An Overview of Vitamins and Supplements in Multiple Sclerosis

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS), leading to a range of symptoms such as muscle weakness, fatigue, and cognitive impairment.¹ The cause of MS remains unknown, but it is believed to involve a combination of genetic, environmental, and immunological factors.¹ In recent years, there has been growing interest in the potential role of dietary supplements in managing MS. Myriad research has been undertaken on various supplements, including vitamin D, probiotics, omega-3 fatty acids, and other vitamins and minerals, to understand their potential benefits and limitations in MS treatment. By examining the evidence, pharmacists can gain insights into whether these supplements could be integrated into MS treatment regimens to improve patient outcomes.

There has been growing interest in the role of dietary supplements in managing MS | Image credit: amixstudio | stock.adobe.com

Vitamin D

Recent research has increasingly focused on the role of vitamin D in MS, exploring its potential as both a preventive measure and a therapeutic intervention. The immunomodulatory properties of vitamin D are well-documented, affecting both innate and adaptive immune responses.^1,2 Vitamin D receptors are present on various cell types, including neurons, oligodendrocytes, astrocytes, and microglia, indicating that vitamin D may also have direct effects on CNS development and function.³ This dual role suggests that vitamin D insufficiency could contribute to MS pathogenesis through both immunological and neuroprotective mechanisms.³

Observational studies suggest a correlation between low serum vitamin D levels and increased risk of developing MS, and several clinical trials have investigated the effects of vitamin D supplementation on clinical outcomes.^1,2 Despite the promising associations, the efficacy of vitamin D supplementation in altering the course of MS remains to be conclusively determined. ¹ Although some studies have reported beneficial effects, the overall evidence is mixed and further research is needed to establish causality and evaluate long-term outcomes.^2,4 Therefore, large-scale, well-designed clinical trials are essential to clarify whether vitamin D supplementation should be integrated into standard MS treatment protocols.

Probiotics

Recently, the relationship between the gut microbiome and CNS diseases has become a topic of interest for the scientific community. Increased research has been done on the gut-brain axis and the way the 2 systems influence each other. Related to MS specifically, there is evidence that the microbiome affects cells involved in MS pathogenesis, such as glial and neuronal cells, as well as cells of the immune system. There is also evidence for the impact of the microbiome on the integrity of the blood brain barrier.⁵

Many reports have shown that there are differences in the main bacterial taxa from the intestines of people with MS versus healthy controls.⁵ Interestingly, the composition of these taxa also differed between patients with different types of MS.⁵ What is less well understood is the causal relationship between the altered microbiota and MS, and whether the imbalance in the microbiome contributes to MS pathogenesis or instead reflects the already dysregulated autoimmune response.

It is logical, then, to wonder what effect, if any, probiotics might have on the development or progression of MS. Results in animal models, unfortunately, have been mixed. One study showed that in mouse models, administration of Lactobacillus, Escheria coli, and Prevotella strains could prevent the development and worsening of experimental autoimmune encephalitis (EAE), an animal model of MS, while another showed that administration of Lactobacillus strains resulted in exacerbation of disease in EAE.⁵

There are little data to support the hypothesis that administration of probiotics has a beneficial effect in people with MS. While some studies have shown that administration of probiotics improved clinical outcome measurements such as measures of disability and depression, it is recommended that these results be interpreted with caution due to small sample sizes and potential confounding variables.⁵ Though no large scale, randomized clinical trials testing the effects of probiotics in MS have been done, it is not uncommon for individuals with MS to supplement their disease modifying therapies (DMTs) with probiotics, considering the data available, the ease of access, and the relative lack of adverse effects.⁶ The National MS Society recommends patients with MS discuss the use of probiotics with their physician.⁷

Use of Omega-3 FA in MS

Saturated fatty acids, found in foods such as whole milk and butter, and trans fatty acids, like those in vegetable oils, have been notorious for contributing to high cholesterol levels and increasing inflammation. On the other hand, omega-3 fatty acids, sourced from vegetables, seafood, and fish oil, have been shown to have the opposite effect. Several studies suggest that omega-3 fatty acids may offer beneficial effects in MS through their anti-inflammatory and immune-modulatory mechanisms.⁸

Growing evidence indicates that omega-3 fatty acids may affect inflammatory markers and immune cells that are crucial in acute neuroinflammation.⁹ Several studies have suggested that omega-3 fatty acids may result in decreased inflammation in MS by competitively inhibiting arachidonic acid, reducing T-cell proliferation, lowering levels of inflammatory markers such as IL-1β, tumor necrosis factor (TNF) and IL-1, decreasing immune cell secretion of MMP-9, and inhibiting migratory activity of leukocytes.^10-18 Additionally, omega-3 supplementation has been linked to improved quality of life, reduced fatigue, and lower relapse rates in patients with MS.¹⁹ It is important to note that though these studies have shown promising results, others have reported mixed outcomes regarding the efficacy of omega-3 fatty acids on inflammation and quality of life. Given this, there is a lack of definitive evidence to support the widespread use of omega-3 fatty acids in MS treatment. Further research, particularly proof-of-concept studies using MRI-based outcomes, is needed to explore the potential role of omega-3 fatty acids in MS treatment.

As a pharmacist, it is crucial to emphasize that although omega-3 fatty acids may offer benefits to patients with MS, they should adhere to the recommended daily dose. Additionally, other medications should be considered, as omega-3 fatty acids can reduce the effectiveness of DMTs such as glatiramer acetate (Copaxone; Teva), interferon b-1a (Avonex; Biogen), and interferon b-1b (Betaseron; Bayer); interact with anticoagulant medications; and decrease the efficacy of insulin, oral diabetes medications, and blood pressure medications.⁷

Additional Supplements

Various additional vitamins and supplements have been explored for their potential benefits in managing MS. Melatonin, known for its antioxidant, anti-inflammatory, and immunomodulatory properties, has been studied for its potential therapeutic effects in MS.²⁰ Research suggests melatonin may regulate immune activity, reduce oxidative damage, and alleviate symptoms. Additionally, its ability to improve sleep quality addresses a common issue among patients with MS.^20,21

B complex vitamins may offer complementary benefits in MS management. Biotin (vitamin B7) has shown potential in progressive MS by promoting energy production in demyelinated neurons.²² Cobalamin (vitamin B12) and folic acid (vitamin B9) supplementation have been linked to reduced serum homocysteine levels, improved anemia status, and better mental health-related quality of life in patients with MS.²³

Coenzyme Q10, known for its antioxidant and anti-inflammatory properties, may help reduce oxidative stress and inflammation in MS, potentially slowing disease progression.²² Additionally, vitamin A, with its immunoregulatory effects, could play a role in modulating the autoimmune response that drives MS pathology, potentially contributing to disease management.²² Although these findings are encouraging, larger clinical trials are necessary to confirm their efficacy and establish optimal use in MS treatment plans.

Conclusion

Exploring dietary supplements presents a promising opportunity for managing symptoms of MS. Research on vitamins, probiotics, omega-3 fatty acids, and other supplements underscores their potential benefits and limitations. Although these supplements may offer advantages, they should be incorporated into MS treatment plans with caution and under medical supervision to avoid interference with existing therapies. Continued research is essential to establish their role in managing this complex disease. Given their knowledge and expertise in supplementation, pharmacists play a vital role and should be aware of these supplements in MS, as they will encounter them when consulting MS patients in the clinic or at the pharmacy.

REFERENCES

1. Sintzel MB, Ramette M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther. 2018;7(1):59-85. doi:10.1007/s40120-017-0086-4

2. Feige J, Moser T, Bieler L, Schwenker K, Hauer L, Sellner J. Vitamin D supplementation in multiple sclerosis: a critical analysis of potentials and threats. Nutrients. 2020;12(3):783. doi:10.3390/nu12030783

3. Gombash SE, Lee PW, Sawdai E, Lovett-Racke AE. Vitamin D as a risk factor for multiple sclerosis: immunoregulatory or neuroprotective? Front Neurol. 2022;13:796933. doi:10.3389/fneur.2022.796933

4. Munger KL, Ascherio A. Prevention and treatment of MS: studying the effects of vitamin D. Mult Scler. 2011;17(12):1405-1411. doi:10.1177/1352458511425366

5. Kujawa D, Laczmanski L, Budrewicz S, Pokryszko-Dragan A, Podbielska M. Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis. Gut Microbes. 2023;15(2):2274126. doi:10.1080/19490976.2023.2274126

6. Ghezzi L, Cantoni C, Pinget GV, Zhou Y, Piccio L. Targeting the gut to treat multiple sclerosis. J Clin Invest. 2021;131(13):e143774. doi:10.1172/JCI143774

7. Riccio P, Rossano R. Nutrition facts in multiple sclerosis. ASN Neuro. 2015;7(1):1759091414568185. doi:10.1177/1759091414568185

8. Mehta LR, Dworkin RH, Schwid SR. Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol. 2009;5(2):82-92. doi:10.1038/ncpneuro1009

9. Callegari PE, Zurier RB. Botanical lipids: potential role in modulation of immunologic responses and inflammatory reactions. Rheum Dis Clin North Am. 1991;17(2):415-425.

10. Gil A. Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother. 2002;56(8):388-396.

11. Namazi MR. The beneficial and detrimental effects of linoleic acid on autoimmune disorders. Autoimmunity. 2004;37(1):73-75. doi:10.1080/08916930310001637968

12. Rossetti RG, Seiler CM, DeLuca P, Laposata M, Zurier RB. Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation. J Leukoc Biol. 1997;62(4):438-443. doi:10.1002/jlb.62.4.438

13. Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989;320(5):265-271. doi:10.1056/NEJM198902023200501

14. Gallai V, Sarchielli P, Trequattrini A, et al. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol. 1995;56(2):143-153. doi:10.1016/0165-5728(94)00140-j

15. DeLuca P, Rossetti RG, Alavian C, Karim P, Zurier RB. Effects of gammalinolenic acid on interleukin-1 beta and tumor necrosis factor-alpha secretion by stimulated human peripheral blood monocytes: studies in vitro and in vivo. J Investig Med. 1999;47(5):246-250.

16. Shinto L, Marracci G, Baldauf-Wagner S, et al. Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis. Prostaglandins Leukot Essent Fatty Acids. 2009;80(2-3):131-136. doi:10.1016/j.plefa.2008.12.001

17. Ferrante A, Goh D, Harvey DP, et al. Neurophil migration inhibitory properties of polyunsaturated fatty acids. The role of fatty acid structure, metabolism, and possible second messenger systems. J Clin Invest. 1994;93(3):1063-1070. doi:10.1172/JCI117056

18. Weinstock-Guttman B, Baier M, Park Y, et al. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids. 2005;73(5):397-404. doi:10.1016/j.plefa.2005.05.024

19. Vitamins, Minerals and Supplements. National Multiple Sclerosis Society. Accessed March 13, 2025. https://www.nationalmssociety.org/managing-ms/living-with-ms/diet-exercise-and-healthy-behaviors/diet-nutrition/vitamin-mineral-and-supplements

20. Muñoz-Jurado A, Escribano BM, Caballero-Villarraso J, et al. Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action. Inflammopharmacology. 2022;30(5):1969-1596. doi:10.1007/s10787-022-01011-0

21. Skarlis C, Anagnostouli M. The role of melatonin in multiple sclerosis. Neurol Sci. 2020;41(4):769-781. doi:10.1007/s10072-019-04137-2

22. Tryfonos C, Mantzorou M, Fotiou D, et al. Dietary supplements on controlling multiple sclerosis symptoms and relapses: current clinical evidence and future perspectives. Medicines (Basel). 2019;6(3):95. doi:10.3390/medicines6030095

23. Nozari E, Ghavamzadeh S, Razazian N. The effect of vitamin B12 and folic acid supplementation on serum homocysteine, anemia status and quality of life of patients with multiple sclerosis. Clin Nutr Res. 2019;8(1):36-45. doi:10.7762/cnr.2019.8.1.36