Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis
Laura Ghezzi, Valeria Tosti, Lisa Shi, Claudia Cantoni, Robert Mikesell, Samantha Lancia, Yanjiao Zhou, Kathleen A. Obert, Courtney Dula, Monokesh K. Sen, Anjie Ge, Miguel Tolentino, Bryan Bollman, Anthony S. Don, Giuseppe Matarese, Alessandra Colamatteo, Claudia La Rocca, Maria Teresa Lepore, Cyrus A. Raji, Farzaneh Rahmani, Gregory F. Wu, Robert T. Naismith, Luigi Fontana, Anne H. Cross, Amber Salter, Laura Piccio
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. Conclusions iCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS. Trial registration number NCT03539094 .