E-ISSN:2456-3110

Review Article

Avascular Necrosis

Journal of Ayurveda and Integrated Medical Sciences

2023 Volume 8 Number 11 November
Publisherwww.maharshicharaka.in

Avascular Necrosis - A Conceptual Interpretation in Ayurveda

Balendu Krishnan V1*
DOI:10.21760/jaims.8.11.18

1* V Balendu Krishnan, Associate Professor, Department Of Kayachikitsa, Shiva Ayurveda Medical College, Himachal Pradesh, India.

Avascular Necrosis is a major health problem which results in the complete collapse of a Bone which may end up in permanent disabilities in the patient. Ayurveda with its vast concept of effective analysis and treatment aspects can be much fruitful in Avascular Necrosis cases without hampering other systems of the body. Here in this article an attempt is made to understand Avascular Necrosis by the concepts of Vatarakta in understanding its pathogenesis and its Treatment.

Keywords: Avascular Necrosis, Vatarakta

Corresponding Author How to Cite this Article To Browse
V Balendu Krishnan, Associate Professor, Department Of Kayachikitsa, Shiva Ayurveda Medical College, , Himachal Pradesh, India.
Email: 		Balendu Krishnan V, Avascular Necrosis - A Conceptual Interpretation in Ayurveda. J Ayu Int Med Sci. 2023;8(11):118-124.
Available From
https://jaims.in/jaims/article/view/2885

Manuscript Received Review Round 1 Review Round 2 Review Round 3 Accepted
2023-09-13 2023-09-23 2023-10-06 2023-10-16 2023-10-21
Conflict of Interest Funding Ethical Approval Plagiarism X-checker Note
None declared Nil Yes 23.96

© 2023by Balendu Krishnan Vand Published by Maharshi Charaka Ayurveda Organization. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ unported [CC BY 4.0].

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Introduction

Avascular Necrosis, also called osteonecrosis is the death of Bone tissue due to a lack of Blood supply. It can lead to tiny breaks in the Bone and the Bone's eventual collapse. As the condition worsens, the affected joint might hurt only when you put weight on it but eventually, patient might feel the pain even when they lie down. Pain can be mild or severe and usually develops gradually. Pain associated with Avascular Necrosis of the hip might center on the groin, thigh or buttock. Besides the Hip, the areas likely to be affected are the Shoulder, Knee, Hand and Foot. Some people develop Avascular Necrosis on both sides (bilaterally) - such as in both Hips or in both Knees.

Causes

Avascular Necrosis occurs when Blood flow to a Bone is interrupted or reduced. Reduced Blood supply can be caused by Joint or Bone Trauma - An injury, such as a dislocated joint, might damage nearby Blood vessels. Cancer treatments involving radiation also can weaken Bone and harm Blood vessels. Fatty deposits in Blood vessels - The fat (lipids) can block small Blood vessels, reducing the Blood flow that feeds Bones. Certain diseases - Pancreatitis, Diabetes, Gaucher’s disease, HIV/AIDS, Systemic lupus erythematous, Sickle cell anemia etc. Other Risk factors for developing Avascular Necrosis include: Trauma - Injuries, such as hip dislocation or fracture, can damage nearby Blood vessels and reduce Blood flow to Bones, Steroid use - Use of high-dose corticosteroids, such as prednisone, is a common cause of Avascular Necrosis. The reason is unknown, but one hypothesis is that corticosteroids can increase lipid levels in your Blood, reducing Blood flow. Excessive alcohol use - Consuming several alcoholic drinks a day for several years also can cause fatty deposits to form in your Blood vessels. Bisphosphonate use - Long-term use of medications to increase Bone density might contribute to developing Osteonecrosis of the Jaw.

This rare complication has occurred in some people treated with high doses of these Medications for Cancers, such as multiple Myeloma and Metastatic Breast Cancer. Certain medical treatments - Radiation Therapy for Cancer can weaken Bone. Organ Transplantation, Especially kidney Transplant, also is associated with Avascular Necrosis.

Complications

Untreated Avascular Necrosis worsens with time. Eventually, the Bone can collapse. Avascular Necrosis also causes Bone to lose its smooth shape, potentially leading to severe osteoporosis, osteomyelitis, osteoarthritis, collapse of the Bone.[1]

Source of Collection of Data

For the present Article, data was collected from Post Graduate library, Department of Kayachikitsa Ayurveda Mahavidyalaya and Hospital Hubli, Ayurvedic classics like Ashtanga Hridaya, Charaka Samhita & Modern available texts, Authentic Research Journals, M.D Dissertations, Research papers & Websites.

Conceptual Analysis in Ayurveda

Before we start let’s see the details of Dhatu which is having the main function to carry out the proper functioning and they co-exist in the Sharira by nourishing each other which is explained in Ayurveda on the basis of various Nyayas “Sareeradharakataya Dhatwantaraposhakataya Cha Dhatu Sabenochyante” and Dhatwagni, which governs metabolic – enzymatic reactions in the body; food transformation producing Saara Bhaga (Proper Dhatu) and Upadhatu and Kitta forming various Malas/ metabolic waste. So, in the case of Asthi Dhatu proper Poshana is done by Dhatu Parinama from Rasa—Rakta—Mamsa—Medo—Asthi—Majja—Sukra where the Poshaka Medo Dhatu is transformed into Asthi Dhatu by the Prithvi, Vayu, and Medasagni.[2]

Asthi Dhatu / Bone tissue

Bone tissue consists of Osteoblasts, Osteoclasts and Matrix in which Mineral Salts are present. Bone cavity consists of Bone Marrow which is rich of Lipids,mostly Triglycerides. Matrix contains group of Proteins and Minerals which are of Cations, Calcium, Sodium, Potassium, Magnesium and Anions, Phosphate, Carbonate, Citrate, Chloride, Fluoride. The Osteoblasts are also rich in Glycolytic Enzymes. For the normal Activity of Osteoblast Vitamin C, A, D is required which is supplied mostly by Jeeva Rakta. So, the Major issue in AVN is the blockage of this Blood supply to a particular site that is Rakta Marga Rodham which in turn affects the Dhatu Parinama resulting in Kshaya of consecutive Dhatus as per Ksheera Dadhi Nyaya, Kedari Kulya Nyaya and Khale Kapotha Nyayas. Modern anatomy clearly


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clarifies this concept as we see to the function of Nutrient Artery - which is a Srotas / Rakta Dhamani that provides nutrition and oxygenated Blood to the Bone. So when a Sankocha is happening to this artery or its supplying arteries or its accessory arteries Disruption of Nutrient Artery occurs which results in necrosis of large portion of marrow & of inner two thirds of cortex; this cortical death does not occur in adult Bone because combined epiphyseal metaphyseal collateral circulation is developed enough to maintain these areas; loss of circulation in terminal vessels of nutrient artery of growing Bone will interfere endochondral ossification resulting in various inflammatory changes (Dhatu Paka) resulting in Dhatu Kshaya (slow necrosis) [3]

Nidana vs Causes

  • Traumatic Injury to the joint or Bone leading to reduced Blood flow : This can be taken as the Abhighata or Marmaabhighata as the Marma resides in such important vital points including Mamsa, Siras, Asthi, Snayu, Dhamani and Sandhi etc.; each Marma there is a dominancy of one of the above elements so any injury in these areas can result in clinical symptoms of that particular element as here in AVN an injury to a particular Dhamani can result in the Srotho Vaigunyam resulting in Kshaya or necrosis of the Asthi Dhatu.
  • Some disorders like Sickle cell anemia - where the Shudha /Jeeva Rakta is not formed and there by the proper Dhatu Parinama doesn’t happen and Aposhaka Dhatus are formed. Other haemoglobinopathies also result in the same conditions.
  • Gaucher’s disease is a genetic disorder, which leads into the deficiency of an Enzyme Called Glucocerebrosidase, that results in the inability of the body to break down a chemical called Glucocerebriside These cells can accumulate in any part of the body such as the Liver, Spleen, Lungs, Lymphatic System and Bones. An enzyme can be considered as an agent that carries out a Parinama /conversion which can be correlated with Agni which is the Biological Energy needed for any sort of process inside a Dhatu Paramanus or cells and its Mandya is Agnimandya at Bhoothagni /Dhatwagni level and as this chemical which is Apakva Janya, accumulates in the body parts it can also be considered as Ama Dosha.
  • Other immune disorders like HIV, SLE, Anti Phospholipid Antibody - where the body cells deteriorate which result in the destruction of proper blood supply to the human body resulting in Necrosis where the concepts of “Vyadhi Kshamathvam - Vyadhi Bala can be taken.
  • Some disorders like Caissons Disease - a condition arising from dissolved gases coming out of solution into bubbles inside the body on Depressurization which can cause obstruction to the Blood flow to a particular area and Hypercoagulable States or Thrombophilia (sometimes hypercoagulability or a prothrombotic state) is an abnormality of Blood Coagulation that increases the risk of Thrombosis (Blood clots in Blood vessels). Excessive Drinking, excess use of Cortico Steroids results in the increase of Lipids in the Body, Hyperlipidemia which gets deposited in the Blood vessels causing the obstruction of Blood flow to a particular area. Here in both these cases, we can take the concept of Sanghatmaka Avarana directly, which is causing obstruction to the flow of Jeeva Rakta to a particular area causing Kshaya.
  • Excessive intake of biophosphonates, other Osteoporotic drugs during Cancer treatments, other Drugs like Steroids, Cancer treatment Drugs, Radiation therapy, Dialysis Drugs and Treatments, Organ Transplants and Heavy Lipid /Cholesterol increasing diet etc., can cause AVN which can all be included under “Ahita Ahara Vihara”.
  • Other disorders like CLD (medicines of CLD /Vit D Deficiencies), Pancreatitis (lipid increase), TB causes improper Agni mechanisms resulting in various Malabsorption Symptoms, Improper Metabolism, Excess production of Ama Dosha all resulting in Dhatu Kshaya and Dosha Prakopa.

So, the general Samprapthi can be taken as Various Nidanas - Rakta Dushti - Rakthvaha Sroto Rodha - Dhatwagni Mandya - Dhatu Parinama Rodham/Apakva Dhatu - Asthi Dhatu Kshaya/Sleshaka Kapha Kshaya in Sandhi - Asthi Dhatu/ Sandhi Dourbalya - Complications

Now let’s try to understand the details of the concepts of Samprapti of AVN in three stages adopting similar Samprapthi Sthitis from other Vyadhis


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  • First Stage of Samprapthi

In Apabahuka, Susrutha Acharya has quoted Vayu in Amsa Desha will cause Shosha on that region by “Sirashcha Akunjanam” or constricting the Siras - lack of proper Jeeva Rakta Paribhramana - Lack of formation of Poshaka Dhatus - Dhatu Kshaya Kshaya or Shosha of Amsa Sandhi which includes Mamsa / Meda / Asthi / Majja etc. which can be taken as first stage of Samprapthi in AVN.[4]

  • Second Stage of Samprapthi

Chakrapanidatta explains that in Avarana as the vitiation of Vata is the result of the Obstruction to spontaneous stimulation for movement. Avarana can also be considered as Sanga, as an obstruction, Samsarga the combination of two Doshas. So here when we explain the Avarana Sidhantha, Vyana Vata comes into the picture Vyana Vata Sthana is at ‘Hridisthitaha’ and is considered as ‘Sarva Dehachari”- that moves all over the body. Astanga Sangrahakara explains in detail about the functions of Vyana Vata can be summarized under the headings Gati (all the movements), Rasa- Rakta Paribhramana (circulation of nutrients), Sweda Srava (excretion of sweat), Anna Aswaadhana (appreciate taste) and Shukra Pratipadhana (carrying semen), dividing food for absorption and excretion and gradually nourishing the Dhatus from the nutrient material. As per the Asraya Asrayibhava, Vata resides in Asthi and that Vata residing in the Asthi brings about the movements. The functions of somatic nervous system can also be ascribed to Vyana Vata as movements like Flexion, Extension, Opening and Closure of Eyelids have said to be under its control. The function of Asrk Sravana is possible by the stimulation of the sympathetic supply to heart. This depends not only on the effective contraction of heart but also on the caliber of the Blood vessels.[5]

  • So, as we see to the condition of AVN, the blockage due to different causes ultimately resulting in the Rodha of Vyana Vata and its function of Rasa Rakta Paribhraman and resulting in further Vata Kopa and Avarana Janya Dhatu Kshaya and specifically blocking its functional aspects of Gati / movements of the joints which also gets hindered in AVN All these explains the concepts of second stage of Samprapthi in AVN.
  • Third Stage of Samprapthi

In the Samprapthi of Prameha /Diabetes – all the Drava Roopi Dhatus

are affected first and finally the Sthira Dhatu Asthi is affected in the form of Osteoporosis and osteopathy. Here Kapha vitiating Medas /Mamsa/Kleda - all Poshaka Amsha is taken out through Mutra - Dhatu Kshaya - Dhatwagni is affected which result in demineralization of bones i.e.; Asthi Kshaya[6]

The same pattern of Asthi Dhatu Kshaya happens in AVN where Poshaka Amsha is not reaching the Dhatus leading to Kshaya in final stage of Samprapthi, so in general all these will result in the Improper or Complete Cessation of the Nutrient supply to the Particular Joint - resulting in destruction of tissues with various Inflammatory Changes (Dhatu Paka) - Results in Dosha Kshaya - leads to complete death of the Tissues Necrosis / Dhatu Kshayavat Ghnanthi occurs.

Once the nourishment to the Sandhi/Asthi is occluded the proper maintenance of Sleshaka Kapha is also hampered which is predominately present within Synovial fluid of the Joints, nourishing the articular surface ensuring lubrication, Stability and Flexibility of the Joints. Vata Kopa in Asthi results in Kshaya of this Sleshaka Kapha leading to degenerative changes within the Skeletal System such as Sandhi Dourbalyatha /Sandhi Saidhilyatha.[7]

Symptoms vs Lakshanas

Pain /Ruk is the main symptom which is presented by the Patient which increases day by day in different patterns / Vedana in Sandhi Asthi Majjasu Lakshanas like Bhedo Asthi Parvanam (breaking type of pain), Sandhi Shoola (Joint Pain), Satata Ruk (continuous pain), Mamsa Bala Kshaya (muscle weakness), Asvapna (loss of sleep) etc.

As the disease progresses, due to the avascularity / Poshaka Dhatu Utpatti Kshaya symptoms like Collapse of the joint / Sandhi Dourbalya, irregular structural formation of the Bone or Joint / Vakri Karana of Sandhyasthi, Osteoporotic Changes / Asthi Majja Kshayam – “Asthanam Majjani Sousheeryam” Results in collapse of the Asthi /Sandhi - Bhagna or Permanent Disability of the Joints like Panguthvam, Khanjathvam, Sandhi Sosham occurs.

Classical Interpretation

In Ashtanga Hridaya Vataraktadhikara Acharya has clearly mentioned,

“Janu Janghoru Katyamsahasthapadanga Sandhishu


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Kkandu Sphurana Nistodabheda Gourava Suptata

Bhutva Bhutva Pranashyanthi Muhuravirbhavanti Cha

Gambhire Adhika Poorva Ruk

Shayvadhurgradhita Paki Vayu Sandhyasthimajjasu

Chindanniva Charatyantharvakrikurvashcha Vegavan

Karothi Khanjam Pangu Va Shareere Sarvathascharan //”[8]

Here Acharya has clearly mentioned the joints afflicted by Vatarakta and progressive nature of Vatarakta, same in the case of AVN, the Disease is very progressive where ‘Vatae Adhikam Adhikam Shoolam” (Ca) as the Avascularity Progress resulting in further aggravation of Vata, resulting in more Ruk and Dhatu Kshaya and the symptomatic similarities which we have already discussed can be seen in this classical verse. While mentioning the progressive nature of Vatarakta, Acharya has mentioned the ideology of Anyonya Avarana where Vata residing in Rakta Marga, Sakha, Sandhi will result in Vividha type of Vedana and while mentioning Vyana Vata, as it is Sarva Dehachari its Prakupitha Avastha can result in Sarvanga Rogas according to the Sthana of Prakopa which explains the occurrence of Avascular Necrosis in different Sthanas.

In the context of Ubhayasrita Vata Raktam, Acharya Charaka mentions,

“Twak Mamsa Asrayam Uthanam Gambhire Tvarantharasrayam

Kandudaharukayamathodasphuranaakunjanaihi

Anvitha Shyavarakta Twak Dahe Thamra Thadheshyathe

Gambhire Shyavathu Sthabdha Kadino Antharbhrisharthiman

Shyava Sthamro Adhava Daha Thoda Sphurana Pakavan

 Ruk Vidahanvitho Abhikshnam Vayuhu Sandhyasthi Majjasu

Chindanniva Charathyantharvakreekurvashcga Vegavan

Karothi Khanjam Pangu Va Shareere Sarvathscharan

Sarvalingaishcha Vijneyo Vatasrik Ubhyasrayam” [9]

Considering these two classical references where the symptoms of AVN can be clearly seen in both Gambhira Vata Rakta and Ubhayasritha Vata Rakta as all the Lakshanas of Sandhi Asthi Majja Gata Vata Lakshanas are mentioned. But AVN also shows some Twak Mamsashraya Asrita Lakshanas too, hence Ubhayasrita Vatarakta concept can be taken as perfect correlation explaining both Samprapthi and Chikitsa.

Why not Gata Vatam??

As per the Lakshanas, Asthimajja Gata Vata and Sira Gata Vata Lakshanas is having much resemblance but when we see to the Samprapthi in detail, the concept of Avarana with Vata and Rakta involvement is seen and Ubhayasrita Vata Rakta explains both Avarana and Lakshanas of “Vayuhu Sandhyasthimajjagata ……..” better explaining concept can be adopted and here Vata is not getting vitiated by Swanidanas and as in Gata Vata, Karma Vridhi of Vata is not happening here as Vyana Vata Karma Hani is seen in the Samprapthi concepts, So Gata Vata concept can be avoided.[10]

Chikitsa Sidhantas

First line of treatment in Modern and Ayurveda is almost same i.e., “Nidana Parivarjana” avoiding the causes mentioned like Abhighata, Ahita Ahara Vihara, treating the Primary Disorders without triggering AVN.

Surgical Management includes Joint Preserving Procedures like Measures to allow better Blood supply, removal of the cortex of the Bone from the Head of the Affected Bone, Local Bone Grafting Procedures, Bone Resurfacing procedures, Non-steroidal Anti-Inflammatory drugs (NSAIDs) like Naproxen (Aleve) and ibuprofen (Motrin, Advil, or others), Osteoporosis drugs like Alendronate (Binosto, Fosamax), Cholesterol-lowering drugs like Statins and Fibrates, that can help to reduce Cholesterol or Fats (Lipids) from the Blood and reduce the propensity for Vessel Blockages, Blood Thinners like Warfarin (Coumadin, Jantoven), which can help patients who experience Blood clotting problems and Progressed stage - Total Joint Replacement Surgery.

  • In Ayurveda, we have to treat this Avarana Janya Vyadhi with both Vataraktavat Chikitsa and Dhatu Bhrimhana Chikitsa

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  • procedures which includes Udwarthana, Abhyanga, Mridu Swedana, Basti Chikitsa, Virechana
  • Starting with Amapachana, External and internal administration of Snehana (Oleation) is the best treatment modality explained for this condition.
  • External Oleation is performed by Abhyanga with medicated oils like Madhuyashti Thailam, Pinda Thailam, Murivenna and Internally it is administered in the form of Paana with Guggulutikthaka Ghrita, Panchatikthaka Ghrita and Basti with Balaguduchyadi Thailam, Guduchi Ghritam, Guduchyadi Ghritam other Tiktha Dravya Sadhita Ghritas.
  • Virechana can be done with Gandharvahastadi Eranda, Nimbamrithadi Eranda, Gandharva Hareetaki.
  • For nourishing Asthi Dhatu, Panchatikthaka Ksheera Basti, Ksheera Basti with Aswagandha Churna, Yashtimadhu Churna, Guduchi, Musta, Saghrita Ksheera Basti (Tikthaka Ghrita with Manjishta, Arjuna as Kalka), Kukudanta Sweda.
  • For treating Bala Mamsa Kshaya, Njavara Kizhi, Ksheera Dhooma which are considered to possess best Bhrimhana
  • Medicines like Kokilaksham Kashayam, Guggulutikthakam Kashayam, Manjishtadi Kashayam, Balaguduchyadi Kashayam.
  • Gutikas like Vatarakshasa, Punarnavadi Guggulu, Amrithadi Guggulu, Abha Guggulu, Ajaasthi Bhasma, Kaishora Guggulu, Shiva Gutika, Kukkutanda Twak Bhasma, Shilajithu Vati.[11]

Sadhyaasadhyata

Prognosis depends on the area of the Bone that is affected, minor or major part of the area involved and how well the rebuilding of the Bone occurs.

However, AVN patients experience rapid break down of the Bone tissues which are not followed by quick repair. If the destruction / necrosis of Bone cells is rapid, prognosis is difficult but can be managed with surgical interventions. Patients may enjoy full recovery after treatment or experience permanent damage of the joints with progression of the disease.

And when we infer in Ayurveda……….

Since it is a Asthi Sandhi Asrita Roga, it’s a Madhyama Roga Marga disease but as Raktadi Dhatu is also involved Bahyaroga Marga too should also be taken into account.

Considering these two factors it is to be considered as a Krichra Sadhya Roga.

Conclusion

Avascular Necrosis is a major disease affecting a large number of population due to different Nidanas. Modern Medical Science has a major role in the severe stages of AVN where there is a complete collapse / Fractural Abnormalities / Permanent Mal Formations, where surgical intervention is needed. But our Acharyas has beautifully explained the Concept of Avarana by which we can break the Pathogenesis / Samprapthi in both its conceptual and treatment aspects. Moreover, Ayurvedic Formulations and Procedures can do Sookshsma Sthoola, Sroto Vishodhanam, Dhathu Brimhanam and Dosha Samshamanam doing wonders in Avascular Necrosis.

By improving the Rakta Paribhramana - Avascular Defects can be resolved and hence arresting the Kshaya of Dhatus / Necrosis.

References

1. Mayo Clinic. Avascular necrosis - Symptoms and causes. [Internet]. Mayo Clinic; [cited 2023 Mar 17]. Available from: https://www.mayoclinic.org/diseases-conditions/avascular-necrosis/symptoms-causes/syc-20369859

2. Charaka. Charaka Samhitha with Deepika Teeka of Chakrapanidatta, edited by A.V. Sri Lalachandra Shastri Vaidya. Agnivesa’s Charaka Samhita, with Ayurveda; Reprint Edition, Krishnadas Academy, Varanasi 2009. Chikitsasthana 8/39 Page no 371; Pp -738.

3. Avss Ramarao. A Book On Biochemistry. New Delhi, UBS Publishers; 1990. P.no 247.

4. Susutha. Susrutha Samhita edited by Vaidya Yadavji Trikamji Acharya, with Nibandha Sangraha commentary by Dalhana and Nyaya Chandrika Panjika of Sri Gayadasa, Reprint Edition, Krishnadas Academy, Varanasi; 2000;2:17.

5. Indu. Astanga Sangraha


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of Vagbhata with Sasilekha Sanskrit commentary. Chaukamba Sanskrit Samsthan; 2006. p.156.

6. Charaka. Charaka Samhita. With Deepika Teeka of Chakrapanidatta, edited by A.V. Sri Lalachandra Shastri Vaidya, Agnivesa’s Charaka Samhita, with Ayurveda; Reprint Edition, Krishnadas Academy, Varanasi 2000. Chikitsa sthana Edition, Krishnadas Academy, Varanasi, 2000 Chikitsa Stana 6/5,6; Pp -738.

7. Vagabhata. Ashtanga Hridaya. Acharya Hari Shastri Paradakara Vaidya, with commentary of Sarvangasundari of Arunadatta and Ayurveda Rasayana of Hemadri, 9th Edition, Chaukhambha Orientalia Publishers, Varanasi, Uttar Pradesh, 2002. A.H. Sutra sthana 12-18; Pp – 956.

8. Vagabhata. Ashtanga Hridaya. Acharya Hari Shastri Paradakara Vaidya, with commentary of Sarvangasundari of Arunadatta and Ayurveda Rasayana of Hemadri, 9th Edition, Chaukhambha Orientalia Publishers, Varanasi, Uttar Pradesh, 2002. A.H. Nidana sthana 16; Pp – 956.

9. Charaka. Agnivesa’s Charaka Samhita. Sri Lalachandra Shastri Vaidya, with Ayurveda Deepika Teeka of Chakrapanidatta, Reprint Edition, Krishnadas Academy, Varanasi, 2000. Cha. Chikitsa sthana 29; Pp -738.

10. Interscience. Prevalence of Avascular Necrosis in Sickle Cell Disease Patients: A Systematic Review and Meta-Analysis. Int J Adv Health Med. [Internet]. 2018;5(5):12–8.

11. Charaka. Agnivesa’s Charaka Samhita. Sri Lalachandra Shastri Vaidya, with Ayurveda Deepika Teeka of Chakrapanidatta, Reprint Edition, Krishnadas Academy, Varanasi, 2000. Cha. Chikitsa sthana 29 Page no 627; Pp -738.


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