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Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification?

Sweeney MR, Staines A, Daly L, Traynor A, Daly S, Bailey SW, Alverson PB, Ayling JE, Scott JM - BMC Public Health (2009)

Bottom Line: However due to safety considerations this decision is now on hold.Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.This has implications for those with responsibility for drafting legislating in this area.

View Article: PubMed Central - HTML - PubMed

Affiliation: UCD School of Public Health and Population Science, University College Dublin, and Coombe Women's and Infant's Hospital, Dublin, Ireland. maryrose.sweeney@dcu.ie

ABSTRACT

Background: Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI 1 recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification.

Methods: Study 1.

Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n=50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2.

Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n=20), and from their infant's umbilical-cords (n=20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.

Results: Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%-99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%-96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%-99.9%), comprising 2.25% of total plasma folate,

Conclusion: While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.

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Related in: MedlinePlus

Individual level data for the blood donor's (unfasted group) showing unmetabolised folic acid nM/L plotted against plasma total folate nM/l. Outliers are included in this figure. The box plots on the x and y axis respectively indicate the univariate distribution of plasma folate and plasma unmetabolised folic acid. In each box plot the line across the box indicates the median point, the whiskers indicate the range of the data, and the 25 and 75% centiles are indicated by the box itself. the first. At this lower voltage specifically the folic acid peak decreases by about 95%, thus permitting not only its definitive identification, but also facilitation of placement of baselines for quantification of peak heights using an Empower (Waters) data system. The limit of detection (S/N = 3) was 0.15 nM in plasma, and the intra assay CV = 3%.
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Figure 2: Individual level data for the blood donor's (unfasted group) showing unmetabolised folic acid nM/L plotted against plasma total folate nM/l. Outliers are included in this figure. The box plots on the x and y axis respectively indicate the univariate distribution of plasma folate and plasma unmetabolised folic acid. In each box plot the line across the box indicates the median point, the whiskers indicate the range of the data, and the 25 and 75% centiles are indicated by the box itself. the first. At this lower voltage specifically the folic acid peak decreases by about 95%, thus permitting not only its definitive identification, but also facilitation of placement of baselines for quantification of peak heights using an Empower (Waters) data system. The limit of detection (S/N = 3) was 0.15 nM in plasma, and the intra assay CV = 3%.

Mentions: Unmetabolised folic acid was present in 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%) (Table 2 and 3, & Figure 2). After removing 2 samples, which were outliers, with very high unmetabolised folic acid levels relative to the others sampled, we examined inter-relationships between plasma unmetabolised folic acid, plasma folate, red cell folate, habitual folic acid and recent folic acid intakes using regression techniques. Our results show that habitual folic acid intakes are significantly correlated with plasma folate levels (p = 0.009 r2 = 0.115). In addition we find that plasma folate is related to plasma unmetabolised folic acid concentrations (p = 0.011, r2 = 0.110).


Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification?

Sweeney MR, Staines A, Daly L, Traynor A, Daly S, Bailey SW, Alverson PB, Ayling JE, Scott JM - BMC Public Health (2009)

Individual level data for the blood donor's (unfasted group) showing unmetabolised folic acid nM/L plotted against plasma total folate nM/l. Outliers are included in this figure. The box plots on the x and y axis respectively indicate the univariate distribution of plasma folate and plasma unmetabolised folic acid. In each box plot the line across the box indicates the median point, the whiskers indicate the range of the data, and the 25 and 75% centiles are indicated by the box itself. the first. At this lower voltage specifically the folic acid peak decreases by about 95%, thus permitting not only its definitive identification, but also facilitation of placement of baselines for quantification of peak heights using an Empower (Waters) data system. The limit of detection (S/N = 3) was 0.15 nM in plasma, and the intra assay CV = 3%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2734856&req=5

Figure 2: Individual level data for the blood donor's (unfasted group) showing unmetabolised folic acid nM/L plotted against plasma total folate nM/l. Outliers are included in this figure. The box plots on the x and y axis respectively indicate the univariate distribution of plasma folate and plasma unmetabolised folic acid. In each box plot the line across the box indicates the median point, the whiskers indicate the range of the data, and the 25 and 75% centiles are indicated by the box itself. the first. At this lower voltage specifically the folic acid peak decreases by about 95%, thus permitting not only its definitive identification, but also facilitation of placement of baselines for quantification of peak heights using an Empower (Waters) data system. The limit of detection (S/N = 3) was 0.15 nM in plasma, and the intra assay CV = 3%.
Mentions: Unmetabolised folic acid was present in 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%) (Table 2 and 3, & Figure 2). After removing 2 samples, which were outliers, with very high unmetabolised folic acid levels relative to the others sampled, we examined inter-relationships between plasma unmetabolised folic acid, plasma folate, red cell folate, habitual folic acid and recent folic acid intakes using regression techniques. Our results show that habitual folic acid intakes are significantly correlated with plasma folate levels (p = 0.009 r2 = 0.115). In addition we find that plasma folate is related to plasma unmetabolised folic acid concentrations (p = 0.011, r2 = 0.110).

Bottom Line: However due to safety considerations this decision is now on hold.Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.This has implications for those with responsibility for drafting legislating in this area.

View Article: PubMed Central - HTML - PubMed

Affiliation: UCD School of Public Health and Population Science, University College Dublin, and Coombe Women's and Infant's Hospital, Dublin, Ireland. maryrose.sweeney@dcu.ie

ABSTRACT

Background: Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI 1 recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification.

Methods: Study 1.

Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n=50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2.

Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n=20), and from their infant's umbilical-cords (n=20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.

Results: Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%-99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%-96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%-99.9%), comprising 2.25% of total plasma folate,

Conclusion: While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.

Show MeSH
Related in: MedlinePlus