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| CLINICAL RESEARCH |
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| Year : 2019 | Volume
: 40
| Issue : 3 | Page : 171-178 |
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Clinical study of Arogyavardhini compound and lifestyle modification in management of metabolic syndrome: A double-blind placebo controlled randomized clinical trial
Bharatkumar Chhaganbhai Padhar1, Alankruta R Dave2, Mandip Goyal2
1 Department of Kayachikitsa, National Institute of Ayurveda, Jaipur, Rajasthan, India
2 Department of Kayachikitsa, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India
| Date of Submission | 05-May-2019 |
| Date of Decision | 30-Aug-2019 |
| Date of Acceptance | 03-May-2020 |
| Date of Web Publication | 08-Aug-2020 |
Correspondence Address:
Dr. Bharatkumar Chhaganbhai Padhar
Department of Kayachikitsa, National Institute of Ayurveda, Jorawar Singh Gate, Amer Road, Jaipur - 302 002, Rajasthan
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ayu.AYU_79_19
 Abstract | | |
Background: Metabolic syndrome (MS) is a cluster of obesity, hypertriglyceridemia, impaired glucose tolerance, and insulin resistance. The sedentary lifestyle settles on the phenotypical expression of a genetically acquired trait in an obese person. Weight control and a healthy lifestyle remain primary and effective strategies for prevention and management of the MS. The lifestyle modifications mentioned for Santarpanjanya (disorders due to over nutrition) diseases and Arogyavardhini compound that can improve metabolism and reduce weight were selected for a present clinical trial to assess and compare their efficacy in the management of the MS. Materials and Methods: Seventy-five patients were registered for the trial and randomly divided into two groups. Patients were treated with lifestyle modification with and without Arogyavardhini compound for 8 weeks. Results: Thirty-five patients in each group could complete the course of treatment. Lifestyle modification alone and with Arogyavardhini compound resulted in 1.32% and 3.06% decrease in waist circumference, 5.81% and 18.03% decrease in serum triglycerides, 4.43% and 6.89% decrease in systolic blood pressure, 3.82% increase and 2.48% decrease in fasting blood sugar, 9.13% and 5.56% increase in high-density lipoprotein, respectively. The decrease in waist circumference, systolic blood pressure was statistically significant in the both groups. Conclusion: Arogyavardhini compound, along with lifestyle modification was found more effective than lifestyle modification alone in the management of MS.
Keywords: Apathyanimittaja Prameha, Arogyvardhini compound, Ayurveda, Medavaha Sroto-Dushti, metabolic syndrome
How to cite this article:
Padhar BC, Dave AR, Goyal M. Clinical study of Arogyavardhini compound and lifestyle modification in management of metabolic syndrome: A double-blind placebo controlled randomized clinical trial. AYU 2019;40:171-8 |
How to cite this URL:
Padhar BC, Dave AR, Goyal M. Clinical study of Arogyavardhini compound and lifestyle modification in management of metabolic syndrome: A double-blind placebo controlled randomized clinical trial. AYU [serial online] 2019 [cited 2023 Mar 31];40:171-8. Available from: https://www.ayujournal.org/text.asp?2019/40/3/171/291636 |
| Introduction | |  |
Metabolic syndrome (MS) is a constellation of three or more metabolic disorders, including obesity, insulin resistance, hypertension and dyslipidemia occurring due to improper diet and lifestyle. It is believed as one of the major public health burdens worldwide, especially in the Indian subcontinent.[1],[2] Approximately 25% of the world's population is suffering from MS, and it will increase up to 38% by the year 2023.[3] The prevalence of the MS is higher in adult population throughout the world.[4] People with abdominal obesity are at high risk of having MS, and a sedentary lifestyle settles on the phenotypical expression of a genetically acquired trait. Adoption of a healthy lifestyle and weight control is the effective and primary strategies for the prevention and treatment of the MS.[5] In the etiopathogenesis of MS, reactive oxygen species play an essential role in multiple physiological systems under conditions of oxidative stress and contribute to cellular dysfunction. Oxidative stress also plays a major role in the pathogenesis of a variety of human diseases, including diabetes, hypertension, atherosclerosis, aging, Alzheimer's disease, kidney disease and malignancies. It has been found that in MS, dyslipidemia and elevated extra and intra-cellular glucose concentrations result in oxidative stress, which is defined as an imbalance between oxidants and antioxidants.[6] Lifestyle factors such as a dietary habit, physical activity, smoking habit, and physiological stress are the modifiable determinants of the oxidative stress and the chronic low-grade inflammation is involved in the pathogenesis and progression of many aging-associated diseases, including MS.[7]
Clinical features of MS resemble Apathya Nimittaja Prameha or Avarana Janya Madhumeha (type 2 diabetes) mentioned in Ayurveda.[8] The initial stage of MS can be compared with Medavaha Sroto-Dushti (vitiation of micro-channels of lipid metabolism and transportation), which manifests as a group of symptoms of Atisthula (obesity) and premonitory symptoms and signs of Prameha (diabetes). Apathya Nimittaja Prameha or Medavaha Sroto-Dushti which occurs due to Santarpaka Ahara and Vihara (over nutrition and sedentary lifestyle), can be said Santarpanjanya diseases. Disturbed metabolism, fat accumulation, production of Ama (reactive oxygen species) and obstructed channels for lipid transportation are the key factors in the pathogenesis of the MS.
There is no well-established therapeutic intervention for the management of MS in contemporary medical science. Patients of MS are treated with anti-diabetic, antihypertensive, anti-hyperlipidemic, anti-obesity drugs and lifestyle modifications. These drugs have several side effects and patients have to take it for long life.
Arogyavardhini compound is a formulated medicine. The contents of Arogyavardhini compound [Table 1] like Tamra Bhasma (incinerated copper), Guggulu, Katuki, Triphala are having Lekhana (weight-reducing), Dipana (improving digestion and metabolism) and Medadoshahara (correcting lipid metabolism and transportation) properties,[9]Lasuna (garlic) is having Avaranahara (removal of obstruction in micro channels), Rasayana (antioxidant) properties, which may be useful to correct the underline pathology of disease and establish the normal physiology.[10] Recent researches on Arogyavardhini Rasa have proved its anti-dyslipidemic and weight lowering effect.[11] Anti-hypertensive, anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects of Lasuna (garlic) are also proven by various researches.[12]. Furthermore, Acharya Charaka has mentioned that daily exercise, taking food after complete digestion of previously eaten food and eating food articles prepared with wheat and barley flour is beneficial for the prevention and treatment of diseases occurring due to over nutrition, especially obesity.[13] Obesity being the main culprit in the pathogenesis of MS, patients were also advised to avoid diet and lifestyle factors vitiating Medavaha Srotas and later helping for manifestation of obesity and type 2 diabetes, such as daytime sleep, sedentary lifestyle, Kapha and fat, increasing foods.[14]
The study design is a double-blind randomized clinical trial; placebo (capsules filled with roasted sooji/semolina powder) was given to patients of one of the group where only lifestyle modification was advised, to make the interventions of both the groups appearing identical. The research work was planned to assess the clinical safety and efficacy of Arogyavardhini compound and lifestyle modification in the management of the MS. Primary objective of the study was changes in components of MS. While secondary objective was changes in Framingham 10 years' cardiac risk score.
| Materials and Methods | | |
Trial design
Patients, who reported to the Outpatient Department of the Kayachikitsa, I. P. G. T and R. A. Hospital, Jamnagar, were investigated for diagnosis of MS. A total of 495 patients having complaint of weight gain and increased waist circumference were screened for the present clinical trial and diagnosed with MS as per National Cholesterol Education Program (NCEP), adult treatment panel III (revised in 2005) guideline.[15] Among them, 75 patients fulfilling the inclusion criteria were included in the study. Selected patients were randomly divided into two groups, irrespective of their age, sex, caste and religion, by computer-generated randomization method. Masking of interventions was done by the neutral third person nominated by the departmental research committee. Patients and researchers were kept blind until the completion of clinical trial and data analysis. The study was approved by the Institutional Ethics Committee of I. P. G. T and R. A., Gujarat Ayurved University, Jamnagar (No. PGT/7-A/2014-15/2652, Dt. 19/12/2014) and the trial was also registered in the clinical trial registry of India (CTRI No: CTRI/2015/06/005833, Date: 01/06/2015.) Prior informed written consent was taken from each patient before including in the study. A detailed clinical research pro forma, incorporating all the points of history taking, physical examination, and assessment of the treatment, was maintained for record and analysis purpose.
Inclusion criteria
- Patients having age between 20 and 60 years of either sex
- Abdominal obesity (waist circumference >90 cm in men and >80 cm in women)
- Hyper-triglyceridaemia (s. triglycerides level 150–600 mg/dl)
- Low high density lipoprotein (HDL) cholesterol (S. HDL cholesterol <40 mg/dl for men and <50 mg/dl for women)
- Elevated blood pressure (systolic blood pressure 130–139 mmHg and/or diastolic blood pressure 85–90 mmHg)
- Impaired fasting glucose (fasting plasma glucose 100–125 mg/dl).
Exclusion criteria
- Age below 20 and above 60 years
- Patients suffering from diabetes mellitus, hypertension, and taking anti-diabetic and antihypertensive or anti-hyperlipidemic drugs
- Systemic illness such as tuberculosis, carcinoma and endocrine disorders like Cushing's syndrome, hypothyroidism
- Patient having the history of myocardial infarction or unstable angina
- The patients suffering from congestive cardiac failure
- Patients having major renal or liver disorders.
Medication and treatment plan
Details about trial drugs
Arogyavardhini compound
Arogyavardhini compound is a formulated medicine, which contains Arogyavardhini Rasa and single bulb Lasuna powder in equal (1:1) proportion. The ingredients of Arogyavardhini compound are depicted in [Table 1]. Most of the raw materials of Arogyavardhini compound were procured from Pharmacy, Gujarat Ayurved University, Jamnagar. Lasuna was purchased from Ahmedabad, Gujarat. All herbal raw drugs were authenticated by Pharmacognosy laboratory, I. P. G. T, and R. A, Gujarat Ayurved University, Jamnagar.
For the preparation of Arogyavardhini Rasa, Shodhana (purification) of Guggulu was carried out by the Swedana (steaming) method using Triphala decoction.[16] Herbal ingredients were powdered by grinding and sieving and passed through sieve no # 80. Fresh juice of Nimba leaves(Azadirachta indica A. Juss.) was prepared by grinding and squeezing.[17]Dhatukajjali, which is the mixture of Kajjali (black sulfide of mercury), Lauha Bhasma (incinerated ash of purified iron), Abhraka Bhasma (incinerated ash of purified mica) and Tamra Bhasma (incinerated ash of purified copper) was made by sequential Mardana (trituration).[18]Dhatu-Kajjali was taken in a polythene bag with the addition of powdered drugs and mixed thoroughly by shaking. Then, the mixture was added little by little in a butterfly wet– grinder, initially containing a mixture of Guggulu, (Commiphora mukul (Stocks) Hook.) Shilajatu (purified asphaltum) and Nimba leaves juice. The required quantity of Nimba leaves juice for optimum levigation was added until the mixture was immersed completely. Approximately 300–310 ml leaves juice was added three hourly. Grinding and soaking was carried out for 12 h/day for 2 days. The final material of Arogyavardhini was subjected to complete drying and was powdered, weighed, packaged, labeled, and stored in a glass container.
Good quality of Lasuna (garlic) bulbs, were selected to prepare powder. Lasuna was added little by little in a butterfly wet-grinder to make its paste. The paste was dried for 5 days. When paste became slightly reddish yellow and brittle enough to be powdered, it was added into the grinder to make powder. The fine powder of Lasuna was sieved in mesh no. 80.
Then, equal quantity of garlic powder and Arogyavardhini Rasa was mixed well with each other in the mass mixing machine until the homogeneous mixture was obtained. The final product, namely Arogyavardhini compound, was packaged, labeled, and stored in a glass container.
Lifestyle modification
The lifestyle modification was advised to patients in both the groups like to perform;
- Exercise like -brisk walking for 30 min daily in the morning.[13] To take food only when previously taken food is properly digested, Jirna Ahara (complete digestion of food) with symptoms like as good appetite, lightness of body, clear belching, proper evacuation of stool and urine and cheerfulness of mind[19]
- They were advised to eat food prepared with wheat and barley.[19] Patients were asked to avoid day sleep, milk and dairy products, sweets and sedentary lifestyles.[14]
Grouping and posology
Patients in one group were treated with lifestyle modifications and Arogyavardhini compound capsule, while in another group lifestyle modification and placebo capsule (filled with roasted Sooji powder), each capsule of 500 mg, two capsules twice a day before lunch and dinner with Anupana of water for 8 weeks. De-masking the interventions after completion of the clinical trial, it was found that patients in Group A had received the placebo capsules, while patients in Group B had received Arogyavardhini compound capsules.
Investigations
Following investigations were carried out at baseline and after completion of 8 weeks' course of treatment;
- Routine hematological investigations such as hemoglobin, total white blood cell (WBC) count, differential WBC count, red blood cell count, platelet count and erythrocytes sedimentation rate
- Complete lipid profile and fasting blood sugar, renal function test (serum creatinine, serum proteins, serum albumin, serum Globulin, and blood urea.), liver function test (serum glutamic pyruvic transaminase [SGPT], serum glutamic oxaloacetic transaminase [SGOT], serum alkaline phosphates, total bilirubin, direct bilirubin and indirect bilirubin)
- Physical, chemical and microscopic urine investigations.
Sample size
It was estimated that a total of 70 patients, 35 patients in each group would be needed to detect a difference between groups, with a two-tailed α of 0.05 and a (1-β) of 0.80, for a comparison of two independent proportions, if there was an absolute decrease of 12% in the composite outcome measure. As 5%–10% drop out was expected, so sample size of total of 75 patients for this trial was kept.
Assessment criteria
Differences of initial and after 8 weeks' observations on waist circumference, s. triglycerides, s. HDL, fasting blood sugar, systolic blood pressure, and Framingham's 10 years cardiac risk score were used to assess the effect of therapy. The information gathered based on observations was subjected to statistical analysis. Sigma state software (3.5 Version) was used to find the SD, SE, “t,” and “P” values.
To check the significance of changes due to intervention in a single group, student paired “t”-test was applied and P < 0.05 was considered as statistically significant changes. The effect of both the drugs on various objective parameters was compared and unpaired “t”-test was used to check the statistical significance of changes in outcomes.
| Results | | |
Patients for the present clinical trial were registered between June 2015 and July 2016. A total of 75 patients were registered for the present study, among them 70 patients, 35 patients in each group completed the course of treatment. One patient in group A drop out due to shifting of his job to another city and 2 patients in group A were dropped out due to irregular follow-up of the treatment. One patient in group B drop out due to unknown reasons while another patient in group B dropped out due to personal reasons [Figure 1].
Group A and group B provided 1.32% and 3.06% decrease in waist circumference, 5.81% and 18.03% decrease in serum triglycerides, 3.82% increase and 2.48% decrease in fasting blood sugar, 9.13% and 5.56% increase in serum HDL, 4.43% and 6.89% decrease in systolic blood pressure, respectively. The reduction in waist circumference in both the groups was statistically highly significant. Reduction in serum triglycerides in group B was statistically significant. An increase in fasting blood sugar in the placebo controlled group (group A) and a reduction in fasting blood sugar in group B were statistically insignificant. An increase in serum HDL in placebo controlled group was statistically significant while the increase in serum HDL in group B was statistically insignificant. The decrease in systolic blood pressure in both the groups was statistically highly significant [Table 2].
Group A and group B provided 40.87% and 51.66% decrease in Framingham coronary heart disease risk score, respectively. The decrease in Framingham coronary heart disease risk score in both the groups was statistically highly significant [Table 3].
On applying the Un-paired “t”-test, the difference of decrease in waist circumference in group A and group B was statistically highly significant while the difference of decrease in systolic blood pressure was statistically significant [Table 4].
On applying the Un-paired “t”-test, the difference of decrease in Framingham coronary heart disease risk score in group A and group B was statistically insignificant. This indicates that the difference of decrease in Framingham coronary heart disease risk score in group A and group B was due to chance [Table 5].
Group A and group B provided 5.85% increase and 4.62% decrease in SGOT, 7.70% increase and 1.24% decrease in SGPT, 13.07% and 0.37% decrease in alkaline phosphatase, 6.90% increase and 3.45% decrease in the direct bilirubin, 2.22% and 10.87% decrease in indirect bilirubin, respectively. No change was observed in total bilirubin in group A, while an 8% decrease was observed in total bilirubin in group B, which were statistically insignificant. The decrease in serum alkaline phosphates in group A was statistically significant, while it was statistically insignificant in group B [Table 6].
Group A and group B provided 0.58% decrease and 3.57% increase in blood urea, 1% decrease, and 1.12% increase in serum creatinine, 4.45%, and 7.85% decrease in total serum proteins, respectively. The decrease in total serum proteins in group A was statistically significant while decrease in total serum proteins in group B was statistically highly significant. Changes in other renal function parameters were statistically insignificant [Table 7].
Liver function parameters (SGOT, SGPT, s. alkaline phosphatase, total serum bilirubin) and renal function parameters (blood urea, serum creatinine and total serum proteins) were within normal limit before and after treatment. No adverse drug reaction was observed in any of the groups throughout the study.
| Discussion on the Result on Primary Outcomes | | |
Waist circumference
Lifestyle modifications such as regular exercise, avoidance of Adhyashana (eating food before complete digestion of previously taken food) and daytime sleep can improve the condition of MS in several ways. Intensive and regular practice of exercise stimulates adipose tissue to utilize fatty acid for energy production instead of glucose, which results in the decrement of triglycerides and increment of serum HDL. Owing to regular exercise, increased usage of fatty acids by adipose tissues decreases fat accumulation and obesity, resulting in diminished insulin resistance and prevents the occurrence of type 2 diabetes and co-morbidities related to obesity.
The habit of eating before complete digestion of previous food is defined as Adhyashana, which stimulates and accelerates the secretion of insulin. Adipose tissues use glucose for energy production instead of fatty acid in the presence of insulin, leading to less expenditure and thus, storage of fatty acids in adipose tissue, result in obesity and insulin resistance. Avoidance of Adhyashana increases the post-absorptive period and decreases insulin levels in the blood. Adipose tissues utilize fatty acids for energy production at a lower level of insulin in the blood, which results in depletion of fatty acids, decreased fat mass and triglycerides, the increment of HDL, and improvement in insulin sensitivity resulting in fall of fasting blood sugar.
Contents of Arogyavardhini compound like, Tamra Bhasma (incinerated copper),[20]Guggulu[21] and garlic[22] are having Lekhana, Pachana, Medodoshahara properties and hence due to their effect, on fat metabolism and lipolysis, becomes accelerated which results in burning of fat from the abdomen and waist region, resulting in the reduction of waist circumference.
Fasting blood sugar
Contents of Arogyavardhini compound like; Tamra Bhasma plays an important role in carbohydrate metabolism by stimulating insulin binding, hexose transport and lipogenesis.[20]Katuki (Picrorhiza kurroa Royle ex Benth.) increases the insulin-mediated translocation of glucose transporter type 4from the cytosol to the plasma membrane which results in better glucose uptake by skeletal muscles and improves glycemic control.[23]Triphala lowers fasting blood sugar and inhibit lipid peroxide formation and scavenge hydroxyl and superoxide radicals.[24]Shilajatu (Asphaltum Punja-Bianum) reduces uptake of sugar and lipid from the gut.[25]
Serum triglycerides
Contents of Arogyavardhini compound like Tamra Bhasma decrease serum triglycerides by activating lysyl oxidase enzyme and improving fat metabolism.[26] The other contents of Arogyavardhini compound such as Guggulu,[27]Lasuna,[28]Triphala[29] having anti-hyperlipidemic activity has caused decrease in serum cholesterol and triglycerides. Guggulsterone present in Guggulu having hypolipidemic, antioxidant, and anti-inflammatory activities had provided cardiovascular benefits through various mechanisms. Farnesoid x receptor, the key transcriptional regulator for the maintenance of cholesterol and bile acid homeostasis gets blocked by guggulsterone, results in the hypolipidemic effect of Guggulu. Guggulsterone also up-regulates bile salt export pump, an efflux transporter responsible for the removal of cholesterol metabolites and bile acids from the liver, which results in cholesterol metabolism into bile acids, and thus reduces lipid levels.[30] Garlic reduces lipid levels through inhibition of HMG-CoA reductase and 14-alpha-demethylase.[31]
S. high density lipoprotein
Obesity is one of the causes of the decrease in serum HDL. Lifestyle modification, as well as Arogyavardhini compound, has reduced weight and body mass index. Hence, the improvement in obesity increased serum HDL.[32]
Systolic blood pressure
Sulfides present in garlic decrease metabolism of bradykinin, inhibit prostaglandin synthesis; produce H2S and nitrous oxide which results in vasodilation. It also inhibits the renin-angiotensin-aldosterone system. The combined effect of these sulfides results in low blood volume and cardiac output which decreases systolic blood pressure.[33]
Effect of trial drug on secondary outcomes-Framingham coronary heart disease risk score
Framingham coronary heart disease risk score estimates the chance of heart attack or death in 10 years. It was calculated by the use of software MD + CALC. Age of patients, sex (gender), smoking history, total cholesterol, HDL cholesterol, systolic blood pressure, and history of use of antihypertensive drugs were taken into consideration to calculate the coronary heart disease risk score.[34]
In both groups, patients were advised to quit smoking. Furthermore, lifestyle modification and Arogyavardhini compound resulted in a reduction of total cholesterol, systolic blood pressure, and an increase of HDL-cholesterol, which resulted in the lowering of coronary heart disease risk score.
Vitiation of Jatharagni (factor responsible for digestion), Rasa and Meda Dhatvagni (factor responsible for the formation of Rasa and Meda Dhatu), Rasa, Mamsa, Meda Dhatu, Kapha and Vata Dosha, Rasavaha and Medavaha Srotasa are the key components in the pathogenesis of the MS. The contents of Arogyavardhini compound like Tamra Bhasma, Triphala, Lasuna, Guggulu having Dipana, Pachana properties correct the functions of Agni and removes Ama (intermediate product of digestion and metabolism), Triphala, Shilajita, Kutaki reduces Kleda (fluidity) and Meda, Lasuna and Guggulu remove Avarana of Vata and clear the channels of lipid transportation. Lifestyle modifications like; daily exercise improve the function of Agni and reduce Kapha, Meda, and Mamsa, avoidance of Adhyashana helps to maintain the normal function of Agni and prevent Ama formation; avoidance of day time sleep and Kapha, Meda increasing foods improve functions of Meda Dhatvagni and Medavaha Srotasa. Hence, the lifestyle modification and Arogyavardhini compound having their multivariate effect on normalizing the various components of the pathogenesis of metabolic syndrome (MS) resulted in the overall improvement in metabolic syndrome.
| Conclusion | | |
Arogyavardhini compound combined with lifestyle modification had provided statistically highly significant improvement in reduction in waist circumference, systolic blood pressure and a statistically significant decrease in serum triglycerides. Hence, it can be stated that Arogyavardhini compound along with lifestyle modification is more effective than lifestyle modification alone in the management of metabolic syndrome.
Data access and responsibility
The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgment
Authors are very thankful to authority of Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar for their financial support for drugs, investigations and equipments required for present clinical trial.
Financial support and sponsorship
Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar, supported for drugs, investigations and equipment required for present clinical trial.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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