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| PROTOCOL |
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| Year : 2021 | Volume
: 5
| Issue : 4 | Page : 192-196 |
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Efficacy and safety of Ayurveda interventions for diabetes mellitus—A systematic review protocol
Shyam Gyanoba Kale1, Kalpana Budhaji Kachre2, Bidhan Mahajan2, Parth Prakashbhai Dave1, Azeem Ahmad2, Milind Suryawanshi1, Bhogavalli Chandrasekhar Rao2, Narayanam Srikanth3
1 R.R.A. Podar Central Ayurveda Research Institute (CCRAS), Mumbai-18, India
2 CCRAS Headquarters, New Delhi, India
3 Deputy Director General, Central Council For Research In Ayurvedic Sciences, Ministry Of Ayush, Govt. of India, India
| Date of Submission | 22-Jul-2021 |
| Date of Decision | 15-Mar-2022 |
| Date of Acceptance | 21-Mar-2022 |
| Date of Web Publication | 29-Apr-2022 |
Correspondence Address:
Shyam Gyanoba Kale
R.R.A. Podar Central Ayurveda Research Institute (CCRAS), Mumbai-18
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jras.jras_8_21
INTRODUCTION: Ayurvedic treatments are in use to treat Diabetes Mellitus (DM), either as a stand-alone treatment or as an adjunct to conventional care. There is need for a comprehensive assessment of the efficacy and safety of Ayurvedic interventions in DM through a systematic review. Therefore present work is planned to create quality based evidence on the efficacy and safety of Ayurvedic intervention for DM. MATERIALS AND METHODS: The data for systematic review will be collected by a comprehensive search of databases will be made to get maximum research articles on clinical trials such as randomized, non-randomized controlled, multiple arm, and quasi-randomized controlled trials. The primary outcome will be treatment response on improvement in subjective criteria, i.e. associated symptoms with DM, effect on fasting blood glucose level, postprandial blood glucose level and HbA1C level. The secondary outcome will be the assessment of the health-related quality of life and safety of interventions. For the systematic review three reviewers will extract the data separately in a pre-determined format. For each included study, a narrative synthesis will be conducted. A meta-analysis will be performed if the collected data is suitable for meta-analysis. CONCLUSION: The systematic review serves as a representative of the evidence of safety and efficacy of Ayurveda interventions in treating DM. Outcome of the review may also provide scope for planning further researches. PROSPERO STUDY REGISTRATION NO: PROSPERO 2020 CRD42020159659 Keywords: Ayurveda, diabetes mellitus, madhumeha, systemic review
How to cite this article:
Kale SG, Kachre KB, Mahajan B, Dave PP, Ahmad A, Suryawanshi M, Rao BC, Srikanth N. Efficacy and safety of Ayurveda interventions for diabetes mellitus—A systematic review protocol. J Res Ayurvedic Sci 2021;5:192-6 |
How to cite this URL:
Kale SG, Kachre KB, Mahajan B, Dave PP, Ahmad A, Suryawanshi M, Rao BC, Srikanth N. Efficacy and safety of Ayurveda interventions for diabetes mellitus—A systematic review protocol. J Res Ayurvedic Sci [serial online] 2021 [cited 2023 Mar 27];5:192-6. Available from: http://www.jrasccras.com/text.asp?2021/5/4/192/344414 |
| Introduction | |  |
Diabetes Mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia with or without glycosuria. DM is classified into two types namely insulin-dependent (IDDM) or type 1 DM and non-insulin-dependent (NIDDM) or type 2DM. It is characterized by recurring or chronic high blood sugar levels and is diagnosed by demonstrating fasting plasma glucose level, Oral glucose tolerance test (OGTT), and Glycated hemoglobin (HBA1C).[1],[2] The global prevalence of DM was estimated at 8.8% of the world population in 2017.[3]
Conventional DM treatment involves lifestyle management in addition to weight management, exercise, and nutritional treatment for medicinal purposes, as well as oral glucose-lowering drugs and insulin therapy.[4] In Ayurveda point of view, DM is mentioned under the heading of Madhumeha. The treatment for DM described in classical texts of Ayurveda includes avoiding diet and lifestyle which is narrated as etiological factors for DM, bio-cleansing therapy, pacifying treatment, and disease-specific rejuvenation. DM is treated with a multipronged approach by Ayurvedic practitioners, which includes bio-cleansing of the body, use of anti-diabetic and rejuvenating herbal remedies, performing Yoga, breathing exercises, and adoption of specific dietary regiments.[5] Ayurveda bio-cleansing of the body i.e. Panchakarma by procedures such as Snehana (therapeutic oleation), Swedana (sudation therapy), Vamana (medicated emesis), Virechana (therapeutic purgation) and Basti (therapeutic enema) have been proven to be highly effective in treatment of DM.[6],[7],[8] Considering the observed efficacy of Ayurveda various intervention in treating DM published in various studies an attempt is made for systematic review.
The rationale of the study
Ayurvedic interventions are used as a stand-alone treatment or as an adjunct to conventional medicine to treat DM as well as related manifestations. Systematic reviews and protocols assessing the efficacy and safety of herbal medicines in DM have been published, but most of them have not assessed the effectiveness of Ayurveda interventions as a whole. Considering the diverse nature of Ayurveda management, there is need to determine the overall evidence on efficacy and safety of Ayurveda intervention as a whole in DM, irrespective of the type of intervention given, whether it may be in form of Panchakarma procedures, or intake of single herb/ polyherbal/ herbo-mineral /metallic preparation, or combination of above both, irrespective of any duration, dose, vehicle, etc. In view of this need, a systematic review is planned to generate data regarding the quality of reported studies, and for designing future clinical studies based on pros, cons and scope of the previous studied.
Objective
To conduct a systematic review on the published clinical studies in terms of safety and efficacy of Ayurvedic intervention for the treatment of DM. If sufficient numbers of studies are available, then meta-analysis will be performed.
| Materials and Methods | | |
Inclusion criteria
Population
Studies in which diagnosis of DM was done either based on Ayurveda criteria narrated for diagnosis of Madhumeha, or according to WHO guidelines (fasting plasma glucose more than or equal to 7mmol/l (126 mg/dl) or a random plasma glucose level of 11.1 mmol/l (200 mg/dl)), will be included for the systematic review.[9] There will be no restriction in the inclusion of the type of DM, associated co-morbidity, complication, etc.
Intervention
This review will include studies in which Ayurveda intervention are gives either as stand-alone or in combination with conventional medicine. The term Ayurveda intervention includes any treatment/practices based on fundamental principles of Ayurveda such as internal or topical medications, Panchakarma therapy, lifestyle advocacy, diet therapy, administration of herbs/medicinal plants described in Ayurvedic literature, polyherbal, herbomineral, metallic formulation or extract in any form (such as powdered, decoction, tablet, butter oil, etc.) of any dosage. There will be no restriction for tThe type of vehicle used along with the drug/formulation and total duration of treatment.[10]
Comparisons/control groups
Studies that compare Ayurveda intervention with placebo and/or sham treatment, conventional medicine, combination of Ayurveda and non-Ayurveda intervention, or Ayurveda intervention as a comparator in comparative clinical trials will be included.
Outcomes
Primary outcomes will be efficacy of the intervention on reducing blood suger level. The secondary outcome will be safety profile of the interventions. The primary outcome will be assessed by improvement noted in fasting blood glucose level, 2 –hour postprandial blood level, and HbA1C level. The secondary outcome will be assessed by patient or laboratory based reporting of adverse events. We will also report the number of withdrawals, dropouts, and any specific adverse events.
Study design
This systematic review will include studies such as Randomized controlled trials, multi-arm clinical trials, non-randomized clinical trials, and quasi-randomized controlled trials. We will also include P.G./PhD. dissertations if it contains sufficient data for evaluation.
Exclusion criteria
Studies that describe treatments other than Ayurveda such as Chinese tradition of medicine, Yoga, Homeopathy, and others not based on principles of Ayurveda will be excluded. In addition to the above, animal trials, editorials, abstracts, meetings, and studies with insufficient information on DM will be excluded. Herbs/medicinal plants that are not described in Ayurveda literature or not found in the Indian continent (such as Chinese herbal medicine) will also be excluded. Studies published in other than English or Indian language will be excluded.
Information sources
The electronic databases such as PubMed, Cochrane Library, Science Direct, AYUSH Research portal, DHARA (Digital Helpline for Ayurveda Research Abstracts), Ayurveda Research Database (ARD), and Shodhganga: a reservoir for Indian theses; will be searched. Hand searching of selected Ayurveda journals will be also undertaken to complement the electronic search. Further, the bibliographic references of the included studies will also be reviewed to identify other relevant studies. The searches will be re-run shortly before the final analysis, and additional papers if found any will be retrieved for inclusion.
Search strategy
A systematic and comprehensive search will be conducted for several databases. The search strategy will comprise of combining MeSH (Medical Subject headings) terms, and using Boolean operators ‘AND’ and ‘OR’. The key search terms will be related to “Diabetes Mellitus” and “Ayurveda”. The search term for each database will be adapted for use with database-specific filters.
The following search algorithm will be adopted(“diabetes mellitus”[MeSH Major Topic] OR insulin dependent diabetes mellitus[Abstract]) OR NIDDM[Abstract]) OR IDDM[Abstract]) OR type 1 diabetes[Abstract]) OR type 2 diabetes[Abstract]) OR madhumeh[Abstract]) AND (ayurveda treatment[Abstract] OR (ayurved[All Fields] AND (“medicine”[MeSH Terms] OR “medicine”[All Fields]))) OR alternative medicine[Abstract]) OR herbal medicine[Abstract]) OR polyherbal medicine[Abstract]) OR herbomineral[Abstract]) OR metallic[All Fields]) OR mercurial[All Fields]) OR Rasaushadhi[All Fields]) as title/abstract/keyword.
Study records
Data collection and management
A pre-designed data extraction form will be used to extract data from the included studies for quality assessment and data analysis. Extraction form will include details like name of author with a year of publication, study setting, study population, participant demographics, study methodology, details of intervention/comparator, outcome measures, result of the study, etc. in accordance with the standard prescribed in PRISMA guideline. Two review authors (SK and BM) will extract data independently, and any discrepancy identified will be discussed and resolved in consultation with third reviewer (PD) wherever necessary. If data reported is insufficient or needs clarity, contact will be made with the corresponding author of the study to seek for more additional information or clarification. The data retrieved through the searches will be stored on a secure computer with a password protected files and an external data storage device in duplicate, with restricted access to the reviewer team only
Selection process
Three of the review authors (SK, KK, and BM) will independently assess the titles and/or abstracts of the studies retrieved using the search strategy. After the exclusion of duplicates from eligible articles, full-text articles will be reviewed completely to determine the inclusion and exclusion criteria as outlined. Any disagreement, if arises will be resolved through discussion with a fourth reviewer (PD). An attempt will also be made to retrieve additional information if found missing or unclear from authors via email or telephone. The studies excluded will be documented with reasons. The details of the study selection process will be shown as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart.
Assessment of risk of bias in the included studies
Two of the review authors (SK and BM) will independently assess the risk of the bias in included studies. RCTs will be assessed by using the Cochrane Risk of Bias tool – 2 which are classified as some concern, low or high risk of bias by evaluating domains like randomization process, deviation from the intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. The findings in risk of bias will be summarized as ‘risk of bias summary’ and ‘risk of bias graph’. An attempt will also be made to assess the risk of bias in non-randomized studies by using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. We will resolve disagreements through discussions, with the involvement of a third reviewer (PD), if required.
Data analysis
Descriptive analysis
A narrative review of findings from the included studies will be presented in the final review structured around the population characteristics, type of Ayurvedic intervention used, outcome measures, and its overall effect at the end of treatment. For continuous data, mean change from baseline for each group with corresponding standard deviations (SDs) at 95% confidence interval (CI), and for dichotomous data, the risk ratio (RR) with 95% CI will be recorded. We will use Review Manager Software (RevMan V.5.3) to calculate treatment effect as Mean difference (MD) with a 95% CI, or standardized mean difference (SMD) with a 95% CI in case of outcomes with different scales.
Statistical analysis
The study aims to find the overall evidence of efficacy and safety of Ayurveda interventions in DM. Given the complexity of Ayurvedic interventions preferred in the management of DM, we anticipate that there will be little scope for performing meta-analyses. However, if there are enough publications studying the same Ayurveda interventions with placebo / or sham treatment/ or standard carethe meta-analysis will be undertaken.
We will use I2 statistics to calculate statistical heterogeneity, and a value greater than 75% will be considered significant. An attempt would be made to determine the potential reasons for it by examining individual study and subgroup characteristics. The overall treatment effect will be calculated by using a random effect model in case of moderate to severe heterogeneity, otherwise, a fixed-effect model will be used. We will generate a Forest plot for a graphical display of results from individual studies and estimates of the overall treatment effect. In addition, publication bias will be assessed by using a Funnel plot, if sufficient studies are available.
Meta-analysis
Meta analysis will be performed if a significant number of studies can be retrieved. To avoid bias in meta analysis, efforts will be made to avoid bias by including relevant research based on inclusive criteria, using adequate statistical methodology, and interpreting results based on the context and available evidence during the search for studies, selection of the identified studies for meta-analysis, and extraction of data from the selected studies.
| Discussion | | |
The proposed systematic review will gather evidence for the efficacy and safety of Ayurvedic intervention in DM, and may help to generate a database for subsequent studies. It may serve as a guiding tool for reproducing the same results in a transparent manner for the systematic review. This systematic review may also provide a bird eye view on the pros and cons of the adopted study methodologies/design and outcome parameters. The analysis may provide initiatives for necessary care in effective planning and execution of future clinical trials to generate high-level evidence. The results of a systematic review published in a peer-reviewed journal will be communicated electronically and in print to reach clinicians and the general public to give knowledge and guidance to policymakers.
| Conclusions | | |
The findings of this systematic review will assist in establishing effectiveness and safety of Ayurveda measures and interventions in treatment of DM. It may also provide scope for future research in order to generate quality evidences pertaining to management of DM through Ayurvedic interventions.
Study registration
The International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020159659).
Acknowledgement
The authors would like to thank Dr. Manohar S Gundeti, Research Officer (Ay.), and Dr. Kuldeep Choudhary, Research officer (Ay.) from Central Ayurveda Research Institute, Mumbai, for their important contributions during the manuscript’s finalization.
Financial support and sponsorship
Central Council for Research in Ayurvedic Sciences [CCRAS], Ministry of Ayush.
Conflicts of interest
There is no conflict of interest.
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