# Abstract

 In order to assess the effects of juice feedings during acute diarrhea a double-blind, randomized study was performed in 90 children, mean age of 10 ± 4.28 months. Thirty patients with acute diarrhea were fed twice-daily 15 ml/kg of Apple Juice (AJ), 30 received White Grape Juice (WGJ), and 30 were given colored and flavored water (WA) as part of their age appropriate dietary intake. The duration and severity of diarrhea were the main endpoint variables of the study performed in a metabolic unit. The patients were similar among the 3 groups, had diarrhea for 50--64 hours prior to admission, and were dehydrated when admitted to the unit for study. Half of the patients in each group were well nourished and the others had mild to moderate degrees of malnutrition. Rotavirus infection was the agent causing the illness in 63% of the patients. The infants fed juice ingested 14--17% more calories than those given WA, (those receiving AJ and WGJ ingested 95 and 98 Calories/Kg/d respectively) whereas those receiving WA consumed 81 cal/kg/d). The increased energy intake was not at the expense of other foods or milk formula. The mean body weight gain was greater among patients receiving WGJ (+ 50.7 gm) as compared with the patients in the AJ group (+ 18.3 gm) or the patients fed WA (- 0.7 gm) (p = 0.08). The duration of the illness was longer in the infants fed juice as compared with those given WA (p = 0.006), the mean +/- SD duration in hours was 49.4 ± 32.6, 47.5 ± 38.9 and 26.5 ± 27.4 in patients fed AJ, WGJ and WA respectively. All patients improved while ingesting juice and none of them developed persistent diarrhea; most recovered within 50 hours of the beginning of treatment and less than one fourth had diarrhea longer than 96 hours in the unit. The fecal losses were also increased among the juice fed patients (p = 0.001); the mean ± SD fecal excretion in g/kg/h was 3.94 ± 2.35, 3.59 ± 2.35, and 2.19 ± 1.63 in AJ, WGJ and WA respectively. The stool output was highest during the first day of treatment among all the patients, though those fed AJ had the highest volume of fecal losses and those who received WA had the lowest stool excretion. After the first day of treatment the differences in fecal excretion were not significant. The ability to tolerate carbohydrates during the illness and immediately after recovery was similar among the 3 groups of patients. Intake of juices with different fructose/glucose ratios and osmolarities resulted in more fecal losses and more prolonged diarrhea as compared with water feedings, but the patients given juice ingested more calories and gained more weight, particularly among those being fed the juice with equimolar concentrations of fructose and glucose. # Results The clinical characteristics and the laboratory data of the patients on admission are shown in tables [2](#) and [3](#). The patients in each of the 3 groups were similar in age, duration and severity of diarrhea, presence of fever and vomiting. Also there were no differences in the proportion of patients who received breast feedings or in their nutritional status. Over 46% of patients studied in each group, were well nourished, more than 33% showed mild body weight deficits (\<1 SD) and the others had mild to moderate malnutrition (>2 SD). All patients presented some dehydration (mild to moderate), and required no intravenous hydration therapy. Differences in clinical characteristics were not significant among groups. ::::table-wrap

::: caption
Clinical Characteristics of Patients on Admission
:::

```
                             Apple Juice n = 30   White Grape Juice n = 30   Water* n= 30                    
```

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```
                             χ                    *SD*                       χ               *SD*    χ        SD
```

Age (months) 10.27 4.75 10.27 4.14 11.09 4.00
Diarrhea Duration (hr) 56.37 33.90 64.17 38.95 53.47 33.35
Fever Duration (hr) 37.77 33.46 47.11 49.62 41.04 38.11
Vomiting (h) 41.57 35.45 46.97 39.54 44.33 31.44
Breastfeeding 13 (n) 43.3% 16 (n) 53.3% 09 (n) 30.0 %
Well Nourished 16 (n) 53.3% 15 (n) 50.0% 14 (n) 46.6%
Nutritional Risk\*\* 08(n) 26.6% 10(n) 33.3% 15(n) 50.0%
Mild Malnutrition 03 (n) 10.0% 05(n) 16.6% 01(n) 3.4%
Moderate/Severe Malnutrition 03(n) 10.0% 00(n) 0.0% 00(n) 0.0%

There were no statistically significant differences among groups,
Analysis of Variance (ANOVA) p > 0.05. Fever was considered above 37.5
C temperature. Nutritional risk indicated body weight deficit < 1 SD,
Mild malnutrition < 2 SD and Moderate/Severe Malnutrition > 2 SD.

n = number of patients and % of patients in each category.

*Colored/flavored to resemble juice:::: ::::table-wrap
::: caption
Laboratory Data of Patients on Admission*
:::

```
                        Apple Juice n = 30   White Grape Juice n = 30   Water^*^ n = 30                     
```

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```
                        χ                    *SD*                       χ                  *SD*     χ        *SD*
```

Serum Sodium (mEq/l) 142.03 5.45 140.96 3.51 140.51 5.39
Serum Potassium (mEq/l) 3.99 0.59 3.95 0.81 4.27 0.78
Hematocrit (%) 31.17 3.29 30.93 2.50 32.03 3.55
Hemoglobin (g/dl) 10.28 1.13 10.24 0.87 10.58 1.19
No Anemia 06(n) 20.0 % 02(n) 6.7 % 07(n) 23.3 %
Mild Anemia † 20(n) 66.7 % 26(n) 86.6% 20(n) 66.7 %
Severe Anemia† 04(n) 13.3 % 02(n) 6.7 % 03(n) 10.0 %

Rotavirus 19(n) 63.3 % 18(n) 60.0 % 18(n) 60.0 %
Parasites‡ 05(n) 16.7%. 04(n) 13.3 % 01(n) 3.3 %

\*There were no significant differences among groups by ANOVA p > 0.05.

† The criteria for mild Anemia was a hemoglobin less than 11.0 g/dl and
for severe anemia was a hemoglobin less than 9 g/dl (WHO, 1989)

‡ The parasites detected were: Ascaris lumbricoides (4), Giardia lamblia
(1) Blastocytes hominis (1) Entamoeba coli (1) and Cryptosporidium
parvum (3).

n = number of patients and % of patients in each category

^x^Coloured/flavoured to resemble juice:::: The serum electrolyte levels on admission to the hospital were similar among the 3 groups of patients (Table [3](#)). The hemoglobin (Hb) and hematocrit levels were also similar among groups, but two thirds of the patients exhibited mild degrees of anemia (Hb < 11 g), and in 9 infants there was a more severe degree (Hb < 9 g). In all instances iron supplementation was prescribed at the completion of the study. Rotavirus was identified in the stools of 55 of the patients, in 4 there was a pathogenic Escherichia Coli, in 10 there were parasites detected, and in the remaining 21 infants there were no stool pathogens identified. The daily intake of the patients while in the study is shown in table [4](#). The amount of water, milk formula, and breast milk feedings did not differ among the groups. However, the infants given WGJ readily consumed more juice than those fed AJ or WA. The total energy intake was higher in the juice fed groups as compared with the WA one. The WGJ patients ingested an average of 17% more calories on a daily basis, and the AJ infants consumed a mean of 14% more than the WA group. The increased energy intake was not at the expense of the other foods; both milk formula and complementary foods were ingested in similar quantities among the 3 groups of patients. The mean body weight gain was also higher among the juice fed patients; there was a mean weight gain of 18.3 gm in the AJ fed patients and of 50.6 gm in those given WGJ, whereas there was a mean loss of body weight (- 7.0 gm) among the WA group patients (p = 0.08). ::::table-wrap
::: caption
Daily intake of patients throughout the study (Kcal/Kg/day)
:::

```
                    Apple Juice n = 30   White Grape Juice n = 30   Water^*^ n = 30   P value                      
```

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```
                    χ                    *SD*                       χ                  *SD*      χ          *SD*    
```

Total Calories 95.84 22.42 98.65 30.52 81.43 23.09 0.02\*
Milk Formula 54.49 23.43 50.21 34.57 52.68 17.93 0.81
Breast Milk 08.71 11.57 15.80 18.56 05.45 10.96 0.06
Water 30.67 9.25 30.27 09.57 26.98 9.37 0.25
ORS 45.52 31.17 39.12 25.10 25.10 17.91 0.01\*\*
"Juices" 18.61 3.93 20.98 5.35 17.32^x^ 4.37 0.01\*\*\*
Total Liquids 157.90 38.26 158.42 50.35 127.70 28.25 0.001\*\*\*\*
Complementary Foods 23.90 11.61 25.12 13.97 26.92 11.59 0.64

- Significant differences for Juice Groups vs Water, by ANOVA
  (Bonferroni)

\*\* Significant differences for Water vs both juice groups

\*\*\* Significant differences for WGJ vs each other group

\*\*\*\* Significant Differences for Water vs each other group

^x^ Colored flavored water to resemble juice

Data are means +/- SD:::: The duration of diarrhea differed among the 3 groups of patients (Table [5](#)). The total duration of diarrhea from the start of the illness through their recovery was decreased among the WA fed patients as compared with the AJ and WGJ: groups 111.7 ± 48.2, 105.4 ± 44.9 and 80.0 ± 39.6 hours in AJ, WGJ and WA respectively. The differences in the duration of diarrhea were more marked while being treated in the hospital, the illness being shorter among patients given water instead of juice. However the majority of the patients recovered promptly regardless of the treatment given (Figure [1](#)). Most of the patients improved within 50 hours after treatment was instituted, less than one forth of them had diarrhea persisting more than 96 hours and no one had it for more than 7 days. ::::table-wrap
::: caption
Duration of diarrhea in hours after randomization. Duration of diarrhea
:::

```
                  Mean   SD
```

______________________________________________________________________

Apple Juice 49.4 32.6
White Grape Juice 47.5 38.9
Water * 26.5 27.4

\*Significant differences detect by Kruskal-Wallis p < 0.05. Water vs
Juice groups. Data are hours +/- SD

Water coloured and flavored to resemble juice.:::: <figure> <p><img src="" /></p> <figcaption>Survival analysis of total of diarrhea – Kaplan-Meier, per group. * Statistic difference were found, p < 0,05, among water group and apple juice (P = 0,03) or white grape juice (P = 0,00).</figcaption> </figure> The severity of diarrhea also differed among the treatment groups (Table [6](#)). The stool output among the WA group of patients was significantly decreased as compared with those fed juice. During the first day of treatment those fed water had a mean stool output of 40% less than those fed juice. With improvement the differences among the treatments were minimized, and were no longer significant after the 2^nd^ day of the illness. There were also significant differences in the severity of diarrhea among AJ and WGJ feedings (Table [6](#)). During the first 24 hours of treatment of the illness the patients receiving AJ had more marked stool losses than those fed WGJ. The mean excretion of stools was 21% higher in AJ fed patients than in the WGJ fed group. ::::table-wrap
::: caption
Fecal losses throughout the study and on the first day after
randomization
:::

```
                  **Total Losses (g/kg/hr)**   **First Day Losses g/kg/hr**                
```

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```
                  Mean                         SD                             Mean         SD
```

Apple Juice 3.94 2.35 4.13\*\* 2.90
White Grape Juice 3.59 2.35 3.28\*\* 2.39
Water^x^ 2.19\* 1.63 1.78\*\*\* 1.80

\*Differences Among groups Water vs each of the juice groups
(Kruskal-Wallis test) (p = 0.001)

\*\* Differences between WGJ and AJ (p = 0.02)

\*\*\* Differences between Water and each of the juice groups (p =
0.001)

^x^Coloured/flavoured to resemble juice:::: The stool excretion data were treated for possible confounding and co-variables which could play a role in determining the final results. The covariance analysis and the robust regression showed a possible influence of ORS intake in the differences detected among the 3 groups of patients. The stool output was not different when the ORS intake was adjusted for the 3 groups of patients and the urinary outputs were also similar. Vomitus losses were not different among the 3 groups of patients, vomiting being present primarily during the first 24 hrs. of treatment. There were 2 patients who had severe diarrhea during the treatment period (>10 ml/kg/hr). These patients were in the AJ group, one of these patients had acid stools and none had carbohydrates in feces. These 2 patients were treated with a lactose free formula, with improvement in stool output. There were three other patients who showed carbohydrate intolerance with acid stools or sugars in feces among the 3 groups, they improved without any dietary modifications. Vomiting was present in all groups of patients: 22 (AJ), 26 (WGJ), and 19 (WA) during the first day of treatment; nevertheless this did not represented a limitation for Oral Rehydration Therapy (ORT) or feeding regimen and no patient was withdrawn or shifted to another therapy due to vomiting. The response to juice feedings, as determined by breath hydrogen excretion after improvement of the illness, was not different among the 3 groups of patients. Most infants did not show breath hydrogen excretion levels above 20 ppm; and there were 17, 16 and 10 patients among the AJ, WGJ and WA groups respectively, who failed to show BH2 levels above 5 ppm at any time. Only 18 patients demonstrated a delta BH2 level increase above the basal value of more than 20 ppm. Eight of them were given AJ, 6 were fed WGJ and 4 received WA. There were 11, 16, and 13 patients in each group who exhibited a BH2 value above 20 ppm independent of the delta differences from basal among the WGJ, AJ and WA fed groups respectively. The differences in BH2 levels among groups were not significant.


Extracted trial result:
Outcome: The mean body weight gain (continuous)
Intervention: White Grape Juice (WGJ)
Comparator: colored and flavored water (WA)
Intervention group size: 30
Intervention mean: 50.6
Comparator group size: 30
Comparator mean: -0.7
Notes: Missing standard deviations