Hyperhomocysteinemia, or the rise of plasmatic
homocysteine levels above 15 mug/dL, is accepted nowadays as an independent risk factor for
cardiovascular disease in men and women.
Homocysteine (Hcy) is a non-
protein forming aminoacid (aa) derivated from the loss of the methyl group, found within
methionine.
Methionine regenerates by retrieving the
methyl radical from
5-methyltetrahydrofolate (5-MTHF) creating
tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate
reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine-beta-syntetase (CBS), it irreversibly converted into cystationine, a precursor of
cysteine,
glutathione, and other substances that are finally excreted in the urine.
Hyperhomocysteinemia results from inhibition of the remethylation route, or inhibition or saturation of the transsulfuration pathway. Main factors causally associated increased plasmatic Hcy are mutations of the
enzymes MTHFR and CBS; varying nutritional and health states; demographic factors; and, others. The most accepted hypotheses about Hcy action in
cardiovascular disease are direct endothelial and vessel wall damage; oxidative stress generation; and, stimulation of a procoagulant and proinflammatory state of blood components. Since
hyperhomocysteinemia can be effectively treated with
folic acid, prospective trials are underway to determine if
folate therapy is required to lower Hcy levels in plasma. These studies also attempt to address the impact, if any, of
folate therapy in the reduction of cardiovascular risk, and to demonstrate if
hyperhomocysteinemia is actually an independent risk factor that can be effectively treated.