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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2685-2690, October 2004


Nutritional Epidemiology

Fortifying Food with Folic Acid Improves Folate Intake in German Infants, Children, and Adolescents1

Wolfgang Sichert-Hellert2 and Mathilde Kersting

Research Institute of Child Nutrition (FKE), University of Bonn, D-44225 Dortmund, Heinstueck 11, Germany

2To whom correspondence should be addressed. E-mail: sichert{at}fke-do.de.


    ABSTRACT
 TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Folate is a critical nutrient and programs to enhance folate intake have been established or are under consideration. We investigated to what extent consumers (C) profit from folic acid–fortified food and dietary supplements compared to nonconsumers (NC) of these products. A total of 6135 weighed records from 861 subjects (47% males, 53% females, age 6 mo to 18 y) from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study between 1990 and 2001 were evaluated. In 61% of the records, at least 1 item fortified with folic acid was reported, and in total 644 different items with a wide range of fortification levels were found. These were primarily commercial infant food (i.e., infant formula, weaning food) (44%), breakfast cereals (20%), and soft drinks (11%). Median dietary folate equivalents (DFEs) in NC increased from 65 and 62 µg/d in boys and girls at 6–12 mo of age, respectively, to 184 and 143 µg/d in adolescents 15–18 y of age. In C, DFEs increased from 109 and 100 µg/d in boys and girls at 6–12 mo of age, respectively, to 370 and 276 µg/d in adolescents 15–18 y of age. Irrespective of gender, NC had 50–70% the DFE intakes of C with a tendency for higher percentages in younger than in older children and adolescents. Folate intakes by male and female consumers of fortified food or supplements exceeded the upper levels in 1.7 and 1.2% of subjects, respectively. Currently, a fortification program for staple foods (e.g., grain products) does not seem necessary in Germany if children and adolescents consume food already fortified with folic acid.


KEY WORDS: • fortification • folate intake • infants • children • adolescents • dietary records

Folate coenzymes are involved in many processes including DNA synthesis, normal cell division, purine synthesis, and amino acid interconversions, especially in growing individuals (1). For women of child-bearing age, folate is also a critical nutrient because it can reduce the risk of neural tube defects (1). Furthermore, folic acid deficiency is considered the most common cause of hyperhomocysteinemia (2). Many studies consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease (2).

Dietary studies often report estimated folate intakes below references. There are nationwide fortification programs of staple foods established (UK, United States: grain products) or under consideration (Germany) to enhance folate intake. In Germany at present various food products are fortified with folic acid and subjects may consume additional folic acid with dietary supplements. Dietary evaluations are likely to be misleading if fortified food and dietary supplement consumption are not quantified. However, dietary surveys regarding folate generally deal with adults and little is known about the consumption of fortified food and supplements in children and adolescents. Weighed dietary records together with a detailed food and nutrient database of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD)3 Study allow an evaluation of folate intake in children and adolescents with respect to age, gender, and time trends.

We therefore examined folate intake in infants, children, and adolescents (age 6 mo to 18 y from the DONALD Study) and focused especially on the consumption patterns of consumers of folic acid–fortified food and dietary supplements vs. nonconsumers of these products. In addition we investigated time trends of folate intake in the period from 1990 to 2001 and estimated the risk of high intakes of folate.


    SUBJECTS AND METHODS
 TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
    Study design. The DONALD Study is a longitudinal (open cohort) study collecting detailed data on diet, metabolism, growth, and development from healthy subjects between infancy and adulthood, every 3 mo in y 1, twice in y 2, and once a year thereafter. The study is purely observational and noninvasive as approved by the International Scientific Committee of the Research Institute of Child Nutrition. The study started in the middle of 1985. Details were described elsewhere (3,4).

    Recording. Parents of the children or the older subjects themselves kept 3-d weighed dietary records, i.e., they weighed and recorded all foods and fluids consumed as well as leftovers using electronic food scales (±1 g). Product information from wrappers, cartons, etc., including any types of preparations (e.g., medicines, supplements) was kept and evaluated with the dietary records by our dieticians. Semiquantitative recording (e.g., numbers of cups, spoons) was allowed if weighing was not possible. However, in 75% of the completed records > 90% of the food items were weighed. Weekdays (68%) and weekend days (32%) were proportionally distributed in the sample.

    Food and nutrient database. Nutrient contents of staple foods were taken from standard nutrient tables (57) and that of commercial food products was taken from product labels or estimated by simulated recipes from the ingredients listed by the manufacturers. Nutrient contents of all recorded food items were entered in our nutrient database LEBTAB (containing about 5000 different items at present) (8).

Fortified food was identified by the product labels and the content of fortified nutrients according to the declaration by the manufacturer was stored in our database separately for each product. Food products are defined as fortified if folic acid was added. Infant formulae and weaning food was aggregated to commercial infant food. In food items fortified with folic acid only the folic acid content as declared by the manufacturer was used. With the exception of vitamins A and D no limits of fortification with vitamins are regulated in Germany for food products. But there is an expert agreement that fortification levels should not exceed 3 times the recommendations. Due to a commission directive (91/321/ECC; 14. May 1991) of the European communities a minimal folic acid content of 4 µg/100 kcal (418.4 kJ) in infant formulae is mandated and the folic acid content of weaning food for infants (98/36/ECC; 2. June 1998) must not exceed 50 µg/100 kcal (418.4 kJ).

Dietary supplements were defined according to the FDA as products in capsule, tablet, or liquid form that provide essential nutrients (9). Here only "over-the-counter" supplements containing folic acid were considered.

Subjects reporting a fortified food or a supplement containing folic acid at least once in the 3-d recording period were defined as consumers (C) and as nonconsumers (NC) if no product fortified with folic acid was reported. Folate intake was evaluated as the dietary folic equivalent (DFE) according to the U.S. dietary reference intakes (1). Folic acid from supplements or fortified food was converted with a factor of 1.7 to DFEs. To adjust for losses due to food preparation the folate content of raw food as ingredients in recipes was reduced by 35% (10). Age group categories and reference intakes for DFEs were taken from the German references (10) and tolerable upper intake levels from the U.S. references (1) (see Table 3). To estimate the risk from folate intake above the upper level (UL), percentages of consumers of fortified food or supplements exceeding the UL were calculated (Table 3). To validate dietary recording the ratio of reported energy intake and predicted basal metabolic rate was calculated (11).


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TABLE 3 DFE intakes by infants, children, and adolescents of the DONALD Study between 1990 and 2001 and consumers of fortified food with intakes above the UL

 
SAS procedures (Version 8.02) were used for data analysis. Energy and DFE intakes were calculated as individual means of the 3-d records. Results are means ± SD, or as means, medians, and percentiles. To analyze time trends and the influence of effects (y, y2, age, gender) on the outcome variables, a mixed linear model was used in which the means of the data and the covariance structure (children of the family, repeated measurements) were modeled (PROC MIXED). An exponential structure of covariance was specified to consider correlation of repeated measurements dependent on the absolute time interval of repeated measurements within the same subject. The level of significance was set at P < 0.05.


    RESULTS
 TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Of the DONALD Study, 6135 3-d weighed dietary records collected between 1990 and 2001 from 861 subjects (47% males, 53% females) between 6 mo and 18 y of age were evaluated (Table 1). In 61% of the records at least 1 item of food fortified with folic acid or a dietary supplement was reported. A total of 644 different items in 8 food groups (Table 2)—primarily commercial infant food (44%), breakfast cereals (20%), and soft drinks (11%)—with a wide range of fortification levels (Fig. 1) were found. The median value of folic acid was ≤100 µg/100 g for infant food, dairy products, soft drinks, and juices, ≤300 µg/100 g (or per capsule, respectively) for supplements (capsules), breakfast cereals, and sweets, and ≤400 µg/100 g for sweets, supplements, and instant beverages.


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TABLE 1 Numbers of records and subjects by age and gender and consumers of fortified food or dietary supplements containing folic acid

 

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TABLE 2 Products fortified with folic acid in different food groups reported in the DONALD Study sample 1990–2001

 


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FIGURE 1 Distribution of folic acid contents of fortified food items and supplements. Values are means, medians, and 10th, 25th, 75th, and 90th percentiles, n = 14–282 (see Table 2). *90th percentile for instant beverages = 1700 µg/100 g.

 
With the exception of the infants, median (and mean) intakes by the age subgroups by far did not attain the reference values for folate (Table 3). Mean intake expressed as a percentage of reference values was lower in girls (53–72%) than in boys (64–79%).

Median DFEs in NC increased with age from 65 and 62 µg/d in boys and girls 6–12 mo of age, respectively (Fig. 2), to 184 and 143 µg/d in adolescents 15–18 y of age. Median DFEs in C increased with age from 109 and 100 µg/d in boys and girls 6–12 mo of age, respectively, to 370 and 276 µg/d in adolescents 15–18 y of age. Irrespective of gender, NC had 50–70% the DFE intakes of C with a tendency for higher percentages in younger than in older children and adolescents. Except for infants 6 to 12 mo of age, NC (irrespective of gender) even at high levels of intake (90th percentile) missed the references. However, in 6/8 age subgroups of male C and 4/8 of female C, 75% or more of subjects exceeded the references. The contribution of supplements to total DFE intakes was small in younger children and increased with age but to no greater than 8% in the adolescents 10 to 18 y of age (data not shown).



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FIGURE 2 Distributions of DFE intakes including supplements of C vs. NC boys (upper panel) and girls (lower panel) in the DONALD Study and DFE reference values (10). Values are means, medians, and 10th, 25th, 75th, and 90th percentiles (see Fig. 1), n = 72–220 (see Table 1).

 
Expressed as a percentage of reference values, mean intakes increased significantly (P < 0.02) and linearly over time from 25% in 1990 to 28% in 2000 (about +0.3%/y) in the total sample (Fig. 3). Age and gender had no significant effects in the model (DFE expressed as a percentage of reference values = 24.22 + 0.31 y –0.15 y + 1.27 gender). Nonlinear models gave no better fit than the linear model.



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FIGURE 3 Distributions of DFE intakes including supplements expressed as percentages of DFE reference values (10) in infants, children, and adolescents of the DONALD Study between 1990 and 2001 (total sample). Values are means, medians, and 10th, 25th, 75th, and 90th percentiles (see Fig. 1), n = 104–607 (see Table 1).

 
In all C subjects, 1.7% of males and 1.2% of females exceeded the UL for folate intake. Of the C age subgroups the boys 1–3 y of age (2.3–2.4%) and the girls 7–9 y of age (3%) had the greatest percentages exceeding the UL (Table 3).


    DISCUSSION
 TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
The DONALD Study is a longitudinal, nonintervention study. Uniform methodology including 3-d dietary records and the nutrient database especially containing fortified food items and dietary supplements consumed by infants, children, and adolescents was used from the start. Therefore micronutrient intake, especially in connection with fortified food, can be evaluated in a wide age range between infancy and adolescence. Furthermore, time trends of nutrient intakes can be investigated.

The main findings from the present analysis of the DONALD Study can be summarized: (a) We found a great variety of fortified products and dosages of folic acid in fortified food or supplements. (b) There was a marked difference in folate intake between C and NC with very low intakes in NC. (c) Dietary supplements contributed only marginally to folate intake. (d) Folate intake from fortified food or supplements increased only slightly in the past 10 y. (e) In some subgroups we found up to 3% of subjects with intakes above the UL, especially in connection with the use of supplements.

Labeled folic acid contents of food given by the manufacturers were used in our assessment. According to a recent investigation in the United States, these data may not be valid. In 28 cereals analyzed, values for folate ranged from 98 to 320% of label values and in 14/28 cereals analyzed values exceeded label declarations by >150%. The authors concluded that daily consumption of breakfast cereals may contribute to excessive intakes of folate (12). If this holds true for Germany, differences in folate intake between C and NC would be even more pronounced than reported here with higher frequencies of intakes above the UL.

    Folate intake. There are many data in the literature concerning folate intake and status in adults mainly due to the discussion of the prevention of neural tube defects and vascular disease [overview given in (1,13,14)]. But only a few recent studies report folate intakes (measured as total folate and not as DFEs) in adolescents and almost no data are available for infants or children.

In 3-d dietary records of British schoolchildren (1990, age 11–12 y) mean folate intakes of 166 and 153 µg/d in males and females, respectively, were reported (15). Another British study conducted in 1990/1991 with a dietary history method found folate intakes of 129 and 114 µg/d in males and females, respectively, 12 y of age and 156 and 121 µg/d in males and females, respectively, 15 y of age (16). Another British study with 7-d weighed food records reported mean folate intakes of 167 and 142 µg/d in males and females 12–13 y of age, respectively (17).

In a meta-analysis of food records and 24-h recalls between 1990 and 1998 in Spain mean folate intake of 203 and 194 µg/d in males and females 4–12 y of age, respectively, and of 250 and 211 µg/d in males and females 13–18 y of age were evaluated (18). A Swedish study conducted in 1993/1994 with adolescents 15 y of age and 7-d dietary records found mean intakes of folate of 236–243 and 183–200 µg/d in males and females, respectively, and about 60% reported daily consumption of vitamin supplements (19). Danish adolescents (age 15–18 y) in a study conducted in 1995 had mean folate intakes of 295 and 265 µg/d in males and females, respectively, measured with 7-d dietary records and in The Netherlands a 2-d dietary record measured 274 and 227 µg/d in males and females 16–18 y of age in 1992 [according to (13)].

    Food fortification. Although we found about 7% of fortified products as supplements (Table 2) in German children and adolescents the consumption of supplements plays only a minor role in folate intake. Similar results were reported in a recent evaluation of consumption patterns of vitamin supplements (20).

In total we found 644 different items, predominantly commercial infant food and ready-to-eat breakfast cereals, fortified with folic acid with a wide range of dosages. Therefore, identifying these products correctly and measuring the amount consumed are critical for assessing folate intake. In our study we saw a marked difference in intake between C and NC: NC had only about 50–70% of DFE intakes in comparison to C. These findings are supported by reports from other countries. In a study on British adolescents 12 y of age regular consumers of breakfast cereals had about 27–34% higher mean folate intakes than nonregular consumers (16). In British adolescents 12–13 y of age more frequent consumers of fortified breakfast cereals had about 47% higher folate intakes than less frequent consumers (17) and in another study on French children and adolescents 2–18 y of age frequent consumers had about 14% higher folate intakes (21). In an intervention study, adults achieved increases in folate intake using fortified foods more easily than by merely consuming folate-rich nonfortified foods (22). In France, consumers of fortified breakfast cereals 2 to 18 y of age had better blood folate biomarkers than nonconsumers (21). A study on U.S. adults showed that the introduction of folic acid fortification significantly improved folate intake (23) and folate nutritional status (24). In a U.S. study in adult women, recorded folate intake from nonfortified food was 288 µg/d; with fortification folate intake increased up to 550 µg/d and the authors concluded that routine supplementation was not necessary to achieve folate intakes of 400 µg/d in the majority of the participants (25). On the contrary, excluding food fortified with folic acid significantly reduced folate status (26).

    Risk and UL. One concern with any fortification program is that it will increase the proportion of the population with potentially unsafe folic acid intakes. For infants, children, and adolescents the UL was adjusted on the basis of relative body weight using the UL for adults (see Table 3). To prevent high levels of folate intake, the only source of intake for infants should be food (1). In the current study, 1.3% of the participants exceeded the UL for folate from fortified food alone and 1.4% exceeded the UL if supplements were included. Depending on the survey, estimated folate intakes suggested that ~15–25% of U.S. children 1 to 8 y of age had intakes above the newly established UL (27). However, in the United States folic acid fortification of cereal-grain products has been mandatory since 1998. Fortification in Germany at the present level seems to minimally affect the proportion of children and adolescents exceeding the UL.

However, there are no data regarding the effects of long-term exposure of, e.g., young children to several times their daily recommended folate intake (28). Kelly et al. (29) point to the appearance of unmetabolized folic acid in serum in response to the consumption of fortified food. Oral doses of folic acid at the threshold of 200 µg/meal were shown to bypass the normal absorption mechanisms, resulting in unmetabolized folic acid appearing in the serum, presenting a problem in the early diagnosis of pernicious anemia.

The American Academy of Pediatrics sees no evidence for routine supplementation of healthy growing children who consume a varied diet [(30), p. 127]. Evaluations of the DONALD Study demonstrate that with a few exceptions the average vitamin intake of children in Germany already reaches the recommendations by diet alone, including fortification (31). One of these exceptions is folate. At present mandatory fortification of basic foods (e.g., flour) with folic acid is being discussed in Germany. But current fortification of products preferred by children and adolescents may be sufficient to reach intake levels near the references. Unfortunately there is a lack of institutional or preventive strategy of the food industry to fortify food preferred by children and adolescents in Germany with folic acid. A former evaluation found large variations in the numbers and amounts of fortified nutrients of food items marketed in Germany. In a considerable number of fortified products, especially fortified beverages, amounts of single fortified nutrients reached >100% (maximum 660%) of daily reference doses in an average portion, while other fortified nutrients made up no more than about 30% of the same product. In about 50% of the fortified products at least 6 nutrients were added simultaneously (32). Another previous evaluation of the DONALD Study, where a wide use of multivitamin foods was found, points to overfortification without a sound nutritional policy in Germany (33). However, at present there is no agreement within the scientific community as to whether to fortify food or to educate people or to use supplements. But there is widespread agreement that priority should be given to a balanced food choice combined with nutrition education, especially in children and adolescents.

In a fortification program, inadequate intakes among "low" consumers (the primary target population subgroup) may not be remedied simply by increasing the level of a nutrient fortified in the general food supply. However, fortification always increases intakes in those consumers whose intakes may already be high. Therefore the effectiveness of a fortification program for low consumers and the safety of high consumers are always competing concerns (28). The findings of this evaluation of the DONALD Study support the call to explore ways to improve folate intakes in targeted subgroups, while not putting other population groups at the risk of excessive intakes (27). At present, a fortification program for staple foods (e.g., grain products) does not seem necessary in Germany if children and adolescents consume food already fortified with folic acid.


    ACKNOWLEDGMENTS
 
We are very grateful to Christa Chahda and Ruth Schäfer for collecting and coding the dietary records in the DONALD Study and to Diane Pavlitzek for proofreading.


    FOOTNOTES
 
1 Funded by the Federal Institute for Risk Assessment, Germany. The DONALD Study is supported by the Ministry of Education, Science, and Research North Rhine-Westphalia, Germany, and the German Federal Ministry of Consumer Protection, Food, and Agriculture. Back

3 Abbreviations used: C, consumers of folic acid fortified food; DFE, dietary folate equivalent; DONALD, Dortmund Nutritional and Anthropometric Longitudinally Designed; LEBTAB, food and nutrient data base in DONALD; NC, nonconsumers of folic acid fortified food; UL, tolerable upper intake level; Back

Manuscript received 17 March 2004. Initial review completed 13 April 2004. Revision accepted 25 June 2004.


    LITERATURE CITED
 TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

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