analysis and synthesis in literature review

Literature Syntheis 101

How To Synthesise The Existing Research (With Examples)

By: Derek Jansen (MBA) | Expert Reviewer: Eunice Rautenbach (DTech) | August 2023

One of the most common mistakes that students make when writing a literature review is that they err on the side of describing the existing literature rather than providing a critical synthesis of it. In this post, we’ll unpack what exactly synthesis means and show you how to craft a strong literature synthesis using practical examples.

This post is based on our popular online course, Literature Review Bootcamp . In the course, we walk you through the full process of developing a literature review, step by step. If it’s your first time writing a literature review, you definitely want to use this link to get 50% off the course (limited-time offer).

Overview: Literature Synthesis

• What exactly does “synthesis” mean?
• Aspect 1: Agreement
• Aspect 2: Disagreement
• Aspect 3: Key theories
• Aspect 4: Contexts
• Aspect 5: Methodologies
• Bringing it all together

What does “synthesis” actually mean?

As a starting point, let’s quickly define what exactly we mean when we use the term “synthesis” within the context of a literature review.

Simply put, literature synthesis means going beyond just describing what everyone has said and found. Instead, synthesis is about bringing together all the information from various sources to present a cohesive assessment of the current state of knowledge in relation to your study’s research aims and questions .

Put another way, a good synthesis tells the reader exactly where the current research is “at” in terms of the topic you’re interested in – specifically, what’s known , what’s not , and where there’s a need for more research .

So, how do you go about doing this?

Well, there’s no “one right way” when it comes to literature synthesis, but we’ve found that it’s particularly useful to ask yourself five key questions when you’re working on your literature review. Having done so,  you can then address them more articulately within your actual write up. So, let’s take a look at each of these questions.

1. Points Of Agreement

The first question that you need to ask yourself is: “Overall, what things seem to be agreed upon by the vast majority of the literature?”

For example, if your research aim is to identify which factors contribute toward job satisfaction, you’ll need to identify which factors are broadly agreed upon and “settled” within the literature. Naturally, there may at times be some lone contrarian that has a radical viewpoint , but, provided that the vast majority of researchers are in agreement, you can put these random outliers to the side. That is, of course, unless your research aims to explore a contrarian viewpoint and there’s a clear justification for doing so. 

Identifying what’s broadly agreed upon is an essential starting point for synthesising the literature, because you generally don’t want (or need) to reinvent the wheel or run down a road investigating something that is already well established . So, addressing this question first lays a foundation of “settled” knowledge.

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2. Points Of Disagreement

Related to the previous point, but on the other end of the spectrum, is the equally important question: “Where do the disagreements lie?” .

In other words, which things are not well agreed upon by current researchers? It’s important to clarify here that by disagreement, we don’t mean that researchers are (necessarily) fighting over it – just that there are relatively mixed findings within the empirical research , with no firm consensus amongst researchers.

This is a really important question to address as these “disagreements” will often set the stage for the research gap(s). In other words, they provide clues regarding potential opportunities for further research, which your study can then (hopefully) contribute toward filling. If you’re not familiar with the concept of a research gap, be sure to check out our explainer video covering exactly that .

3. Key Theories

The next question you need to ask yourself is: “Which key theories seem to be coming up repeatedly?” .

Within most research spaces, you’ll find that you keep running into a handful of key theories that are referred to over and over again. Apart from identifying these theories, you’ll also need to think about how they’re connected to each other. Specifically, you need to ask yourself:

• Are they all covering the same ground or do they have different focal points  or underlying assumptions ?
• Do some of them feed into each other and if so, is there an opportunity to integrate them into a more cohesive theory?
• Do some of them pull in different directions ? If so, why might this be?
• Do all of the theories define the key concepts and variables in the same way, or is there some disconnect? If so, what’s the impact of this ?

Simply put, you’ll need to pay careful attention to the key theories in your research area, as they will need to feature within your theoretical framework , which will form a critical component within your final literature review. This will set the foundation for your entire study, so it’s essential that you be critical in this area of your literature synthesis.

If this sounds a bit fluffy, don’t worry. We deep dive into the theoretical framework (as well as the conceptual framework) and look at practical examples in Literature Review Bootcamp . If you’d like to learn more, take advantage of our limited-time offer to get 60% off the standard price.

4. Contexts

The next question that you need to address in your literature synthesis is an important one, and that is: “Which contexts have (and have not) been covered by the existing research?” .

For example, sticking with our earlier hypothetical topic (factors that impact job satisfaction), you may find that most of the research has focused on white-collar , management-level staff within a primarily Western context, but little has been done on blue-collar workers in an Eastern context. Given the significant socio-cultural differences between these two groups, this is an important observation, as it could present a contextual research gap .

In practical terms, this means that you’ll need to carefully assess the context of each piece of literature that you’re engaging with, especially the empirical research (i.e., studies that have collected and analysed real-world data). Ideally, you should keep notes regarding the context of each study in some sort of catalogue or sheet, so that you can easily make sense of this before you start the writing phase. If you’d like, our free literature catalogue worksheet is a great tool for this task.

5. Methodological Approaches

Last but certainly not least, you need to ask yourself the question: “What types of research methodologies have (and haven’t) been used?”

For example, you might find that most studies have approached the topic using qualitative methods such as interviews and thematic analysis. Alternatively, you might find that most studies have used quantitative methods such as online surveys and statistical analysis.

But why does this matter?

Well, it can run in one of two potential directions . If you find that the vast majority of studies use a specific methodological approach, this could provide you with a firm foundation on which to base your own study’s methodology . In other words, you can use the methodologies of similar studies to inform (and justify) your own study’s research design .

On the other hand, you might argue that the lack of diverse methodological approaches presents a research gap , and therefore your study could contribute toward filling that gap by taking a different approach. For example, taking a qualitative approach to a research area that is typically approached quantitatively. Of course, if you’re going to go against the methodological grain, you’ll need to provide a strong justification for why your proposed approach makes sense. Nevertheless, it is something worth at least considering.

Regardless of which route you opt for, you need to pay careful attention to the methodologies used in the relevant studies and provide at least some discussion about this in your write-up. Again, it’s useful to keep track of this on some sort of spreadsheet or catalogue as you digest each article, so consider grabbing a copy of our free literature catalogue if you don’t have anything in place.

Bringing It All Together

Alright, so we’ve looked at five important questions that you need to ask (and answer) to help you develop a strong synthesis within your literature review.  To recap, these are:

• Which things are broadly agreed upon within the current research?
• Which things are the subject of disagreement (or at least, present mixed findings)?
• Which theories seem to be central to your research topic and how do they relate or compare to each other?
• Which contexts have (and haven’t) been covered?
• Which methodological approaches are most common?

Importantly, you’re not just asking yourself these questions for the sake of asking them – they’re not just a reflection exercise. You need to weave your answers to them into your actual literature review when you write it up. How exactly you do this will vary from project to project depending on the structure you opt for, but you’ll still need to address them within your literature review, whichever route you go.

The best approach is to spend some time actually writing out your answers to these questions, as opposed to just thinking about them in your head. Putting your thoughts onto paper really helps you flesh out your thinking . As you do this, don’t just write down the answers – instead, think about what they mean in terms of the research gap you’ll present , as well as the methodological approach you’ll take . Your literature synthesis needs to lay the groundwork for these two things, so it’s essential that you link all of it together in your mind, and of course, on paper.

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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• Write a Literature Review
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Get Organized

• Lit Review Prep Use this template to help you evaluate your sources, create article summaries for an annotated bibliography, and a synthesis matrix for your lit review outline.

Synthesize your Information

Synthesize: combine separate elements to form a whole.

Synthesis Matrix

A synthesis matrix helps you record the main points of each source and document how sources relate to each other.

After summarizing and evaluating your sources, arrange them in a matrix or use a citation manager to help you see how they relate to each other and apply to each of your themes or variables.  

By arranging your sources by theme or variable, you can see how your sources relate to each other, and can start thinking about how you weave them together to create a narrative.

• Step-by-Step Approach
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How to Write a Literature Review

• 6. Synthesize
• Literature Reviews: A Recap
• Reading Journal Articles
• Does it Describe a Literature Review?
• 1. Identify the Question
• 2. Review Discipline Styles
• Searching Article Databases
• Finding Full-Text of an Article
• Citation Chaining
• When to Stop Searching
• 4. Manage Your References
• 5. Critically Analyze and Evaluate

Synthesis Visualization

Synthesis matrix example.

• 7. Write a Literature Review

• Synthesis Worksheet

About Synthesis

Approaches to synthesis.

You can sort the literature in various ways, for example:

How to Begin?

Read your sources carefully and find the main idea(s) of each source

Look for similarities in your sources – which sources are talking about the same main ideas? (for example, sources that discuss the historical background on your topic)

Use the worksheet (above) or synthesis matrix (below) to get organized

This work can be messy. Don't worry if you have to go through a few iterations of the worksheet or matrix as you work on your lit review!

Four Examples of Student Writing

In the four examples below, only ONE shows a good example of synthesis: the fourth column, or  Student D . For a web accessible version, click the link below the image.

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Click on the example to view the pdf.

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Literature Reviews

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• 1. Define your research question
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In the synthesis step of a literature review, researchers analyze and integrate information from selected sources to identify patterns and themes. This involves critically evaluating findings, recognizing commonalities, and constructing a cohesive narrative that contributes to the understanding of the research topic.

Here are some examples of how to approach synthesizing the literature:

💡 By themes or concepts

🕘 Historically or chronologically

📊 By methodology

These organizational approaches can also be used when writing your review. It can be beneficial to begin organizing your references by these approaches in your citation manager by using folders, groups, or collections.

Create a synthesis matrix

A synthesis matrix allows you to visually organize your literature.

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Writing a Literature Review

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

Literature Review Basics

• What is a Literature Review?
• Synthesizing Research
• Using Research & Synthesis Tables
• Additional Resources

Synthesis: What is it?

First, let's be perfectly clear about what synthesizing your research isn't :

• - It isn't  just summarizing the material you read
• - It isn't  generating a collection of annotations or comments (like an annotated bibliography)
• - It isn't  compiling a report on every single thing ever written in relation to your topic

When you  synthesize  your research, your job is to help your reader understand the current state of the conversation on your topic, relative to your research question.  That may include doing the following:

• - Selecting and using representative work on the topic
• - Identifying and discussing trends in published data or results
• - Identifying and explaining the impact of common features (study populations, interventions, etc.) that appear frequently in the literature
• - Explaining controversies, disputes, or central issues in the literature that are relevant to your research question
• - Identifying gaps in the literature, where more research is needed
• - Establishing the discussion to which your own research contributes and demonstrating the value of your contribution

Essentially, you're telling your reader where they are (and where you are) in the scholarly conversation about your project.

Synthesis: How do I do it?

Synthesis, step by step.

This is what you need to do  before  you write your review.

• Identify and clearly describe your research question (you may find the Formulating PICOT Questions table at  the Additional Resources tab helpful).
• Collect sources relevant to your research question.
• Organize and describe the sources you've found -- your job is to identify what  types  of sources you've collected (reviews, clinical trials, etc.), identify their  purpose  (what are they measuring, testing, or trying to discover?), determine the  level of evidence  they represent (see the Levels of Evidence table at the Additional Resources tab ), and briefly explain their  major findings . Use a Research Table to document this step.
• Study the information you've put in your Research Table and examine your collected sources, looking for  similarities  and  differences . Pay particular attention to  populations ,   methods  (especially relative to levels of evidence), and  findings .
• Analyze what you learn in (4) using a tool like a Synthesis Table. Your goal is to identify relevant themes, trends, gaps, and issues in the research.  Your literature review will collect the results of this analysis and explain them in relation to your research question.

Analysis tips

• - Sometimes, what you  don't  find in the literature is as important as what you do find -- look for questions that the existing research hasn't answered yet.
• - If any of the sources you've collected refer to or respond to each other, keep an eye on how they're related -- it may provide a clue as to whether or not study results have been successfully replicated.
• - Sorting your collected sources by level of evidence can provide valuable insight into how a particular topic has been covered, and it may help you to identify gaps worth addressing in your own work.
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Library Guides

Literature reviews: synthesis.

• Criticality

Synthesise Information

So, how can you create paragraphs within your literature review that demonstrates your knowledge of the scholarship that has been done in your field of study?  

You will need to present a synthesis of the texts you read.  

Doug Specht, Senior Lecturer at the Westminster School of Media and Communication, explains synthesis for us in the following video:  

Synthesising Texts  

What is synthesis? 

Synthesis is an important element of academic writing, demonstrating comprehension, analysis, evaluation and original creation.  

With synthesis you extract content from different sources to create an original text. While paraphrase and summary maintain the structure of the given source(s), with synthesis you create a new structure.  

The sources will provide different perspectives and evidence on a topic. They will be put together when agreeing, contrasted when disagreeing. The sources must be referenced.  

Perfect your synthesis by showing the flow of your reasoning, expressing critical evaluation of the sources and drawing conclusions.  

When you synthesise think of "using strategic thinking to resolve a problem requiring the integration of diverse pieces of information around a structuring theme" (Mateos and Sole 2009, p448). 

Synthesis is a complex activity, which requires a high degree of comprehension and active engagement with the subject. As you progress in higher education, so increase the expectations on your abilities to synthesise. 

How to synthesise in a literature review: 

Identify themes/issues you'd like to discuss in the literature review. Think of an outline.  

Read the literature and identify these themes/issues.  

Critically analyse the texts asking: how does the text I'm reading relate to the other texts I've read on the same topic? Is it in agreement? Does it differ in its perspective? Is it stronger or weaker? How does it differ (could be scope, methods, year of publication etc.). Draw your conclusions on the state of the literature on the topic.  

Start writing your literature review, structuring it according to the outline you planned.  

Put together sources stating the same point; contrast sources presenting counter-arguments or different points.  

Present your critical analysis.  

Always provide the references. 

The best synthesis requires a "recursive process" whereby you read the source texts, identify relevant parts, take notes, produce drafts, re-read the source texts, revise your text, re-write... (Mateos and Sole, 2009). 

What is good synthesis?  

The quality of your synthesis can be assessed considering the following (Mateos and Sole, 2009, p439):  

Integration and connection of the information from the source texts around a structuring theme. 

Selection of ideas necessary for producing the synthesis. 

Appropriateness of the interpretation.  

Elaboration of the content.  

Example of Synthesis

Original texts (fictitious): 

Synthesis: 

Animal experimentation is a subject of heated debate. Some argue that painful experiments should be banned. Indeed it has been demonstrated that such experiments make animals suffer physically and psychologically (Chowdhury 2012; Panatta and Hudson 2016). On the other hand, it has been argued that animal experimentation can save human lives and reduce harm on humans (Smith 2008). This argument is only valid for toxicological testing, not for tests that, for example, merely improve the efficacy of a cosmetic (Turner 2015). It can be suggested that animal experimentation should be regulated to only allow toxicological risk assessment, and the suffering to the animals should be minimised.   

Bibliography

Mateos, M. and Sole, I. (2009). Synthesising Information from various texts: A Study of Procedures and Products at Different Educational Levels. European Journal of Psychology of Education,  24 (4), 435-451. Available from https://doi.org/10.1007/BF03178760 [Accessed 29 June 2021].

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Literature Review How To

• Things To Consider
• Synthesizing Sources
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What is Synthesis

What is Synthesis? Synthesis writing is a form of analysis related to comparison and contrast, classification and division. On a basic level, synthesis requires the writer to pull together two or more summaries, looking for themes in each text. In synthesis, you search for the links between various materials in order to make your point. Most advanced academic writing, including literature reviews, relies heavily on synthesis. (Temple University Writing Center)  

How To Synthesize Sources in a Literature Review

Literature reviews synthesize large amounts of information and present it in a coherent, organized fashion. In a literature review you will be combining material from several texts to create a new text – your literature review.

You will use common points among the sources you have gathered to help you synthesize the material. This will help ensure that your literature review is organized by subtopic, not by source. This means various authors' names can appear and reappear throughout the literature review, and each paragraph will mention several different authors. 

When you shift from writing summaries of the content of a source to synthesizing content from sources, there is a number things you must keep in mind: 

• Look for specific connections and or links between your sources and how those relate to your thesis or question.
• When writing and organizing your literature review be aware that your readers need to understand how and why the information from the different sources overlap.
• Organize your literature review by the themes you find within your sources or themes you have identified. 
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What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis

Kara schick-makaroff.

1 Faculty of Nursing, University of Alberta, Edmonton, AB, Canada

Marjorie MacDonald

2 School of Nursing, University of Victoria, Victoria, BC, Canada

Marilyn Plummer

3 College of Nursing, Camosun College, Victoria, BC, Canada

Judy Burgess

4 Student Services, University Health Services, Victoria, BC, Canada

Wendy Neander

Associated data, additional file 1.

When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings.

We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained.

We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach.

Conclusions

The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.

1. Introduction

Since the turn of the century, public health emergencies have been identified worldwide, particularly related to infectious diseases. For example, the Severe Acute Respiratory Syndrome (SARS) epidemic in Canada in 2002-2003, the recent Ebola epidemic in Africa, and the ongoing HIV/AIDs pandemic are global health concerns. There have also been dramatic increases in the prevalence of chronic diseases around the world [1] – [3] . These epidemiological challenges have raised concerns about the ability of health systems worldwide to address these crises. As a result, public health systems reform has been initiated in a number of countries. In Canada, as in other countries, the role of evidence to support public health reform and improve population health has been given high priority. Yet, there continues to be a significant gap between the production of evidence through research and its application in practice [4] – [5] . One strategy to address this gap has been the development of new research synthesis methodologies to deal with the time-sensitive and wide ranging evidence needs of policy makers and practitioners in all areas of health care, including public health.

As doctoral nursing students facing a review of the literature for our dissertations, and as a faculty member teaching a research methods course, we encountered several ways of conducting a research synthesis but found no comprehensive resources that discussed, compared, and contrasted various synthesis methodologies on their purposes, processes, strengths and limitations. To complicate matters, writers use terms interchangeably or use different terms to mean the same thing, and the literature is often contradictory about various approaches. Some texts [6] , [7] – [9] did provide a preliminary understanding about how research synthesis had been taken up in nursing, but these did not meet our requirements. Thus, in this article we address the need for a comprehensive overview of research synthesis methodologies to guide public health, health care, and social science researchers and practitioners.

Research synthesis is relatively new in public health but has a long history in other fields dating back to the late 1800s. Research synthesis, a research process in its own right [10] , has become more prominent in the wake of the evidence-based movement of the 1990s. Research syntheses have found their advocates and detractors in all disciplines, with challenges to the processes of systematic review and meta-analysis, in particular, being raised by critics of evidence-based healthcare [11] – [13] .

Our purpose was to conduct an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis [14] – [15] . We synthesize and critique the main approaches to research synthesis that are relevant for public health, health care, and social scientists. Research synthesis is the overarching term we use to describe approaches to combining, aggregating, integrating, and synthesizing primary research findings. Each synthesis methodology draws on different types of findings depending on the purpose and product of the chosen synthesis (see Additional File 1 ).

3. Method of Review

Based on our current knowledge of the literature, we identified these approaches to include in our review: systematic review, meta-analysis, qualitative meta-synthesis, meta-narrative synthesis, scoping review, rapid review, realist synthesis, concept analysis, literature review, and integrative review. Our first step was to divide the synthesis types among the research team. Each member did a preliminary search to identify key texts. The team then met to develop search terms and a framework to guide the review.

Over the period of 2008 to 2012 we extensively searched the literature, updating our search at several time points, not restricting our search by date. The dates of texts reviewed range from 1967 to 2015. We used the terms above combined with the term “method* (e.g., “realist synthesis” and “method*) in the database Health Source: Academic Edition (includes Medline and CINAHL). This search yielded very few texts on some methodologies and many on others. We realized that many documents on research synthesis had not been picked up in the search. Therefore, we also searched Google Scholar, PubMed, ERIC, and Social Science Index, as well as the websites of key organizations such as the Joanna Briggs Institute, the University of York Centre for Evidence-Based Nursing, and the Cochrane Collaboration database. We hand searched several nursing, social science, public health and health policy journals. Finally, we traced relevant documents from the references in obtained texts.

We included works that met the following inclusion criteria: (1) published in English; (2) discussed the history of research synthesis; (3) explicitly described the approach and specific methods; or (4) identified issues, challenges, strengths and limitations of the particular methodology. We excluded research reports that resulted from the use of particular synthesis methodologies unless they also included criteria 2, 3, or 4 above.

Based on our search, we identified additional types of research synthesis (e.g., meta-interpretation, best evidence synthesis, critical interpretive synthesis, meta-summary, grounded formal theory). Still, we missed some important developments in meta-analysis, for example, identified by the journal's reviewers that have now been discussed briefly in the paper. The final set of 197 texts included in our review comprised theoretical, empirical, and conceptual papers, books, editorials and commentaries, and policy documents.

In our preliminary review of key texts, the team inductively developed a framework of the important elements of each method for comparison. In the next phase, each text was read carefully, and data for these elements were extracted into a table for comparison on the points of: key characteristics, purpose, methods, and product; see Additional File 1 ). Once the data were grouped and extracted, we synthesized across categories based on the following additional points of comparison: complexity of the process, degree of systematization, consideration of context, underlying assumptions, unit of analysis, and when to use each approach. In our results, we discuss our comparison of the various synthesis approaches on the elements above. Drawing only on documents for the review, ethics approval was not required.

We identified four broad categories of research synthesis methodology: Conventional, quantitative, qualitative, and emerging syntheses. From our dataset of 197 texts, we had 14 texts on conventional synthesis, 64 on quantitative synthesis, 78 on qualitative synthesis, and 41 on emerging syntheses. Table 1 provides an overview of the four types of research synthesis, definitions, types of data used, products, and examples of the methodology.

Although we group these types of synthesis into four broad categories on the basis of similarities, each type within a category has unique characteristics, which may differ from the overall group similarities. Each could be explored in greater depth to tease out their unique characteristics, but detailed comparison is beyond the scope of this article.

Additional File 1 presents one or more selected types of synthesis that represent the broad category but is not an exhaustive presentation of all types within each category. It provides more depth for specific examples from each category of synthesis on the characteristics, purpose, methods, and products than is found in Table 1 .

4.1. Key Characteristics

4.1.1. what is it.

Here we draw on two types of categorization. First, we utilize Dixon Woods et al.'s [49] classification of research syntheses as being either integrative or interpretive . (Please note that integrative syntheses are not the same as an integrative review as defined in Additional File 1 .) Second, we use Popay's [80] enhancement and epistemological models .

The defining characteristics of integrative syntheses are that they involve summarizing the data achieved by pooling data [49] . Integrative syntheses include systematic reviews, meta-analyses, as well as scoping and rapid reviews because each of these focus on summarizing data. They also define concepts from the outset (although this may not always be true in scoping or rapid reviews) and deal with a well-specified phenomenon of interest.

Interpretive syntheses are primarily concerned with the development of concepts and theories that integrate concepts [49] . The analysis in interpretive synthesis is conceptual both in process and outcome, and “the product is not aggregations of data, but theory” [49] , [p.12]. Interpretive syntheses involve induction and interpretation, and are primarily conceptual in process and outcome. Examples include integrative reviews, some systematic reviews, all of the qualitative syntheses, meta-narrative, realist and critical interpretive syntheses. Of note, both quantitative and qualitative studies can be either integrative or interpretive

The second categorization, enhancement versus epistemological , applies to those approaches that use multiple data types and sources [80] . Popay's [80] classification reflects the ways that qualitative data are valued in relation to quantitative data.

In the enhancement model , qualitative data adds something to quantitative analysis. The enhancement model is reflected in systematic reviews and meta-analyses that use some qualitative data to enhance interpretation and explanation. It may also be reflected in some rapid reviews that draw on quantitative data but use some qualitative data.

The epistemological model assumes that quantitative and qualitative data are equal and each has something unique to contribute. All of the other review approaches, except pure quantitative or qualitative syntheses, reflect the epistemological model because they value all data types equally but see them as contributing different understandings.

4.1.2. Data type

By and large, the quantitative approaches (quantitative systematic review and meta-analysis) have typically used purely quantitative data (i.e., expressed in numeric form). More recently, both Cochrane [81] and Campbell [82] collaborations are grappling with the need to, and the process of, integrating qualitative research into a systematic review. The qualitative approaches use qualitative data (i.e., expressed in words). All of the emerging synthesis types, as well as the conventional integrative review, incorporate qualitative and quantitative study designs and data.

4.1.3. Research question

Four types of research questions direct inquiry across the different types of syntheses. The first is a well-developed research question that gives direction to the synthesis (e.g., meta-analysis, systematic review, meta-study, concept analysis, rapid review, realist synthesis). The second begins as a broad general question that evolves and becomes more refined over the course of the synthesis (e.g., meta-ethnography, scoping review, meta-narrative, critical interpretive synthesis). In the third type, the synthesis begins with a phenomenon of interest and the question emerges in the analytic process (e.g., grounded formal theory). Lastly, there is no clear question, but rather a general review purpose (e.g., integrative review). Thus, the requirement for a well-defined question cuts across at least three of the synthesis types (e.g., quantitative, qualitative, and emerging).

4.1.4. Quality appraisal

This is a contested issue within and between the four synthesis categories. There are strong proponents of quality appraisal in the quantitative traditions of systematic review and meta-analysis based on the need for strong studies that will not jeopardize validity of the overall findings. Nonetheless, there is no consensus on pre-defined criteria; many scales exist that vary dramatically in composition. This has methodological implications for the credibility of findings [83] .

Specific methodologies from the conventional, qualitative, and emerging categories support quality appraisal but do so with caveats. In conventional integrative reviews appraisal is recommended, but depends on the sampling frame used in the study [18] . In meta-study, appraisal criteria are explicit but quality criteria are used in different ways depending on the specific requirements of the inquiry [54] . Among the emerging syntheses, meta-narrative review developers support appraisal of a study based on criteria from the research tradition of the primary study [67] , [84] – [85] . Realist synthesis similarly supports the use of high quality evidence, but appraisal checklists are viewed with scepticism and evidence is judged based on relevance to the research question and whether a credible inference may be drawn [69] . Like realist, critical interpretive syntheses do not judge quality using standardized appraisal instruments. They will exclude fatally flawed studies, but there is no consensus on what ‘fatally flawed’ means [49] , [71] . Appraisal is based on relevance to the inquiry, not rigor of the study.

There is no agreement on quality appraisal among qualitative meta-ethnographers with some supporting and others refuting the need for appraisal. [60] , [62] . Opponents of quality appraisal are found among authors of qualitative (grounded formal theory and concept analysis) and emerging syntheses (scoping and rapid reviews) because quality is not deemed relevant to the intention of the synthesis; the studies being reviewed are not effectiveness studies where quality is extremely important. These qualitative synthesis are often reviews of theoretical developments where the concept itself is what is important, or reviews that provide quotations from the raw data so readers can make their own judgements about the relevance and utility of the data. For example, in formal grounded theory, the purpose of theory generation and authenticity of data used to generate the theory is not as important as the conceptual category. Inaccuracies may be corrected in other ways, such as using the constant comparative method, which facilitates development of theoretical concepts that are repeatedly found in the data [86] – [87] . For pragmatic reasons, evidence is not assessed in rapid and scoping reviews, in part to produce a timely product. The issue of quality appraisal is unresolved across the terrain of research synthesis and we consider this further in our discussion.

4.2. Purpose

All research syntheses share a common purpose -- to summarize, synthesize, or integrate research findings from diverse studies. This helps readers stay abreast of the burgeoning literature in a field. Our discussion here is at the level of the four categories of synthesis. Beginning with conventional literature syntheses, the overall purpose is to attend to mature topics for the purpose of re-conceptualization or to new topics requiring preliminary conceptualization [14] . Such syntheses may be helpful to consider contradictory evidence, map shifting trends in the study of a phenomenon, and describe the emergence of research in diverse fields [14] . The purpose here is to set the stage for a study by identifying what has been done, gaps in the literature, important research questions, or to develop a conceptual framework to guide data collection and analysis.

The purpose of quantitative systematic reviews is to combine, aggregate, or integrate empirical research to be able to generalize from a group of studies and determine the limits of generalization [27] . The focus of quantitative systematic reviews has been primarily on aggregating the results of studies evaluating the effectiveness of interventions using experimental, quasi-experimental, and more recently, observational designs. Systematic reviews can be done with or without quantitative meta-analysis but a meta-analysis always takes place within the context of a systematic review. Researchers must consider the review's purpose and the nature of their data in undertaking a quantitative synthesis; this will assist in determining the approach.

The purpose of qualitative syntheses is broadly to synthesize complex health experiences, practices, or concepts arising in healthcare environments. There may be various purposes depending on the qualitative methodology. For example, in hermeneutic studies the aim may be holistic explanation or understanding of a phenomenon [42] , which is deepened by integrating the findings from multiple studies. In grounded formal theory, the aim is to produce a conceptual framework or theory expected to be applicable beyond the original study. Although not able to generalize from qualitative research in the statistical sense [88] , qualitative researchers usually do want to say something about the applicability of their synthesis to other settings or phenomena. This notion of ‘theoretical generalization’ has been referred to as ‘transferability’ [89] – [90] and is an important criterion of rigour in qualitative research. It applies equally to the products of a qualitative synthesis in which the synthesis of multiple studies on the same phenomenon strengthens the ability to draw transferable conclusions.

The overarching purpose of emerging syntheses is challenging the more traditional types of syntheses, in part by using data from both quantitative and qualitative studies with diverse designs for analysis. Beyond this, however, each emerging synthesis methodology has a unique purpose. In meta-narrative review, the purpose is to identify different research traditions in the area, synthesize a complex and diverse body of research. Critical interpretive synthesis shares this characteristic. Although a distinctive approach, critical interpretive synthesis utilizes a modification of the analytic strategies of meta-ethnography [61] (e.g., reciprocal translational analysis, refutational synthesis, and lines of argument synthesis) but goes beyond the use of these to bring a critical perspective to bear in challenging the normative or epistemological assumptions in the primary literature [72] – [73] . The unique purpose of a realist synthesis is to amalgamate complex empirical evidence and theoretical understandings within a diverse body of literature to uncover the operative mechanisms and contexts that affect the outcomes of social interventions. In a scoping review, the intention is to find key concepts, examine the range of research in an area, and identify gaps in the literature. The purpose of a rapid review is comparable to that of a scoping review, but done quickly to meet the time-sensitive information needs of policy makers.

4.3. Method

4.3.1. degree of systematization.

There are varying degrees of systematization across the categories of research synthesis. The most systematized are quantitative systematic reviews and meta-analyses. There are clear processes in each with judgments to be made at each step, although there are no agreed upon guidelines for this. The process is inherently subjective despite attempts to develop objective and systematic processes [91] – [92] . Mullen and Ramirez [27] suggest that there is often a false sense of rigour implied by the terms ‘systematic review’ and ‘meta-analysis’ because of their clearly defined procedures.

In comparison with some types of qualitative synthesis, concept analysis is quite procedural. Qualitative meta-synthesis also has defined procedures and is systematic, yet perhaps less so than concept analysis. Qualitative meta-synthesis starts in an unsystematic way but becomes more systematic as it unfolds. Procedures and frameworks exist for some of the emerging types of synthesis [e.g., [50] , [63] , [71] , [93] ] but are not linear, have considerable flexibility, and are often messy with emergent processes [85] . Conventional literature reviews tend not to be as systematic as the other three types. In fact, the lack of systematization in conventional literature synthesis was the reason for the development of more systematic quantitative [17] , [20] and qualitative [45] – [46] , [61] approaches. Some authors in the field [18] have clarified processes for integrative reviews making them more systematic and rigorous, but most conventional syntheses remain relatively unsystematic in comparison with other types.

4.3.2. Complexity of the process

Some synthesis processes are considerably more complex than others. Methodologies with clearly defined steps are arguably less complex than the more flexible and emergent ones. We know that any study encounters challenges and it is rare that a pre-determined research protocol can be followed exactly as intended. Not even the rigorous methods associated with Cochrane [81] systematic reviews and meta-analyses are always implemented exactly as intended. Even when dealing with numbers rather than words, interpretation is always part of the process. Our collective experience suggests that new methodologies (e.g., meta-narrative synthesis and realist synthesis) that integrate different data types and methods are more complex than conventional reviews or the rapid and scoping reviews.

4.4. Product

The products of research syntheses usually take three distinct formats (see Table 1 and Additional File 1 for further details). The first representation is in tables, charts, graphical displays, diagrams and maps as seen in integrative, scoping and rapid reviews, meta-analyses, and critical interpretive syntheses. The second type of synthesis product is the use of mathematical scores. Summary statements of effectiveness are mathematically displayed in meta-analyses (as an effect size), systematic reviews, and rapid reviews (statistical significance).

The third synthesis product may be a theory or theoretical framework. A mid-range theory can be produced from formal grounded theory, meta-study, meta-ethnography, and realist synthesis. Theoretical/conceptual frameworks or conceptual maps may be created in meta-narrative and critical interpretive syntheses, and integrative reviews. Concepts for use within theories are produced in concept analysis. While these three product types span the categories of research synthesis, narrative description and summary is used to present the products resulting from all methodologies.

4.5. Consideration of context

There are diverse ways that context is considered in the four broad categories of synthesis. Context may be considered to the extent that it features within primary studies for the purpose of the review. Context may also be understood as an integral aspect of both the phenomenon under study and the synthesis methodology (e.g., realist synthesis). Quantitative systematic reviews and meta-analyses have typically been conducted on studies using experimental and quasi-experimental designs and more recently observational studies, which control for contextual features to allow for understanding of the ‘true’ effect of the intervention [94] .

More recently, systematic reviews have included covariates or mediating variables (i.e., contextual factors) to help explain variability in the results across studies [27] . Context, however, is usually handled in the narrative discussion of findings rather than in the synthesis itself. This lack of attention to context has been one criticism leveled against systematic reviews and meta-analyses, which restrict the types of research designs that are considered [e.g., [95] ].

When conventional literature reviews incorporate studies that deal with context, there is a place for considering contextual influences on the intervention or phenomenon. Reviews of quantitative experimental studies tend to be devoid of contextual considerations since the original studies are similarly devoid, but context might figure prominently in a literature review that incorporates both quantitative and qualitative studies.

Qualitative syntheses have been conducted on the contextual features of a particular phenomenon [33] . Paterson et al. [54] advise researchers to attend to how context may have influenced the findings of particular primary studies. In qualitative analysis, contextual features may form categories by which the data can be compared and contrasted to facilitate interpretation. Because qualitative research is often conducted to understand a phenomenon as a whole, context may be a focus, although this varies with the qualitative methodology. At the same time, the findings in a qualitative synthesis are abstracted from the original reports and taken to a higher level of conceptualization, thus removing them from the original context.

Meta-narrative synthesis [67] , [84] , because it draws on diverse research traditions and methodologies, may incorporate context into the analysis and findings. There is not, however, an explicit step in the process that directs the analyst to consider context. Generally, the research question guiding the synthesis is an important factor in whether context will be a focus.

More recent iterations of concept analysis [47] , [96] – [97] explicitly consider context reflecting the assumption that a concept's meaning is determined by its context. Morse [47] points out, however, that Wilson's [98] approach to concept analysis, and those based on Wilson [e.g., [45] ], identify attributes that are devoid of context, while Rodgers' [96] , [99] evolutionary method considers context (e.g., antecedents, consequences, and relationships to other concepts) in concept development.

Realist synthesis [69] considers context as integral to the study. It draws on a critical realist logic of inquiry grounded in the work of Bhaskar [100] , who argues that empirical co-occurrence of events is insufficient for inferring causation. One must identify generative mechanisms whose properties are causal and, depending on the situation, may nor may not be activated [94] . Context interacts with program/intervention elements and thus cannot be differentiated from the phenomenon [69] . This approach synthesizes evidence on generative mechanisms and analyzes contextual features that activate them; the result feeds back into the context. The focus is on what works, for whom, under what conditions, why and how [68] .

4.6. Underlying Philosophical and Theoretical Assumptions

When we began our review, we ‘assumed’ that the assumptions underlying synthesis methodologies would be a distinguishing characteristic of synthesis types, and that we could compare the various types on their assumptions, explicit or implicit. We found, however, that many authors did not explicate the underlying assumptions of their methodologies, and it was difficult to infer them. Kirkevold [101] has argued that integrative reviews need to be carried out from an explicit philosophical or theoretical perspective. We argue this should be true for all types of synthesis.

Authors of some emerging synthesis approaches have been very explicit about their assumptions and philosophical underpinnings. An implicit assumption of most emerging synthesis methodologies is that quantitative systematic reviews and meta-analyses have limited utility in some fields [e.g., in public health – [13] , [102] ] and for some kinds of review questions like those about feasibility and appropriateness versus effectiveness [103] – [104] . They also assume that ontologically and epistemologically, both kinds of data can be combined. This is a significant debate in the literature because it is about the commensurability of overarching paradigms [105] but this is beyond the scope of this review.

Realist synthesis is philosophically grounded in critical realism or, as noted above, a realist logic of inquiry [93] , [99] , [106] – [107] . Key assumptions regarding the nature of interventions that inform critical realism have been described above in the section on context. See Pawson et al. [106] for more information on critical realism, the philosophical basis of realist synthesis.

Meta-narrative synthesis is explicitly rooted in a constructivist philosophy of science [108] in which knowledge is socially constructed rather than discovered, and what we take to be ‘truth’ is a matter of perspective. Reality has a pluralistic and plastic character, and there is no pre-existing ‘real world’ independent of human construction and language [109] . See Greenhalgh et al. [67] , [85] and Greenhalgh & Wong [97] for more discussion of the constructivist basis of meta-narrative synthesis.

In the case of purely quantitative or qualitative syntheses, it may be an easier matter to uncover unstated assumptions because they are likely to be shared with those of the primary studies in the genre. For example, grounded formal theory shares the philosophical and theoretical underpinnings of grounded theory, rooted in the theoretical perspective of symbolic interactionism [110] – [111] and the philosophy of pragmatism [87] , [112] – [114] .

As with meta-narrative synthesis, meta-study developers identify constructivism as their interpretive philosophical foundation [54] , [88] . Epistemologically, constructivism focuses on how people construct and re-construct knowledge about a specific phenomenon, and has three main assumptions: (1) reality is seen as multiple, at times even incompatible with the phenomenon under consideration; (2) just as primary researchers construct interpretations from participants' data, meta-study researchers also construct understandings about the primary researchers' original findings. Thus, meta-synthesis is a construction of a construction, or a meta-construction; and (3) all constructions are shaped by the historical, social and ideological context in which they originated [54] . The key message here is that reports of any synthesis would benefit from an explicit identification of the underlying philosophical perspectives to facilitate a better understanding of the results, how they were derived, and how they are being interpreted.

4.7. Unit of Analysis

The unit of analysis for each category of review is generally distinct. For the emerging synthesis approaches, the unit of analysis is specific to the intention. In meta-narrative synthesis it is the storyline in diverse research traditions; in rapid review or scoping review, it depends on the focus but could be a concept; and in realist synthesis, it is the theories rather than programs that are the units of analysis. The elements of theory that are important in the analysis are mechanisms of action, the context, and the outcome [107] .

For qualitative synthesis, the units of analysis are generally themes, concepts or theories, although in meta-study, the units of analysis can be research findings (“meta-data-analysis”), research methods (“meta-method”) or philosophical/theoretical perspectives (“meta-theory”) [54] . In quantitative synthesis, the units of analysis range from specific statistics for systematic reviews to effect size of the intervention for meta-analysis. More recently, some systematic reviews focus on theories [115] – [116] , therefore it depends on the research question. Similarly, within conventional literature synthesis the units of analysis also depend on the research purpose, focus and question as well as on the type of research methods incorporated into the review. What is important in all research syntheses, however, is that the unit of analysis needs to be made explicit. Unfortunately, this is not always the case.

4.8. Strengths and Limitations

In this section, we discuss the overarching strengths and limitations of synthesis methodologies as a whole and then highlight strengths and weaknesses across each of our four categories of synthesis.

4.8.1. Strengths of Research Syntheses in General

With the vast proliferation of research reports and the increased ease of retrieval, research synthesis has become more accessible providing a way of looking broadly at the current state of research. The availability of syntheses helps researchers, practitioners, and policy makers keep up with the burgeoning literature in their fields without which evidence-informed policy or practice would be difficult. Syntheses explain variation and difference in the data helping us identify the relevance for our own situations; they identify gaps in the literature leading to new research questions and study designs. They help us to know when to replicate a study and when to avoid excessively duplicating research. Syntheses can inform policy and practice in a way that well-designed single studies cannot; they provide building blocks for theory that helps us to understand and explain our phenomena of interest.

4.8.2. Limitations of Research Syntheses in General

The process of selecting, combining, integrating, and synthesizing across diverse study designs and data types can be complex and potentially rife with bias, even with those methodologies that have clearly defined steps. Just because a rigorous and standardized approach has been used does not mean that implicit judgements will not influence the interpretations and choices made at different stages.

In all types of synthesis, the quantity of data can be considerable, requiring difficult decisions about scope, which may affect relevance. The quantity of available data also has implications for the size of the research team. Few reviews these days can be done independently, in particular because decisions about inclusion and exclusion may require the involvement of more than one person to ensure reliability.

For all types of synthesis, it is likely that in areas with large, amorphous, and diverse bodies of literature, even the most sophisticated search strategies will not turn up all the relevant and important texts. This may be more important in some synthesis methodologies than in others, but the omission of key documents can influence the results of all syntheses. This issue can be addressed, at least in part, by including a library scientist on the research team as required by some funding agencies. Even then, it is possible to miss key texts. In this review, for example, because none of us are trained in or conduct meta-analyses, we were not even aware that we had missed some new developments in this field such as meta-regression [117] – [118] , network meta-analysis [119] – [121] , and the use of individual patient data in meta-analyses [122] – [123] .

One limitation of systematic reviews and meta-analyses is that they rapidly go out of date. We thought this might be true for all types of synthesis, although we wondered if those that produce theory might not be somewhat more enduring. We have not answered this question but it is open for debate. For all types of synthesis, the analytic skills and the time required are considerable so it is clear that training is important before embarking on a review, and some types of review may not be appropriate for students or busy practitioners.

Finally, the quality of reporting in primary studies of all genres is variable so it is sometimes difficult to identify aspects of the study essential for the synthesis, or to determine whether the study meets quality criteria. There may be flaws in the original study, or journal page limitations may necessitate omitting important details. Reporting standards have been developed for some types of reviews (e.g., systematic review, meta-analysis, meta-narrative synthesis, realist synthesis); but there are no agreed upon standards for qualitative reviews. This is an important area for development in advancing the science of research synthesis.

4.8.3. Strengths and Limitations of the Four Synthesis Types

The conventional literature review and now the increasingly common integrative review remain important and accessible approaches for students, practitioners, and experienced researchers who want to summarize literature in an area but do not have the expertise to use one of the more complex methodologies. Carefully executed, such reviews are very useful for synthesizing literature in preparation for research grants and practice projects. They can determine the state of knowledge in an area and identify important gaps in the literature to provide a clear rationale or theoretical framework for a study [14] , [18] . There is a demand, however, for more rigour, with more attention to developing comprehensive search strategies and more systematic approaches to combining, integrating, and synthesizing the findings.

Generally, conventional reviews include diverse study designs and data types that facilitate comprehensiveness, which may be a strength on the one hand, but can also present challenges on the other. The complexity inherent in combining results from studies with diverse methodologies can result in bias and inaccuracies. The absence of clear guidelines about how to synthesize across diverse study types and data [18] has been a challenge for novice reviewers.

Quantitative systematic reviews and meta-analyses have been important in launching the field of evidence-based healthcare. They provide a systematic, orderly and auditable process for conducting a review and drawing conclusions [25] . They are arguably the most powerful approaches to understanding the effectiveness of healthcare interventions, especially when intervention studies on the same topic show very different results. When areas of research are dogged by controversy [25] or when study results go against strongly held beliefs, such approaches can reduce the uncertainty and bring strong evidence to bear on the controversy.

Despite their strengths, they also have limitations. Systematic reviews and meta-analyses do not provide a way of including complex literature comprising various types of evidence including qualitative studies, theoretical work, and epidemiological studies. Only certain types of design are considered and qualitative data are used in a limited way. This exclusion limits what can be learned in a topic area.

Meta-analyses are often not possible because of wide variability in study design, population, and interventions so they may have a narrow range of utility. New developments in meta-analysis, however, can be used to address some of these limitations. Network meta-analysis is used to explore relative efficacy of multiple interventions, even those that have never been compared in more conventional pairwise meta-analyses [121] , allowing for improved clinical decision making [120] . The limitation is that network meta-analysis has only been used in medical/clinical applications [119] and not in public health. It has not yet been widely accepted and many methodological challenges remain [120] – [121] . Meta-regression is another development that combines meta-analytic and linear regression principles to address the fact that heterogeneity of results may compromise a meta-analysis [117] – [118] . The disadvantage is that many clinicians are unfamiliar with it and may incorrectly interpret results [117] .

Some have accused meta-analysis of combining apples and oranges [124] raising questions in the field about their meaningfulness [25] , [28] . More recently, the use of individual rather than aggregate data has been useful in facilitating greater comparability among studies [122] . In fact, Tomas et al. [123] argue that meta-analysis using individual data is now the gold standard although access to the raw data from other studies may be a challenge to obtain.

The usefulness of systematic reviews in synthesizing complex health and social interventions has also been challenged [102] . It is often difficult to synthesize their findings because such studies are “epistemologically diverse and methodologically complex” [ [69] , p.21]. Rigid inclusion/exclusion criteria may allow only experimental or quasi-experimental designs into consideration resulting in lost information that may well be useful to policy makers for tailoring an intervention to the context or understanding its acceptance by recipients.

Qualitative syntheses may be the type of review most fraught with controversy and challenge, while also bringing distinct strengths to the enterprise. Although these methodologies provide a comprehensive and systematic review approach, they do not generally provide definitive statements about intervention effectiveness. They do, however, address important questions about the development of theoretical concepts, patient experiences, acceptability of interventions, and an understanding about why interventions might work.

Most qualitative syntheses aim to produce a theoretically generalizable mid-range theory that explains variation across studies. This makes them more useful than single primary studies, which may not be applicable beyond the immediate setting or population. All provide a contextual richness that enhances relevance and understanding. Another benefit of some types of qualitative synthesis (e.g., grounded formal theory) is that the concept of saturation provides a sound rationale for limiting the number of texts to be included thus making reviews potentially more manageable. This contrasts with the requirements of systematic reviews and meta-analyses that require an exhaustive search.

Qualitative researchers debate about whether the findings of ontologically and epistemological diverse qualitative studies can actually be combined or synthesized [125] because methodological diversity raises many challenges for synthesizing findings. The products of different types of qualitative syntheses range from theory and conceptual frameworks, to themes and rich descriptive narratives. Can one combine the findings from a phenomenological study with the theory produced in a grounded theory study? Many argue yes, but many also argue no.

Emerging synthesis methodologies were developed to address some limitations inherent in other types of synthesis but also have their own issues. Because each type is so unique, it is difficult to identify overarching strengths of the entire category. An important strength, however, is that these newer forms of synthesis provide a systematic and rigorous approach to synthesizing a diverse literature base in a topic area that includes a range of data types such as: both quantitative and qualitative studies, theoretical work, case studies, evaluations, epidemiological studies, trials, and policy documents. More than conventional literature reviews and systematic reviews, these approaches provide explicit guidance on analytic methods for integrating different types of data. The assumption is that all forms of data have something to contribute to knowledge and theory in a topic area. All have a defined but flexible process in recognition that the methods may need to shift as knowledge develops through the process.

Many emerging synthesis types are helpful to policy makers and practitioners because they are usually involved as team members in the process to define the research questions, and interpret and disseminate the findings. In fact, engagement of stakeholders is built into the procedures of the methods. This is true for rapid reviews, meta-narrative syntheses, and realist syntheses. It is less likely to be the case for critical interpretive syntheses.

Another strength of some approaches (realist and meta-narrative syntheses) is that quality and publication standards have been developed to guide researchers, reviewers, and funders in judging the quality of the products [108] , [126] – [127] . Training materials and online communities of practice have also been developed to guide users of realist and meta-narrative review methods [107] , [128] . A unique strength of critical interpretive synthesis is that it takes a critical perspective on the process that may help reconceptualize the data in a way not considered by the primary researchers [72] .

There are also challenges of these new approaches. The methods are new and there may be few published applications by researchers other than the developers of the methods, so new users often struggle with the application. The newness of the approaches means that there may not be mentors available to guide those unfamiliar with the methods. This is changing, however, and the number of applications in the literature is growing with publications by new users helping to develop the science of synthesis [e.g., [129] ]. However, the evolving nature of the approaches and their developmental stage present challenges for novice researchers.

4.9. When to Use Each Approach

Choosing an appropriate approach to synthesis will depend on the question you are asking, the purpose of the review, and the outcome or product you want to achieve. In Additional File 1 , we discuss each of these to provide guidance to readers on making a choice about review type. If researchers want to know whether a particular type of intervention is effective in achieving its intended outcomes, then they might choose a quantitative systemic review with or without meta-analysis, possibly buttressed with qualitative studies to provide depth and explanation of the results. Alternately, if the concern is about whether an intervention is effective with different populations under diverse conditions in varying contexts, then a realist synthesis might be the most appropriate.

If researchers' concern is to develop theory, they might consider qualitative syntheses or some of the emerging syntheses that produce theory (e.g., critical interpretive synthesis, realist review, grounded formal theory, qualitative meta-synthesis). If the aim is to track the development and evolution of concepts, theories or ideas, or to determine how an issue or question is addressed across diverse research traditions, then meta-narrative synthesis would be most appropriate.

When the purpose is to review the literature in advance of undertaking a new project, particularly by graduate students, then perhaps an integrative review would be appropriate. Such efforts contribute towards the expansion of theory, identify gaps in the research, establish the rationale for studying particular phenomena, and provide a framework for interpreting results in ways that might be useful for influencing policy and practice.

For researchers keen to bring new insights, interpretations, and critical re-conceptualizations to a body of research, then qualitative or critical interpretive syntheses will provide an inductive product that may offer new understandings or challenges to the status quo. These can inform future theory development, or provide guidance for policy and practice.

5. Discussion

What is the current state of science regarding research synthesis? Public health, health care, and social science researchers or clinicians have previously used all four categories of research synthesis, and all offer a suitable array of approaches for inquiries. New developments in systematic reviews and meta-analysis are providing ways of addressing methodological challenges [117] – [123] . There has also been significant advancement in emerging synthesis methodologies and they are quickly gaining popularity. Qualitative meta-synthesis is still evolving, particularly given how new it is within the terrain of research synthesis. In the midst of this evolution, outstanding issues persist such as grappling with: the quantity of data, quality appraisal, and integration with knowledge translation. These topics have not been thoroughly addressed and need further debate.

5.1. Quantity of Data

We raise the question of whether it is possible or desirable to find all available studies for a synthesis that has this requirement (e.g., meta-analysis, systematic review, scoping, meta-narrative synthesis [25] , [27] , [63] , [67] , [84] – [85] ). Is the synthesis of all available studies a realistic goal in light of the burgeoning literature? And how can this be sustained in the future, particularly as the emerging methodologies continue to develop and as the internet facilitates endless access? There has been surprisingly little discussion on this topic and the answers will have far-reaching implications for searching, sampling, and team formation.

Researchers and graduate students can no longer rely on their own independent literature search. They will likely need to ask librarians for assistance as they navigate multiple sources of literature and learn new search strategies. Although teams now collaborate with library scientists, syntheses are limited in that researchers must make decisions on the boundaries of the review, in turn influencing the study's significance. The size of a team may also be pragmatically determined to manage the search, extraction, and synthesis of the burgeoning data. There is no single answer to our question about the possibility or necessity of finding all available articles for a review. Multiple strategies that are situation specific are likely to be needed.

5.2. Quality Appraisal

While the issue of quality appraisal has received much attention in the synthesis literature, scholars are far from resolution. There may be no agreement about appraisal criteria in a given tradition. For example, the debate rages over the appropriateness of quality appraisal in qualitative synthesis where there are over 100 different sets of criteria and many do not overlap [49] . These differences may reflect disciplinary and methodological orientations, but diverse quality appraisal criteria may privilege particular types of research [49] . The decision to appraise is often grounded in ontological and epistemological assumptions. Nonetheless, diversity within and between categories of synthesis is likely to continue unless debate on the topic of quality appraisal continues and evolves toward consensus.

5.3. Integration with Knowledge Translation

If research syntheses are to make a difference to practice and ultimately to improve health outcomes, then we need to do a better job of knowledge translation. In the Canadian Institutes of Health Research (CIHR) definition of knowledge translation (KT), research or knowledge synthesis is an integral component [130] . Yet, with few exceptions [131] – [132] , very little of the research synthesis literature even mentions the relationship of synthesis to KT nor does it discuss strategies to facilitate the integration of synthesis findings into policy and practice. The exception is in the emerging synthesis methodologies, some of which (e.g., realist and meta-narrative syntheses, scoping reviews) explicitly involve stakeholders or knowledge users. The argument is that engaging them in this way increases the likelihood that the knowledge generated will be translated into policy and practice. We suggest that a more explicit engagement with knowledge users in all types of synthesis would benefit the uptake of the research findings.

Research synthesis neither makes research more applicable to practice nor ensures implementation. Focus must now turn seriously towards translation of synthesis findings into knowledge products that are useful for health care practitioners in multiple areas of practice and develop appropriate strategies to facilitate their use. The burgeoning field of knowledge translation has, to some extent, taken up this challenge; however, the research-practice gap continues to plague us [133] – [134] . It is a particular problem for qualitative syntheses [131] . Although such syntheses have an important place in evidence-informed practice, little effort has gone into the challenge of translating the findings into useful products to guide practice [131] .

5.4. Limitations

Our study took longer than would normally be expected for an integrative review. Each of us were primarily involved in our own dissertations or teaching/research positions, and so this study was conducted ‘off the sides of our desks.’ A limitation was that we searched the literature over the course of 4 years (from 2008–2012), necessitating multiple search updates. Further, we did not do a comprehensive search of the literature after 2012, thus the more recent synthesis literature was not systematically explored. We did, however, perform limited database searches from 2012–2015 to keep abreast of the latest methodological developments. Although we missed some new approaches to meta-analysis in our search, we did not find any new features of the synthesis methodologies covered in our review that would change the analysis or findings of this article. Lastly, we struggled with the labels used for the broad categories of research synthesis methodology because of our hesitancy to reinforce the divide between quantitative and qualitative approaches. However, it was very difficult to find alternative language that represented the types of data used in these methodologies. Despite our hesitancy in creating such an obvious divide, we were left with the challenge of trying to find a way of characterizing these broad types of syntheses.

6. Conclusion

Our findings offer methodological clarity for those wishing to learn about the broad terrain of research synthesis. We believe that our review makes transparent the issues and considerations in choosing from among the four broad categories of research synthesis. In summary, research synthesis has taken its place as a form of research in its own right. The methodological terrain has deep historical roots reaching back over the past 200 years, yet research synthesis remains relatively new to public health, health care, and social sciences in general. This is rapidly changing. New developments in systematic reviews and meta-analysis, and the emergence of new synthesis methodologies provide a vast array of options to review the literature for diverse purposes. New approaches to research synthesis and new analytic methods within existing approaches provide a much broader range of review alternatives for public health, health care, and social science students and researchers.

Acknowledgments

KSM is an assistant professor in the Faculty of Nursing at the University of Alberta. Her work on this article was largely conducted as a Postdoctoral Fellow, funded by KRESCENT (Kidney Research Scientist Core Education and National Training Program, reference #KRES110011R1) and the Faculty of Nursing at the University of Alberta.

MM's work on this study over the period of 2008-2014 was supported by a Canadian Institutes of Health Research Applied Public Health Research Chair Award (grant #92365).

We thank Rachel Spanier who provided support with reference formatting.

List of Abbreviations (in Additional File 1 )

Conflict of interest: The authors declare that they have no conflicts of interest in this article.

Authors' contributions: KSM co-designed the study, collected data, analyzed the data, drafted/revised the manuscript, and managed the project.

MP contributed to searching the literature, developing the analytic framework, and extracting data for the Additional File.

JB contributed to searching the literature, developing the analytic framework, and extracting data for the Additional File.

WN contributed to searching the literature, developing the analytic framework, and extracting data for the Additional File.

All authors read and approved the final manuscript.

Additional Files: Additional File 1 – Selected Types of Research Synthesis

This Additional File is our dataset created to organize, analyze and critique the literature that we synthesized in our integrative review. Our results were created based on analysis of this Additional File.

Literature Reviews

• Introduction
• Tutorials and resources
• Step 1: Literature search
• Step 2: Analysis, synthesis, critique
• Step 3: Writing the review

If you need any assistance, please contact the library staff at the Georgia Tech Library Help website . 

Analysis, synthesis, critique

Literature reviews build a story. You are telling the story about what you are researching. Therefore, a literature review is a handy way to show that you know what you are talking about. To do this, here are a few important skills you will need.

Skill #1: Analysis

Analysis means that you have carefully read a wide range of the literature on your topic and have understood the main themes, and identified how the literature relates to your own topic. Carefully read and analyze the articles you find in your search, and take notes. Notice the main point of the article, the methodologies used, what conclusions are reached, and what the main themes are. Most bibliographic management tools have capability to keep notes on each article you find, tag them with keywords, and organize into groups.

Skill #2: Synthesis

After you’ve read the literature, you will start to see some themes and categories emerge, some research trends to emerge, to see where scholars agree or disagree, and how works in your chosen field or discipline are related. One way to keep track of this is by using a Synthesis Matrix .

Skill #3: Critique

As you are writing your literature review, you will want to apply a critical eye to the literature you have evaluated and synthesized. Consider the strong arguments you will make contrasted with the potential gaps in previous research. The words that you choose to report your critiques of the literature will be non-neutral. For instance, using a word like “attempted” suggests that a researcher tried something but was not successful. For example: 

There were some attempts by Smith (2012) and Jones (2013) to integrate a new methodology in this process.

On the other hand, using a word like “proved” or a phrase like “produced results” evokes a more positive argument. For example:

The new methodologies employed by Blake (2014) produced results that provided further evidence of X.

In your critique, you can point out where you believe there is room for more coverage in a topic, or further exploration in in a sub-topic.

Need more help?

If you are looking for more detailed guidance about writing your dissertation, please contact the folks in the Georgia Tech Communication Center .

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How to Synthesize Written Information from Multiple Sources

Shona McCombes

Content Manager

B.A., English Literature, University of Glasgow

Shona McCombes is the content manager at Scribbr, Netherlands.

Learn about our Editorial Process

Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

On This Page:

When you write a literature review or essay, you have to go beyond just summarizing the articles you’ve read – you need to synthesize the literature to show how it all fits together (and how your own research fits in).

Synthesizing simply means combining. Instead of summarizing the main points of each source in turn, you put together the ideas and findings of multiple sources in order to make an overall point.

At the most basic level, this involves looking for similarities and differences between your sources. Your synthesis should show the reader where the sources overlap and where they diverge.

Unsynthesized Example

Franz (2008) studied undergraduate online students. He looked at 17 females and 18 males and found that none of them liked APA. According to Franz, the evidence suggested that all students are reluctant to learn citations style. Perez (2010) also studies undergraduate students. She looked at 42 females and 50 males and found that males were significantly more inclined to use citation software ( p < .05). Findings suggest that females might graduate sooner. Goldstein (2012) looked at British undergraduates. Among a sample of 50, all females, all confident in their abilities to cite and were eager to write their dissertations.

Synthesized Example

Studies of undergraduate students reveal conflicting conclusions regarding relationships between advanced scholarly study and citation efficacy. Although Franz (2008) found that no participants enjoyed learning citation style, Goldstein (2012) determined in a larger study that all participants watched felt comfortable citing sources, suggesting that variables among participant and control group populations must be examined more closely. Although Perez (2010) expanded on Franz’s original study with a larger, more diverse sample…

Step 1: Organize your sources

After collecting the relevant literature, you’ve got a lot of information to work through, and no clear idea of how it all fits together.

Before you can start writing, you need to organize your notes in a way that allows you to see the relationships between sources.

One way to begin synthesizing the literature is to put your notes into a table. Depending on your topic and the type of literature you’re dealing with, there are a couple of different ways you can organize this.

Summary table

A summary table collates the key points of each source under consistent headings. This is a good approach if your sources tend to have a similar structure – for instance, if they’re all empirical papers.

Each row in the table lists one source, and each column identifies a specific part of the source. You can decide which headings to include based on what’s most relevant to the literature you’re dealing with.

For example, you might include columns for things like aims, methods, variables, population, sample size, and conclusion.

For each study, you briefly summarize each of these aspects. You can also include columns for your own evaluation and analysis.

The summary table gives you a quick overview of the key points of each source. This allows you to group sources by relevant similarities, as well as noticing important differences or contradictions in their findings.

Synthesis matrix

A synthesis matrix is useful when your sources are more varied in their purpose and structure – for example, when you’re dealing with books and essays making various different arguments about a topic.

Each column in the table lists one source. Each row is labeled with a specific concept, topic or theme that recurs across all or most of the sources.

Then, for each source, you summarize the main points or arguments related to the theme.

The purposes of the table is to identify the common points that connect the sources, as well as identifying points where they diverge or disagree.

Step 2: Outline your structure

Now you should have a clear overview of the main connections and differences between the sources you’ve read. Next, you need to decide how you’ll group them together and the order in which you’ll discuss them.

For shorter papers, your outline can just identify the focus of each paragraph; for longer papers, you might want to divide it into sections with headings.

There are a few different approaches you can take to help you structure your synthesis.

If your sources cover a broad time period, and you found patterns in how researchers approached the topic over time, you can organize your discussion chronologically .

That doesn’t mean you just summarize each paper in chronological order; instead, you should group articles into time periods and identify what they have in common, as well as signalling important turning points or developments in the literature.

If the literature covers various different topics, you can organize it thematically .

That means that each paragraph or section focuses on a specific theme and explains how that theme is approached in the literature.

Source Used with Permission: The Chicago School

If you’re drawing on literature from various different fields or they use a wide variety of research methods, you can organize your sources methodologically .

That means grouping together studies based on the type of research they did and discussing the findings that emerged from each method.

If your topic involves a debate between different schools of thought, you can organize it theoretically .

That means comparing the different theories that have been developed and grouping together papers based on the position or perspective they take on the topic, as well as evaluating which arguments are most convincing.

Step 3: Write paragraphs with topic sentences

What sets a synthesis apart from a summary is that it combines various sources. The easiest way to think about this is that each paragraph should discuss a few different sources, and you should be able to condense the overall point of the paragraph into one sentence.

This is called a topic sentence , and it usually appears at the start of the paragraph. The topic sentence signals what the whole paragraph is about; every sentence in the paragraph should be clearly related to it.

A topic sentence can be a simple summary of the paragraph’s content:

“Early research on [x] focused heavily on [y].”

For an effective synthesis, you can use topic sentences to link back to the previous paragraph, highlighting a point of debate or critique:

“Several scholars have pointed out the flaws in this approach.” “While recent research has attempted to address the problem, many of these studies have methodological flaws that limit their validity.”

By using topic sentences, you can ensure that your paragraphs are coherent and clearly show the connections between the articles you are discussing.

As you write your paragraphs, avoid quoting directly from sources: use your own words to explain the commonalities and differences that you found in the literature.

Don’t try to cover every single point from every single source – the key to synthesizing is to extract the most important and relevant information and combine it to give your reader an overall picture of the state of knowledge on your topic.

Step 4: Revise, edit and proofread

Like any other piece of academic writing, synthesizing literature doesn’t happen all in one go – it involves redrafting, revising, editing and proofreading your work.

Checklist for Synthesis

•   Do I introduce the paragraph with a clear, focused topic sentence?
•   Do I discuss more than one source in the paragraph?
•   Do I mention only the most relevant findings, rather than describing every part of the studies?
•   Do I discuss the similarities or differences between the sources, rather than summarizing each source in turn?
•   Do I put the findings or arguments of the sources in my own words?
•   Is the paragraph organized around a single idea?
•   Is the paragraph directly relevant to my research question or topic?
•   Is there a logical transition from this paragraph to the next one?

Further Information

How to Synthesise: a Step-by-Step Approach

Help…I”ve Been Asked to Synthesize!

Learn how to Synthesise (combine information from sources)

How to write a Psychology Essay

• Research Guides

Literature Review: A Self-Guided Tutorial

Using a synthesis matrix.

• Literature Reviews: A Recap
• Peer Review
• Reading the Literature
• Using Concept Maps
• Developing Research Questions
• Considering Strong Opinions
• 2. Review discipline styles
• Super Searching
• Finding the Full Text
• Citation Searching This link opens in a new window
• When to stop searching
• Citation Management
• Annotating Articles Tip
• 5. Critically analyze and evaluate
• How to Review the Literature
• 7. Write literature review

A synthesis matrix visually represents your research by organizing your sources by themes:

• Sample Synthesis Matrix Example provided by Ashford University Writing Center .
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Writing a Literature Review: Organize, Synthesize, Evaluate

• Literature Review Process
• Literature Search
• Record your Search
• Organize, Synthesize, Evaluate
• Getting help

Table of Contents

On this page you will find:

Organizing Literature and Notes

How to scan an article.

• Reading for Comprehension
• Synthesis Matrix Information

Steps to take in organizing your literature and notes:

• Find common themes and organize the works into categories.
• Develop a subject level outline with studies you’ve found
• Expand or limit your search based on the information you found.
• How the works in each category relate to each other
• How the categories relate to each other and to your overall theme.

Available tools:

• Synthesis Matrix The "synthesis matrix" is an approach to organizing, monitoring, and documenting your search activities.
• Concept Mapping Concept Maps are graphic representations of topics, ideas, and their relationships. They allow users to group information in related modules so that the connections between and among the modules become more readily apparent than they might from an examination of a list. It can be done on paper or using specific software.
• Mind Mapping A mind map is a visual representation of hierarchical information that includes a central idea surrounded by connected branches of associated topics.
• NVIVO NVIVO is a qualitative data analysis software that can be applied for engineering literature review.

Synthesis Matrix

• Writing A Literature Review and Using a Synthesis Matrix Writing Center, Florida International University
• The Matrix Method of Literature Reviews Article from Health Promotion Practice journal.

Sample synthesis matrix

Synthesis matrix video

Skim the article to get the “big picture” for relevancy to your topic. You don’t have to understand every single idea in a text the first time you read it.

• Where was the paper published?
• What kind of journal it is? Is the journal peer-reviewed?
• Can you tell what the paper is about?
• Where are they from?
• What are the sections of the article?
• Are these clearly defined?  
• Can you figure out the purpose of the study, methodology, results and conclusion?
• Mentally review what you know about the topic
• Do you know enough to be able to understand the paper? If not, first read about the unfamiliar concepts  
• What is the overall context?
• Is the problem clearly stated?
• What does the paper bring new?
• Did it miss any previous major studies?
• Identify all the author’s assumptions.  
• Analyze the visuals for yourself and try to understand each of them. Make notes on what you understand. Write questions of what you do not understand. Make a guess about what materials/methods you expect to see. Do your own data interpretation and check them against the conclusions.  
• Do you agree with the author’s opinion?
• As you read, write down terms, techniques, unfamiliar concepts and look them up  
• Save retrieved sources to a reference manager

Read for Comprehension and Take Notes

Read for comprehension

• After first evaluation of sources, critically read the selected sources. Your goal is to determine how much of it to accept, determine its value, and decide whether you plan to include it in your literature review.
• Read the whole article, section by section but not necessarily in order and make sure you understand:

Introduction : What is known about the research and what is still unknown. Methods : What was measured? How was measured? Were the measurement appropriate? Did they offer sufficient evidence? Results : What is the main finding? Were there enough data presented? Were there problems not addressed? Discussions : Are these conclusions appropriate? Are there other factors that might have influenced? What does it need to be done to answer remaining questions?

• Find answers to your question from first step
• Formulate new questions and try to answer them
• Can you find any discrepancies? What would you have done differently?
• Re-read the whole article or just sections as many times you feel you need to
• When you believe that you have understood the article, write a summary in your own words (Make sure that there is nothing left that you cannot understand)

As you read, take (extensive) notes. Create your own system to take notes but be consistent. Remember that notes can be taken within the citation management tool.

What to write in your notes:

• identify key topic, methodology, key terms
• identify emphases, strengths, weaknesses, gaps (if any)
• determine relationships to other studies
• identify the relationship to your research topic
• new questions you have  
• suggestions for new directions, new sources to read
• everything else that seems relevant
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How can we help?

• [email protected]
• Consultation
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• Library Guides

Literature Reviews

• Synthesizing your findings
• Literature Review
• Developing your research question
• Managing your search results
• Reading critically

The synthesis

• Writing the review
• Researcher Tool Kit

The synthesis is not just a summary of each reading that you've decided to include in your review. The purpose of your synthesis is to bring together all of your research findings to:

• Describe main themes in the literature you've found and deemed relevant.
• Demonstrate any relationships between those themes.
• Explain how all of the selected sources fit into the body of literature you are evaluating, and how they interrelate.
• Identify any gaps in the literature. (This is the starting point for your justification of your future work on the gap you plan to fill.)

You're going to need to sort and collate your references by main topics and themes, so you can see which arguments they support. This allows you to pull these ideas together to frame coherent arguments and provide supporting evidence from what you've read.

This is where your literature matrix is useful. You can sort it by category (heading). For example, you could sort it to group your references by key themes or by the section of your research question they are related to, which makes it easier to start your analysis and synthesis of your findings.

If your original matrix is too unwieldy for this stage, you could use copies of it create smaller, separate matrices for each theme or topic or section of your review. The original matrix will retain all of your information, but the smaller ones only need the columns of information that are relevant to this process. This means that you have less information to wade through and enables you to focus on each theme or section one at a time.

Note: There is a large volume of work in this stage of your review so breaking it up in to easier stages is a good idea.

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Synthesis and Making Connections for Strong Analysis

by acburton | Apr 25, 2024 | Resources for Students , Writing Resources

If Russian Dolls Aren’t For You, Here Are a Few Other Ways to Think About Synthesis

‘Joining the Conversation’: When we perform synthesis in our writing and engage with making connections, we are joining a wider conversation. We are seeing what has already been said about the topic, seeking out what these many perspectives and viewpoints have in common and/or how they differ, and then interpreting these relationships to form our own input to the conversation. We must directly engage with our sources to draw insightful conclusions and share what we think as a result. ‘Building the Bridge’: Synthesis is building the bridge between your sources for the reader. To synthesize or make connections, we must figure out how we get from one source to the other. In other words, we cannot present our sources in isolation (this wouldn’t help create any new meaning). Instead, we need to build the bridge between source A and source B so that our readers can understand what the two, together, suggest about our understanding of a topic. Then, we build a bridge from this new understanding to source C and source D, and so on.

Start Synthesizing

So you want to synthesize information? To start, review the existing literature on your selected topic. When searching for resources, aim to collect a number from various authors, subjects, and settings to broaden your understanding of the material – giving yourself more information to consider in the next stage. Ultimately, you’ll want to find the main idea presented in each source, as well as how the author supports or argues against it, as well as why.

• Compare and Contrast

Compare and contrast the main idea found in each source reviewed. What does each perspective have in common? What are their differences? Begin to consider how these sources  ‘fit together’ (or, in other words, build the bridge!). During this stage, you may find that some of your collected resources don’t have as much depth or go into as much detail as you’d like. That’s okay, but you’ll want to consider what effect this might have on your ability to draw a meaningful conclusion once synthesized with other source material.

• Ask, What’s the Significance?

By evaluating the quality and significance of each source, you can begin to consider its relevance within the context of your research or in relation to your topic. How does the relationship of one source to another further your understanding of the topic you are focusing on? What is the larger impact of what is being said or argued?

• Infer the Relationship and Draw Conclusions

By this point, you have gone through the existing literature surrounding your subject and compared/contrasted it, finding the main idea of each, as well as their intended purpose, possible criticisms, strengths, and weaknesses. Finally, you have related these ideas to your own research. Although you may have found that your sources agree or disagree on minor (or major) key details, it is the writer’s job to seek the relationship between these sources, put them in conversation together, and draw meaning through analysis. In some cases, you’ll be asked to offer your own perspective or argumentation. Consider, how might you add to the existing conversation?

Synthesis is all about meaningful connections, it is not summarizing sources side by side. Before you make larger claims about a topic, make sure you build those bridges between the sources you found through research. Nestle them together. Move beyond summary. Then, you can create an interesting and compelling argument. For additional help, make an appointment with the Writing Center!

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https://medium.com/azure-s-whereabouts/the-matryoshka-doll-effect-be9d2760d2e2 (Image)

Should I do a synthesis (i.e. literature review)?

• Questions & Quandaries
• Published: 18 April 2024

Cite this article

• H. Carrie Chen 1 ,
• Ayelet Kuper 2 , 3 , 4 ,
• Jennifer Cleland 5 &
• Patricia O’Sullivan 6  

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This column is intended to address the kinds of knotty problems and dilemmas with which many scholars grapple in studying health professions education. In this article, the authors address the question of whether one should conduct a literature review or knowledge synthesis, considering the why, when, and how, as well as its potential pitfalls. The goal is to guide supervisors and students who are considering whether to embark on a literature review in education research.

Avoid common mistakes on your manuscript.

Two junior colleagues come to you to ask your advice about carrying out a literature review on a particular topic. “Should they?” immediately pops into your mind, followed closely by, if yes, then what kind of literature review is appropriate? Our experience is that colleagues often come to suggest a literature review to “kick start” their research (in fact, some academic programs require them as part of degree requirements), without a full understanding of the work involved, the different types of literature review, and what type of literature review might be most suitable for their research question. In this Questions and Quandaries, we address the question of literature reviews in education research, considering the why, when, and how, as well as potential pitfalls.

First, what is meant by literature review? The term literature review has been used to refer to both a review of the literature and a knowledge synthesis (Maggio et al., 2018 ; Siddaway et al., 2019 ). For our purposes, we employ the term as commonly used to refer to a knowledge synthesis , which is a formal comprehensive review of the existing body of literature on a topic. It is a research approach that critically integrates and synthesizes available evidence from multiple studies to provide insight and allow the drawing of conclusions. It is an example of Boyer’s scholarship of integration (Boyer, 1990 ). In contrast, a review of the literature is a relatively casual and expedient method for attaining a general overview of the state of knowledge on a given topic to make the argument that a new study is needed. In this interpretation, a literature review serves as a key starting point for anyone conducting research by identifying gaps in the literature, informing the study question, and situating one’s study in the field.

Whether a formal knowledge synthesis should be done depends on if a review is needed and what the rationale is for the review. The first question to consider is whether a literature review already exists. If no, is there enough literature published on the topic to warrant a review? If yes, does the previous review need updating? How long has it been since the last review and has the literature expanded so much or are there important new studies that need integrating to justify an updated review? Or were there flaws in the previous review that one intends to address with a new review? Or does one intend to address a different question than the focus of the previous review?

If the knowledge synthesis is to be done, it should be driven by a research question. What is the research question? Can it be answered by a review? What is the purpose of the synthesis? There are two main purposes for knowledge synthesis– knowledge support and decision support. Knowledge support summarizes the evidence while decision support takes additional analytical steps to allow for decision-making in particular contexts (Mays et al., 2005 ).

If the purpose is to provide knowledge support, then the question is how or what will the knowledge synthesis add to the literature? Will it establish the state of knowledge in an area, identify gaps in the literature/knowledge base, and/or map opportunities for future research? Cornett et al., performed a scoping review of the literature on professional identity, focusing on how professional identity is described, why the studies where done, and what constructs of identity were used. Their findings advanced understanding of the state of knowledge by indicating that professional identity studies were driven primarily by the desire to examine the impact of political, social and healthcare reforms and advances, and that the various constructs of professional identity across the literature could be categorized into five themes (Cornett et al., 2023 ).

If, on the other hand, the purpose of the knowledge synthesis is to provide decision support, for whom will the synthesis be relevant and how will it improve practice? Will the synthesis result in tools such as guidelines or recommendations for practitioners and policymakers? An example of a knowledge synthesis for decision support is a systematic review conducted by Spencer and colleagues to examine the validity evidence for use of the Ottawa Surgical Competency Operating Room Evaluation (OSCORE) assessment tool. The authors summarized their findings with recommendations for educational practice– namely supporting the use of the OSCORE for in-the-moment entrustment decisions by frontline supervisors in surgical fields but cautioning about the limited evidence for support of its use in summative promotions decisions or non-surgical contexts (Spencer et al., 2022 ).

If a knowledge synthesis is indeed appropriate, its methodology should be informed by its research question and purpose. We do not have the space to discuss the various types of knowledge synthesis except to say that several types have been described in the literature. The five most common types in health professions education are narrative reviews, systematic reviews, umbrella reviews (meta-syntheses), scoping reviews, and realist reviews (Maggio et al., 2018 ). These represent different epistemologies, serve different review purposes, use different methods, and result in different review outcomes (Gordon, 2016 ).

Each type of review lends itself best to answering a certain type of research question. For instance, narrative reviews generally describe what is known about a topic without necessarily answering a specific empirical question (Maggio et al., 2018 ). A recent example of a narrative review focused on schoolwide wellbeing programs, describing what is known about the key characteristics and mediating factors that influence student support and identifying critical tensions around confidentiality that could make or break programs (Tan et al., 2023 ). Umbrella reviews, on the other hand, synthesize evidence from multiple reviews or meta-analyses and can illuminate agreement, inconsistencies, or evolution of evidence on a topic. For example, an umbrella review on problem-based learning highlighted the shift in research focus over time from does it work, to how does it work, to how does it work in different contexts, and pointed to directions for new research (Hung et al., 2019 ).

Practical questions for those considering a literature review include whether one has the time required and an appropriate team to conduct a high-quality knowledge synthesis. Regardless of the type of knowledge synthesis and use of quantitative or qualitative methods, all require rigorous and clear methods that allow for reproducibility. This can take time, up to 12–18 months. A high-quality knowledge synthesis also requires a team whose members have expertise not only in the content matter, but also in knowledge synthesis methodology and in literature searches (i.e. a librarian). A team with multiple reviewers with a variety of perspectives can also help manage the volume of large reviews, minimize potential biases, and strengthen the critical analysis.

Finally, a pitfall one should be careful to avoid is merely summarizing everything in the literature without critical evaluation and integration of the information. A knowledge synthesis that merely bean counts or presents a collection of unconnected information that has not been reflected upon or critically analyzed does not truly advance knowledge or decision-making. Rather, it leads us back to our original question of whether it should have been done in the first place.

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Chen, H.C., Kuper, A., Cleland, J. et al. Should I do a synthesis (i.e. literature review)?. Adv in Health Sci Educ (2024). https://doi.org/10.1007/s10459-024-10335-1

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• Published: 26 April 2024

Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis

• Zara Siu Wa Chui   ORCID: orcid.org/0009-0001-3722-2374 1 ,
• Lily Man Lee Chan   ORCID: orcid.org/0000-0003-3665-1449 2 ,
• Esther Wan Hei Zhang 3 ,
• Suisha Liang   ORCID: orcid.org/0000-0003-0426-9827 4 , 6 ,
• Edmond Pui Hang Choi   ORCID: orcid.org/0000-0002-8388-7342 2 ,
• Kris Yuet Wan Lok   ORCID: orcid.org/0000-0002-3227-0799 2 ,
• Hein Min Tun   ORCID: orcid.org/0000-0001-7597-5062 5 , 6 , 7 &
• Jojo Yan Yan Kwok   ORCID: orcid.org/0000-0001-7444-6935 2 , 8  

Scientific Reports volume  14 , Article number:  9558 ( 2024 ) Cite this article

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• Neurodegenerative diseases

Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, − 0.57; 95% CI − 0.93 to − 0.21; I 2  = 42%; P  = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.

Introduction

Neurodegenerative diseases (NDDs) are a diverse spectrum of disorders characterized by the progressive loss of neurons and deterioration in the central or peripheral nervous system, resulting in long-term motor and nonmotor impairments 1 . NDDs include Parkinson’s disease (PD), Alzheimer’s disease (AD), frontotemporal dementia and its variants, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). As the population ages, the incidence rate and prevalence of NDDs increase modestly, as demonstrated by an incidence estimated annual percentage changes of 0.52 for PD and 0.13 in men and 0.06 in women for AD 2 , 3 . Affecting millions of people worldwide, NDDs are a major public health concern; yet, despite decades of research effort, no effective treatments for curing or reversing their progression have been realized 3 . The exact pathophysiology of NDDs is also not fully elucidated owing to the heterogeneity and complexity of these diseases 4 , 5 , 6 . However, emerging evidence suggests that the gut microbiome (GM), the collection of microorganisms that inhabit the gastrointestinal (GI) tract, may play a role in modulating the risk and severity of NDDs.

GM, often called the second brain, harbors nearly 100 trillion bacteria, yeast, and other microorganisms, functioning symbiotically in day-to-day activities 7 . Host genetics, lifestyle, and environmental factors, such as diet, chemical exposure, infection, and host comorbidity, shape GM through the modulation of gut motility and secretion, which in turn affects various aspects of the host physiology, including immunomodulation, metabolic activity, and neuronal development and function. The connection between GM and metabolic and immune-related diseases is well established 8 . For example, obesity, as a complex metabolic disorder, is associated with decreased diversity and richness and altered composition in GM 9 . Wells et al. also identified that Prevotella correlates with the genetic risk and anticitrullinated protein antibody level of rheumatoid arthritis, suggesting the role of Prevotella as a potential mediator in disease progression 10 .

A growing body of evidence has suggested that GM also communicates bidirectionally via multiple pathways, which collectively is described by the gut–brain axis. The brain communicates with the gut through neuronal and hormonal pathways, including the hypothalamic pituitary adrenal axis (HPA) and sympathoadrenal axis 11 . The vagal nerves relay most signals from the brain to the gut 12 and coordinate stress and anti-inflammatory activities with HPA to regulate gut motility, intestinal permeability, and mucosal immune activity 13 . At the same time, GM can affect the brain by producing and releasing various molecules, such as metabolites, neurotransmitters, and cytokines; these molecules can reach the brain through multiple pathways and may be a key modulator in NDDs 14 .

Disruption of GM balance caused by host and environmental factors may lead to diseases or disorders 15 . Romano et al. performed a meta-analysis of 21 case–control studies to compare the GM composition of 1083 PD patients and 1213 healthy controls and revealed a lower abundance of Prevotellaceae and Lachnospiraceae families and higher abundance of Enterobacteriaceae and Akkermansiaceae families in patients than in controls 16 . Similarly, patterns of dysbiosis in other NDDs, including AD, MS, and ALS, have been reported in recent systematic review and meta-analysis 17 , 18 , 19 . Sampson et al. reported the requisite involvement of gut microbiota to elicit synucleinopathies in a PD model using wild-type and Thy1-α-synuclein genotype mice, in which the germ-free Thy1-α-synuclein genotype demonstrated limited motor and GI dysfunction compared with specific pathogen-free counterparts 20 . These findings suggest that GM may play a key role in the pathophysiology of NDDs, and modulating GM may be a potential strategy for preventing or treating NDDs.

However, many challenges and limitations remain in this research field. For example, most animal studies rely on germ-free or genetic models of NDDs, which may not fully recapitulate the human disease phenotypes or etiologies 21 . Standardized methods for assessing and manipulating GM across different studies are also lacking. Meanwhile, human studies, are mostly observational and cross-sectional, which cannot establish causality or directionality between GM and NDDs 22 .

In the recent decade, clinical trials have been conducted to investigate the efficacy of interventions modulating GM in alleviating or reversing disease progression. Yet, comprehensive synthesis of the available evidence in understanding microbiome-modulating methods is lacking. Therefore, this systematic review aims to summarize and critically appraise the current evidence regarding the effects of microbiome-modulating interventions on NDD-related clinical outcomes and to discuss the translatability and implementation potentials for future research and clinical application.

Inclusion criteria and search strategy

This protocol-based systematic review (PROSPERO ID: CRD42023437490) was conducted and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 23 and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement 24 . Studies were selected in accordance with predefined inclusion and exclusion criteria. Randomized controlled trials (RCTs), quasi-experimental studies, single-arm studies, and pilot studies with microbiome-modulating intervention were included if studies (1) were conducted in adults (age > 18 years) with a diagnosis of NDDs, such as AD, PD, MS, and ALS, and (2) reported any microbiome outcomes. Microbiome-modulating intervention is defined as any treatment or intervention that alters the composition, diversity, or functionality of GM. The intervention can be, but not limited to, changes in diet or lifestyle, use of biotics, fecal microbiota transplantation (FMT), or other medications. The methods of microbiome analysis are not restricted, which may include, but not limited to, 16S ribosomal (r) RNA sequencing, shotgun metagenomic sequencing, and fluorescence in situ hybridization. Studies were excluded if they were not published in English.

PubMed, Ovid-Embase, and Web of Science were searched from inception to January 11, 2023. The search strategy was summarized as follows: [neurodegenerative diseases] AND [microbiome assessment] AND [microbiome-modulating methods: (diet) OR (supplement or biotics) OR (FMT)]. Online Resource 1 presents the full search strategy. Duplicate records were removed with EndNote and manually.

Data extraction and quality assessment

Two independent reviewers (ZSW Chui and EWH Zhang) extracted data from each trial using a pre-specific, standardized form and evaluated the risk of bias via the Cochrane Risk-of-Bias Tool 2 for RCTs 25 and the Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) for non-RCTs 26 . Discrepancies were identified and resolved by consensus with a third reviewer (LML Chan) and the supervisor (JYY Kwok).

A narrative synthesis was conducted for all trials to describe study design, country and setting of study, characteristics of participants and interventions, assessment time points, microbiota sequencing technique, main microbiota, and clinical outcomes (Table 1 ). Meta-analyses were performed among microbiota and clinical outcomes if they were reported by at least three studies. In view of wide variations in instruments used between trials to assess the primary outcomes, pooled effects were summarized as standardized mean differences (SMDs). SMD is a summary statistic used to report intervention effects in standardized units, rather than the original units of measurement for each scale. The total sample size, mean with standard deviation (SD) or median, and interquartile range of disease progression pre- and post-intervention were extracted to calculate SMD and SD. Twenty-five individual study results were corrected for directionality when appropriate. Considering the substantial variations in microbiome-modulating interventions and study design, we utilized a random-effect model to conduct the analysis using RevMan 5.4 27 , 28 . All significance tests were 2-tailed, and P value of < 0.05 was considered statistically significant. The heterogeneity among studies was assessed using I 2 statistic.

Study selection

The PRIMSA 2020 flow diagram (Fig.  1 ) shows the flow of the study selection process. A total of 7269 unique records identified from the search, of which 25 were deemed eligible for full review. Fourteen trials were included for qualitative synthesis. Seven trials were included in the meta-analyses.

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart.

Study characteristics

Table 1 shows a systematic presentation of information regarding the study characteristics. Fifteen articles comprised 14 trials that involved 445 patients: 5 trials/6 articles on sclerosis (n = 112), 6 trials on PD (n = 235), and 3 trials on AD and related disorders (n = 98). Of the 14 trials, 6 studies adopted single-arm design, 5 studies were RCT, and 3 were non-RCT.

Quality assessment

The quality of the methodology and risk of bias of the 15 articles were assessed in accordance with Cochrane RoB2 for randomized trials and ROBINS-I for nonrandomized trials 25 , 26 (Table 2 and 3 ).

Bias in the selection of reports is a common concern among studies; here, three out of five RCTs and seven out of nine non-RCTs were of moderate-to-high risk in the concerning domain owing to multiple measurements of disease progression. In general, RCTs had a lower risk of bias, in which no high-risk RCTs were included. The RCT performed by Al et al. was terminated early because of the sudden death of the principal investigator 22 ; nevertheless, results were analyzed in such a way that no directional bias toward or against the intervention exists, and this RCT was therefore assessed to have a moderate risk.

For non-RCTs, 66.78% of the studies were of serious risk of bias, and the remaining were of moderate risk 29 , 34 , 36 , 39 , 40 , 42 . Apart from reporting bias (D7), major concerns of bias included confounding bias (D1), selection bias (D2), and bias in data measurement (D6). Serious confounding bias mainly contributed to the lack of control of diet, which can affect the microbiome composition, leading to less conclusive results. In addition, many of the non-RCTs relied on self-reporting, while the participants were aware of the interventions. Becker et al. conducted an open-label study to modify GM in PD patients with resistance starch and collected subject-reported nonmotor data; consequently, the measurement could be inaccurate owing to subjective reporting 34 . Poor selection of participants and missing data were also common among nonrandomized clinical trials.

MS and amyotrophic lateral sclerosis

Five studies focusing on MS 22 , 29 , 30 , 31 , 32 and one study specifically on ALS 33 were included. These studies comprised three RCTs 22 , 32 , 33 and two single-arm studies 29 , 30 , 31 . The sample sizes of MS studies were small, ranging from 9 22 to 22 30 , 31 , whereas the study on ALS recruited 50 samples 33 . The study durations varied from 1 week 29 to 1 year 22 . A spectrum of microbiome-modulating interventions were used, ranging from probiotic supplementation 30 , 31 , 33 , dietary intervention (intermittent fasting) 32 , FMT 22 , and a multidimensional program consisting of dietary intervention and physical activities 29 . All studies used 16 s rRNA sequencing to analyze microbiome composition, covering V3 and/ or V4 regions. In addition to V3 and V4 regions, V13 region was also covered by Cignarella et al. to distinguish specific species of Lactobacillus , as well as V1 and V2 regions 32 .

MS is characterized with chronic inflammatory response in the central nervous system, which leads to pronounced Th1/Th17-mediated inflammation and increased proinflammatory cytokine concentration 43 , 44 . Therefore, improvement in MS progression can be evaluated by measuring inflammatory response and clinical functional and nonfunctional outcomes. Three out of four studies focusing on MS reported reduced inflammatory response or improved autoimmune response 29 , 30 , 31 , 32 , while the remaining underpowered study showed insignificant difference post-modulation 22 .

All of the studies had diverse microbiome patterns. The two studies on probiotic supplementation showed time-related changes in microbiome composition but had different microbiota outcomes despite using similar bacterial families, that is, Di Gioia et al. used Streptococcaceae and Lactobacillaceae families, while Tankou et al. used Bifidobacteriaceae family in addition to Streptococcaceae and Lactobacillaceae families 30 , 31 , 33 . Di Gioia et al. found no significant alterations in microbiota and probiotic supplementation, except for Rikenellaceae and trends of increase in Bateroidaceae and decrease in Prevotellaceae and Clostridiales , and no clinical improvement in ALS 33 . Tankou et al. reported enrichment of Lactobacillaceae , Streptococcaceae , and Bifidobacteriaceae and reduction of Akkermansia , Blautia , and Dorea , which were enriched in MS patients at baseline. They also observed reduced intermediate monocytes, increased effector memory CD8 T cells, and anti-inflammatory gene expression, with some association with microbiome changes, therefore suggesting an implication of synergistic effect with current therapies 30 , 31 .

Dietary interventions significantly improved disease progression and inflammatory tone in both studies 29 , 32 . Cignarella et al. reported increased Faecalibacterium, Lachnospiracea incertae sedis , and Blautia, improved Expanded Disability Status Scale (EDSS), and reduced serum leptin and peripheral blood leukocyte profile changes after 15 days of intermittent fasting in conjunction with corticosteroid treatment 32 . However, the difference in improvement of EDSS between the ad libitum control group and the intermittent fasting group was insignificant, and the MS Functional Composite was insignificantly different from the baseline in both groups, possibly due to the short intervention duration 32 . Barone et al. conducted a 1-week multidimensional program involving Mediterranean diet, neuromotor rehabilitation, and mindfulness 29 . They reported partial recovery of gut dysbiosis with reduced Collinsella , Actinobacteria , and Ruminococcus and increased Bacteroidetes and some short-chain fatty acid (SCFA) producers. They also observed reduced inflammatory tone and serum lipopolysaccharide, increased anti-inflammatory gene expression, and some associations with microbiome changes. Considering the significant improvement in the total score in the Modified Fatigue Impact Scale, the author concluded that the multidimensional approach may be effective in mitigating MS progression.

Al et al. conducted an RCT on FMT, in which they randomized participants into early (received FMT with 6-month follow-up, n = 4) or late intervention group (6-month observation, substantiated by FMT and 1-month follow-up, n = 5); however, the study was terminated early and underpowered because of the unexpected death of the principal investigator 22 . Preliminary results showed that FMT was well-tolerated without serious adverse events. Microbiome changes recapitulated the microbiome composition of the donor and had the potential to improve elevated intestinal permeability. Insignificant clinical changes were noted on disease severity measured by EDSS, without new MRI activity, and the inflammatory levels in terms of serum cytokines showed insignificant changes.

We identified six articles that fulfilled all criteria 34 , 35 , 36 , 37 , 38 , 39 . They included one RCT 38 , two non-RCT 34 , 36 , and three single-arm studies 35 , 37 , 39 , which used diversified microbiome-modulating methods, including prebiotics, FMT, dietary interventions, and probiotics. The sample size was in the range of 8–11 for non-RCTs and single-arm studies and 87–100 for RCTs. The study lasted 7 weeks to 1 year.

Two of the studies investigated GM with metagenomic sequencing 34 , 38 , while others used 16 s rRNA sequencing, despite sequencing different variable regions. Although different interventions were used, the alpha and beta diversities did not differ significantly in all studies. No consensus existed in terms of the change in a particular family, genus, or species.

Despite using different microbiome-modulating strategies, these studies showed a significant impact on alleviating disease burden. Motor functions, as measured by Unified PD Rating Scale (UPDRS), were significantly improved in four of the six studies that used FMT, probiotics, ovo-lacto diet, ovo-lacto diet with enema, and Mediterranean diet 35 , 36 , 38 , 39 , while others did not measure motor function. Apart from the study that used resistant starch 34 , constipation and GI-related symptoms were also improved in the three studies that used probiotics, FMT, and Mediterranean diet 35 , 37 , 38 . Other nonmotor symptoms, including anxiety and depression, were improved 34 , 35 , 38 , and inflammatory and PD-related fecal markers decreased 34 , 39 .

Sun et al. provided the only RCT that measured motor, nonmotor, and constipation symptoms, as well as microbiome-related metabolites 38 . Their study evaluated the synergistic effects of probiotics with conventional PD treatment (benserazide and dopamine agonist) by comparing it with a placebo group (placebo with conventional regimen) for 3 months. The probiotics led to increased Bifidobacterium animalis, Ruminococcaceae , and Lachnospira and decreased Lactobacillus fermentum and Klebsiella oxytoca , which might be related to changes in microbiome-related metabolites and neurotransmitter, consequently leading to a beneficial effect in PD patients.

Three included studies focused on AD or mild cognitive impairment, and the study designs were diversified: one single-arm 42 , RCT 41 , and non-RCT 40 . Changes in microbiome were measured by qPCR of designated microbial targets 42 , 16 s rRNA 41 , and histology and urease test of Helicobacter pyroli 40 . Given that the focus of the studies varied, they also modified GM with different approaches, including probiotic supplementation 42 , dietary treatment 41 , and antibiotic treatment 40 . The sample sizes ranged from 17 41 to 61 40 , and the studies lasted for 4 weeks 42 to 2 years 40 .

Leblhuber et al. investigated the effects of probiotic supplementation on immune activation 42 . They found that 4-week probiotic supplementation led to increased Faecalibacterium prausnitzii and altered tryptophan metabolites, yet no significant improvement in cognition was observed. Nagpal et al. 41 was the only cross-over study to compare the effects of Mediterranean-keto diet (MMKD) on AD markers. They found increased abundance of several bacterial families and genera, such as Enterobacteriaceae, Akkermansia , and Slackia , after modified MMKD compared with that after American Heart Association Diet (AHAD), which also altered the SCFA profile and was in association with CSF biomarkers, such as Ab40 and Ab42. Kountouras et al. focused on the impact of eradication of H. pylori in infected AD patients 45 . AD patients were significantly more susceptible to H. pylori infection, and the eradication therapy led to improved cognitive and functional status upon the 2-year clinical endpoint compared with infected patients. These studies suggested that modulating GM may alter AD progression via modifying SCFA and immune profile, leading to reduced AD marker and possibly improved status.

SCFA producers and fecal/serum SCFAs

Several included studies have explored the relationship between SCFA producers or fecal/serum SCFA concentration in NDDs. Of the eight studies that reported changes in SCFA producers or SCFA concentration, six reported improved outcomes, as measured by inflammatory tone, functional outcome, or GI symptoms, yet showed inconsistent changes in SCFA producers and SCFA concentration (Table 4 ).

Tankou et al. and Rusch et al. reported decreased Blautia after probiotic supplementation and Mediterranean diet, respectively 30 , 31 , 37 . Barone et al. reported a stable level of Blautia after multidimensional rehabilitation 29 . Kuai et al. and Cignarella et al. reported increased Blautia after FMT and intermittent fasting 32 , 35 . All of them, except Cignarella et al., reported improved clinical outcomes. Faecalibacterium was reported to have increased significantly in three studies after intermittent fasting, FMT, and probiotic supplementation. Sun et al. reported increased diversity of SGBs involved in SCFA synthesis after probiotic supplementation, in which the acetate and dopamine concentrations increased significantly, whereas the glutamine and tryptophan concentrations decreased 38 . The patients also exhibited improved clinical outcomes.

Meta-analysis: effect of microbiome modulation on clinical outcomes

We pooled all clinical trials to investigate the overall effectiveness of modulating the microbiome on motor symptom progression in NDD. Of the eight studies that assessed motor symptom progression, five (62.5%) reported statistically significantly improvements in motor symptom progression. We pulled all studies that reported motor symptom progression quantitatively before and after intervention and extracted the mean, interquartile range, or SD to calculate the standard mean differences of the studies, resulting in six studies. We did not include Al et al.’s study in meta-analysis, despite the reported EDSS, due to the study’s early termination, which resulted in incomplete and varied treatment conditions in the two groups 22 . Additionally, we excluded the study conducted by Cignarella et al. as it did not report numerical data for EDSS 32 . In the meta-analysis involving six studies with seven intervention groups (n = 249), microbiome-modulating interventions were significantly associated with a lower motor symptom burden (SMD, − 0.57; 95% CI − 0.93 to − 0.21; I 2  = 42%; P  = 0.002; Fig.  2 ). They used different strategies, such as probiotics, antibiotics, FMT, and dietary changes, to alter the gut microbiota 33 , 35 , 36 , 38 , 39 , 40 . Four out of the six studies included patients with PD 30 , 31 , 35 , 36 , 39 , and the remaining involved patients with ALS 33 and AD 40 . The primary outcome measures were UPDRS for PD, ALS Functional Rating Scale-Revised for ALS, and Functional Rating Scale for Symptoms of Dementia for AD. Hegelmaier et al. compared the clinical outcomes of PD patients receiving ovo-lacto diet, with a subgroup receiving additional enema 36 . Considering that the aim of this meta-analysis was to study the pooled effect of microbiome-modulating methods, we compared the clinical outcomes before and after interventions and segregate the enema subgroup. We did not include studies on MS because they did not report numerical results on functional outcomes or were underpowered.

Random-effects meta-analysis of trials on the association between microbiome modulating intervention and clinical outcomes. AD Alzheimer’s disease; ALS amyotrophic lateral sclerosis; IV inverse variance; PD Parkinson’s disease; error bars represent 95% CIs; size of the shaded square indicates study weight; diamond represents pooled standardized mean difference and 95% CI.

Constipation and GI symptoms

Of the four trials that assessed constipation and GI-related symptoms 33 , 34 , 35 , 37 , three studies reported significant improvement compared with the baseline or placebo, whereas the remaining reported insignificant changes in bowel habits. The meta-analysis did not include Hegelmaier et al.’s study because they used the Bristol stool scale, a noncontinuous scale, in measuring constipation syndrome 36 . In the meta-analysis involving three trials (n = 76), microbiome-modulating interventions were insignificantly associated with improving constipation (SMD, − 1.01; 95% CI − 3.01 to 1.00; I 2  = 93%; P  = 0.33; Fig.  3 ). The primary outcome measures included the Constipation Scoring System 34 , Wexner 35 , and GI Symptom Rating Scale 37 constipation scores.

Random-effects meta-analysis of trials on the association between microbiome modulating intervention and constipation symptoms. IV inverse variance; PD Parkinson’s disease; error bars represent 95% CIs; size of the shaded square indicates study weight; diamond represents pooled standardized mean difference and 95% CI.

This study is the first systematic review and meta-analysis to date synthesizing the current evidence from clinical trials that examined the effects of microbiome-modulating interventions on the disease burden of NDDs. Our meta-analysis demonstrated that microbiome-modulating interventions are significantly associated with reduction in motor symptom burden in NDDs, including PD, ALS, and AD. Findings from qualitative synthesis also suggested that microbiome-modulating interventions may reduce inflammation and alleviate GI symptoms, including constipation. Despite the promising effects of microbiome-modulating interventions, the relationships and mechanisms underpinning GM modulation and clinical outcomes remain inconclusive owing to the lack of high-quality clinical trials, the heterogeneity in study design, and the diverse nature of interventions among the included studies.

Microbiome modulation may improve motor symptoms and inflammatory tone

Our meta-analysis revealed that microbiome-modulating interventions can generally lower motor symptom burden in patients with NDDs. In addition, qualitative findings showed that inflammatory tone was generally improved in different NDDs by various microbiome-modulating interventions. NDDs are characterized by chronic inflammation, leaky gut, and decreased production of neuroactive substances, in which the degeneration and loss of neurons lead to long-term motor and nonmotor impairment 45 , 46 . The effect on alleviation on symptom burden might be explained by the restoration of GM to reduce inflammation 47 , re-establish intestinal permeability 22 , 37 , 48 , and enhance neuroactivity through the production of neurotransmitters 49 .

Xiang et al. performed systematic review and meta-analysis on the use of probiotics in AD and PD and suggested that probiotics improve AD possibly through anti-inflammatory pathways, as demonstrated by a decrease in the GSH level after probiotic supplementation 50 . In line with our study findings, microbiome modulation, not limited to probiotic supplementation, was found to reduce inflammation and thereby disease burden, which also applies to other NDDs including MS and ALS 22 , 29 , 30 , 31 , 32 , 33 , 39 .

Restoration of gut dysbiosis can reduce inflammation by multiple pathways, with many of the modulation methods focusing on increasing SCFA-producing bacteria, such as Roseburia spp., Blautia , and Prevotella spp., to increase serum or fecal SCFAs 30 , 31 , 34 , 38 , 42 or on reducing pathogenic bacteria, such as H. pyroli 39 , 40 . SCFAs, including butyrate, propionate, and acetate, exert anti-inflammatory effects by inhibiting the activation of nuclear factor-kappa B and the production of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin-6 51 , 52 . They can also promote the differentiation of regulatory T cells (Tregs) and suppress that of Th17 cells 53 . Apart from indirect homeostasis through SCFAs, some bacteria in the microbiome, such as Bacteroides fragilis , can directly induce Treg differentiation to maintain immune intolerance and prevent autoimmunity.

Along with consistent findings of decreased Lactobacillus in MS, Tankou et al. reported an enrichment of SCFA producers, including Akkermansia , Blautia , and Dorea , in MS patients at baseline . After probiotic supplementation, these SCFA producers decreased, but the expression of proinflammatory genes, such as HLA.DPA1 and MS risk allele HLA.DQA1, also decreased 30 , 31 . Our qualitative finding also showed that no consistency was established in the changes in SCFA producers or SCFA concentration, but clinical outcomes were improved in general (Table 4 ). In particular, while some studies suggested that certain species of Blautia and Dorea were associated with decreased levels of inflammatory markers 54 , 55 , others indicated that they had proinflammatory effects 56 , 57 . The activity of SCFA producers can vary depending on several factors and contribute differently in terms of SCFA production in the gut 58 , 59 . Given the complex nature of GM, additional studies are needed to elucidate other factors that influence its interactions with the immune system, such as its abundance, diversity, metabolites, or co-occurrence with other bacteria.

Microbiome modulation may alleviate constipation and GI symptoms

Constipation is common in NDDs and can affect the quality of life of patients. Constipation can be caused by the accumulation of pathological proteins in the GI tract, such as amyloid beta in AD, α-synuclein in PD, or myelin basic protein in MS, which induce dysfunction of the enteric nervous system (ENS) to affect gut motility and barrier 59 , 60 . Our study found that, qualitatively, microbiome-modulating interventions may also alleviate constipation. A reduction in constipation might be explained by the enhancement in the integrity and permeability of the intestinal barrier through restoring the microbiome 61 , 62 . In addition, SCFAs produced by bacteria can modulate intestinal peristalsis and upregulate the expression of tight junction proteins to strengthen the integrity of the gut barrier 63 . Secretion of neurotransmitters to stimulate ENS may also play a role in constipation 64 . However, available evidence remains inadequate, and the results have not reached statistical significance because of the lack of high-quality studies, which should ideally be blinded RCTs with appropriate sample size and statistical power.

Microbiome-modulating interventions and related GM changes

Although all of the included studies reported some degree of changes in GM composition, no consistent changes in GM were found in relation to the overall improvement in clinical outcomes. The inconsistency might be explained by the heterogeneity in interventions and disease nature, while other systematic reviews also observed diverging GM patterns 65 , 66 . In terms of studies that involved the use of probiotics, Lactobacillus and Bifidobacterium were commonly used, yet they resulted in different GM changes: one reported increased Lactobacillus and Bifidobacterium 30 , 31 , one reported increased B. animalis but decreased Lactobacillus fermentum 38 , and one reported an increase in F. prausnitzii only 42 . These observations are in line with other probiotic systematic reviews 67 . The exact relationship between GM and NDDs remains unknown, and further studies are needed to understand the impact of individual bacteria, the co-occurrence, and the molecular pathway in GM and diseases.

Strengths and limitations

This is the first comprehensive systematic review that examined the effects of a broad spectrum of microbiome-modulating interventions on NDDs, including MS, ALS, PD, and AD. NDDs represent a broad spectrum of disorders, and clinical microbiome trials remain lacking for some diseases, such as the Huntington disease. In addition, most included studies could only be synthesized qualitatively, and heterogeneity regarding the intervention type, outcome measures, and methodological differences was noted. Therefore, we adopted a random-effect model to account for the statistical heterogeneity among studies. Publication bias assessment was not possible given the limited number of available trials for quantitative synthesis, which may also result in minimal but statistically significant overestimation of effects 68 . Most of the included clinical trials had a small sample size and were of moderate risk of bias mainly subject to the selection of reported results. We also included nonrandomized and single-arm clinical trials, which might have a high risk of bias owing to the lack of comparison group. Studies should include a control group when possible and report the complete effect estimate on the basis of the P value, magnitude, or direction of results 69 , such as fold change in microbiome changes. When evaluating microbiome diversity, using multiple indices can provide a comprehensive and nuanced understanding of the microbiota diversity and composition 70 , yet all results of the chosen indices should be listed and interpreted to prevent reporting bias. The findings indicate that the relationship between microbiome-modulating interventions, GM composition, and clinical outcomes of NDDs has been poorly studied and skewed to certain NDDs, namely, PD.

A spectrum of microbiome-modulating components was identified, ranging from probiotic supplement to multidimensional lifestyle interventions consisting of diet modification, mindfulness, and physical activities. Owing to the large variation in methodology across the included studies, definitive conclusions on how microbiome-modulating interventions modulate the GM composition and clinical outcomes and affect the progression of NDDs were impossible to draw.

Most of the studies did not report on significant confounders, such as comorbidities, medication use, and lifestyle, which could affect microbial and clinical outcomes and thus might limit the transferability of our findings. Control conditions also differed between the studies, given that some control interventions comprised AHAD 41 , a placebo group that received conventional treatments 32 , 38 , or a group that received placebo for the first 3 months and probiotics for the next 3 months 33 , restricting the generalizability of our study findings.

Conclusions and implications

Microbiome-modulating interventions are likely to improve symptom burden, possibly through reducing inflammatory tone in NDD patients via increasing SCFA producers and reducing proinflammatory bacteria. However, the exact relationship remains unknown because no consistent changes in GM composition were identified. High-quality evidence of microbiome-modulating interventions for NDDs is still missing. This review underscores the need for rigorous large-scale studies to examine the effects of microbiome-modulating methods on NDDs.

Future clinical trials of microbiome-modulating methods on NDDs should (1) evaluate the changes in GM through microbiome modulation in terms of alpha and beta diversities and specific phylum, family, and species; (2) assess motor and nonmotor clinical outcomes and incorporate objective data in addition to self-reporting questionnaire; (3) account for confounding factors, including diet, age, medication record, lifestyle, and disease progression. Regarding the diverse methodology of existing GM modulation research, a standardized approach to GM evaluation, such as the STORMS checklist 71 , is necessary to understand the complex mechanisms and relationships between GM-modulating interventions, GM composition, and NDDs further.

Data availability

The dataset analyzed in this study is available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to acknowledge the matching and support received from the Research Platform Hong Kong Student Association of Neuroscience (HKSAN) programme. Dr Jojo Kwok served as the mentor for the programme, while Ms. Zara Chui and Ms. Esther Zhang were the elite students matched from the programme.

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Z.C.: Conceptualization (equal); data curation (lead); methodology (equal); writing—original draft preparation (lead); writing—review & editing (equal). L.C.: Conceptualization (equal); methodology (equal); writing— review & editing (equal). E.Z.: methodology (equal); data curation (equal). Suisha Liang: writing—review & editing (equal). E.C.: writing—review & editing (equal). K.L.: writing—review & editing (equal). J.K.: Writing—conceptualization (lead); methodology (equal); writing—review & editing (equal); supervision (lead). H.T.: Writing—review & editing (equal); supervision (equal).

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Chui, Z.S.W., Chan, L.M.L., Zhang, E.W.H. et al. Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis. Sci Rep 14 , 9558 (2024). https://doi.org/10.1038/s41598-024-59250-w

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Artificial Intelligence: The New Frontier in Digital Humanities

Linguistic analysis of human-computer interaction Provisionally Accepted

• 1 University of California, Davis, United States
• 2 Pomona College, United States

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This article reviews recent literature investigating speech variation in production and comprehension during spoken language communication between humans and devices. Human speech patterns toward voice-AI presents a test to our scientific understanding about speech communication and language use. First, work exploring how human-AI interactions are similar to, or different from, human-human interactions in the realm of speech variation is reviewed. In particular, we focus on studies examining how users adapt their speech when resolving linguistic misunderstandings by computers and when accommodating their speech toward devices. Next, we consider work that investigates how top-down factors in the interaction can influence users’ linguistic interpretations of speech produced by technological agents and how the ways in which speech is generated (via text-to-speech synthesis, TTS) and recognized (using automatic speech recognition technology, ASR) has an effect on communication. Throughout this review, we aim to bridge both HCI frameworks and theoretical linguistic models accounting for variation in human speech. We also highlight findings in this growing area that can provide insight to the cognitive and social representations underlying linguistic communication more broadly. Additionally, we touch on the implications of this line of work for addressing major societal issues in speech technology.

Keywords: Speech variation, human-computer interaction, speech production, Speech Perception, sociolinguistics

Received: 09 Feb 2024; Accepted: 24 Apr 2024.

Copyright: © 2024 Zellou and Holliday. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Georgia Zellou, University of California, Davis, Davis, United States

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• Published: 19 April 2024

Effects of Chronic Static Stretching on Maximal Strength and Muscle Hypertrophy: A Systematic Review and Meta-Analysis with Meta-Regression

• Konstantin Warneke   ORCID: orcid.org/0000-0003-4964-2867 1 , 7 ,
• Lars Hubertus Lohmann 2 ,
• David G. Behm 3 ,
• Klaus Wirth 4 ,
• Michael Keiner 5 ,
• Stephan Schiemann 6 &
• Jan Wilke 7  

Sports Medicine - Open volume  10 , Article number:  45 ( 2024 ) Cite this article

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Increases in maximal strength and muscle volume represent central aims of training interventions. Recent research suggested that the chronic application of stretch may be effective in inducing hypertrophy. The present systematic review therefore aimed to syntheisize the evidence on changes of strength and muscle volume following chronic static stretching.

Three data bases were sceened to conduct a systematic review with meta-analysis. Studies using randomized, controlled trials with longitudinal (≥ 2 weeks) design, investigating strength and muscle volume following static stretching in humans, were included. Study quality was rated by two examiners using the PEDro scale.

A total of 42 studies with 1318 cumulative participants were identified. Meta-analyses using robust variance estimation showed small stretch-mediated maximal strength increases (d = 0.30 p  < 0.001) with stretching duration and intervention time as significant moderators. Including all studies, stretching induced small magnitude, but significant hypertrophy effects (d = 0.20). Longer stretching durations and intervention periods as well as higher training frequencies revealed small (d = 0.26–0.28), but significant effects ( p  < 0.001–0.005), while lower dosage did not reach the level of significance ( p  = 0.13–0.39).

Conclusions

While of minor effectiveness, chronic static stretching represents a possible alternative to resistance training when aiming to improve strength and increase muscle size. As a dose-response relationship may exist, higher stretch durations and frequencies as well as long program durations should be further elaborated.

• While animal research consistently showed chronic stretch-mediated hypertrophy and strength increases, literature in humans draws an inconclusive picture, possibly due to lack of comparability of stretching parameters, such as duration and frequency.

• Our systematic review is the first that included studies using comparable stretching durations of up to two hours in humans, which showed small magnitude maximal strength increases and muscle hypertrophy.

• Even though less effective, high volume stretching might provide a sufficient alternative to strength training when aiming to induce muscle hypertrophy and strength increases. It must be noted that comparatively high training effort is opposed by comparatively small adaptations, suggesting a preference for the more efficient strength training if applicable.

Stretch training is commonly used to achieve improvements in flexibility [ 1 , 2 ], with widespread applications in sports conditioning and orthopedic physical therapy [ 3 , 4 ]. While it was widely accepted in the 1980s that static stretching should be included in warm-up routines [ 5 , 6 , 7 ], current evidence questions the implementation of (static) stretching during warm-up due to its detrimental impact on subsequent sports performance [ 8 , 9 , 10 ].

Despite adverse acute effects, static stretching may be beneficial for athletes if performed in the long-term [ 11 , 12 ]. A recent systematic review with meta-analysis evaluating animal studies found chronic stretching of the anterior latissimus dorsi in chickens and quails (for up to 24 h per day, seven days per week) substantially increased muscle mass by up to 319% (d = 8.5) due to increases in muscle cross-sectional area (up to 142%; d = 7.9). Besides these structural changes, gains in maximal strength (up to 95%; d = 12.4) [ 13 ] were observed. Interestingly, investigations aiming to translate animals’ muscle adaptions to humans were requested as early as in 1983: “Thirty minutes of stretching per day is certainly within normal physiological limits, and as a result may be applied to human muscle with hopes that similar adaptations would occur” [ 14 ].

Stretching effects on hypertrophy [ 15 , 16 ] and strength [ 17 , 18 ] in humans were previously reviewed pointing out only small strength increases (under dynamic conditions [ 17 ]) while muscle hypertrophy was exclusively evident using high intensity stretching [ 16 ]. However, even though recent reviews were performed in 2023, they missed inclusion of new literature that – for the first time – applied static stretching with continuous stretching durations up to two hours [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], which might lead to an under- or overestimation of the current evidence.

Consequently, the aim of this systematic review with meta-analysis was to investigate changes in muscle size and maximum strength following chronic static stretching interventions in humans. We hypothesized that stretching programs, performed in the long-term, would lead to increases in both outcomes. Based on findings from animal research, we assumed that previous stretching volume was not sufficient. Therefore, we hypothesized longer stretching session durations and intervention periods, as well as high training frequencies would trigger improvements, while lower durations/frequencies would not elicit relevant changes.

A systematic review and meta-analysis using robust variance estimation was performed adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The study was registered in the PROSPERO database (CRD42023411225).

Literature Search

Two independent investigators (KoW & LHL) conducted a systematic literature search using MEDLINE/PubMed, Web of Science and SPORTDiscus (March 2023) and updated in January 2024. The following inclusion criteria were applied: (1) randomized, controlled study design; (2) static stretching intervention with a duration of at least two weeks, performed in humans; (3) measurement of (a) maximal strength or related parameters such as active peak torque and/or (b) markers of muscle size (i.e., cross-sectional area, muscle thickness). Studies assessing acute effects, combining static stretch training with other (active) training protocols such as resistance training or neuromuscular facilitation, or including patients were excluded. The search terms (Online Supplemental Material) were created based on the requirements of each database. As an example, the terms for PubMed were as follows:

((stretch*) AND (performance OR strength OR 1RM OR force OR MVC OR (maxim* AND “voluntary contraction”) OR hypertrophy OR “muscle cross-sectional area” OR CSA OR “muscle thickness” OR “muscle mass” OR “muscle volume”) NOT (acute OR postural OR pnf OR “proprioceptive neuromuscular facilitation” OR “stretch shortening”)).

In addition to database searches, the reference lists of all included studies were screened for further eligible articles [ 27 ].

Methodological Study Quality and Risk of Bias

The assessment of study quality was performed by two independent investigators (KW1 & LHL) using the PEDro scale for randomized, controlled trials [ 28 , 29 ]. If consensus could not be reached, a third rater casting the decisive vote was consulted (MK). The PEDro scale (Table A in Supplemental Material) was used in previous reviews with meta-analysis on exercise and exercise therapy [ 30 , 31 ].

Risk of publication bias was examined using visual inspection of funnel plots [ 32 ], which were created using the method of Fernandez-Castilla et al. [ 33 ]. Additionally, Egger’s regression tests incorporating robust variance estimation for funnel plot asymmetry were applied [ 34 ]. The certainty about the evidence was rated as very low, low, moderate or high using the criteria proposed by the GRADE working group [ 35 ]. Generally, the quality of evidence of randomized trials is considered high and thereafter adjusted within the GRADE framework. In case of limitations in study design or execution, inconsistency of results, indirectness of evidence, imprecision or publication bias, one point is subtracted for each weakness. Conversely, large-magnitude effects or a dose-response gradient each lead to addition of one point to the quality of evidence rating.

Data Processing and Statistics

The means (M) and standard deviations (SD) from pre- and post-intervention tests were extracted for all parameters and study arms (stretching and inactive control). In case of missing data, the authors of the primary studies were contacted. Changes from pre to post were computed as M (posttest) – M (pretest) and standard deviations were pooled as

To account for multiple within-study outcome dependency with unknown origin of covariances, meta-analytical calculation was performed using robust variance estimation [ 36 ]. Standardized mean differences (SMD) and 95% confidence intervals (CI) for maximal strength capacity and muscle size changes (including both muscle thickness and muscle cross-sectional area) were pooled from fitting parameters from all included studies. We used R (R Foundation for Statistical Computing, Vienna, Austria) with the robumeta, version 2.0 [ 36 ] and metapackages. Obtained effect sizes (ES) were interpreted as 0 ≤ d < 0.2 trivial, 0.2 ≤ d < 0.5 small, 0.5 ≤ d < 0.8 moderate, or d ≥ 0.8 large [ 37 ], while τ² was used to explore study outcome heterogeneity, with classifications equal to effect sizes.

Meta-regression was performed using the robumeta package for dependent study outcomes, as described by Fisher & Tipton [ 36 ]. Furthermore, to quantify the influence of quantifable outcome moderators (stretching duration, intervention period and training frequency) when aiming to enhance maximal strength and muscle size, sub-analyses were performed for three variables: intervention duration, session duration and exercise frequency. For moderating variables (duration, intervention period and training frequency), we used the median-split for cut-off determination (intervention duration: small: <6 weeks vs. high: ≥ 6 weeks, frequency: low: <5 sessions vs. high: ≥5 sessions, stretching duration: short: <15 min vs. long: ≥15 min. To test for significant differences in mean effect size of sub-groups, the Welsh test was performed due to violation of normal distribution. If several study effects were presented mean effects for each study were calculated to account for within-study dependency in effect size comparsions.

Search Results

Figure 1 displays the flow of the literature search.

Flow chart of literature search

Collectively, the queries in the three databases returned 10,427 hits. After application of inclusion and exclusion criteria, a total of 42 eligible studies with 1318 participants were identified. Among these, 36 studies with 85 ES [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] investigated strength parameters. Nineteen (19) studies [ 21 , 22 , 23 , 24 , 26 , 39 , 66 , 67 , 68 , 51 , 52 , 55 , 57 , 58 , 69 , 70 , 71 , 63 , 65 ] with 45 ES examined markers of muscle size.

Methodological Quality, Risk of Bias and Quality of Evidence

Per average, the methodological quality of the included studies was rated as fair [ 72 ] (mean 4.17 ± 1.4 out of 10 points; range 2 to 8 points; see Table A in Supplemental Material). For both outcomes (muscle volume and maximal strength), the quality of evidence was downgraded by 2 levels (high to low) due to high risk of bias (limitations in study quality: fair PEDro score and heterogeneity in study designs). In case of the sub-analyses for session and intervention duration (outcomes of maximal strength), the quality of evidence was upgraded by one level due to moderate to strong associations (low to moderate effect sizes, mostly on same side effect).

Quantitative Synthesis

Table 1 provides the study characteristics of included articles, while Table 2 summarizes the quantitative analysis results for overall and different subgroups.

Maximal Strength Capacit y

Static stretching showed a small positive effect on maximal strength ( d  = 0.30, p  < 0.001, 95% CI 0.14 to 0.46, τ²=0.01, 36 studies with 85 ES, Table  1 ). The certainty about the evidence is low. Meta-regression showed stretching duration positively influenced maximal strength ( p  = 0.04, estimate: 0.005), while a tendency was reported for intervention period ( p  = 0.06, estimate: 0.06). No significant result could be found for training frequency ( p  = 0.64).

Accordingly, higher stretch durations (≥ 15 min) induced small strength increases ( d  = 0.45, p  < 0.001, 95% CI 0.29 to 0.62, τ²=0.0, 14 studies, 30 ES, Fig.  2 ) which were opposed to shorter durations (< 15 min) which revealed a small-magnitude, not significant effect ( d  = 0.21, p  = 0.06, 95% CI -0.06 to 0.44, 22 studies, 55 ES, Fig.  3 ) with a significant mean ES difference ( p  = 0.01). The certainty about the evidence is moderate.

Illustrates the meta-analytical results of long stretching durations. Legend: 1RM = one repetition maximum, EL = extended leg, FL = flexed leg

Illustrates the meta-analytical results of short stretching durations. Legend: HI = high intensity group, LI = low intensity group, 1RM = one repetition maximum

Similar to stretch duration, longer program durations (> 6 weeks) achieved small strength increases ( d  = 0.36, p  = 0.003, 95%CI 0.13 to 0.59, τ²=0.04, 24 studies with 51 ES) while shorter durations yielded only trivial improvements ( d  = 0.16, p  = 0.006, 95%CI 0.05 to 0.26, τ²=0.0, 12 studies, 34 ES), with a significantly higher mean effect for longer intervention periods ( p  = 0.03). The certainty about the evidence is moderate. High training frequencies (more than five stretching sessions per week) led to small-magnitude strength increases ( d  = 0.32, p  = 0.025, 95% CI 0.05 to 0.6, τ²=0.04, 16 studies, 40 ES). Less than five sessions per week yielded only a small effect size ( d  = 0.26, p  < 0.001, 95%CI 0.14 to 0.38, τ²=0, 20 studies with 45 ES), without a significant difference in group mean effects ( p  = 0.39). The certainty about the evidence is low.

• Hypertrophy

For hypertrophy, a trivial positive effect of stretching was found ( d  = 0.20, p  = 0.003, 95% CI 0.08 to 0.32, τ²=0.0, 19 studies, 45 ES) (see Fig.  4 ). The certainty about the evidence is low. While the meta regression ( p  = 0.23–0.88) revealed no significant influence of any included moderator, long-duration stretching (≥ 15 min) had a small effect size ( d  = 0.28, p  =  0.005, 95% CI 0.12 to 0.44, τ²=0.0, 7 studies, 17 ES) without a significant difference compared to shorter durations ( p  = 0.29) that, in turn, failed reaching a significant effect ( d  = 0.13, p  = 0.14, 95%CI -0.05 to 0.30, τ²=0.0, 12 studies with 28 ES). Similarly, studies that performed stretching for more than 6 weeks revealed d  = 0.26, p  < 0.001 extracted from 16 studies with 35 ES, while shorter training periods failed to reach the level of significance ( d = -0.05, p  = 0.13 from 3 studies and 10 ES) with higher effects for longer periods ( p  = 0.006). If stretching was performed more than 5 times per week, there were significant small magnitude increases in muscle size ( d  = 0.27, p  = 0.002, from 11 studies with 28 ES), opposed by no significant effect for lower training frequencies ( d  = 0.09, p  = 0.39), without a significantly higher mean effect size for higher frequencies ( p  = 0.31). The certainty about the evidence is low for all effects.

Forest plot for all included studies on stretch-mediated hypertrophy

Publication Bias

Visual inspection of funnel plots (Fig.  5 ) revealed no indication of a publication bias for maximal strength as well as for muscle volume. Consistently, for both outcomes, Egger’s regression tests showed no publication bias p  = 0.23–0.31.

Shows funnel plots for visual publication bias inspection, with ( a ) for maximal strength studies and ( b ) for hypertrophy studies. Plot size illustrates the number of outcomes in the respective study that were pooled and weighted in the meta-analytical calculation

In accordance with previous research, the present systematic review found chronic static stretching to increase (a) maximum strength [ 11 , 12 , 17 , 18 ], and (b) muscle size [ 16 ]. With stretching duration and a tendency for intervention time as moderating training parameters for maximal strength, our results indicate longer stretching durations to be of superior effectiveness. While overall stretch-induced hypertrophy showed small effects (d = 0.2), these effects seem attributable to stretching durations of ≥ 15 min, intervention periods of > 6 weeks and training frequencies of ≥ 5 times as lower dosage did not reach the level of significance in subgroup calculations ( p  = 0.14–0.39). The possible necessity of high stretching volumes with regard to improvements in strength and muscle volume is in line with results from animal studies [ 73 , 74 ].

As pointed out, early evidence had mostly suggested that stretching does not modify morphological and functional muscle parameters in humans [ 11 , 12 , 15 ]. However, this assumption was based on a lack of studies using high to very high stretch durations. Even the most recent review of Arntz et al. [ 18 ] did not include long duration studies [ 19 , 20 , 21 , 25 , 26 , 75 , 76 ], while Panidi et al. [ 16 ] included only one long-duration study [ 26 ]. Since animal research indicated a potential dose-reponse relationship [ 14 , 77 ], a meta-regression was performed that confirmed stretching duration to significantly moderate strength adaptations. While in contrast, the regression did not reveal such a relationship for muscle hypertrophy, significant muscle size enhancements were only obtained in higher dosage in subgroup analyses (≥ 15 min stretching, ≥6 weeks intervention period, ≥5x stretching per week). Compared to animals with reported muscle mass increases of up to 300% [ 78 ], human hypertrophy effects must be considered small. These differences could be attributed to diverse factors. Compared to animals, human muscle protein synthesis is slower [ 79 , 80 , 81 ]. This may be one explanation for a lack of hypertrophy in response to 30 min of stretch reported by Yahata [ 65 ]. Nevertheless, by using stretching durations of accumulated 15 min per session, Wohlann et al. [ 20 ] obtained significant muscle hypertrophy. There were differences in the intervened muscle groups, Wohlann used 4x weekly pectoralis stretching, while calf muscle stretching performed by Yahata and colleagues [ 65 ] was applied only twice per week. The potential role of training frequency is supported by consistent hypertrophy effects in all Warneke et al. studies [ 23 , 24 , 26 ], who used daily stretching. The results of the meta-analysis partly confirm this assumption, although meta regression did not reach the level of significance for both, maximal strength and hypertrophy. However, subgroup analysis for hypertrophy showed only more frequent training application to produce significant effects, while no significant influence of frequency was observed for strength increases.

Several mechanisms could explain the stretch-induced increases in muscle size or strength. First and foremost, it may be speculated that time under tension is not only paramount for gains in muscle volume following resistance training [ 82 ] but also following stretching [ 83 ], which would be in agreement with our results, showing the stretching duration to be important for strength (meta regression: p  = 0.038), but also for hypertrophy, as only with ≥ 15 min muscle size did increases occur. Accordingly, the literature shows high mechanical tension imposed on the sarcomere could trigger protein synthesis [ 84 , 85 ]. In quails and chickens, progressive stretching induced fast hypertrophy alongside serial sarcomereogenesis during the first days of the intervention [ 78 ]. However, when the stretching stimulus remained unmodified during such a program, initial increases in muscle cross-sectional area started to disappear [ 86 ]. Ashmore [ 87 ] suggested that the mechanical tension caused by stretching would lead to high stresses and compensatory adaptations in the sarcomere. It has, furthermore, been hypothesized that an increased total amount of sarcomeres reduces tension and with this stress on the individual sarcomere [ 86 ]. Thus, to increase training intensity and to ensure continuously strong tensioning of the sarcomere, the stretching stimulus needs to be re-adjusted. Indeed, Antonio & Gonyea [ 78 ] achieved the highest gains in muscle mass and hypertrophy by increasing the stretch intensity, starting with 10% of the body weight up to 35% after 5 weeks of chronic stretch in quails.

Another theory postulates that chronic stretch creates hypoxic conditions which are similar to those during blood flow restriction. Reducing arterial perfusion has been demonstrated to increase lactate levels, growth hormone concentrations, and inflammatory cytokines such as interleukin-6 [ 88 , 89 ]. Such metabolic milieu may represent a potent stimulus for mTOR signaling [ 90 , 91 , 92 ]. Interestingly, Jessee et al. [ 93 ] showed that blood flow restriction induces hypertrophy, however, it seems of minor relevance for maximum strength increases. Hotta et al. [ 94 ] observed acute decreases of blood flow during 30 min of stretching in animals. Studies measuring the metabolic muscle response to stretching would thus be warranted in order to further delineate the potential relevance of the abovementioned factors.

In sum, irrespective of initial processes, muscle hypertrophy requires an increase in muscle protein synthesis. Suzuki & Takeda [ 95 ] and Kremer [ 96 ] described the activation of stretch-activated channels and thus, the stimulation of the mTOR/p70S6K/PI3K pathway [ 97 , 98 , 99 ]. The literature emphasizes the importance of mechanical tension (e.g., through stretching) to trigger anabolic signaling pathways, with the stimulation of protein synthesis [ 100 , 101 , 102 , 103 ] as an underlying mechanism of hypertrophy (and maximal strength) [ 104 , 105 , 106 ]. Van der Pjil et al. [ 107 , 108 ] indicated the relevance of titin unfolding in hypertrophy (in parallel and longitudinal), supporting the hypothesis of high intensities [ 109 ]. Conversely, Fowles et al. [ 110 ] were not able to show acute increases in protein synthesis after 33-minutes of stretching in humans, although significant increases in protein synthesis rates had been reported in animals [ 100 , 102 , 103 , 111 ]. The stronger response in animals could hence be explained by a higher protein synthesis rate [ 80 , 81 ].

With regard to the increases in maximum strength, it may be expected that the increases in muscle volume would drive the strength gains. This would require hypertrophy to precede enhanced strength. However, no study has investigated the temporal association of both factors. In addition, effect sizes were trivial to small for muscle volume but moderate for strength. Another theory may attribute the improvements to neural adaptations [ 112 , 113 ]. The studies by Warneke et al. [ 19 , 26 ] and Nelson et al. [ 60 ], on the one hand, provide support for this assumption as they detected strength increases in the non-stretched contralateral leg. However, on the other hand, Holly et al. [ 114 ] and Barnett et al. [ 115 ] showed no significant increase in EMG activity during stretching in animals. Furthermore, Sola et al. [ 116 ] found stretch-mediated hypertrophy in denervated muscles, indicating a minor role of neural aspects. Therefore, to clarify the role of neural aspects in stretch-mediated adaptations, further research seems necessary.

Even though muscle hypertrophy only occurs using higher dosage stretching, our work has significant clinical implications. In general, stretching may represent an alternative to conventional resistance training interventions inducing muscle size- and strength increases. Nevertheless, several aspects must be considered. While Currier et al. [ 117 ] showed moderate to large magnitude maximal strength and muscle size increases of ES = 0.51 and ES = 1.60, respectively, when using resistance training, the present study’s small magnitude effect sizes of ES = 0.28 and ES = 0.45, respectively, showed that even long stretching durations were less effective. Assuming about one hour of stretching on one isolated muscle to achieve meaningful muscle hypertrophy [ 83 ] seems, on the one hand, of limited practical relevance [ 85 ]. On the other hand, passively induced mechanical tension via stretch training could be included into daily life, with for example using splints/ortheses during sitting in the office or while watching television [ 118 ]. A further benefit might be the potential applicability for people lacking motivation or ability to perform resistance training (e.g., patients with unstable cardiovascular diseases), if heavy resistance training is contraindicated, or after muscle, ligament or bone injuries leading to prolonged times of immobilization. Thus, (probably only) for conditioned populations, stretching could provide a sufficient alternative, especially since no training supervision is necessary to ensure safe exercise execution. Although stretching could be a valuable training intervention, it should only temporarily substitute or, even better, supplement classical training regimes. This is of importance because although stretching has been shown to be beneficial for cardiovascular health [ 119 ], it may not add as efficiently to the recommended levels of physical activity (e.g. by the World Health Organization, 150 min of moderate or 75 min of vigorous activity per week) as other activities such as walking, running, team sports, or resistance training.

Several aspects call for further research. Even though significant stretch-induced muscle hypertrophy in response to stretching durations of ≥ 15 min was identified, this was based on only 7 studies with a range of 3 × 5 min to one hour of stretching, with the highest effects originating from one research group [ 19 , 20 , 21 , 23 , 24 , 25 , 26 , 76 ]. Thus, further studies are requested to confirm or disconfirm the results. Furthermore, all long-lasting stretch interventions (more than one hour) were performed with high stretching frequency and intervention periods (≥ 6 weeks), increases in maximal strength and muscle volume cannot be clearly ascribed to one of these parameters. Further studies should hence examine long-lasting stretch interventions of < 6 weeks and/or ≤ 5 sessions per week. Moreover, the role of stretch intensity merits further investigation. Reporting stretch intensity using individual pain perception seems of questionable validity [ 120 ]. However, it is well known from strength training that training intensity seems to be of crucial importance for adaptations, especially with regard to maximum strength increases [ 121 ]. Considering the importance of titin unfolding, which is assumed to occur exclusively in maximally stretched sarcomeres, reaching high degrees of stretch could be hypothesized to be of paramount importance [ 109 , 122 ].

Despite some plausible theories [ 83 ], the underlying mechanisms remain speculative. While many physiological parameters were assessed in animals, no studies examined signaling pathways and possible alterations of protein synthesis in humans. Furthermore, research has almost exclusively focused on skeletal muscle. Interestingly, it has been shown that the connective tissue can exert significant force transmission effects [ 123 ]. Therefore, it may be prudent for future trials to consider multiple tissues.

Some increases in the examined parameters were surprisingly high in studies included in our review. Nelson et al. [ 60 ] reported an improvement in maximal strength of 29% (d = 1.48) in the stretched leg and a gain of about 11% (d = 0.46) in the contralateral control leg following 4 × 30 s stretching three times per week for ten weeks. Mizuno [ 55 ] found increases of 24% using static stretching three times per week for eight weeks, while Panidi et al. [ 69 ] detected hypertrophy effects of up to 23%. When these short duration stretching results are compared to those from strength training [ 124 ], the listed stretch-induced adaptations seem unreasonably high, even though participants are partially classified untrained to recreationally active. Against this background, it will be of interest to further identify moderator variables determining strong and weak stretch responders.

Lastly, testing for significant differences of mean effects to provide a valuable statement of subgroup differences was performed using the Welsh test. This testing procedure must be considered a supplementation of the main statistics and must be interpreted with caution, as no specific pooling for dependent outcomes was possible. If one study provided multiple outcomes, effect size means were calculated, meaning each study corresponded to one outcome, which reduced this limitation.

The present systematic review provides low- to moderate-certainty evidence that chronic static stretching increases maximum strength and muscle size. While the overall effects are small if existent, comparatively high effort seems necessary with longer stretching- and intervention periods (≥ 15 min, ≥ 6 weeks) and greater frequencies (≥ 5x/week) seem particularly effective. The exact physiological mechanisms causing potential effects remain a matter of debate. Nevertheless, even though less effective compared to resistance training, high volume stretching might provide a valuable alternative under special circumstances, e.g., if traditional resistance training is contraindicated.

Data Availability

Data can be provided on reasonable request. Supplemental materal associated with this article can be found in the online version.

Abbreviations

confidence interval

effect size

standard deviation

standardized mean differences

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Konstantin Warneke

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KoW wrote the first draft, contributed to the screening of studies, performed the meta-analytic procedure with the help of JW, and performed the graphical illustration with the help of LHL. LHL contributed to study screening, assisted in the writing and helped with the graphical illustration. JW supervised the project, included critical feedback and advised on statistical procedures. MK, KlW, SS and AK included their critical feedback and expertise in the fields to the manuscript. All authors contributed to the manuscript and discussed the final version.

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Warneke, K., Lohmann, L.H., Behm, D.G. et al. Effects of Chronic Static Stretching on Maximal Strength and Muscle Hypertrophy: A Systematic Review and Meta-Analysis with Meta-Regression. Sports Med - Open 10 , 45 (2024). https://doi.org/10.1186/s40798-024-00706-8

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Directional synthesis of aviation-, diesel-, and gasoline range hydrocarbon fuels by catalytic transformations of biomass components: An overview

• Dutta, Saikat
• Madav, Vasudeva
• Joshi, Girdhar
• Naik, Nirmala
• Kumar, Sanjay

Selective conversion of heavily oxygenated biomolecules into hydrocarbon-based liquid transportation fuels with stipulated structural traits is of academic and industrial significance. This work provides an overview of producing fuel precursors from biomass components and their catalytic transformation into aviation-, diesel-, and gasoline-range hydrocarbon fuels (HCFs). Strategic applications of various organic transformations for the molecular design of targeted products have been rationalized. Construction and alteration of the carbon skeletal system in the fuel candidates via chemical-catalytic transformations have been highlighted. Emphasis has also been given to the process conditions and details of the catalysts employed in these processes. Critical analysis of the literature data presented in this review will assist the researchers in developing more proficient processes for the biorenewable production of drop-in HCFs.

• Aviation fuels;
• Biorefinery;
• Biogasoline;
• Hydrocarbon synthesis;
• Angelica lactone;
• Angelica lactone dimer;
• Angelica lactone trimer;
• Angelica lactone tetramer;
• Aqueous phase reforming;
• Benzene-toluene-xylene;
• Catalytic decarbonylation;
• Catalytic decarboxylation;
• Cyclohexanone;
• Cyclopentanone;
• Decarboxylative ketonization;
• 5-Dimethylfuran;
• Ethyl levulinate;
• Free fatty acid;
• Free fatty ester;
• Furfural acetone;
• Furfuryl alcohol;
• 6-(2-Furyl)-4-methylhexa-3;
• 5-dien-2one;
• Hydrocarbon;
• Hydrocarbon fuels;
• Hydrodeoxygenation;
• Hydroxyalkylation and alkylation;
• 5-Bis[(5-Hydroxlmethyl)-2-furanyl]-1;
• 4-pentadien-3-one;
• 5-(Hydroxymethyl)furfural;
• 4-[5-(Hydroxymethyl)-2-furanyl]-3-buten-2-one;
• Ionic liquid;
• Levulinic acid;
• 2-Methylfuran;
• 5-Methylfurfural;
• 8-Nonanetrione;
• Pantanoic acid;
• Techno-economic analysis;
• Turnover number;
• Triglyceride;
• γ-Valerolactone;
• Valeric acid