Evaluation Of The Efficacy And Safety Of Probiotic Formulation With Zinc Enriched Yeast In Children With Acute Diarrhea
M Maladkar, P Moralwar, P Mody, V Yewale, U Kinjawadekar, M Mohite
diarrhea., lactobacillus rhamnosus rosell-11, probiotic, saccharomyces boulardii, zinc enriched yeast
M Maladkar, P Moralwar, P Mody, V Yewale, U Kinjawadekar, M Mohite. Evaluation Of The Efficacy And Safety Of Probiotic Formulation With Zinc Enriched Yeast In Children With Acute Diarrhea. The Internet Journal of Nutrition and Wellness. 2009 Volume 9 Number 2.
Background: Diarrhea is a common and potentially serious illness in early childhood. A child suffers, on an average, 10 to 15 episodes of diarrhea in the first five years of life. Particularly in developing countries like India this problem is much more common and also severe due to poor hygiene and less accessible healthcare facilities compared to western world. Objective: The objective of the study was to evaluate the efficacy and safety of a probiotic formulation with Zinc enriched yeast in children with acute diarrhea.
Acute diarrhea is a sudden change in stool fluid output that increases the number of bowel movements to more than three per day. Diarrhea contributes significantly to infant morbidity and mortality, with the World Health Organization (WHO) estimating that 3 million deaths occur per year as a result of diarrhea. In developing countries, children younger than 5 years of age have an average of 3 episodes of diarrhea per year, compared with 1 to 2 episodes per year in the United States. Almost one in every five children in India below the age of 14 suffers from diarrhea. Acute diarrhea is most commonly caused by infections. Bacterial infections are more apparent in the early months of infancy, whereas from 6 months to 2 years of age, rotavirus accounts for 25% to 40% of acute diarrheal cases . There are many other potential causes of acute diarrhea including drug therapy, food allergies, gastrointestinal disorders, and malnutrition.
Diarrhea is a common but potentially serious illness in early childhood. A child may lose almost as much water and electrolytes from the body during an episode of diarrhea as an adult, since the length and surface area of intestinal mucosa of a child, from where the diarrhea fluids are secreted, are fairly large. Loss of one liter of fluid from the body of a child weighing 7 Kg is much more hazardous compared with a similar depletion from an adult of 70 Kg weight. Significant dehydration disturbing the electrolyte balance and acid-base status of the body occurs in about 2 to 3 per cent of all cases of diarrhea. Some of these cases may prove fatal, if fluids and electrolytes are not replaced to restore normal circulatory levels and body functions which are impaired in the dehydrated state.
Probiotics have been studied for the management of various types of diarrheal disease, including viral diarrhea, bacterial diarrhea, antibiotic-associated diarrhea, and
Probiotics are non-pathogenic microorganisms and are considered to be a safe and effective part of the first-line therapy for acute diarrhea in children and adults. Probiotic microorganisms positively change the intestinal flora, inhibit the growth of pathogenic bacteria, promote adequate digestion, stimulate local immune function and increase resistance to infection. Probiotics exert their beneficial effects by a variety of complementary mechanisms, including an ability to modulate host systemic & local immune responses, secretion of mucin from intestinal goblet cells and competitive exclusion of pathogens.In addition, previous studies have shown that probiotics have the ability to decrease
L. rhamnosus Rosell-11 is a strain of lactobacillus with improved stability and efficacy profile. In vitro tests have shown that
In 2004 WHO and UNICEF released a joint statement for treatment of acute diarrhea recommending therapeutic zinc (20 mg/day) for 10–14 days along with oral rehydration salts containing lower concentrations of glucose and salt.
Different forms of zinc have been evaluated for the efficacy. Zinc-enriched yeast is special yeast which can provide ample organic zinc. Zinc-enriched yeast is derived from cultures of specified strains of Saccharomyces cerevisiae grown in the presence of zinc chloride or zinc sulphate. Fermentation takes place at a specified temperature and pressure for defined periods of time. This is followed by increasing the temperature to kill the yeast. The cell wall is ruptured to release the contents which are then spray dried to form zinc enriched yeast. In addition to zinc, it also contains micronutrients like vitamins and other minerals. Organic form of zinc is more bioavailable compared to other available zinc formulations. One of the studies demonstrated that zinc from zinc-enriched yeast was 3.7 times more bioavailable, i. e. absorbed and found in greater concentration in the liver than the zinc gluconates
The objective of the present study was to evaluate the efficacy and safety of probiotic formulation with zinc enriched yeast in children with acute diarrhea.
Materials And Methods
This was an open label, non-randomized clinical trial to assess the efficacy and safety of probiotics with zinc formulation in the treatment of acute diarrhea in children. The test formulation was supplied by Aristo Pharmaceuticals Pvt. Ltd., Mumbai. Each dose of test medication contains
The study was conducted in 104 pediatric patients with acute diarrhea at five different sites.
After independent ethics committee approval, eligible patients were administered with test formulation and frequency and consistency of stools were recorded daily for the duration of treatment up to 10 days.
Children of age 6-60 months with acute diarrhea (< 48 hrs) reporting for the consultation to the investigators were selected for the study. After thorough physical and clinical examinations, subjects who fulfilled inclusion / exclusion criteria and parents/guardian willing to sign the informed consent form were enrolled into the trial. The inclusion criteria included written consent from parents of the patients, patients who will comply with the procedures and requirements of the study, parents of patients able to read, write, follow instructions and record the data in parent’s daily diary. Patients were excluded from the study in case of severe dehydration requiring hospitalization and I.V. fluids, coexisting acute systemic illnesses, food allergy or other chronic gastrointestinal diseases, use of probiotics in the previous three weeks and diarrhea with blood visible in stools.
Trial medication was administered once a day and efficacy parameters and adverse effects if any were recorded. As per the WHO guidance ORS supplementation was given to study population at an average of 7 unit doses/24 hrs. Patients were monitored by the parents and reported to the physician on 3rd, 5th and 10th day. Patient’s diary was filled by the parent /legal representative. Measured efficacy parameters included, Stool frequency, Consistency of stool, Frequency of urination in 24 hours, Episodes of vomiting and ORS consumption.
Treatment was continued for 10 days even after the patients were completely cured to complete the zinc supplementation course as per WHO guidelines.
The data was then compiled, and subjected for statistical analysis. The data was analyzed as average (mean) during treatment period. For efficacy parameters mean score of baseline was compared with mean score of day 3, day 5 and day 10. T-test (two tails) was applied to compare the efficacy of the treatment on day 0, day 3, day 5 and day 10. For nonparametric symptoms like consistency of stools ANOVA test was applied.
The aim of this multicentric, prospective, phase III clinical trial was to investigate the therapeutic efficacy and safety of orally administered probiotic formulation with zinc enriched yeast in treating acute diarrhea in children. The results showed that probiotic formulation with zinc enriched yeast showed improvement in terms of both time to response and response rate.
Acute diarrhea in children is very often self-limiting within few days. However, children are in danger of developing dehydration and a deteriorating general health. Therefore, an effective antidiarrheal treatment would be beneficial. Several investigations have been carried out with probiotics for the treatment of acute gastroenteritis, and different meta-analyses and systematic reviews have been published in this field. All of these have demonstrated the efficacy of probiotics in treating or preventing diarrhea. On an average, the treatment of diarrhea with lactobacilli, bifidobacteria and/or
Szajewska and Mrukowicz reviewed ten randomized, double-blind, placebo-controlled studies and concluded that the administration of probiotics led to a substantial reduction in the duration of acute diarrheal symptoms, an average of 20 h.  Moreover, a meta-analysis of nine clinical trials conducted by D’Souza et al. demonstrated that probiotics effectively prevented antibiotic-associated diarrhea.  The work of van Niel et al. included nine randomized controlled studies with lactobacilli in acute infectious diarrhea in children. In these studies, the duration of diarrhea was significantly reduced by an average of 0.7 days along with the reduced daily stool frequency.  More recently, McFarland et al. examined the efficacy of probiotics in pediatric diarrhea by analyzing 39 randomized, controlled and blinded clinical trials comprising a total of 41 probiotic treatment arms. Of these, 32 (78%) reported efficacy. The latest meta-analysis of 39 trials by Sazawal et al. showed that probiotics prevented acute diarrhea, with a risk reduction among children of 57% (range: 35–71%). 
In the present trial 104 patients were enrolled, 100 patients completed the trial successfully. Patients who did not come for follow up visit (4 patients) were considered as drop outs. Primary outcome analyzed in this study is duration of diarrhea, frequency and consistency of stools.
All the patients had watery stools and had an average of 8 episodes of diarrhea in 24 hours. Out of 100 patients, 66 patients had moderate dehydration and 4 had severe dehydration. Out of 66 moderately dehydrated patients, 42 (63%) patients were cured by day 3, 22 patients (34%) by day 5 and 2 patients (3 %) by day 10. The 4 severely dehydrated patients were cured by day 5. The rest 5% were cured by day 10 because all the 5 patients were underweight and had malnutrition.
On an average, 60% of patients were cured by day 3 and 35 % were cured by day 5 and the remaining 5 % by day 10. Frequency of stools decreased to almost normal in 24 hrs.
Among 100 patients with diarrhea, 12 patients had vomiting (average 3 episodes in 24 hours), 9 patients had fever and 29 patients had vomiting and fever. Frequency of urination was 4 on an average in 24 hours at base line. On an average, seven unit doses of ORS were consumed by patients in 24 hrs on the day of enrollment. In the present study, decrease in frequency of vomiting was observed which may not be due to medication but overall reduction in disease process and ORS administration. The test medication was well tolerated by the patients with no serious adverse events reported.
This clinical trial clearly demonstrates that the probiotic-zinc combination containing Lactobacillus rhamnosus Rosell-11, Saccharomyces boulardii and zinc enriched yeast provided clinical benefits to the patients of acute diarrhea and showed improvement in terms of both the time to response and response rate to diarrhea. The primary outcome was a statistically significant improvement in frequency and consistency of stools. The secondary outcomes were reduction in other symptoms like vomiting, fever and other signs of dehydration. Probiotic usage resulted in early recovery and prevented prolongation of diarrhea and secondary malabsorption. No adverse events were observed with the usage of the studied antidiarrheal medication. Larger population studies are needed as confirmatory trials for L. rhamnosus Rosell-11 as well as zinc enriched yeast in the antidiarrheal treatment.