Introduction
Acute gastroenteritis is a very common disease. Worldwide, it affects three to five billion children every year and accounts for 1.5 to 2.5 million deaths annually (12% of all deaths) 1,2. It is the reason for significantly high rates of mortality in developing countries and results in significant economic burden to developed countries 3.
Acute diarrhea of all etiologies can be safely treated with oral rehydration solution (ORS). The WHO, the American Academy of Pediatrics (AAP), and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) working group, and the Cochrane Library database recommend oral rehydration therapy and prompt realimentation for mild to moderate gastroenteritis 4,5. Diarrhea control programs have proved to be highly effective 6. The National Control of Diarrheal Diseases Project of Egypt reported a substantial increase in the awareness on and use of oral rehydration in the country between 1981 and 1990 and a fall in the infant diarrheal death rate from 35·7 to 9·3 per 1000 live births – a 74% reduction with no concomitant decrease in diarrheal incidence 7.
Honey has been used as a medicine since ancient times in many cultures and is still used in folk medicine. In fact, honey has been found to be effective against microorganisms isolated from urinary tract infections 8 and in the treatment of infantile gastroenteritis 9. Honey also possesses beneficial anti-inflammatory and antimicrobial properties owing to its high antioxidant content 10.
In the holy book of Muslims the ‘Al Quran’ and in the holy Hadith dating back to the eighth century AD, our gracious Prophet Mohammed recommended bee honey against diarrhea 11. Moreover, the Roman physician Celsius (ca. 25 AD) also used honey as a cure for diarrhea 12. The Islamic scientist Ibn Sina mentioned in detail about the nutrient, laxative, diuretic, and antitussive properties of honey 13.
This study was carried out to evaluate the clinical effectiveness of using bee honey as a form of adjuvant therapy to ORS in the management of acute infantile diarrhea.
Patients and methods
This study was a simple randomized prospective clinical trial carried out on 150 infants (6–24 months old) suffering from acute diarrhea with mild to moderate dehydration. Acute diarrhea is defined as passing three or more loose or watery stools or any number of loose stools containing blood during a 24 h period 14.
All patients were admitted to Al-Zahra University Hospital, Cairo, Egypt. The study was approved by the local ethical committee of the hospital, and informed consent from the infants’ parents was obtained.
Patients were excluded if they presented with severe dehydration (unstable vital signs and poor perfusion), an altered level of consciousness, possible surgical abdomen, bloody or bilious vomiting, bloody diarrhea, abdominal distension and tense, absent bowel sounds, guarding or rigidity, right lower quadrant pain, or chronic health conditions (such as gastric or jejunal feeding tube dependence, known inflammatory bowel disease, known immunodeficiency syndrome, known metabolic disorders, insulin-dependent diabetes, heart or renal disorder, and neurosurgical history).
The patients were divided by simple randomization into one of the following three groups (50 patients each):
Group I
This group included patients who received WHO ORS only. The ORS was administered on the basis of the recommendations of the WHO 15.
Group II
This group included patients who received ORS with honey at a dose of 50 ml dissolved in 1 l of ORS, which resulted in a significant increase in the glucose content (109 mmol/l instead of 75 mmol/l) and osmolarity of ORS (310 mOsmol/l instead of 245 mOsmol/l), 16.
Group III
This group included patients who were rehydrated by WHO ORS. In addition, they were given pure honey at a dose of 5 ml every 6 h/day.
The honey used was pure unprocessed clover honey collected from Shabshir, Gharbia Governorate, Egypt. The honey was obtained directly from the beekeeper and was tested for the presence of Clostridium botulinum spores by centrifugation and filtration of the supernatant, followed by culture on cooked meat medium 17. No spores were detected. The mixture of honey and ORS was prepared fresh and administered within a maximum of 2 h to avoid fungal growth 18.
Primary history of all patients was studied along with a thorough clinical examination, followed by a clinical evaluation every 24 h until full recovery, which included: (a) A dehydration score, according to the scoring system described by Duggan et al.19, to determine the time required for initial rehydration and to maintain the patient in a rehydrated state. The rehydration solutions were administered using cups and spoons or through nasopharyngeal tubes, whenever indicated. Patients were considered fully rehydrated when all signs of dehydration disappeared, and the dehydration score became zero. (b) Number of motions per day. (c) Consistency of stools. (d) Number of episodes of vomiting (if present).
The recovery time was evaluated for all groups, which was defined as the time calculated from initiation of treatment to when normal soft stools were passed, with the patient showing normal hydration and satisfactory weight gain 9.
Laboratory investigations included: (a) stool cultures for Salmonella, Shigella, Escherichia coli, Staphylococcus aureus, Campylobacter, and Yersinia by standard methods 20; (b) daily monitoring of serum sodium and potassium levels 21,22; and (c) daily monitoring of stool pH 23.
Statistical analysis
Statistical analysis was performed using SPSS program, version 20 (IBM SPSS Statistics 20, Fayetteville, Arkansas, USA). Data were statistically described in terms of mean and SD, and the three groups of patients were compared on the basis of the one-way analysis of variance test. A probability value was considered statistically significant when the P value was less than 0.05. The bivariate Pearson correlation was used and was considered significant at a P value less than 0.05 (two tailed).
Results
The descriptive data of the three studied cases groups is summarized in Table 1. In the present study, 81 infants were males (54%) and 69 infants were females (46%); their ages ranged from 6 to 24 months (mean 11.7±5.0 months). Mild dehydration was observed in 69 infants (46% of the studied cases), and 81 infants (54%) were moderately dehydrated. Honey was well tolerated by both honey-treated groups.
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Table 1: Characteristics of the studied patients
The recovery time was significantly shorter in group III (treated with pure honey and ORS) (3.1±0.6 days) as compared with group I and group II (P<0.05). In addition, the recovery time for group II (honey 50 ml+1 l ORS) and group I showed no significant difference (P>0.05) (Table 1).
It was observed that pure honey shortened the recovery time significantly both in infants with bacterial and in those with nonbacterial diarrhea (Table 2).
Table 2: Recovery time among the different groups according to stool culture (one-way analysis of variance test)
A significant positive correlation was found between the degree of dehydration and frequency of diarrhea (r=0.340, P<0.01). The recovery time was significantly negatively correlated with the frequency of diarrhea and stool pH (r=−0.340, P<0.05). However, a nonsignificant positive correlation was found between the recovery time and degree of dehydration (Table 3).
Table 3: Correlations of the recovery time among the three studied groups
Discussion
The medicinal importance of honey has been documented since ancient times, and it has been known to possess antimicrobial and wound-healing properties. More than 1400 years ago, Allah and His messenger Mohammed advocated that honey can heal a variety of medical problems. Allah says, ‘And the Lord inspired the bee, saying “Take your habitations in the mountains and in the trees and in what they erect. Then, eat of all fruits and follow the ways of your Lord made easy (for you)”. There comes forth from their bellies a drink of varying colors wherein is healing for men. Verily in this is indeed a sign for people who think’ 24.
In Prophetic medicine, honey has been reported to have tremendous medicinal value. It is thought to wash away the harmful substances that might have accumulated in the intestines. Treatment with honey promotes rehydration of the body and is a quick cure to diarrhea and any vomiting and stomach upsets 25.
Honey is being accepted as a reputable and effective therapeutic agent by practitioners of conventional medicine and the general public because of its good clinical results 26. Consuming honey in small quantities (1–2 tablespoons) generally has a positive effect on diarrhea due to food or mild infections. However, consuming honey in large quantities generally causes mild to severe constipation. Honey has been reported to be effective in the healing of infected postoperative wounds 27. It has also been reported to inhibit the growth of several bacteria such as Bacillus cereus, Staphylococcus aureus, Salmonella Dublin, and Shigella dysenteriae28,29. It has also been reported to inhibit the growth of anaerobic bacteroides 30.
Moreover, Adebolu reported that, in the absence of antibiotics, natural honey can be used to treat bacterial diarrhea. He found that natural honey was effective in inhibiting the growth of all the test organisms, with zones of inhibition ranging from 5.0 to 20.0 mm, except for C. jejuni. The inhibitory effect of honey on E. coli was comparable to that of amoxicillin (20.0 mm) and chloramphenicol (17.0 mm). Tetracycline had no inhibitory effect on any of the test organisms 31.
This is in favor of our present study. The recovery time of the studied diarrhea patients was significantly shorter in group III (the pure honey+ORS treated group) as compared with the other two patient groups. It was observed that the pure honey could shorten the recovery time significantly both in infants with bacterial and in those with nonbacterial diarrhea. A significant positive correlation was found between the degree of dehydration and frequency of diarrhea. The recovery time was significantly negatively correlated with the frequency of diarrhea and stool pH. However, a nonsignificant positive correlation was found between the recovery time and degree of dehydration.
Honey is a natural product with a very complex chemical composition. It is composed primarily of fructose and glucose but also contains 4–5% fructooligosaccharides, which serve as prebiotic agents 32. It contains more than 180 substances, including amino acids, vitamins, minerals, and enzymes 33. Honey has been reported to clear infection through a number of properties, including boosting the immune system, anti-inflammatory action, antioxidant activity, and stimulation of cell growth 34. Moreover, the antimicrobial properties of hydrogen peroxide and nonperoxide components of honey were tested in several studies 35.
Molan 36 explained the effective role of honey in the treatment of diarrhea and dysentery by the fact that honey is a nutrient source for Lactobacillus bifidus, which by its Lactobacillus bifidus factor restores intestinal flora, changing the environment necessary for the growth of bacteria causing dysentery and leading to their eradication within few days. Wahdan 37 reported that honey increases the immune resistance of the whole body and thus helps control infections.
However, the results of the present study failed to find any significant difference between the results of group II (treated by 50 ml honey added to 1 l ORS) and group I (treated with ORS only). This is in contrast with the results of Abdulrhman et al. 16 who reported that addition of honey to ORS reduces the frequency of diarrhea in patients with gastroenteritis. Haffejee and Moosa 9 studied the effects of a honey–electrolyte solution (containing 50 ml of honey per liter, i.e. 5%) in patients with infantile diarrhea. They found that the presence of honey in the solution could reduce the duration of bacterial infantile diarrhea when compared with controls.
The anti-inflammatory and antibacterial activity of bee honey can be explained by the osmotic effect. Honey is a supersaturated solution of sugars (84% mixture of fructose and glucose); the strong interaction of these sugar molecules with water molecules leaves few water molecules available for microorganisms 38. This high sugar content of honey could be used to promote sodium and water absorption from the bowel.
Moreover, its acidic pH (between 3.2 and 4.5) inhibits many pathogens. The major antibacterial activity in honey has been found to be because of hydrogen peroxide, which is produced enzymatically glucose oxidase and phenolic compounds. The glucose oxidase enzyme is secreted from the hypopharyngeal gland of the bee into the nectar.
Conclusion
Honey is a nonallergic, natural agent of high nutrient value that has well-known antioxidant, anti-inflammatory, and antibacterial activities. Pure honey administered as a form of adjuvant therapy in addition to ORS in acute infantile diarrhea causes significant shortening in the recovery period, decreases the frequency of passing loose stools, and improves stool consistency. Further studies on pure honey as a form of adjuvant therapy in infantile diarrhea are recommended on a large scale.
Table: No title available.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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