Members of the last group have a first-degree relative with premature atherosclerotic vascular disease, are smokers, or have hypertension. Screening can also be considered for patients with chronic medical disorders known to raise homocysteine, particularly chronic renal failure, and those who take medications that augment levels. Testing is appropriate for patients who have experienced unexplained deep venous thrombosis as well, since the condition is commonly linked with elevated homocysteine.

Ingestion of folate (folic acid) will reduce homocysteine levels, regardless of the process responsible for elevations. All patients should be encouraged to take in the recommended dietary allowance (RDA) of folate, vitamin B6, and vitamin B12. This can be accomplished by eating more of the foods that contain these nutrients.14 Folate is found in ready-to-eat fortified cereals, leafy green vegetables, fruits, and legumes. In an effort to reduce the incidence of neural tube birth defects, cereal grains have been fortified with 1.4 mg of folic acid per kg of grain. Ready-to-eat fortified cereals also contain vitamins B6 and B12, as do beef and poultry. Artichokes, asparagus, beans, cabbage, and noncitrus fruits are examples of foods that supply vitamin B6.

This strategy will not be sufficient for everyone. Experts who recommend monitoring and treatment of high homocysteine levels argue that possible benefits of the intervention, though not yet proven to limit CHD, nevertheless outweigh any known drawback.7 After all, supplementation with folic acid is inexpensive, generally safe in dosages up to 10,000 mcg/d (10 mg/d), and does reduce homocysteine concentrations. While some physicians prescribe folic acid empirically, others insist that doing so is akin to selecting a dosage regimen for the patient with type 2 diabetes mellitus without first measuring blood glucose levels.

An acceptable target range for homocysteine is less than 10 µmol/L. Patients with mild to moderate elevations—10 to 15 µmol/L—may do well with a daily multivitamin that contains 400 mcg of folic acid plus the RDA for vitamins B6 and B12. However, patients with moderate to severe hyperhomocysteinemia (15 µmol/L or higher) may need fairly high dosages of folic acid before their levels normalize. One important word of caution: Before starting treatment, exclude vitamin B12 deficiency, as occurs in patients with pernicious anemia with very high levels of homocysteine, since folic acid can camouflage hematological signs, allowing neurological disturbances to worsen. Long-term replacement with vitamin B12 (cyanocobalamin) injections is necessary in these patients.

A response can usually be seen within 6 to 8 weeks. If an initial dosage of folic acid, 400 to 800 mcg/d, proves inadequate, double it and check levels again after 8 weeks. Continue in this fashion until the patient's homocysteine levels reach the desired concentration or until the dosage reaches 10,000 mcg/d. After that, measure homocysteine levels just once or twice a year.