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Jacob Selhub, PhD; Paul F. Jacques, DSc; Peter W. F. Wilson, MD; David Rush, MD; Irwin H. Rosenberg, MD

JAMA. 1993;270(22):2693-2698.

Abstract
Objective.
—To describe the distribution of plasma homocysteine concentrations in an elderly population and to analyze the relationship between homocysteine level and intake of vitamins and serum levels of vitamins that serve as coenzymes in homocysteine metabolism.

Design.
—Cross-sectional analysis of homocysteine levels and vitamin blood levels and intake in elderly participants in the Framingham Study.

Setting.
—Population-based cohort in Framingham, Mass.

Participants.
—A total of 1160 adult survivors, aged 67 to 96 years, from the original Framingham Heart Study cohort.

Main Outcome Measures.
—Plasma homocysteine concentration correlated with plasma folate, vitamin B₁₂, pyridoxal-5'-phosphate (PLP), and oral intakes of these vitamins, and the contribution of these vitamins to the prevalence of elevated homocysteine in the population.

Results.
—Homocysteine levels were positively correlated with age after controlling for vitamin concentrations. After controlling for age, sex, and levels of other vitamins, homocysteine exhibited a strong inverse association with plasma folate. When subjects were grouped by deciles of plasma folate, mean homocysteine was significantly higher in the lowest two folate deciles (15.6 and 13.7 µmol/L, respectively) than in the highest decile (11.0 µmol/L). Homocysteine demonstrated weaker, inverse associations with plasma vitamin B₁₂ and PLP. Similar inverse associations were demonstrated between homocysteine and intakes of folate and vitamin B₆, but not vitamin B₁₂. Prevalence of high homocysteine (>14 µmol/L) was 29.3% in this cohort, and was greatest among subjects with low folate status. Inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine.

Conclusions.
—These results indicate a strong association between homocysteine concentration and folate, vitamin B₁₂, and vitamin B₆ status, as well as age. It is possible that a substantial majority of the cases of high homocysteine in this older population can be attributed to vitamin status.

(JAMA. 1993;270:2693-2698)

Author Affiliations
From the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (Drs Selhub, Jacques, Rush, and Rosenberg), and The Framingham (Mass) Heart Study (Dr Wilson).

Footnotes
Dr Jacques has received honoraria from Hoffman-La Roche Inc and Shaklee US, Inc, for speaking about his research on vitamins and aging.

Reprint requests to USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111 (Dr Selhub).

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