Homocysteinemia, or elevated plasma homocysteine, is a major factor that can influence poor cardiovascular health. High plasma levels of homocysteine appear to have negative effects on the vasculature, impairing the functional abilities of endothelial and smooth muscle cells. Suboptimal intake of several B vitamins, renal failure, environment, diet, stress, and genetic defects in homocysteine metabolism can all contribute to abnormal homocysteine levels.
Homocysteine is a sulfur containing amino acid that is created in the body from methionine, an essential amino acid derived solely from dietary intake. Methionine is metabolized into homocysteine via an intermediate, S-adenosylmethionine. Homocysteine can be metabolized to produce cysteine, a nonessential sulfur-containing amino acid, or it can be remethylated to methionine. Whether the body needs cysteine or methionine will dictate which path homocysteine metabolism will take.
Production of cysteine from homocysteine requires two specific enzymes for which vitamin B-6 is an essential coenzyme. Without adequate vitamin B-6, homocysteine cannot be metabolized into cysteine. The body can also metabolize homocysteine by remethylating it to methionine. The primary route by which homocysteine is remethylated to methionine requires folate in the form of methyltetrahydrofolate as a methyl donor and vitamin B-12 (methylcobalamin) as a coenzyme. Methyltetrahydrofolate, or L-methylfolate, is synthesized in the body from dietary folic acid. However, L-methylfolate can be used directly by the body, without the need for folic acid conversion via the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). In certain populations, the body’s ability to
convert folic acid to 5-MTHF by use of this enzyme may be compromised due to genetic differences.
B vitamins, in particular folate, methylcobalamin, and vitamin B-6 are necessary for the body to metabolize homocysteine. A deficiency or suboptimal levels of any of these essential vitamins may cause plasma homocysteine levels to rise. Dietary surveys and epidemiological studies indicate that suboptimal levels of folate, vitamin B-12, and vitamin B-6 are common in many population groups. Elderly individuals, smokers, alcoholics, and medications users, including estrogens and popular medications for cholesterol and blood glucose control, are at risk for subclinical deficiencies of one or more of these B vitamins.
TMG, trimethylglycine, also known as betaine anhydrous, acts as a methyl donor in the methionine/homocysteine cycle. One route of homocysteine metabolism is by methylation to form methionine, using a methyl group from methylcobalamin or from trimethylglycine. Methionine is then converted to S-adenosylmethione (SAMe). Trimethylglycine is absorbed rapidly and has a high volume of distribution due to extensive distribution to tissues, including the kidneys and liver. When taken orally, trimethylglycine can support normal homocysteine levels.† Improvement in plasma homocysteine may be seen within a week, and steady state could be reached within a month.
Choline, also considered a B vitamin, can be oxidized to betaine which serves as a methyl donor to convert homocysteine to methionine. Dietary intake of choline might also support healthy homocysteine level.† The effect of dietary choline intake may be greatest on those with lower folate levels.