Trial By Error: The Danish ME Association’s Open Letter

By David Tuller, DrPH

The Danish ME Association has sent and posted the following open letter to “Danish health politicians,” with a very impressive list of international signatories. It seemed important to give this letter wide circulation. (Note that footnotes 4 and 5 are linked to the names of two of the signatories, as in the original letter.)

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Open Letter to Danish Health Politicians

On March 14th 2019, a unified Danish Parliament voted to acknowledge WHO’s diagnostic classification of Myalgic Encephalomyelitis (ME – G93.3) as a biological illness and to separate ME from Functional Disorders.

The proposal passed is aligned with the current international scientific knowledge about ME.

Based on analysis of more than 9.000 peer-reviewed studies, the Institute of Medicine [1], Centers for Disease Control (CDC), National Institutes of Health (NIH), as well as the advisory report from the Dutch Health Council [2], conclude that ME is a serious chronic multisystem, biological disease that substantially limits the activities and quality of life of patients.

ME is a complex and physical disease for which there is currently no cure. It is not a psychological or psychosomatic disease. There is strong scientific evidence of neurological/autonomic dysfunction, immunologic and inflammatory pathologies, microbiome perturbation, metabolic/mitochondrial as well as cardiac abnormalities (and more) in patients.

Based on this scientific evidence, there is an imminent need to change the narrative of ME to avoid that patients are misdiagnosed or further stigmatized by falsely equating the disease with (chronic or unexplained) fatigue, deconditioning or psychosomatic classifications, like functional disorders, medically unexplained symptoms, somatoform disorders, somatic symptom disorder, functional somatic syndrome, neurasthenia, or bodily distress disorder/syndrome.

Patients have for decades been prescribed treatments like Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET), based on the idea that they suffer from “false illness beliefs”, fear of exercise or that they are deconditioned. This ‘deconditioning hypothesis’ as well as the ‘psychosomatic hypothesis’ of ME is not supported by biomedical research.

The treatments based on these hypotheses (CBT/GET) have produced no robust evidence in the past two decades, as the US Agency for Healthcare Research and Quality systematic literature review, and reanalysis of the largest ever study on CBT/GET (PACE trial) [3] have shown.

The CDC has recently removed its recommendations for CBT and GET from its website.

Furthermore, and of dire importance, patients internationally for more than 20 years have continually reported deterioration from following the advice of their doctors to gradually increase their exertion levels based on a GET protocol.

Post-exertional malaise (PEM), a worsening of symptoms after minimal physical or mental exertion, is the hallmark characteristic of the disease. GET worsens PEM and has the potential to cause lasting harm for patients with ME.

There is international consensus that funding biomedical ME research is the only way to create better insights into the physiological mechanisms of this debilitating disease, so we can provide better and more efficient care, based on the needs of patients and the biomedical nature of the disease, as well as effective treatments and potentially a cure. Biomarkers are also needed for accurate diagnosis.

More funding for biomedical research into ME is therefore urgently needed.

We ask that the Danish Government will strongly consider a long-term investment in biomedical ME research. It is an absolute priority and the only way to make the necessary progress to help stop what the CDC calls a “hidden health crisis”.

We would be happy to provide you with further insights based on our expertise, if needed.

This letter has also been sent to the Minister of Higher Education and Science, as well as the Danish Health Authority.

Sincerely

DENMARK

Kim Varming
Ledende overlæge
Klinisk Immunologisk Afdeling
Aalborg Universitetshospital

Rikke Katrine Jentoft Olsen, MSc, PhD
Associated Professor
Research Unit for Molecular Medicine
Department for Clinical Medicine
Aarhus University

Henrik Nielsen, MD, DMSC
Specialist i intern medicin og reumatology
Medlem af Radikale Venstres bestyrelse i Gentofte og Region Hovedstaden
MC Members of CA15111 – Member of European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE)

Jesper Mehlsen
Speciallæge
Klinik Mehlsen,
Peter Bangs Vej 7A, 2000 Frederikesberg
Seniorforsker
Enhed for Kirurgisk Patofysiologi
Juliane Marie Center
Rigshospitalet

Ana C. Gonzalez Ebsen 
PhD Student
Molekylær Medicinsk Forskningsenhed (MMF)
Aarhus University, Denmark

Ole Næsh Hendriksen
Speciallæge, dr.med.
Klinik Mehlsen
Peter Bangs Vej 7A
2000 Frederiksberg

Paula Fernandez Guerra, PhD, MSc
Biomedical researcher
Research Unit for Molecular Medicine
Aarhus University Hospital
Denmark

SWEDEN

Jonas Bergquist
Professor Uppsala University
MC Members of CA15111 – European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE)
Sverige

Sture Eriksson
Associated Professor
Vice chairmen
Swedish RME Association

Bo C. Bertilson 
MD, PhD
Research leader Bragee clinics and Musculoskeletal functions and pain
Div. Family Medicine and Primary Care, NVS 
Karolinska Institutet
Academic Primary Health care Center

Anders Rehnström
Specialistläkare
ME-Mottagningen
Stora Sköndal
Stockholm

Åsa Andersson
VD / Direktor
Stora Sköndal, Sverige

Sven Britton
Tidl. professor i infektionssjudomar
Karolinska Institutet
Sverige

Dr Per Julin, MD, PhD
Institution for Neurobiology, Care Sciences and Society (NVS)
Karolinska Instituttet
Senior Consultant
ME/CFS-policlinic, Neurological Rehabilitation Clinic
Stora Sköndal
Expert in SBU (Swedish Agency for Health Technology Assessment and Assessment of Social Services) review of ME/CFS:
https://www.sbu.se/en/publications/sbu-bereder/myalgic-encephalomyelitis-and-chronic-fatigue-syndrome- mecfs/

Muhammad Rizwan
MS Infection Biology
Associate Researcher
Clinical Microbiology Uppsala University Hospital, Sweden

Petter Brodin
Senior Researcher & physician
Department of pediatrics
Karolinska University Hospital

Eirini Apostolou, Ph.D
Dept. of Clin. & Exp. Med.
Division of Cell Biology
Linköping University
58185 Linköping
Sweden

Kumari Ubhayasekera (PhD)
Department of Chemistry-BMC
Uppsala University
Uppsla, Sweden

Carl-Gerhard Gottfries
Professor Emerritus of Psychiatry
Gottfries Clinic Krokslätts Torg 5,
43137 Mölndal

Wimal Ubhayasekera
Uppsala University
Uppsala, Sweeden

Björn Bragée, MD
Specialist in Pain Medicine,
Founder of ME-Center, Stockholm

NORWAY

Olav Mella Department director, professor
Department of Oncology and Medical Physics
Haukeland University Hospital, Bergen, Norway
www.helse-bergen.no

Per Ole Iversen, Professor Department of Nutrition
University of Oslo,
P.O. Box 1046 Blindern, 0317 Oslo

Ola Saugstad
Professor emeritus MD, PhD, FRCPE
Professor of Pediatrics at the University of Oslo.
Director of Department of Pediatric Research
Consultant in Neonatology
Rikshospitalet, University of Oslo,
Norway

Kristian Sommerfelt
Pediatrician
MD, PhD. Professor
Haukeland University Hospital
University of Bergen
Bergen, Norway.

Tor Lea
Professor emeritus, PhD
Dept. of Chemistry, Biotechnology and Food Science
Norwegian University of Life Sciences
Ås, Norway

FINLAND

Olli Polo, MD, PhD
Specialist in Pulmonary Medicine
Expert in Sleep Medicine
Tampere University Hospital, Tampere, Finland

Markku Partinen, MD, PhD, FAAN
Professor, Speclist in Neurology, Research Director
Somnologist, ESRS, Expert in Sleep Medicine
Helsinki Sleep Clinic, Vitalmed Research Centre
Helsinki, Finland

POLAND

Dr Pawel Zalewski
Nicolaus Copernicus University in Torun Collegium Medicum in Bydgoszcz
M. Sklodowskiej-Curie 9, Poland, Bydgoszcz
EUROMENE MC Member

GERMANY

Carmen Scheibenborgen
Professor Dr. Med, Leiterin Immundefekt-Ambulanz
FÄ für Hämatologie, Onkologie und Fachimmunologin. Charite, Berlin

Uta Behrends Prof. Dr. med.
Pediatric hemooncologist
CFS policlinic
Children’s Hospital
Technische Universitaet Muenchen
Munich

BELGIUM

Dr AM Uyttersprot
Neurologist CFS
Maria Theresialaan 33/6
1800 Vilvoorde, Belgium

NETHERLANDS

Prof Dr Frans C Visser, cardiologist
ME/CFS specialist
Stichting CardioZorg
Planetenweg 5, 2132HN Hoofddorp, Holland

Dr C (Linda) MC van Campen, cardiologist ME/CFS specialist
Stichting CardioZorg
Planetenweg 5
2132HN Hoofddorp, Holland

UNITED KINGDOM

Dr Luis Nacul
Clinical Associate Professor,
London School of Hygiene and Tropical Medicine,
London UK

Dr Charles Shepherd MB BS
Hon Medical Advicer
ME Association
7 Apollo Office Court
Radclife Road, Buckingham

Dr Nigel Speight
Paediatrician
Durham, UK

Derek Pheby
Visiting Professor of Epidemiology,
Buckinghamshire New University,
High Wycombe, England,
MC Member of CA15111 – European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE).

Dr. K.N. Hng
MBChB, MRCP, PG Cert in WBME, FHEA
Author of “M.E. and Me: A Doctor’s Struggle with Chronic Fatigue Syndrome”

Professor Chris P Ponting
University of Edinburgh
MRC Human Genetics Unit

Dr Sarah Myhill,
Upper Weston,
Llangunllo, Knighton,
Powys LD7 1SL
Author of the book “Diagnosis and Treatment of Chronic Fatigue Syndrome and Myalgic Encephalitis”

Prof Simon Carding
Head, Gut Microbes and Health Research Programme
Quadram Institute Bioscience,
Norwich Research Park, NR4 7UA

Nina Muirhead BA(oxon) BMBCh(oxon)
MRCS DOHNS MEd PGDipDerm
Specialty Doctor in Dermatologic Surgery
Chair of CFS/ME Research Collaborative (CMRC) Education Working Group Buckinghamshire

William Weir
Consultant Physician
London

Tom Wileman
Professor Molecular Virology
Quadram Institute Bioscience
University of East Anglia
Norwich Research Park
Norwich, NR4 7UQ

Dr Cara Tomas
Research associate,
Newcastle University,
Newcastle upon-Tyne, UK

Dr Penny Powell
Senior Lecturer in Cell and Molecular Virology
Norwich Medical School, University of East Anglia
Norwich Research Park
Norwich NR4 7TJ, UK

Dr Amolak S Bansal
Consultant in Clinical Immunology, allergy and CFS/ME
St Anthony’s Hospital
Cheap, SM3 9DW,
England

Dr Ben Marsh
Consultant Neurodisability Paediatrician
Clinical Director Community Paediatrics
University Hospitals Plymouth NHS Trust
England

AUSTRIA

Francisco Westermeier
Institute of Biomedical Science
University of Applied Sciences, FH JOANNEUM
Graz, Austria
(CA15111) European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE)
Management Committee: Austria

ITALY

Professor Umberto Tirelli
Senior visiting scientist National Cancer Institute
Aviano Italy

Dr. Paolo Cornelio Brambilla
General Practitioner, Psychotherapist.
Italian delegate at European M.E. Alliance
Member of the Scientific Committee of CFS-ME ODV, Italy.

SPAIN

Dr Jose Alegre, MD; PhD
Vall d’Hebron University Hospital
ME/CFS Clinical Unit
Barcelona, Spain
Email: jalegre@vhebron.net

Dr Jesús Castro, PhD
Vall d’Hebron University Hospital
Mediterranea Research Bldg (VHIR)
ME/CFS Research Unit
Barcelona, Spain
E-mail: jesus.castro@vhir.org
ORCID: http://orcid.org/0000-0002-2481-3052

LATVIA

Uldis Berkis, asoc. prof.
Riga Stradins University
Letland

Modra Murovska, MD, PhD;
Riga Stradiņš University,
Riga, Latvia;
CA15111 Action Chair European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE)
Letland

Zaiga Nora-Krukle, Ph.D
Senior researcher at Institute of Virology and microbiology,
Riga Stradins University
COST action CA15111, MC substitute
EATRIS coordinator of Latvia node

BULGARIEN

Assoc.Prof. Evelina Shikova
Head NRL “Herpes and Oncogenic Viruses”
National Center of Infectious and Parasitic Diseases
Sofia,
Bulgaria

ROMANIA

Carmen-Adella Sirbu
Associate Professor of Neurology,
Titu Maiorescu University
Central Military Emergency University Hospotal, Bucharest, Romania.
MC Members of CA15111 – European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE).

SERBIA

Sekulic Slobodan
Full research professor
MC member of CA15111
Medical Faculty Novi Sad, Serbia

USA

Ronald G. Tompkins, M.D., Sc.D.
Sumner M Redstone Professor of Surgery
Harvard Medical School
Massachusetts General Hospital
USA

Linda Tannenbaum
Founder and CEO
Open Medicine Foundation
USA

Robert D Phair PhD
Chief Science Officer
Integrative Bioinformatics Inc
Mountain View, CA
USA

Ronald W. Davis, PhD
Stanford University
Director, Stanford Genome Technology Center
Director, ME/CFS Collaborative Research Center at Stanford
Director, Open Medicine Foundation Scientific Advisory Board
USA

Wenzhong Xiao
Assistant professor of Bioinformatics
Director of the Inflammation & Metabolism Computational Center
Harvard Medical School & Massachusetts General Hospital
USA

Mady Hornig, MA, MD [4]
Associate Professor of Epidemiology
Columbia University Mailman School of Public Health
USA

Leonard A. Jason, Ph.D. 

Professor of Psychology | DePaul University
Director, Center for Community Research
990 W. Fullerton Ave., Suite 3119
Chicago, Il. 60614
Telephone: 773-325-2018
Website: http://leonardjason.com/
USA

Michael VanElzakker, PhD
Research Fellow, Neuroscience & Neurotherapeutics
Harvard Medical School & Massachusetts General Hospital
Instructor, Tufts University
USA

Betsy Keller, PhD
Professor, Exercise Science
Ithaca College, Ithaca, NY
Co-Coordinator, Clinical Core
NIH-funded Collaborative Research Center for the Study of ME/CFS Cornell University, Ithaca, NY,
USA

H. Craig Heller, Professor
Biology Department
Stanford University
Stanford, CA 94305-5020 USA

Jennifer Frankovich, MD MS
Clinical Associate Professor
Pediatric Rheumatology
Stanford University
Co-Director, Stanford PANS Clinic
Director, Stanford PANS research program
USA

Mario R. Capecchi
Distinguished Professor
University of Utah School of Medicine
USA

Todd E. Davenport, PT, DPT, MPH, OCS
Professor & Program Director
University of the Pacific
Thomas J. Long School of Pharmacy & Health Sciences
Department of Physical Therapy
USA

Robert K. Naviaux, MD, PhD
Professor of Genetics
Biochemical Genetics and Metabolism
Departments of Medicine, Pediatrics, and Pathology
Co-director, The Mitochondrial and Metabolic Disease Center (MMDC)
UCSD School of Medicine
214 Dickinson St., Room C-107
San Diego, CA 92103-8467
USA

Amel Karaa, MD
Assistant Professer,
Harvard Medical School
Director, Mitochondrial Disease Program,
Massachusetts General Hospital

Lars Steinmetz, Ph.D.
Professor of Genetics, Stanford University
Co-Director, Stanford Genome Technology Center
Principal Investigator & Senior Scientist, Genome Biology Unit, EMBL
USA

J. Mark VanNess, Ph.D.
Professor – Health and Exercise Science
University of the Pacific
Stockton, CA 95211
Scientific Advisor – WorkWell Foundation, Ripon, CA
USA

Derya Unutmaz, M.D.
Professor, Jackson Laboratory for Genomic Medicine
Professor, University of Connecticut School of Medicine
Farmington, CT, 06032,
USA

Staci R. Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation is a fiscally sponsored program of United Charitable
P.O. Box 1435
Ripon, CA 95366
USA

Dr. Alan R. Light, Ph.D.
Professor
Depts. of Anesthesiology and Neurobiology and Anatomy
3C 444 SOM
University of Utah
30N 1900 E.
Salt Lake City, UT 84132

Lucinda Bateman, MD
Chief Medical Director
24 South 1100 East, Suite 205
Salt Lake City, Utah 84102
P 801.359.7400 | F 801.359.7404
lbateman@batemanhornecenter.org

Maureen R. Hanson
Liberty Hyde Bailey Professor
Director, Cornell University Center for Enervating Neuroimmune Disease
Ithaca, NY, USA

Joyce Ferrone,
FNP-BC Nurse Practitioner
24 South 1100 East, Suite 205
Salt Lake City, Utah 84102, USA

Benjamin H. Natelson, MD
Director, Pain & Fatigue Study Center
Professor of Neurology
Icahn School of Medicine at Mount Sinai
New York, NY 10029, USA

Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD 21287
USA

CANADA

Alain Moreau PhD
Director / Directeur
Interdisciplinary Canadian Collaborative Myalgic Encephalomyelitis Research Network (ICanCME)
Full Professor
Department of Stomatology, Faculty of Dentistry
Department of Biochemistry and Molecular Medicine, Faculty of Medicine
Université de Montréal
Scientific Director
Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases
Sainte-Justine University Hospital Research Center,
3175 Cote-Ste-Catherine Road, Montreal, Qc, H3T 1C5, Canada

Patrick O. McGowan, PhD
Associate Professor Departments of Biological Sciences, Cell and Systems Biology, Psychology, Physiology University of Toronto SW-548,
1265 Military Trail, Toronto ON M1C1A4 Canada
www.utsc.utoronto.ca/~pmcgowan
Lab Twitter: @MethylNation

NEW ZEALAND

Rosamund Vallings MNZM, MBBS
Howick Health and Medical Clinic
Howick, Auckland
New Zealand

Lynette Hodges, PhD
Clinical Exercise Physiologist/Senior Lecturer in Exercise Science.
School of Sport, Exercise and Nutrition,
Massey University,
Private Bag 11-222
Palmerston North, New Zealand

Dr Eiren Sweetman
Department of Biochemistry,
University of Otago, New Zealand

Don Baken PhD, PGDipClinPsych
Registered Clinical Psychologist
Research Coordinator
Massey University
New Zealand

AUSTRALIEN

Sonya Marshall-Gradisnik
Co- Director National Centre for Neuroimmunology and Emerging Diseases
Professor lmmunology, Menzies Health Institute Queensland,
Gold Coast campus,
Griffith University, QLD 4222,

Neil R. McGregor BDS, MDSc, PhD [5]
Clin. Assoc. Prof. University of Melbourne
Adj. Prof. Victoria University

Professor Donald R Staines
National Centre for Neuroimmunology and Emerging Diseases
Griffith University

Dr Brett A. Lidbury, Ph.D. FFSc (RCPA)
Associate Professor, The National Centre for Epidemiology and Population Health, RSPH, College of Health and Medicine,
The Australian National University
Canberra ACT 2601 Australia.
W: http://nceph.anu.edu.au/about-us/people/brett-lidbury
T: 02-6125 7875

Paul Fisher
Professor of Microbiology,
La Trobe University,
VIC 3086,

Leighton Barnden
Medical scientist,
National Centre for Neuroimmunology and Emerging Diseases,
Menzies Health Institute Queensland, Griffith University

___________________________

[1] IOM 2015 report

[2] https://www.gezondheidsraad.nl/en/task-and-procedure/areas-of-activity/optimale-gezondheidszorg/mecfs

[3] https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3

[4] Indeed, there is evidence that such approaches (CBT/GET) may not only be ineffective, but may actually be harmful to patients. (Davenport TE et al. Checking our blind spots: current status of research evidence summaries in ME/CFS.Br J Sports Med 2019;53:1198. doi: 10.1136/bjsports-2018-099553)

[5] Post-exertional malaise is associated with changes in glycolysis and acetylation in ME/CFS patients. These changes are consistent with a hypo-acetylation state and are likely to significantly alter histone acetylation and the actions of acetylation and deacetylation in controlling cellular enzymatic events. Well-designed studies evaluating these important factors are warranted (McGregor Neil R. et al: Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Caseshttps://www.mdpi.com/2075-4418/9/3/70)

{ 7 comments… add one }
  • Guido Den Broeder 8 January 2020, 7:42 pm

    Once again you are supporting something that will do more harm than good. Can you tell why it will? You’re supposed to be a journalist and you’ve been given all the relevant information.

  • Richard Vallee 8 January 2020, 8:31 pm

    This is a fantastic letter. One of the best demands for change I have seen. High praise to whoever wrote it.

    And enormous thanks to those who signed it. I hope we can add many more in the near future.

    Speaking of which, do you think it would be a good idea to do something similar for the UK GWAS? If ME researchers want a future in this field, it’s crucial that they voice it. We all know it will be vindicated, whatever happens.

    Heck, refusal despite such strong support could even make a pretty good Streisand effect, maybe a pivotal moment after years of MRC promises that ME research is a priority. It kind of was in Canada with Moreau’s research. Although we do have the benefit of a functioning government…

  • Peter Trewhitt 8 January 2020, 9:32 pm

    A big thank you to the Danish ME Association for sharing this clear, concise and well argument statement of the need for funding for research into ME.

    It should ideally be considered by all governments.

  • @MECFSNews 9 January 2020, 5:34 am

    Great letter!

  • Pia 9 January 2020, 10:15 am

    Thank you for sharing the open letter!

  • Ken Lassesen 11 January 2020, 4:51 pm

    I would love to see Danish research focus on the microbiome. That is a big data/data science research that needs a good sample base. Denmark is good (Iceland is ideal) because of a more homogenous DNA population, more homogenous eating habits then many other places (specifically the US which is “Heinz 57” for both.

    The cost is **low**, likely the Danish outfit, https://www.gutxy.com/, could be talked into doing this at cost.

    Already, a citizen science initiative have already found statistically significant microbiome patterns ( P < 0.0000002 ) matching specific symptoms.

    The ideal sample would be **every ME/CFS** in Denmark with at least one non-ME/CFS blood relative (Since the microbiome tend to be inherited to a significant extent).

    The ideal would be to make this data set available to citizen data scientist to discover patterns. Example of such availability: http://lassesen.com/ubiome

    It is an approach that may easily get significant results within 6 months to a year, that can actually be applied to patients.

  • rdg 12 January 2020, 6:12 am

    Thank you so much for sharing the open letter, and good luck to the Danish ME-association. Keep up the good work!

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