An Open-Label Single-Arm Clinical Study to Evaluate Effectiveness of Polyherbal Ayurveda Formulation in Alcoholic Liver Disease : Journal of Ayurveda

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CLINICAL STUDY: Original Article

An Open-Label Single-Arm Clinical Study to Evaluate Effectiveness of Polyherbal Ayurveda Formulation in Alcoholic Liver Disease

Kumar Jain, M. J. Sushruth; Shrilata, 1,; Savitha, H. P.2; Adiga, Manjunatha3; Shetty, Suhas Kumar4; Kumar, T. Sanath5

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Journal of Ayurveda 17(1):p 10-14, Jan–Mar 2023. | DOI: 10.4103/joa.joa_127_22
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Abstract

Introduction

Indiscriminate and repeated use of alcohol produces a gradual, physical, and moral deterioration of the individual, culminating in crimes or perversions. Despite the untoward effects of alcohol, alcoholism is a major problem in India, with an estimated prevalence rate of 16%–50%.[1,2] Daily alcohol use of more than 60–80 g/day for males and 20–40 g/day for females for 10–12 years is attributed to a 25-fold greater risk of developing alcoholic liver disease (ALD).[3] This concomitant is referred to as Madya Janya Yakrit vikara in Ayurveda, and it manifests as Pandu (anemia), Kamala (jaundice), and Udara (ascites), with yakritodara (hepatomegaly) being the cardinal symptom.[4] There is a need for medicine that can act on every unit of health while also ensuring safety and efficacy. Therefore, a polyherbal formulation, Patoladi Gana Kashaya, having hepatoprotective, nootropic, antihyperlipidemic, and choleretic properties, was opted to investigate its effectiveness in ALD (Madya Janya Yakrit Vikara).

Materials and Methods

Research design

This study was an open-label, single-arm (uncontrolled) before and after study, with pre- and posttest design in 30 individuals. The ethical clearance was obtained from the Institutional Ethics Committee (IEC No: SDM/IEC/33/2014–2015). The study was registered under the Clinical Trial Registry India (REF/2016/06/011559). The study individuals were recruited from the Outpatient Department of SDM College of Ayurveda Hospital, Hassan, based on diagnostic criteria such as clinical findings, an elevated liver function test with or without symptoms of jaundice, and a predefined symptom scale.

Inclusion criteria

Consenting (in written form) individuals diagnosed with per aforesaid criteria, aged between 30 and 60 years, irrespective of gender, socioeconomic, and religious background, were included.

Exclusion criteria

Individuals with advanced stages of ALD, other systemic illnesses, or suffering from other chronic psychiatric illnesses, organic brain diseases, and under hormonal or psychiatric treatment were not included in the study.

Withdrawal criteria

Individuals were allowed to withdraw from the trial in case of any adverse reaction from the trial drug or worsening of clinical condition.

Intervention

All individuals were treated with polyherbal formulation Patoladi Gana Kashaya[5] two pala (90 ml) in three divided doses of 30 ml after food with equal warm water for 30 days. The trial drug was purchased from an authentic pharmacy. Ingredients are tabulated in Table 1.

T1
Table 1:
Ingredients of Patoladi gana kashaya

Outcome measures

Subjective parameters such as Mandagni (reduced appetite), Jwara (fever), Chardi (vomiting), Peetanetrata, Peetashakrith, Peetamutrata (yellowish discoloration of conjunctiva, feces, and urine, respectively), Udarashula (pain abdomen), Baddhashakrith (constipation), and Daaha (burning sensation) were ranked either present or absent and were assessed pre- and posttest. Objective parameters such as liver function test and lipid profile were employed in the study.

Overall assessment

The overall effect of the therapy was graded in terms of complete remission (100%), marked improvement (75%–99%), moderate improvement (50%–74%), mild improvement (25%–49%), and unchanged (<24% reduction in chief complaints).

Statistical analysis

SPSS (Statistical Package for the Social Sciences) version 23 (IBM Corp., Armonk, N.Y., USA) was used to tabulate and analyze the collected data. Descriptive statistics were used to analyze demographic data and other relevant information. Ordinal data were analyzed using nonparametric tests such as Cochran‘s Q, McNemar test, and objective parameters by t-test. The changes (one tailed) with P < 0.05 were considered statistically significant.

Results

Study population

Thirty-six individuals diagnosed with Madyajanya Yakrit Vikara and who fulfilled the eligibility criteria were enrolled in the study. Six individuals dropped out due to personal commitments. Thirty individuals completed the study. The incidences of age, sex, religion, socioeconomic status, occupation, etc., noted in the patients of this study were as follows. Of the maximum individuals, 97.2% were male aged between 40 and 50 years (41.70%). Seventy percent of individuals were from the middle class, 72.2% were married, and 55.6% were business owners. Among the total number of individuals (36 patients), 80.6% of them had their first drink in life between 20 and 30 years of age. For 1–5 years, 72.2% of people consumed alcohol daily, with rum (47.2%) and brandy (38.9%) being the most common. The majority of patients (58.2%) drank between 90 and 180 ml of alcohol. The individuals had a conflicted family atmosphere. About 58.33% of individuals had a conflicted family atmosphere.

Clinical presentation

Most prevalent symptoms were Mandagni (97.2%), Peetamootrata (80.6%), Peetashakrith (66.7%), Udarashoola (58.3%), Baddhashakrith (50%), and Peeta netrata (41.7%). Eighty percent had a mild level of severity.

Effect of intervention

The polyherbal formulation Patoladi gana kashaya has shown a 46.28% improvement in total bilirubin level, a 47.7% and 55.42% improvement in direct and indirect bilirubin levels, respectively, with statistical significance. With statistical significance [Table 2], there was a 58.58% and 68.9% improvement in serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase levels, respectively. Overall, total cholesterol levels improved by 5.5%, high-density lipoprotein levels improved by 5.4%, and low-density lipoprotein levels improved by 8.7% with statistical significance [Table 3]. In subjective parameters, statistical significance was obtained in Mandagni, Jwara, Chardi, Udarashoola, Baddhashakrith, and Peetanetrashakruthmootrata (P < 0.05) [Tables 4 and 5]. Overall Patoladi Gana Kashaya has shown marked improvement in 40% of patients and moderate improvement in 60% of patients.

T2
Table 2:
The effect of Patoladi gana kashaya on liver function test of Madyayajanya yakrit vikara (alcohol liver disease)
T3
Table 3:
The effect of Patoladi gana kashaya on lipid profile of Madyayajanya yakrit vikara (alcohol liver disease)
T4
Table 4:
The effect of Patoladi gana kashaya on symptoms of Madyayajanya yakrit vikara (alcohol liver disease) (pretest-Cochran` Q)
T5
Table 5:
The effect of Patoladi gana kashaya on symptoms of Madyayajanya yakrit vikara (alcohol liver disease) (posttest-McNemar’s test)

Discussion

The study showed a higher incidence of the subject population in the fourth decade of life, and the first drink to be in the second decade of life. The finding is similar to the study by Benegal et al. (2005) who also reported the average duration of abuse to be 10–12 years.[6] Mohan et al. the majority of drinkers were moderate drinkers, which is also seen in this study.[7] The role of alcohol in domestic violence is seen in this study and also cited in an Indian study which found that 33% of spouse-abusing husbands were using alcohol and more than half of the spousal abuse took place during the period of intoxication.[8] Regardless of the severity of the disease process, the most common physical examination finding in patients with either steatosis or alcoholic hepatitis is hepatomegaly[9] which was found in our study. The classic also suggests the cardinal symptom of Yakrit Vikara (liver disease) to be Yakritodara (hepatomegaly). The vast majority of patients with ALD will have elevated liver function along with an altered lipid profile, which was seen in this study as well.[10] Excessive alcohol (Madya), Vidahi, and Abhishyandi Ahara vitiates Agni, Pitta, and Yakrit (liver) resulting in Rakta Pradoshaja Vyadhi and/or Yakrit Vikara.[4] From this perspective, we can deduce that excessive alcohol consumption deteriorates liver functions, resulting in liver disease, and hence clinical features of ALD counterpart Madya Janya Yakrit Vikara.

In general, liver disorders are contemplated as disorders of Pitta origin. It is due to the invariable relationship between rakta-pitta-agni (the vital components of metabolism).[11] The line of management opted is virechana-madhyama shodhana (moderate elimination of deranged pitta)). In this regard, the trial drug Patoladi Gana Kashaya aims at breaking the chain of disease manifestation. It is tikta rasa (bitter taste) predominant, ushna veerya (hot potency), katu vipaka (hot potency), rooksha (dry), and laghu (light) in nature.[5] It mostly targets pitta and kapha dosha, and contains pittasaraka (thaw pitta out of the body), deepana (kindle digestion), pachana (digestive), anulomana (corrects functioning of vata dosha), and bhedana (choleretics)[12,13] properties. The drug which has cholesteric properties stimulates the secretion of bile and causes virechana. The laghu guna aids easy absorption, assimilation, and anulomana. Individually, Patola has been shown in animal studies to have adaptogenic,[14] anti-inflammatory,[15] anti-proliferative,[16] and laxative effects.[17] Katukarohini picrosides I and II have been shown in molecular studies to have hepatoprotective, anti-toxin, and antioxidant properties.[18,19] The ethanol and aqueous stem bark extract of Raktachandana afforded significant protection against CCl4-induced hepatocellular injury.[20]Neema et al. (2011)[21] investigated the hepatotoxicity of murva. The antihepatotoxic activity of Guduchi has been demonstrated in CCl4-induced liver damage, normalizing liver function as assessed by morphological and biochemical parameters.[22]Patha has also been shown in experimental models to have anti-inflammatory, diuretic, hepatoprotective, antioxidant, and immune modulator activity.[23] Patola[24] and Chandana[25] have been shown to have antihyperlipidemic activity in studies. This formulation also possesses medahara (antihyperlipidemic), kaphahara (reducing kapha dosha) actions, thus yielding better results in improving the lipid profile. In short, choleretic, hepatoprotective, hepatocurative,[20] and antihyperlipidemic properties of the trial drug might have yielded a better outcome when compared to the baseline value. Overall, Patoladi Gana Kashaya has shown marked improvement in 40% of patients and moderate improvement in 60% of patients.

Considering the complication of ALD to be cirrhosis, ascites, and portal hypertension, the study limits itself in generalizing its results. The small sample size and restricted resources for conducting the trial are also drawbacks. As the majority of the participants were alcoholic dependants, additional trials involving psychotherapy might be conducted to see if it has a potentiating effect on pharmaceutical intervention, independent therapeutic outcomes, or both.

The polyherbal formulation (Patoladi Gana Kashaya-30 ml t.i.d. after food with 30 ml of warm water) is an effective option clinically in the management of Madya Janya Yakrit Vikara (alcohol liver disease). The polyherbal formulation is also helpful in the restoration of normal liver function and lipid profile. We assume that the ingredients initially acted on agni as deepana and pachaka and later as pitta rechaka. No adverse effects were reported by the individuals during the study. It is important to reproduce this study using larger samples and standard assessment tools.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

F1

Acknowledgment

We acknowledge our Principal, Dr. (Prof) Prasanna Narasimha Rao for invariable support and guidance throughout the study period. We also acknowledge all the subjects for their active participation.

References

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Keywords:

Alcohol; liver disease; Madatyaya; madya; patoladi gana kashaya; substance abuse; yakrit vikara

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