Royal Jelly by Nutrients for Health

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Chemotherapy-related infection. It is unclear if oral fermented wheat germ extract is effective for the prevention of febrile neutropenia in children receiving chemotherapy. Details: A small, open-label clinical study in children undergoing chemotherapy shows that a specific fermented wheat germ extract (Avemar) 6 grams/m2 dissolved in water and taken by mouth twice daily along with standard chemotherapy for an average of 10-11 chemotherapy cycles (approximately 29 months) reduces the frequency of febrile neutropenia when compared with chemotherapy alone. Thirty episodes of febrile neutropenia were reported for children receiving fermented wheat germ extract, compared to 46 episodes reported for children receiving chemotherapy alone (27702).
• Colorectal cancer. It is unclear if oral fermented wheat germ extract is beneficial in patients with colorectal cancer. Details: Small non-randomized, open-label clinical studies in patients with colorectal cancer show that taking a specific fermented wheat germ extract (Avemar) 9 grams once or twice daily for at least 6 months in addition to chemotherapy reduces colon cancer progression, the frequency of new metastases, and the risk of mortality when compared with chemotherapy alone (27703,27704). The validity of these findings is limited by a lack of randomization and blinding.
• Melanoma. It is unclear if oral fermented wheat germ extract is beneficial in patients with melanoma. Details: A small clinical study in patients with melanoma shows that a specific fermented wheat germ extract (Avemar) 8.5 grams mixed in a drink and taken once daily in addition to dacarbazine (DTIC)-based chemotherapy for 12 months increases overall survival after 7 years of follow-up by around 22 months and progression-free survival by around 26 months when compared with dacarbazine (DTIC)-based chemotherapy alone (27707).
• Prostate cancer. It is unclear if oral fermented wheat germ extract is beneficial in patients with prostate cancer. Details: A small clinical study in patients with castration-resistant prostate cancer shows that a specific fermented wheat germ extract (Avemar) 8.5 grams mixed in a drink and taken once or twice daily in addition to a gonadotropin releasing hormone analog for at least 4 months increases the doubling time for prostate specific antigen levels in most patients, but does not seem to improve quality of life, when compared to baseline (109632). The validity of these findings is limited by a lack of control group.
• Rheumatoid arthritis (RA). It is unclear if oral fermented wheat germ extract is beneficial in patients with RA. Details: A small, uncontrolled clinical study in females with RA shows that taking a specific fermented wheat germ extract (Avemar) 8.5 grams by mouth in a drink twice daily in addition to disease-modifying anti-rheumatic drug (DMARD) and steroid therapies for 12 months reduces morning stiffness and the dose of steroid drug needed when compared to baseline (27706). The validity of these findings is limited by a lack of control group.
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral fermented wheat germ extract for SLE, there is insufficient reliable information about the clinical effects of fermented wheat germ extract for this purpose. More evidence is needed to rate fermented wheat germ extract for these uses.

(Read more about FERMENTED WHEAT GERM EXTRACT)

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.

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LIKELY INEFFECTIVE

• Alzheimer disease. Lecithin does not improve daily functioning in patients with Alzheimer disease. Details: In patients with Alzheimer disease, taking various types of lecithin, 1.2-45 grams daily for up to 6 months, alone or in combination with various conventional medications, does not improve cognitive function or other measures of disease progression (5149,5151,5152,5156,14817,14823,14825,14837,14838).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral lecithin can slow age-related cognitive decline. Details: A small clinical crossover study in healthy adults aged 64 years and older shows that taking lecithin 26 grams orally daily, alone or in combination with physostigmine, for 5 weeks does not seem to improve memory when compared with placebo (19204).
• Anxiety. Although there is interest in using oral lecithin for anxiety, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Atopic dermatitis (eczema). Although there is interest in using oral lecithin for atopic dermatitis, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Bipolar disorder. It is unclear if oral lecithin is beneficial in patients with bipolar disorder. Details: A clinical study in six patients with mania shows that taking lecithin 10 mg three times daily improves symptoms of delusions, incoherent speech, and hallucinations when compared with placebo (14839).
• Dry skin. Although there is interest in using topical lecithin for dry skin, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Friedreich ataxia. Small clinical studies suggest that oral lecithin is not beneficial in people with Friedreich ataxia. Details: Preliminary clinical research shows that taking lecithin 25 grams orally daily for 1 month does not have any benefit in people with Friedreich ataxia (59298). Other preliminary clinical research shows that taking lecithin for a longer period of 6 months also does not improve performance (19211).
• Hyperlipidemia. Although lecithin may lower cholesterol in healthy people, it does not seem to improve cholesterol levels in people with hyperlipidemia. Details: Some clinical research shows that taking lecithin 20-30 grams daily for up to 11 months decreases cholesterol in healthy people (5147,14820). However, other clinical research shows that lecithin has no effect on low-density lipoprotein cholesterol or total cholesterol levels in people with hyperlipidemia (5148,14820).
• Parkinson disease. It is unclear if oral lecithin is beneficial in patients with Parkinson disease. Details: Preliminary clinical research in patients with Parkinson disease shows that taking lecithin 32 grams daily for 8 weeks does not improve symptoms when compared with placebo (19212).
• Postoperative pain. It is unclear if oral lecithin is beneficial for reducing postoperative pain. Details: Preliminary clinical research shows that taking lecithin 20 grams prior to surgery increases choline levels, but does not reduce postoperative pain after gynecological surgery, when compared with placebo (91231).
• Tardive dyskinesia. It is unclear if oral lecithin is beneficial in patients with tardive dyskinesia. Details: Two small clinical studies in patients with tardive dyskinesia shows that taking lecithin orally for 2 months, alone or in combination with lithium, does not improve symptoms when compared with placebo (14822,14824).
• TPN-associated hepatic steatosis. It is unclear if oral lecithin is beneficial in patients with hepatic steatosis associated with long-term total parenteral nutrition (TPN). Details: A small clinical study in patients on long-term TPN with low choline levels suggests that taking lecithin 20 grams orally twice daily for 6 weeks reduces the degree of hepatic steatosis, compared with no significant changes in those taking placebo (5140).
• Ulcerative colitis. Oral lecithin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a disease-specific medical food (Profermin, Nordisk Rebalance) containing lecithin, fermented oats, barley malt, and lactobacillus plantarum, as 250 mL twice daily for 24 weeks, decreases disease activity by over 56% when compared with baseline and leads to remission in 46% of patients with mild-to-moderate ulcerative colitis (91228). Other preliminary clinical research in this population shows that taking Profermin 250 mL twice daily for 8 weeks improves disease activity and remission rate when compared with another medical food (Fresubin Original, Fresenius Kabi) (90271). The effects of lecithin alone are unclear. More evidence is needed to rate lecithin for these uses.

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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).
• 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. A specific fermented wheat germ extract (Avemar) has been used safely in clinical research at doses of 8.5-9 grams once or twice daily for up to 12 months (27703,27704,27706,27708,109632). There is insufficient reliable information available regarding the safety of fermented wheat germ extract when applied topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. A specific fermented wheat germ extract (Avemar) has been used safely in clinical research at a dose of 6 grams/m2 twice daily for approximately 29 months (27702).

PREGNANCY AND 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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LIKELY SAFE ...when used orally in amounts commonly found in foods. Lecithin has Generally Recognized As Safe (GRAS) status in the US (2619,105544). ...when used orally and appropriately in medicinal amounts. Lecithin has been used safely in doses of up to 30 grams daily for up to 6 weeks (5140,5149,5152,5156,14817,14822,14838,19212). ...when used topically (4914).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts. Lecithin has Generally Recognized As Safe (GRAS) status in the US (105544). There is insufficient reliable information available about the safety of medicinal amounts of lecithin during pregnancy or lactation; avoid using.

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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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IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fermented wheat germ extract might decrease the effects of immunosuppressants.  Details Animal research suggests that fermented wheat germ extract can stimulate immune function (27709,27712,27713,27714,27727).

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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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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, fermented wheat germ extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, nausea.

Gastrointestinal ...Orally, fermented wheat germ extract may cause diarrhea, nausea, flatulence, satiation, soft stools, and constipation. In one clinical study, diarrhea and nausea with or without vomiting were reported in 6% and 3% of patients, respectively (27703).

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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, lecithin is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, fullness, and nausea.

Dermatologic ...Orally, lecithin can cause allergic skin reactions in people with egg or soy allergies (15705).

Gastrointestinal ...Orally, lecithin may cause abdominal pain, diarrhea, fullness, and nausea (5140,6243,14817,14822,14838,19204,59281).

Neurologic/CNS ...Orally, lecithin caused CNS complaints and agitation in one patient in a clinical trial (59261).

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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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