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Supplemental Material can be found at:
Erythrocyte Folate and Its Response to Folic Acid Supplementation Is
Assay Dependent in Women1,2
Andrew J. Clifford,3 Elizabeth M. Noceti, Amy Block-Joy, Torin Block,* and Gladys Block†
Department of Nutrition, University of California, Davis, CA 95616; *Block Dietary Data Systems, 2634 LeConte Avenue, Berkeley, CA 94709; and †University of California, Berkeley School of Public Health,Berkeley, CA 94720
Optimizing folate status requires continued monitoring of erythrocyte (RBC) folate and folate intake.
The accuracy of RBC folate assays remains a concern. Therefore, we measured RBC folate with 4 different assays,examined the interassay correlations, and compared RBC folate with folate intake as measured by an abbreviatedfolate-targeted food/supplement screener. The screener had 21 questions (19 diet, 2 supplement) and measuredusual and customary intakes of dietary folate equivalents (DFEs). Our design was a 4 ⫻ 2 ⫻ 2 factorial, 4 assaysin pregnant and nonpregnant women before and after each group received a folic acid supplement (1814 nmol/d)for 30 – 60 d. Folate assays included L. casei
, chemiluminescence, GC-MS, and radioassay (RA). Baseline RBC
folate levels ranked low to high by assay (mean ⫾ SE) were as follows: 1155 ⫾ 44 nmol/L (L. casei
) ⬍ 1390 ⫾ 43nmol/L (chemiluminescence) ⬍ 1531 ⫾ 39 nmol/L (GC-MS) ⬍ 1727 ⫾ 55 nmol/L (RA) (P
⬍ 0.0001). Supplemen-tation raised RBC folate levels (mean ⫾ SE) as follows: 138 ⫾ 63 nmol/L (chemiluminescence) ⬍ 267 ⫾ 64 nmol/L(GC-MS) ⫽ 285 ⫾ 75 nmol/L (L. casei
) ⬍ 351 ⫾ 87 nmol/L (RA). Pregnant women had higher RBC folate thannonpregnant women using chemiluminescence and RA. Interassay correlations (r
) ranged from 0.4679 to 0.8261
⬍ 0.001). Correlations of RBC folate with folate intake ranged from 0.2676 to 0.4622 (P
⬍ 0.0004). We concludethat RBC folate levels are assay dependent, as is the definition of optimized status; there continues to be a needfor an accurate assay of RBC folate. RBC folate correlated with total folate intake using a folate-targetedfood/supplement screener.
J. Nutr. 135: 137–143, 2005.
KEY WORDS: RBC folate analytical method low-income women folate-targeted food screener
Adequate intake of folate is important to minimize the risk
Women who fall below 185% of the Federal Poverty Level
of neural tube defects (NTDs)4 (1,2), cardiovascular disease
(FPL ⱕ 1.85) are an important target population group for
(3), and some cancers (4). An adequate folate intake by
improving folate status. They may not fully appreciate the
women of child-bearing age is especially important because it
importance of folate (8). The correlation between folate in-
can raise RBC folate levels, and has been shown to reduce the
take and RBC folate concentrations has not been adequately
risk of NTDs by ⬃70% (5). The RBC folate level is rated a
studied in this population; we were prompted to measure their
good biomarker for nutritional status of this important nutri-
folate status using their RBC folate levels and to examine its
ent because of its correlation with liver folate, a significant
correlation with their folate intake. The intake was measured
tissue store (6). Cell accumulation of folate may be key to
with a new abbreviated folate-targeted food/supplement fre-
ameliorating NTD susceptibility with increased folate intake
quency screener that was developed for this study.
(7). Therefore, the strength of the relations between folate
Plasma and serum folate concentrations are commonly ac-
intake and biomarkers of folate status such as RBC folate is of
cepted to reflect recent dietary folate intake. Although eryth-
rocyte (RBC) folate is considered to be a better indicator ofbody stores and hence nutritional status (9), there is consid-
erable uncertainty about the reliability of the analytical meth-
The semiquantitative Block Dietary Folate Equivalents screener is available
with the online posting of this paper at www.nutrition.org.
ods for RBC folate (10,11). An interlaboratory comparison of
2 Supported by Grant/Cooperative Agreement (RO1 8928) from the Centers
popular analytical methods for folate revealed large differences
for Disease Control and Prevention (CDC) and National Institutes of Health DK
among laboratories analyzing a common set of serum and
45939. The contents are the sole responsibility of the authors and do not neces-sarily represent the official views of the CDC. The microbiologic assays were
whole-blood specimens (10). Results of the interlaboratory
conducted in the Clinical Nutrition Research Unit, at the University of California,
comparison prompted the recent development of promising
Davis, which is supported by Grant DK 35747 from NIH.
new hyphenated methods that included LC-MS and LC-
To whom correspondence should be addressed.
MS-MS for plasma and serum folate (12–15) and GC-MS for
4 Abbreviations used: DFE, dietary folate equivalents; FPL, federal poverty
RBC folate (16 –18). Like the microbiologic assay methods,
level; NF, natural food; NHANES, National Health and Nutrition Examination
the new hyphenated methods can be internally and externally
Survey; NTD, neural tube defect; PCV, packed cell volume; RA, radioassay; SFA,synthetic folic acid; WBC, white blood cell; WIC, Women, Infants, and Children.
0022-3166/05 $8.00 2005 American Society for Nutritional Sciences.
Manuscript received 4 August 2004. Initial review completed 8 September 2004. Revision accepted 1 October 2004.
CLIFFORD ET AL.
Here we present a feasibility study in which we compared a
vitamin tablets (with the same amount of folic acid/tablet, Longs
GC-MS assay to 3 other common assays for RBC folate. Also,
Drug Store Brand) to match the pregnant group. In addition to folic
we examined the correlation between RBC folate levels and
acid, each tablet also supplied vitamin B-12, 4 g (3 nmol); vitamin
folate intake as measured by an 18-item folate-targeted food/
B-6, 2.6 mg (11 mol); and iron, 27 mg (490 mol). All women were
supplement Dietary Folate Equivalents (DFE) screener devel-
instructed to take 1 prenatal tablet/d until their 2nd clinic visit. A$25 gift certificate to a local supermarket (for food only) was given to
oped for this study. The time required to complete the DFE
each woman at the end of the visit.
screener (6 –12 min) makes it an attractive alternative to
The 2nd clinic visit occurred 30 – 60 d after supplementation first
longer FFQs and for epidemiologic investigations focused on
began. Only 3 of 38 nonpregnant women were lactating at this visit.
folate status. If further research demonstrates the validity of
All women again completed the 1-page folate-targeted food/supple-
the DFE screener when it is self-administered, as opposed to
ment intake screener, and blood was drawn again from each woman
administered by clinic staff via interview, this instrument may
as described above. All women were queried about compliance with
prove useful as a classification tool for clinical settings.
supplement use, i.e., how often they took/missed taking the supple-ment. The overall compliance was determined from the 1-page folate-targeted food/supplement intake screener, interviews, and queries,.
Pregnant women were asked about their start date for receiving WIC
SUBJECTS AND METHODS
benefits. At the end of the visit, another $25 gift certificate to a localsupermarket (for food only) was given to each woman.
The University of California Davis Institutional Review Board
Folate-Targeted Semiquantitative Block DFE screener.
approved the study, and it was conducted according to Good Clinical
semiquantitative Block Dietary Folate Equivalents (DFE) screener
Practice guidelines and the Declaration of Helsinki, version 1989.
was designed to measure usual and customary intake of DFEs and was
Informed consent was discussed and obtained from each woman
optimized for use in low-income populations.1 The questions on the
before study participation. Women were excluded for any history of
screener were identified by examining the food records reported by
serious medical conditions or use of medications that would interfere
individuals ⱖ 17 y old in the National Health and Nutrition Exam-
with folate metabolism (dilantin, phenytoin, primidone, metformin,
ination Survey (NHANES) 1999 –2000. To develop the screener, all jn.nutrition.org
sulfasalazine, triamterene, or methotrexate). Intermittent users of a
4368 food items and beverages in that dataset were divided into 152
multivitamin supplement (1–2 times/wk) were included, whereas
food groups (questions). Each question represented a similar type of
prenatal-vitamin supplement users were excluded. All pregnant
food item (for example, pinto, red, black, or refried beans, separately,
women were enrolled at the time of their first prenatal visit and were
or as part of another food such as a "burrito," were coded together as
not taking any prenatal vitamins.
beans). The folate contributed as DFE by each food in the NHANES
Enrollment occurred from March through
dataset was calculated by multiplying, for each NHANES respondent,
September 2003. Pregnant women (n
⫽ 29), and nursing or non-
the mass of the food consumed by its folic acid concentration, and
pregnant low-income women (n
⫽ 39) who were at least 18 y old, and
then summing across all of the respondents. To calculate DFEs from
who were eligible or who had begun the Women, Infants, and
the NHANES data, the estimated synthetic folic acid (SFA) content
Children (WIC) program during the preceding 2 wk, were enrolled in
of each food was multiplied by 1.7, the bioavailability correction
this study. All study instruments (consent, 1-page folate-targeted food
factor provided by the Institute of Medicine (21). Food groups (ques-
screener) were translated into Spanish, back translated into English,
tions) were then ranked according to their contribution to total DFE
and administered by bilingual research staff.
The pregnant women were enrolled primarily from 6 local com-
intake; 19 questions, representing foods contributing the top 60% of
munity clinics in Sacramento, CA. The clinics were providers of the
U.S. DFE intake, were included in the Block DFE screener. The total
county Comprehensive Perinatal Services Program (CPSP) and
DFE consumed by each woman enrolled in our study was calculated
Medi-Cal programs. CPSP and Medi-Cal are statewide government
as the cumulative sum of DFEs contributed by each food group on the
programs that provide comprehensive prenatal care to low-income
screening questionnaire. Folate values for the questions on the DFE
women. To be eligible for these programs, a family's income must be
screener were identified by analysis of the USDA Nutrient Database
ⱕ185% of the Federal Poverty Level (FPL ⱕ 1.85), i.e., gross
for Standard Reference, Release 15 (August, 2002). Synthetic folic
monthly income of $1400-$5000 for a family unit of 1 to 8 persons,
acid values used for the computation of DFEs from vitamin supple-
respectively. We targeted pregnant women who were scheduled for
ments were identified by reference to label claims on commonly
their first obstetrics appointment because they were most likely to
available dietary supplements.
have not started using supplements. We also targeted women who
Blood drawing and analysis.
Blood was drawn from each woman
were newly recruited into the WIC program. WIC is a federal grant
into 4 separate 4-mL tubes that contained spray-dried K -EDTA and
program that provides vouchers for supplemental foods, nutrition
one SST tube for vitamin B-12. The tubes were inverted gently to
education, and prenatal counseling to low-income women. WIC food
prevent clotting. All EDTA tubes for whole-blood folate were
vouchers are special checks for purchasing health-promoting foods
promptly wrapped in aluminum foil (to exclude light) and immedi-
such as milk, juice, eggs, peanut butter, and so forth. The WIC
ately stored on dry ice. One EDTA tube and the SST tube were stored
authorized food list of July 2003 targeted foods rich in vitamins A and
at ⬃5°C during transit (⬃2 h) to the University of California Davis,
C, protein, and fiber, but not folate. Women enrolled in this federal
Sacramento Medical Center (UCDMC) Pathology Department Lab-
program have been shown to improve their nutritional status and
oratory where complete blood count, packed cell volume (PCV), and
pregnancy outcome (19,20). Community healthcare practitioners
serum vitamin B-12 (SimulTRAC Radioassay Kit, Vitamin
refer pregnant women to the WIC program to initiate nutrition
B-12[57Co]/Folate[125I] from ICN Diagnostics) measurements were
made. Also, one frozen tube of whole blood was analyzed for folate
The nonpregnant women were enrolled from a local Woman's
using chemiluminescence technology (Bayer Diagnostics ADVIA
Center. This Center is a nonprofit organization in Sacramento, CA
Centaur, Bayer Corporation Diagnostics Division) at the UCDMC
that serves low-income women and their children by providing them
Pathology Department Laboratory. The remaining 3 EDTA tubes
a daily meal, and referrals to local state agencies for food, housing,
were stored on dry ice during transit (⬃2 h) to the laboratories where
they were stored at ⫺70°C for RBC folate analysis using GC-MS
Women enrolled at the 1st clinic visit (baseline
(16 –18), Lactobacillus casei
(22), and radioassay (RA; SPNB Dual
values) were questioned about their general medical history, dietary
Count 125I, Diagnostic Products) methods. The L. casei
habits, length of time on WIC, and demographics. Each woman
assays were conducted at the UCD-Clinical Nutrition Research Unit
completed a 1-page folate-targeted food/supplement intake screener,
(UCD-CNRU). The Chemiluminescence, L. casei
, and RA assays
and blood was drawn as described below. Pregnant women began
were performed on whole-blood lysates (prepared with ascorbic acid).
taking a standard over-the-counter prenatal vitamin supplement (800
Folate concentrations of whole blood were divided by the PCV
g or 1814 nmol folic acid/tablet) as prescribed by their healthcare
(fraction) and expressed as nmol folate/L erythrocytes. A pool of
provider. All nonpregnant women received one bottle of 100 prenatal
freshly drawn blood was promptly divided into small aliquots and
RBC FOLATE LEVELS BY FOUR ASSAYS AND FOLATE INTAKE
stored ⫺70°C; aliquots from the pool were analyzed with each batch
women were in wk 18 ⫾ 2 of gestation and they were currently
of study samples to serve as a control monitor for day-to-day varia-
not receiving WIC benefits. The pregnant group had fewer
tion. Finally, all RBC folate assays were performed within 3 wk from
⫽ 0.0140) than the nonpregnant group, but the
the date the blood was drawn.
difference would likely disappear when the pregnant group was
Calculations and data analysis.
The data were checked for
normality, and descriptive statistics were calculated for each response
as old as the nonpregnant group.
variable. The data were analyzed by repeated-measures ANOVA.
As expected, the pregnant women had a lower PCV (P
The 3-way interaction (assay ⫻ supplementation ⫻ pregnancy status)
⬍ 0.0001), RBC count (P
⬍ 0.0001), blood hemoglobin (P
was not significant; thus, only main effects (Table 1) and the 2-way
⬍ 0.0001), and plasma vitamin B-12 levels (P
interactions, assay ⫻ supplement and assay ⫻ pregnancy status (Figs.
compared with nonpregnant women. Also, the pregnant
1, 2) are presented. Regression analysis of RBC folate levels by the 4
women had a higher white blood cell (WBC) count (P
assay methods and by folate intake were also calculated. All statistical
⫽ 0.0073) than the nonpregnant women. Folic acid supple-
analyses were conducted with StatView 5.0.1 software program (Aba-
mentation did not significantly affect PCV, WBC count, RBC
count, hemoglobin, or plasma vitamin B-12. The study popu-lation was normal.
RBC folate levels were dependent on assay method and
Of the 30 pregnant women, 24 completed the study as did
supplement (Table 1, Fig. 1
). The overall mean concentra- Downloaded from
29 of the 38 nonpregnant women. Those who did not com-
tions (main effects of assay method ranked low to high) were
plete the study were lost to follow-up for not keeping their
as follows: 1278 ⫾ 39 nmol/L by L. casei
⬍ 1450 ⫾ 32 nmol/L
scheduled clinic appointments, termination of pregnancy, or
by chemiluminescence ⬍ 1646 ⫾ 34 nmol/L by GC-MS
moving out of the area. Of the 30 pregnant women, 6 were
⬍ 1877 ⫾ 46 nmol/L by RA (P
⬍ 0.001). In addition, the
Caucasian, 8 were African American, 14 were Latina His-
magnitude of the increases in RBC folate (nmol/L) in response
panic, 2 were other (Native American); 17 were single and 13
to supplementation (ranked low to high) were as follows: 138 jn.nutrition.org
were married; 4 lived alone, 24 lived with others, and 2 were
⫾ 63 nmol/L by chemiluminescence ⬍ 267 ⫾ 64 nmol/L by
homeless. Of the 38 nonpregnant women, 8 were Caucasian,
GC-MS ⫽ 285 ⫾ 75 nmol/L by L. casei
⬍ 351 ⫾ 87 nmol/L
15 were African American, 13 were Latina Hispanic, and 2
by RA. RBC folate levels were dependent on assay method
were other (Asian); 26 were single and 12 were married; 6
and pregnancy status (Table 1, Fig. 2
) with pregnant women
lived alone, 28 lived with others, and 4 were homeless. The
having a higher RBC folate concentration only when analyzed
pregnant and nonpregnant women had similar education lev-
by chemiluminescence and RA.
els, 11 ⫾ 0.3 y (mean ⫾ SE), also similar to that of women
The Block DFE screener had 21 questions (19 diet, 2
participating in the NHANES III (11.3 ⫾ 0.06 y, mean ⫾ SD)
supplement) and measured usual and customary intake of
for which the data were collected between 1988 and 1994 (23).
DFEs. It included the 19 questions that account for 60% of
Other characteristics of the study participants are summa-
total folate intake as DFEs in the U.S. diet, and 2 questions
rized in Table 1
. The pregnant women were younger than the
concerning vitamin supplements. The women enrolled in our
nonpregnant women by approximately a decade. The pregnant
study completed the screener in 6 –12 min.
Characteristics, hematology, erythrocyte folate, and folate intake of women in the study
Number of children, n
Weeks pregnant, n
Plasma vitamin B-12, pmol/L
RBC folate, nmol/L
Food NF, g/d
Food SFA, g/d
Food NF ⫹ SFA, DFE/d
Supplement SFA, g/d
Total SFA, g/d
1 Values are means ⫾ SEM.
2 The estimated SFA content of each food was multiplied by 1.7, the bioavailability correction factor provided by the IOM (21).
CLIFFORD ET AL.
nmol folic acid for 30 – 60 d. Also, we measured folate intakewith a 1-page folate-targeted food/supplement frequencyscreener designed specifically for our study (Block DFEscreener), and determined whether folate intake was corre-lated with RBC folate.
Maternal RBC folate ⬎ 906 nmol/L, measured with Quan-
taphase IR Folate Radioassay (5), is considered optimal forprevention of folate-responsive neural tube defects (28).
When we used chemiluminescence, GC-MS, and RA meth-ods, only 5, 1, and 3 women, respectively, had RBC folate
⬍ 906 nmol/L. However, when we used L. casei
, 24 women
had RBC folate ⬍ 906 nmol/L. A goal of Healthy People 2010
is to increase RBC folate of nonpregnant women to 500nmol/L (29) and only the L. casei
assay identified women (n
⫽ 3) with RBC folate ⬍ 500 nmol/L in our study. Another
research group (30) used the L. casei
assay to determine RBCfolate status in a similar population of women residing in Downloaded from California postfortification and not taking any supplements.
Their respective levels for socioeconomically disadvantaged
Effect of the assay used and folate supplementation on
and advantaged women were 1172 ⫾ 342 nmol/L and 1387
RBC folate concentrations in women (n
⫽ 68) before (baseline) and after
⫾ 329 nmol/L, levels similar to ours. Our mean RBC folate
they consumed ⬃600 g/d (1360 nmol/d) SFA supplements for 30 – 60
levels and those of Caudill et al. (29) both far exceeded 362
d. Baseline levels and the increase upon supplementation were assay
nmol/L (9), a concentration that is widely considered an jn.nutrition.org
acceptable cutoff value.
Only 1 subject in our present study had an RBC folate level
The intake of natural food (NF) folate was the same for the
⬍ 362 nmol/L; the lowest individual RBC folate values were
pregnant and nonpregnant women (Table 1). Because the
333 nmol/L by L. casei
, 653 nmol/L by chemiluminescence,
pregnant group had a higher intake of SFA from fortified foods
806 nmol/L by RA, and 894 nmol/L by GC-MS. Of the
(breakfast cereals) than the nonpregnant group (P
women in our study, 65% had RBC folate ⬎ 906 nmol/L,
there was a trend (P
⫽ 0.0644) for them to have a higher
which compares well with the value of 78% reported by
intake of total food folate (NF ⫹ SFA). Differences in the food
another research group (30). Using the L. casei
(NF ⫹ SFA) intake did not differ between the baseline and
mean RBC folate concentration in the Framingham Offspring
supplementation periods (P
Cohort study after fortification was 1020 nmol/L (31), which
The overall compliance with taking the folic acid supple-
agreed with L. casei
-measured baseline values in Table 1. Our
ment was as follows: 64% of women reported taking the
30- to 60-d supplementation period was chosen to equal or
supplement every day; 21% reported taking it 4 – 6 d/wk; 7.5%
exceed the recommended 4-wk period of folic acid use before
reported taking it 1–3 d/wk; and 7.5% reported that they had
conception to improve folate status (21,32,33) and/or the
stopped taking it 30 – 60 d before giving birth. This level of
4-wk period used in another study (34).
compliance resulted in the supplement providing 596 ⫾ 56
Since 1998, women capable of becoming pregnant have
and 680 ⫾ 39 g/d (1351 ⫾ 127 and 1542 ⫾ 88 nmol/d) of
been advised to consume 907 nmol folic acid/d from fortified
SFA to pregnant and nonpregnant women (Table 1).
foods and supplements, in addition to dietary folate (21). The
The interassay correlation coefficients (r
) for RBC folate
ranged from 0.4679 (GC-MS vs. chemiluminescence) to
0.8261 (L. casei
vs. RA) (Fig. 3
). The r
-value for RA vs.
GC-MS was 0.7063, the 4th highest of 6.
Relations between RBC folate levels (using 4 analytical
methods) and folate intake as DFEs ranged from 0.2676 with
chemiluminescence to 0.4622 with RA (Fig. 4
). The r
for folate intake vs. GC-MS-assayed RBC folate was 0.4343 (P
⬍ 0.0001), the 3rd highest of 4. Although the r
significant, only 16% (a modest portion) of the variation in adependent variable was explained by the independent variablewhen r
Because RBC folate reflects intracellular and tissue folate
stores, it was chosen as the preferred indicator of folate nutri-tional status in establishing the new dietary reference intakes(21). At the same time, there are concerns over the accuracyof existing analytical methods for RBC folate (10,11) and onlya few groups (16,17,25–27) report within-laboratory compar-isons of several RBC folate assays. Therefore, we used 4 dif-
Effect of the assay used and pregnancy status on RBC
ferent methods to measure RBC folate levels in small popula-
folate concentrations in pregnant (n
⫽ 30) and nonpregnant (n
tions of pregnant and nonpregnant women (FPL ⱕ 1.85)
women. Pregnant women had higher RBC folate than nonpregnant
before and after each received a daily supplement of 1814
women when measured with chemiluminescence and RA.
RBC FOLATE LEVELS BY FOUR ASSAYS AND FOLATE INTAKE
RBC folate concentrations measuredin the women (n
⫽ 120) by chemilumi-nescence, L. casei
, GC-MS, and RA.
values ranged from 0.4679 forGC-MS vs. chemiluminescence (A
) to0.8261 for L. casei
vs. RA (F
). S , S ,
and S represent the standard errors of
the intercept, slope, and estimate, re-spectively.
fortified foods and supplements together provided the pregnant
creases in RBC folate (nmol/L) upon supplementation had a
and nonpregnant groups with 939 ⫾ 55 and 950 ⫾ 64 g/d
-value with chemiluminescence (P
⬍ 0.0171) than
(2129 ⫾ 125 and 2154 ⫾ 145 nmol/d) of SFA, respectively
with the RA assay (P
⬍ 0.0001), whereas the magnitude of the
). These quantities of SFA almost matched those
rise with the L. casei
and GC-MS assays did not differ (Table
recommended since 1998 (21).
1, Fig. 1). When the protein-binding assays were employed,
Participants in the present study consumed ⬃600 g/d
pregnant women had higher RBC folate levels than nonpreg-
(1360 nmol/d) supplement (SFA) and experienced (mean)
nant women (Table 1, Fig. 2), suggesting that these assays may
increases in RBC folate of 138 –351 nmol/L, depending on the
be hormone sensitive. Finally, RBC folate, as determined by L.
assay used. Had we doubled the duration of the supplementa-
was correlated with the concentration measured by GC-
tion period to match the ⬃120-d lifespan of RBCs, and/or
MS with an r
⫽ 0.7185, the 4th highest of 6 (Fig. 3, Panel B
increased the amount of the SFA supplement, we might have
Therefore, it seems that the L. casei
and GC-MS methods may
achieved a higher rise in RBC folate in response to supple-
offer hope for accurate RBC folate determinations that can
mentation. The rise in RBC folate remained linear with no
serve as guides to optimal folate status.
evidence of saturation as total folate intake increased irrespec-
The RBC folate as determined by RA was correlated with
tive of the assay method (Fig. 3); therefore, the plateau level
the concentration measured by GC-MS with an r
of RBC folate remains unknown. Further investigation is war-
(Fig. 3, Panel C
); this did not differ from the r
⫽ 0.7010 value
ranted to establish a reference range for RBC folate levels to
reported by another group (26) who compared a number of
prevent anemia and another to minimize the risk of more
commercially available protein-binding assay kits.
serious defects (35).
The Block DFE screener was effective in assessing dietary
The protein binding folate assays (chemiluminescence and
intake of folate because the DFEs measured by the screener
RA) are facile compared with the L. casei
and GC-MS assays,
were positively (and modestly) correlated with the results of all
which require several steps in sample preparation (16,17,36).
4 folate assay methods (r
⫽ 0.26 – 0.46) and the r
Among the protein-binding assays, the magnitude of the in-
⬍ 0.0001) for all measures (Fig. 4). Yen et al.
CLIFFORD ET AL.
total folate intake and RBC folate con-centration measured by GC-MS (A
), chemiluminescence (C
), andRA (D
) in all women (n
⫽ 120). The r
values ranged from 0.2676 with chemi-luminescence (C
) to 0.4622 with RA(D
). The abbreviated folate targetedfood/supplement screener was effec-tive in assessing folate intake. S , S ,
and S represent the standard errors of
the intercept, slope, and estimate, re-
(37) found a similarly modest correlation (r
⫽ 0.354, P
randomised controlled trial of periconceptional multivitamin supplementation.
0.06) when they compared folate intake measured by 7 d of
Final report. Arch. Gynecol. Obstet. 255: 131–139.
3. Boushey, C. J., Beresford, S. A., Omenn, G. S. & Motulsky, A. G.
"focused recalls" with plasma folate levels. They also found no
A quantitative assessment of plasma homocysteine as a risk factor for vascular
significant correlations between the Fred Hutchinson Cancer
disease. Probable benefits of increasing folic acid intakes [see comments]. J. Am.
Research Center FFQ and plasma folate (37). Comparisons
Med. Assoc. 274: 1049 –1057.
between correlations reported by Yen et al. (37) and those
4. Jennings, E.
Folic acid as a cancer-preventing agent. Med.
Hypotheses 45: 297–303.
presented here for the Block DFE screener should be inter-
5. Brown, J. E., Jacobs, D. R., Jr., Hartman, T. J., Barosso, G. M., Stang,
preted with caution, because the 2 dietary instruments have
J. S., Gross, M. D. & Zeuske, M. A.
Predictors of red cell folate level in
different purposes. The instrument of Yen et al. (37) was
women attempting pregnancy. J. Am. Med. Assoc. 277: 548 –552.
6. Wu, A., Chanarin, I., Slavin, G. & Levi, A. J.
Folate deficiency in
designed to measure short-term folate intake and to compare it
the alcoholic–its relationship to clinical and haematological abnormalities, liver
with plasma folate, whereas the Block DFE screener was de-
disease and folate stores. Br. J. Haematol. 29: 469 – 478.
signed to measure usual, long-term folate intake and to com-
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data at this time and setting cutoff values. Further comparisons
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among assay methods are warranted to identify the method
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subjects) reflects the fortified diets.
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SANOFI A global integrated healthcare leader, focused on patients' needs CORPORATE PRESENTATION 2013 CONTENTS OUR GROWTH PLATFORMS INNOVATION IN R&D OUR RESPONSIBILITY CORPORATE PRESENTATION 2013 CORPORATE PRESENTATION 2013 BMP Sunstone, Medley , Merial, Nepentes, Zentiv a, Kendricks, Oenobiol, Chattem,
Brain Advance Access published December 3, 2007 Brain (2007) Page 1 of 15 Neural correlates of tic severity and cognitivecontrol in children with Tourette syndrome C. L. Baym,1,4, B. A. Corbett,1,2,3, S. B. Wright1,5 and S. A. Bunge1,5,6 1Center for Mind and Brain, 2Department of Psychiatry and Behavioral Sciences, 3MIND Institute, University of Californiaat Davis, 4Department of Psychology, University of Illinois at Urbana-Champaign, 5Helen Wills Neuroscience Institute and6Department of Psychology, University of California at Berkeley, USA