Background: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments.

Objective: The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS.

Method: In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale.

Results: Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n=4/6), ginkgo biloba (n=3/5), vitamin A (n=2/2), biotin (n=1/2), carnitine (n=1/2), green tea (n=1/2), coenzyme Q10 (n=1/1), probiotics (n=1/1), curcumin (n=1/1), andrographis paniculata (n=1/1), ginseng (n=1/1), and lemon verbena (n=1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average total study sample n=55) and there were few replicate studies per nutraceutical to validate the reported results. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale.

Conclusion: The existing literature provides preliminary support for the use of several nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as mitochondrial dysfunction and the gut microbiome.