Biological aging, a better indicator of health than chronological age, may be reversible with targeted interventions. Fasting-mimicking diets such as intermittent calorie restriction (CR) and ketogenic diets (KD) improve immune function, reduce inflammation, and improve clinical outcomes in PwMS. However, it remains unclear whether these improvements are reflected by changes in biological age, as captured using metabolomic profiling. 

To evaluate whether biological aging, as measured by metabolomic age, in people with multiple sclerosis (PwMS) can be reversed through dietary interventions.

Plasma samples from two previously conducted dietary intervention studies, with slightly different sets of measured metabolites on distinct platforms, were used to calculate metabolomic age, pre- and post-intervention. The metabolomic age clock, based on plasma metabolomic profiles from 11,977 healthy individuals, was utilized. In the first study, 36 people with relapsing-remitting MS (RRMS) were randomized into three groups for eight weeks: daily CR (22% caloric reduction), intermittent CR (75% reduction for 2 days/week), or a weight-stable control diet (100% of daily caloric needs). In the second study, 39 RRMS patients followed a KD for six months, and metabolomic age was measured before and after intervention. Between-group and within-person comparisons were performed using models allowing for correlated data.

Participants randomized to the intermittent CR diet experienced a significant reduction in metabolomic age compared to those on the weight-stable control diet (mean difference in metabolomic age for intermittent CR vs. control diets per week: -1.25 years; 95% CI: -2.46, -0.04 years; p=0.04). Additionally, adherence to the KD for six months resulted in a mean reduction of 1.12 years per month (95% CI: 0.36, 1.89 years; p=0.007) in metabolomic age.

Intermittent calorie restriction and ketogenic diets significantly reduced metabolomic age in people with RRMS, demonstrating that biological aging is modifiable through lifestyle interventions.