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

Background: The concentration of circulating total homocysteine is a sensit ive marker of inadequate folate and vitamin B-12 status. Elevated homocyste ine concentrations are associated with an increased risk for vascular disea se. Objective: To identify reference ranges for serum total homocysteine concen tration in U.S. residents and quantify the contribution of circulating vita min 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 t hird National Health and Nutrition Examination Survey. Measurements: Reference ranges (5th and 95th percentiles) for the total hom ocysteine concentration were defined among participants who were folate- an d vitamin B-12-replete and had normal creatinine concentrations. A high tot al homocysteine concentration was defined as one that exceeded the sex-spec ific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to dete rmine the contribution of low folate (<11 nmol/L) and vitamin B-12 (<185 pm ol/L) concentrations to a high homocysteine concentration. Results: Reference ranges for serum total homocysteine concentration increa sed with age; these ranges were 4.3 to 9.9 mu mol/L for male participants a nd 3.3 to 7.2 mu mol/L for female participants 12 to 19 years of age and fr om 5.9 to 15.3 mu mol/L for men and 4.9 to 11.6 mu mol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 mu mol/L for male participants and at least 10.4 mu mol/L for female participants. Approximately two thirds of the cases of high homocysteine co ncentrations were associated with low vitamin concentrations. Conclusions: Upper reference limits for the serum total homocysteine concen tration increased with age and were higher for male participants than for f emale participants at all ages. In most cases, high homocysteine concentrat ions were associated with low serum vitamin concentrations.