JRAS

Renu Singh et al 10.5005/jp-journals-10064-0015

Research Article

Clinical Safety of Selected Ayurvedic Formulations in

Management of Irritable Bowel Syndrome
1
Renu Singh, 2Punendu Panda, 3Laxman W Burke, 4Harbans Singh, 5Surendra K Sharma, 6Krishna Kumari
7
Om Raj Sharma, 8Meda M Rao, 9Rinku Tomar, 10Shweta Chaudhary, 11Shruti Khanduri, 12Gurucharan Bhuyan
13
Babita Yadav, 14Pradeep Dua, 15Rakesh K Rana, 16Richa Singhal, 17Adarsh Kumar

ABSTRACT A p-value < 0.05 was considered significant. Drug compliance

and adverse drug reaction/adverse events, if any, were noted.
Introduction: Irritable bowel syndrome (IBS) is a part of the larger
group of functional gastrointestinal (GI) disorders that despite Conclusion: The analysis of two different clinical studies
differences in location and symptom patterns share common clearly reveals that Bilvadi Leha and Kutajarishta are clinically
features with regard to their motor and sensory physiology and safe, effective, and tolerable.
central nervous system relationships. It generates a significant Keywords: Bhayaja Atisara, Bilvadi Leha, Grahani, Kaphaja
health care burden and can severely impair quality of life. It is Pravahika, Kutajarishta, Shokaja Atisara.
characterized by symptoms of abdominal pain and discomfort
that is associated with disturbed defecation. Ayurveda compares How to cite this article: Singh R, Panda P, Burke LW, Singh H,
the symptoms of IBS with some of the diseases like Grahani, Sharma SK, Kumari K, Sharma OR, Rao MM, Tomar R,
Kaphaja Pravahika, Shokaja Atisara, Bhayaja Atisara, etc. Bilvadi Chaudhary S, Khanduri S, Bhuyan G, Yadav B, Dua P, Rana RK,
Leha and Kutajarishta are two common Ayurvedic formulations Singhal R, Kumar A. Clinical Safety of Selected Ayurvedic
that are currently used for the management of such diseases. Formulations in Management of Irritable Bowel Syndrome.
However, the safety of these drugs was not evaluated until now. J Res Ayurvedic Sci 2017;1(3):136-141.

Objective: Analysis of clinical safety and efficacy outcomes of Source of support: Nil
Bilvadi Leha and Kutajarishta in IBS generated through multi- Conflict of interest: None
center open-label clinical studies at different CCRAS centers.
Materials and methods: Analysis of data collected from
INTRODUCTION
two different clinical studies was critically evaluated. Safety
assessments were done through analyzing liver function tests Irritable bowel syndrome is a GI disorder characterized
(LFTs), alanine aminotransferase, aspartate aminotransferase,
by altered bowel habits in association with abdominal
serum alkaline phosphatase, serum protein, albumin, globulin,
and bilirubin, and kidney function tests (KFTs) before and after discomfort or pain in the absence of detectable structural
the trial period. Paired sample t-test was used for comparison. and biochemical abnormalities.1 It basically happens due
to alteration in GI motility, secretion, and sensation.2,3 The
symptomatic analysis of IBS, points to Grahani, Kaphaja
1-4,9-14
Research Officer (Ayurveda), 5,6,17Assistant Director Pravahika, Shokaja Atisara, Bhayaja Atisara, etc., mentioned
(Ayurveda), 7Former Assistant Director (Ayurveda), 8Director in Ayurveda classics which are characterized by altered
(Ayurveda), 15Statistical Officer (Ayurveda), 16Statistical Assistant
bowel habits and other GI symptoms.
(Ayurveda)
1,10,11,13-17
The pathogenesis of Grahani 4 begins with the
Central Council for Research in Ayurvedic Sciences
vitiation of Agni (digestive fire) in terms of its quality,
New Delhi, India
2
quantity, and function. All metabolic physiological
National Research Institute of Ayurvedic Drug Development
Bhubaneswar, Odisha, India
transformations in the body are carried out under the
3,6
influence of Agni. Mandagni (quantitative, qualitative,
Regional Ayurveda Research Institute for Urinary Disorders
Jammu, Jammu and Kashmir, India and functional decrease of Agni) is the root cause of Ama
4 Dosha, and it is a crucial factor for manifestation of most
Central Ayurveda Research Institute for Respiratory Disorders
Patiala, Punjab, India of the diseases.5 Ama Dosha, resulting from Mandagni,
5,7 plays a pivotal role in the pathogenesis of GI disorders,
Regional Ayurveda Research Institute for Nutritional
Disorders, Mandi, Himachal Pradesh, India such as Grahani Roga, Bhayaj Atisara, Shokaj Atisara, etc.
8,12
Central Ayurveda Research Institute for Hepatobiliary
Vitiation of Samana and Apana Vayu affects the enteric
Disorders, Bhubaneswar, Odisha, India nervous system, alters the GI motility and hormone
9
Regional Ayurveda Research Institute for Mother and Child
activity producing the symptoms of Grahani. All these
Health, Nagpur, Maharashtra, India diseases have psychological factors, such as fear and
Corresponding Author: Renu Singh, Research Officer anxiety as etiology, and IBS also has psychological
(Ayurveda), Central Council for Research in Ayurvedic Sciences factors responsible for its origin.
New Delhi, India, Phone: +911128520945, e-mail: drrenusingh@ The modern IBS therapies include bulk-forming
yahoo.com
agents, antidiarrheal, antispasmodics, antidepressants,

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 JRAS

Clinical Safety of Selected Ayurvedic Formulations in Management of Irritable Bowel Syndrome

etc., which lack demonstrable efficacy. While considering food (trial 2). Follow-up was done every 2 weeks in
the cost and potential risks (severe constipation, severe both the trials to record the onset of any adverse reac-
diarrhea, ischemic colitis) against potential benefits, tion during the intervention. Total intervention period
potential risks outweigh the possible benefits.6 Therefore, was 12 weeks. The data obtained from the completed
exploring alternative medicines for therapeutic options, clinical studies were analyzed retrospectively to assess
which are effective, economical, and safe, is needed. the safety profile of Bilvadi Leha and Kutajarishta through
Bilvadi Leha and Kutajarishta are two of the drugs used LFTs and KFTs.
in diseases which are symptomatically similar to IBS
and have been practiced by many practitioners. This set Statistical Analysis
of studies was done to analyze the safety of Bilvadi Leha Data of LFTs and KFTs collected at the beginning and at
and Kutajarishta in IBS. the end of the trial period were compared using paired
t-tests. A p-value <0.05 was considered significant. Clini-
Drug Profile
cal symptoms have been reported as n (%) and have been
The drugs that act on regulating the Agni and movement compared as percentage change before and after the
of Koshta must contain the following properties: Agnideep- treatment.
ana (enhancing the digestive activity), Amapachana (elimi-
nating undigested metabolic products), Vata Anulomana OBSERVATION AND RESULTS
(regulating samana and apana and normalising its activ- Bilvadi Leha
ity) and should act at the level of Kostha and modulate
the altered GI activity. The set of two studies was done A total of 171 patients were enrolled in study I entitled
to analyze the safety of Bilvadi Leha and Kutajarishta in Clinical Evaluation of Bilvadi Leha in the Management of
patients with IBS. Bilvadi Leha7 is a formulation mentioned IBS of which 22 patients dropped out in the course of the
in Sahasrayoga (Lehaprakaran-1), Kutajarishta8 is described study. Among the total dropouts, 8 were not included for
in the context of Atisara in Bhaishajya Ratnawali (atisar analysis. Last observation carried forward was applied on
adhikar). 14 patients who had completed at least two visits. Thus,
data of 163 (171 – 22 + 14) patients were used for analysis.
OBJECTIVE Among the dropout patients, no one quit the study for
the reason of drug’s safety or palatability issues, so it is
Critical analysis and presentation of clinical safety out-
clear that the medicine had not any adverse effect on
comes of classical Ayurvedic formulations Bilvadi Leha
their health.
and Kutajarishta in IBS, generated through multicenter
Among the total analyzed 163 patients, 66.9% were
open-label clinical studies at different CCRAS centers.
males and remaining 33.1% were females. The mean age
of 163 patients was observed to be 42.88. Total 54% of the
MATERIALS AND METHODS
patients hailed from urban area. Maximum number of
Two different clinical trials, viz. Clinical Evaluation of patients (47.8%) was doing desk work with less physical
Bilvadi Leha in the Management of IBS (trial 1) with CTRI activity, and 84% were above poverty line. About 92.6%
number CTRI/2012/04/002577 and Clinical Evaluation of of the patients were able to read and write. The history
Kutajarishta in the Management of IBS (trial 2) with CTRI of stress was identified in 50.9% of patients, and 55.8% of
number CTRI/2014/09/005066, were done separately at the population were vegetarian. Irregular bowel habits
three different centers. The formulations fulfilling the were seen in 92.0% patients. Loose stool consistency was
physicochemical standards and quality parameters and seen in 67.5% cases.
prepared as per standard operating procedures laid down Effect of Bilvadi Leha on disease-specific symptoms,
in Ayurvedic Pharmacopia of India (Part II) were procured IBS severity score, and WHO quality of life (QOL)-
from good manufacturing practices-certified companies BREF score was statistically significant (p-value < 0.001).
for both the studies. Both the clinical studies were also Chronic or recurrent abdominal discomfort was present
approved by institutional ethics committee and done in in 90.8% of cases at baseline, and after completion of
accordance with World Health Organization (WHO)— treatment it remained only in 26.4%. Likewise, abdominal
Good Clinical Practice Guidelines. Sample size used for bloating was present in 89.6% cases at the baseline, which
analysis was 163 for trial 1 and 178 for trial 2. was reduced to 42.3% at the end of day 84. No significant
Bilvadi Leha was given as the dose of 10 gm BD with adverse events or adverse reactions were observed during
lukewarm water after food (trial 1) and Kutajarishta was the study. Both, the LFTs and KFTs were found to be in
given as 25 mL BD with equal amount of water after normal limits before and after the trial.
Journal of Research in Ayurvedic Sciences, July-September 2017;1(3):136-141 137
Renu Singh et al

Kutajarishta Table 1: Demographic profile of the patients in

both clinical trials
A total of 180 patients were enrolled in the study entitled Bilvadi Leha Kutajarishta
Clinical Evaluation of Kutajarishta in the Management of Demographic profile (n = 163) (n = 178)
IBS of which 10 patients dropped out in the course of the Sex
study. Last observation carried forward was applied on  Male 109 (66.9%) 108 (60.7%)
8 patients who had completed at least two visits. Thus,  Female 54 (33.1%) 70 (39.3%)
Education
data of 178 (180 – 10 + 8) patients was used for analysis.
  Not able to read and write 12 (7.4%) 13 (7.3%)
The dropout patients were not included in the study, as
 Literate 151 (92.6) 165 (92.7%)
they could not turn up for follow-up in time due their Socioeconomic status
prior engagement out of the city. One patient reported   Below poverty line 26 (16.0%) 13 (7.3%)
increased frequency of bowels and did not continue the   Above poverty line 137 (84.0%) 165 (92.7%)
study. Diet
Among those 178 patients, majority of patients were  Vegetarian 91 (55.8%) 121 (68.0%)
under the age group from 39 to 48 years, i.e., 37.6% (67  Nonvegetarian 72 (44.2%) 57 (32.0%)
Prakriti
patients). About 60.7% of them were males and remain-
  Vataja 1 (0.6%) –
ing 39.3% were females. Total 92.7% were literate, and
  Pittaja 10 (6.1%) –
majority of them were having desk work. Also, 92.7%   Kaphaja 2 (1.2%) –
of them were having good socioeconomic status. Urban   Vata-Pittaja 91 (55.8%) 65 (36.1%)
area-residing patients were 68.5%. Among the total, 68%   Pitta-Kaphaja 56 (34.4%) 92 (51.1%)
of the patients were vegetarian. Major symptoms noted   Vata-Kaphaja 1 (0.6%) 23 (12.8%)
in the patients were irregular bowel habits in 81.5% cases   Sannipataja 2 (1.2%) –
and loose stools in 81.5% cases. Effect of Kutajarishta on Patients completing the trial
from different geographical
chief complaints, disease-specific symptoms, IBS severity locations
score, and WHO QOL-BREF score was highly significant  Jammu 52 (31.9%) 59 (33.1%)
(p < 0.001), for example, chronic or recurrent abdominal  Mandi 53 (32.5%) 60 (33.8%)
discomfort or pain was present in 99.4% of cases at base-  Patiala 58 (35.6%) 59 (33.1%)
line, and after completion of treatment it was present in
24.7% of cases. Likewise, urgency of bowel movements
parameters obtained from the three centers are given in
was present in 86.5% cases at the baseline, which was
Table 2 and Graphs 1 to 4.
reduced to 16.3% at the end of day 84. No significant
adverse events or adverse reactions were observed during
DISCUSSION
the study. Both, the LFTs and KFTs were found to be in
normal limits before and after the trial. The data regard- Irritable bowel syndrome is a functional GI disorder
ing demographic profile are given in Table 1, and safety characterized by abdominal pain or discomfort, altered

Table 2: Efficacy and safety profile of the patients in both the clinical trials
Bilvadi Leha Kutajarishta
Parameters Baseline Day 84   p-value Baseline Day 84 p-value
LFT
Conjugated bilirubin (mg/dL) 0.18 (0.113) 0.16 (0.096)   0.047 0.14 (0.096) 0.14 (0.089) 0.966
bilirubin (mg/dl) bilirubin (mg/dl)
Unconjugated bilirubin (mg/dL) 0.49 (0.215) 0.49 (0.162)   0.910 0.55 (0.242) 0.55 (0.305) 0.860
SGPT (ALT) (IU/L) 26.39 (12.925) 23.78 (11.324) <0.001 30.21(14.948) 30.10 (15.350) 0.916
SGOT (AST) (IU/L) 26.85 (8.988) 25.81(7.628)   0.093 25.85 (8.152) 25.06 (8.661) 0.242
Serum alkaline phosphatase (IU/L) 148.02 (83.018) 118.11 (91.841) <0.001 127.20 (71.525) 124.73 (66.722) (90.40) 0.291
Total protein (gm/dL) 7.23 (0.609) 7.23 (0.570)   0.988 7.12 (0.551) 7.09 (0.582) 0.523
Serum albumin (gm/dL) 4.32 (0.489) 4.21 (0.488)   0.008 4.11 (0.386) 4.06 (0.376) 0.115
Serum globulin (gm/dL) 2.92 (0.533) 3.02 (0.475)   0.086 2.99 (0.525) 3.02 (0.565) 0.517
KFT
Blood urea (mg/dL) 24.87 (5.276) 25.09 (5.937)   0.626 24.76 (6.594) 24.30 (6.136) 0.446
Serum creatinine (mg/dL) 0.90 (0.150) 0.86 (0.158)   0.002 0.93 (0.512) 0.92 (0.454) 0.871
Serum uric acid (mg/dL) 5.18 (1.099) 5.22 (1.102)   0.593 5.41 (1.1258) 5.35 (1.170) 0.585
p-value <0.05 is considered significant; AST: Aspartate transaminase; ALT: Alanine transaminase

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Clinical Safety of Selected Ayurvedic Formulations in Management of Irritable Bowel Syndrome

Graph 1: Liver function tests (SGOT and SGPT) before and Graph 2: Liver function test (serum alkaline phosphatase)
after the trial before and after the trial in both the studies

Graph 3: Liver function test (total protein, serum albumin, and serum globulin) before and after the trial in both the studies

intestines is either too slow or too fast. Although IBS

does not cause any threat to life, it can be a long-lasting
problem affecting the quality of life. Therefore, treatment
of IBS is very important for improving the quality of
life in such patients. In Ayurveda, we use drugs having
properties like Ama Pachana, Agnideepana, Vatanulomana,
and Sangrahi which have nature to treat conditions like
Grahani, Kaphaja Atisara, Bhayaja Atisara, Pravahika, etc.,
which have symptoms similar to IBS. Thus, these two
studies were done to see the safety and efficacy of Kuta-
jarishta and Bilvadi Leha in the management of IBS.
On analysis, it was observed that majority of IBS
patients were having desk work with minimal physical
activity as their profession. Physical inactivity may have an
Graph 4: Kidney function test (blood urea and serum indirect role in altering the intestinal motility and may lead
creatinine) before and after the trial in both the studies
to apana vayu vaigunya in koshtha producing alteration in
bowel habits. The disease was found mostly in residents of
bowel habit, and psychiatric symptoms, such as anxiety urban region, which may be due to the unhealthy dietary
or depression in the absence of any detectable organic habits and stressful life. Common symptoms manifested
pathology. Movement of food and the faces in the were chronic or recurrent abdominal discomfort or pain,
Journal of Research in Ayurvedic Sciences, July-September 2017;1(3):136-141 139
Renu Singh et al

abdominal bloating, urgency of bowel movements, feeling and Vata in the intestine are the key factors in managing
of incomplete evacuation, passage of mucous, straining, IBS. Kutajarishta and Bilvadi Leha act by regulating the
distension of abdomen, etc., due to agnimandya leading to activity of Doshas and Agni in Koshta. From this study, it
ama formation, which causes obstruction (srotoavarodha) in can be concluded that in spite of the differences in gender,
the GI pathways. The IBS is a disease that responds well socioeconomic status, age group, Prakrti, and geographic
with proper alterations in diet (using food that are easily region, Kutajarishta and Bilvadi Leha proved to be very
digestible without stress to GI tract), physical activity much safe, effective, and tolerable in the management of
and with decrease in stress levels. But, once the disease IBS. No adverse reactions or adverse events pertaining
manifests, maintenance of Agni and Vatanulomana is the to drug interaction were noticed during the trial period.
right path to relieve symptoms.
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Clinical Safety of Selected Ayurvedic Formulations in Management of Irritable Bowel Syndrome

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Journal of Research in Ayurvedic Sciences, July-September 2017;1(3):136-141 141