Homocysteine Trials — Clear Outcomes for Complex Reasons

Abstract

In 1969, McCully first proposed that homocysteine causes atherosclerosis.¹ His hypothesis was based on the finding of atherosclerotic plaque at autopsies of young people with homocystinuria. This hypothesis was later modified to include a broader population, positing that mild hyperhomocysteinemia caused by dietary deficiencies of the vitamin cofactors required for the metabolism of homocysteine — folic acid, vitamin B₁₂, and vitamin B₆ — is a risk factor for atherothrombosis. In developed countries, these vitamins are partially removed from foods during processing,² and typical diets are rich in the precursor amino acid methionine (which is derived from animal . . .