DefinePK

Abstract

Background: Chronic fatigue syndrome (CFS) is a debilitating disorder that can cause chronic fatigue, physical function impairment, and impaired quality of life. The pathophysiology is unclear but mitochondrial dysfunction, impaired energy metabolism, and micronutrient deficiencies have been implicated. B-complex vitamins are known to have fundamental functions in the production of cellular energy, in the synthesis of neurotransmitters, and in regulating the immune system, hence a therapeutic role in relieving symptoms of fatigue can be presumed. Objectives: This systematic review and meta-analysis was undertaken to assess the efficacy of B-complex vitamin supplementation in relieving the symptoms of CFS and specifically fatigue severity, functional outcomes, and quality of life. Methodology: An electronic search of PubMed, Scopus, and Web of Science databases was performed for original clinical studies until August 2025. Results: Six studies were included: three randomized controlled trials, two observational studies, and one open-label trial. Information concerning the type of intervention, the dose, the duration of the intervention, and the outcome measures, including fatigue severity scale, global health score and the biomarker were extracted. Random-effects model meta-analysis was conducted to allow heterogeneity. Results: A total of six studies were included of which the two RCTs with sufficient quantitative data, there was no statistically significant reduction (SMD: -0.12; p = 0.48). However, when all eligible studies were pooled, there was a significant reduction in fatigue severity (SMD: -0.42; p = 0.002). Moderate heterogeneity (I2 = 42%) was found, mainly due to variation in formulation, length of treatment and outcome measures. Narrative synthesis of the remaining open-label and observational studies reported modest improvements in self-reported outcomes of fatigue and functional status; however, results were inconsistent. There were no major adverse events reported in any of the included studies. Conclusion: B-complex vitamin supplementation has been shown to have a positive impact on fatigue and functional outcomes in patients with CFS. Results are promising but further large-scale randomised trials using standardised supplementation protocols are necessary to establish efficacy and optimal dosing strategies.