Table 1. Summary of included studies showing the correlation between Vitamin D and MS risk.

FDE - First Demyelinating Event, CNS - Central Nervous System, GEMS - Genes and Environment in Multiple Sclerosis, EIMS - Epidemiological Investigation of Multiple Sclerosis, NHS - Nurses Health Study, RRMS - Relapsing-Remitting Multiple Sclerosis, VDR - Vitamin D Receptor, GWAS - Genome-Wide Association Studies, IEU - Integrative Epidemiology Unit, NHGRI-EBI - National Human Genome Research Institute-European Bioinformatics Institute 

Langer-Gould et al. [21]; Lucas et al. [23] ; Hedstrom et al., [24]; Munger et al., [26]; Munger et al., (2006) [27]; Harroud et al., [28]; Cancela Díez et al., [33]; Jiang et al., [34]; Wang R [35] 

REFERENCES	DESIGN	SAMPLE SIZE	POPULATION	OBJECTIVES	CONCLUSIONS
Langer-Gould et al., (2018)	case-control	Blacks (116 cases/131 controls); Hispanics (183/197); whites (247/267)	members of Kaiser Permanente, Southern California	To examine the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups	Higher serum 25OHD levels were associated with a decreased risk of MS in whites but not in other racial groups.
Lucas et al., (2011)	case-control study	216 cases and 315 controls	people between the age of 18 to 59 years with an FDE living in Australia	measures of skin phenotype and actinic damage, and vitamin D status	Sun exposure and vitamin D status independently affect the risk of CNS demyelination.
Hedstrom et al., (2019)	case-control study	7069 cases and 6632 matched controls	GEMS study and  EIMS study	To determine whether the influence of low sun exposure on MS risk is mediated by low vitamin D levels	Low sun exposure acts both directly on MS risk as well as indirectly, by leading to low vitamin D levels
Munger et al., (2004)	Prospective cohort study	NHS: 92,253  NHS II: 95,310	NHS and NHS II	To assess the protective effect of vitamin D on the risk of MS.	Intake of vitamin D supplements was associated with reduced MS risk. No such association was found with dietary vitamin D
Munger et al., (2006)	Prospective nested case-control study	Whites (148 cases, 296 controls)  Blacks and Hispanics (109 cases, 218 controls)	More than 7 million US military personnel	To examine whether 25(OH)D levels are associated with the risk of MS	High circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.
Harroud et al., (2021)	Mendelian randomization study	14,802 cases and 26,703 controls		The relative role of serum vitamin D levels and varying levels of adiponectin and leptin in the association between obesity and MS.	A minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect
Cancela Díez et al., (2021)	Retrospective case-control study	209 cases and 836 controls	Patients with RRMS and healthy controls of Caucasian origin from Southern Spain.	To evaluate the association between polymorphisms in the VDR gene and the risk of MS	Only the VDR FokI (rs2228570) polymorphism was associated with developing MS.
Jiang et al., (2021)	Mendelian randomization study	Sample size ranged from 9,954 to 1,030,836 (median 112,561; mean 148,179)	190 GWAS from IEU OpenGWAS Project and NHGRI-EBI GWAS catalogue	To examine a causal role of vitamin D in various phenotypic traits and diseases	Genetically predicted 25(OH)D levels are inversely linked with the risk of MS
Wang R (2022)	Mendelian randomization study	14,498 cases and 24,091 controls	GWAS of European ancestry	To examine a causal role of vitamin D in MS risk	A causal link between genetically predicted serum 25(OH)D levels and MS risk