Effect of KiwiBiotic on functional constipation and related symptoms: A prospective, single-center, randomized, comparative, crossover study

Abstract

BACKGROUND

Functional constipation (FC) is a common gastrointestinal disorder characterized by abdominal pain and bloating, which can greatly affect the quality of life of patients. Conventional treatments often yield suboptimal results, leading to the exploration of alternative therapeutic approaches.

AIM

To evaluate the efficacy of KiwiBiotic in the management of FC and related symptoms.

METHODS

This prospective, interventional, single-center, crossover study compared the safety and effectiveness of KiwiBiotic^®vs psyllium husk in managing FC, abdominal pain, and bloating. Participants diagnosed with FC were randomly assigned to receive KiwiBiotic or psyllium husk during the two treatment periods, with a 14-day washout period between them.

RESULTS

Seventy participants were enrolled, 32 of whom received KiwiBiotic followed by psyllium husk, and 33 received KiwiBiotic. KiwiBiotic showed superiority over psyllium husk in alleviating abdominal pain and bloating, as evidenced by significantly lower mean scores. Furthermore, KiwiBiotic resulted in more than 90.0% of patients experiencing relief from various constipation symptoms, while psyllium husk showed comparatively lower efficacy.

CONCLUSION

KiwiBiotic is an effective treatment option for FC, abdominal pain, and bloating, highlighting its potential as a promising alternative therapy for patients with FC and its associated symptoms.

Key Words: KiwiBiotic; Psyllium husk; Constipation; Abdominal pain; Bloating

Core Tip: Functional constipation (FC) significantly affects the quality of life of patients due to symptoms such as abdominal pain and bloating. Conventional treatments often fail, necessitating alternative therapies. Phytotherapeutic product KiwiBiotic has emerged as a promising alternative treatment for FC, abdominal pain, and bloating, offering superior efficacy, improved quality of life, and higher patient satisfaction than conventional options such as psyllium husk. Its effectiveness in symptom relief, demonstrated in more than 90% of patients, highlights its potential as a safe and comprehensive therapeutic option.

INTRODUCTION

Constipation is characterized by a decrease in the regularity of bowel movements or challenges in stool discharge. Symptoms commonly linked to this condition include hard stool, effortful strain, blockage sensation in the anal region, sense of incomplete bowel emptying, abdominal pain, and swelling[1]. This condition is divided into several categories, including functional, chronic idiopathic, and secondary constipation, all of which are distinguished by specific causes and clinical characteristics[2]. Functional constipation (FC) is a type of functional bowel disorder characterized by symptoms such as difficulty in defecating, infrequent bowel movements, or a feeling of incomplete bowel evacuation, with a prevalence of approximately 20% in adults[3,4]. Constantly constipated patients are associated with higher all-cause mortality and are at higher risk of mental health issues[5]. Risk factors for constipation include living conditions, dietary patterns, and unhealthy lifestyle choices[6].

Many people with FC resort to self-medication, which can affect the ideal timing of treatment and worsen their condition[7]. Due to variables such as decreased mobility, polypharmacy, and coexisting medical diseases, older people frequently have poor tolerance to non-pharmacological treatments such as lifestyle changes (e.g., exercise, high-fiber foods, and increased fluid intake)[8,9]. The underlying causes of FC are complex and involve multiple factors, including genetics. However, specific genes linked to this condition have not been identified. This absence of genetic markers leads some experts to propose that lifestyle and environmental influences within certain families could actually explain the observed patterns of constipation rather than hereditary factors[10]. The quality of life and psychological well-being of patients are significantly affected by repeated consultations, unnecessary investigations, and prolonged disease duration, which impose substantial financial burdens and pose considerable challenges in managing the condition[11].

Bulk-forming drugs are usually recommended as first-line treatment for constipation. These substances absorb water to increase the amount of feces and facilitate bowel movements. Adequate fluid intake is crucial when using bulk-forming medications to prevent bloating and, more importantly, reduce the likelihood of intestinal obstruction associated with dehydration[12]. In addition to bulk-forming medications, various drugs are used to treat constipation, including stimulants, stool softeners, and osmotic agents, depending on the severity of the condition[13-16]. Although conventional treatment is established and considered safe, it often does not provide satisfactory improvement in many patients, leading them to explore alternative therapeutic approaches[17]. Complementary and alternative medicines are gaining popularity due to their perceived safety and efficacy[18].

Consequently, there is an incentive to consider medications from complementary and alternative medical systems as potential treatment options for constipation. The formulation used in the current study, KiwiBiotic, was in liquid form and contained mainly kiwi pulp. This study aimed to evaluate the safety and effectiveness of KiwiBiotic compared to psyllium husk in the management of FC, abdominal pain, and bloating.

MATERIALS AND METHODS

Study design

In this prospective, interventional, single-center, crossover study, participants diagnosed with FC were randomly assigned to groups in a 1:1 ratio. The trial was carried out at Healing Hands Clinic Pvt. Ltd., DP Road, Pune, Maharashtra, India. The study was registered with the Clinical Trial Registry of India (CTRI/2023/09/058081, dated 27^th September 2023) and the Institutional Ethics Committee of the Healing Hands Clinic, DP Road, Pune-411001 (HHCRS/HH&HPL-002/23-24). This study complied with the ethical guidelines of the 1975 Declaration of Helsinki.

Study products

The phytotherapeutic products, KiwiBiotic^® and psyllium husk, were provided by Healing Hands and Herbs Pvt. Ltd., located in Pune, India, www.myhealinghands.in. KiwiBiotic was manufactured and marketed by Healing Hands and Herbs Pvt., Ltd.

Participants

Eligible participants were aged ≥ 18 years and diagnosed with FC, abdominal pain, or bloating according to the ROME IV criteria[19,20]. Participants are only included if the participants, their parents, or any legal guardian are willing to give their written informed consent or parental consent or consent form and if they are willing to strictly adhere to the investigator’s prescription. Patients were excluded if they had taken any medication that could interfere with the action of the medication before or during the start of the study. Furthermore, patients with pre-existing conditions that could compromise their safety or participation in the study were excluded.

Randomization

Participants were randomly assigned in a 1:1 ratio to receive KiwiBiotic (50 mL orally twice daily) during period 1, followed by psyllium husk (1.82 g orally once daily) during period 2 (sequence 1), or psyllium husk during period 1, followed by KiwiBiotic during period 2 (sequence 2).

Procedures

During the screening visit, the participants underwent assessments of their medical history and concomitant medications, along with physical examinations. The patients were randomly assigned to undergo two treatment periods of 14 days each, with a 14-day washout period between them. Vital signs, such as body temperature, heart rate, blood pressure, oxygen saturation, and respiratory rate, were assessed at each visit (days 0, 14, 28, 42, and 49) to ensure safety. The last follow-up visit, scheduled for day 49, aimed to confirm whether symptoms had recurred after the completion of the final treatment on day 42 (Figure 1). Participants were assessed for efficacy following the administration of the study products. This includes an assessment of FC according to the ROME IV criteria and an assessment of abdominal pain and bloating using a visual analog scale. At the end of each treatment period, quality of life was evaluated using the gastrointestinal quality of life questionnaire, and the overall treatment evaluation score was measured.

Figure 1  Trial profile.

Outcomes

The primary efficacy endpoint was changes in FC symptoms, abdominal pain, and bloating. Secondary endpoints included the assessment of gastrointestinal quality of life using the gastrointestinal quality of life index (GIQLI), overall treatment evaluation scores by physicians, and incidence of adverse events, with data collected up to the 5^th visit.

Statistical analysis

The trial sample size was determined to detect a standardized difference of 0.6 with 90% power and significance level α = 5%, which represents a 10% dropout rate, resulting in the recruitment of 70 participants. Demographics and baseline characteristics of the participants were summarized using mean, SD, and range for continuous variables, and frequencies and percentages for categorical variables. Equivalence tests were conducted to compare abdominal pain and abdominal bloating at a significance level of 5%. For the symptoms of FC, we used a two-sided McNemar’s test, with a P-value < 0.05 indicating statistical significance. Two-sided paired t-tests were used to compare the overall GIQLI scores and their domains.

RESULTS

Between October 20, 2023 and February 12, 2024, a total of 70 patients were recruited. Of the initial 70 patients, 35 were randomly assigned to receive KiwiBiotic during period 1, followed by psyllium husk during period 2; the remaining 35 received psyllium husk during period 1, followed by KiwiBiotic during period 2. In this study, 44 females (62.86%) and 26 males (37.14%) were enrolled, with a mean age of 43.61 years (SD = 13.41). The average weight of all participants was 60.65 kg (SD = 8.09) and the average height was 163.42 cm (SD = 7.2). The mean body mass index of the entire cohort was 22.68 kg/m² (SD 2.48) (Table 1). During the second visit, three patients from sequence 1 and two patients from sequence 2 were excluded due to loss of follow-up. Thirty-two patients in the KiwiBiotic group and 33 patients in the psyllium husk group completed the study. At the 5% level of significance, no significant differences were observed between the groups, as P > 0.05.

Table 1 Patient characteristics at baseline (n = 70), n (%).

Demographics	KiwiBiotic	Psyllium husk	Total	P value
Gender				0.138a
Female	25 (71.43)	19 (54.29)	44 (62.86)
Male	10 (28.57)	16 (45.71)	26 (37.14)
Age (year)				0.156
Mean (SD)	41.4 (10.96)	45.83 (14.84)	43.61 (13.14)
Range	18-65	23-73	18-73
Weight (kg)				0.064
Mean (SD)	58.89 (7.88)	62.41 (8.03)	60.65 (8.092)
Range	42-80.9	47-79.3	42-80.9
Height (m)				0.123
Mean (SD)	162.1 (6.68)	164.73 (7.54)	163.42 (7.2)
Range	152-176.7	152-177	152-177
BMI (kg/m2)				0.291
Mean (SD)	22.37 (2.40)	23.00 (2.56)	22.68 (2.48)
Range	17.3-28.8	17.3-28.3	17.3-28.8

^aChi-square test.

BMI: Body mass index.

Changes in abdominal pain

The results showed that for the KP sequence, the mean score of abdominal pain was 1.4688 (SD = 0.87931) at visit 2 in period 1 and 6.2188 (SD = 2.4591) at visit 4 in period 2. In contrast, for the PK sequence, the mean score was 7.2121 (SD = 2.342) at visit 2 in period 1 and 1.6667 (SD = 1.0206) at visit 4 in period 2 (Table 2) (Figure 2A). These findings indicate that KiwiBiotic is more effective than psyllium husk in reducing abdominal pain.

Figure 2 Graphical representation of change in abdominal pain and abdominal bloating for sequence 1 (KP) and sequence 2 (PK). A: Abdominal pain; B: Abdominal bloating.

Table 2 Descriptive statistics for abdominal pain at visit 2 and visit 4.

	Sequence	n	Period 1		Period 2
			Mean	SD	Mean	SD
Abdominal pain	KP	32	1.4688	0.87931	6.2188	2.4591
	PK	33	7.2121	2.342	1.6667	1.0206

KP: KiwiBiotic during period 1 and psyllium husk during period 2; PK: Psyllium husk during period 1 and KiwiBiotic during period 2.

The crossover effect and analysis of abdominal pain showed that the estimated carryover effect was -1.1913 with a corresponding P-value of 0.092, exceeding = 0.05, indicating that the carryover effect was not statistically significant. Conversely, the estimated treatment effect was -5.1477, with a P-value of 0.000, demonstrating statistical significance at the 0.05 level and indicating that one treatment has a superior effect compared to the other. Furthermore, the estimated period effect was -0.39773, but the P-value of 0.175 exceeded = 0.05 (Table 3) (Figure 3A), indicating that the period effect was not statistically significant.

Figure 3 Period-wise change in abdominal pain and abdominal bloating for sequence 1 (KP) and sequence 2 (PK). A: Abdominal pain; B: Abdominal bloating.

Table 3 Cross-over effects and analysis details for abdominal pain.

	Effect	SE	DF	T value	P value	95%CI	Significance
Carryover	-1.1913	0.69641	63	-1.7106	0.092	-2.5830, 0.20038	No
Treatment	-5.1477	0.28995	63	-17.754	0.000	-5.7271, -4.5683	Yes
Period	-0.39773	0.28995	63	-1.3717	0.175	-0.97714, 0.18169	No

DF: Degrees of freedom; CI: Confidence interval.

Changes in abdominal bloating

The findings revealed that the average abdominal bloating score for the KP sequence was 1.3125 (SD = 0.7378) during visit 2 in period 1 and 4.9375 (SD = 1.7949) during visit 4 in period 2. The mean score for sequence PK was 5.4848 (SD = 1.8392) at visit 2 in period 1 and 1.4545 (SD = 0.6657) at visit 4 in period 2 (Figure 2B) (Table 4). Ultimately, these results suggest that KiwiBiotic showed a more substantial improvement in abdominal bloating than psyllium husk.

Table 4 Descriptive statistics for abdominal bloating at visit 2 and visit 4.

	Sequence	n	Period 1		Period 2
			Mean	SD	Mean	SD
Abdominal bloating	KP	32	1.3125	0.7378	4.9375	1.7949
	PK	33	5.4848	1.8392	1.4545	0.66572

The crossover effect and analysis of abdominal bloating show that the determined carryover effect was -0.68939. However, the P-value (0.178) exceeded = 0.05, indicating a lack of statistical significance for the carryover effect. The estimated treatment effect was -3.8277, with a P-value of 0.000, indicating statistical significance at the 0.05 level. This notable treatment effect implies that one treatment showed superior efficacy over the other. The estimated period effect was -0.20265 with a P-value of 0.382 (Table 5), surpassing = 0.05, making the period effect statistically insignificant.

Table 5 Cross-over effects and analysis details for abdominal blotting.

	Effect	SE	DF	T value	P value	95%CI	Significance
Carryover	-0.68939	0.50583	63	-1.3629	0.178	(-1.7002, 0.32143)	No
Treatment	-3.8277	0.22994	63	-16.646	0.000	(-4.2872, -3.3681)	Yes
Period	-0.20265	0.22994	63	-0.88131	0.382	(-0.66216, 0.25686)	No

DF: Degrees of freedom; CI: Confidence interval.

A one-sided t-test (5% level of significance) was performed for abdominal pain and abdominal bloating to determine the significant differences between treatments. The mean response to abdominal pain was 1.5692 for KiwiBiotic treatment and 6.7231 for psyllium husk treatment. Similarly, for abdominal bloating, the mean response was 1.3846 for KiwiBiotic treatment and 5.2154 for psyllium husk treatment (Table 6) (Figure 3B). These findings indicate a significant difference between the two treatments (P < 0.05).

Table 6 T-test for abdominal pain and abdominal bloating (one-sided).

	Mean (KiwiBiotic)	Mean (Psyllium husk)	SE	DF	T value	P value	Significance
Abdominal pain	1.5692	6.7231	0.28995	63	-17.754	< 0.05	Yes
Abdominal bloating	1.3846	5.2154	0.22994	63	-16.646	< 0.05	Yes

DF: Degrees of freedom.

Evaluation of FC using the Mcnemar test

After KiwiBiotic treatment, 39 patients reported no straining, while only one patient experienced the same result after psyllium husk treatment. Regarding the presence of lumpy or hard stool, 39 patients achieved complete relief with KiwiBiotic treatment, compared to only one patient with psyllium husk treatment. Similarly, for the feeling of incomplete evacuation of more than one-fourth (25%) of defecations, 37 patients found complete relief with KiwiBiotic treatment, while only one patient did so with psyllium husk treatment (Table 7).

Table 7 Assessment of functional constipation.

Symptoms of functional constipation	Number of subjects experiencing symptom relief from functional constipation after consuming KiwiBiotic but not after psyllium husk	Number of subjects experiencing symptom relief from functional constipation after consuming psyllium husk but not after KiwiBiotic	P value for MC-Nemar’s test
Straining during more than ¼ 25% of excretion	39	1	< 0.05
Lumpy or hard stools (BSFS type 1 or 2) more than 25% of defecations	39	1	< 0.05
Sensation of incomplete evacuation of more than one-fourth (25%) of defecations	37	1	< 0.05
Sensation of anorectal obstruction/blockage more than ¼ (25%) of defecations	33	0	< 0.05
Manual manoeuvres to facilitate more than ¼ (25%) of defecation	33	1	< 0.05
Fewer than three spontaneous bowel movements per week	11	2	< 0.05

In the evaluation of anorectal obstruction or sensation of blockage, nearly 33 patients experienced total relief after KiwiBiotic treatment, while none experienced relief after psyllium husk treatment. Concerning manual maneuvers to facilitate more than 25% defecation, 33 patients achieved complete relief with KiwiBiotic treatment, compared to only one patient with psyllium husk treatment. Similarly, among individuals who experienced fewer than three spontaneous bowel movements per week, 11 patients achieved complete relief with KiwiBiotic treatment, while only one patient reported complete relief with psyllium husk treatment (Table 7).

Rejecting the null hypothesis implies that one treatment is superior because it has more successful patient outcomes. McNemar’s test, which yields a two-sided P-value of < 0.05, for all FC symptoms, rejects the null hypothesis of no difference between treatments with KiwiBiotic and psyllium husk. Consequently, the test results significantly favored KiwiBiotic, as it was more effective in alleviating FC symptoms.

Table 8 indicates that patients treated with KiwiBiotic experienced relief of symptoms that exceeded 90% in various symptoms related to FC, exceeding the relief observed in patients treated with psyllium husk.

Table 8 Percentage of subjects improved their symptoms of functional constipation.

Symptoms of functional constipation	After the KiwiBiotic treatment (%)	After the psyllium husk treatment (%)
Straining during more than ¼ 25% of excretion	91.0	32.0
Lumpy or hard stools (BSFS type 1 or 2) more than 25% of defecations	91.0	32.0
Sensation of incomplete evacuation of more than one-fourth (25%) of defecations	91.0	35.0
Sensation of anorectal obstruction/blockage more than ¼ (25%) of defecations	95.0	45.0
Manual manoeuvres to facilitate more than ¼ (25%) of defecation	94.0	45.0
Fewer than three spontaneous bowel movements per week	97.0	83.0

Assessment of the GIQLI

Following treatment with KiwiBiotic, the overall score of the gastrointestinal symptom questionnaire was -39.69 (SD = 6.3), compared to -10.78 (SD = 15.7) after psyllium husk treatment. Regarding the psychological questionnaire, the mean score was -10.19 (SD = 2.2), compared to -0.415 (SD = 5.5) after psyllium husk treatment. After KiwiBiotic treatment, the mean score for the physical questionnaire was -16.71 (SD = 3.3) and for the social questionnaire, it was -2.37 (SD = 3.6). On the contrary, after psyllium husk treatment, the mean scores were -3.23 (SD = 7.1) for the physical questionnaire and -0.077 (SD = 2.0) (Table 9) for the social questionnaire. The overall mean score for the KiwiBiotic treatment was -68.95 (SD = 10.5) and for the psyllium husk treatment, it was -14.51 (SD = 26.8) (Table 9) (Figure 4). These findings suggest that KiwiBiotic generally provides a greater improvement in GIQLI and its domains, such as gastrointestinal symptoms and psychological, physical, and social well-being, compared to psyllium husk treatment, as evidenced by the statistically significant differences in mean scores.

Figure 4  Box-plot for overall gastrointestinal quality of life index after treatment.

Table 9 Effect of treatments on gastrointestinal quality of life index and its domain and estimation for paired differences (two-sided).

	KiwiBiotic			Psyllium-husk
	Estimation for paired difference
GIQLI domains	Mean (SD)	95%CI	P value	Mean (SD)	95%CI	P value
GI-symptoms	-39.69 (6.3)	-41.264, -38.121	< 0.05	-10.78 (15.7)	-14.67, -6.90	< 0.05
Psychological	-10.19 (2.2)	-10.744, -9.626	< 0.05	-0.415 (5.5)	-1.787, 0.956	0.547
Physical	-16.71 (3.3)	-17.533, -15.883	< 0.05	-3.23 (7.1)	-4.999, -1.463	0.001
Social	-2.37 (3.6)	-3.262, -1.476	< 0.05	-0.077 (2.0)	-0.571, 0.417	0.757
Overall	-68.95 (10.5)	-71.56, -66.35	< 0.05	-14.51 (26.8)	-21.15, -7.86	< 0.05

CI: Confidence interval; GI: Gastrointestinal; GIQLI: Gastrointestinal quality of life index.

Overall treatment evaluation

Approximately 53.38% of the patients experienced a complete resolution of the condition, 41.54% of the patients reported a significant improvement in their condition, and only 3.08% of the patients reported a slight improvement in their condition after KiwiBiotic treatment (Table 10). Overall, the table shows that a higher percentage of patients experienced positive outcomes, including resolution and significant improvement, when treated with KiwiBiotic than with psyllium Husk.

Table 10 Overall treatment evaluation score.

Condition	KiwiBiotic (%)	Psyllium-husk
Resolved	55.38	0.00
Much better	41.54	9.23
Little better	3.08	13.85
The same	0.00	33.85
Worse	0.00	43.08

DISCUSSION

In this single-center study conducted in a single center, the findings underscore the safety and efficacy of KiwiBiotic in managing symptoms associated with FC, abdominal pain, and bloating compared to psyllium husk. This study revealed significant improvements in various parameters, including symptom relief, quality of life, and overall treatment evaluation, in patients treated with KiwiBiotics. More than 90.0% of the patients experienced symptom relief from FC following treatment with KiwiBiotic. Generally, most of the participants exhibited good tolerance to treatment.

The inherent properties of kiwifruit have shown their effectiveness in reducing symptoms such as constipation, abdominal pain, and discomfort[21-23]. KiwiBiotic contains mainly kiwi pulp and a required quantity of excipients. KiwiBiotic demonstrated a marked decrease in abdominal pain and bloating, supported by notably lower mean scores of 6.2188 and 4.9375, respectively, at visit 4. The analysis of crossover effects indicated statistically significant treatment effects for both abdominal pain and bloating, with a P-value of 0.000 for each, further highlighting the superior efficacy of KiwiBiotic compared to psyllium husk in relieving these symptoms. In the management of FC, more than 90.0% of the patients found relief from symptoms such as straining, lumpy or hard stools, the feeling of incomplete evacuation, the feeling of anorectal obstruction or blockage, the need for manual maneuvers, and fewer than three spontaneous bowel movements per week after treatment with KiwiBiotic. In contrast, after psyllium husk treatment, only 32.0% of the patients experienced relief from straining and lumpy or hard stools, 35.0% from the sensation of incomplete evacuation, 45.0% from the sensation of anorectal obstruction or blockage and the need for manual maneuvers, and 83.0% from fewer than three spontaneous bowel movements per week.

Importantly, the evaluation of GIQLI and its domains revealed that KiwiBiotic significantly improved overall gastrointestinal symptoms, psychological well-being, physical health, and social aspects compared to psyllium husk. These findings underscore the extensive benefits of KiwiBiotic in enhancing the patient’s quality of life beyond symptom relief alone. Furthermore, the overall treatment showed a substantially higher percentage of patients experiencing resolution or significant improvement with KiwiBiotic than with psyllium husk. Collectively, these results suggest that KiwiBiotic is a promising treatment option for managing constipation, abdominal pain, and bloating, offering superior efficacy and patient satisfaction compared to psyllium husk.

CONCLUSION

In conclusion, our study demonstrates that KiwiBiotic is a safe and effective treatment option for managing symptoms of FC, abdominal pain, and bloating. Its superior efficacy, favorable impact on the quality of life, and high patient satisfaction make it a promising alternative to conventional treatments such as psyllium husk. Further research, including larger sample size and long-term follow-up studies, is warranted to validate these findings and establish KiwiBiotics as a standard therapeutic option for individuals with FC and related symptoms.