Currently, ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults. Nutrition is a modifiable risk factor for stroke. B-vitamins are part of a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. These vitamins play an essential role in the regulation of cell proliferation, stress resistance, and embryo development. A deficiency in vitamin B12 is common in older adults and has been reported to be implicated in ischemic stroke. The aim of this review was to investigate whether vitamin B12 deficiencies impact the risk and outcome of ischemic stroke. Clinical data from our literature review strongly suggest that a deficiency in vitamin B12 is a risk factor for ischemic stroke and possible outcome. Our survey of the literature has identified that there is a gap in the understanding of the mechanisms through which a vitamin B12 deficiency leads to an increased risk of stroke and outcome. A vitamin B12 deficiency can increase homocysteine levels, which are a well-established risk factor for ischemic stroke. Another potential mechanism through which vitamin B12 deficient may impact neurological function and increase risk of stroke, is changes in myelination, however this link requires further investigation. Further studies are required in model systems to understand how a vitamin B12 deficiency changes the brain.

Purpose of review Ischemic stroke results in disability and mortality worldwide. Nutrition is a modifiable risk factor for stroke. For example, deficiencies in one-carbon metabolism have been linked to increased risk of stroke through elevated levels of homocysteine. Some countries world-wide fortify their diets with folates to prevent neural tube defects, but deficiencies in other one-carbon metabolites, such as vitamin B12 and choline are still present in many populations. The aim of this review is to understand the current evidence on how dietary supplementation by nutrients which modulate one-carbon metabolism impact stroke outcome. Recent findings The results from clinical studies evaluating lowering homocysteine through B-vitamin supplementation on stroke risk remain unclear. Other clinical and preclinical studies have shown increasing dietary intake of one-carbon metabolism has some benefit on stroke outcome. Preclinical studies have shown that increased levels of nutrients which modulate one-carbon metabolism help facilitate recovery in damage models of the central nervous system. One the mechanisms driving these changes is neuroplasticity. Summary The data suggest that increasing dietary nutrients that modulate one-carbon metabolites in patients that are at a higher risk for and suffer from central nervous system diseases, such as stroke, could benefit in addition to other therapies.

Objectives The majority of the world's population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Methods At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding Sources Midwestern University Start-Up Funds.