Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Letter

Metabolic features of chronic fatigue syndrome revisited

Henrik Vogt, Elling Ulvestad, and Vegard Bruun Wyller
  1. aGeneral Practice Research Unit, Department of Public Health and General Practice, Norwegian University of Science and Technology, 8905 Trondheim, Norway;
  2. bDepartment of Microbiology, Haukeland University Hospital, 5021 Bergen, Norway;
  3. cDepartment of Pediatrics and Adolescent Medicine, Akershus University Hospital, 1478 Lørenskog, Norway

See allHide authors and affiliations

PNAS November 15, 2016 113 (46) E7140-E7141; first published November 3, 2016; https://doi.org/10.1073/pnas.1615143113
Henrik Vogt
aGeneral Practice Research Unit, Department of Public Health and General Practice, Norwegian University of Science and Technology, 8905 Trondheim, Norway;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: henrik.vogt@ntnu.no
Elling Ulvestad
bDepartment of Microbiology, Haukeland University Hospital, 5021 Bergen, Norway;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vegard Bruun Wyller
cDepartment of Pediatrics and Adolescent Medicine, Akershus University Hospital, 1478 Lørenskog, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • PDF
Loading

In a recent paper in PNAS by Naviaux et al. (1) on metabolomics in chronic fatigue syndrome (CFS), the authors claim to have discovered an objective, diagnostically useful “chemical signature” of the condition, and that this signature corresponds to a “hypometabolic response to environmental stress similar to dauer.” Although we salute the authors’ methodological efforts and interesting findings, we have serious concerns regarding their interpretation.

First, by stating that CFS has a chemical “signature,” the authors suggest that they have discovered something very specific. However, findings of metabolic differences between patients with CFS and healthy controls do not automatically yield a test that can single out a specific disease. The authors have not investigated the diagnostic specificity in relation to other conditions with a phenotype similar to CFS, such as fibromyalgia (2). They have also not explored metabolomics in otherwise healthy subjects who have been in a state of prolonged, profound inactivity and stress, or in other chronic conditions characterized by reduced bodily activity, such as cardiac failure. For all we know, a similar metabolic response might be present in all these conditions. Moreover, the clinical definitions of CFS are based on pragmatic agreements among researchers, and lack proper validation (3). Thus, the scientific reasoning comes close to a tautology. First, one defines a clinical syndrome and assumes that it represents a specific disease; then, one finds a correlate to one’s own construct and uses this correlate as “proof” of its specificity. The authors’ own statement that “comparison with related medical disorders like depression and posttraumatic stress disorder will be needed to validate the universality and specificity of these findings” (1) also makes it clear that their discovery of a signature of CFS/myalgic encephalomyelitis is invalidated.

Second, when discussing the possibilities of novel therapeutics, the authors seem to assume that their findings of metabolic alterations in CFS suggest a causal explanation of patients’ clinical symptoms. Evidently, the cross-sectional nature of their design does not allow causal claims to be made. More generally, results obtained at the metabolic level do not automatically mean that a disease should be understood at that level or that “personal” or “psychosocial” causes can be ruled out. A metabolic correlate to a clinical syndrome does not explain why these abnormalities are there.

Third, their discussion of a dauer response to environmental stress involves two references that mostly concern the nematode Caenorhabditis elegans (4, 5). Although this reference may not be irrelevant, the authors missed the opportunity to contextualize their findings in relation to clinical CFS research and stress theories (6⇓–8). In humans, stress responses necessarily involve orchestrated neuroendocrine signaling, which, in turn, is influenced by mental states, such as conscious and unconscious interpretation of the surroundings (8). Thus, the findings of a possible dauer response in CFS might add to the growing body of evidence suggesting that complex relationships between different levels of biological organization, from the behavior of the whole organism trying to adapt to a (social) environment, via organs and cells to genetic variants, are core characteristics of this syndrome (6).

New technologies and diagnostic strategies that enable increased understanding of the fatigued person are much needed. However, to avoid undue hype, false hopes, and body/mind pitfalls, results should be interpreted with caution.

Footnotes

  • ↵1To whom correspondence should be addressed. Email: henrik.vogt{at}ntnu.no.
  • Author contributions: H.V., E.U., and V.B.W. wrote the paper.

  • The authors declare no conflict of interest.

References

  1. ↵
    1. Naviaux RK, et al.
    (2016) Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci USA 113(37):E5472–E5480.
    .
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Borchers AT,
    2. Gershwin ME
    (2015) Fibromyalgia: A critical and comprehensive review. Clin Rev Allergy Immunol 49(2):100–151.
    .
    OpenUrlCrossRefPubMed
  3. ↵
    1. Brurberg KG,
    2. Fønhus MS,
    3. Larun L,
    4. Flottorp S,
    5. Malterud K
    (2014) Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): A systematic review. BMJ Open 4(2):e003973.
    .
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Lant B,
    2. Storey KB
    (2010) An overview of stress response and hypometabolic strategies in Caenorhabditis elegans: Conserved and contrasting signals with the mammalian system. Int J Biol Sci 6(1):9–50.
    .
    OpenUrlPubMed
  5. ↵
    1. McElwee JJ,
    2. Schuster E,
    3. Blanc E,
    4. Thomas JH,
    5. Gems D
    (2004) Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279(43):44533–44543.
    .
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Wyller VB,
    2. Eriksen HR,
    3. Malterud K
    (2009) Can sustained arousal explain the Chronic Fatigue Syndrome? Behav Brain Funct 5:10.
    .
    OpenUrlCrossRefPubMed
  7. ↵
    1. McEwen BS
    (2006) Protective and damaging effects of stress mediators: Central role of the brain. Dialogues Clin Neurosci 8(4):367–381.
    .
    OpenUrlPubMed
  8. ↵
    1. Ursin H,
    2. Eriksen HR
    (2010) Cognitive activation theory of stress (CATS). Neurosci Biobehav Rev 34(6):877–881.
    .
    OpenUrlCrossRefPubMed
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Metabolic features of chronic fatigue syndrome revisited
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Metabolic features of chronic fatigue syndrome
Henrik Vogt, Elling Ulvestad, Vegard Bruun Wyller
Proceedings of the National Academy of Sciences Nov 2016, 113 (46) E7140-E7141; DOI: 10.1073/pnas.1615143113

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Metabolic features of chronic fatigue syndrome
Henrik Vogt, Elling Ulvestad, Vegard Bruun Wyller
Proceedings of the National Academy of Sciences Nov 2016, 113 (46) E7140-E7141; DOI: 10.1073/pnas.1615143113
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Medical Sciences

This Letter has a Reply and related content. Please see:

  • Relationship between Letter and Reply - November 03, 2016
  • Metabolic features of chronic fatigue syndrome - August 29, 2016
Proceedings of the National Academy of Sciences: 113 (46)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Footnotes
    • References
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Illustration of groups of people chatting
Exploring the length of human conversations
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490