Research Review: New Evidence on Gluten-Free Diets for MS + My Testing Strategy

A comprehensive research paper caught my attention this week, and it reinforced something I've observed in my clinical practice for years: wheat and gluten may be contributing to MS symptoms in some people.

The Role of Nutrition and Physical Activity in Modulating Disease Progression and Quality of Life in Multiple Sclerosis (Nutrients, 2025)

This comprehensive review examined 46 prospective studies on how diet and exercise affect multiple sclerosis progression and quality of life. The most compelling section focused on emerging research about gluten-free diets and a specific wheat protein called amylase trypsin inhibitors (ATI).⁽¹⁾

ATI are non-gluten proteins found in wheat that may trigger immune responses separate from celiac disease. When researchers fed mice with MS-like conditions wheat-based food containing ATI, the animals developed much more aggressive disease compared to those eating ATI-free diets.⁽²⁾

The human research is equally intriguing. One study followed people with MS for 4.5 years, comparing those who adhered to a gluten-free diet versus those who didn't. People with better adherence to the gluten-free diet experienced significantly less disability progression and fewer new inflammatory brain lesions on MRI scans.⁽³⁾

The review also highlighted research from my own lab, where we studied a modified Paleolithic elimination diet (which excludes gluten along with other potentially inflammatory foods). Participants experienced significant reductions in fatigue and improved quality of life, as well as better hand function and cognitive performance.^(4,5)

Notably, when researchers combined data from multiple diet studies, the gluten-free Paleolithic approach showed the largest improvements in fatigue reduction and both mental and physical quality of life measures.⁽⁶⁾

My Takeaway

Gluten and wheat aren't necessarily problematic for every person with MS or autoimmune conditions, but they may be generating abnormal immune responses in some people. Since we don't yet know which specific wheat molecules trigger these reactions, I recommend a systematic approach to testing whether gluten affects you.

Here's the strategy I use with my patients:

Step 1: Get a baseline measurement. Complete a medical symptoms questionnaire to calculate your current symptom burden with a numeric score.

Step 2: Go carefully gluten AND dairy-free for 3 months.  I recommend removing dairy simultaneously because the protein sequences in dairy and gluten are similar enough that your immune system may cross-react between them.

Step 3: Focus on naturally gluten-free whole foods. Rather than substituting gluten-free processed products (which are often nutrient-poor), emphasize vegetables, fruits, meats, and fish. If you prefer a Mediterranean approach, add legumes while keeping the diet gluten-free.

Step 4: Reassess after 3 and 6 months. Retake the symptoms questionnaire. If your scores improve, gluten may have been contributing to your symptoms

For me personally, gluten and wheat exposure triggers trigeminal neuralgia flares, so I'm very careful about what I eat. When I travel, I take digestive enzymes like Gluten Shield to help protect against cross-contamination in restaurants—they don't allow me to eat wheat-based foods, but they make dining out less stressful.

If you discover gluten sensitivity, carrying digestive enzymes for restaurant meals can significantly reduce your stress around eating away from home.

Citations

1. Grosu C, Ignat EB, Alexa D, Ciubotaru A, Leon MM, Mastaleru A, et al. The Role of Nutrition and Physical Activity in Modulating Disease Progression and Quality of Life in Multiple Sclerosis. Nutrients. 2025;17(16).
2. Zevallos VF, Yogev N, Hauptmann J, Nikolaev A, Pickert G, Heib V, et al. Dietary wheat amylase trypsin inhibitors exacerbate CNS inflammation in experimental multiple sclerosis. Gut. 2023;73(1):92-104.
3. Rodrigo L, Hernandez-Lahoz C ,Fuentes D,Mauri G, Alvrez N Vega J, G onzalez S. Randomised Clinical Trial Comparing the Efficacy of A Gluten-Free Diet Versus A Regular Diet in A Series of Relapsing-Remitting Multiple Sclerosis Patients. International Journal of Neurology and Neurotherapypy 2014;1(1).
4. Wahls TL, Titcomb TJ, Bisht B, Eyck PT, Rubenstein LM, Carr LJ, et al. Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial. Mult Scler J Exp Transl Clin. 2021;7(3):20552173211035399.
5. Crippes LJ, Saxby SM, Shemirani F, Bisht B, Gill C, Rubenstein LM, et al. Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial. Mult Scler J Exp Transl Clin. 2023;9(4):20552173231209147.
6. Snetselaar LG, Cheek JJ, Fox SS, Healy HS, Schweizer ML, Bao W, et al. Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials. Neurology. 2023;100(4):e357-e66.