Fasting, ketogenic, and anti-inflammatory diets in multiple sclerosis: a randomized controlled trial with 18-month follow-up
Lina S. Bahr,
Judith Bellmann-Strobl,
Daniela A. Koppold,
Rebekka Rust,
Tanja Schmitz-Hübsch,
Maja Olszewska,
Jean Stadlbauer,
Markus Bock,
Michael Scheel,
Claudia Chien,
Jan Multmeier,
Alexander Krannich,
Andreas Michalsen,
Friedemann Paul,
Anja Mähler
Affiliations
Lina S. Bahr
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Judith Bellmann-Strobl
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Daniela A. Koppold
Institute of Social Medicine, Epidemiology, and Health Economics, corporate member of Freie Universität Berlin and Humboldt-Universität, Charité - Universitätsmedizin
Rebekka Rust
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Tanja Schmitz-Hübsch
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Maja Olszewska
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Jean Stadlbauer
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Markus Bock
Department of Hand Surgery, Upper Extremity and Foot Surgery, Center for Orthopedic Rheumatology and Trauma Surgery, Hospital Waldfriede
Michael Scheel
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Claudia Chien
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Jan Multmeier
BioStats GmbH
Alexander Krannich
Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin
Andreas Michalsen
Institute of Social Medicine, Epidemiology, and Health Economics, corporate member of Freie Universität Berlin and Humboldt-Universität, Charité - Universitätsmedizin
Friedemann Paul
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Anja Mähler
Experimental and Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin
Abstract Background Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adulthood leading to disability and early retirement. Ketone-based diets improve the disease course in MS animal models and health outcomes in different pilot studies of neurodegenerative diseases. Methods We enrolled 105 individuals with relapsing-remitting MS (RRMS) in an 18-month, randomized, controlled study, and randomized them into (1) standard healthy diet (SD) as recommended by the German Nutrition Society, (2) fasting diet (FD) with 7-day fasts every 6 months with intermittent fasting at 6 of 7 days a week or (3) ketogenic diet (KD) with 20–40 g carbohydrates per day. Primary outcome was the number of new MRI lesions after 18 months in the KD and FD compared to SD and compared to baseline. Secondary outcomes included further MRI outcomes, disease biomarkers as well as metabolic, and clinical MS outcomes. Results Eighty-one participants completed the study. The primary endpoint number of new T2 lesions after 18 months did not change in any of the groups (SD 0 (0-(-1)), FD 0 (2 − 0), KD 0 (2 − 0)). Secondary endpoints were analyzed exploratorily: Compared to baseline, in the FD group, Neurofilament light chain (NfL) -concentrations were lower at 9 months (-1.94 pg/mL, p = 0.042) and depressive symptoms improved slightly at 18 months (p = 0.079). In the KD group, cognition improved at 18 months (symbol digit modalities test + 3.7, p = 0.020). Cardiometabolic risk markers (body mass index, abdominal fat, blood lipids, adipokines, blood pressure) improved in all three groups at 9 months differently and were partially associated with clinical outcomes in the FD and KD group. Conclusion The results suggest beneficial effects of dietary interventions, underscoring their potential as a complementary strategy in the treatment of RRMS. To further clarify the impact of such interventions on the disease course and patient-centered outcomes — such as cognitive function and depressive symptoms —future studies with larger, more homogeneous study populations are warranted. Trial registration ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.
