Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.

Ghezzi, Laura; Tosti, Valeria; Shi, Lisa; Cantoni, Claudia; Mikesell, Robert; Lancia, Samantha; Zhou, Yanjiao; Obert, Kathleen; Dula, Courtney; Sen, Monokesh K; Ge, Anjie; Tolentino, Miguel; Bollman, Bryan; Don, Anthony S; Matarese, Giuseppe; Colamatteo, Alessandra; La Rocca, Claudia; Lepore, Maria Teresa; Raji, Cyrus A; Rahmahi, Farzaneh; Wu, Gregory F; Naismith, Robert T; Fontana, Luigi; Cross, Anne H; Salter, Amber; Piccio, Laura

Ghezzi, Laura; Tosti, Valeria; Shi, Lisa; Cantoni, Claudia; Mikesell, Robert; Lancia, Samantha; Zhou, Yanjiao; Obert, Kathleen; Dula, Courtney; Sen, Monokesh K; Ge, Anjie; Tolentino, Miguel; Bollman, Bryan; Don, Anthony S; Matarese, Giuseppe; Colamatteo, Alessandra; La Rocca, Claudia; Lepore, Maria Teresa; Raji, Cyrus A; Rahmahi, Farzaneh; Wu, Gregory F; Naismith, Robert T; Fontana, Luigi; Cross, Anne H; Salter, Amber; Piccio, Laura.

Afiliação

Ghezzi L; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milano, Italy.
Tosti V; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy.
Shi L; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Cantoni C; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Mikesell R; Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona, USA.
Lancia S; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Zhou Y; Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, Texas, USA.
Obert K; UConn Health, Farmington, Connecticut, USA.
Dula C; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Sen MK; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Ge A; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Tolentino M; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Bollman B; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Don AS; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Matarese G; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Colamatteo A; Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Napoli, Campania, Italy.
La Rocca C; Consiglio Nazionale delle Ricerche (IEOS-CNR), Istituto per l'endocrinologia e l'oncologia Gaetano Salvatore, Naples, Campania, Italy.
Lepore MT; Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Napoli, Campania, Italy.
Raji CA; Consiglio Nazionale delle Ricerche (IEOS-CNR), Istituto per l'endocrinologia e l'oncologia Gaetano Salvatore, Naples, Campania, Italy.
Rahmahi F; Consiglio Nazionale delle Ricerche (IEOS-CNR), Istituto per l'endocrinologia e l'oncologia Gaetano Salvatore, Naples, Campania, Italy.
Wu GF; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Naismith RT; Washington University School of Medicine, Mallinckrodt Institute of Radiology, Saint Louis, Missouri, USA.
Fontana L; Washington University School of Medicine, Mallinckrodt Institute of Radiology, Saint Louis, Missouri, USA.
Cross AH; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Salter A; Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
Piccio L; The University of Sydney, Charles Perkins Centre, Sydney, New South Wales, Australia.

J Neurol Neurosurg Psychiatry ; 2024 Aug 13.

Article em En | MEDLINE | ID: mdl-39137977

ABSTRACT

ABSTRACT

BACKGROUND:

Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures. This trial studied the effects of 12-week iCR on metabolic, immunological, and clinical outcomes in pwMS.

METHOD:

Relapsing-remitting MS participants were randomised to iCR or a control group. Study visits were conducted at baseline, 6 and 12 weeks. The primary outcome was reduction in serum leptin levels at 12 weeks. Feasibility and safety were assessed by diet adherence and adverse events (AEs). Secondary outcomes included changes in anthropometric and body composition measures, metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate outcome differences between and within groups over time.

RESULTS:

Forty-two pwMS were randomised, 34 completed the study (17/group). Leptin serum levels at 12 weeks were significantly lower in the iCR versus the control group (mean decrease -6.98 µg/dL, 95% CI -28.02 to 14.06; p=0.03). Adherence to iCR was 99.5% and 97.2% at 6 and 12 weeks, respectively, and no serious AEs were reported. An increase in blood CD45RO+ regulatory T-cell numbers was seen after 6 weeks of iCR. Exploratory cognitive testing demonstrated a significant improvement in the Symbol Digit Modality Test Score in the iCR group at 12 weeks.