Emergent Cardiovascular Risk Factor

Factors Contributing to High Homocysteine

Homocysteine concentration is influenced by age, gender, and medication and by genetic, nutritional, and pathologic factors.^[3,4] Plasma homocysteine increases with age, possibly due to renal impairment.^[3] There is a positive correlation between creatinine levels and plasma homocysteine.^[3] In general, men have higher levels of homocysteine than women, most likely due to higher creatinine values and greater muscle mass.^[3] Women, before menopause, have lower levels of homocysteine than do postmenopausal women.^[3]

Use of some medications raises homocysteine levels. Methotrexate, nitrous oxide, phenytoin (Dilantin), and carbamazepine (Tegretol) all increase homocysteine levels.^[3,12] Azaribine, which also raises homocysteine, was prohibited by the Food and Drug Administration in 1976 because it was associated with increased risk of thromboembolism.^[3] Estrogen-containing oral contraceptives may alter the metabolism of homocysteine. Usually, women taking oral contraceptives have lower homocysteine, but higher levels have been seen in some.^[3] The lipid-lowering agents colestipol and niacin, in combination with thiazide diuretics, may raise homocysteine levels.^[3,12]

Some rare genetic disorders that include deficiencies of cystathionine b-synthase, methionine synthase, and 5-methyltetrahydrofolate reductase (enzymes necessary for the metabolism of methionine) result in elevated homocysteine.^[3,12] In 1962 a group of children in northern Ireland with thromboembolic disease and neurologic, skeletal, and ocular abnormalities were found to have a rare autosomal recessive trait that was characterized by elevated homocysteine levels.^[3,11] Men who have high homocysteine and factor V Leiden, an inherited blood clotting disorder, have a much greater risk of developing venous thrombosis than men who have either condition alone.^[13] Hormonal abnormalities, such as thyroid deficiency and decreased estrogen levels, can also raise homocysteine. In studies of normal subjects there is a strong genetic influence on plasma homocysteine concentration.^[3]

Environmental toxins, such as tobacco smoke and carbon disulfide, can raise homocysteine levels. Carbon disulfide is used in the manufacture of cellophane and pesticides, and as solvent for fats, resins, and rubber.^[2]

Nutritional deficiencies of folic acid or vitamin B12 raise homocysteine levels. Deficiency of vitamin B6 may also be associated with high homocysteine, but less commonly than folic acid.^[3,4] The more coffee consumed, decaffeinated or regular, and especially unfiltered, the higher the levels of homocysteine.^[14,15]

Certain diseases, such as breast, ovarian, and pancreatic cancers, acute lymphoblastic leukemia, and severe psoriasis, are also linked to high homocysteine levels. Chronic renal failure contributes to high homocysteine, which increases when creatinine increases.^[3] Both heart and kidney transplant recipients have very high homocysteine levels.^[16,17]

Cite this: Emergent Cardiovascular Risk Factor: Homocysteine - Medscape - Jan 01, 2002.

Table 2. Factors contributing to elevated homocysteine levels
Increased age^[3,10,12] Being male or postmenopausal female^[3,10,12] Medications: anticonvulsants, lipid-lowering agents in combination with thiazide diuretics, estrogen-containing oral contraceptives, nitrous oxide, methotrexate^{[3,4,10,11,12]} Low estrogen levels^[3] Tobacco smoke and exposure to carbon disulfide^[2,6] Nutritional vitamin deficiencies of folic acid, vitamin B6, and vitamin B12^[3,4,11,12] Excessive coffee consumption^[14,15] Chronic diseases: severe psoriasis, some cancers, systemic lupus erythematosus, renal failure, hypothyroidism, heart or kidney (recipients) transplantation^{[3,4,10,11,12]} Inherited errors of methionine metabolism: cystathionine b-synthase deficiency, methionine synthase deficiency, 5-methyltetrahydrofolate reductace deficiency^[2,3,11,12]

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