Indian Journal of Ayurveda & Research

ANTI-HYPERLIPIDEMIC EFFECT OF HRIDAYARNAVA RASA

– A RANDOMIZED DOUBLE BLIND CLINICAL STUDY

ChaudhariSwapnil1 ,Galib R, Patgiri BJ3 , Prajapati PK4

  1. Central Ayurveda Research Institute for Drug Development, Kolkata 70009.
  2. Dept of Rasashastra and bhaishajyakalpana, All Indian Institute of Ayurveda, New Delhi, India 110076.
  3. Dept of Rasashastra and BhaishajyaKalpana, IPGT&RA, Gujarat Ayurved University, Jamnagar, Gujarat

ABSTRACT

Background: Hyperlipidemia is modifiable risk factor for cardiovascular diseases, and its prevalence is alarmingly increasing in India. Though different treatment modalities are effectively used in the conventional system, they have certain limitations including certain adverse effects. Ayurvedic metallic and herbo-mineral formulations are safely practiced in Indian subcontinent without any evident side effects. Hridayarnava Rasa is one such Ayurvedic herbo-metalo-mineral formulation containing Tamra Bhasma(incinerated copper) that is being successfully prescribed in the management of lipid disorders.
Aims and Objectives: To evaluate anti-hyperlipidemic effect of two samples of Hridayarnava Rasaprepared by using Tamra Bhasma processed in Surana Kanda (HRTBS) and Panchamrita during Amritikarana (HRTBP).
Materials and methods: Total 126 patients of hyperlipidemiafulfilling inclusion criteria were randomly grouped into two. Patients registered in one group  (n= 62) were administered with 125 mg of HRTBP (Hridayarnava Rasa prepared by using Tamra Bhasma processed in Panchamrita for Amritikarana) and another Group (n =64) with HRTBS (Hridayarnava Rasa prepared by using Tamra Bhasma processed in Suranakanda for Amritikarana) twice daily for 8 weeks along with honey as an adjuvant in both groups.
Results and Conclusion: Both the drugs have shown significant effect in reducing lipid parameters but the difference in between the groups is statistically insignificant. On comparison, HRTBP showed better results than HRTBS.
KEY WORDS: Copper, Hridayarnava Rasa, Hyperlipidemia, Tamra
Address for correspondence:
Dr R Galib, Dept of Rasashastra and bhaishajyakalpana, All Indian Institute of Ayurveda, New Delhi, India 110076 Email: galib14.yahoo.co.in
Financial support: NIL, Conflict of interest : None

How to cite this article: Chaudhari S ,GalibR,PatgiriBJ,PrajapatiPK.Anti-hyperlipidemic effect of Hridayavarana Rasa -A randomized double blind clinical study.Indian JAyurveda Res 2018;1:4-10

INTRODUCTION:
Prevalence of cardiovascular diseases are emerging as global threat and estimated to account for 26% mortality due to non-communicable diseases in India.[1]Raised lipid levels are well reported as major predictive risk factors for cardiovascular diseases and atherosclerosis.[2,3]About 79% of the general adult Indian population has abnormalities in not less than one of the lipid parameters with no urban, rural differences.[4] Statins and fibrates are most commonly prescribed medications as hypolipidemic agents.[5,6] Though, there is extensive evidence about their safety and efficacy but use of these synthetic drugs has certain adverse effects. Myalgia, hepatopathy, renal failure, increased risk of diabetes and rhabdomyolysis are the most common side effects from statin use.[7,8,9,10]
Considering wide magnitude of lipid disorders in Indian subcontinent and absence of promising therapy with safety in conventional systems; suffering population is turning towards certain other alternatives for safe and effective remedies.

Hridayarnava Rasa, one such herbometalo-mineral compound formulation explained in Ayurveda classics containing Tamra Bhasma (incinerated copper) as an integral component is indicated in the treatment of abnormal lipid levels. Previous studies reported safety of both Tamra Bhasma and Hridayarnava Rasa in experimental animals up to genotoxic levels.[11,12,13]Tamra Bhasma (copper) is claimed to possess Medopaha (reducing fats/lipids) and Lekhana (scraps excessive fat) activities. [14,15] Diet rich in copper has a beneficial effect on blood cholesterol.[16]Such evidences substantiate the role of copper as a lipid lowering agent. Tamra Bhasma is also reported to have anti-hyperlipidemic action through experimental studies.[17] As no clinical evidences are available on copper based formulation, Hridayarnava Rasa; the present study is planned to evaluate therapeutic effect of the same in hyperlipidemia.

MATERIALS AND METHODS

Design

An interventional, randomized double blind clinical trial. Registered patients were grouped into two by using computer generated randomization sequence.

Participants

Subjects presentingwith increased levels of any of the serum lipids such as S. cholesterol (>200 mg/dL), S. triglycerides (>150 mg/dL), S. LDL (>130 mg/dL), S. VLDL (>40 mg/dL) were selected from outpatient department of Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar, Gujarat between June 2015 to September 2016 after obtaining informed consent from them. Ethical clearance was obtained from Institutional Ethics Committee vide Lr No. (PGT/7A/2014-2015/2652 dated 19/12/2014). Study was registered in Clinical Trial Registry of India (CTRI/2015/08/006127 dated 20/08/2015). Each patient was examined in detail with relevant pathological and biochemical investigations before and after treatment.(Chart No.1)

Inclusion criteria

Patients of either sex aged between 20 to 60 years with increased levels of any of the serum lipids were included in the study.

Exclusion criteria

Patients with pathologies of liver, heart, kidney, lungs and other organs were excluded from the study. Poorly controlled hypertension (≥200/120mm Hg), uncontrolled diabetes mellitus type II (Fasting blood sugar>250mg/dl), impaired renal function (serum creatinine ≥1.2 mg/dl), pregnancy and lactation were also excluded from study.

A total of 180 patients were screened for hyperlipidemia. Among them 126 patients satisfying inclusion criteria were enrolled into the study and grouped into two groups

Study drugs

Hridayarnava Rasa

Hridayarnava Rasa was prepared by triturating equal proportions of Kajjali (black sulphide of mercury) and Tamra Bhasma (incinerated copper) with the decoction of Triphala (three myrobalans) and juice of Solanumnigrum Linn. Copper scraps with 99.89% pure copper was procured from local industrial area, Jamnagar, India was used in Tamra Bahsma preparation. In current study, Hridayarnava Rasa was prepared by using Tamra Bhasma processed in SuranaKanda (HRTBS) and Panchamrita during Amritikarana(HRTBP).Trial drugs were prepared at department of Rasashastra and Bhaishajya Kalpana, IPGT and RA, Gujarat Ayurveda University, Jamnagar.[18]

Intervention

Both the trial drugs were administered at a dose of 125mg twice a day with honey as Anupana (adjuvant) for eight weeks. As, current study type was randomized double blind, selected patients were randomly divided into two groups viz; group A and B using computer generated randomization sequence.Patients of Group A were administered with Hridayarnava Rasa prepared by using Tamra Bhasma processed in Panchamrita for Amritikarana (HRTBP) while the patients of Group B with Hridayarnava Rasa prepared by using Tamra Bhasma processed in Surana Kanda for Amritikarana(HRTBS).

 

Subjective parameters

The assessment of the signs and symptoms were done on day 0 and 56. Severity was assessed by grading 0 to 3 (absence to severe) for symptoms described for Medoroga like Kshudra Shwasa (exertional dyspnoea), Trishna (increased thirst), Swedadhikya (excessive sweating), Nidradhikya (excessive sleep), Atikshudha (increased appetite), Sada (fatigue) and Daurgandhya (bad odour). [19] Score adopted for the main signs and symptoms was based on WHO – guidelines for clinical research methodology in Ayurveda. [20]

Objective parameters

Assessments was done based on changes observed in lipid parameters like S. cholesterol, S. triglycerides, S. LDL, S. VLDL before and after treatment in terms of percentage relief.

Investigations

Haematological parameters like total leucocytes count (TLC), red blood cells (RBC), haemoglobin (Hb), white blood cells (WBC), erythrocyte sedimentation rate (ESR) and biochemical investigations like lipid profile, Blood urea, RBS, S. Creatinine, SGOT, SGPT, Alk. Phosphatase etc. were carried out to assess the condition of disease and to exclude any underlying pathology

Chart I:  Assessment for eligibility

 

STATISTICAL ANALYSIS
Wilcoxon signed Rank Test was applied to evaluate effect of therapy in individual group for Subjective criteria. Paired ‘t’ test was applied to evaluate effect of therapy on Haematological, Biochemical parameters. Coefficient of variation (CV) was applied to the statistical data to evaluate the differences in the effect of two therapies in Lipid profile. Overall effect of therapy on each scale was calculated with reference to percentage improvement in all inclusion criteria. A p < 0.05 was used to test the significance. Statistical analysis was performed using Sigma Stat 3.1 software.[21]

OBSERVATIONS:
In the present study 126 patients were registered, of which 103 participants completed the study. The socio demographic data of the participants shows that 51.59% (65) were female and the rest 48.41% (61) were males. The age groups of 41-50, 51-60 years consisted of 43.65% (55), 33.3% (42) participants respectively. The major Participants (96.03%, 121) of the study belonged to the Hindu religion. The family history of the participants revealed that 50.79% (64) had positive family history for DM followed by 29.37% (37) for hypertension, 20.63% (26) for obesity and 9.52% (12) for hyperlipidaemia. Out of the registered patients in the trial; 95.24% (120) were consuming tea or coffee on daily basis whereas 10.32% (13) of patients were having tobacco chewing as addiction. Maximum 51.59% (65) patients were under psychological stress, while 32.54% (41) patients were sentimental. 65.08% (82) of patients were doing routine work, while 18.25% (23) patients do exercise regularly. Irregularity in exercise was found in 16.67% (21) patients. Sleep pattern showed that maximum 87.3% (110) of patients have habit of day sleep. Fifteen (11.9%) patients have type-2 diabetes and 4.76% (06) have Hypertension. Prakriti (genetic phenotype) of the majority of enrolled patients was KaphaVataja (60, 47.62%), while 23.02% (29) patients were of KaphaPittaja.

RESULTS
Chief complaints reported were KshudraShwasa among 21.36% (22), Trisha 25.24% (26), Nidradhikya 14.56% (15), Sada 47.57% (49), Kshudhadhikya 12.62% (13), Swedadhikya 51.46% (53) and Daurgandhya 21.36% (22). Within the group, (Wilcoxon signed ranks test) statistical significance (p<0.05) on signs and symptoms of hyperlidemia was found for both Hridayarnava Rasa interventions except on Kshudhadhikya. HRTBP exhibitedinsignificant decrease (P> 0.05) in Daurgandhya. (Table 1)  On the lipid profile, HRTBP exhibited better results in reducing S. Cholesterol 2.05%, S. Triglyceride 14.39% and VLDL level 14.00%, whereas in HRTBS reduction was found 0.61% in S. Cholesterol, 4.25% in S. Triglyceride and 2.67% in VLDL level. Comparative efficacy of both the test drugs on subjective and lipid parameters have been assessed and results are shown in Table 2 and 3. Overall effect of therapy is also assessed in percentage involvement. (Table 4)

SAFETY AND TOLERABILITY
All haematological and biochemical variables were within normal limits in both the treatment groups at the baseline. (Table 5 and 6) Twenty-three patients were dropped out from the study. Six patients of group A and five patients of group B were irregular in further visits during treatment course. Five patients of group A and four patients of group B have discontinued treatment due to their service related hectic schedules. Three patients of group B have left the city due to other reasons. No adverse reactions were reported during the clinical trial indicating safety of Hridayarnava Rasa when administered along with honey as adjuvant at a dose of 250mg/day for eight weeks.

TABLES:
Table 1: Effect of Hridayarnava Rasa on signs and symptoms of hyperlipidemia (BT and AT) – test statistics within group (Wilcoxon signed ranks test)

Signs and symptoms HRTBS HRTBP
Mean ± SEM P Mean ± SEM P
KshudraShwasa 0.800±0.01 0.008 0.833±0.01 0.002
Trisha 0.941±0.01 0.001 0.889±0.01 0.008
Nidradhikya 1.143±0.02 0.016 0.875±0.04 0.016
Sada 0.600±0.00 0.001 0.708±0.01 0.001
Kshudhadhikya 0.333±0.21 0.50 0.286±0.18 0.50
Swedadhikya 0.965±0.03 0.001 0.667±0.03 0.001
Daurgandhya 0.562±0.12 0.004 0.667±0.06 0.250

Table – 2: Effect of test drugs on chief complaints in comparison to HRTBP and HRTBS

Chief complaints No Mean SD CV Better group
Groups HRTBP HRTBS HRTBP HRTBS HRTBP HRTBS HRTBP HRTBS
KshudraShwasa 12 10 1.16 0.8 0.93 0.42 80.35 52.70 HRTBS
Trisha 9 17 0.88 0.94 0.33 0.24 37.5 25.76 HRTBP
Nidradhikya 8 7 0.87 1.14 0.35 0.37 40.40 33.07 HRTBS
Sada 24 25 0.70 0.6 0.46 0.57 65.54 96.22 HRTBP
Kshudhadhikya 7 6 0.28 0.33 0.48 0.51 170.78 154.91 HRTBS
Swedadhikya 24 29 0.66 0.96 0.56 0.68 84.69 70.47 HRTBS
Daurgandhya 6 16 0.66 0.56 0.81 0.51 122.47 91.08 HRTBS

Table – 3: Comparative effect of test drugs on lipid profile

Parameter No Mean SD CV Better group
Groups HRTBP HRTBS HRTBP HRTBS HRTBP HRTBS HRTBP HRTBS
S. Cholesterol (mg/dl) 51 52 3.76 1.19 34.12 44.43 906.39 3726.88 HRTBP
S. Triglycerides (mg/dl) 51 52 27.90 8.73 108.94 103.43 390.46 1184.66 HRTBP
Serum HDL (mg/dl) 51 52 1.33 1.65 10.96 10.31 822.35 623.77 HRTBS
Serum LDL (mg/dl) 51 52 0.84 0.90 33.91 37.68 4022.11 4168.95 HRTBP
Serum VLDL (mg/dl) 51 52 5.43 1.09 22.18 20.59 408.47 1878.87 HRTBP

Table No. 4:  Overall effect of therapy

Groups HRTBP HRTBS Total
Relief No. % No. % No. %
Excellent response 00 00 00 00 00 00
Markedly Improved 1 1.96 02 3.85 03 2.91
Moderately Improved 19 37.25 19 36.54 38 36.89
Mildly improved 23 45.09 18 34.62 41 39.80
Unchanged 08 15.69 13 25.00 21 20.39
Total patients 51 100 52 100 103 100

Table 5: Effect of Hridayarnava Rasa on hematological investigations (BT and AT) – paired sample test (paired t test)

Parameters

HRTBS HRTBP
Mean difference SD t P Mean difference SD t P
T WBC(103 /dl) 132.69 1624.41 0.58 >0.05 486.27 1345.21 2.58 <0.05
Neutrophills (%) 2.36 9.33 1.82 >0.05 1.43 8.038 1.272 >0.05
Lymphocytes (%) 0.51 6.67 0.56 >0.05 0.05 11.613 0.0362 >0.05
Eosinophills (%) 1.17 4.66 1.81 >0.05 0.33 2.075 1.147 >0.05
Monocytes (%) 0.05 0.72 0.57 >0.05 0.05 0.810 0.518 >0.05
Hb (g/dl) 0.24 0.89 1.95 >0.05 0.07 0.805 0.644 >0.05
PCV (%) 0.48 2.29 1.52 >0.05 0.27 2.427 0.796 >0.05
RBC (106 /dl) 0.009 0.28 0.25 >0.05 0.12 0.455 1.070 >0.05
Platelet (103 /dl) 10.25 41.68 1.77 >0.05 0.05 65.90 0.006 >0.05
ESR 4.00 25.26 1.14 >0.05 5.33 26.463 1.439 >0.05

 

Table 6: Effect of Hridayarnava Rasa on biochemical investigations (BT and AT) – paired sample test (paired t test)

Parameters HRTBS HRTBP
Mean difference Standard

Deviation

t P Mean difference Standard

Deviation

t P
Blood sugar (mg/dl) 0.01 28.72 0.004 >0.05 0.37 21.13 0.126 >0.05
Blood urea (mg/dl) 3.01 11.44 1.90 >0.05 0.54 6.47 0.605 >0.05
S. creatinine (mg/dl) 0.04 0.17 1.74 >0.05 0.003 0.17 0.161 >0.05
SGPT (IU/L) 1.03 12.54 0.59 >0.05 1.62 10.37 1.120 >0.05
SGOT (IU/L) 1.55 10.08 1.11 >0.05 0.843 9.37 0.64 >0.05
Total protein (g/dl) 0.08 0.72 0.81 >0.05 0.03 0.62 0.44 >0.05
Albumin (g/dl) 0.52 4.14 0.91 >0.05 0.005 0.298 0.14 >0.05
Globulin (g/dl) 1.26 8.91 1.02 >0.05 0.06 0.62 0.73 >0.05
Alkaline phosphate (IU/L) 3.08 17.84 1.24 >0.05 5.39 21.70 1.77 >0.05
Bilirubin(T)(mg/dl) 0.02 0.23 0.89 >0.05 0.002 0.25 0.05 >0.05
Bilirubin(D) (mg/dl) 0.07 0.53 1.06 >0.05 0.01 0.10 0.64 >0.05
Uric acid (mg/dl) 0.49 1.25 2.820 <0.01 0.45 0.91 3.52 >0.05
S calcium (mg/dl) 0.025 0.942 0.19 >0.05 0.49 19.24 0.18 >0.05

 

DISCUSSION

Oxidative stress, diet rich in cholesterol and hypercholesterolemia increases LDL resulting higher risk for development of atherosclerosis.[22] The first line defensive enzymes against the free radical produced during the oxidative stress are the antioxidant enzymes, mainly superoxide dismutase (SOD) and catalase.[23] Copper is one of vital trace element of body required for normal physiological functions.[24] Deficiency of copper leads to nervous weakness, anemia, connective tissue weakness and the hypo activity of cytochrome C oxidase, lysyl oxidase and SOD etc.[25] Published reports provided scientific evidences for linkage between cholesterol metabolism and copper utilization.[26,27]  Copper deficiency leads to hypercholesterolemia in several species as reported in different laboratories.[28] Tamra Bhasma possess rich source of copper. Earlier studies report that, Tamra Bhasma inhibits lipid peroxidation and induces the activity of SOD; providing scientific evidence for its anti-oxidant agent.[29,30] Tamra Bhasma is prepared with two different Amritikarana methods which helps in elimination of  blemishes from the end product and increases its therapeutic efficacy. Hence, Hridayarnava Rasa was prepared by using Tamra Bhasma processed in SuranaKanda and Panchamrita during Amritikarana and evaluated for anti-hyperlipidemic activity

Ingredients of Triphala are reported with different pharmacological actions. Haritaki (Terminalia chebula) is reported to have anti-oxidant, cardio-protective actions.[31,32] Bibhitaki (Terminalia belerica) has been reported to have antioxidant, hepato-protective activities.[33] Amalaki (Embelica officinalis) has anti-oxidant, cardio-protective and  hepato-protective actions.[34,35,36] Kakamachi (Solanum nigrumL.) has anti-hyperlipidemic, hepato-protective and anti-oxidant activities.[37,38,39] Observed anti-hyperlipidemic activity of both the samples of Hridayarnava Rasa may be attributed to involvement of one or more mechanisms mentioned above.

CONCLUSION

Both the trial drugs provided significant results in reducing level of lipid parameters. The difference in between the groups is statistically insignificant. On comparison, HRTBP has shown better results than HRTBS. Considering the encouraging results, it can be said that both the drugs can be successfully used in cases of hyperlipidemia. However, the observations can be revalidated through clinical trials involving larger sample size.

ACKNOWLEDGEMENT: Authors acknowledge the support received from Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar – 361 008, Gujarat, India.

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