Girish Tillu

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial

OBJECTIVE To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). METHODS Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. RESULTS Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. CONCLUSION In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. TRIAL REGISTRATION Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Ayurveda-modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis

The potential of Ayurvedic philosophy and medicines needs to be recognized and converted into real life treatment paradigm. This article describes a comprehensive therapeutic approach used in Ayurveda and modern medicine to treat arthritis. We present concise summary of various controlled drug trials carried out by us to validate standardized Ayurvedic drugs using modern medicine protocol to treat Rheumatoid Arthritis and Osteoarthritis knees. Several of the latter are published. The trials consistently demonstrate excellent safety of Ayurvedic medicines but often fail to unequivocally show superior efficacy. Some key findings of a recently unpublished trial in OA knees are also presented to show equivalence between Ayurvedic medicine and celecoxib and glucosamine, and we speculate that equivalence trials may be a way forward. The data from the trials also supports the Ayurvedic ‘Rasayana’ concept of immune-modulation and healing. We need to interpret logic of Ayurveda when, adopting modern science tools in drug development and validation and much research is required. Validation of Ayurvedic medicines using the latter approach may lead to an evidence based Ayurveda – Modern Medicine interface. Also, in pursuit of finding better treatment solutions, we ought to step beyond the realm of only drugs and attempt validation of comprehensive specific treatment package as per classical Ayurveda. Finally, validation of a combined (Ayurveda and modern medicine) therapeutic approach with superior efficacy and safety is likely to be a major leap in overcoming some of the current frustrations to treat difficult disorders like arthritis using only modern medicines.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project

The multidisciplinary “New Millennium Indian Technology Leadership Initiative” Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, “C” formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Cancer, Inflammation, and Insights from Ayurveda

A recent, exciting discovery relates to the concept of “shared pathology” between cancer and metabolic syndrome. One major pathway common to cancer and metabolic syndrome is chronic inflammation, which is a major driving force in carcinogenesis. Indeed, chronic inflammation precedes most cancers and is considered a “hallmark” of the neoplastic process. We discuss molecular and biochemical evidence which links diet, obesity, abnormal lipid metabolism, and type 2 diabetes mellitus with chronic inflammation. We also explain how each of these factors is linked with biochemical aberrations of carcinogenesis and the prevalence and risk of cancer. While there are reliable biomarkers for chronic inflammation, there are few markers for a mechanistic link between early inflammation and digestive disorders. Discovery of such a marker could lead to identification of a new subtype of patients with digestive disorders that predispose them to cancer and/or metabolic syndrome. In this context, we discuss the ayurvedic concept of “Ama” which is thought to be a toxic, proinflammatory waste-product of improper digestion. We then develop hypotheses and outline preclinical and clinical experiments designed to prove whether “Ama” can serve as a novel and reliable biomarker that links abnormal digestive status, with the onset of chronic inflammation.

Efficacy and safety of Ayurvedic medicines: Recommending equivalence trial design and proposing safety index

Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The trials, often placebo controlled, are usually designed to demonstrate superiority. Though the results have been usually reported as encouraging, statistical significance has been elusive. In this melee to show efficacy, several positive results related to safety and other purported advantages with Ayurvedic drugs, including improved quality of life, easy drug availability and less cost, get drowned. Though safety is the prime concern, efficacy ultimately matters in trials. Excellent safety profile offset modest efficacy, especially for long-term management of chronic difficult to treat disorders. There is a trade-off between efficacy and safety but we have no means to put them together in a mathematical evaluation to judge the overall performance of a drug. However, we need more suitable modern science methods/techniques to unravel the true therapeutic role of Ayurvedic drugs. We propose “equivalence trials” using modern medicine benchmark as a comparator and a “safety/tolerability index” on this perspective. We believe that several Ayurvedic drugs are capable of demonstrating equal efficacy but superior safety. Our concept may also be applicable for pragmatic trials that are more suitable for Ayurvedic therapy.

Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project

Background: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were “platform combination+Withania somnifera+Tribulus terrestris” (formulation B) and “platform combination+Emblica officinale” (formulation C). This paper reports safety of these formulations when used in higher doses (1.5–2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). Materials and Methods: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. Results: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut–related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5–2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22–2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. Conclusion: The results suggested that despite higher doses, standardized Ayurvedic formulations demonstrated a good safety profile. An improved efficacy and likely chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with adequate power and sample size was planned based on the learning from this trial.

Diet, Ayurveda and interface with biomedicine

We thank Dr Kontum for his interesting and useful comments to our paper[1] and further reference to the address by one of the authors (AC) to the recently concluded World Ayurveda Congress 2010 in Bangalore on the subject of ‘Ayurveda Biomedicine Interface’. Kontum has very rightly highlighted the ‘holistic approach’ as a contrast to just focusing on ‘drugs’. Also, he has described a relatively simple method of cooking rice practiced by his family that apparently enriches the health promotion and preventive value. Several such healthy practices advocated by Ayurveda could be included in the daily life style and living in modern times in addition to the one he suggested.

Good practices of publishing AYUSH research: A practical checklist for authors

Since its inception, Journal of Ayurveda and Integrative Medicine (J-AIM) has been constantly striving to create an environment that inculcates and strengthens “Good Publication Practices (GPP)” amongst students, practitioners and researchers in AYUSH community. The J-AIM has been doing this in the form of conducting workshops on scientific writing and research methods on different platforms. This article is based on our experiences and varied discussions that we have had with students, teachers, practitioners and researchers during these interactive sessions, and is intended at addressing the gap that prevails in the domain. The need for such awareness is felt even more strongly ever since the Bealls list of predatory journals has been unpublished. This article tries to fill the void this disappearance has created. We analyze the current scenario of AYUSH publications, enumerate the common perceptions and concerns among the workers in the field, and consider the periodicals where the doctoral and postgraduate level of Ayurveda research works are being published at present. The article also presents a practical checklist that will be helpful for students and teachers to refer authentic resources and submit their work to an appropriate scholarly journal.

Lifestyle and Behavior

This chapter discusses the role of lifestyle and behavior in health and disease. The authors suggest that therapeutic approaches should be holistic, involving body and mind. In recent times, many new approaches such as behavioral medicine, lifestyle medicine, mind–body medicine, and mindfulness have emerged. This may be due to growing dissatisfaction with current drugs, and their limitations to treat psychosomatic conditions. Most of them draw from traditional knowledge systems like Ayurveda, yoga, tai chi, and qigong, among others. Ayurvedic therapeutics involves drugs, diet, and lifestyle advice as a part of a healthy living doctrine known as Swasthavritta ; and body cleansing detox procedures known as Panchakarma . Yoga involves physical exercise and mental interventions through specific postures, and meditation. Integrative approaches involving biomedicine, Ayurveda, and yoga can offer effective remedies for chronic, psychosomatic, and lifestyle-related diseases. A few case studies related to the application of lifestyle medicine in health care are discussed.

Concepts of Health and Disease

This chapter discusses concepts and definitions of health, wellness, illness, and medicine. A discussion on determinants, indicators, and dimensions of health help to understand the limitations of the definition of health. The authors highlight health as a positive concept where an individual actively participates in a process of attainment of health; treatment of disease is a passive process where doctors and hospitals have larger roles. The individuals quest for health is based on many factors including lifestyle, behavior, attitudes, and philosophy of life. The authors suggest that mainly due to reasons of convenience, our current health care approach focuses on diseases and treatments, which has led to the medicalization of society. The authors discuss concepts of health and disease from the viewpoints of modern and traditional medicine. The Ayurvedic concept of health is holistic at the levels of body/mind/spirit, where the three Dosha are in a homeostatic state leading to well-being and bliss. Ayurveda and Yoga emphasize lifestyle, cultural practices, and harmony with nature. They offer advice for seasonal changes in lifestyle, daily activity, diet, and meditation practices. Health as a transborder subject has to be considered from individual to planetary levels.