The Evidence for Dietary Interventions and Nutritional Supplements as Treatment Options in Multiple Sclerosis: a Review
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Purpose of review
This review aims to critically evaluate published studies examining diets and nutritional supplements (excepting vitamin D) for the impact on prevention and prognosis of multiple sclerosis (MS).
There is a negative relationship between the Mediterranean diet and vascular disease, and vascular co-morbidities are associated with a worse MS prognosis. Low-fat, fish-based diets, sodium-restricted diets, calorie restriction, the paleo diet, and gluten-free diets have been examined, mostly in observational studies; results are inconclusive. With regard to nutritional supplements, pilot data show a possible benefit of biotin with respect to disability worsening in people with progressive MS (PMS). The best designed randomized controlled trials (RCTs) for PUFA supplementation have not shown significant impact, but several weaker RCTs have. Many other nutritional supplements have been tested, including several anti-oxidants. While some early studies show positive results, no result has been definitive.
Unfortunately, there is no strong evidence for a direct benefit of any given dietary intervention on MS risk or prognosis. However, due to its relationship with vascular co-morbidities, the Mediterranean diet has the strongest rationale for employment in PwMS. Higher-quality clinical trials are needed to ascertain the possible benefits of nutritional supplements.
KeywordsMultiple sclerosis Dietary interventions Nutritional supplements
Compliance with Ethical Standards
Conflict of Interest
Leah J. Mische declares no conflict of interest.
Ellen M. Mowry reports a grant from and serving as site PI on projects sponsored by Biogen, grants from Genzyme, non-financial support from Teva, serving as site PI on a trial sponsored by Sun Pharma, personal fees from UpToDate, outside the submitted work.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 3.Wallin M. The Prevalence of Multiple Sclerosis in the United States: A Population-Based Healthcare Database Approach. Eur Comm Treat Res Mult Scler. 2017.Google Scholar
- 9.Bhargava P. Diet and Multiple Sclerosis. In: Natl Mult Scler Soc. 2012. http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Documents/Diet-and-Multiple-Sclerosis-Bhargava-06-26-15.pdf.
- 10.Yang CY, Leung PSC, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: A comprehensive review. Clin Rev. Allergy Immunol. 2013;45:217–26.Google Scholar
- 12.James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013; https://doi.org/10.1177/1352458513489756.
- 15.Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010; https://doi.org/10.1016/S1474-4422(10)70086-7.
- 18.Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early pediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017.Google Scholar
- 20.Hadgkiss EJ, Jelinek GA, Weiland TJ, Pereira NG, Marck CH, van der Meer DM. The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis. Nutr Neurosci. 2015; https://doi.org/10.1179/1476830514Y.0000000117.
- 27.•• Marrie RA, Elliott L, Marriott J, Cossoy M, Blanchard J, Leung S, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurol. 2015;85:240–7. This is a large case-control study with an approximate 5:1 control to case ratio, matched based on sex, age and area code. The study demonstrated an increased risk of death when PwMS had cardiovascular co-morbidities. This study shows a strong relationship between MS outcomes and cardiovascular disease.CrossRefGoogle Scholar
- 28.•• Marrie RA, Elliott L, Marriott J, Cossoy M, Tennakoon A, Yu N. Comorbidity increases the risk of hospitalizations in multiple sclerosis. Neurol. 2015;84:350–8. This is a large case-control study with an approximate 5:1 control to case ratio, matched based on sex, age and area code. The study demonstrated an increased risk of hospitalization when PwMS had cardiovascular co-morbidities. This study shows a strong relationship between MS outcomes and cardiovascular disease.CrossRefGoogle Scholar
- 37.• Cortese M, Yuan C, Chitnis T, Ascherio A, Munger KL. No association between dietary sodium intake and the risk of multiple sclerosis. Neurol. 2017;89:1322–9. This data was extracted from a large prospective cohort study, the Nurse’s Health Study. While it was limited by methodology of accounting for inaccurate reporting of sodium consumption, it showed that there was no association between MS risk and sodium consumption.CrossRefGoogle Scholar
- 38.• Farez MF, Fiol MP, Gaitán MI, Quintana FJ, Correale J. Sodium intake is associated with increased disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2015;86:26–31. This cohort study examined sodium consumption and MS disease outcomes and demonstrated a striking relationship between PwMS who consumed high quantities of sodium compared to those who consumed low quantities in terms of MRI lesions and relapses. However, the study was limited by only taking one random urine sample per participant to estimate 24 h urine sodium levels.CrossRefPubMedGoogle Scholar
- 39.•• Fitzgerald KC, Munger KL, Hartung HP, et al. Sodium intake and multiple sclerosis activity and progression in BENEFIT. Ann Neurol. 2017; https://doi.org/10.1002/ana.24965. This study attempted to replicate the findings from the Farez et al. work. This study was superior in design because it included more random sodium samples which were used to estimate 24 h urine sodium levels. No relationship between estimated sodium levels and relapse activity or MRI lesions was found.
- 41.Piccio L, Stark JL, Cross AH. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol. 2008; https://doi.org/10.1189/jlb.0208133.
- 43.• Choi IY, Piccio L, Childress P, et al. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016;15:2136–46. This was the first randomized clinical trial using a ketogenic diet or calorie restriction in PwMS. The results were notable for determining improvement in quality of life and a small improvement in EDSS. However, the study design was limited by measuring outcomes long after the intervention ended and once the participants had been started on a Mediterranean diet.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Fitzgerald KC, Vizthum D, Henry Barron, Bobbie Sullivan P, Baer D, Cassard S, Kossoff E, Shoemaker T, Hartman A, Appel L, Mowry EM. A Pilot Study of Intermittent Calorie Restriction in Multiple Sclerosis. Baltimore, MD. This trial used a more rigorous study design with three arms: intermittent calorie restriction, continuous calorie restriction and controlled calorie intake to maintain BMI. Results are in review. 2017.Google Scholar
- 46.Lee JE, Bisht B, Hall MJ, Rubenstein LM, Louison R, Klein DT, et al. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis. J Am Coll Nutr. 2017;5724:1–19.Google Scholar
- 60.Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Khodadadi B, Jazayeri S, et al. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci. 2015; https://doi.org/10.1179/1476830513Y.0000000106.
- 66.Jelinek GA, De Livera AM, Marck CH, Brown CR, Neate SL, Taylor KL, et al. Associations of Lifestyle, Medication, and Socio-Demographic Factors with Disability in People with Multiple Sclerosis: An International Cross-Sectional Study. PLoS One. 2016;11:e0161701.CrossRefPubMedPubMedCentralGoogle Scholar
- 67.• Hoare S, Lithander F, van der Mei I, Ponsonby A-L, Lucas R. Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune Study. Mult Scler. 2015; https://doi.org/10.1177/1352458515604380. This is a moderately sized case-control study that showed participants who ate higher quantities of omega 3 fatty acids had a higher odds of developing their first clinically demyelinating event. The relationship was found to be dose-responsive.
- 69.Pantzaris MC, Loukaides GN, Ntzani EE, Patrikios IS. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomized, double-blind, placebo-controlled proof-of-concept clinical trial. BMJ Open. 2013;3:e002170.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, Pacheco-Moises F, Torres-Sanchez ED, Sorto-Gomez TE, et al. Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b. Oxid Med Cell Longev. 2013;2013:709493.CrossRefPubMedPubMedCentralGoogle Scholar
- 72.• Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: A pilot study. Mult Scler Relat Disord. 2015;4:159–69. This was the first randomized controlled trial conducted using high-dose biotin in people with progressive MS. While it was a pilot study and not powered to show efficacy, approximately half of involved participants had some degree of benefit in disability.CrossRefPubMedGoogle Scholar
- 73.•• Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomized, double-blind, placebo-controlled study. Mult Scler. 2016; https://doi.org/10.1177/1352458516667568. This slightly larger randomized controlled trial showed statistically significant improvement in EDSS and the timed 25 ft walk for participants who were randomized to high-dose biotin. Participants also had a significant improvement in clinical global outcomes.
- 74.• (2016) Effect of MD1003 in Progressive Multiple Sclerosis. In: clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT02936037?term=biotin&cond=multiple+sclerosis&rank=3#contacts. This is a large, Phase III multi-site study with high-dose biotin still ongoing. Results are pending.
- 75.Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004; https://doi.org/10.1007/s00415-004-0348-9.
- 78.Lovera J, Ramos A, Devier D, Garrison V, Kovner B, Reza T, et al. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies. J Neurol Sci. 2015;358:46–52.CrossRefPubMedPubMedCentralGoogle Scholar
- 82.Spagnuolo C, Moccia S, Russo GL Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem. (2017);1–11.Google Scholar
- 84.Qureshi M, Al-Suhaimi EA, Wahid F, Shehzad O, Shehzad A. Therapeutic potential of curcumin for multiple sclerosis. Neurol Sci. 2017; https://doi.org/10.1007/s10072-017-3149-5.
- 85.Sternberg Z, Chadha K, Lieberman A, Drake A, Munschauer F. Quercetin and Interferon-beta modulate immune response(s) in Peripheral Blood Mononuclear Cells Isolated from Multiple Sclerosis Patients. J Neuroimmunol. 2008; https://doi.org/10.1016/j.jneuroim.2008.09.008.
- 86.Skaper SD, Barbierato M, Facci L, Borri M, Contarini G, Zusso M, et al. Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells. Mol Neurobiol. 2017; https://doi.org/10.1007/s12035-017-0722-0.
- 94.Johnson S, Diamond B, Rausch S, Kaufman M, Shiflett S, Graves L. The Effect of Ginkgo biloba on Functional Measures in Multiple Sclerosis: A Pilot Randomized Controlled Trial. Explor J Sci Heal. 2006;2:19–24.Google Scholar
- 95.Noroozian M, Mohebbi-Rasa S, Tasviechi A, Sahraian M, Karamghadiri N, Akhondzadeh S. Ginkgo biloba for improvement of memory and quality of life in multiple sclerosis: An open trial. J Med Plants. 2011;10:33–42.Google Scholar
- 101.Motl RW, Mowry EM, Ehde DM, et al. Wellness and multiple sclerosis: The National MS Society establishes a Wellness Research Working Group and research priorities. Mult Scler J 1352458516687404. 2017.Google Scholar