In Reply

We thank Pfnür and Lösch for their readers’ letters and wish to comment on the aspects raised as follows.

The data on myalgic encephalomyelitis (or encephalomyelopathy)/chronic fatigue syndrome (CFS) are voluminous and sometimes controversial. A brief summary in our review article would not have done justice to this situation (1). Since 1986, more than 20 definitions of the syndrome have been published. Euromene, the European expert consensus group for ME/CFS, in 2020 recommended the criteria from the US Institute of Medicine (IOM) as ideal for use in primary care and the criteria from the US Centers for Disease Prevention and Control (CDC) as a screening alternative but as obligatory in the context of the so far optional symptom “post-exertional malaise” (PEM) (2). The criteria from the Canadian consensus conference are recommended for secondary care and research. In the opinion of the Euromene group, the diagnosis of ME/CFS is a purely clinical decision in view of the lack of biomarkers, the causes of the syndrome remain unknown causes, and treatment is symptomatic as causal treatment does not exist. The recently updated ME/CFS guideline from the UK Institute for Health and Care Excellence (NICE) basically underlines the importance of the named definitions but considers that a diagnosis can be made after three months, rather than the six months recommended by the IOM criteria (3). In Germany, IQWiG (the Institute for Quality and Efficiency in Health Care) is currently working on a report on ME/CFS, which will probably be published in 2023. Because of the inconclusive state of research, we avoided in our article to commit to unknown etiology (1). In our view, laboratory tests, in combination with a medical history, clinical examination, and if needed further technical investigations should be used to exclude other disorders that may be of noteworthy in terms of a differential diagnosis and for which specific treatments exist, in the sense of an avertible dangerous disease course. Non-targeted laboratory tests would not be helpful in view of the lack of ME/CFS biomarkers and would only increase the risk of false positive findings, with well known negative consequences.

A long-term vegan or vegetarian diet, illness-related resorption disorders, or resorption inhibiting medications can without question result in substitution dependent deficiencies in vitamin B12, iron, and—depending on the extent of exercise taken and exposure to sunlight—vitamin D. Questions regarding previous illnesses and medications taken are components of our recommendation for taking medical histories, as well as the question what the patients themselves think might be the cause, in the context of which special dietary regimens are often mentioned. In the additional DEGAM patient questionnaire on fatigue that we recommended in our article, questions about nutritional changes, special diets, and medicines taken require mandatory answers. We do, however, regard critically the premature explanation of fatigue in the absence of the named risk factors with moderately lowered vitamin or ferritin concentrations without existing anemia or neurological disorders. This poses the risk of overlooking important other causes. In the absence of concomitant anemia fatigue improved as a result of iron supplementation only in premenopausal women with low ferritin concentrations. In low normal concentrations of vitamin B12, cognitive performance and depression did not improve after vitamin substitution, for the symptom fatigue, no robust data exist (4). Vitamin D deficiency does not correlate with increased fatigue (5).