Conceptual Study

Non Alcoholic Fatty Liver Disease (NAFLD) is simply fat deposition in the liver that is not caused by chronic ingestion of alcohol. NAFLD encompasses a spectrum of liver disorders characterized by macro vesicular hepatic fat accumulation alone (steatosis), or accompanied by signs of hepatocyte injury, mixed inflammatory cell infiltrate and variable hepatic fibrosis (Non-Alcoholic Steato Hepatitis - NASH), leading to cirrhosis. Approximately, 20% to 30% of adults in the general population in western countries have NAFLD and its prevalence increases to 70% to 90% among persons who are obese or have diabetes. Epidemiological studies suggest prevalence of NAFLD in around 9% to 32% of general population in India with a higher prevalence in those with obesity and diabetes/prediabetes. NASH can progress to cirrhosis and end-stage liver disease and is projected to be the leading cause of liver transplantation by 2020. NAFLD is overall associated with an increased cardio metabolic risk

NAFLD is a disease occurring as a result of improper energy utilization and disturbed metabolism, owing to hampered function of Agni. The consumption of high calorie food like oily , fried food, fast food, milk products, artificial sweetners, sweetened beverages, fermented food along with sedentary lifestyle and reduced physical work results in storage of energy, which ultimately impede function of Agni, which leads to the formation of Apakva Anna rasa, Kapha Dushti and Medo vridhi esp. at Yakrit. Considering the etiological factors of NAFLD, it can be included under the broad heading of Santarpanajanya Vyadhi, which simulates Agni Vikriti ie. Ajirna ; and Medoroga ie. Sthoulya in etio- pathogenesis and clinical presentation. The conditions which mentions the term ‘Yakrit’ in Ayurvedic classics are Yakriddalyudara, Yakritvidradhi and Yakritgulma  which can be considered as the end stage of Fatty Liver.

.Plan of Study

·         Study type           :           Randomized, placebo-controlled, open label, clinical trial

·         No. of groups       :           Two

Group A                      -           Sharapunkhadi Yoga Capsules and lifestyle modification

Group B                      -           Placebo (roasted sooji powder) Capsules and lifestyle modification

                       Method of randomization        -  Computer generated randomization method

·         Sample size        :           Total 93 patients

Ø  Group A            -           No. of patients enrolled          –         46

                                                            No. of drop out                        -          3

                                                            No. of completed patients      -          43

Ø  Group B            -           No. of patients enrolled          –         47

                                                            No. of drop out                        -          7

                                                            No. of completed patients      -          40

Treatment Protocol

Sharapunkhadi Yoga is a formulated combination comprises of  equal quantities of  extracts of  Sharapunkha, Bhoomiamalaki and Katuki. Placebo capsule was prepared with roasted sooji powder. Mriduvirechana with Haritaki Churna was performed in both the groups prior to the trial. In both groups, two capsules (each 500mg) were administered thrice daily with luke warm water, before meals. Duration of the trial was 8 weeks. Patients in both groups were advised for lifestyle modification. Detailed Pathyaapathya chart was prepared and given to patients. Follow up was done for four weeks after the completion of treatment to assess the long-standing effect of the drug. During follow-up period, no any specific medical treatment was given to the patients.

Assessment and Analysis

            Assessment was made mainly based on the improvement observed in the subjective parameters - Agnivaishamya, fatigue, nausea, belching, vomiting, itching, burning abdomen, burning chest, abdominal pain, heaviness and distention, flatulence, diarrhea and constipation and objective parameter - grade of fatty liver; before treatment and after treatment. Statistical analysis was done with the help of paired ‘t’ test to assess the effect of intervention within the group with unpaired ‘t’ test to assess the comparative effect of intervention between the groups.

Demographic observations

v  In the study populace, maximum number of patients belonged to age group of 41-50 years (37.63%)  followed by 27.96% patients of 51-60 years age group. 53.76% patients were males. Majority of them belonged to Hindu religion (87%) and urban area(73.12%). 37.63% patients were having college education and 40% patients were of mid to high school level education. 39.78% patients were housewives and 34.41% patients doing deskwork. Maximum number of  patients (58.06%) were from middle socio-economic class, followed by poor patients(39.79%). Maximum reported chronicity is 1-5 years in 49.46% of patients, followed by less than 1 year period chronicity in 29.03% of patients.

v  While analyzing the dietary habits of patients, maximum number of patients were afflicted to Katu Rasa Ahara (46.24%) followed by Madhura Rasa Ahara (35.48%); Guru Guna Pradhana (64.52) and Snigdha Guna Pradhana (63.44%) Ahara followed by Ushna Guna Pradhana Ahara (39.78%); observing irregular dietary habit (67.74%) and vegetarian food (76.34%). Most of patients were reported having the habit of Diwaswapa (94.62%) and Avyayama (50.54%).

v  30.11% patients were suffering from Tikshnagni, followed by Mandagni  (25.8%) and Vishamagni (13.98%) .46.24%% patients were observed having Krura Koshtha and 19.35% patients having Mridu Koshtha. 52.69% patients were observed with Achintana and 44.09% patients with Atichintana. Maximum number of patients had Kaphapittaja Prakriti (45.15%) followed by Vatapitta Prakriti (40.86%)

v  The symptoms reported include  abdominal distention in maximum number of patients(91.4%), followed by abdominal heaviness (88.17%), fatigue (77.42%), abdominal pain (64.52%), belching (61.29%), flatulence (52.69%), burning abdomen (51.61%), constipation (46.24%), nausea (40.86%), increased appetite and itching (31.18% each) and decreased appetite (29.03%). 19.35% patients were reported to have suffering from vomiting and diarrhea. 6.45% patients were having fever and 5.38% were having burning chest.

v  Maximum number of  patients (73.12%) were reported having BMI more than 25kg/m²; overweight patients (39.79%), grade 1 obese (22.58%), grade 2 obese (6.45%) and grade 3 obese (4.3%).

v  Majority of the patients were diagnosed having grade 1 fatty liver (93.55%), followed by 5.37% patients of grade 2 and 3.5% patients of grade 3 fatty liver.

v  Maximum number of patients were reported having the symptoms of Vata Vridhi (98.92%) and Vata Prakopa (31.18%), followed by Pitta Vridhi (65.59%) and Pitta Prakopa (2.15%); and Kapha Vridhi (36.56%) and Kapha Prakopa(13.98%).

v  All patients included in the study were observed having Annavaha Srotodushti. Purishavaha Srotodushti in 91.4% of patients, Rasavaha Srotodushti in 68.82% patients, Medovaha Srotodushti in 66.67% of patients; and Swedavaha Srotodushti reported in 56.99% of patients.

Effect of intervention

v  On completion of eight weeks of treatment, 72.1% decrease was reported for Agnivaishamya in group A and 23.36% decrease in group B. Fatigue was decreased by 77.48% in group A and 38.03% in group B. Nausea was decreased by 74.11% in group A and 29% in group B. Belching was decreased by 76.19% in group A and 29.76% in group B. 74.94% decrease was reported for itching in group A and 24.07% decrease in group B. Relief of 73.64% for abdominal pain in group A and 21.49% in group B. All these differences were statistically significant. On comparing the effect of therapy between two groups, it was found that the difference of percentage decrease in above mentioned symptoms of both groups was statistically significant and group A provided better relief than  group B.

v  Burning abdomen was relieved by 56.34%  in group A and 22.73% in group B. 80.82% relief was reported for abdominal heaviness in group A and 28.37% in group B. Relief of 78.89% was observed for abdominal distention in group A and 27.21% in group B. 71.45% decrease for flatulence in group A and 26.87% decrease in group B. Diarrhea was relieved by 68.75%  in group A and 26.22% in group B. Decrease of 67.69% was reported for constipation in group A and 18.01% decrease in group B. All the above differences were statistically significant. On comparing the effect of therapy between two groups, it was found that the difference of percentage decrease in above mentioned symptoms of both groups was statistically significant and group A provided better results than  group B

v  In case of vomiting, 73.33% decrease was reported in group A after treatment and the difference is statistically significant. 21.74% relief was obtained in group B for vomiting, but the difference was non-significant.  In burning chest, both the groups failed to provide significant results.

v  There was statistically significant improvement by about 39.25% in Group A and 31.82% in group B, in the grades of fatty liver.

v  All the biochemical parameters including blood sugar level, lipid profile, liver function test, renal function test are within the normal range before starting the trial and after completion of the trial.

v  Group B has shown statistically significant increase in FBS, PPBS and serum cholesterol after the trial period by about 14.46%, 11.47% and 9.8% respectively. Although the increase in the mean values were reported within the normal limits, this shows that lifestyle modification may not be sufficient for preventing the building up of insulin resistance and alterations for lipid metabolism.

v  Significant decrease for about 11% was reported for S. creatinine in group A. This shows that Sharapunkhadi Yoga is safe and can be administered without any adverse reaction in the kidney.

v  Significant increase of haemoglobin by 2.69% and RBC by 2.59% was reported in group B. All the other haematological parameters were not significantly affected in both the groups after the trial period

Overall effect of therapy

In group A, complete remission was not observed in any of the patients. Excellent improvement was observed in 15(34.88%) patients. Marked improvement was observed in 8(18.6%) patients. Moderate improvement was observed in 20(46.51%) patients. Mild and nil response were not observed in any of the patients. In group B, complete remission, excellent response and nil response were not observed in any of the patients. Marked improvement was observed in 2(5%) patients. Moderate improvement was observed in 10(25%) patients. Mild improvement was observed in 28(70%) patients. This shows that the combination of Sharapunkhadi Yoga and lifestyle modification can yield more significant result in the management of NAFLD, than lifestyle modification alone.

Probable mode of action of Sharapunkhadi Yoga

All the ingredients in Sharapunkhadi Yoga are having Tikta Rasa. Tikta Rasa possess Deepana, Pachana, Lekhana, Medashoshana properties. The formulation is having Tikta Kashaya Rasa, Ruksha Laghu Guna, Sheeta Veerya, Katu Vipaka and Kapha Pitta Shamaka properties.  Sharapunkha  and Katuki  have Deepana  property. Deepana, Pachana properties of Sharapunkhadi Yoga corrects the digestive process and prevent formation of Ama. Bhoomiamalaki and Katuki due to its Lekhana  property can open the obstructed channel and remove Srotorodha and thus prevent Vatakopa. Excessive amount of Meda accumulated can be removed only by means of Shoshana, which is done by Tikta Rasa and Ruksha Guna. Sharapunkha and Katuki have Yakriduttejaka and  Pittavirechaka  property. Bhoomiamalaki and Katuki are having Medohara property, thus decrease the level of circulating lipids and prevent hepatic accumulation of lipids.

Tephrosea purpurea contain flavonoids which produce hepatocellular membrane stability, prevention of cellular leakage and increasing of hepatic regeneration. Poly phenolic compounds and flavonoids in leaves having anti-oxidant, free radical scavenging  and hepatoprotective activity. Hepatoprotective and anti-oxidant activity of Phyllanthus niruri have been attributed to two novel lignin phytochemicals named phyllanthin and hypophyllanthin. Methanolic extract of Phyllanthus species was found to inhibit lipid peroxidation & scavenge hydroxyl and superoxide radicals. Hepatoprotective effect of Katuki is due to the presence of picroside I, picroside II and kutkoside which are present in rich quantities in the roots and rhizomes of P. kurroa. Apocynin is a constituent of root extracts of Katuki which possess anti inflammatory properties. Therapeutic action on NAFLD of Sharapunkhadi Yoga may be attributed  to its pharmacological properties and presence of phytoconstituents.

Lifestyle Modification

All the international guidelines report that lifestyle changes that include diet and exercise are the only therapeutic approach recommended for NAFLD. Regular Yogic practices can play a big role in maintaining the body weight, reducing waist circumference, decreasing levels of circulatory lipids and are more sufficient than vigorous exercise in the management fatty liver. Gomukhasana, Ardhamatsyendrasana, Pavanamuktasana, Dhanurasana, Bhujangasana, Kapalabhati etc. have been adviced to the patients according to BMI and flexibility. Walking in the fresh air was also advised. Patients were advised to practice Kalabhojana for proper functioning of Agni and Upavasa at times to burn out excess Meda. Intake of vegetables and fruits rich in flavonoids and polyphenols was encouraged. Rooksha Dravas like Takra and Ushnajala were recommended as they are having Medoshoshana property.

As all lifestyle disorders , NAFLD can also be considered as a psychosomatic disease, Eershya, Bhaya, Kroda, Shoka, Achintana, Atichintana are instructed to be avoided and Dhyana, Patana, Madhyama Marga Sheelana are to be followed. Instruction was given to avoid Avyayama, Avyavaya, Svapnaviparyaya, Divasvapna, Vegadharana, Atapa anala sevana, Atimatrabhojana, Heenabhojana, Akalabhojana etc. as all these habits will provoke Agni and Vata and increase the amount of Sthayi and Asthayi Medo dhatu. Continuous and strict followal of lifestyle intervention can prevent the incidence of NAFLD in normal subjects, reverse the pathology, regain normalcy and can prevent progression to further stages such as NASH in NAFLD patients

 Adverse drug reaction

No undesirable effect was observed in patients during the clinical trials. This shows that the Sharapunkhadi Yoga is a formulation which is quite safe for internal administration. No exaggeration of symptoms was reported in placebo group also, as lifestyle modification can prevent the sudden flaring up of the disease.