Nutr Metab (Lond). 2026 May 1. doi: 10.1186/s12986-026-01125-0. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiovascular diseases is the most common cause of mortality in the world. B vitamins (B₁-B₁₂) control how mitochondria make energy, how nitric oxide is made, how one-carbon is used, and how genes work. A deficiency leads to hyperhomocysteinemia, oxidative stress, and endothelial dysfunction, all of which are important to vascular disease. Observational studies consistently associate low B-vitamin levels with an elevated risk of cardiovascular diseases; nevertheless, randomized supplementation trials have demonstrated only modest reductions in significant events.
METHODS: This narrative review summarizes molecular, epidemiological, and clinical evidence on the role of B vitamins in cardiovascular health. Special focus was paid to functional biomarkers and gene-nutrient interactions that affect how well a therapy works. The literature was identified through targeted searches of PubMed, Scopus, and Google Scholar. Priority was given to high-quality evidence, including mechanistic studies, observational cohorts, randomized controlled trials, meta-analyses, and major review articles relevant to cardiovascular outcomes.
RESULTS: Functional indicators, such as methylmalonic acid and holotranscobalamin, offer superior accuracy compared to blood levels in assessing vitamin status. Nutrigenetic interactions, particularly the effects of folate and riboflavin on methylenetetrahydrofolate reductase polymorphisms, exhibit blood pressure-lowering and stroke-preventive advantages. The clinical efficacy of B-vitamin supplementation is highly dependent on baseline nutritional status and regional food fortification policies. For example, folic acid supplementation significantly reduces stroke incidence in populations who lack mandatory folate fortification, whereas trials conducted in folate-sufficient cohorts generally demonstrated no added cardiovascular benefit. Recognizing this population-specific variability helps explain the historical discrepancy between the strong mechanistic potential of B-vitamins and the mixed results observed in large-scale clinical trials.
CONCLUSION: While adequate B-vitamin status remains mechanistically essential for cardiovascular homeostasis, the clinical benefits of routine supplementation are nuanced and highly population-dependent. Consequently, ubiquitous supplementation is unlikely to produce extensive advantages. A precision strategy that combines biomarkers, genotype stratification, and population context can help find their therapeutic potential. Future methods should integrate diet with precision cardiology to enhance vascular prevention.
PMID:42067935 | DOI:10.1186/s12986-026-01125-0