J Nutr 1996 Apr;126(4 Suppl):1276S-1280S
Vitamins as homocysteine-lowering agents.
Department of Medicine, County Hospital, Kalmar, Sweden.
Moderate hyperhomocysteinemia is, today, considered an established risk factor for cardiovascular disease. A graded dose-response relationship between plasma homocysteine concentration over its full range and cardiovascular risk strongly supports causality. Therefore, intervention studies with homocysteine-lowering vitamins are needed. This mini review shows that supplementation with folic acid not only markedly reduces elevated plasma homocysteine concentrations but also reduces normal homocysteine concentrations. Folic acid doses of < 1 mg/d may be effective. Supplementation with a combination of folic acid and cyanocobalamin will secure full homocysteine-lowering effect and prevent occurrence of vitamin B12 deficiency during the course of therapy.
J Nutr 1996 Apr;126(4 Suppl):1266S-1272S
The use of homocysteine and other metabolites in the specific diagnosis of vitamin B12 deficiency.
Stabler SP, Lindenbaum J, Allen RH
University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Vitamin B12 (cobalamin) is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase. The serum vitamin B12 concentration has been shown to have limitations in specificity and sensitivity in diagnosing vitamin B12 deficiency and predicting response to therapy in subjects with clinical deficiency syndromes. Serum methylmalonic acid and/or total homocysteine concentrations have been shown to be elevated in almost every patient who has a clinical response to vitamin B12. In elderly populations serum methylmalonic acid concentrations are elevated in the majority (60-66%) of subjects who have elevated total homocysteine concentrations, suggesting that vitamin B12 deficiency (with or without associated folate deficiency) and/or chronic renal insufficiency may be the primary cause of most of the elevated total homocysteine concentrations in elderly populations. In such subjects vitamin B12 and folate concentrations are both frequently in the low or low normal range, making differentiation of the clinical syndromes by use of serum vitamin concentrations problematic. Elevations of 2 methylcitric acid and cystathionine also result from vitamin B12 deficiency. Serum N-methylglycine concentrations are normal in cobalamin deficiency but are increased in 40% of patients deficient in folate. In conclusion, elevations of methylmalonic acid and total homocysteine are very sensitive and specific in diagnosing vitamin B12 deficiency and can be used to help differentiate vitamin B12 deficiency from folate deficiency. Elevated total homocysteine concentrations that may have been attributed to folate deficiency in elderly subjects may in many instances be the result of vitamin B12 deficiency even though serum vitamin B12 concentrations are within normal limits.
J Nutr 1996 Apr;126(4 Suppl):1273S-1275S
Treatment of hyperhomocysteinemia: physiological basis
Department of Pediatrics, Section of Genetics, Rush Medical College and Rush-Presbyterian St. Luke’s Medical Center, Chicago, IL 60612, USA.
Hyperhomocysteinemia (HCY) is caused either by genetic or nongenetic defect(s), and the clinical severity of HCY is correlated with the biochemical abnormality. Treatment of HCY is approached on the basis of its etiology and severity of defect. The preferred method of treatment for genetic HCY is activation of mutant enzyme activity with the cofactor or the precursor of cofactor. If HCY does not respond to this treatment, pharmacological doses of betaine or folic acid should be used to enhance the alternative pathway of homocysteine turnover. Phenotypic expression of minor genetic defects, such as heterozygous cystathionine synthase deficiency and thermolabile methylenetetrahydrofolate reductase (MTHFR) can be amplified or masked by nongenetic (nutritional) factor(s). Hence, supplementation of folic acid, vitamin B12, pyridoxine and choline to maintain their serum concentrations above low normal range may satisfactorily prevent the development of moderate HCY due to a minor genetic defect.