Metabolic Changes, Cognitive Improvements in Multiple Sclerosis Observed Through Intermittent Calorie Restriction

Laura Piccio, MD, PhD

Findings from a short-term, 12-week study of patients with multiple sclerosis (MS) indicated that intermittent calorie restriction (iCR) is a safe and effective method for this patient population, with several positive metabolic, immunologic, and cognitive changes observed.

These data were presented at the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 23-25, in San Diego, California, by Laura Piccio, MD, PhD, a neurologist and physician scientist at Washington University in St. Louis. In the analysis, investigators assessed the effects of iCR on adipokines levels, metabolic and immune/inflammatory biomarkers, clinical and brain MRI measures in a cohort of 42 patients with MS.

Patients were randomly assigned to either iCR or unrestricted diet (Ctr) for 12 weeks. Those in the iCR group ate 1-2 salads with non-starchy vegetables with a light dressing, totaling 400-500 calories, for 2 days of the week, with the remaining 5 eating normally. Participants had a diagnosis of relapsing MS, had Expanded Disability Status Scale scores less than 6, had body mass index (BMI) between 22 and 38, and were stable for 1 year.

At the 12-week follow-up, 17 of the 22 from the iCR group and 17 of the 20 from controls completed the study. Compared with baseline, those randomly assigned to iCR demonstrated significant decreases in weight, BMI, and waist circumference over time at both the 6- and 12-week observed time points. Specifically, investigators recorded a mean decrease of 2.2 kg in total body fat at the conclusion of the analysis in the iCR group.

"In this particular area [of research], there’s a lot of information, but quite often claims are not supported by robust scientific evidence,” Piccio told NeurologyLive^®. "It’s important to maintain a healthy body weight, because we’ve seen that being obese or overweight, based on a number of epidemiological evidence, can predispose patients to the development of autoimmunity. For a patient with MS, the fact of being obese or overweight is associated with more worse disease outcomes."

At the 6- and 12-week time points, patients in the iCR group showed significantly lower leptin serum levels (week 6: P = .04; week 12: P = .03) and significantly increased adiponectin levels relative to controls (P = .01). T-cell subsets were also modulated by 12-week iCR, as represented by significantly lower counts of effector memory CD4+ T-cells at both time points, and significantly increases in naïve CD4+ T-cells at the conclusion of the study. Notably, there were statistically significant differences in the increase in regulatory T-cells as well.

"We know, based on our preclinical studies, that changes in adiponectin could impact the overall balance of pro or anti-inflammatory molecules in circulation," Piccio added. "The changes of these adipokines are a reflection of the diet, which works toward influencing inflammation by reducing systemic inflammation, which is a positive outcome."

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Additional findings from the study showed significant upregulation of lysophospholipids following iCR. All told, adiponectin levels in plasma were positively correlated with 9 of the 16 lipids that changed significantly after 12 weeks of iCR relative to controls. Changes in cognition were also observed in the iCR group, as demonstrated by increases in Symbol Digit Modalities Test (SDMT) scores at 6 (mean increase, 3.5; 95% CI, 0.6-6.3; P = .01) and 12 (mean increase, 6.2; 95% CI, 3.4-9.5; P = .00004) weeks. For context, no significant differences were observed in the control group over time. Patients on iCR also showed improvements in self-reported outcomes, specifically Modified Fatigue Impact Scale and Multiple Sclerosis Impact Scale.

Piccio believes that the results seen in the study should be taken with caution, as it was a relatively shorter trial. She noted, "Were still at the beginning. We need more studies like this that are larger and longer. An important factor that is limiting this research is the fact that they are difficult studies to conduct. It’s much easier to give a drug to a patient than to change their lifestyle. It’s a lot of discipline to stick to a specific diet intervention."

Piccio added, "Another limit is the funding. The community, scientific community, has been skeptical on the potential role of lifestyle factors and diet, but there is an increased interest in this particular type of research. Not as a way to treat the disease—because we have effective medications—but as an add-on to the current treatment or as an intervention to prevent the disease from happening. We have learned from other studies that have linked obesity in children and young adults with increased risk of developing MS later on in life."

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REFERENCES
1. Ghezzi L, Tosti V, Cantoni C, et al. Randomized clinical trial of intermittent calorie restriction in people with multiple sclerosis: effects on immunometabolic and cognitive measures. Presented at: 2023 ACTRIMS Forum; February 23-25; San Diego, CA. Cutting Edge Developments.