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What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

• Quick Run-through
• Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and scholarly context
• Develop a theoretical framework and methodology for your research
• Position yourself in relation to other researchers and theorists
• Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

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Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

• Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
• Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, 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 transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarise yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

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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.

Libraries | Research Guides

Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

• Next: Planning the Review >>
• Last Updated: May 2, 2024 10:39 AM
• URL: https://libguides.northwestern.edu/literaturereviews

• UConn Library
• Literature Review: The What, Why and How-to Guide
• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

• Getting Started
• How to Pick a Topic
• Strategies to Find Sources
• Evaluating Sources & Lit. Reviews
• Tips for Writing Literature Reviews
• Writing Literature Review: Useful Sites
• Citation Resources
• Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
• << Previous: Getting Started
• Next: How to Pick a Topic >>
• Last Updated: Sep 21, 2022 2:16 PM
• URL: https://guides.lib.uconn.edu/literaturereview

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• 04 December 2020
• Correction 09 December 2020

How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

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Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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doi: https://doi.org/10.1038/d41586-020-03422-x

Interviews have been edited for length and clarity.

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Correction 09 December 2020 : An earlier version of the tables in this article included some incorrect details about the programs Zotero, Endnote and Manubot. These have now been corrected.

Hsing, I.-M., Xu, Y. & Zhao, W. Electroanalysis 19 , 755–768 (2007).

Article   Google Scholar  

Ledesma, H. A. et al. Nature Nanotechnol. 14 , 645–657 (2019).

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Brahlek, M., Koirala, N., Bansal, N. & Oh, S. Solid State Commun. 215–216 , 54–62 (2015).

Choi, Y. & Lee, S. Y. Nature Rev. Chem . https://doi.org/10.1038/s41570-020-00221-w (2020).

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Literature Reviews

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What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

• Provide a comprehensive and updated review of the literature;
• Explain why this review has taken place;
• Articulate a position or hypothesis;
• Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

• Demonstrate how a study fills a gap in research
• Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

• Organizes or describes a topic
• Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

• It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
• It may be too focused. Some niche studies may miss the bigger picture.
• It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
• It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

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For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

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• Steps in Conducting a Literature Review

What is a literature review?

A literature review is an integrated analysis -- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.  That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

A literature review may be a stand alone work or the introduction to a larger research paper, depending on the assignment.  Rely heavily on the guidelines your instructor has given you.

Why is it important?

A literature review is important because it:

• Explains the background of research on a topic.
• Demonstrates why a topic is significant to a subject area.
• Discovers relationships between research studies/ideas.
• Identifies major themes, concepts, and researchers on a topic.
• Identifies critical gaps and points of disagreement.
• Discusses further research questions that logically come out of the previous studies.

APA7 Style resources

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1. Choose a topic. Define your research question.

Your literature review should be guided by your central research question.  The literature represents background and research developments related to a specific research question, interpreted and analyzed by you in a synthesized way.

• Make sure your research question is not too broad or too narrow.  Is it manageable?
• Begin writing down terms that are related to your question. These will be useful for searches later.
• If you have the opportunity, discuss your topic with your professor and your class mates.

2. Decide on the scope of your review

How many studies do you need to look at? How comprehensive should it be? How many years should it cover? 

• This may depend on your assignment.  How many sources does the assignment require?

3. Select the databases you will use to conduct your searches.

Make a list of the databases you will search. 

Where to find databases:

• use the tabs on this guide
• Find other databases in the Nursing Information Resources web page
• More on the Medical Library web page
• ... and more on the Yale University Library web page

4. Conduct your searches to find the evidence. Keep track of your searches.

• Use the key words in your question, as well as synonyms for those words, as terms in your search. Use the database tutorials for help.
• Save the searches in the databases. This saves time when you want to redo, or modify, the searches. It is also helpful to use as a guide is the searches are not finding any useful results.
• Review the abstracts of research studies carefully. This will save you time.
• Use the bibliographies and references of research studies you find to locate others.
• Check with your professor, or a subject expert in the field, if you are missing any key works in the field.
• Ask your librarian for help at any time.
• Use a citation manager, such as EndNote as the repository for your citations. See the EndNote tutorials for help.

Review the literature

Some questions to help you analyze the research:

• What was the research question of the study you are reviewing? What were the authors trying to discover?
• Was the research funded by a source that could influence the findings?
• What were the research methodologies? Analyze its literature review, the samples and variables used, the results, and the conclusions.
• Does the research seem to be complete? Could it have been conducted more soundly? What further questions does it raise?
• If there are conflicting studies, why do you think that is?
• How are the authors viewed in the field? Has this study been cited? If so, how has it been analyzed?

Tips: 

• Review the abstracts carefully.  
• Keep careful notes so that you may track your thought processes during the research process.
• Create a matrix of the studies for easy analysis, and synthesis, across all of the studies.
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What Is A Literature Review?

A plain-language explainer (with examples).

By:  Derek Jansen (MBA) & Kerryn Warren (PhD) | June 2020 (Updated May 2023)

If you’re faced with writing a dissertation or thesis, chances are you’ve encountered the term “literature review” . If you’re on this page, you’re probably not 100% what the literature review is all about. The good news is that you’ve come to the right place.

Literature Review 101

• What (exactly) is a literature review
• What’s the purpose of the literature review chapter
• How to find high-quality resources
• How to structure your literature review chapter
• Example of an actual literature review

What is a literature review?

The word “literature review” can refer to two related things that are part of the broader literature review process. The first is the task of  reviewing the literature  – i.e. sourcing and reading through the existing research relating to your research topic. The second is the  actual chapter  that you write up in your dissertation, thesis or research project. Let’s look at each of them:

Reviewing the literature

The first step of any literature review is to hunt down and  read through the existing research  that’s relevant to your research topic. To do this, you’ll use a combination of tools (we’ll discuss some of these later) to find journal articles, books, ebooks, research reports, dissertations, theses and any other credible sources of information that relate to your topic. You’ll then  summarise and catalogue these  for easy reference when you write up your literature review chapter. 

The literature review chapter

The second step of the literature review is to write the actual literature review chapter (this is usually the second chapter in a typical dissertation or thesis structure ). At the simplest level, the literature review chapter is an  overview of the key literature  that’s relevant to your research topic. This chapter should provide a smooth-flowing discussion of what research has already been done, what is known, what is unknown and what is contested in relation to your research topic. So, you can think of it as an  integrated review of the state of knowledge  around your research topic. 

What’s the purpose of a literature review?

The literature review chapter has a few important functions within your dissertation, thesis or research project. Let’s take a look at these:

Purpose #1 – Demonstrate your topic knowledge

The first function of the literature review chapter is, quite simply, to show the reader (or marker) that you  know what you’re talking about . In other words, a good literature review chapter demonstrates that you’ve read the relevant existing research and understand what’s going on – who’s said what, what’s agreed upon, disagreed upon and so on. This needs to be  more than just a summary  of who said what – it needs to integrate the existing research to  show how it all fits together  and what’s missing (which leads us to purpose #2, next). 

Purpose #2 – Reveal the research gap that you’ll fill

The second function of the literature review chapter is to  show what’s currently missing  from the existing research, to lay the foundation for your own research topic. In other words, your literature review chapter needs to show that there are currently “missing pieces” in terms of the bigger puzzle, and that  your study will fill one of those research gaps . By doing this, you are showing that your research topic is original and will help contribute to the body of knowledge. In other words, the literature review helps justify your research topic.  

Purpose #3 – Lay the foundation for your conceptual framework

The third function of the literature review is to form the  basis for a conceptual framework . Not every research topic will necessarily have a conceptual framework, but if your topic does require one, it needs to be rooted in your literature review. 

For example, let’s say your research aims to identify the drivers of a certain outcome – the factors which contribute to burnout in office workers. In this case, you’d likely develop a conceptual framework which details the potential factors (e.g. long hours, excessive stress, etc), as well as the outcome (burnout). Those factors would need to emerge from the literature review chapter – they can’t just come from your gut! 

So, in this case, the literature review chapter would uncover each of the potential factors (based on previous studies about burnout), which would then be modelled into a framework. 

Purpose #4 – To inform your methodology

The fourth function of the literature review is to  inform the choice of methodology  for your own research. As we’ve  discussed on the Grad Coach blog , your choice of methodology will be heavily influenced by your research aims, objectives and questions . Given that you’ll be reviewing studies covering a topic close to yours, it makes sense that you could learn a lot from their (well-considered) methodologies.

So, when you’re reviewing the literature, you’ll need to  pay close attention to the research design , methodology and methods used in similar studies, and use these to inform your methodology. Quite often, you’ll be able to  “borrow” from previous studies . This is especially true for quantitative studies , as you can use previously tried and tested measures and scales. 

How do I find articles for my literature review?

Finding quality journal articles is essential to crafting a rock-solid literature review. As you probably already know, not all research is created equally, and so you need to make sure that your literature review is  built on credible research . 

We could write an entire post on how to find quality literature (actually, we have ), but a good starting point is Google Scholar . Google Scholar is essentially the academic equivalent of Google, using Google’s powerful search capabilities to find relevant journal articles and reports. It certainly doesn’t cover every possible resource, but it’s a very useful way to get started on your literature review journey, as it will very quickly give you a good indication of what the  most popular pieces of research  are in your field.

One downside of Google Scholar is that it’s merely a search engine – that is, it lists the articles, but oftentimes  it doesn’t host the articles . So you’ll often hit a paywall when clicking through to journal websites. 

Thankfully, your university should provide you with access to their library, so you can find the article titles using Google Scholar and then search for them by name in your university’s online library. Your university may also provide you with access to  ResearchGate , which is another great source for existing research. 

Remember, the correct search keywords will be super important to get the right information from the start. So, pay close attention to the keywords used in the journal articles you read and use those keywords to search for more articles. If you can’t find a spoon in the kitchen, you haven’t looked in the right drawer. 

Need a helping hand?

How should I structure my literature review?

Unfortunately, there’s no generic universal answer for this one. The structure of your literature review will depend largely on your topic area and your research aims and objectives.

You could potentially structure your literature review chapter according to theme, group, variables , chronologically or per concepts in your field of research. We explain the main approaches to structuring your literature review here . You can also download a copy of our free literature review template to help you establish an initial structure.

In general, it’s also a good idea to start wide (i.e. the big-picture-level) and then narrow down, ending your literature review close to your research questions . However, there’s no universal one “right way” to structure your literature review. The most important thing is not to discuss your sources one after the other like a list – as we touched on earlier, your literature review needs to synthesise the research , not summarise it .

Ultimately, you need to craft your literature review so that it conveys the most important information effectively – it needs to tell a logical story in a digestible way. It’s no use starting off with highly technical terms and then only explaining what these terms mean later. Always assume your reader is not a subject matter expert and hold their hand through a journe y of the literature while keeping the functions of the literature review chapter (which we discussed earlier) front of mind.

Example of a literature review

In the video below, we walk you through a high-quality literature review from a dissertation that earned full distinction. This will give you a clearer view of what a strong literature review looks like in practice and hopefully provide some inspiration for your own. 

Wrapping Up

In this post, we’ve (hopefully) answered the question, “ what is a literature review? “. We’ve also considered the purpose and functions of the literature review, as well as how to find literature and how to structure the literature review chapter. If you’re keen to learn more, check out the literature review section of the Grad Coach blog , as well as our detailed video post covering how to write a literature review . 

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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16 Comments

Thanks for this review. It narrates what’s not been taught as tutors are always in a early to finish their classes.

Thanks for the kind words, Becky. Good luck with your literature review 🙂

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This is review is amazing. I benefited from it a lot and hope others visiting this website will benefit too.

Timothy T. Chol [email protected]

Thank you very much for the guiding in literature review I learn and benefited a lot this make my journey smooth I’ll recommend this site to my friends

This was so useful. Thank you so much.

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The review is really helpful to me especially during this period of covid-19 pandemic when most universities in my country only offer online classes. Great stuff

Great Brief Explanation, thanks

So helpful to me as a student

GradCoach is a fantastic site with brilliant and modern minds behind it.. I spent weeks decoding the substantial academic Jargon and grounding my initial steps on the research process, which could be shortened to a couple of days through the Gradcoach. Thanks again!

This is an amazing talk. I paved way for myself as a researcher. Thank you GradCoach!

Well-presented overview of the literature!

This was brilliant. So clear. Thank you

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What is a Literature Review? How to Write It (with Examples)

A literature review is a critical analysis and synthesis of existing research on a particular topic. It provides an overview of the current state of knowledge, identifies gaps, and highlights key findings in the literature. 1 The purpose of a literature review is to situate your own research within the context of existing scholarship, demonstrating your understanding of the topic and showing how your work contributes to the ongoing conversation in the field. Learning how to write a literature review is a critical tool for successful research. Your ability to summarize and synthesize prior research pertaining to a certain topic demonstrates your grasp on the topic of study, and assists in the learning process. 

Table of Contents

• What is the purpose of literature review? 
• a. Habitat Loss and Species Extinction: 
• b. Range Shifts and Phenological Changes: 
• c. Ocean Acidification and Coral Reefs: 
• d. Adaptive Strategies and Conservation Efforts: 

How to write a good literature review 

• Choose a Topic and Define the Research Question: 
• Decide on the Scope of Your Review: 
• Select Databases for Searches: 
• Conduct Searches and Keep Track: 
• Review the Literature: 
• Organize and Write Your Literature Review: 
• How to write a literature review faster with Paperpal? 
• Frequently asked questions 

What is a literature review?

A well-conducted literature review demonstrates the researcher’s familiarity with the existing literature, establishes the context for their own research, and contributes to scholarly conversations on the topic. One of the purposes of a literature review is also to help researchers avoid duplicating previous work and ensure that their research is informed by and builds upon the existing body of knowledge.

What is the purpose of literature review?

A literature review serves several important purposes within academic and research contexts. Here are some key objectives and functions of a literature review: 2  

1. Contextualizing the Research Problem: The literature review provides a background and context for the research problem under investigation. It helps to situate the study within the existing body of knowledge. 

2. Identifying Gaps in Knowledge: By identifying gaps, contradictions, or areas requiring further research, the researcher can shape the research question and justify the significance of the study. This is crucial for ensuring that the new research contributes something novel to the field. 

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3. Understanding Theoretical and Conceptual Frameworks: Literature reviews help researchers gain an understanding of the theoretical and conceptual frameworks used in previous studies. This aids in the development of a theoretical framework for the current research. 

4. Providing Methodological Insights: Another purpose of literature reviews is that it allows researchers to learn about the methodologies employed in previous studies. This can help in choosing appropriate research methods for the current study and avoiding pitfalls that others may have encountered. 

5. Establishing Credibility: A well-conducted literature review demonstrates the researcher’s familiarity with existing scholarship, establishing their credibility and expertise in the field. It also helps in building a solid foundation for the new research. 

6. Informing Hypotheses or Research Questions: The literature review guides the formulation of hypotheses or research questions by highlighting relevant findings and areas of uncertainty in existing literature. 

Literature review example

Let’s delve deeper with a literature review example: Let’s say your literature review is about the impact of climate change on biodiversity. You might format your literature review into sections such as the effects of climate change on habitat loss and species extinction, phenological changes, and marine biodiversity. Each section would then summarize and analyze relevant studies in those areas, highlighting key findings and identifying gaps in the research. The review would conclude by emphasizing the need for further research on specific aspects of the relationship between climate change and biodiversity. The following literature review template provides a glimpse into the recommended literature review structure and content, demonstrating how research findings are organized around specific themes within a broader topic. 

Literature Review on Climate Change Impacts on Biodiversity:

Climate change is a global phenomenon with far-reaching consequences, including significant impacts on biodiversity. This literature review synthesizes key findings from various studies: 

a. Habitat Loss and Species Extinction:

Climate change-induced alterations in temperature and precipitation patterns contribute to habitat loss, affecting numerous species (Thomas et al., 2004). The review discusses how these changes increase the risk of extinction, particularly for species with specific habitat requirements. 

b. Range Shifts and Phenological Changes:

Observations of range shifts and changes in the timing of biological events (phenology) are documented in response to changing climatic conditions (Parmesan & Yohe, 2003). These shifts affect ecosystems and may lead to mismatches between species and their resources. 

c. Ocean Acidification and Coral Reefs:

The review explores the impact of climate change on marine biodiversity, emphasizing ocean acidification’s threat to coral reefs (Hoegh-Guldberg et al., 2007). Changes in pH levels negatively affect coral calcification, disrupting the delicate balance of marine ecosystems. 

d. Adaptive Strategies and Conservation Efforts:

Recognizing the urgency of the situation, the literature review discusses various adaptive strategies adopted by species and conservation efforts aimed at mitigating the impacts of climate change on biodiversity (Hannah et al., 2007). It emphasizes the importance of interdisciplinary approaches for effective conservation planning. 

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Writing a literature review involves summarizing and synthesizing existing research on a particular topic. A good literature review format should include the following elements. 

Introduction: The introduction sets the stage for your literature review, providing context and introducing the main focus of your review. 

• Opening Statement: Begin with a general statement about the broader topic and its significance in the field. 
• Scope and Purpose: Clearly define the scope of your literature review. Explain the specific research question or objective you aim to address. 
• Organizational Framework: Briefly outline the structure of your literature review, indicating how you will categorize and discuss the existing research. 
• Significance of the Study: Highlight why your literature review is important and how it contributes to the understanding of the chosen topic. 
• Thesis Statement: Conclude the introduction with a concise thesis statement that outlines the main argument or perspective you will develop in the body of the literature review. 

Body: The body of the literature review is where you provide a comprehensive analysis of existing literature, grouping studies based on themes, methodologies, or other relevant criteria. 

• Organize by Theme or Concept: Group studies that share common themes, concepts, or methodologies. Discuss each theme or concept in detail, summarizing key findings and identifying gaps or areas of disagreement. 
• Critical Analysis: Evaluate the strengths and weaknesses of each study. Discuss the methodologies used, the quality of evidence, and the overall contribution of each work to the understanding of the topic. 
• Synthesis of Findings: Synthesize the information from different studies to highlight trends, patterns, or areas of consensus in the literature. 
• Identification of Gaps: Discuss any gaps or limitations in the existing research and explain how your review contributes to filling these gaps. 
• Transition between Sections: Provide smooth transitions between different themes or concepts to maintain the flow of your literature review. 

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Conclusion: The conclusion of your literature review should summarize the main findings, highlight the contributions of the review, and suggest avenues for future research. 

• Summary of Key Findings: Recap the main findings from the literature and restate how they contribute to your research question or objective. 
• Contributions to the Field: Discuss the overall contribution of your literature review to the existing knowledge in the field. 
• Implications and Applications: Explore the practical implications of the findings and suggest how they might impact future research or practice. 
• Recommendations for Future Research: Identify areas that require further investigation and propose potential directions for future research in the field. 
• Final Thoughts: Conclude with a final reflection on the importance of your literature review and its relevance to the broader academic community. 

Conducting a literature review

Conducting a literature review is an essential step in research that involves reviewing and analyzing existing literature on a specific topic. It’s important to know how to do a literature review effectively, so here are the steps to follow: 1  

Choose a Topic and Define the Research Question:

• Select a topic that is relevant to your field of study. 
• Clearly define your research question or objective. Determine what specific aspect of the topic do you want to explore? 

Decide on the Scope of Your Review:

• Determine the timeframe for your literature review. Are you focusing on recent developments, or do you want a historical overview? 
• Consider the geographical scope. Is your review global, or are you focusing on a specific region? 
• Define the inclusion and exclusion criteria. What types of sources will you include? Are there specific types of studies or publications you will exclude? 

Select Databases for Searches:

• Identify relevant databases for your field. Examples include PubMed, IEEE Xplore, Scopus, Web of Science, and Google Scholar. 
• Consider searching in library catalogs, institutional repositories, and specialized databases related to your topic. 

Conduct Searches and Keep Track:

• Develop a systematic search strategy using keywords, Boolean operators (AND, OR, NOT), and other search techniques. 
• Record and document your search strategy for transparency and replicability. 
• Keep track of the articles, including publication details, abstracts, and links. Use citation management tools like EndNote, Zotero, or Mendeley to organize your references. 

Review the Literature:

• Evaluate the relevance and quality of each source. Consider the methodology, sample size, and results of studies. 
• Organize the literature by themes or key concepts. Identify patterns, trends, and gaps in the existing research. 
• Summarize key findings and arguments from each source. Compare and contrast different perspectives. 
• Identify areas where there is a consensus in the literature and where there are conflicting opinions. 
• Provide critical analysis and synthesis of the literature. What are the strengths and weaknesses of existing research? 

Organize and Write Your Literature Review:

• Literature review outline should be based on themes, chronological order, or methodological approaches. 
• Write a clear and coherent narrative that synthesizes the information gathered. 
• Use proper citations for each source and ensure consistency in your citation style (APA, MLA, Chicago, etc.). 
• Conclude your literature review by summarizing key findings, identifying gaps, and suggesting areas for future research. 

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How to write a literature review faster with Paperpal?

Paperpal, an AI writing assistant, integrates powerful academic search capabilities within its writing platform. With the Research feature, you get 100% factual insights, with citations backed by 250M+ verified research articles, directly within your writing interface with the option to save relevant references in your Citation Library. By eliminating the need to switch tabs to find answers to all your research questions, Paperpal saves time and helps you stay focused on your writing.   

Here’s how to use the Research feature:  

• Ask a question: Get started with a new document on paperpal.com. Click on the “Research” feature and type your question in plain English. Paperpal will scour over 250 million research articles, including conference papers and preprints, to provide you with accurate insights and citations. 
• Review and Save: Paperpal summarizes the information, while citing sources and listing relevant reads. You can quickly scan the results to identify relevant references and save these directly to your built-in citations library for later access. 
• Cite with Confidence: Paperpal makes it easy to incorporate relevant citations and references into your writing, ensuring your arguments are well-supported by credible sources. This translates to a polished, well-researched literature review. 

The literature review sample and detailed advice on writing and conducting a review will help you produce a well-structured report. But remember that a good literature review is an ongoing process, and it may be necessary to revisit and update it as your research progresses. By combining effortless research with an easy citation process, Paperpal Research streamlines the literature review process and empowers you to write faster and with more confidence. Try Paperpal Research now and see for yourself.  

Frequently asked questions

A literature review is a critical and comprehensive analysis of existing literature (published and unpublished works) on a specific topic or research question and provides a synthesis of the current state of knowledge in a particular field. A well-conducted literature review is crucial for researchers to build upon existing knowledge, avoid duplication of efforts, and contribute to the advancement of their field. It also helps researchers situate their work within a broader context and facilitates the development of a sound theoretical and conceptual framework for their studies.

Literature review is a crucial component of research writing, providing a solid background for a research paper’s investigation. The aim is to keep professionals up to date by providing an understanding of ongoing developments within a specific field, including research methods, and experimental techniques used in that field, and present that knowledge in the form of a written report. Also, the depth and breadth of the literature review emphasizes the credibility of the scholar in his or her field.  

Before writing a literature review, it’s essential to undertake several preparatory steps to ensure that your review is well-researched, organized, and focused. This includes choosing a topic of general interest to you and doing exploratory research on that topic, writing an annotated bibliography, and noting major points, especially those that relate to the position you have taken on the topic. 

Literature reviews and academic research papers are essential components of scholarly work but serve different purposes within the academic realm. 3 A literature review aims to provide a foundation for understanding the current state of research on a particular topic, identify gaps or controversies, and lay the groundwork for future research. Therefore, it draws heavily from existing academic sources, including books, journal articles, and other scholarly publications. In contrast, an academic research paper aims to present new knowledge, contribute to the academic discourse, and advance the understanding of a specific research question. Therefore, it involves a mix of existing literature (in the introduction and literature review sections) and original data or findings obtained through research methods. 

Literature reviews are essential components of academic and research papers, and various strategies can be employed to conduct them effectively. If you want to know how to write a literature review for a research paper, here are four common approaches that are often used by researchers.  Chronological Review: This strategy involves organizing the literature based on the chronological order of publication. It helps to trace the development of a topic over time, showing how ideas, theories, and research have evolved.  Thematic Review: Thematic reviews focus on identifying and analyzing themes or topics that cut across different studies. Instead of organizing the literature chronologically, it is grouped by key themes or concepts, allowing for a comprehensive exploration of various aspects of the topic.  Methodological Review: This strategy involves organizing the literature based on the research methods employed in different studies. It helps to highlight the strengths and weaknesses of various methodologies and allows the reader to evaluate the reliability and validity of the research findings.  Theoretical Review: A theoretical review examines the literature based on the theoretical frameworks used in different studies. This approach helps to identify the key theories that have been applied to the topic and assess their contributions to the understanding of the subject.  It’s important to note that these strategies are not mutually exclusive, and a literature review may combine elements of more than one approach. The choice of strategy depends on the research question, the nature of the literature available, and the goals of the review. Additionally, other strategies, such as integrative reviews or systematic reviews, may be employed depending on the specific requirements of the research.

The literature review format can vary depending on the specific publication guidelines. However, there are some common elements and structures that are often followed. Here is a general guideline for the format of a literature review:  Introduction:   Provide an overview of the topic.  Define the scope and purpose of the literature review.  State the research question or objective.  Body:   Organize the literature by themes, concepts, or chronology.  Critically analyze and evaluate each source.  Discuss the strengths and weaknesses of the studies.  Highlight any methodological limitations or biases.  Identify patterns, connections, or contradictions in the existing research.  Conclusion:   Summarize the key points discussed in the literature review.  Highlight the research gap.  Address the research question or objective stated in the introduction.  Highlight the contributions of the review and suggest directions for future research.

Both annotated bibliographies and literature reviews involve the examination of scholarly sources. While annotated bibliographies focus on individual sources with brief annotations, literature reviews provide a more in-depth, integrated, and comprehensive analysis of existing literature on a specific topic. The key differences are as follows: 

References 

• Denney, A. S., & Tewksbury, R. (2013). How to write a literature review.  Journal of criminal justice education ,  24 (2), 218-234. 
• Pan, M. L. (2016).  Preparing literature reviews: Qualitative and quantitative approaches . Taylor & Francis. 
• Cantero, C. (2019). How to write a literature review.  San José State University Writing Center . 

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A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

• Give a new interpretation of old material or combine new with old interpretations,
• Trace the intellectual progression of the field, including major debates,
• Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
• Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

• Place each work in the context of its contribution to understanding the research problem being studied.
• Describe the relationship of each work to the others under consideration.
• Identify new ways to interpret prior research.
• Reveal any gaps that exist in the literature.
• Resolve conflicts amongst seemingly contradictory previous studies.
• Identify areas of prior scholarship to prevent duplication of effort.
• Point the way in fulfilling a need for additional research.
• Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE : Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

• An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
• Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
• An explanation of how each work is similar to and how it varies from the others,
• Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

• Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
• Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
• Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
• Persuasiveness -- which of the author's theses are most convincing or least convincing?
• Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

• Current Situation : Information necessary to understand the current topic or focus of the literature review.
• Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
• History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
• Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
• Standards : Description of the way in which you present your information.
• Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

• Sources in your literature review do not clearly relate to the research problem;
• You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
• Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
• Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
• Does not describe the search procedures that were used in identifying the literature to review;
• Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
• Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

• How are they organizing their ideas?
• What methods have they used to study the problem?
• What theories have been used to explain, predict, or understand their research problem?
• What sources have they cited to support their conclusions?
• How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

• Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
• Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
• Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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How to Write a Literature Review

What is a literature review.

• What Is the Literature
• Writing the Review

A literature review is much more than an annotated bibliography or a list of separate reviews of articles and books. It is a critical, analytical summary and synthesis of the current knowledge of a topic. Thus it should compare and relate different theories, findings, etc, rather than just summarize them individually. In addition, it should have a particular focus or theme to organize the review. It does not have to be an exhaustive account of everything published on the topic, but it should discuss all the significant academic literature and other relevant sources important for that focus.

This is meant to be a general guide to writing a literature review: ways to structure one, what to include, how it supplements other research. For more specific help on writing a review, and especially for help on finding the literature to review, sign up for a Personal Research Session .

The specific organization of a literature review depends on the type and purpose of the review, as well as on the specific field or topic being reviewed. But in general, it is a relatively brief but thorough exploration of past and current work on a topic. Rather than a chronological listing of previous work, though, literature reviews are usually organized thematically, such as different theoretical approaches, methodologies, or specific issues or concepts involved in the topic. A thematic organization makes it much easier to examine contrasting perspectives, theoretical approaches, methodologies, findings, etc, and to analyze the strengths and weaknesses of, and point out any gaps in, previous research. And this is the heart of what a literature review is about. A literature review may offer new interpretations, theoretical approaches, or other ideas; if it is part of a research proposal or report it should demonstrate the relationship of the proposed or reported research to others' work; but whatever else it does, it must provide a critical overview of the current state of research efforts. 

Literature reviews are common and very important in the sciences and social sciences. They are less common and have a less important role in the humanities, but they do have a place, especially stand-alone reviews.

Types of Literature Reviews

There are different types of literature reviews, and different purposes for writing a review, but the most common are:

• Stand-alone literature review articles . These provide an overview and analysis of the current state of research on a topic or question. The goal is to evaluate and compare previous research on a topic to provide an analysis of what is currently known, and also to reveal controversies, weaknesses, and gaps in current work, thus pointing to directions for future research. You can find examples published in any number of academic journals, but there is a series of Annual Reviews of *Subject* which are specifically devoted to literature review articles. Writing a stand-alone review is often an effective way to get a good handle on a topic and to develop ideas for your own research program. For example, contrasting theoretical approaches or conflicting interpretations of findings can be the basis of your research project: can you find evidence supporting one interpretation against another, or can you propose an alternative interpretation that overcomes their limitations?
• Part of a research proposal . This could be a proposal for a PhD dissertation, a senior thesis, or a class project. It could also be a submission for a grant. The literature review, by pointing out the current issues and questions concerning a topic, is a crucial part of demonstrating how your proposed research will contribute to the field, and thus of convincing your thesis committee to allow you to pursue the topic of your interest or a funding agency to pay for your research efforts.
• Part of a research report . When you finish your research and write your thesis or paper to present your findings, it should include a literature review to provide the context to which your work is a contribution. Your report, in addition to detailing the methods, results, etc. of your research, should show how your work relates to others' work.

A literature review for a research report is often a revision of the review for a research proposal, which can be a revision of a stand-alone review. Each revision should be a fairly extensive revision. With the increased knowledge of and experience in the topic as you proceed, your understanding of the topic will increase. Thus, you will be in a better position to analyze and critique the literature. In addition, your focus will change as you proceed in your research. Some areas of the literature you initially reviewed will be marginal or irrelevant for your eventual research, and you will need to explore other areas more thoroughly. 

Examples of Literature Reviews

See the series of Annual Reviews of *Subject* which are specifically devoted to literature review articles to find many examples of stand-alone literature reviews in the biomedical, physical, and social sciences. 

Research report articles vary in how they are organized, but a common general structure is to have sections such as:

• Abstract - Brief summary of the contents of the article
• Introduction - A explanation of the purpose of the study, a statement of the research question(s) the study intends to address
• Literature review - A critical assessment of the work done so far on this topic, to show how the current study relates to what has already been done
• Methods - How the study was carried out (e.g. instruments or equipment, procedures, methods to gather and analyze data)
• Results - What was found in the course of the study
• Discussion - What do the results mean
• Conclusion - State the conclusions and implications of the results, and discuss how it relates to the work reviewed in the literature review; also, point to directions for further work in the area

Here are some articles that illustrate variations on this theme. There is no need to read the entire articles (unless the contents interest you); just quickly browse through to see the sections, and see how each section is introduced and what is contained in them.

The Determinants of Undergraduate Grade Point Average: The Relative Importance of Family Background, High School Resources, and Peer Group Effects , in The Journal of Human Resources , v. 34 no. 2 (Spring 1999), p. 268-293.

This article has a standard breakdown of sections:

• Introduction
• Literature Review
• Some discussion sections

First Encounters of the Bureaucratic Kind: Early Freshman Experiences with a Campus Bureaucracy , in The Journal of Higher Education , v. 67 no. 6 (Nov-Dec 1996), p. 660-691.

This one does not have a section specifically labeled as a "literature review" or "review of the literature," but the first few sections cite a long list of other sources discussing previous research in the area before the authors present their own study they are reporting.

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• Last Updated: Jan 11, 2024 9:48 AM
• URL: https://libguides.wesleyan.edu/litreview

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What is the Purpose of a Literature Review?

4-minute read

• 23rd October 2023

If you’re writing a research paper or dissertation , then you’ll most likely need to include a comprehensive literature review . In this post, we’ll review the purpose of literature reviews, why they are so significant, and the specific elements to include in one. Literature reviews can:

1. Provide a foundation for current research.

2. Define key concepts and theories.

3. Demonstrate critical evaluation.

4. Show how research and methodologies have evolved.

5. Identify gaps in existing research.

6. Support your argument.

Keep reading to enter the exciting world of literature reviews!

What is a Literature Review?

A literature review is a critical summary and evaluation of the existing research (e.g., academic journal articles and books) on a specific topic. It is typically included as a separate section or chapter of a research paper or dissertation, serving as a contextual framework for a study. Literature reviews can vary in length depending on the subject and nature of the study, with most being about equal length to other sections or chapters included in the paper. Essentially, the literature review highlights previous studies in the context of your research and summarizes your insights in a structured, organized format. Next, let’s look at the overall purpose of a literature review.

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Literature reviews are considered an integral part of research across most academic subjects and fields. The primary purpose of a literature review in your study is to:

Provide a Foundation for Current Research

Since the literature review provides a comprehensive evaluation of the existing research, it serves as a solid foundation for your current study. It’s a way to contextualize your work and show how your research fits into the broader landscape of your specific area of study.  

Define Key Concepts and Theories

The literature review highlights the central theories and concepts that have arisen from previous research on your chosen topic. It gives your readers a more thorough understanding of the background of your study and why your research is particularly significant .

Demonstrate Critical Evaluation 

A comprehensive literature review shows your ability to critically analyze and evaluate a broad range of source material. And since you’re considering and acknowledging the contribution of key scholars alongside your own, it establishes your own credibility and knowledge.

Show How Research and Methodologies Have Evolved

Another purpose of literature reviews is to provide a historical perspective and demonstrate how research and methodologies have changed over time, especially as data collection methods and technology have advanced. And studying past methodologies allows you, as the researcher, to understand what did and did not work and apply that knowledge to your own research.  

Identify Gaps in Existing Research

Besides discussing current research and methodologies, the literature review should also address areas that are lacking in the existing literature. This helps further demonstrate the relevance of your own research by explaining why your study is necessary to fill the gaps.

Support Your Argument

A good literature review should provide evidence that supports your research questions and hypothesis. For example, your study may show that your research supports existing theories or builds on them in some way. Referencing previous related studies shows your work is grounded in established research and will ultimately be a contribution to the field.  

Literature Review Editing Services 

Ensure your literature review is polished and ready for submission by having it professionally proofread and edited by our expert team. Our literature review editing services will help your research stand out and make an impact. Not convinced yet? Send in your free sample today and see for yourself! 

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Thymosin alpha 1: A comprehensive review of the literature

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Krunal Pandav

Wanessa matos, sharmi biswas, gowry reddy, sindhu thevuthasan, muhammad adnan khan, anoopa mathew, sarabjot singh makkar, madiha zaidi, michael maher mourad fahem, renato beas, valeria castaneda, trissa paul, john halpern, diana baralt.

Corresponding author: Donald Hathaway III, BSc, Division of Research and Academic Affairs, Larkin Health System, 7032 SW 62nd Avenue, South Miami, FL 33143, United States. [email protected]

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.

Core Tip: Thymosin alpha 1 is a naturally occurring peptide in the human thymus, which has long been recognized for its immune-modulating properties. The synthetic analog of thymosin alpha 1 has various clinical applications, such as in infectious diseases, malignancies and in immunocompromised states. There is emerging data postulating that this peptide could be of benefit in the treatment of severe acute respiratory syndrome coronavirus-2 infection. We herein discuss the underlying knowledge, current clinical uses and results of recent studies of thymosin alpha 1.

INTRODUCTION

Thymosin alpha 1 is a 28 amino acid peptide originally isolated from the thymus[ 1 ], which has been extensively studied in terms of its functions in the immune system. Thymosin alpha 1 has long been recognized as an immune enhancing, immune modulating, as well as an immune restoring agent[ 2 ], and as such it has been utilized in several clinical and research settings. The synthetic form of thymosin alpha 1, thymalfasin, is approved in more than 35 countries for the treatment of hepatitis B and C and as an immune enhancer in several other diseases[ 1 ]. More specifically, it has been of benefit as a means of augmenting immune response in immune deficiencies[ 3 ], psoriatic arthritis[ 4 ], aging[ 3 ], as well as in increasing response to vaccines[ 3 ] and decreasing chemotherapy-induced toxicity[ 5 ]. It has additionally been of value in treating oncologic patients, especially those with hepatocellular carcinoma, renal cell carcinoma and non-small cell lung cancer[ 5 ]. Last but not least, it has been used in the fight of numerous infections, such as human immunodeficiency virus (HIV)[ 6 ], pseudomonas[ 1 ], and mold toxicity[ 7 ], as well as sepsis[ 8 ], and recently in severely ill coronavirus disease 2019 (COVID-19) patients[ 9 ]. In light of the current pandemic situation, efforts are being made worldwide to understand the impact of infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on the immune system in the hopes of getting closer to an effective treatment. To this end, it would be worthwhile to further investigate thymosin alpha 1 through the relevant published literature. In this review, we aim to understand the characteristics of thymosin alpha 1, from its chemical structure and biological properties all the way to its clinical applications, their safety and efficacy which would provide an insight on whether it could be used as a therapeutic option to help curb mortality and improve outcomes in severely ill COVID-19 patients.

BIOCHEMISTRY

Thymosin proteins are short, positively charged, and inherently unregulated peptides. Induction of thymosin protein configuration via organic reagents, such as trifluoroethanol, hexafluoroisopropanol, dodecyl trimethylammonium bromide, and Zn 2+ ions, charges the proteins neutralizing them at a low PH to potentiate their absolute effects[ 10 ]. The nuclear magnetic resonance structure of thymosin alpha 1 has been determined by mixing in 40% trifluoroethanol/60% water (v/v) solvent. The study has determined 800 MHz of a polypeptide chain consisting of 28 residues. To comprehend its distinct structure, multiple molecular trials with solvent composed of 40% trifluoroethanol/60% transferable intermolecular potential with 3 points water (v/v) were utilized to create a three-dimensional configuration of the peptide. Ultimately, it was able to depict a distorted helical configuration with two stable regions: Alpha-helix site from 14-26 residues and two double turns in the β region in the N-terminal site consisting of 12 residues[ 11 ].

Thymalfasin, the synthetic analog of thymosin alpha 1, induces interleukin (IL)-2 production, differentiation of immature cord blood lymphocytes, production of B cell growth factors, and increased macrophage antigen presentation efficiency. It is used to treat chemotherapy-induced immunosuppression and to enhance the efficacy of influenza and hepatitis B vaccines in immunocompromised patients[ 12 ]. Thymosin alpha 1 therapy modulates and partially normalizes T-lymphocyte numbers and function. T cell rosette percentages have been shown to increase in patients with T cell lymphopenia. Thymalfasin may benefit conditions such as T cell lymphopenia, immunosuppression, and immune dysregulation seen in COVID-19 due to SARS-CoV-2 induced cytokine storm and the immunosuppressive effects of its viral envelope proteins[ 13 ]. This may be why Thymalfasin has been used in China for general treatment of COVID-19 patients since April 2020[ 14 ].

EXTRACTION AND ANALYSIS

Thymosin alpha 1 is a peptide hormone that is endogenously produced by the thymus gland and potentiates T cell-mediated immune responses via differentiation and maturation of T-cell progenitor cells, activation of dendritic and natural killer cells, and stimulation of cytokine-mediated inflammation[ 15 ]. Since first isolated from a preparation of bovine thymuses, named the thymosin fraction 5 in 1977, thymosin alpha 1 has been widely recognized for its immune-enhancing properties. Therefore, various efforts have been made towards finding the most efficient method for its production and purification. There are currently three distinct ways bioactive thymosin alpha 1 can be obtained. The first method of extraction is via isolation from calf thymuses. It can also be extracted from thymosin fraction 5, which was first isolated from calf thymuses using the technique described in 1975[ 12 ]. The second method is through solid-phase synthesis, which is a purely chemical way of peptide synthesis and is nowadays the only method accepted for production of thymosin alpha 1 for clinical use. Lastly, genetic engineering expression makes use of the advances in biotechnology to produce purified recombinant thymosin alpha 1 from either prokaryotic organisms such as Escherichia coli , or eukaryotic organisms such as yeast, plants or Pichia Pastoris. Regarding thymosin alpha 1 expression in Escherichia coli , numerous expression systems have been developed based on the insertion of the recombinant gene for human thymosin alpha 1 in different vectors, such as pGEX-2T, pThioHis B, pBV222. According to Antachopoulos et al [ 7 ] (2012), the most promising results came from the BL21/pET-28a system, with thymosin alpha 1 being 70% of total bacterial protein production. The protein can then be analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis or by measuring ultraviolet light absorbance at 215 nm. For purification, the primary methods proposed are nickel affinity chromatography, thermal denaturation, and high-performance liquid chromatography. Thymosin alpha 1 expression in yeast is an attractive alternative because post-translational modifications and the development of stable cell lines are made possible[ 6 ].

Chen et al [ 16 ] describe their own yeast-based expression system for thymosin alpha 1, which proved to be effective in producing thymosin alpha 1 capable of increasing CD8+ counts in mice pre-treated with cyclophosphamide. An example of thymosin alpha 1 expression in plants (transgenic tomato Solanum Lycopersicum) is described by Chen et al [ 17 ]. As promising as it may seem, the genetic engineering method for thymosin alpha 1 production has not yet been introduced into clinical practice, primarily due to difficulties pertaining to extraction and purification. Other than direct extraction from calf thymus, which can only produce trace amounts of the peptide, thymosin alpha 1 used for therapeutic purposes comes from chemical synthesis.

Enzyme-linked immunosorbent assay and radioimmunoassay are the most commonly used methods for quantitative analysis of the peptide. Tuthill et al [ 18 ] also suggest liquid chromatography with tandem mass spectrometry, which has proven to be accurate, precise, and sensitive for measurement of thymosin alpha 1 in the serum[ 18 ].

STORAGE OF THYMOSIN ALPHA 1

Thymosin alpha 1 should be stored at -20 degrees Celsius. Lyophilized thymosin alpha 1 may remain stable for up to three weeks at room temperature; however, for long term storage, it should be kept below -180 degrees Celsius and stored in the desiccated form. When ready to use, it may be reconstituted and subsequently stored at 40 degrees Celsius for a period of two to seven days. If the intention is to store thymosin alpha 1 for a longer period of time, then it is advised to store it in combination with a carrier protein such as 0.1% human serum albumin or bovine serum albumin. It is recommended to avoid repeated freezing and thawing[ 19 ].

BIOLOGICAL ACTIVITIES AND HEALTH BENEFITS

Thymosin alpha 1 functions as a toll-like receptor (TLR)-9 and TLR-2 agonist in both myeloid and dendritic cells, the professional antigen-presenting cells[ 20 ]. By targeting TLRs, thymosin alpha 1 can stimulate the adaptive immune response, which is essential for fighting viral, bacterial, and fungal infections and cancers, as well as stimulation of posterior humoral immunity[ 20 - 22 ]. Additionally, thymosin alpha 1 can increase levels of IL-2, IL-10, IL-12, interferon (IFN)-α, and IFN-γ[ 23 ]. The role of thymosin alpha 1 in stimulating T-cell dependent antibody production is also the reason why it has been considered as a vaccine adjuvant for enhancing response to vaccines[ 24 ].

Thymosin alpha 1 has a wide range of biological activities that range from anti-tumor to immune-modulating properties (Figure ​ (Figure1). 1 ). The immune response of thymosin alpha 1 is due to its action in elevating the activity of T cell maturation into CD4+/CD8+ T cells. It works to directly activate natural killer cells as well as CD8+ T cells through which it kills virally infected cells. Thymosin alpha 1 has a negative effect on IL-1β and tumor necrosis factor-α, which in turn leads to a decreased inflammatory response and is quite beneficial in conditions such as chronic hepatitis and acute pancreatitis. Not only does it play a role in enhancing cytokine expression, but it also increases the prominence of major histocompatibility complex I/viral antigens on their respective target infected cells and decreases viral replication[ 6 ]. Naylor and his associates pointed out that thymosin alpha 1 does not only have one but rather a varied range of targets for its immune-enhancing activity[ 25 ].

Thymosin alpha 1 has a wide range of biological activities. IL: Interleukin; IFN: Interferon; TLR: Toll-like receptors.

Thymosin alpha 1 has exhibited the ability to restrain tumor growth, hence its use in the treatment of various cancers. It has anti-proliferative properties which have been exhibited in lung and liver tumor metastases. According to studies conducted by Moody et al [ 25 ], the anti-tumor activity of thymosin alpha 1 worked best with small tumor size. Overall, thymosin alpha 1 works via two main mechanisms: Either stimulating the immune system or employing its anti-proliferative activities on tumor cells. The protective action of thymosin alpha 1 against oxidative damage as a result of its effect on liver superoxide dismutase and glutathione peroxidase has been explored by Armutcu et al [ 26 ].

Since thymosin alpha 1 is a polypeptide naturally present in the thymus, it plays a fundamental role in the control of inflammation, immunity, and tolerance. Thymosin alpha 1 has an immune-modulating action through its interaction with toll-like receptors. Due to the action of thymosin alpha 1 on other cell types, it is used as a therapeutic agent for diseases with evident immune dysfunction[ 4 ]. Clinical trials with thymosin alpha 1 for diseases like DiGeorge syndrome, non-small cell lung cancer, hepatocellular carcinoma, hepatitis B and C, HIV, and melanoma have been conducted and yielded promising results[ 27 , 28 ]. FDA approved the orphan drug thymalfasin (Zadaxin) for treatment of malignant melanoma, chronic active hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma due to its immunomodulatory and anti-tumor effect.

CLINICAL AND COMMERCIAL APPLICATIONS

Thymosin alpha 1 has been extensively tested and its synthetic form, thymalfasin, is widely used in the clinical field (Figure ​ (Figure2). 2 ). Some of its applications are as follows.

Clinical applications of thymosin alpha 1.

Hepatitis B

The safety and efficacy of thymosin alpha 1 in patients with chronic hepatitis B have been tested through clinical trials. Thymosin alpha 1 has been tested as monotherapy as well as in combination with interferon-alpha and other nucleoside analogs. There has been found a complete virological response rate [clearance of serum hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen] of 40.6% in patients given 1.6 mg subcutaneous injection twice a week and 26.5% in patients given the same regimen for 52 wk[ 29 ]. However, it is important to note that treatment of Hepatitis B using thymosin alpha 1 was only used in the era of interferon and is now obsolete in the era post-discovery of direct antiviral agents.

Hepatitis C

Thymosin alpha 1 as a monotherapy does not seem to be useful in treating hepatitis C infection. However, combination therapy of thymosin alpha 1 and pegylated interferon alpha 2a could effectively repress viral replication in hepatitis C patients. Thymosin alpha 1, in combination with interferon-alpha 1 has also been tested for treatment in patients with chronic hepatitis C. Moreover, thymosin alpha 1 is well tolerated, with no significant adverse effects observed. A meta-analysis conducted by Sherman, included many trials showing the superiority of the combination of thymosin alpha 1 and interferon alpha 1 compared to interferon alpha mono-therapy[ 30 ]. It remains important to note that similar to Hepatitis B, the treatment of Hepatitis C with thymosin alpha 1 has been discontinued in favor of direct antiviral agents.

The use of thymosin alpha 1 in patients with sepsis has shown a significant decrease in mortality due to multiple-organ failure, which is the primary cause of death in sepsis[ 8 ].

HIV infection

Thymosin alpha 1, interferon alpha 1, and zidovudine combination therapy has been well-tolerated in HIV patients. Thymosin alpha 1 enhances the function and increases the number of CD4+ T cells, while it also decreases viral load. Thymosin alpha 1 influences thymic T-cell output. The safety and efficacy of thymosin alpha 1 in combination with highly-active antiretroviral therapy in stimulating immune reconstitution has been proven[ 6 ]. It has been shown that thymosin alpha 1 is well tolerated, and could dramatically increase the levels of signal joint T cell receptor excision circles in patients with advanced HIV disease. Prolonged use of high-dose thymosin alpha 1 is more effective[ 2 ].

Pseudomonas - bone marrow transplant patients

Thymosin alpha 1 is also used in other infections like pseudomonas or infections following bone marrow transplant[ 1 ].

Mold toxicity

This thymic peptide has the ability to prime dendritic cells and to enhance Th1 and Treg cells so that inflammation is balanced, and an antifungal response is generated. Th1 response will activate the production of Th2 cytokines (IFN-γ, IL-2, IL-12, IL-18), stimulating phagocytic activity. Therefore, cytotoxic CD4+, CD8+, and T cells and opsonizing antibodies will be produced, generating a protective effect against fungal pathogens[ 7 ].

Immune deficiency

Treatment with thymosin alpha 1 serves as a stimulus for IL-2 receptor expression and IL-2 internalization. It also has a restoring effect on patients with a suppressed lymphokine-activated killer cell activity and with immunodeficiency[ 29 ]. Acting through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, thymosin alpha 1 stimulates the signaling pathways and initiates the production of immune-related cytokines. Thus, thymosin alpha 1 is anticipated to bring about encouraging results in the treatment of immunocompromised patients. Overall, it improves immune system function without causing adverse events[ 13 ].

Psoriatic arthritis

Thymosin alpha 1 is a potent modulator of immunity and inflammation. Evidence is growing that diseases characterized by deregulation of the immune system and inflammation, such as psoriatic arthritis, are associated with serum levels of thymosin alpha 1 significantly lower than those of healthy individuals. The data is consistent with the role of thymosin alpha 1 as a regulator of immunity, tolerance and inflammation in patients with psoriatic arthritis[ 4 ].

Vaccine adjuvant

The use of thymosin alpha 1 as an adjuvant to the influenza vaccine has shown promising results, especially among elderly and immunocompromised patients[ 31 ]. Thymosin alpha 1 has also been shown to improve the immunogenicity of the influenza vaccine[ 3 ].

Decreasing toxicity from chemotherapy

Clinical studies show that thymosin alpha 1 has been utilized in patients with different malignancies, reducing the toxicity of chemotherapy, and improving the quality of life. An increase in the numbers and functions of immune cells and the decrease of toxicity from chemotherapy was also an effect of utilizing this medication. In general, fewer infections occurred during chemotherapy, neurotoxicity decreased, and the quality of life improved[ 5 ].

Oxidative damage, pancreatic lesions and diabetes

Many studies have shown that thymosin alpha 1 has protective effects against oxidative damage. By remarkably amplifying the activity of catalase, superoxide dismutase, and glutathione peroxidase, thymosin alpha 1 reduces the production of reactive oxygen species and prevents oxidative damage to hepatic tissue. Thymosin alpha 1 has well-established antiproliferative properties seen with various human malignancies and this is a result of its capacity to decrease oxidative stress[ 6 ]. It also helps ameliorate pancreatic damage and the resulting diabetes by reducing the production of malondialdehyde and by improving the function of superoxide dismutase and catalase. The antioxidant properties of thymosin alpha 1 are considered to be of great benefit in the treatment of pancreatic lesions[ 32 ].

Applications in oncologic patients

Multiple studies have shown promising results for the use of thymosin alpha 1 in patients with metastatic melanoma, head and neck carcinoma, lung cancer, breast cancer, and hepatocellular carcinoma[ 33 ]. Thymosin alpha 1 is indicated as adjuvant for chemotherapy-induced immune depression, immune insufficiency, and immune suppression in patients[ 5 ]. In addition, it has been shown that thymosin alpha 1 in combination with chemotherapy or radiation improves survival rate in patients with non-small cell lung cancer, which accounts for 85% of all lung cancers and is known for its low responsiveness to chemotherapy[ 5 ].

SAFETY AND DOSES

Thymosin alpha 1 is usually found in an injection form and is commonly prescribed by a primary care physician. Thymosin alpha 1 is usually administered twice a week via a subcutaneous route. The standard single dosage ranges from 0.8 to 6.4 mg, while multiple doses range from 1.6 to 16 mg for five to seven days. Utilized in various illnesses such as liver disease, cancer, and autoimmune diseases, thymosin alpha 1 has been shown to be well-tolerated and safe[ 34 ].

ADVERSE EFFECTS AND CONTRAINDICATIONS

Thymalfasin, the synthetic form of thymosin alpha 1, is usually well tolerated. The most common adverse effects include local irritation, redness, or discomfort at the site of injection. In clinical trials, the combination of thymalfasin with interferon 2b was reported to have rare side effects such as fever, fatigue, muscle aches, nausea, vomiting, and neutropenia when compared to interferon-alpha 2b alone or with placebo[ 34 ]. Thymalfasin is contraindicated in patients with hypersensitivity to thymosin alpha 1 or any of the components of the injection. Due to the immunomodulatory action of thymalfasin, it is also contraindicated in immu-nosuppressed patients, such as organ transplant recipients, unless the benefits of the treatment exceed the risks[ 35 ].

EVIDENCE FROM PREVIOUS HUMAN CLINICAL STUDIES

Thymosin alpha 1 has been utilized in various cases to enhance cell-mediated immunity and for the treatment of a multitude of different diseases (Table ​ (Table1). 1 ). A study was performed to demonstrate the effect of thymosin alpha 1 in the human breast cancer lines ZR-75-1, MCF-7, MDA-MB-231, MCF-10A and BT-549. For this experiment, thymosin alpha 1 was dissolved in sterile water and stored in 2 mL plastic tubes at -20 °C. Results showed that thymosin alpha 1 inhibited cell proliferation and induced apoptosis in human leukemia, non-small cell lung cancer, melanoma, and other cancers. Apoptosis was significantly induced in human breast cancer and leukemia cell lines with a thymosin alpha 1 concentration of 100 to 160 IM. Additionally, data exhibited that ZR-75-1 and MCF-7 cells display different sensitivities to thymosin alpha 1. In general, the study revealed that thymosin alpha 1 could be a possible approach to breast cancer treatment[ 36 ]. Other studies demonstrate that thymosin alpha 1 could be a promising therapy for severe sepsis. Various small-scale studies as well as a large-scale, multicenter, single-blinded, and randomized control trial were conducted in six tertiary teaching hospitals in China, with the purpose of demonstrating the vital role thymosin alpha 1 plays in sepsis therapy. Patients admitted to the intensive care unit with severe sepsis were distributed randomly among the control group and the thymosin alpha 1 group. Hypodermic injections of 1.6 mg of thymosin alpha-1 or normal saline were distributed to all individuals two times a day for five days; afterwards, the dose was reduced to once per day. Results showed that the thymosin alpha 1 group was 9.0% lower in mortality rate than the control group[ 21 ].

Summarizing pre-clinical and clinical studies

IL: Interleukin; sjTREC: Signal joint T cell receptor excision circles; HIV: Human immunodeficiency virus; ALT: Glutamic-pyruvic transaminase; HBV: Hepatitis B virus; DNA: Deoxyribonucleic acid.

As discussed above, one of the strongest properties of thymosin alpha 1 is its role in the activation of T cell responses in the body. A study in seven patients with chronic hepatitis caused by hepatitis B virus tried to identify the immunomodulatory properties of thymosin alpha 1. Each individual was treated for a total of 24 wk with a hypodermic injection at a dose of 1.29/0.4 mg/body/day six times weekly for the first 2 wk and then twice weekly for an additional 22 wk. Subsequently, liver biopsies were performed to gather data. The serum alanine transaminase levels improved to 47.39/17.0 IU/L and normalized in 42.9% of patients after 48 wk of treatment. However, complete disappearance of serum hepatitis B virus deoxyribonucleic acid was seen in 28.6%. Thymosin alpha 1 also affected maturation of T-cells, demonstrating its high immunomodulatory properties. Overall, it has been reported that combination therapy with thymosin alpha 1 and IFN-α has demonstrable biological activity in patients with viral hepatitis[ 37 ].

THYMOSIN ALPHA 1/THYMALFASIN VS THYMOSIN BETA 4/TIMBETASIN

Thymosin alpha 1 and thymosin beta 4 are two hormone peptides that are secreted from the thymus and have vastly different chemical compositions and immunological actions. These proteins are separated from thymosin fraction 5 and have the potential to change a variety of immune functions in mammals. Thymosin alpha 1 is thought to be responsible for rebuilding the immune system by enhancing cell-mediated immunity in animals without a thymus gland. Thymosin beta 4 is in the family of actin monomer-sequestering proteins which essentially regulate unpolymerized actin and have an active role in maintaining the free G-actin monomers in the cytoplasm. Thymosin alpha 1 is clinically relevant in various types of cancer, specifically hepatocellular carcinoma, lung cancer and melanomas. Thymosin beta 4, has a strong response to virally infected cells. It is currently being tested as a possible therapy against influenza, HIV, and acquired immune deficiency syndrome[ 38 - 41 ].

COULD THYMOSIN ALPHA 1 IMPROVE THE OUTCOMES IN COVID-19 PATIENTS?

The COVID-19 pandemic has had a worldwide impact and multiple studies have shown the immunological effects of this disease. All countries affected by SARS-CoV-2 are focused on searching for an effective treatment. Thymosin alpha 1 has a very prominent role in both immunity control and inflammation (Table ​ (Table2). 2 ). So far, it has been used in various pathologic conditions: Infections, sepsis, immune deficiencies and malignancies, just to name a few. It has also been found to curb mortality in several of them, such as sepsis and HIV infection. Although clinical studies on the efficiency of thymosin alpha 1 in treating COVID-19 are still limited, it would be of great value to further explore the potential benefits that this drug can bring about in mitigating the devastating effects of the current pandemic.

Summary of ongoing clinical trials of thymosin and coronavirus disease 2019

Data retrieved from clinicaltrials.gov on October 5 th , 2020. COVID-19: Coronavirus disease 2019.

A recent study in COVID-19 patients demonstrated how thymosin alpha 1 significantly promoted the proliferation of activated T cells and this led to a critical prevention of lymphopenia in infected patients. In total, there were 25 severely and critically ill patients who participated in the study. Eleven of them received daily treatment of thymosin alpha 1 for one week, while the rest of the patients remained untreated. Data illustrates that patients in the thymosin alpha 1 treatment group had a higher number of lymphocytes than patients without treatment[ 42 ]. In another retrospective study conducted in China, patients in the treatment group received subcutaneous injections of 10 mg thymosin alpha 1 once per day for at least seven consecutive days. Thymosin alpha 1 supplementation showed improvement and restoration of T cell counts in COVID-19 patients with severe lymphocytopenia and, in the end, thymosin alpha 1 supplementation reduced mortality in patients severely ill with COVID-19[ 30 ].

In COVID-19 treatment, it has been postulated to administer thymosin alpha 1 as an intramuscular injection for 7 d for patients who have CD8 cells less than 400/μL and CD4 cells less than 650/μL. This is postulated on the understanding that thymosin alpha 1 induction showed improvement in T cell number in elderly patients with comorbidities like hypertension and cardiovascular diseases. Healthy people who are older than 60 years of age should receive thymosin alpha 1 as a supplement to prevent COVID-19 infection[ 43 ]. It has also been suggested that thymosin alpha 1 taken before administration of methylprednisolone in COVID-19 patients may prevent steroid-induced death of thymocytes[ 44 ]. The National Health Commission of China included thymosin alpha 1 as an alternative treatment option for patients with lymphocytopenia or immunodeficiency.

Currently, there are various ongoing clinical trials registered on clinicaltrials.gov of thymosin in COVID-19 patients (Table ​ (Table2 2 ).

Thymosin alpha 1 is a thymus peptide with recognized immune modulating capacity and biochemical properties. The synthetic analogue of thymosin alpha 1, thymalfasin, induces IL-2 and B cell growth factor production, differentiation of immature cord blood lymphocytes, raises efficiency of macrophage antigen presentation, and the modulation and partial normalization of function and number of T-lymphocytes. The effects of immune stimulation occur through TLR action in both the myeloid and plasmacytoid dendritic cells with production of cytokines. The immunosuppressive effects of the SARS-CoV-2 viral envelope in inducing cytokine storm may be modulated with thymosin alpha 1 therapy. This would be especially beneficial in preventing catastrophic events such as cytokine storm in more severe cases. Thymosin alpha 1 and its synthetic analogue thymalfasin have well-studied safety profiles and are well-tolerated with only minor side effects. Clinical studies have demonstrated the significant role of thymosin alpha 1 in immune and inflammatory responses, and extensive research has shown its effective use in a myriad of diseases ranging from hepatitis and HIV to immune deficiencies and cancers, as well as its use as a vaccine adjuvant.

Within the context of COVID-19 infection, it has been shown to reduce mortality in those with severe disease and aid in restoring some immune function through increasing thymic activity. Further study would be highly beneficial in determining if thymosin alpha 1 could serve as a therapeutic agent or in combination with other treatments to mitigate the progression and severity of the disease. For this purpose, we can conclude that further studies are mandated for using thymosin alpha 1 in these patients.

ACKNOWLEDGEMENTS

The authors would like to acknowledge Dr. Marcos A Sanchez-Gonzalez, MD, PhD for actively providing valuable advice and suggestions during the course of the project.

Conflict-of-interest statement: Authors declare no conflict of interests for this article.

Manuscript source: Unsolicited manuscript

Peer-review started: October 13, 2020

First decision: November 18, 2020

Article in press: December 2, 2020

Specialty type: Infectious diseases

Country/Territory of origin: United States

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Contributor Information

Asimina Dominari, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Donald Hathaway III, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States. [email protected] .

Krunal Pandav, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Wanessa Matos, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Sharmi Biswas, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Gowry Reddy, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Sindhu Thevuthasan, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Muhammad Adnan Khan, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Anoopa Mathew, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Sarabjot Singh Makkar, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Madiha Zaidi, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Michael Maher Mourad Fahem, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Renato Beas, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Valeria Castaneda, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Trissa Paul, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

John Halpern, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.

Diana Baralt, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States.