麻豆传媒

Intermittent fasting -- defined as restricting food and drink to 500 calories a day, twice a week -- was safe and successful in a small randomized trial of patients with relapsing-remitting multiple sclerosis (MS).

The study met its primary outcome of reduced serum leptin levels after 12 weeks compared with controls, according to Laura Piccio, MD, PhD, of the University of Sydney in New South Wales, Australia, and co-authors.

Leptin, a proinflammatory adipokine that may have a pathogenic role in MS, was lower in the intermittent fasting group (P=0.03) after adjusting for age, sex, and disease-modifying therapy, Piccio and colleagues reported in the .

No serious adverse events emerged. At 6 weeks, the intermittent fasting group had an increase in blood CD45RO+ regulatory T-cell numbers. In exploratory testing, the group also showed improvement at 12 weeks on the Symbol Digit Modality Test, a measure of cognitive processing speed.

The findings provide mechanistic insights and support the potential role of diet as an add-on lifestyle intervention, the researchers noted.

"Diet is a topic that interests many people with MS," Piccio told 麻豆传媒. "It is one of the main topics they want to discuss, especially at time of diagnosis to find a way to 'control' their disease."

However, there's not much evidence showing how different diets might influence MS disease development or progression, she pointed out.

"We show that 12 weeks on this diet -- which had a very high compliance, around 98% to 99% -- had a significant impact on several markers," Piccio said. "This shows that a relatively minor change in diet has an impact on the metabolic-immune-inflammatory profile of patients."

Leptin is an adipokine released by adipose tissue proportionally to body fat. Leptin levels are risk, are higher in the cerebrospinal fluid and serum of MS patients, and are inversely correlated with circulating regulatory T-cell numbers, the researchers noted.

Obesity early in life has been associated with an of developing MS. In adult MS patients, obesity correlates with worse progression and disability.

Piccio and colleagues randomized 42 relapsing-remitting MS patients at Washington University School of Medicine in St. Louis to intermittent calorie restriction or a control group from 2018 to 2021. A total of 34 patients, 17 in each group, completed the .

Most participants were women. Mean baseline BMI was 28.7 and median (EDSS) score was 2. Patients were untreated or on disease-modifying therapy for at least 3 months. Initially, treatments that were allowed included only interferon-beta or glatiramer acetate (Copaxone); later, dimethyl fumarate (Tecfidera), teriflunomide (Aubagio), and natalizumab (Tysabri) were permitted.

Participants in the intermittent calorie restriction group were instructed to limit their intake to 500 calories or less for 2 non-consecutive days a week. On fasting days, they could consume only non-starchy vegetables, plain or with oil (maximum 2 tablespoons/day), vinegar, lemon juice, and/or seasonings, and non-caloric drinks. On non-fasting days, they could have their usual diet but were asked to monitor portion sizes and food choices and not overeat.

Those in the control group continued with their regular diet and had unrestricted access to food, but were asked to eat 1 to 1.5 cups of vegetables daily so all participants could have similar vegetable consumption. In both groups, participants were asked to maintain their usual activity levels.

In the intermittent calorie restriction group, adherence to the 2 fasting days per week was 99.5% for the first 6 weeks of the study and 97.2% for the second 6 weeks. At weeks 6 and 12, these participants had an overall calorie reduction of 21.5% and 23.1%, compared with baseline.

No grade 3 or higher adverse events were seen in either group. Three participants in the intermittent calorie restriction group reported mild symptoms like headache, lightheadedness, and tiredness on fasting days.

Limitations included the study's small sample size and short duration. The ongoing trial is larger and longer, and is evaluating not only reduced calorie intake but diet quality in people with MS, Piccio noted. It will assess functional outcomes, cognition, MRI data, and other measures.

"We do not propose diet as a cure-therapy for MS," Piccio said. "There are some effective medications, but diet could work in synergy with these current medications. Also, following a correct diet could be a way to prevent the disease -- in general, autoimmune diseases -- from developing."

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