Abdulrhman, M.A., Hamed, A.A., Mohamed, S.A., & Hassanen, N.A. (2016). Effect of honey on febrile neutropenia in children with acute lymphoblastic leukemia: A randomized crossover open-labeled study. Complementary Therapies in Medicine, 25, 98–103. 

To test the effects of 12 weeks of honey consumption on the development of febrile neutropenia (FN) among children with acute lymphoblastic leukemia (ALL)

Patients were randomized to the order in which they received the honey or control interventions. Subjects took 2 ml (2.5 g) honey/kg body weight twice weekly for 12 weeks. In the control condition, no honey was ingested. Patients were directly observed taking the honey in the outpatient clinic to ensure compliance with the regimen. Raw and unprocessed honey was used. All patients were on standardized antibiotic prophylaxis. Patient with diabetes mellitus were excluded from the study. Blood counts were done on a weekly basis, and data analysis was done at baseline, 12 weeks, and 24 weeks. Patient who developed FN were hospitalized and treated with empiric antibiotics.

• N = 40   
• MEAN AGE = 5.4 years
• AGE RANGE = 2.5–10 years
• MALES: 50%, FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had ALL and were receiving maintenance therapy.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Egypt

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

• Randomized, crossover, open-label

• Absolute neutrophil count (ANC)
• Complete blood counts

During the control period, the hemoglobin, ANC, and platelet counts decreased (p = 0). At the end of the intervention period, a significant increase was observed in the hemoglobin, ANC, and platelet counts (p = 0). Fewer patients developed FN while taking honey (p = 0.00004); however, no differences existed between periods in measures of FN, such as duration of FN or hospitalization. Of the patients, 22.7% developed undesirable effects of abdominal pain, vomiting, or diarrhea after taking the honey, and three patients stopped the intervention because of these effects.

The ingestion of honey may have beneficial effects among children with ALL to reduce the incidence of FN, and may have positive effects on hemoglobin and platelet counts.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• The definition of FN is not provided.
• The prevalence of FN was high in this study compared to some other published results from higher income countries; therefore, the findings may not be applicable in higher socioeconomic groups.  
• The duration of any effects of honey ingestion are unknown, so there is no way to know if there were carry-over effects in the crossover design.

Honey ingestion may be helpful in reducing the frequency of FN among patients with ALL. The mechanism of effect is unclear. Hypotheses suggest that honey's effects on FN may be related to its antimicrobial, antioxidant, and immunomudulator properties.