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Unpredictable intra-individual variations in serum homocysteine levels on folic acid supplementation


Objective: To determine if changes in serum homocysteine values during folic acid supplementation can identify objectively healthy subjects with subclinical folate deficiency.

Design: Blood drawn and processed in a regimented fashion from fasting subjects. Serum homocysteine values determined by gas chromatography-mass spectrometry twice before and on days 5 and 8 of daily folic acid supplementation.

Setting: Outpatient University Hospital Clinical Research Center, Denver, Colorado.

Subjects: Subjectively healthy adults with normal hematologic and biochemical screening tests.

Intervention: Folic acid 1 mg daily for eight consecutive days.

Results: Homocysteine values of the group fell significantly during folic acid supplementation. Values pre-supplementation were 7.8±1.8 and 7.4±2.4 μmol/L while values on days 5 and 8 of supplementation were 6.5±2.2 and 6.3±2.2 μmol/L. However, the homocysteine values of any given individual varied up to 60% (rises up to 7 μmol/L and falls of 5 μmol/L) during folic acid supplementation despite the controlled circumstances of blood handling, and an assay coefficient of variation of 8%.

Conclusions: Although group values of serum homocysteine fall during folic acid supplementation, intraindividual variation is so great that subjects with subclinical folate deficiency can not be identified using this study design. Furthermore, these data suggest than an individuals homocysteine values vary enough that single values must be interpreted with caution.

Sponsorship: Supported in part by The Marcellus S. Merrill Memorial Research Fund, the Muscular Dystrophy Association and the Clinical Research Center at the University of Colorado Health Sciences Center.

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Santhosh-Kumar, C., Deutsch, J., Ryder, J. et al. Unpredictable intra-individual variations in serum homocysteine levels on folic acid supplementation. Eur J Clin Nutr 51, 188–192 (1997).

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  • homocysteine
  • folic acid

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