might increase the risk of bleeding when taken with warfarin.  Details In one case, an 87-year-old male who was previously stabilized on warfarin developed hematuria and was found to have an INR of 7.29 after taking a royal jelly supplement for one week (14303).

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General ...Orally, bee pollen seems to be well tolerated in most patients.
Serious Adverse Effects (Rare):
Orally: Acute hepatitis, allergic reactions, interstitial nephritis, kidney failure.

Dermatologic ...Orally, a case of photosensitivity has been reported for a 32-year-old patient who took a dietary supplement containing ginseng, goldenseal, bee pollen, and other ingredients. Symptoms included a pruritic, erythematous rash that was localized to the sun-exposed surfaces of the neck and extremities. Following treatment with topical and subcutaneous corticosteroids and discontinuation of the supplement, the skin rash slowly resolved. It is not known if this effect was due to the bee pollen, one of the other ingredients, or their combination (33954).

Hepatic ...Orally, there have been two cases of acute hepatitis associated with bee pollen use. One case involved ingestion of two tablespoons of pure bee pollen daily for several months. Another case involved ingestion of 14 tablets per day of a combination herbal product containing bee pollen, chaparral, and 19 other herbs for 6 weeks (1351). In this case, it is not known if bee pollen or another herb might have caused the adverse event.

Immunologic ...Patients with a history of seasonal pollen allergies, particularly allergies to plants in the Asteraceae/Compositae family, including ragweed, chrysanthemums, marigolds, daisies, and many other herbs, are at risk for serious allergic reactions to oral bee pollen. Allergic reactions can include itching, swelling, shortness of breath, lightheadedness, and anaphylaxis (5,6,11,13480,33952,33965,91981,91984,109991). In one case, exercise may have contributed to the reaction. A 15-year-old male developed generalized urticaria, facial angioedema, and dyspnea 30 minutes into a vigorous exercise session and an hour after ingesting bee pollen granules. The patient experienced abdominal cramps within minutes of consuming bee pollen on 3 previous occasions and had a positive skin prick test for bee pollen after the anaphylactic reaction (109991). Allergy symptoms due to chronic intake of bee pollen include gastrointestinal and neurologic symptoms and eosinophilia (2627,33964).
A case of allergic eosinophilic gastropathy has been reported for a 5 year-old child who was given bee pollen daily to strengthen the immune system. Symptoms included abdominal pain, vomiting, and swelling of the eyelids and legs (91981).

Neurologic/CNS ...Orally, there is one report of dizziness in a patient who took a combination product containing royal jelly, bee pollen extract, and a bee pollen plus pistil extract (12008). It is not known if this effect was due to the bee pollen, another ingredient, or the combination.

Renal ...Orally, there is one report of a patient taking a bee pollen-containing supplement for greater than 5 months who developed breathing difficulties, edema with weight gain, and loss of appetite. The patient was diagnosed with interstitial nephritis and drug-induced acute kidney failure. The supplement was discontinued and the patient was started on hemodialysis. The patient improved after several sessions of hemodialysis (18068).

Other ...Although some research has shown a lack of mycotoxins in twenty samples of bee pollen, analysis of other ready-to-eat bee pollen products have revealed contamination with potential mycotoxin producing species, including Penicillium verrucosum, Aspergillus niger aggregate, Aspergillus carbonarius, Aspergillus ochraceus, Aspergillus flavus, Aspergillus parasiticus, and Alternaria spp. (33959,33961).

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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 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).

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General ...Orally and topically, royal jelly seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dyspnea, eczema, oral allergy syndrome, pruritus, and urticaria in people with a history of asthma or atopy.
Topically: Contact dermatitis and skin irritation.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, status asthmaticus, and death in people with a history of asthma or atopy.

Gastrointestinal ...There is one case report of hemorrhagic colitis with abdominal pain, bloody diarrhea with concomitant hemorrhagic and edematous mucosa of the sigmoid colon after ingestion of royal jelly. Symptoms resolved within 2 weeks following discontinuation of royal jelly and conservative treatment (3516).

Immunologic ...In people with a history of atopy or asthma, royal jelly taken orally appears to cause a high rate of allergic symptoms including pruritus, urticaria, eczema, eyelid and facial edema, conjunctivitis, rhinorrhea, dyspnea, oral allergy syndrome, and asthma (7314,7315,7316,10623,95872). In severe cases, royal jelly can cause status asthmaticus, anaphylaxis, and death (792,7315,7316,10623,10624,108511). Allergic symptoms are associated with IgE-mediated hypersensitivity reactions (3513,10623).
Topically, skin irritation, exacerbation of dermatitis, or contact dermatitis may occur (791).
From occupational exposure, royal jelly can cause allergic rhinoconjunctivitis and asthma (95868).

Neurologic/CNS ...There is one report of dizziness in a patient who took a combination product containing royal jelly, bee pollen extract, and a bee pollen plus pistil extract (12008).

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