:Sulfur containing nonessential
amino acid that is not found in the
diet. Dietary methionine is
converted to homocysteine.
CH3-S-Ch2-CH2-CH-CO2- → +H3N-C-COO-
70-80% bound to albumin via a disulfide link
20-30% either as a homocysteine dimer or a
* The type(s) of species responsible for the CVD
pathology have yet to be determined.
(MTHFR) polymorphism due to a point
mutation on chromosome 1.
Cystathione β-synthase deficiency
Methionine synthase deficiency
* Both are rare autosomal recessive disorders that are
correlated with hyperhomocysteinemia and vascular
Chronic renal failure regardless of etiology, duration, or
type of dialysis
Possibly through increased cell turnover
Cholestryamine (reduces cholesterol in blood)
Impairs folate absorption
Methotrexate (treatment of psoriasis)
Depletes folate metabolites
Anti-epileptics (carbemazapine, phenytoin)
Lower folate concentrations
*Tobacco and caffeinated coffee are also
associated with increased homocysteine
Homocysteine is one of many damaging
agents to endothelial cells
LDL and platelets invade
Platelets secrete chemoattractants for monocytes
PDGF - Platelet derived growth factor stimulates smooth
muscle proliferation and thickening of the tunica media.
Smooth muscle cells from the tunica media invade the
Monocytes invade and are activated to
Smooth muscle cells and macrophages
Foam cells/Fatty streaks
The high amounts of cholesterol ester consumed
will precipitate into crystalline deposits.
Deposits calcify and become rough stimulating
clot formation creating a fibrous plaque.
Narrows the lumen of the vessels, restricting blood
1969 – Dr. Kilmer McCully, M.D.
Compared an 8 y/o patient with homocysteinuria
who died of a stroke and an infant with an inherited
defect of cobalamine metabolism who died of
Concluded that elevated homocysteine levels result
in premature atherosclerosis.
Later expanded to include general populations with
mild hyperhomocysteinemia, typically associated
with dietary deficiencies.
Vitamins to Prevent Stroke
Stated that an adjustment for renal function
eliminated the relationship between total
homocysteine levels and intima media thickness
as well as flow-mediated dilation of the brachial
Vitamin Intervention for Stroke Prevention
Reduction in total plasma homocysteine
concentration was reported at 21% in participants
after exclusion of those with impaired renal
status, those with malabsorption of B vitamins, or
those taking other B vitamins not associated with
Heart Outcomes Prevention Evaluation
For patients with vascular disease, B vitamin
therapy significantly reduced stroke by 25% but
not myocardial infarction or death.
Treatment with high-dose B vitamins in combination
with dietary methionine restriction resulted in
markedly reduced results.
* Results for mild homocysteinuria have not shown
such significant results. Contradictory results may
be due to trial design, adverse effects from vitamin
supplementation, and using homocysteine as a risk
factor or not as a risk factor.
Supplementation of B vitamins
Folate, B6, and B12
Restriction of methionine containing
Sesame seeds, brazil nuts, fish, meats
Gauthier, G.M., Keevil, J.G., McBride, P.E., The
Association of Homocysteine and Coronary Artery
Disease. Clin. Cardiol. 2003; 26:563-8.
Gropper, S.S., Groff, J.L., and Smith, J.L., Advanced
Nutrition and Human Metabolism. 5th Edition,
Wadsworth Publishing, 2009.
Lavie, C.J., Milani, R.V., Homocysteine The Rubik’s
Cube of Cardiovascular Risk Factors. Mayo Clinic
Proceedings. 2008; 83(11):1200-02.
Scott, J., Weir, D. Homocysteine and cardiovascular
disease. Q J Med. 1996; 89:561-3.