Several interesting papers came out in the last few months that I wanted to share with you. Below you’ll find a high-level overview of what each study entailed and what the results might mean for people with MS.
A Multi-Domain Lifestyle Intervention in Multiple Sclerosis: A Longitudinal Observational Study (PMID: 40553232)
This first paper comes from the Netherlands.
This was a non-randomized, observational study to evaluate the effects of a multi-domain lifestyle —diet, physical activity, stress management, and sleep — on people with MS. Patients were assessed at four points throughout the study:
- The beginning of an initial 3-month waiting period;
- The start and end of a 3-month intervention period; and
- A 3-month follow-up.
These assessments consisted of patient-reported outcomes. Participants were also followed for an additional 21 months after the 3-month intensive.
The intervention was an online program that encouraged people to improve their nutrition by adopting a modified Mediterranean diet. Patients received recipes, had access to an online community, and were able to ask questions of a registered dietitian and/or a lifestyle coach.
In the second month, participants were encouraged to increase their physical activity; relaxation strategies were covered in the third month. Throughout this 3-month intensive period, participants were invited to attend small group coaching meetings.
Of the 688 participants who enrolled, 579 participants completed at least one measurement.
The impact of MS on functioning was stable during the observation phase but reduced during the three-month intensive phase. The impact of the reduction in functioning slowly diminished over the 21-month period. The largest gains were observed in those who were obese, had lower education and higher levels of adherence to study interventions. Randomized, controlled studies are the next step.(1)
Results: The impact of MS on daily functioning was significantly reduced during the 3-month intensive, though it had been stable during the initial waiting period. This reduction on daily functioning was maintained at the 3-month follow-up, but slowly diminished over the subsequent 21 months following the study. The largest gains were observed in those who were obese, had lower education, and showed higher levels of adherence to the 3-month intensive.
Takeaway: An online program that supports people to adopt a modified Mediterranean diet, improve their physical activity, and improve their sleep may benefit people with MS, especially when it is combined with a virtual meeting space for participants, opportunities for peer-to-peer interaction, and access to support.
Randomized, controlled studies would the next step in order to determine causality.(1)
Efficacy of Fingolimod in Multiple Sclerosis Patients with Spinal Cord Involvement (PMID 4057039)
This next paper covers an open-label, prospective cohort study that looked at how well fingolimod (Gilenya®) works for people with spinal cord lesions (compared to those without) over one year. Out of 119 people who enrolled in the study, 68 had spinal cord lesions.
For those without spinal lesions, the fingolimod was found to reduce their annual relapse rate, decrease the number of enhancing brain lesions, and decrease their disability (EDSS score).
Patients with spinal cord lesions also showed a reduction in the number of new lesions and relapses in those with lesions — but their EDSS score (worse disability) increased, and they were more likely to experience disability progression that happened independently of new MS attacks. (This is called PIRA, for “progression independent of relapse activity”).
This confirms why spinal cord lesions are considered a significant risk factor for worsening disability.(2)
Takeaway: My interpretation of this study is that highly effective disease modifying treatments (DMTs) — like fingolimod — are good at preventing disability that occurs during MS relapses, but they're not as effective at stopping the type of disability progression that happens even without new attacks.
My theory is that PIRA is related to ongoing brain inflammation and problems with cellular energy production in the brain. Both of those issues are more responsive to improving nutrition and other lifestyle factors like sleep, exercise and stress management than they do to medications alone.
The Relationship Between Autoimmune Disorders and Multiple Sclerosis: Clinical Insights and Therapeutic Approaches (PMID 40563763)
This study looked at medical records from 580 people with MS in Poland to understand the connection between MS and other autoimmune diseases. The researchers found that people with MS who also developed a second autoimmune condition were more likely to be women, older, and had been living with MS for a longer time than those without.
The gender difference was striking: 20.24% of women developed a secondary autoimmune disease compared to only 8.13% of men. Autoimmune thyroid disease (like Hashimoto's thyroiditis) was the most common additional condition.
Takeaway: This study reinforces that autoimmune processes are more active in women than men, and the risk of developing additional autoimmune conditions increases over time. This is why I recommend investigating the underlying factors that may be contributing to ongoing autoimmune activity — things like gut bacteria imbalances, poor nutrition, and accumulated toxins in the body.
Addressing these issues may reduce the developing secondary autoimmune diseases and potentially lessen the severity of MS symptoms as well.
Research Progress On Microglial Pyroptosis And Inflammasomes: A Comprehensive Analysis (PMID: 40552323)
This study examines a cutting-edge area of research, pyroptosis and inflammasomes, specifically focusing on a molecule called NLRP3. When brain immune cells (microglia) are activated by NLRP3 (a molecule that signals cellular damage), it leads to the death of these immune cells and causes a rapid escalation of inflammation, ultimately worsening disability for patients.
This destructive process, called pyroptosis, occurs in people with MS, Parkinson's disease, and Alzheimer's disease.(4) Current therapies being investigated include some pharmaceutical drugs (like MCC950), as well as natural compounds like quercetin and melatonin.
Takeaway: I've been discussing the importance of NLRP3 since the 2020 revised version of the Wahls Protocol. The key message for me is that paying attention to how we can reduce the cellular damage signals that trigger this inflammatory cycle is important to stop disability progression. It's encouraging to see researchers exploring natural supplements that can lower NLRP3 activity. I'm particularly interested in whether Pectasol (which helps clear another cellular danger molecule called Galectin-3) might also be beneficial for this process.
Citations
- Nauta IM, Loughlin KNM, Gravesteijn AS, van Wegen J, Hofman RP, Wilmsen N, et al. A multi-domain lifestyle intervention in multiple sclerosis: a longitudinal observational study. J Neurol. 2025;272(7):476.
- Ashtari F, Pirmoradian M, Kavosh A, Arabi S, Adibi I, Feizi A, et al. Efficacy of fingolimod in multiple sclerosis patients with spinal cord involvement: an open-label study. Mult Scler Relat Disord. 2025;101:106590.
- Iwan M, Wojtowicz W, Milczarek J, Wyroba N, Wydrych Z, Falger O, et al. The Relationship Between Autoimmune Disorders and Multiple Sclerosis: Clinical Insights and Therapeutic Approaches. Brain Sci. 2025;15(6).
- Wang X, Li Z, Ma B, Jia Q. Research progress on microglial pyroptosis and inflammasomes: a comprehensive analysis. Front Aging Neurosci. 2025;17:1582579.
