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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #203708
Title: Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia?

Author
item Rosenberg, Irwin
item MULROW, CYNTHIA - AM. COLLEGE OF PHYSICIANS

Submitted to: Annals of Internal Medicine
Publication Type: Other
Publication Acceptance Date: 7/1/2006
Publication Date: 8/1/2006
Citation: Rosenberg, I., Mulrow, C. 2006. Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia? Annals Of Internal Medicine. 145(3): 226-227.

Interpretive Summary:

Technical Abstract: Several observational studies involving healthy populations in the 1990s showed positive associations between elevated homocysteine level and increased risk for ischemic heart disease and stroke. Several small trials conducted in western populations in the early and mid-1990s suggested that “daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 mol/l to 8-9 mol/l).” In 1998, the U.S. Food and Drug Administration mandated fortification of enriched cereal grain flour products with 140 g of folic acid per 100 g of flour. The prevalence of folate deficiency and hyperhomocysteinemia fell sharply. A population cohort study that assessed the impact of folic acid fortification found a decrease in stroke deaths in the year after fortification. Several large secondary prevention trials in patients with vascular disease began. One of the first trials, the Vitamin Intervention for Stroke Prevention (VISP) trial, found that a moderate reduction of total homocysteine level after nondisabling cerebral infarction had no statistically significant effect on vascular outcomes during 2 years of follow-up. The trial was designed with the expectation of lowering homocysteine levels by 5 mol/L, but a lower than expected average baseline homocysteine level permitted only a 2-mol decrease in plasma homocysteine. Two larger, double-blind, placebo-controlled trials with longer follow-up followed: the Heart Outcomes Prevention Evaluation (HOPE) 2 and the Norwegian Vitamin (NORVIT) Trial.