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Influence of Vitamin-optimized Plasma Homocysteine Cutoff Values on the Prevalence of Hyperhomocysteinemia in Healthy Adults

Departments of
¹ Pathology and Laboratory Medicine and
² Internal Medicine, University Hospital Groningen, NL-9700 RB Groningen, The Netherlands.

^aAddress correspondence to this author at: Department of Pathology and Laboratory Medicine, University Hospital Groningen, CMC-V, Room Y1.165, PO Box 30.001, NL-9700 RB Groningen, The Netherlands. Fax 31-50-3612290; e-mail m.r.fokkema{at}path.azg.nl.

Background: Hyperhomocysteinemia is a cardiovascular disease (CVD) risk factor. We determined plasma homocysteine (Hcy) reference values at optimized vitamin status and investigated their influence on the prevalence of hyperhomocysteinemia in healthy adults. Results were compared with those obtained using European Concerted Action Project (ECAP) cutoff values.

Methods: Healthy adults (n = 101) received folic acid (5 mg/day) and vitamin B₁₂ (1 mg/day) for 2 weeks and the same dosages of folic acid and vitamin B₁₂ plus vitamin B₆ (1 mg · kg^-1 · day^-1) during the following 2 weeks. Hcy concentrations, both fasting and 6-h post-methionine load, were determined at baseline and after 4 weeks.

Results: Baseline (4 weeks) fasting and 6-h postload Hcy reference values were 4.7–14.6 (4.1–9.3) and 18.8–49.7 (12.9–35.1) µmol/L, respectively. Mean fasting and 6-h postload Hcy decreased after 4 weeks of vitamin supplementation by 3.5 µmol/L (33.5%) and 8.5 µmol/L (26.3%), respectively. The percentages of subjects exhibiting significant decreases in fasting Hcy following vitamin supplementation were 88% (all subjects), 92% (non-vitamin users), and 72% (vitamin users). The prevalences of hyperhomocysteinemia with use of ECAP cutoff values were 29% for all groups, 29% for men, 27% for premenopausal women, and 53% for postmenopausal women. With vitamin-optimized cutoff values, prevalences were 58%, 58%, 76%, and 89%, respectively. Use of vitamin-optimized cutoff values increased the diagnostic value of fasting Hcy and decreased that of a 6-h postload Hcy compared with use of ECAP cutoff values.

Conclusions: Use of vitamin-optimized cutoff values gives rise to high hyperhomocysteinemia pretest probabilities in the general population and, therefore, precludes any meaningful role for Hcy testing. Future demonstration of a beneficial effect of decreasing Hcy on CVD risk would justify use of vitamin-optimized cutoff values for assessment of CVD risk.

The following articles in journals at HighWire Press have cited this article:

				H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF]