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, Rahmani Farzaneh, Wu Gregory F, Naismith Robert T, Fontana Luigi, Cross Anne H, Salter Amber, Piccio Laura
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milano, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy.
J Neurol Neurosurg Psychiatry. 2025 Jan 16;96(2):158-169. doi: 10.1136/jnnp-2024-333465.
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.
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.
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.
iCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS.
NCT03539094 .
热量限制（CR）通过多种机制改善多发性硬化症（MS）的临床前模型。这些机制包括降低瘦素水平，瘦素是一种促炎脂肪因子，但缺乏对人类的机制研究。对多发性硬化症患者（pwMS）进行每日和间歇性热量限制（iCR）的测试显示，疲劳和幸福感指标有所改善。本试验研究了12周iCR对pwMS的代谢、免疫和临床结局的影响。
复发缓解型MS参与者被随机分为iCR组或对照组。在基线、6周和12周进行研究访视。主要结局是12周时血清瘦素水平降低。通过饮食依从性和不良事件（AE）评估可行性和安全性。次要结局包括人体测量和身体成分指标、代谢和免疫谱以及临床指标的变化。使用混合效应线性回归模型评估组间和组内随时间的结局差异。
42名pwMS被随机分组，34名完成研究（每组17名）。iCR组12周时的血清瘦素水平显著低于对照组（平均降低-6.98µg/dL，95%CI：-28.02至14.06；p=0.03）。iCR在6周和12周时的依从性分别为99.5%和97.2%，未报告严重不良事件。iCR 6周后血液中CD45RO调节性T细胞数量增加。探索性认知测试表明，iCR组在12周时符号数字模态测试得分有显著改善。
iCR有可能改善代谢和免疫谱，在pwMS中是安全可行的。
NCT03539094 。
