Table 3. Summary of included studies assessing the effect of vitamin D on long term outcomes of MS .

CIS - Clinically Isolated Syndrome, BENEFIT - Betaferon / Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment, EBV - Ebstein Barr Virus, RRMS - Relapsing-Remitting Multiple Sclerosis, BMI - Body Mass Index, HOLISM - Health Outcomes and Lifestyle In a Sample of People with Multiple Sclerosis, QoL - Quality of Life 

Ascherio et al., [49]; Cortese et al., [50]; Wesnes et al., [51]; Simpson-Yap et al., [52]  

REFERENCES	SAMPLE SIZE	POPULATION	OBJECTIVE	CONCLUSION
Ascherio et al., (2004)	468	Patients with CIS from 18 European countries, Israel and Canada, participants of the BENEFIT trial	To evaluate serum25 (OH)D levels as a prognostic marker for MS outcomes in patients with CIS	Higher serum 25(OH)D levels were associated with reduced disease activity and rates of progression
Cortese et al., (2020)	278	Patients with CIS from 18 European countries, Israel and Canada, participants of the BENEFIT trial	To assess the effect of serum vitamin D levels, smoking and anti EBV antibody concentrations on long term cognitive status in MS patients	Reduced vitamin D levels and smoking during the course of disease results in worse outcomes
Wesnes et al., (2021)	88	Patients with RRMS aged between 18 and 55 years in Norway	To determine the association of vitamin D, tobacco use and BMI with disability progression in MS	Only lower vitamin D levels were associated with worse long term disability progression in MS
Simpson-Yap et al., (2021)		Participants of the HOLISM international cohort	To examine the effect of sun exposure and vitamin D on quality of life	Vitamin D supplement use was linked to higher physical and mental quality of life cross-sectionally, but only with increased physical QoL prospectively.