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FOLATE, VITAMIN B[12] LEVELS SHOW INVERSE CORRELATION TO HOMOCYSTEINEMIA

This article was originally published in The Tan Sheet

Executive Summary

FOLATE, VITAMIN B[12] LEVELS SHOW INVERSE CORRELATION TO HOMOCYSTEINEMIA in elderly subjects, according to a cross- sectional analysis of homocysteine, vitamin intake and serum levels of participants in the Framingham Heart Study published in the Dec. 8 Journal of the American Medical Association. The study authors, Jacob Selhub, PhD, Tufts University, et al., also found that pyridoxal-5'-phosphate (PLP) -- or vitamin B[6] -- levels had an inverse association with homocysteine levels in the blood. In addition, the study showed a general inverse association between vitamin intake and homocysteine levels. High homocysteine levels have been shown in other studies to be associated with an increased risk of cardiovascular disease. Selhub et al. used both food-frequency questionnaires and plasma analysis to determine the vitamin status and intake of 1,160 test subjects aged 67 to 96 years. For the purpose of analysis, the researchers calculated homocysteine levels among test subjects by decile groups and established two B-vitamin indexes, one of corresponding decile levels for intake and another of blood concentration deciles for the three nutrients. The study defined "high" homocysteine levels as greater than 14 mcmol/L. "Mean homocysteine and the prevalence of high homocysteine increased dramatically across categories of the B vitamin indexes," Selhub et al. reported. "The prevalence of high homocysteine was almost six-fold greater among subjects in the lowest index category compared with subjects in the highest category for both the plasma and intake [vitamin] indexes." Selhub et al. found an inverse association between homocysteine levels and folate and B[6] when both plasma levels and nutrient intake were considered. However, only B[12] plasma levels were inversely associated with homocysteine. The researchers suggested that "the discordance between vitamin B[12] intake and circulating B[12] levels is the result of diminished vitamin B[12] absorption from foods associated with the age-related increase in incidence of atrophic gastritis." The study showed significant differences between the homocysteine levels of subjects in different deciles of plasma levels of the three vitamins. Mean plasma homocysteine concentration for subjects in the lowest decile of plasma folate was 15.6 mcmol/L, compared with 11 mcmol/L for those in the highest quintile. The mean homocysteine level for subjects in the lowest decile of PLP concentration was 14.3 mcmol/L; for subjects in the highest, it was 10.9 mcmol/L. Subjects in the lowest decile of vitamin B[12] levels had mean homocysteine levels of 15.4 mcmol/L, while those in the highest had levels of 10.9 mcmol/L. Selhub et al. found that low levels of each vitamin usually meant high plasma homocysteine concentrations and that individuals with moderate vitamin levels "had dramatically lower homocysteine concentrations." However, the authors noted that homocysteine levels "did not differ substantially between individuals with moderate and high vitamin concentrations." The study also showed an association between vitamin intake and homocysteine, although it was not as strong as the plasma level correlation. Mean homocysteine concentration for subjects in the lowest decile of folate intake ( <186 mcg/d) was 13.7 mcmol/L, compared with 10.4 mcmol/L for subjects in the highest decile. Subjects in the lowest decile of vitamin B[6] intake (< 1.33 mg/d) had a mean homocysteine concentration of 13.4 mcmol/L, while subjects in the highest decile had a mean of 10.1 mcmol/L. Vitamin B[12] intake did not appear to affect homocysteine levels, however. Selhub et al. concluded that "vitamin B[12] intake appears unrelated to mean homocysteine concentration, even though subjects in the fifth decile had significantly higher homocysteine concentrations than subjects in the highest decile." Based on the findings of their study, Selhub et al. "estimated that approximately two-thirds of the cases of elevated homocysteine concentrations in this cohort were associated with low or moderate levels of one or more of the three [B] vitamins." The authors concluded that "the normative criteria for plasma folate and vitamin B[12] concentrations may be too low." They pointed out that "there are no commonly accepted normative levels for PLP." "It may still be worth noting that homocysteine concentrations were elevated among individuals with folate intakes up to 280 mcg/d, which is higher than the current Recommended Dietary Allowances (RDAs) of 200 and 180 mcg/d for adult men and women, respectively, and vitamin B[6] intakes as high as 1.92 mg/d, which is less than the RDA of 2.0 mg/d for men but greater than the RDA of 1.6 mg/d for women," Selhub et al. said. "In the absence of intervention studies, we cannot conclude that lowering plasma homocysteine by increasing vitamin intake will reduce the risk of cardiovascular disease," Selhub et al. concluded. "However, a strong case can be made for prevention of the marginal or manifest vitamin deficiency states that may contribute substantially to this potentially important factor for vascular disease, the largest cause of mortality in elderly individuals." The researchers also found a "strong association" between high homocysteine levels and advanced age, even "after adjustment for plasma B vitamin levels." They reported that "the prevalence of high homocysteine concentration was 29.3% for the entire cohort and over 40% for individuals aged 80 years and older."
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