Table 1.

Summary of clinical studies investigating vitamin B12 in patients

Reference	Study design	Sample size	Country	Fortification present	Measure used to determine vitamin B12 levels	Major findings
He et al. (2004)	Longitudinal Cohort study/large prospective follow-up study	725 stroke cases (455 ischemic, 125 hemorrhagic, 145 unknown) *Men only	USA	Yes	Studied intake levels only. Dietary information was assessed every 4 years for 14 years using detailed and validated semiquantitative food frequency questionnaire.	Intake of vitamin B12 and folate, but not B6 was inversely related to risk of ischemic stroke. No statisticgroupy significant associations with hemorrhagic stroke risk.
van Guelpen et al. (2005)	Prospective, Nested Case-Refernt Study, population based	396 (334 ischemic and 62 hemorrhagic stroke cases) from Northern Sweden Health and Disease Cohort	Sweden	No	Venous blood samples drawn with minimum of 4-hour fasting, Folate and B12 levels were analyzed by Quantaphase II radioassay in heparinized serum/plasma.	Neither plasma nor dietary vitamin B12 was statisticgroupy significantly associated with either stroke type.
Zacharia et al. (2017)	Unusual case	1 (35-year-old male vegetarian)	USA	Yes	Tested serum B12 levels before and after supplementation over 18 months.	Two months after beginning vitamin B12 supplemental treatment, patient’s symptoms improved dramaticgroupy. This included resolution of aphasia and improvement of hemiparesis. Vitamin B12 increased from 206 to 1249 ng/L and homosystein levels decreased from 55.7 to 28.5 μM.
Ahmed et al. (2019)	Cohort study	4055 patients	Canada	Yes	Serum B12 levels measured by immunoassay.	In stroke patients, 8.2% of patients were biochemicgroupy deficient in vitamin B12, 10.6% patients were deficient in metabolic B12, and 19.1% had high homocysteine levels. In patients aged 80 years or older, 18.1% of patients were deficient in metabolic B12 and 35% had high homocysteine levels.