Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials

Background and objective: Emerging evidence suggests a role for diet in multiple sclerosis (MS) care; however, owing to methodological issues and heterogeneity of dietary interventions in preliminary trials, the current state of evidence does not support dietary recommendations for MS. The objective of this study was to assess the efficacy of different dietary approaches on MS-related fatigue and quality of life (QoL) through a systematic review of the literature and network meta-analysis (NMA).

Methods: Electronic database searches were performed in May 2021. Inclusion criteria were (1) randomized trial with a dietary intervention, (2) adults with definitive MS based on McDonald criteria, (3) patient-reported outcomes for fatigue and/or QoL, and (4) minimum intervention period of 4 weeks. For each outcome, standardized mean differences (SMDs) were calculated and included in random effects NMA to determine the pooled effect of each dietary intervention relative to each of the other dietary interventions. The protocol was registered at PROSPERO (CRD42021262648).

Results: Twelve trials comparing 8 dietary interventions (low-fat, Mediterranean, ketogenic, anti-inflammatory, Paleolithic, fasting, calorie restriction, and control [usual diet]), enrolling 608 participants, were included in the primary analysis. The Paleolithic (SMD -1.27; 95% CI -1.81 to -0.74), low-fat (SMD -0.90; 95% CI -1.39 to -0.42), and Mediterranean (SMD -0.89; 95% CI -1.15 to -0.64) diets showed greater reductions in fatigue compared with control. The Paleolithic (SMD 1.01; 95% CI 0.40-1.63) and Mediterranean (SMD 0.47; 95% CI 0.08-0.86) diets showed greater improvements in physical QoL compared with control. For improving mental QoL, the Paleolithic (SMD 0.81; 95% CI 0.26-1.37) and Mediterranean (SMD 0.36; 95% CI 0.06-0.65) diets were more effective compared with control. However, the NutriGRADE credibility of evidence for all direct comparisons is very low because of most of the included trials having high or moderate risk of bias, small sample sizes, and the limited number of studies included in this NMA.

Discussion: Several dietary interventions may reduce MS-related fatigue and improve physical and mental QoL; however, because of the limitations of this NMA, which are driven by the low quality of the included trials, these findings must be confirmed in high-quality, randomized, controlled trials.