High-density lipoprotein cholesterol is associated with multiple sclerosis fatigue: A fatigue-metabolism nexus?

Fatigue is a frequent symptom in multiple sclerosis (MS). The role of cholesterol and lipids in MS fatigue has not been investigated.

To investigate the associations of cholesterol biomarkers and serum neurofilament light chain (sNfL) with fatigue in relapsing-remitting MS.

This cross-sectional study included 75 relapsing-remitting MS patients (69% female, mean age ± SD: 49.6 ± 11 years and median Expanded Disability Status Scale score: 2.0). Fatigue, disability, and depression were assessed with Fatigue Severity Scale (FSS), Expanded Disability Status Scale, and the Beck Depression Index-Fast Screen, respectively. sNfL was measured using single-molecule array technology. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and an apolipoprotein panel data were obtained. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), chemokine (C-C motif) ligand 5 (CCL5 or RANTES), and CCL18 levels were measured to assess inflammation.

The mean FSS was 4.27 ± 1.73, and 57% had severe fatigue status (SFS, FSS ≥ 4.0). In regression analyses adjusted for age, sex, disability, and depression, lower FSS and SFS were associated with greater HDL-C (P = .006 for FSS, and P = .016 for SFS) and lower TC to HDL-C ratio (P = .011 for FSS, and P = .009 for SFS). Apolipoprotein A-II was also associated with FSS (P = .022). sNfL, CCL5, CCL18, sICAM-1, and sVCAM-1 levels were not associated with fatigue after adjusting for disability and depression.

TC to HDL-C ratio is associated with MS fatigue. Our results implicate a potential role for the HDL-C pathway in MS fatigue and could provide possible targets for the treatment of MS fatigue.