Abstract
Objective To 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).
Methods Sixty-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.
Results Acute 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.
Conclusion Future 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.
Glossary
- CV=
- coefficient of variation;
- EDSS=
- Expanded Disability Status Scale;
- HIIT=
- high-intensity interval training;
- HPLC-MS/MS=
- high-performance liquid chromatography–tandem mass spectrometry;
- IL-6=
- interleukin-6;
- KA=
- kynurenic acid;
- KYN=
- kynurenine;
- MCT=
- moderate continuous training;
- pNfL=
- plasma neurofilament light chain;
- pwMS=
- persons with multiple sclerosis;
- QA=
- quinolinic acid;
- TRP=
- tryptophan
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
↵* These authors contributed equally to this work.
↵† These authors share senior authorship.
The Article Processing Charge was funded by the authors.
- Received October 21, 2020.
- Accepted in final form January 21, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Letters: Rapid online correspondence
NOTE: All contributors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.nn.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within the last 8 weeks.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.