Dietary Supplements in MS: Exercising Caution With OTC Remedies

In healthy individuals and individuals with chronic conditions, vitamins and dietary supplements have emerged as an important and growing component of health and wellness. In 2017, 76% of US adults surveyed said that they use dietary supplements, representing a 5% increase from 2016 and 12% from 2008.¹

Vitamins/minerals were the largest category of supplements consumed by 98% of supplement users, which includes multivitamins (73%), vitamin D (37%), and vitamin C (32%), among others. Nearly 50% and 40% of supplement users also take specialty vitamins and herbals/botanicals, respectively, including omega-3/fatty acids (21%), probiotics (16%), green tea (14%), and ginseng (8%).¹ Unlike pharmaceutical products for which safety and efficacy must be demonstrated via rigorous clinical trials before they are approved by the US Food and Drug Administration (FDA), supplements are regulated through the FDA by the Dietary Supplement Health and Education Act of 1994, which only requires that post-marketing adverse effects be reported.²

Recommendations for the use of vitamins and dietary supplements are generally based on anecdotal evidence obtained via personal research and from friends and family, or advice from a physician. The challenge is the paucity of clinical studies, and the lack of empirical evidence to support their safety and efficacy. Yet 87% of US adults surveyed said that they have confidence in the safety, quality, and effectiveness of dietary supplements overall.¹

Individuals with multiple sclerosis (MS) are no exception. Surveys of patients with MS have found that they are interested in using dietary supplements as an adjunct to treatment to reduce the severity and symptoms of their disease. Dietary supplementation is an important consideration, particularly in patients in whom polypharmacy may increase the risk of drug-drug interaction and pose unintended health risks. In fact, the National Multiple Sclerosis Society clearly states in their patient brochure that some nutritional supplements may cause adverse immune system events, interact with common MS medications, or result in other serious adverse events.³ Further, in 2017, the FDA issued a safety alert for the B-vitamin biotin, stating that it can significantly interfere with certain lab tests, causing falsely high or falsely low test results that may go undetected.⁴ Therefore, knowing which vitamins and dietary supplements to take is as important as knowing which to avoid.

Although there are many FDA-approved disease-modifying treatments for MS, the broad spectrum of MS symptoms is not always well-controlled, leaving many patients in search of alternative treatments. The increasing understanding of the link between various chronic diseases and modifiable risk factors such as diet and exercise has fueled interest in dietary modifications, including the use of vitamins and dietary supplements. Despite the lack of unequivocal evidence regarding the safety and efficacy of dietary supplements, they are extensively used by as much as 75% of individuals with MS, the most common being polyunsaturated fatty acids (PUFA), allergen-free diets, vitamins, micronutrients, and antioxidants.⁶

PUFAs are particularly popular in this population, as some isolated studies have suggested diets rich in PUFAs may help improve outcomes in people with MS.^7-9 The evidence, however, varies, and the improvements seen are often vaguely characterized. The benefits of PUFAs, including omega-3 and -6 fatty acids and linoleic acid, was investigated in a Cochrane systematic review of 6 randomized control trials involving a total of 794 patients with MS.⁶ Overall, the analysis found no benefit of PUFAs in limiting disease progression, but some positive effect was noted in the reduction of relapse frequency. However, the strength and generalizability of the findings were limited by the quantity and quality of the available studies.

A recent review by Evans and colleagues of available studies provides the most current evidence on the efficacy and safety of commonly used vitamins and dietary supplements in this population. Of the vitamins evaluated (vitamins A to E), in both animal models and people with MS only vitamin D (D3, cholecalciferol, D2, and ergocalciferol) demonstrated a benefit in reducing the rate of relapse and number of lesions seen on magnetic resonance imaging (MRI). However, toxicity associated with vitamin D included kidney stones, hypercalcemia, and arrhythmias.¹⁰ Several vitamins, including A, B3, B6, C, and E, were associated with serious toxicity, including psychiatric complications, liver toxicity/liver failure, cerebral edema, sensory neuropathy, and excessive bleeding risk.¹⁰ The optimal dosage of vitamin D that provides benefit while minimizing the risk for toxicity is unknown.

In a similar fashion, studies of various dietary supplements, including caffeine, gingko biloba, green tea extract, lipoic acid, and probiotics were inconclusive, primarily due to insufficient evidence or poor quality of the studies evaluated.¹⁰ The review investigators emphasized that caution must be exercised in extrapolating the findings from these studies to inform clinical practice, especially findings that are based on animal models of MS. Such models do not parallel human MS and small-scale clinical studies are not representative of the larger population of patients with MS. The benefits of vitamin D and biotin in MS are currently being evaluated in larger randomized trials and other studies are investigating the benefits of supplements such as lipoic acid and probiotics.^11-14

As vitamins and nutritional supplements are increasingly used by patients with MS, it becomes critical for clinicians and patients to be knowledgeable about their benefits and potential toxicities, including the risk for interactions with prescribed medications. Clinicians should encourage a dialogue with patients about their use of over-the-counter supplements, and counsel them on their use as appropriate.

References

1. CRN 2017 Annual Survey on Dietary Supplements. www.crnusa.org/resources/crn-2017-annual-survey-dietary-supplements. Accessed June 11, 2018.
2. US Food and Drug Administration (FDA). Dietary supplements. Last updated 04/13/2018. www.fda.gov/Food/DietarySupplements/. Accessed June 11, 2018.
3. National Multiple Sclerosis Society. Vitamins, minerals & herbs in MS. An introduction. 2015. www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/ Brochure-Vitamins,-Minerals,-and-Herbs-in-MS_-An-Introduction.pdf. Accessed June 11, 2018.
4. US Food and Drug Administration (FDA). Biotin (vitamin B7): Safety communication – may interfere with lab tests. Posted 11/28/2017. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ ucm586641.htm. Accessed June 11, 2018.
5. Altowaijri G, Fryman A, Yadav V. Dietary interventions and multiple sclerosis. Curr Neurol Neurosci Rep. 2017;17(3):28.
6. Farinotti M, Vacchi L, Simi S, Di Pietrantonj C, Brait L, Filippini G. Dietary interventions for multiple sclerosis. Cochrane Database Syst Rev. 2012;12:CD004192.
7. Yadav V, Shinto L, Bourdette D. Complementary and alternative medicine for the treatment of multiple sclerosis. Expert Rev Clin Immunol. 2010;6(3):381-395.
8. Riccio P, Rossano R, Larocca M, et al. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study. Exp Biol Med (Maywood). 2016;241(6):620-635.
9. Kes VB, Cesarik M, Matovina LZ, et al. The role of complementary and alternative medicine in therapy of multiple sclerosis. Acta Clin Croat. 2013;52(4):464-471.
10. Evans E, Piccio L, Cross AH. Use of vitamins and dietary supplements by patients with multiple sclerosis: a review [published online April 23, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.0611
11. ClinicalTrials.gov. Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS). https://clinicaltrials.gov/ct2/show/NCT01440062. Accessed June 12, 2018.
12. ClinicalTrials.gov. Vitamin D supplementation in multiple sclerosis. https://clinicaltrials.gov/ct2/show/results/NCT01490502. Accessed June 12, 2018.
13. ClinicalTrials.gov. Lipoic acid for progressive multiple sclerosis (MS). https://clinicaltrials.gov/ct2/show/NCT03161028. Accessed June 12, 2018.
14. ClinicalTrials.gov. Gut microbiota and multiple sclerosis. https://clinicaltrials.gov/ct2/show/NCT03262870. Accessed June 12, 2018.