Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials

  title={Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials},
  author={Robert J. Clarke and Jim Halsey and Derrick A Bennett and Sarah Lewington},
  journal={Journal of Inherited Metabolic Disease},
Moderately elevated homocysteine levels have been associated with a higher risk of cardiovascular disease in observational studies, but whether these associations are causal is uncertain. Randomized trials of dietary supplementation with B vitamins were set up to assess whether lowering homocysteine levels could reduce the risk of vascular disease. This review is based on a meta-analysis of published results of eight homocysteine-lowering trials for preventing vascular disease. The eight trials… 

Homocysteine – from disease biomarker to disease prevention

It is concluded that total homocysteine values in adults of 10 μmol/L or below are probably safe, but that values of 11 μmol /L or above may justify intervention.

Link between Homocysteine and Cardiovascular Diseases

A correlation between Hcy and hypertension indicates that Hcy levels could be used as a potential marker for atherosclerosis progression, and the combination of consuming supplements of B12, B6, and folate on a daily basis reduces the progression of Atherosclerosis.

The Association Between the Risk of Hypertensive Disorders of Pregnancy and Folic Acid: A Systematic Review and Meta-Analysis.

  • Yahui YuXimu SunXinrui WangXin Feng
  • Medicine
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
  • 2021
LD-FA significantly decreased the risk of PE but not GH, and post-conception LD-FA and pre- Conception BMI<25 kg/m2 were considered as protective factors to reduce the riskof PE.

Mediterranean Diet and Cardiovascular Risk: Beyond Traditional Risk Factors

This article will mainly focus on reviewing the current evidence about the effects that this dietary pattern exerts on alternative factors, including postprandial lipemia or coagulation, among others, as well as providing a short review on future directions.

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Analyzing over 1500 subjects, an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction is found.

Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients

Large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation.

An Overview of Methods and Exemplars of the Use of Mendelian Randomisation in Nutritional Research

The selected exemplars demonstrate the importance of well-conducted Mendelian randomization studies as a robust tool to prioritize nutritional exposures for further investigation.

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

It seems reasonable to conclude that lowering homocysteine alone is probably insufficient to mitigate the risk of thromboembolic, cardiovascular and neurodegenerative disorders inasmuch as this bizarre amino acid acts in strict synergy with other probably more powerful risk factors.

Multivitamin-mineral use is associated with reduced risk of cardiovascular disease mortality among women in the United States.

An association between MVM use of >3 y and reduced CVD mortality risk for women is found when models controlled for age, race, education, body mass index, alcohol, aspirin use, serum lipids, blood pressure, and blood glucose/glycated hemoglobin.



Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals.

Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.

Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial.

The findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease or aortic valve stenosis and mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12).

Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.

Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease and under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided.

Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.

Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.

Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis.

This meta-analysis of observational studies suggests that elevated homocysteine is at most a modest independent predictor of IHD and stroke risk in healthy populations.

Homocysteine lowering and cardiovascular events after acute myocardial infarction.

Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction and a harmful effect from combined B vitamin treatment was suggested.

Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial.

After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.

Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials.

The objectives were to ascertain the lowest dose of folic acid associated with the maximum reduction in homocysteine concentrations and to determine the additional relevance of vitamins B-12 and B-6.