Serum Total Homocysteine Concentrations in the Third National Health and Nutrition Examination Survey (1991–1994): Population Reference Ranges and Contribution of Vitamin Status to High Serum Concentrations

  1. Jacob Selhub, PhD;
  2. Paul F. Jacques, ScD;
  3. Irwin H. Rosenberg, MD;
  4. Gail Rogers, BA;
  5. Barbara A. Bowman, PhD;
  6. Elaine W. Gunter, MT;
  7. Jacqueline D. Wright, MPH; and
  8. Clifford L. Johnson, MSPH
  1. From Tufts University, Boston, Massachusetts; and Centers for Disease Control and Prevention, Hyattsville, Maryland, and Atlanta, Georgia.

    Abstract

    Background: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease.

    Objective: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations.

    Design: Cross-sectional prevalence study.

    Setting: United States.

    Patients: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey.

    Measurements: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B12-replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B12 (<185 pmol/L) concentrations to a high homocysteine concentration.

    Results: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 µmol/L for male participants and 3.3 to 7.2 µmol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 µmol/L for men and 4.9 to 11.6 µmol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 µmol/L for male participants and at least 10.4 µmol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations.

    Conclusions: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.

    Article and Author Information

    • Acknowledgments: The authors thank Marie Nadeau and Gayle Petty for technical assistance and the NHANES III Surplus Sera Bank Steering Committee for support.

    • Grant Support: By the U.S. Department of Agriculture (agreement no. 58-1950-9-001) and the National Institutes of Health, National Heart, Lung, and Blood Institute (grant no. R01 HL52630). Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture.

    • Requests for Reprints: Jacob Selhub, PhD, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.

    • Current Author Addresses: Drs. Selhub, Jacques, and Rosenberg and Ms. Rogers: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.

    • Dr. Bowman: Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Highway, MS K261, Atlanta, GA 30341.

    • Ms. Gunter: Division of Environmental Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA 30341.

    • Ms. Wright and Mr. Johnson: Division of Health Examination Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention, 6525 Belcrest Road, Hyattsville, MD 20782.

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    1. Ann Intern Med September 7, 1999 vol. 131 no. 5 331-339
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