Does Lowering Homocysteine Cut CVD Risk?

In 1969 it was proposed that elevated homocysteine (Hcy) levels in the blood played a role in promoting atherosclerosis. People born with a genetic defect leading to very high Hcy levels in the blood are known to develop severe atherosclerosis. Population studies have shown an association of elevated Hcy levels and a higher risk of CVD.1 Several large studies showed people with a 25% lower Hcy level had an 11% lower risk of coronary heart disease and a 19% lower risk of stroke.2 People with a genotype that results in a less efficient metabolism of Hcy have an increased risk of CVD.3

Moderately elevated Hcy levels can usually be reduced by increasing the intake of several B-vitamins. This gave rise to hopes that giving these B-vitamins supplements to people with moderately elevated Hcy levels reduce the risk of CVD. Several double blind controlled clinical trials were conducted to determine whether or not lowering Hcy levels with supplements of B-vitamins would cut the risk of CVD. Unfortunately these studies showed that while B-vitamin supplements do lower Hcy levels they do not cut the risk of CVD. The longest and most recent trial had women at high risk for CVD take 2.5mg of folic acid, 1mg of vitamin B-12, and 50mg of vitamin B-6 for over 7 years. Results showed plasma Hcy levels dropped by 18.5% on average but there was no reduction in the risk of CVD or total mortality in those taking the B-vitamins versus the placebo.4

 

The failure of B-vitamin supplements to cut the risk of CVD could mean:

 

a) Moderately elevated Hcy levels do not increase CVD risk.

 

b) People with reduced renal function have an increased risk of CVD and higher Hcy. Taking B-vitamins would lower their Hcy level but not improve renal function.

 

c) high levels of synthetic folate used in these studies might damage the artery wall and offset the potential benefit of lower Hcy.5 Until more is known there seems little reason to routinely recommend B-vitamins to lower moderately elevated Hcy levels.

 

By Dr. James Kenney, PhD, RD, FACN.

 

1. JAMA 1995:274:1049-57

 

2. JAMA 2002;288:2015-22

 

3. Ann Intern Med 1999;131:363-75

 

4. JAMA 2008;299:2027-36

 

5. N Engl J Med 2006;354:1629-32

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