Effect of Therapeutic Sneha on Lipid Profile—A Systematic Review Protocol

Abstract

Background:

Snehapana (internal oleation/therapeutic intake of medicated unctuous substance) constitutes a unique treatment entity in the Ayurveda medical system. It comprises intake of any form of Sneha (lipid medium/fat) orally. Still, there are prevailing concerns about whether administration of escalating doses of medicated lipids leads to dyslipidemia and whether dyslipidemic patients can safely undergo Snehapana. Hence, the present systematic review is planned to systematically evaluate the available evidence on the therapeutic efficacy and safety of Snehapana on lipid profile. The objective of the study is to conduct a systematic review and meta-analysis of published clinical data and grey literature in view of evaluating the effect of medicated Snehapana on lipid profile by keeping the non-medicated Snehapana group as a comparator in the participants undergoing Snehapana.

Methods:

Randomized controlled trials (RCT), quasi-randomized controlled trials, controlled clinical trial (CCT), comparative clinical trial, and multi-arm clinical trials will be included in the study. The study participants include those who have undergone medicated Snehapana in any module. Data from the electronic databases such as PubMed, Cochrane CENTRAL, AYUSH Research Portal, DHARA, Shodhganga, Ayurvedic Research Database, Institute for Teaching and Research in Ayurveda, Gujarat Ayurveda University, Jamnagar, and other relevant journals will be searched. Two investigators will independently screen all the potentially eligible articles identified by a primary comprehensive search. Data from the selected studies will be extracted separately by two review authors for data analysis. The risk of bias will be evaluated using appropriate available tools. Meta-analysis will be done if studies are found eligible. If a sufficient number of studies are not available and if heterogeneity is detected, systematic qualitative synthesis shall include case series, case reports, and single-case study designs.

Discussion:

The proposed review is focused on addressing the concerns related to the effect of snehapana on lipid status. In addition, the study shall identify the future areas of research related to the safety of Snehapana, considering the lacunas of the existing literature. The study is prospectively registered with PROSPERO with registration number CRD42022376754.

Background

Snehapana (internal oleation/therapetic intake of medicated unctuous substance) constitutes a unique treatment entity as far as the Ayurveda medical system is concerned. It comprises intake of any form of sneha (lipid medium/fat) orally with two objectives. Either to lubricate or liquefy the cellular wastes for facilitating purification at the cellular level or to subside certain pathologies by making use of the lipid medium at its site itself. In order to achieve or accomplish these two objectives, sneha has to be administered in two controlled manners following peculiar dosage patterns. ¹ The first methodology of making the administered sneha capable of liquefying the cellular wastes constitutes sodhananga snehapana (administration of lipids aiming at body purification) ² and the second methodology of using the sneha to subside diseases constitute samana snehapana (administration of lipids aiming at subsidence of diseases). ³ The first methodology of administration of sneha for liquefying the cellular waste is done prior to Panchakarmas (fivefold bio-purification therapy) especially before vamana therapy (controlled emesis procedure) and virechana therapy (controlled purgation procedure). The second methodology is usually practiced either without purification or after purification, fully aiming at subsidence of pathology alone. There are also many other modules like avapeedaka snehapana, outtarabhaktika snehapana, etc., but the lipid metabolic pathway followed by the sneha will come under either the sodhana or samana modules.

The main lacuna in the area lies in the fact that there is a dilemma regarding whether administration of lipid in escalating high doses in a short period of time of 7 days, as in sodhananga snehapana, causes serious changes in lipid profile. Whether chathur sneha kalpana (taila, ghrtha, vasa, and majja) can be safely administered in high doses in a short period of time without an adverse rise in blood lipid parameters. Whether it is safe to use all formulations of ghee/taila available in the market in escalating high doses in a short period of 7 days. The same concerns arise with respect to samana snehapana also, that is, intake of sneha in small doses for a short period of time. There is also serious concern regarding whether patients with dyslipidemia can safely undergo snehapana, and if yes, which snehapana package. The present systematic review is planned to scientifically address the abovementioned concerns by using robust research methodology techniques.

Objectives

A systematic review of published clinical data and grey literature in view of the evaluation of the effect of medicated snehapana on lipid profile by keeping the non-medicated snehapana group as a comparator in the participants undergone snehapana is the primary objective of the present review. Meta-analysis of published clinical data and grey literature in view of evaluation of the effect of medicated versus nonmedicated snehapana on lipid profile in the participants who undergone snehapana is the secondary objective.

Methods

The study type is systematic review and meta-analysis. The aim of the study is evidence generation of the effect of Snehapana on lipid profile parameters.

Eligibility criteria

Randomized controlled trials (RCT, quasi-randomized controlled trials (Q-RCT), controlled clinical trial (CCT), comparative clinical trial, and multi-arm clinical trials shall be included. Single-arm pre-post studies, case reports, and case series are included when a sufficient number of studies are not obtained. Published data available in search engines like PubMed, Cochraine database, DHARA, Ayush Research Portal, Shodhganga, and grey literature available at Ayurveda colleges and National Institutes at the pan-India level shall be selected.

Data items

Participants

The study participants (diseased or healthy individuals) include those who have undergone medicated snehapana in any module irrespective of sex, age, etc., suffering from any ailments in which snehapana is practiced and sodhana/rithu sodhana (seasonal purification) in swastha (healthy volunteers). Dyslipidemic patients who are on dyslipidemic medications will be excluded.

Interventions

Sodhana sneha pana, samana sneha pana, avapeeda sneha pana, outtara bhaktika sneha pana, and sadya sneha pana will be taken as interventions for the present systematic review.

Comparators/Control

The participants who have undergone snehapana with non-medicated ghee, taila (oil), vasa (animal fat), and majja (bone marrow) in any mode will be taken as control.

Outcomes

Primary outcome

The effect of medicated/non-medicated snehapana on lipid profile is kept as the primary outcome. Administration time varies from 3 days to 60 days for different modules of snehapana will be included for review.

Secondary outcomes

Serious adverse events related to snehapana, change in lipid profile w.s.r. to different modes of snehapana, change in lipid profile w.s.r. to different co-morbidities, change in lipid profile w.s.r. to different sneha formulations used are taken as secondary outcome. During the study period or up to 2 months (60 days) after the completion of the study, it is kept as a timing and effect measures.

Study design

All RCT, Q-RCT, CCT, comparative clinical trial, and multi-arm clinical trials conducted sneha pana in which the effect on lipid profile will be assessed. The published studies and preprints available in the public domain will be electronically searched. A manual search for grey literature at Ayurveda colleges and the National Institute at pan-India level will also be performed.

Timings: From inception till June 2023.

Information sources

The following information sources will be searched:

1. 1.

Databases: AYUSH Research Portal, PubMed, Cochrane Central Register of Controlled Trials, DHARA, IndMED, Shodhganga, and Google Scholar databases, snowbowling strategy to get maximum published data. Study authors will be contacted if any information is required regarding the study. The search will be subsequently updated to include the most up-to-date data in the publication.

2.

A manual search for grey literature at Ayurveda colleges and the National Institute in pan-India level through hand search in department libraries and contacting universities for thesis works will be done.

Selection process

Two authors (PP and DN) will independently screen all the results. If any disagreement evolves between these two authors, it will be tried to resolve by a discussion with the third author (A.K.R.). If ambiguity still exists, the full article will be acquired for further analysis. Once the full article is obtained, two authors (P.P. and D.N.) will decide whether the study met the review criteria.

Data collection process

A pre-designed format to extract data from the included studies will be made for further data analysis. The following study items will be extracted: authorship, publication-related information, methodology, participants, interventions, comparators, and outcomes. If any lack of clarity arises, the investigators of eligible trials will be contacted through email to seek clarity of desired information.

Data synthesis

Continuous data will be summarized by arithmetic means and standard deviations and will be combined using weighted mean differences in 95% confidence intervals. For dichotomous data, odds ratio will be used. Risk of bias assessment will be performed using the revised tool to assess the risk of bias in randomized trials (RoB 2). The data will be quantitatively synthesized (meta-analysis) using Review Manager 5.4. If heterogeneity is detected and meta-analysis cannot be performed, systematic qualitative synthesis will be done. Heterogeneity among trials will be assessed by applying the chi-square test and using the I² statistic. A random-effects model will be used. ⁴

Risk of bias in individual studies

The quality of methodology adopted by RCTs will be assessed by using the revised tool to assess the risk of bias in randomized trials (RoB2), which is available online. Five domains viz., randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results, will be assessed with the help of predefined algorithms. ⁵ The results will be represented in a traffic light plot and a weighted summary plot. Risk of bias of QRCT will be performed by ROBINS-1 tool. ⁶ If meta-analysis can’t be performed, case series, case reports, and single case study designs shall be included in the study. In that situation, a risk of bias assessment for case series and case studies will be performed by using the JBI critical appraisal tool ⁷ for analysis of the methodological quality of case reports and case series studies. In studies having single-case designs, the single-case design risk of bias tool developed by Brian Reichow et al. ⁸ shall be adopted.

Discussion

The proposed review is focused to address the concerns related to the effect of Snehapana on lipid status. In addition, this study shall identify the future areas of research related to the safety of Snehapana, considering the lacunas of the existing literature. According to pilot search, the effect of Snehapana on lipid profile varies as per the mode of procedure employed, that is, sodhana or samana.

Analysis of subgroups/subsets

If significant heterogeneity exists, subgroup analysis will be performed to explore the possible causes. Pre-planned categories for subgroup analyses:

Patient demographics (e.g., participant types, age, co-morbidities)

Study characteristics (e.g., study design, sample size, duration of follow-up, study quality, etc.)

Different sneha formulations used

Meta-bias

Publication bias and selective reporting of outcomes within the included studies will also be assessed.

Confidence in cumulative evidence

The Grading of Recommendations Assessment, Development, and Evaluation framework will be used to evaluate the strength of the cumulative evidence. The assessment will include all the studies included in the review.