A RUN-IN STUDY ON THE SAFETY AND TOLERABILITY OF A FASTING MIMICKING DIET IN RELAPSING REMITTING MULTIPLE SCLEROSIS TREATED WITH FIRST LINE THERAPIES (FAST-MS RUN-IN STUDY)

Scientific interest in the role of diet and its potential impact on the course of MS has significantly grown in recent years. Researchers have explored the role of various dietary patterns in the onset and progression of MS, and over the past century, several diets have been proposed for individuals with this condition. In recent decades, there has been discussion about caloric restriction (CR) and fasting as preventative measures to attenuate the aging process, and postpone the onset of various chronic and autoimmune diseases in both humans and various animal models under diverse conditions. In experimental autoimmune encephalomyelitis (EAE) mice subjected to 3-day cycles of Fasting mimicking diet (FMD), there was an improvement in demyelination and symptoms, with a reduction in symptom severity. Through this small, run-in clinical trial (NCT06039007), we demonstrated that 3 bimonthly cycles of a 7-day FMD were feasible and safe in relapsing-remitting multiple sclerosis (RRMS) patients at low nutritional risk. Given the critical need for more definitive evidence linking specific diets to clinical outcomes, we aimed to evaluate the safety and tolerability of FMD among people with RRMS. This is the first study to assess the feasibility of 3 cycles of FMD in RRMS patients. We observed a good adherence to the FMD. Out of the 24 participants enrolled, 2 withdrew their informed consent prior to commencement. Of the remaining 22 participants who initiated the diet, 18 successfully completed all 3 cycles, accounting for 81.81%; The adverse events (AE) reported, according to the CTCAE, version 5.0, were solely of grade G1 and G2, with the most frequently reported side effects being fatigue and headache. From a nutritional perspective, the three cycles of 7-day FMD in patients with RRMS not only maintain stability in terms of weight, the ECM/BCM ratio, and the phase angle (PhA) but they also appear to confer improvements in terms of fat-free mass (FFM), skeletal muscle mass index (SMI), and total body water (TBW), all of which tended to exhibit an increase. The diet was generally well-tolerated. Nutritional status, and haematological parameters demonstrated overall stability. Adherence to the dietary interventions was satisfactory. These results substantiate the safety and tolerability of the FMD, leading to an acceptable level of compliance among individuals diagnosed with RRMS. No relapses were observed in any of the 22 patients involved. No changes in disability status or magnetic resonance imaging (MRI) disease activity were observed in the 18 patients that completed the experiment. Nonetheless, there is a crucial need for phase II clinical trials evaluating laboratory parameters and disease-related metrics, as well as large-scale randomized clinical trials to strengthen the evidence base regarding the clinical benefits of dietary modification in individuals with MS.