Norwegian Doctor Slams Lipkin and Fluge/Mella


Founder of Health Rising and Phoenix Rising
Staff member
Norwegian Doctor pushes back against idea of immune problems in ME/CFS calling the Rituximab trial "weird" and the Lipkin findings "Problematic"

Experimental tests and treatments for CFS / ME

Doctors in Bergen will now examine whether the chemo cyclophosphamide works on CFS / ME. The ethical approval approval for such a risky treatment, seem strange when there is no evidence that there is anything wrong with patients immune system.

THE BIG Swedish newspaper Dagens Nyheter (1) recently reported that "Scientists have found clear changes in the immune system in people with chronic fatigue syndrome (CFS / ME)." The scientific article "Distinct plasma immune signatures in ME / CFS are presented early in the course of illness" (2) is published in the newly established journal Science Advances.

I am a paediatrician and have no detailed knowledge of cytokines, but as far as I understand, this is an exploratory study that measured levels of over 50 different cytokines on about 300 patients with CFS / ME. Patients were then compared with 350 healthy control subjects to see if a changed immune response was seen. It was not.

MATHEMATICS? But when they chose to analyse only those patients who had been sick for a maximum of three years, they found up regulation of many different cytokines (3), both pro-inflammatory and anti-inflammatory - if one can make such a simplification.

Those who had been sick for more than three years, had instead lower levels, so it must be mathematically since there was no difference for the whole group, which should not be surprising. “We were surprised to find that the levels of so many cytokines were higher in short-duration cases than in healthy controls. Equally surprising was the observation that these same cytokines were lower in long-duration cases than in healthy controls”.

HOW? One should be critical of studies that do not test a previously stated hypothesis, especially if the material must be broken down into subgroups, to look at the p value sky. Some call this type of study a type of fish expedition. How did they come to the conclusion that three-year disease was an appropriate cut-off to break up the material?

The researchers write that they did not engage in recruiting, and that it obviously can be difficult to find patients early in the disease. They also claim that the timing is based on how the immune system is affected by chronic viral infections: "A 3-year cutoff for early ME / CFS cases was used on the basis of feasibility of recruitment and longitudinal changes in immune profiles in persistent infections with West Nile virus, HCV and HIV. " But a 3 year cut off (or change) in these infections do not seem to exist.

BIOMARKERS? It is difficult to liberty oneself from the suspicion that the material possibly were analysed several times, with different cut-offs, and found a point where they found measurable change. In addition, the time when the disease actually began, is not clearly defined: Illness onset was defined as the date when a patient reported the onset of the clinical features that led to a later diagnosis of ME/CFS illness, rather than the date when a physician made the diagnosis of ME/CFS. Discrepancies were resolved by clinician consensus ratings after review of all available data”.
One can at best look at this as a study in which hypotheses are generated, and then using those hypotheses be tested on a new group of patients and controls. My guess is that this is unlikely to lead to any useful biomarkers for CFS / ME diagnosis, but obviously I can be wrong.

Problematic. It is possibly also problematic that many of the authors of this study already treat CFS / ME patients with various drugs. Three of them; José G. Montoya, Nancy G. Klimas and Lucinda Bateman, is involved in a treatment study, where patients receive supplements and ADHD drug Ritalin (4).

More common is that CFS / ME patients are treated with antivirals or antibiotics, although this does not have any proven effect today. Martin Lerner, who along with Klimas and Bateman was coauthor of the new IOM report that will rename CFS (5), looking for CMV, EBV and HHV-6, but also the parasite Babesia and bacteria Mycoplasma, Borrelia, Anaplasma and streptococci.

WEIRD. In Norway, researchers in Bergen use treatment that weakens the immune system. They believe that rheumatism medication rituximab, which removes B cells, has helped CFS / ME patients, and is now used in a proper double-blind study in Norway.

The same researchers wanted to test TNF-alpha inhibitor Enbrel on CFS / ME patients who did not respond to rituximab. This experiment was stopped after two of the four initial pilot patients were deteriorating (6). Rituximab is expensive, and doctors at Haukeland University Hospital will now examine whether the much cheaper chemo cyclophosphamide works on CFS / ME. Being given ethical approval (7) for such a risky treatment, seem strange when there is no evidence that patients have something wrong with immune system.

No conflicts of interest

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Well-Known Member
I completely understand why someone would doubt a study especially when they feel they "stumbled" onto something (I think that is what he meant) but I think it would be much more constructive to suggest ways to tighten up the study when moving forward. Scientists stumble onto things all the time. You don't ignore the results you try to replicate perhpas with a study that tightens up the process. Now that part takes money and that is our problem. There isn't enough money to go around for everyone to do their studies, put the information out and start replicating studies.

To me as a patient that has suffered for 40 years I find this to be exactly what has destroyed our being able to move forward and why here in the US the NIH is not terribly interested in giving us money. (Although that isn't really a good enough reason but they will use it.)

The only studies that should be shredded to bits at this point are those based on the UK criteria which has a heavy psychiatric dependent process. GET should be thrown out of the journals with PACE following.


New Member
The doctor who wrote this piece, Mats Reimer, is a very active proponent of the PACE trial results and is always very dismissive of the patient community and not the least interested in the biomedical aspects of ME/CFS. CBT and GET is what is evidence based in his opinion, and as you can see any biomedical findings are weird or problematic since they put the focus somewhere else than where the important stuff is – psychological causes and psychologically based treatments. Commonly a substantial part of his argument is about trying to tell incriminating facts about those he is opposing rather than discussing the facts. (He's from Sweden, mostly blogs on the swedish version of the Dagens Medicin site, but sometimes on the Norwegian sister site.)

He's not stumbled on this actually, he's been an active critic for many years, and has gotten references to all the important information in the comments to his articles...

Fluge and Mella now have published a very thorough reply to his article, very well written.


The critiques of this study deserves serious consideration rather than ad hominnum attacks. The associations and correlations found in this study as stated may be the result of chance. The multiple comparisons hazard is common in data dredging, It is the conclusions drawn as well as the correlations that are problematic at this time. They ave been critqued as being the result off post hoc fishing. Nevertheless the study, as a valid exploritory effort needs followup testing of the suggested hypothesis. The validity of the conclusions will only be determined by future studies. That is the way science works. Therefore, at this time, it is a fact that any statements that the study shows "definitive biomarkers" in the specified cytokines are premature and not supported by the evidence presented.


New Member
Yes, dean, I agree that the critiques deserves serious consideration. I see that my comment was an ad hominem attack, I guess it's where it's very easy to wind up when ad hominem attacks is one of Reimer's own primary lines of argumentation. It's downright impossible to get out of the polarization that he's very active in creating, even if one wants to. So even if it's got nothing to do with his arguments I just can't stop it – he's not new to the field, and he aggressively opposes that ME/CFS patients need something other than all other (in his view) chronic fatigue and functional somatic syndrome patients. Once in the comments sections of his blog posts he got the question about his own clinical experience with ME/CFS patients, and he answered something like ”I've met e few teenagers with what I suppose someone would call ME/CFS, and I'm pretty convinced that their problems were mainly psychosocial.”. Of course he can raise valid points about the research anyway, and he does often have valid points interwoven in the ramblings, but he also regularly attacks doctors working with ME/CFS-patients because he's ”heard” that someone does this or that, that the doctor some time in history has been interested in something that Reimer considers unscientific, and so on. It's pretty clear that he is convinced that the terms ME, CFS, SEID etc are silly in themselves (=it's not a disease) and that ME/CFS patients need nothing other than standard medical care, and he's kind of is using any argument he can find to slam ME/CFS research, ME/CFS patient communities and doctors working with ME/CFS. And regular doctors seem to listen to him and get reinforced in their belief that ME/CFS is primarily in the patients mind. So, yes, definitely, I and a lot of other ME/CFS patients in Sweden have trouble taking his arguments seriously, and he, on his hand, shows very little interest in listening to us, or ME/CFS researchers or doctors.

But I agree with him that the Hornig et al (2015) study shouldn't be taken for more than it is – being exploratory and definitely not showing any definitive biomarkers. I'm a patient of De Meirleir's, and following his work with testing patients for cytokine profiles since many years it seems reasonable to question the possiblity to find distinctive cytokine profiles that can be used as biomarkers for the whole ME/CFS patient group at all. The cytokine profiles of individual patients seem to often be very disturbed, but in a lot of different ways due to individual factors, and fluctuating a lot over the course of the disease. My guess is that something like Broderick's modelling of hormones and immune factors is needed, but that it might be possible to find 10 or 15 markers and use the network of relationships between them as a biomarker for ME/CFS (or a subgroup).


My comments only related to the unsupportable conclusions beging drawn from the Lipkin cytokine study as to finding "definitive biomarkers" . Fluge and Mella's responce do not refer to this study but rather to other issues related to treatments.

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