# Vitamin B Therapy, Methionine Synthase and Cystathionine Beta-Synthase (CBS) Gene Polymorphisms, and Their Impact on Homocysteine and Cardiovascular Events in Ischemic Stroke With Normal Renal Function: A Randomized Controlled Trial

## TL;DR

This study shows vitamin B therapy lowers homocysteine and improves outcomes in ischemic stroke patients, with less impact from genetic variations in a hilly region.

## Contribution

The study provides novel evidence on vitamin B therapy's efficacy in stroke patients with normal renal function and limited genetic polymorphism influence in a specific geographic region.

## Key findings

- Vitamin B therapy significantly reduced homocysteine levels compared to standard therapy.
- MS-AG and CBS-TT polymorphisms were less prevalent in the studied population.
- Vitamin B12 deficiency and low green vegetable intake were key predictors of hyperhomocysteinemia.

## Abstract

Background: Hyperhomocysteinemia cases were found to be higher in hilly regions due to factors such as high altitude and dehydration. There is limited research on methionine synthase (MS) and cystathionine beta-synthase (CBS) gene polymorphisms among stroke patients in Southeast Asia. The primary objective of the study was to determine the efficacy of vitamin B therapy in lowering homocysteine levels, and the secondary objective was to investigate the prevalence and impact of MS and CBS gene polymorphisms on treatment outcomes and cardiovascular events.

Methods: A randomized controlled trial was conducted on 90 ischemic stroke patients at a tertiary care hospital, Rishikesh, India. Participants received either vitamin B therapy (B6, B9, B12) or standard therapy for four months. Tools were genetic polymorphisms (polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)) testing, National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores, mean homocysteine, mean vitamin B12, and mean folate levels.

Results: The prevalence of MS-AG and CBS-TT polymorphism frequencies was 6% and 12%, respectively. At four months, the vitamin group showed a significant reduction in homocysteine as 8.6 vs. 19 µmol/L in standard therapy, improved mRS scores, and improved vitamin B12 and folate levels with p < 0.001. Vitamin B12 deficiencies and green vegetable intake were key predictors of hyperhomocysteinemia. Clinical outcomes included one recurrent stroke, eight cardiovascular events, and six vascular deaths.

Conclusion: Our observations indicated that vitamin B therapy effectively reduced homocysteine and addressed deficiencies in ischemic stroke patients. However, genetic polymorphism was found to be less prevalent in this hilly region. Combining the role of vitamin B on homocysteine, along with reducing stroke severity and functional disability, leads to early recovery of the stroke patient and reduces rehospitalisation.