The aim of the animal-model study, conducted by a group of researchers from Carleton University in Ottawa, Health Canada, and the Center for Stroke Research Berlin, was to understand the role of B-vitamins in stroke pathology using in vivo and in vitro mouse models.
Results in reducing homocysteine levels—the plasma linked to risk of cardiovascular disease such as stroke—using vitamin B supplementation has been a focus of many studies, though researchers of this current study argued that because some countries have mandatory folic acid fortifications and others do not, “the results remain inconsistent.”
Divided into two components, the first portion of the study assessed the impact of folate (a B-vitamin) deficiency prior to ischemic damage followed by B-vitamins and choline supplementation in mice. The second portion assessed how a genetic deficiency of an enzyme involved in folate metabolism (MTHFR) increases vulnerability to stroke.
Folic acid deficient diet, followed by supplementation
The study involved 32 male mice put on either a folic acid-deficient diet to increase homocysteine levels or a normal diet (control). Both groups were on the diet for four weeks prior to ischemic damage surgery to simulate stroke.
After the brain damage, mice on the folic acid deficient diet were placed on a supplement diet, increasing folic acid intake from 0.3 mg/kg to 5 mg/kg, while the control diet mice kept their same routine, which contains 2 mg/kg folic acid.
In addition, the supplement group also consumed increased riboflavin (from 6 mg/kg to 10 mg/kg), vitamin B12 (0.5 mg/kg from 0.025 mg/kg) and choline bitrate (1150 mg/kg to 4950 mg/kg). “These levels of vitamins were chosen because they have previously been reported to be beneficial in vivo,” explained the researchers.
Behavioral tests and analyses
Four weeks after ischemic damage, researchers assessed motor function using a range of different tests, with results showing improved motor function of the supplemented diet group compared to the control diet mice. The data also showed that mice on the supplement diet had a higher movement score when compared to the control diet mice.
“These data suggest that supplementation with B-vitamins and choline in preconditioned folic acid deficient animals is beneficial in reducing behavioral deficits associated with ischemic damage to the sensorimotor cortex,” wrote the researchers.
B-vitamins and choline not neuroprotective, but may induce neuroplastic changes
Analysis of the mice’s brains after ischemic damage and the supplementation period revealed that, among the supplement diet group, there was reduced post-operative levels of homocysteine and more anti-oxidant activity, suggesting improved neuroplasticity.
Though other studies have shown how folic acid promotes regeneration and functional outcomes in animals with spinal cord injuries, “we are the first to show an increase in neuroplasticity after ischemic damage in the brain,” they wrote.
“B-vitamins and choline may promote neuroplasticity through their role in nucleotide synthesis, DNA repair, and methylation.”
These findings, the researchers argued, supports positive effects of supplementation of B-vitamins and choline in ischemic stroke individuals with elevated levels of homocysteine because of folate deficiency. “This dietary supplementation can easily be implemented in combination with other therapies, since it is relatively inexpensive and safe,” they added.
Source: Neurobiology of Disease
Pulbished online ahead of print, https://doi.org/10.1016/j.nbd.2017.04.001
B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke
Authors: Nafisa M. Jadavji, et al.