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The Effect of Polyphenol Supplementation in People with Multiple Sclerosis: A Systematic Review of Clinical Trials.

  • 2026-06-10
  • Nutrients 18(12)
    • Lauren Brooks
    • Aqif Farhan Bin Azmil Farid
    • Amudha Poobalan
    • Alexandra Johnstone
    • Phyo Kyaw Myint

Study Design

Type
Systematic Review
Population
785 patients with multiple sclerosis (MS)
Methods
Systematic search of Embase, Medline, and ClinicalTrials.gov on 19 June 2025; inclusion of eligible clinical trials; risk of bias evaluated using Cochrane tool; certainty of evidence appraised with GRADE.
  • Rigorous Journal
Background/Objectives: Multiple sclerosis (MS) is an autoimmune neuroinflammatory disease affecting 2.9 million worldwide. Current immunosuppressive treatments offer limited neuroprotection and often cause adverse effects. Polyphenols with antioxidant and anti-inflammatory properties have been investigated as adjuncts in MS. Methods: On 19 June 2025, Embase, Medline, and ClinicalTrials.gov were systematically searched. Eligible clinical trials assessing polyphenol supplementation in MS were included. Outcomes of interest were Expanded Disability Status Scale (EDSS), annualised relapse rate (ARR), magnetic resonance imaging (MRI) changes, safety, and tolerability. Risk of bias was evaluated using the Cochrane tool, and certainty of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The protocol was registered with PROSPERO (CRD420251052042). Results: Of 870 records identified, 13 trials (n = 785) met inclusion. Nanocurcumin consistently improved EDSS in relapsing-remitting MS (3 trials, n = 150; p = 0.039-0.041), while epigallocatechin-3-gallate, silymarin (SM), cranberry extract, and bio-enhanced curcumin extract (BCM-95) curcumin showed no significant impact on disability, relapse rates, or MRI outcomes. Intervention adverse events were generally mild. SM showed potential hepatoprotective effects. Risk of bias was determined as low risk for seven of the trials and of some concern for five of the studies. Most often raising concerns because of selective reporting. Certainty of evidence, assessed using GRADE, was generally moderate, indicating some uncertainty regarding the outcomes. Meta-analysis was not possible due to the heterogeneity of included studies. Conclusions: Nanocurcumin may contribute to improvements in disability outcomes in Relapse Remitting Multiple Sclerosis (RRMS), whereas other polyphenols lack consistent efficacy. However, the evidence base remains limited by small sample sizes and methodological concerns. Larger, multicentre randomised controlled trials are required to establish optimal dosing, long-term safety, and therapeutic potential.

Research Insights

  • Camellia→Improved Expanded Disability Status Scale

    epigallocatechin-3-gallate, silymarin (SM), cranberry extract, and bio-enhanced curcumin extract (BCM-95) curcumin showed no significant impact on disability

    Effect
    Neutral
    Effect size
    Small
  • Camellia→Improved Magnetic Resonance Imaging Change

    epigallocatechin-3-gallate, silymarin (SM), cranberry extract, and bio-enhanced curcumin extract (BCM-95) curcumin showed no significant impact on disability, relapse rates, or MRI outcomes

    Effect
    Neutral
    Effect size
    Small
  • Camellia→Reduced Annualized Relapse Rate

    epigallocatechin-3-gallate, silymarin (SM), cranberry extract, and bio-enhanced curcumin extract (BCM-95) curcumin showed no significant impact on disability, relapse rates, or MRI outcomes

    Effect
    Neutral
    Effect size
    Small

Adverse Events Reported

  • Camellia→Overall tolerability

    Intervention adverse events were generally mild.

    Finding
    Reported
    Grade
    mild
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