(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1157-1162.)


The Effects of Folic Acid Supplementation on Plasma Total Homocysteine Are Modulated by Multivitamin Use and Methylenetetrahydrofolate Reductase Genotypes
M.R. Malinow; F.J. Nieto; W.D. Kruger; P.B. Duell; D.L. Hess; R.A. Gluckman; P.C. Block; C.R. Holzgang; P.H. Anderson; D. Seltzer; B. Upson; ; Q.R. Lin

Abstract
Elevated concentration of plasma total homocysteine (tHcy) is a common risk factor for arterial occlusive diseases. Folic acid (FA) supplementation usually lowers [homocysteine] tHcy levels , but initial tHcy and vitamin levels, multivitamin use, and polymorphisms in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) may contribute to variability in reduction. We tested the effects of a 3-week daily intake of 1 or 2 mg of FA supplements on tHcy levels in patients with and without coronary heart disease (CHD) who were analyzed for the C677T MTHFR mutation. Prior multivitamin intake and baseline vitamin and tHcy levels were also compared with responsiveness to folate supplementation. Both dosages of FA lowered tHcy levels similarly, regardless of sex, age, CHD status, body mass index, smoking, or plasma creatinine concentration. In non–multivitamin users, FA supplements reduced tHcy by 7% in C/C homozygotes and by 13% or 21% in subjects with one or two copies of the T677 allele, respectively; the corresponding reductions were smaller in users of multivitamins. Moreover, T/T homozygotes had elevated tHcy and increased susceptibility to high levels of tHcy at marginally low plasma folate levels, as well as enhanced response to the tHcy-lowering effects of FA. Although other factors are probably involved in the responsiveness of tHcy levels to FA supplementation, about one third of heterogeneity in responsiveness was attributable to baseline tHcy and folate levels and to multivitamin use.


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American Journal of Clinical Nutrition, Vol. 76, No. 2, 301-302, August 2002

Methylenetetrahydrofolate reductase: a link between folate and riboflavin?
Rima Rozen

In this issue, McNulty et al (1) present data suggesting that the plasma homocysteine concentration in individuals with a mutation in methylenetetrahydrofolate reductase (MTHFR; EC 1.7.99.5) is influenced by riboflavin status. Hyperhomocysteinemia has received considerable attention as a possible risk factor for cardiovascular disease. It has also been observed in several other common conditions, including birth defects, pregnancy complications, and Alzheimer disease. Homocysteine concentrations can certainly be reduced with folate, vitamin B-6, and vitamin B-12 supplementation, but the benefit of riboflavin in hyperhomocysteinemia is a relatively new concept.