Related Experiment Video
Updated: Aug 10, 2026
Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
Homocysteine lowering with folic acid and B vitamins in vascular disease
Eva Lonn1, Salim Yusuf, Malcolm J Arnold
1Population Health Research Institute, Hamilton General Hospital, McMaster University, and the Department of Medicine, Division of Cardiology, Hamilton Health Sciences, Hamilton, Ont. lonnem@mcmaster.ca
Insights
Folic acid and B vitamins did not reduce major cardiovascular events in patients with vascular disease, despite lowering homocysteine. The study found no significant benefit for heart attack or stroke risk, but did note a reduction in stroke events.
Area of Science:
- Cardiovascular Medicine
- Nutritional Science
- Clinical Trials
Background:
- Lower homocysteine levels correlate with reduced coronary heart disease and stroke risk.
- Folic acid and vitamins B6/B12 are known to decrease homocysteine levels.
- This study investigated if vitamin supplementation could mitigate cardiovascular events in patients with existing vascular disease.
Purpose of the Study:
- To determine if daily supplementation with folic acid, vitamin B6, and vitamin B12 reduces the risk of major cardiovascular events.
- To assess the impact of these vitamins on mortality, myocardial infarction, and stroke in high-risk patients.
Main Methods:
- A randomized controlled trial involving 5522 patients aged 55+ with vascular disease or diabetes.
- Participants received either a combination of folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) or a placebo daily for five years.
- The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke.
Main Results:
- Active treatment significantly lowered plasma homocysteine levels compared to placebo.
- No significant reduction was observed in the primary composite outcome (cardiovascular death, myocardial infarction, stroke) between groups.
- A notable decrease in stroke events was observed in the active treatment group, but hospitalizations for unstable angina increased.
Conclusions:
- Combination supplements of folic acid, vitamin B6, and vitamin B12 did not significantly reduce the risk of major cardiovascular events in patients with vascular disease.
- While homocysteine levels were reduced, this did not translate to a lower risk of the primary composite outcome.
- Further research may be needed to clarify the specific role of these vitamins in cardiovascular health.
Background:
In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease.
Methods:
We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke.
Results:
Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49).
Conclusions:
Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).
Related Concept Videos
01:26Atherosclerosis III: Management
01:30Vitamins
01:28Hypertension IV: Drug Therapy and Lifestyle Modifications
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...