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Trends in Circulating Concentrations of Total Homocysteine among US Adolescents and Adults: Findings from the 1991–1994 and 1999–2004 National Health and Nutrition Examination Surveys

¹ National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA; ² National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD; ³ Office of Dietary Supplements, National Institutes of Health, Bethesda, MD; ⁴ Office of Regulatory Science, Food and Drug Administration, College Park, MD.

^aAddress correspondence to this author at: Centers for Disease Control and Prevention, 4770 Buford Hwy, MS F55, Atlanta, GA 30341. Fax 770-488-4139; e-mail cpfeiffer{at}cdc.gov.

Background: The National Health and Nutrition Examination Survey (NHANES) has monitored total homocysteine (tHcy) concentrations in a nationally-representative sample of the US population since 1991. Until recently, however, data could not be compared across survey periods because of changes in analytical methods and specimen matrices. Such an analysis of these data could supplement current knowledge regarding whether the US folic acid fortification program has modified national plasma tHcy concentrations.

Methods: We examined tHcy data in the prefortification NHANES III survey (phase II, 1991–1994) and in 3 postfortification survey periods (1999–2000, 2001–2002, and 2003–2004). We applied method adjustment equations to the survey data based on method comparison studies of separate samples. Persons with chronic kidney disease were excluded from the analyses.

Results: Mean plasma tHcy concentrations decreased by 8%, 9%, and 10% for adolescent, adult, and older men and by 6%, 3%, and 13% for women, respectively, from before to after fortification. Concentrations remained unchanged between the first and third postfortification survey periods. Prevalence estimates of increased plasma tHcy concentrations (>13 µmol/L) for older men and women decreased from prefortification (32% and 20%, respectively) to postfortification (14% and 5%, respectively) but remained unchanged thereafter (16% and 14%, respectively [males] and 5% and 9%, respectively [females]).

Conclusions: After adjusting for method changes, we quantified a prefortification to postfortification decrease in circulating tHcy concentrations of about 10% in a national sample of the US population. This change is similar to effects seen in intervention trials with folic acid and in smaller observational studies.

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