Effect of Vitamin D Supplementation on Fatigue in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I2 = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.

Effect of Unmodulated 5-kHz Alternating Currents Versus Transcutaneous Electrical Nerve Stimulation on Mechanical and Thermal Pain, Tactile Threshold, and Peripheral Nerve Conduction: A Double-Blind, Placebo-Controlled Crossover Trial.

OBJECTIVE: To investigate the effect of unmodulated 5-kHz alternating current on mechanical pain threshold (MPT), heat pain threshold (HPT), tactile threshold (TT), and peripheral nerve conduction (PNC) compared with transcutaneous electrical nerve stimulation (TENS) and sham stimulation. SETTING: National referral center. DESIGN: Randomized, double-blind, placebo-controlled crossover trial. PARTICIPANTS: Healthy volunteers (N=38). No dropouts or adverse events were reported. INTERVENTION: TENS, unmodulated 5-kHz currents, and sham stimulation were applied on the radial nerve for 20 minutes with a 24-hour washout period between them and concealed intervention allocation. MAIN OUTCOME MEASURES: Four measures were taken: before, during, and 2 after the interventions. Algometry was used to assess MPT, a Peltier thermode for HPT using the method of limits, Von Frey filaments for TT, and radial nerve compound action potential. RESULTS: No differences were observed on MPT, HPT, and PNC when 5-kHz current and TENS were compared. However, TT increased 56.2mN (95% confidence interval [CI], 28.8-83.6) in the TENS group compared with the 5-kHz current group during intervention. Compared with sham stimulation during intervention, MPT increased 4.7N (95% CI, 0.3-9.2) using 5-kHz current and 10.4N (95% CI, 3.5-17.3) with TENS. TT increased 17.2mN (95% CI, 4.7-29.7) with 5-kHz current and 73.4mN (95% CI, 47.5-99.2) with TENS. However, HPT increased 1.0°C (95% CI, 0.2-2.0) only with TENS. For the PNC, no differences were found among the 3 groups. CONCLUSIONS: Unmodulated 5-kHz current produced an increase in somatosensory thresholds that was greater than placebo but not when compared with TENS; however, participants perceived 5-kHz currents to be more comfortable and showed more habituation to them.