The Controversial Role of HCY and Vitamin B Deficiency in Cardiovascular Diseases

Area of Science:

• Cardiovascular Research
• Nutritional Science
• Biochemistry

Background:

• Plasma homocysteine (HCY) is a known risk factor for cardiovascular disease (CVD) and stroke.
• Despite extensive research, B-vitamin supplementation has not proven effective in reducing CVD risk by lowering HCY levels.
• This has raised questions about the causal role of hyperhomocysteinemia (HHcy) and B-vitamin deficiencies in atherosclerosis.

Purpose of the Study:

• To critically review the existing literature on the role of HHcy and B-vitamin deficiencies in CVD.
• To evaluate the current understanding of the mechanisms linking HHcy to CVD, including oxidative stress, ER stress, and DNA methylation.
• To assess the clinical implications and actionable insights regarding HHcy screening and B-vitamin supplementation for CVD prevention.

Main Methods:

• Comprehensive literature review of experimental and human studies.
• Analysis of mechanistic evidence regarding HHcy's impact on cellular processes.
• Evaluation of clinical trial data on B-vitamin supplementation for CVD risk reduction.

Main Results:

• HHcy contributes to CVD through oxidative stress, ER stress, altered DNA methylation, and protein binding.
• Evidence suggests HHcy and B-vitamin deficiencies may accelerate telomere shortening, potentially promoting CVD.
• Current evidence indicates that HCY-lowering interventions with high-dose B vitamins lack efficacy in secondary CVD prevention.

Conclusions:

• The clinical utility of routine HCY screening for CVD patients is limited as the associated risk is not effectively actionable.
• B-vitamin depletion is common in the elderly and should be addressed, though high-dose supplementation does not prevent secondary CVD events.
• The role of HCY in primary CVD prevention remains understudied, necessitating further intervention and experimental research.