Homocysteine Trials — Clear Outcomes for Complex Reasons

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 . . .