Trial reportNeurology(R) neuroimmunology & neuroinflammation2021
Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis.
2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph
Trial report in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 49 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 8% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Influence of Different Rehabilitative Aerobic Exercise Programs on (Anti-) Inflammatory Immune Signalling, Cognitive Performance and Processing Skills in Persons With MS - A Randomized Controlled Trial
The Influence of High-Intensity Interval Training Compared to Moderate Continuous Training on Cardiorespiratory Fitness, Symptom Improvement, and Disease-specific Biomarkers in Primary Progressive Multiple Sclerosis
Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Exercise-induced adaptations in the kynurenine pathway: implications for health and disease management.Frontiers in sports and active living · 2025Pooled it
- Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review.Frontiers in immunology · 2022Pooled it
- Functional Training Mitigates Reduced Circulating Indole-3-Lactate Levels in Persons With Relapsing-Remitting Multiple Sclerosis.Acta physiologica (Oxford, England) · 2026Trial
- Hypoxic conditioning in Parkinson's disease: randomized controlled multiple N-of-1 trials.Nature communications · 2025Trial
- Can non-pharmacological interventions change levels of neurofilament light in older adults at risk of dementia? A secondary analysis of the SCD-Well randomized clinical trial.The journal of prevention of Alzheimer's disease · 2025Trial
- Arterial stiffness moderates the link between NfL and cognition: The IGNITE study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Exercise-induced neuropeptidergic and neurochemical neuroadaptation in stress regulation and emotional disorders.Acta neurologica Belgica · 2026Review
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Thermoregulatory and plasma neurobiomarker responses to heat tolerance assessment in exertional heat illness and matched controls.Experimental physiology · 2026Article
- Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.Journal of neurology · 2026Article
- Review
- The kynurenine pathway storm in epilepsy: mechanisms and therapeutic implications.Acta epileptologica · 2026Review
- Physical activity, aerobic fitness, and AD blood biomarkers: The IGNITE study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Preventive strategies in neuroimmunology.Neurological research and practice · 2026Review
- Tryptophan metabolism in glaucomatous optic neuropathy: from metabolic dysregulation to therapeutic opportunities.Journal of translational medicine · 2026Review
- Serum neurofilament light chain in fibromyalgia: comparative evidence of neuronal injury across chronic pain conditions.Pain reports · 2026Article
- Exercise Training and Biomarkers of Neuroaxonal Injury in Multiple Sclerosis: Narrative Review.International journal of environmental research and public health · 2026Review
- Targeting low-grade inflammation in multiple sclerosis through the Wim Hof method or lifestyle intervention: a pilot comparative study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Synaptic Plasticity in Neurodegenerative Diseases: Impact of Exercise as Promising Therapeutic Tool.Cells · 2026Review
- Biomarkers associated with blood-brain interface regulation and relationships to exercise and epilepsy: a brief review.Frontiers in rehabilitation sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Niklas JoistenFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Annette RademacherFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Clemens WarnkeFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Sebastian ProschingerFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Alexander SchenkFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
David WalzikFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Andre KnoopFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Mario ThevisFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Falk SteffenFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Stefan BittnerFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Roman GonzenbachFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Jan KoolFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Wilhelm BlochFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Jens BansiFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland.
Philipp ZimmerFrom the Department of "Performance and Health (Sports Medicine)" (N.J., A.S., D.W., P.Z.), Institute of Sport and Sport Science, Technical University Dortmund; Department for Molecular and Cellular Sports Medicine (A.R., S.P., W.B.), Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne; Department of Neurology (C.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne; Center for Preventive Doping Research/Institute of Biochemistry (A.K., M.T.), German Sport University Cologne; Department of Neurology (F.S., S.B.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, Germany; and Department of Neurology (R.G., J.K., J.B.), Clinics of Valens, Rehabilitation Centre Valens, Switzerland. philipp.zimmer@tu-dortmund.de.
University of Cologne · DEUniversity Hospital Cologne · DEGerman Sport University Cologne · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DEJohannes Gutenberg University Mainz · DE
Funding
EPA EP-C-18-007
Abstract
objectiveTo examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).
methodsSixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention.
resultsAcute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT.
conclusionFuture studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS. TRIAL REGISTRATION INFORMATION: Clinical trial registration number: NCT03652519.
Indexed as
AdultAgedAged, 80 and overExerciseExercise TherapyFemaleHumansKynurenineMaleMiddle AgedMultiple SclerosisNeurofilament ProteinsProspective StudiesSingle-Blind MethodTryptophanKynurenineNeurofilament ProteinsTryptophan
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
NCT03652519ClinicalTrials.gov
NCT05229861ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.