Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States

Abstract

Background: Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer.

Objective: The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged > or =60 y.

Design: Surplus sera were analyzed with the use of data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002, a cross-sectional, nationally representative survey (n = 1121).

Results: UMFA was detected in 38% of the population, with a mean concentration of 4.4 +/- 0.6 nmol/L (median: 1.2+/- 0.2 nmol/L). The group with UMFA (UMFA+) had a significantly higher proportion of folic acid supplement users than did the group without UMFA (60% compared with 41%). UMFA+ men and women also had higher supplemental and total (food + supplements) folic acid intakes than did their counterparts without UMFA. Forty percent of the UMFA+ group was in the highest quartile of total folic acid intake, but total folic acid intake was only moderately related to UMFA concentrations (r(2) = 0.07). Serum folate concentrations were significantly higher in the UMFA+ group and were predictive of UMFA concentrations (r(2) = 0.15). Serum 5-methyltetrahydrofolate and vitamin B-12 concentrations were higher in the UMFA+ group, whereas there was no difference between the 2 UMFA groups in red blood cell folate, serum homocysteine, or methylmalonic acid concentrations.

Conclusions: Approximately 40% of older adults in the United States have UMFA that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted.

FIGURE 1

Mean (A) and percentage concentrations (B) of unmetabolized serum folic acid (UMFA) and serum 5-methyltetrahydrofolate (MTHF, 5-methylTHF) in US adults aged ≥60 y with detectable UMFA by 5-methylTHF quartile. Data are from the National Health and Nutrition Examination Survey (http://www.cdc.gov/nchs/nhanes/about_nhanes.htm). Reasons for exclusion were elevated concentrations of serum creatinine or alanine amino transferase, self-reported anemia, use of folate-blocking cancer therapy, missing or incomplete dietary data, or self-reported folic acid supplement use in the fasting period before blood draw. UMFA and 5-methylTHF in serum were measured by using affinity/HPLC with electrochemical (coulometric) detection. ^*Quartile 4 was significantly different from other quartiles, P ≤ 0.006 (Bonferroni-adjusted for multiple comparisons). Numbers above each bar represent the black portion of that bar.

FIGURE 2

The percentage of US adults (aged ≥60 y) without detectable concentrations of unmetabolized serum folic acid (UMFA−) and with detectable concentrations of UMFA (UMFA+) by quartiles of serum 5-methyltetrahydrofolate (5-Methyl THF) concentration (A), quartiles of total folic acid intake (B), red blood cell (RBC) folate concentration (C), and serum folate concentration (D). Data are from the National Health and Nutrition Examination Survey (http://www.cdc.gov/nchs/nhanes/about_nhanes.htm). Reasons for exclusion were elevated serum creatinine or alanine amino transferase concentration, self-reported anemia, use of folate-blocking cancer therapy, missing or incomplete dietary data, or self-reported folic acid supplement use in the fasting period before blood draw. UMFA and 5-methylTHF in serum were measured by using affinity/HPLC with electrochemical (coulometric) detection. Serum folate and RBC folate were assessed by radioassay. There was a significant P for trend across quartiles of 5-methylTHF (A), total folic acid intake (B), RBC folate (C), and serum folate (D). P ≤ 0.006 across quartiles for the UMFA+ group (Bonferroni-adjusted).