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Multiple sclerosis
Original research
Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits
  1. J Nicholas Brenton1,
  2. Diana Lehner-Gulotta1,
  3. Emma Woolbright2,
  4. Brenda Banwell3,
  5. A G Christina Bergqvist3,
  6. Shanshan Chen4,
  7. Rachael Coleman2,
  8. Mark Conaway5,
  9. Myla D Goldman6
  1. 1 Department of Neurology, Division of Child Neurology, University of Virginia, Charlottesville, Virginia, USA
  2. 2 Division of Child Neurology, Children’s Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. 3 Department of Neurology, Universitygi of Virginia, Charlottesville, Virginia, USA
  4. 4 Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA
  5. 5 Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA
  6. 6 Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA
  1. Correspondence to Dr J Nicholas Brenton, Neurology, University of Virginia, Charlottesville, VA 22908, USA; jnb8h{at}virginia.edu

Abstract

Background Dietary changes impact human physiology and immune function and have potential as therapeutic strategies.

Objective Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics.

Methods Sixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseline, fatigue, depression and quality of life (QoL) scores were obtained in addition to fasting adipokines and MS-related clinical outcome metrics. Baseline metrics were repeated at 3 and/or 6 months on-diet.

Results Eighty-three percent of participants adhered to the KD for the study duration. Subjects exhibited significant reductions in fat mass and showed a nearly 50% decline in self-reported fatigue and depression scores. MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001) composite scores increased on-diet. Significant improvements were noted in Expanded Disability Status Scale scores (2.3±0.9 vs 1.9±1.1, p<0.001), 6-minute walk (1631±302 vs 1733±330 ft, p<0.001) and Nine-Hole Peg Test (21.5±3.6 vs 20.3±3.7 s, p<0.001). Serum leptin was lower (25.5±15.7 vs 14.0±11.7 ng/mL, p<0.001) and adiponectin was higher (11.4±7.8 vs 13.5±8.4 µg/mL, p=0.002) on the KD.

Conclusion KDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS.

Trial registration information Registered on ClinicalTrials.gov under registration number NCT03718247, posted on 24 October 2018. First patient enrolment date: 1 November 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

  • MULTIPLE SCLEROSIS
  • NEUROIMMUNOLOGY

Data availability statement

Data are available upon reasonable request. Any data not published within the article are available, and the anonymised data will be shared by request from any qualified investigator.

https://doi.org/10.1136/jnnp-2022-329074

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    Data availability statement

    Data are available upon reasonable request. Any data not published within the article are available, and the anonymised data will be shared by request from any qualified investigator.

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    Footnotes

    • Contributors JNB's contributions included study concept and study design, acquisition of data, analyses and interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. JNB (guarantor) accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish. DL-G's contributions included acquisition of data, interpretation of data and critical revision of the manuscript for important intellectual content. EW's contributions included acquisition of data and critical revision of the manuscript for important intellectual content. BB's contributions included study design, interpretation of data and critical revision of the manuscript for important intellectual content. AGCB's contributions included study design, interpretation of data and critical revision of the manuscript for important intellectual content. SC's contributions included interpretation of data and critical revision of the manuscript for important intellectual content. RC's contributions included acquisition of data and critical revision of the manuscript for important intellectual content. MC's contributions included study design, interpretation of data and critical revision of the manuscript for important intellectual content. MDG's contributions included study design, interpretation of data and critical revision of the manuscript for important intellectual content.

    • Funding JNB’s work with the iTHRIV Scholars Program is supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers UL1TR003015 and KL2TR003016. A portion of this study was also funded via private foundational funding provided by the ZiMS Foundation.

    • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    • Competing interests JNB’s research is funded by the National Institutes of Health (NIH) and National Institute of Neurological Diseases and Stroke (NINDS) (grant number: K23NS116225) and by the iTHRIV Scholars Program via the National Center For Advancing Translational Sciences of the NIH under award numbers UL1TR003015 and KL2TR003016. Research support is also provided by the ZiMS Foundation. DL-G serves as a consultant for Functional Formularies. BB serves as a consultant to Novartis, Roche, UCB, Teva Neuroscience, Biogen and Sanofi. AGCB has served as a paid speaker for Nutricia North America. EW, SC, RC and MC have no competing interests. MDG has served on the DSMB for Anokion SMC and Immunic. She has received consulting fees from ADAMAS Pharmaceuticals, Biogen IDEC, Brainstorm Cell Therapeutics, EMD Serono, Genetec, Greenwich Biosciences, Horizons, Immunic, Merk, Novartis, Sanofi Genzyme and Vebrilio.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.