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Letters to the Editor |
Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Mailstop K26, Atlanta, GA 30341, E-mail: esf2{at}cdc.gov
Dear Sir:
Baggott questions why low mean serum folate concentrations are associated with low mean serum homocysteine concentrations in Mexican American women sampled in the third National Health and Nutrition Examination Survey (NHANES III), because lower serum folate concentrations are usually associated with increased circulating homocysteine concentrations (1, 2). Our response includes epidemiologic and statistical perspectives on the biology of homocysteine and its relation to folate and vitamin B-12 status.
Baggott's observation illustrates the difficulty in inferring associations between variables from group-level data, a phenomenon referred to as ecologic fallacy (3). First, several factors are determinants of circulating homocysteine concentrations (4). Folate status is one factor; others include vitamin B-12 status, vitamin B-6 status, genetic disorders, and metabolic disorders such as chronic renal disease. The relative importance of these factors varies significantly among population groups as well as individuals. Thus, it is highly unlikely that differences could be explained by measures of folate status alone.
For serum homocysteine, Jacques et al reported a significant age-sex interaction and also differences by race or ethnicity in females but not males (2). Because we presented folate concentration results for phase 1 and Jacques et al presented total plasma homocysteine concentration results for phase 2 of NHANES III, we thought it would be useful to present folate concentration data for phase 2 for participants aged 
17 y (Table 1
). In NHANES III, median serum vitamin B-12 concentrations in phase 2 were lowest for non-Hispanic whites, intermediate for Mexican Americans, and highest for non-Hispanic blacks (5). Also, although mean serum and red blood cell folate concentrations generally increased after the age of 20 y in adults, median serum vitamin B-12 concentrations were higher for the youngest age group (aged 4–5 y) and the serum vitamin B-12 distribution was highly skewed, especially among Mexican Americans (5). Because vitamin B-12 and several other factors affect circulating homocysteine concentrations, it is not surprising that the simple, expected relation between folate and homocysteine was not observed in all groups.
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). Although some variation was present, all correlation coefficients were negative and the size of the correlation coefficients was generally similar. Thus, based on individual-level data, folate and vitamin B-12 concentrations were inversely related to total plasma homocysteine concentrations in all 6 groups.
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14 nmol/L may also explain Baggott's observation. If serum folate concentrations are already sufficient to lower homocysteine nearly to its nadir (and 7.9 compared with 7.4 nmol/L is unlikely to be a biologically significant difference), then the observation can be explained physiologically and parsimoniously.
REFERENCES
This article has been cited by other articles:
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  A. Must, P. F. Jacques, G. Rogers, I. H. Rosenberg, and J. Selhub Serum Total Homocysteine Concentrations in Children and Adolescents: Results from the Third National Health and Nutrition Examination Survey (NHANES III) J. Nutr., August 1, 2003; 133(8): 2643 - 2649. [Abstract] [Full Text] [PDF]
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