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Observational Study
. 2025 Jun 24;272(7):476.
doi: 10.1007/s00415-025-13196-9.

A multi-domain lifestyle intervention in multiple sclerosis: a longitudinal observational study

Ilse M Nauta #  1 , Keeva N M Loughlin #  2 , Arianne S Gravesteijn  1   3 , Jade van Wegen  1 , Rosa P Hofman  1 , Nathalie Wilmsen  4 , Emma Coles  4 , Zoé L E van Kempen  1 , Joep Killestein  1 , Bob W van Oosten  1 , Eva M M Strijbis  1 , Bernard M J Uitdehaag  1 , Brigit A de Jong  5   6
Affiliations
Observational Study

A multi-domain lifestyle intervention in multiple sclerosis: a longitudinal observational study

Ilse M Nauta et al. J Neurol. .

Abstract

Objective: To examine the effects of a multi-domain lifestyle intervention that advocated a Mediterranean style diet, and concurrently targeted physical activity, stress and sleep, on multiple sclerosis.

Methods: A longitudinal observational study investigating the effect of a multi-domain lifestyle intervention (i.e., diet, exercise, stress, and sleep management) at four timepoints: start run-in, start and stop 3-month intensive interval, and 3-month follow-up. The primary outcome (i.e., impact of multiple sclerosis on daily functioning) and secondary outcomes (i.e., quality of life, general health, multiple sclerosis-specific symptoms, and lifestyle factors) were analyzed using mixed models. Analyses were repeated among subgroups based on program compliance, body mass index, education level, and multiple sclerosis-subtype.

Results: Out of 668 participants, 579 were included (age 46.2 ± 10.5 years, 84.5% women, and 71% relapsing-remitting multiple sclerosis). The impact of multiple sclerosis on physical functioning remained stable during the run-in period, but reduced significantly from baseline to both post-intervention (β = -2.50 [-3.40, -1.60]) and to 3-month follow-up (β = -2.00 [-2.93, -1.07]). The impact of multiple sclerosis on mental functioning decreased significantly across all time periods (run-in β = 1.86 [0.78, 2.94], post-intervention β = -3.48 [-4.58, -2.39], and 3-month follow-up β = -2.44 [-3.56, 1.31]). Effect size was greatest among participants with higher compliance, lower education, and obesity.

Interpretation: The lifestyle program was associated with reduced impact of multiple sclerosis on daily functioning, multiple sclerosis-related symptoms, mental quality of life, and general health determinants. Future randomized trials are needed to establish causal effects of lifestyle adjustments on multiple sclerosis.

Keywords: Health behavior; Mediterranean diet; Nutrition; Physical activity; Relaxation; Sleep.

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Conflict of interest statement

Declarations. Conflicts of interest: Ilse Nauta and Arianne Gravesteijn were supported by the Dutch National MS Foundation. Keeva Loughlin, Jade van Wegen, Rosa Hofman, and Zoé van Kempen have nothing to report. Bob van Oosten had received grants from Treatmeds and the Dutch MS Research Foundation, serves on data safety monitoring or advisory boards has royalties/licensees with Springer Media B.V. and is chair of the MS working group of the Netherlands Society of Neurology. Eva Strijbis has received research grants from ZonMW and the Dutch MS research foundation, and reports speaker relationships with Merck and Novartis. Nathalie Wilmsen and Emma Coles are employed by Voeding Leeft. Joep Killestein has received research grants for multicenter investigator initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd, Biogen, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd, Biogen, Immunic, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trials of Immunic (payments to institution only). Bernard Uitdehaag reports consultancy fees from Immunic Therapeutics. Brigit A. de Jong reported receiving grants from Dutch MS Research Foundation (project number 15-911), National MS Foundation, and Dutch MS Society. B.A. de Jong received research support from the Dutch National MS Foundation and the Dutch Ms Research foundation, she is member of the medical advisory board of the Dutch MS Society, chair of the committee for the revision of the guideline on disease-modifying therapy and MS for the Netherlands Society of Neurology, and chair of the committee of the Dutch National MS registration of the Netherlands Society of Neurology.

Figures

Fig. 1
Fig. 1
Flowchart of the LIMS study. Abbreviations: Post-int = post-intervention measurement; 3-mo. FU = 3-month follow-up measurement
Fig. 2
Fig. 2
Outcome measures at each time-point. The means and 95% confidence intervals at each time-point regarding the following outcome measure: a MSIS-29 physical; b MSIS-29 psychological. *Significant change between baseline assessment and other time-points. For p values, see Table 2. Abbreviations: MSIS-29 = Multiple Sclerosis Impact Score; Post-int. = post-intervention; 3-mo. FU = 3-month follow-up measurement
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