Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons: A Pharmacoepidemiological Perspective

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1 Bhagwan Sahai Sharma et al RESEARCH ARTICLE /jp-journals Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons: A Pharmacoepidemiological Perspective 1 Bhagwan S Sharma, 2 Pitta Srinivas, 3 G Venkateswarlu, 4 Manohar S Gundeti, 5 Sneha Marlewar, 6 Kishore Kumar, 7 Banamali Das, 8 Rohit Ravte, 9 Vanmala B Wakode, 10 Shruti Khanduri, 11 Rakesh Rana, 12 Richa Singhal ABSTRACT Introduction: Rasayana drugs are a group of medicinal preparations having Balya (improving physical strength), Agnivardhaka (stimulating digestive activity), Medhya(improving intellect), Ojovardhaka (enhancing immunity) and Vayasthapana( delaying ageing) properties. Rasayana therapy (Rejuvenating group of medicines) aims specially at the promotion of strength and vitality by replenishing rasa and other dhatus. Objective: Critical analysis and presentation of clinical safety and efficacy outcomes of classical Ayurvedic formulations, viz. Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha in apparently healthy elderly persons, generated through multicentre open label studies conducted at different CCRAS centres. Materials and Methods: Analysis of data collected from three different clinical studies that had been completed in peripheral institutes of Central Council for Research in Ayurvedic Sciences (CCRAS), were critically evaluated to assay the safety profile of three formulations, namely Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha. Clinical safety assessments were done through analyzing liver function tests (LFT) and renal function tests (RFT) before and after the administration of rasayana. Parameters like hamilton depression rating scale, PGI memory scale and world health organization quality 1,3,5-10 Research Officer, 2 S-2, Research Officer, 4 Research Officer (Ay.), 11 Statistical Officer, 12 Statistical Assistance 1,9-12 Central Council for Research in Ayurvedic Sciences, New Delhi, India 2 Captain Srinivasa Murthy Regional Ayurveda Drug Development Institute, Chennai, Tamil Nadu, India 3,6 Regional Ayurveda Research Institute for Nutritional Disorder, Bengaluru, Karnataka, India 4 Raja Ramdeo Anandilal Podar (RRAP) Central Ayurveda Research Institute for Cancer, Mumbai, Maharashtra, India 5 Central Ayurveda Research Institute for Cancer, Mumbai, Maharashtra, India 7 Central Ayurveda Research Institute for Hepatobiliary Disorders, Bhubaneswar, Odisha, India 8 Central Ayurveda Research Institute for Drug Development, Kolkata, West Bengal, India Corresponding Author: Bhagwan Sahai Sharma, Research Officer, Central Council for Research in Ayurvedic Sciences, Delhi, India, Phone: , bss_ro@rediffmail.com of life instrument-abbrivated version (WHO QOL-BREF) scale were also assessed before and after administration of Rasayana. Paired t-test was used to compare mean change from baseline to end of the trial period. Drug compliance and adverse events (AE)/adverse drug reaction (ADR)s, if any were also noted. Conclusion: The findings in the three different clinical studies clearly reveal that Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha are clinically safe, tolerable and effective in apparently healthy elderly persons. Keywords: Ashwagandhadi leha, Brahma Rasayana, Chyavanaprasha, Healthy elderly persons, Safety profile How to cite this article: Sharma BS, Srinivas P, Venkateswarlu G, Gundeti MS, Marlewar S, Kumar K, Das B, Ravte R, Wakode VB, Khanduri S, Rana R, Singhal R. Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons: A Pharmacoepidemiological Perspective. J Res Ayurvedic Sci 2018;2(2): Source of support: Nil Conflict of interest: None INTRODUCTION Ayurveda defines health as a state where, the three dosha (regulatory functional factors of the body) are in equilibrium and act harmoniously, Dhatu (major structural components of the body) are well formed with maximum efficiency, Agni (digestive/metabolic factors) is in a balanced state regulating metabolic process in a proper way, there is proper and timely elimination of Mala and the soul, mind and sensory organs are in a present state. 1 Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. 2 Aging is related to the decline of the organ systems essential for the control and maintenance of other systems within an organism, and the ability of organisms to communicate and adapt to the environment in which they live. The nervous, endocrine, and immune systems play a key role by their ubiquitous actions in coordinating all other systems and in their interactive and defensive responsiveness to external and internal stimuli and they are the most often affected

2 Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons Rasayana is one among the eight major branches of Ayurveda as mentioned by Ashtanga Hridaya and is often used in both preventive and curative aspects. The word rasayana is composed of two words; rasa and ayana, which literally indicates that which brings about functional, qualitative and quantitative excellence to rasa dhatu. Rasa is the nutritional component which keeps on circulating within body providing nourishment to all other dhatu. Ayana means the channels of circulation. So the word Rasayana refers to nutrition or nourishment at all levels. Rasayana is a specialised treatment influencing the fundamental aspects of the organ system i.e. dhatu, agni and srotas (structural or functional channels), leading to overall improvement in the organism, which affords prevention of ageing, resistance against diseases, bodily strength and improvement in mental faculties. Rasayana is advocated in early or middle age of life, to help prevent the onslaught of ageing and diseases. Elaborate description of various types of Rasayana is available in Ayurveda classic Charaka Samhita Chikitsasthana, Ayurveda classic Sushruta Samhita Chikitsasthana and Ayurveda classic Astanga Hridaya Uttara Tantra. Ashwagandhadi Leha can be used as Balya (strength, stamina and immunity promoter) Rasayana and Vajikarana (aphrodisiac) and is effective against diseases such as Raktavikara (disorders of blood), Krishatva (emaciation), Arsha (haemorrhoids) and Upadamsha (syphilis/soft chancre). Brahma Rasayana is used in conditions such as Tandra (lassitude), Shrama (fatigue/lethargy), Klama (tiredness without exertion/langour), Manodaurbalya (weakness of the mind), Jara (senility), Vali-Palita (wrinkles in skin and greying of hair) and Smrtibhramsha (impairment of memory). Chyavanaprasha is an excellent rejuvenative and is also effective against kasa (cough), shwasa (dyspnoea), Agnimandya (digestive impairment), Uroroga (diseases of thorax), Vatarakta (gout), Pipasa (thirst), Mutraroga (urinary diseases), Sukra Dosa (vitiation of semen) and Jara (senility). It is also effective as Medhya (intellect promoting) and Smrtiprada (promotes intellect and memory). Drug Profile Ashwagandha is the major component of Ashwagandhadi leha, 4 which is known for its wide ranging Rasayana benefits. The adaptogenic properties of Ashwagandha has been proven scientifically in various studies. 5 Brahma Rasayana 6 is the first Rasayana mentioned by Acharya Charaka in Charaka Samhita Chikitsasthana. The chief ingredients are Haritaki and Amalaki. Brahma rasayana can effectively counteract the effects of aggravated Vata dosha in jaraavastha and hence it is effective in reducing the effects of ageing and has great potential as an stimulant of agni. Chyavanaprasha 7 is mentioned in the Rasayana pada of Charaka Samhita Chikitsasthana first chapter. Amalaki is the chief component of Chyavanaprasha which is known for its antioxidant properties and is a known source of vitamin C. It contains almost 50 herbs. The components of the three formulations are detailed in Table 1. Table 1: Constituents of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha. S. No. Sanskrit name Ashwagandhadi leha Botanical/English name Part used 1. Sharkara Sugar - 2. Ashvagandha Withania somnifera Root 3. Sariva Hemidesmus indicus Root 4. Jiraka Cuminum cyminum Fruit 5. Madhusnuhi Smilax glabra Root tuber 6. Draksha Vitis vinifera Dry fruit 7. Ghrta Clarified butter from - cow milk 8. Madhu Honey - 9. Ela Elettaria cardamomum Brahma Rasayana Seed 1. Haritaki Terminalia chebula Pericarp 2. Amalaki Emblica officinalis Pericarp 3. Bilva Aegel marmelos Root/stem bark corr 4. Shyonaka Oroxylum indicum Root/stem bark vnt 5. Gambhari Gmelina arborea Root/stem bark linn. 6. Patala Stereospermum Root/stem bark suaveolens dc. 7. Agnimantha Premna integrifolia Root/stem bark linn. 8. Shalaparni Desmodium Plant (whole) gangeticum dc 9. Prshniparni Uraria picta Desv Plant (whole) 10. Brhati Solanum indicum linn. Plant (whole) 11. Kantakari Solanum surattense Plant (whole) 12. Goksura Tribulus terrestris Root 13. Bala Sida cordifolia Root 14. Punarnava Boerhaavia diffusa Root 15. Eranda Ricinus communis Root linn. 16. Mashaparni Teramnus labialis Plant (whole) Spreng. 17. Mudgaparni Vigna trilobata Plant (whole) 18. Shatavari Asparagus Root recemosus Willd. 19. Meda Polygonatum Root tuber cirrhifolium 20. Jivanti Leptadenia Plant (whole) reticulata 21. Jivaka Malaxis acuminata Root tuber contd... Journal of Research in Ayurvedic Sciences, April-June 2018;2(2):

3 Bhagwan Sahai Sharma et al contd... S. No. Sanskrit name Botanical/English name 22. Risabhaka Malaxis muscifera(lindl) kuntze Part used Root tuber 23. Shali Oryza sativa Root 24. Kasa Saccharum Root spontaneum 25. Shara Saccharum Root bengalense Retz. Syn. 26. Darbha Imperata cylindrica Root () 27. Ikshu Saccharum Root officinarum 28. Tvak Cinnamomum Stem bark zeylanicum Blume 29. Ela Elettaria Seed cardamomum 30. Musta Cyperus rotundus Rhizome 31. Haridra Curcuma longa Rhizome 32. Pippali Piper Fruit longum 33. Agaru Aquiariaaga ocha Heart wood roxb. 34. Chandana Santalum album Heart wood 35. Mandukaparni Centella asiatica Plant (whole) () 36. Kanaka Mesua ferrea Stamens 37. Shankhapuspi Convolvulus Plant (whole) pluricaulis Choisy 38. Vacha Acorus calamus Rhizome 39. Plava Cyperus scariosus Rhizome 40. Yasti Glycyrrhiza glabra Root 41. Vidanga Embelia ribes Fruit Burm. f. 42. Sitopala Sugar 43. Ghrita Clarified butter from cow s milk 44. Taila Sesamum indicum Oil 45. Kshudra Honey - Chyavanaprasha 1. Bilva Aegle marmelos Root/stem bark 2. Agnimantha Premna integrifolia Root/stem bark 3. Shyonaka Oroxylum indicum Root/stem bark 4. Kashmiri Gmelina arborea Root/stem bark 5. Patala Stereospermum Root/stem bark suaveolens 6. Bala Sida cordifolia Root 7. Shalaparni Desmodium Plant (whole) gangeticum 8. Prishniparni Uraria picta Plant (whole) 9. Mudgaparni Phaseolus trilobus Root / Plant (whole) 10. Mashaparni Teramnus labialis Root/ Plant (whole) 11. Pippali Piper longum Fruit S. No. Sanskrit name 12. Svadamstra (Goksura) Botanical/English name Tribulus terrestris Part used Plant (whole) 13. Brhati Solanum indicum Plant (whole) 14. Kantakari Solanum surattense Plant (whole) 15. Shringi Pistacia integerrima Gl 16. Tamalaki Phyllanthus amarus Plant (whole) 17. Draksha Vitis vinifera Dry fruit 18. Jivanti Leptadenia Root reticulate 19. Pushakara Inula racemosa Root 20. Aguru Aquilaria agallocha Heart wood 21. Abhaya (Haritaki) Terminalia chebula Pericarp 22. Amrita (Guduci) Tinospora cordifolia Stem 23. Riddhi Habenaria intermedia Subterranean root tuber 24. Jivaka Malaxis acuminate Pseudo bulb 25. Rishabhaka Malaxis muscifera Root tuber 26. Shathi Hedychium Rhizome spicatum 27. Musta Cyperus rotundus Root tuber 28. Punarnava Boerhaavia diffusa Plant (whole) 29. Meda Polygonatum Root tuber cirrhifolium 30. Ela Elettaria Seed cardamomum 31. Chandana Santalum album Heart wood 32. Utpala Nymphaea stellata Flower 33. Vidari Pueraria tuberosa Root tuber 34. Vrishamula Adhatoda vasica Root 35. Kakoli Lilium polyphyllum Subterranean root 36. Kakanasika Martynia annua Fruit 37. Amalaki Phyllanthus emblica Pericarp 38. Ghrita Clarified butter from - cow s milk 39. Taila Sesamum indicum Oil 40. Matsyandika Sugar Madhu Honey Tugakshiri Bambusa bambos Siliceous concretion 43. Pippali Piper longum Fruit 44. Tvak Cinnamomum Stem bark zeylancium 45. Ela Elettaria Seed cardamomum 46. Patra Cinnamomum Leaf tamala 47. Kesara Mesua ferrea Stamens OBJECTIVE Critical analysis of clinical safety and efficacy outcomes of classical Ayurvedic formulations, viz. Ashwagandhadi Leha, Brahma Rasayana and Chyavanaprasha in apparently healthy elderly persons, generated through multicentre open label studies at different CCRAS centres. 124

4 Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons MATERIALS AND METHODS The formulations fulfilling the physico-chemical standards and quality parameters, prepared as per standard operating procedures (SOP) were used for all the studies. These three different clinical studies were approved by Institutional Ethics Committee of all the participating centres and done in accordance with World Health Organisation good clinical practice guidelines. The study medications included Ashwagandhadi leha (10 gm bd with luke warm milk after food), Brahma Ramayana (15 g bd with luke warm milk after food) and Chyavanaprasha (12 gm bd with milk after food) and were used in apparently healthy elderly persons for a period of 12 weeks. Chyavanaprasha and Brahma Rasayana were procured from Ms Indian Medicine Pharmaceuticals Corporation Limited, Mohan and Ashwagandhadi leha was procured from Ms Dabur India Ltd. Open label multicentre clinical trials were done in selected peripheral institutes of CCRAS to evaluate the safety and rasayana efficacy of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha in apparently healthy elderly persons. All the three studies were registered in Clinical Trial Registry of India. The details of the three trials are briefed in the Table 2. Laboratory investigations were done at National Accreditation Board for Laboratories (NABL) approved laboratories. The data obtained from the completed clinical studies were analysed to assess the safety profile of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha through liver function tests (LFT) and renal function tests (RFT) before and after the trial. Statistical Analysis Laboratory parameters including safety parameters liver function test (LFT), renal function test (RFT), WHO QOL BREF scale, Postgraduate Institute (PGI) Memory scale and Hamilton depression rating scale score were assessed before and after the administration of therapy. Paired t-test was used to compare mean change from baseline to 84th day. A p-value of <0.05 was considered statistically significant. All statistical analysis were performed using Statistical package for Social Sciences (SPSS) version 15.0 The brief description of the three trials has been provided in Table 2. OBSERVATION Ashwagandhadi Leha Among the total 154 patients who completed the trial, majority were males and maximum of the patients belonged to the age group years, i.e, 86 patients % were literate and 23.4% hailed from lower socioeconomic stratum. Ashwagandhadi leha provided significant improvement in qualitative parameters, such as dizziness, constipation, urge incontinence, aching muscle, pain in joints, stiffness in the joints, abnormal sleep, loss of appetite, fatigue and generalised weakness with p-values < It also had shown highly significant improvement on PGI Memory scale, Hamilton s depression rating scale and WHO QOL-BREF scale. No significant change was observed in all parameters except serum lipid profile such as serum cholesterol, low density lipoprotein, high density lipoprotein, serum albumin and serum creatinine. In these parameters also, the values were within normal limits during the entire period. No adverse drug reactions or adverse events were observed during the study. Brahma Rasayana Among the 180 patients who were selected for the study, 70% were males. Eighty-four point four per cent of patients were above poverty line and 17.2% were vegetarians. Fortythree point nine of patients were belonging to Vata-Pittaja Prakrti. When compared with the baseline, significant improvement was observed in the qualitative parameters such as dizziness, constipation, urge incontinence, aching muscle, pain in joints, stiffness in the joints, abnormal sleep, loss of appetite, fatigue, generalized weakness and sense of wellbeing, with p-values < It also had shown highly significant effect on PGI memory scale, Hamilton s depression rating scale and WHO QOL-BREF scale. The therapy showed no significant change in all parameters except serum triglycerides, very low density lipoprotein and serum globulin. In these parameters also, the values were within normal limits during the entire period. No adverse drug reactions or adverse events were observed during the study. Chyavanaprasha Among the total 214 patients enrolled in the study, maximum numbers of patients (52.8%) were found to be in the age group of years followed by 32.7% in the age group of years and 57% of the patients were males. The majority of subjects were observed to be non-vegetarian (63.1%). Maximum patients were of Pitta-Kaphaja Prakrti (27.3%). Chyavanaprasha shows statistically significant change was observed in 4 parameters of WHO QOL-BREF scores Domain 1 (physical health) (p < 0.001), domain 2 (psychological) (p < 0.001), domain 3 (social relationship) (p < 0.001) and Domain 4 (environment) (p < 0.001) at 84th day compared with baseline. No adverse reactions were noticed during the trial period. Journal of Research in Ayurvedic Sciences, April-June 2018;2(2):

5 Bhagwan Sahai Sharma et al Table 2: Brief description of 3 trials using Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha in apparently healthy elderly Persons. Sr no Name of study 1. Clinical evaluation of Rasayana effect of Ashwagandhadi Lehya in apparently healthy elderly persons CTRI/2012/ 05/ Evaluation of Clinical Efficacy and Safety of Brahma Rasayana in apparently healthy elderly persons CTRI/2015/03/ Study No. of Current names of period Study design centres centre Open label interventional single arm prospective multicentre study Open label interventional single arm prospective multicentre study 3 1. Regional Ayurveda Research Institute for Metabolic Disorders, Jayanagar, Bengaluru 2.Dr. Achanta Lakshmipati Research Center for Ayurveda, Chennai. 3.Raja Ramdeo Anandilal Podar Central Ayurveda Research Institute for Cancer, Mumbai 3 1 Regional Ayurveda Research Institute for Metabolic Disorders, Jayanagar, Bengaluru. 2 Central Ayurveda Research Institute for Hepatobiliary Disorders, Bhubaneswar. 3 Central Ayurveda Research Institute for Drug Development. Kolkata. 180 Brahma Rasayana Sample Study interventions size 154 Ashwagandhadi Leha Intervention Dosage schedule period For oral- 10 gm BD 12 weeks with luke warm milk. after food 15 g BD 12 weeks with luke warm milk. 3. Clinical trial to study the effect of Chyavanaprasha on Aging In Apparently healthy elderly subjects CTRI/2016/03/ Open label interventional Prevention single arm prospective multicentre study 3 1 Raja Ramdeo Anandilal podar central Ayurveda Research Institute for Cancer, RA Podar College Worli, Mumbai Dr. Achanta Lakshmipati Research Center for Ayurveda, Chennai. 3 Regional Ayurveda Research Institute for Metabolic Disorders, Jayanagar, Bengaluru. 214 Chyavanaprasha For oral- 12 gm BD with milk 12 weeks The therapy showed no significant change in parameters such as serum cholesterol, serum triglycerides, low density lipoprotein, serum bilirubin, serum glutamic pyruvic transaminase (SGPT), serum glumatic oxaloacetic transaminase (SGOT), serum alkaline phosphatase, total protein, albumin, globulin, bood urea and serum creatinine. Significant change was observed in high density lipoprotein values but even in this, the values were within normal limits during the entire period. The data, regarding demographic profile have been provided in Table 3 and data relating to safety profile obtained from the three studies are given in Table 4. The comparison of safety related data obtained from the three trials has been provided in Graphs 1 to 4. DISCUSSION Ayurveda has explained the Rasayana as one among the eight parts of treatment. Acharya Charaka has opined that use of Rasayana promotes longevity, memory, intellect, youth, luster, complexion, excellence of voice, physical strength, enhancement of sensory functions and oratory skills. Rasayana acts by nutritive enhancement of Rasadhatu and hence ensures increased nourishment of other Dhatus. 8 In Ayurveda, Ojas is considered as the fine essence of all Dhatu in the body and only those substances that can bring qualitative and quantitative enhancement of Ojas can provide rejuvenation to body. Quality of Ojas is maintained by Rasadi Dhatu which in turn is maintained by the Ahararasa 9 and promoting Agni and removing Srotorodha is the mechanism to promote rejuvenation 126

6 Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons Graph 1: Comparison of liver function test (SGOT, SGPT) of Ashwagandhadi leha, Brahma Rasayana and Cyavanaprasa before and after the trial in healthy elderly persons. Graph 2: Comparison of liver function test (Serum Alkaline Phosphatase) of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha before and after the trial in healthy elderly persons. of body. Three types of Rasayana has been mentioned in Ayurveda, Naimittika (Rasayana that can be used for specific purpose), Kamya (Rasayana used for maintenance of health in normal persons) and Ajasrika (Rasayana that has to be used daily for maintaining equilibrium of Dosa, Dhatu, e.g., Dugdha, Ghrta). 10 The three Rasayana used here come under the Naimittika type of Rasayana. Ashwagandhadi Rasayana, Chyavanaprasha and Brahmarasayana are some among the most commonly used rasayana that has been used since time immemorial in both preventive and curative aspects of treatment. Ashwagandha (Withania somnifera) is the chief ingredient of Ashwagandhadi Rasayana and has pharmacological value as an adaptogen, aphrodisiac, diuretic, narcotic, sedative, and tonic. 11 Ashwagandha (Withania somnifera) is useful for generalized weakness and to improve speed and lower limb muscular strength and neuro-muscular coordination. 12 Ashwagandhadi leha acts by enhancing the quality of body tissues and aids in regulating psychosomatic activity of the body. Chyavanaprasha is a famous Rasayana that has Agnivridhikara (digestion and metabolism enhancing), Vatanulomana (regularizing physiological movement of Vata) and rejuvenative properties. 13 Studies have proven that use of Chyavanaprasha reduces free radical genera- Graph 3: Comparison of liver function test (total protein, globulin and albumin) of Ashwagandhadi leha, Brahma Rasayana and Cyavanaprasa before and after the trial in healthy elderly persons. Journal of Research in Ayurvedic Sciences, April-June 2018;2(2):

7 Bhagwan Sahai Sharma et al Table 3: Demographic profile of the patients in Rasayana Demographic Profile Ashwagandhadi Leha (N = 154) Brahma Rasayana (N = 180) Chyavanaprasha (N = 214) Sex Male 86 (55.8%) 126 (70.0%) 122 (57.0%) Female 68 (44.2 %) 54 (30.0%) 92 (43.0%) Education Not able to read and write 19 (12.3 %) 25 (13.9%) 21 (9.8%) Literate 135 (87.7 %) 155 (86.1%) 193 (90.2%) Socio-economic status Below poverty line 36 (23.4%) 28 (15.6%) 17 (7.9%) Above poverty line 118 (76.6 %) 152 (84.4%) 197 (92.1%) Diet Vegetarian 52 (33.8 %) 31 (17.2%) 79 (36.9%) Non-vegetarian 102 (66.2 %) 149 (82.8%) 135 (63.1%) Prakriti Vataja 2 (1.3 %) - 27 (9.6%) Pittaja 18 (11.7 %) 12 (6.7%) 48 (17.0%) Kaphaja - 1 (0.6%) 45(16.0%) Vata-Pittaja 42 (27.3 %) 79 (43.9%) 56 (19.9%) Pitta-Kaphaja 79 (51.3%) 78 (43.3%) 77 (27.3%) Vata-Kaphaja 13 (8.4 %) 9 (5.0%) 28 (9.9%) Sannipataja - 1 (0.6%) 1 (0.4%) Patients completing the trial from different geographical locations Bengaluru 55 (35.7%) 60 (33.3%) 70 (32.7%) Chennai 49 (31.8%) - 70 (32.7%) Mumbai 50 (32.4%) - 74 (34.5%) Bhubaneswar - 60 (33.3%) - Kolkata - 60 (33.3%) - tion and increases free radical scavenging 14 which is an acclaimed mechanism for delaying ill consequences of ageing. Brahmarasayana is reported to have antioxidant, myeloprotecting, immunostimulatory, anti-inflammatory, radioprotective and antitumour properties The Parameters Serum Cholesterol (mg/ dl) Serum Triglycerides (mg/dl) Low Density Lipoprotein (LDLc) (mg/dl) High Density Lipoprotein (HDLc) (mg/dl) Very Low Density Lipoprotein (VLDL) (mg/dl) Liver Function Test Ashwagandhadi leha Brahma Rasayana Chyavanaprasha leha BT AT p-value BT AT p-value BT AT p-value (42.363) (74.255) (37.511) (40.570) (65.777) (36.507) (35.405) (50.216) (28.862) (9.872) (9.261) (10.860) (17.880) (15.637) (34.685) (75.815) (29.405) (13.334) (8.789) (16.630) (40.734) (42.518) (56.408) (51.276) (37.669) (38.788) (10.941) (11.326) (11.256) (10.231) S.Bilirubin (Indirect) (mg/ 0.54 (0.256) 0.52 (0.257) (0.298) (0.532) (0.300) 0.54 (0.269) dl) S.Bilirubin (Direct) (mg/ dl) 0.16(0.097) 0.16 (0.085) (0.322) 0.45 (0.340) (0.166) 0.18 (0.175) SGPT (IU/L) (9.281) (8.457) (11.146) (9.653) (11.425) (11.114) SGOT (IU/L) (7.382) (6.976) (8.261) (8.800) (8.648) (9.190) S.Alkaline Phosphatase (IU/L) Table 4: Safety profile of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha (24.076) (23.352) (57.847) (62.329) (22.909) (22.805) Total Protein (gm/dl) 7.11 (0.443) 7.08 (0.475) (0.609) (5.475) (0.484) 7.05 (0.461) Albumin (gm/dl) 4.29(0.246) 4.21 (0.246) < (0.399) 4.52 (0.390) (0.265) 4.21 (0.251) Globulin (gm/dl) 2.82 (0.425) 2.86 (0.425) (0.446) 2.59(0.531) (0.526) 2.84 (0.503) Serum hs CRP 1.87(1.932) 2.02(2.332) (1.522) 2.35(19.932) (2.602) 2.89(3.103) Kidney function test Blood urea (mg/dl) (5.835) 22.0(6.027) (6.540) (5.717) (6.840) (6.886) S.creatinine (mg/dl) 0.85(0.162) 0.83 (0.175) (0.159) 0.84(0.161) (0.196) 0.94 (0.198) Uric Acid (mg/dl) (1.241) (1.260) (1.098) (1.065) (1.250) 5.45 (1.23)

8 Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons Graph 4: Comparison of kidney function test (blood urea and s creatinine) of Ashwagandhadi leha, Brahma Rasayana and Cyavanaprasa before and after the trial in healthy Elderly Persons. formulation counteracts Vata due to its Guru and Snigdha Guna; Madhura Rasa and Vipaka; and Dhatu Pushtikara karma. Due to its Rochana, Dipana and Pachana Karma, it kindles the Agni, which in turn influences Dhatvagni, preventing the formation of Amadosha, which is the root cause of all the disease. 21 As more and more medications and health tonics are gaining momentum in medical industry in the context of maintaining health, there has become an increase in the onset of various adverse drug reactions (ADRs) especially in the elderly population. This might be attributed to the weakened immune system, declining health, degenerations in the cellular and tissue level and also due to interactions of concomitant medications safe use of these types of preparations can be promoted by regular monitoring for adverse effects through laboratory and clinical investigations and frequent review for any drug interactions. The safety assessment of these Rasayana was conducted through evaluating serum cholesterol, serum triglycerides, low density lipoprotein, serum bilirubin, SGPT, SGOT, serum alkaline phosphatase, total protein, albumin, globulin, blood urea and serum creatinine before and after the trial and was observed to be within normal limits during the trial. No ADR or adverse event (AE) could be observed in these patients and hence can be said to be used for rasayana purpose; safely and effectively. CONCLUSION The study to evaluate the safety and rasayana efficacy of Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha as a rasayana were conducted at peripheral institutes of CCRAS spread throughout various bio-geographical areas of India. The analysis of outcome of these scientifically planned studies demonstrates that, inspite of the differences in gender, socioeconomic status, age group, Prakrti and geographic region; Ashwagandhadi leha, Brahma Rasayana and Chyavanaprasha proved to be very much safe, effective as rasayana and tolerable in apparently healthy elderly persons. No adverse drug reaction or adverse events (AE) were noticed during the trial period. REFERENCES 1. Vaidya Jadavji Tri kamji Acharya, editor. Susruta Samhita of Susruta, Sutra Sthana, Ch. 15/Ver. 15. Reprint ed. Varanasi: Chaukambha Sanskrit Sansthan; Harman D. The aging process. Proc Natl Acad Sci U S A. 198;78(11): Weinert BT, Timiras PS. Invited review: Theories of aging. J Appl Physiol (1985). 2003;95(4): Anonymous. The Ayurvedic Pharmacopoeia of India, Part - II, Vol - III. 1st ed. Delhi: The Controller of Publications, (Ministry of Health and Family Welfare, Govt. of India); Singh N, Singh SP, Sinha JN, Shanker K, Kohli RP. Withania somnifera (Ashwagandha) A rejuvenator herbal drug which enhances survival during stress (An adaptogen). Int J Crude Res. 1982;3: Anonymous. The Ayurvedic Pharmacopoeia of India, Part- II, Vol - III. 1st ed. Delhi: The Controller of Publications, (Ministry of Health and Family Welfare, Govt. of India); Anonymous. The Ayurvedic Pharmacopoeia of India, Part - II, Vol - I. 1st ed. Delhi: The Controller of Publications, (Ministry of Health and Family Welfare, Govt. of India); Charak samhita commented by Chakrapanidatta Ayurveda Dipika Commentry,Chaukhamba Sanskrit sansthan Varanasi Chikitsa sthan 1(8) Vaidya Jadavji Tri kamji Acharya, editor. Charaka Samhita of Agnivesha, Sutra Sthana, Ch. 18/Ver. 4. Delhi: Munshiram Manoharlal Publishers Pvt Ltd; 1982.p Vaidya Jadavji Tri kamji Acharya, editor. SusrutaSamhita of Susruta. Reprint ed. Varanasi: 11. Chaukambha Sanskrit Sansthan; Savitha HP, Shetty SK, Prakash N. An observational study on the efficacy of Ashwagandhadi Lehya in healthy elders. Journal of Research in Ayurvedic Sciences, April-June 2018;2(2):

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10 Clinical Safety of Selected Ayurvedic Formulations as Rasayana in Apparently Healthy Elderly Persons Journal of Research in Ayurvedic Sciences, April-June 2018;2(2):