Introduction
Many studies show the health benefits of natural food folate (reduced methyl and formyl folates) and of folic acid from supplements and fortified foods (pteroylmonoglutamic acid). An adequate folate intake during the periconception period helps to prevent congenital malformations (including neural tube defects) and pregnancy complications [
1‐
3]. Low levels of folate can lead to homocysteine accumulation [
4] and impairment of DNA repair mechanisms [
5]. Epidemiological studies have suggested an association between high intake of folate and lower risk of cardiovascular disease, some cancers and age-related cognitive decline [
6‐
8]. However, the results of randomized controlled trials with folic acid did not support these findings in general [
9‐
14].
In addition to the risks of a low folate intake, potential risks of high intakes of folic acid have moved into the focus of the discussion over the past years. New scientific evidence has emerged suggesting a possible link between high intake of folic acid and various types of cancer, particularly colorectal cancer [
15‐
19]. Animal studies suggest that high folic acid intakes may have a dual effect: inhibiting the formation of neoplastic lesions in normal tissues and accelerating the malignant transformation of existing neoplasms [
20]. Other postulated adverse effects of high folic acid intake include acceleration of cognitive decline during ageing (in combination with a vitamin B-12 deficiency) [
21‐
23] and a reduction of the efficacy of antifolate drugs (used to treat cancer, epilepsy, rheumatic disease, psoriasis or malaria) [
24‐
26]. A high intake of folic acid may result from supplements and/or from fortified foods.
To prevent neural tube defects, a mandatory fortification of flour with folic acid is practiced in over 50 countries, but has not been introduced in any European country [
27]. In Germany, folic acid supplements are recommended during the periconceptional period [
28] and folic acid is added to many foods, such as breakfast cereals, multivitamin juices (mixed fruit juice fortified with several vitamins) and other beverages, margarines, dairy products, sweets, convenience foods, and table salt. The amount of added folic acid varies widely between different products, brands, and storage time. Information on the consumption of fortified foods collected in nutrition surveys contains a degree of uncertainty, and actual folic acid contents in foods may differ from those presented in nutrient databases or on product labels.
Therefore, the objectives of this study were as follows:
1.
to investigate the potential intake of dietary folate and folic acid of the German population based on the data of the German National Nutrition Survey II (NVS II) under consideration of different food fortification levels (no fortification with folic acid, low and high fortification level) and
2.
to evaluate the percentage of the population meeting the recommended intake or exceeding the tolerable upper intake level (UL) of different food fortification levels.
The calculations were executed for the total population, for women of childbearing age (because of a more serious impact of a low intake) and for supplement users (because of a potentially higher risk of a too high intake of folic acid).
Discussion
The present study describes several scenarios of folic acid fortification based on the representative data of the NVS II. The results show a low intake of natural food folate (scenario 1) in Germany with respect to the recommended 300-µg DFE per day [
28]. Without fortification, only 12.4 % (men) and 5.9 % (women) met this recommendation. A low folate intake has also been shown in previous studies in Germany [
41,
42] and for most countries in Europe [
43‐
45]. In Germany, major food sources for DFE are bread, vegetables, fruits, beverages as well as milk and dairy products [
46].
In 2013, the nutrition societies of Germany, Austria and Switzerland lowered the recommendation for folate from 400 to 300 µg DFE per day for adolescents and adults (nonpregnant women) [
28], now corresponding with the recommendation in the Scandinavian countries [
35]. Even lower amounts (200 µg/d) are recommended in Great Britain and by the European Commission [
36,
37], while in the USA the recommendation of the Institute of Medicine lies highest with 400 µg/d [
38]. The current German recommendation of 300-µg DFE per day includes a safety margin and not meeting this intake level can therefore not be judged as an inadequate folate intake [
28]. Taking this into account, different cut-off points based on different international recommendations are presented in this work. With respect to the lowest recommended intake of 200 µg/d (Great Britain and European Union) [
36,
37], the folate intake in Germany is less critical.
The intake of DFE among German adolescents and adults can be increased by the consumption of fortified foods or of large amounts of one fortified food item (e.g. multivitamin juices).
Different fortification scenarios (partly in combination with supplements) reveal a wide range of potential folic acid intake levels. The consumption of foods with a low fortification level does not lead to a substantial increase of the proportion of the population meeting the recommendation of the German-speaking countries. However, with a high fortification level, almost 70 % of the men and about 55 % of the women met the recommended 300 µg/d, whereas about 80 % met the level of 200 µg/d. But this also results in a higher proportion of persons exceeding the UL (1.9 % of the men and 0.8 % of the women). The UL is an estimation of the maximum level of chronic daily intake, which carries no considerable risk of adverse health effects, whereas occasionally exceeding the UL does not seem to be a severe health threat [
39].
The Scientific Committee on Food and the EFSA have set the UL for folic acid at 1,000 µg/d [
39] because higher doses of folic acid could delay the diagnosis of vitamin B-12 deficiency by masking the anaemia of vitamin B-12 deficiency, which can lead to irreversible neurological damage. With respect to a potential tumour progression, the current UL of 1,000-µg folic acid per day may be too high, but the EFSA Scientific Cooperation Working Group concluded that there is no sufficient data to allow a full quantitative risk assessment of folic acid and cancer [
27]. The possible harm of high folic acid intake depends most likely on additional factors such as age, individual supply status (e.g. vitamin B-12 status) and genetic polymorphisms [
15,
21,
47‐
50]. With a lower UL, the percentage of persons exceeding the UL would be higher than presented in this study.
Particularly for women of childbearing age, a deficient intake can have serious consequences (neural tube defects or other prenatal malformations) but the intake of natural food folate within this group was even lower than within the total group of women. Without fortification with folic acid, only 4.8 % of the women between 15 and 45 years met the recommended daily intake of 300 µg DFE (scenario 1a). With a high fortification level of foods, 58.6 % met this recommendation (scenario 4). In Germany, it is recommended that women of childbearing age take an additional amount of 400 µg folic acid via supplements [
28]. However, the proportion of woman meeting this recommendation was very low. This underlines that efforts have to be continued for more education about a diet rich in folate (such as green vegetables, fruits and wholegrain-products), fortified foods and a well-timed use of folic acid supplements as important prevention measures to reduce the risk of a pregnancy affected by neural tube defects.
The proportion of adults with a folic acid intake above the UL increases if folic acid supplements are taken (about 5 % among supplement users). The proportion of persons with folic acid supplement use is higher in the upper than in the lower age groups. A high intake of folic acid within the upper age groups may lead to critical situations due to a higher probability of occurrence of vitamin B-12 deficiency and/or undiagnosed preneoplastic lesions whose progression might be promoted by folic acid. Taking a closer look at the supplement users reveals a higher intake of natural food folate compared to the total population. These results suggest that particularly health-conscious people take folic acid supplements, who may not really need them, as well as elderly persons, who may have a higher health risk with high intakes of folic acid.
Because of the current fortification practice, i.e. products changing frequently and an amount of added folic acid that varies widely, the calculation of folic acid intake includes an uncertainty for scientific investigations and for consumers. Corresponding products from different brands are offered without fortification and with fortification at different levels. In addition, the exact content of folic acid in fortified foods is not known. In the European Union, the producers only have to declare the sum of natural folate and the added amount of folic acid on the label [
34]. Furthermore, due to the instability of folic acid, variability in the declared content of ±30 % is accepted in Germany [
51]. In some cases, including fruit juices, the tolerable deviation to the declared content may be more than +50 %. In other countries, a wide variability regarding the declared value is also reported for beverages, bread and breakfast cereals with −64 to +198 % [
52] and −2 to +220 % [
53].
In the present calculation, the variability of the folic acid content in multivitamin drinks (mixed fruit juices fortified with several vitamins, 100 % juice or water diluted) was considered (Table
1). Analyses of folic acid in nine multivitamin juices at the Max Rubner-Institut confirm the variability of the folic acid content depending on brand and storage time [
40]. The consumption of several fortified foods or large amounts of one fortified food item (beverages especially can be consumed quickly in large amounts) may lead to a high intake of folic acid. At the individual level, the UL can easily be reached, e.g. by one glass of multivitamin juice (250 mL) plus 60 g breakfast cereal plus 250 g yoghurt drink (all with the highest fortification level of the corresponding food group). With multivitamin juice consumed right after production, the UL can be reached by consuming only 600 mL multivitamin juice. Considering the high contents of folic acid in freshly bottled multivitamin juices, the results support the discussion regarding the need for a restriction of folic acid fortification in selected foods such as beverages.
The estimates in the current study are subjected to several limitations. A limitation to dietary assessment methods is underreporting [
54]. With the 24-h recalls used in NVS II, the energy intake is underestimated for 23 % of the study participants. Underreporting was calculated by the quotient (=cut-off level) of energy intake and resting metabolic rate considering sex, age, body height and body weight [
55‐
57]. An exclusion of these so-called under-reporters and further of adolescents and of persons with incomplete data with respect to physical activity, body height and weight in further calculations of the Max Rubner-Institut (data not shown) leads to a higher median DFE intake of 20 µg/d for the remaining group.
In general, data from 24-h recalls reflect short-term food consumption. A statistical method for estimating usual food consumption distribution was not applied to the calculations in this study. Methods such as the National Cancer Institute Method (NCI) [
58] or the Multiple Source Method (MSM) [
59] correct the within-person variation of short-term measured data to reach a narrower intake distribution. Even if an overestimation of the presented proportions of adults with DFE intake above the recommended intakes cannot be excluded, exceeding the UL remains a relevant subject.
Another limitation is that in the present study only the dietary intake of natural food folate and folic acid could be considered, but not the folate status (e.g. folate concentrations in red blood cells). The latter depends on multiple factors as intake of folate and other factors, e.g. interactions with other nutrients (e.g. vitamin C) and genetic polymorphisms [
60] and may lead to partly different results.
The scenarios 2, 3 and 4 are based on the assumption that all participants consuming multivitamin juices, mixed fruit beverages, lemonades (soda), breakfast cereals, margarines, packet soups, cocoa powder and cocoa drinks, certain dairy products, and certain sweets do this exclusively in a fortified form. It is hypothesized that the intake of folic acid in these scenarios reaches the theoretically possible maximum. However, there are some fortified foods, which could not be considered in the analysis, e.g. ready-to-bake bread mixes and convenience products. The higher stability of folic acid compared with natural food folate during cooking could not be included in the BLS calculation algorithm (scenario 4). Furthermore, adding salt at the table could not be considered in scenario 4, but only 5.5 % of the participants of the NVS II declared using table salt fortified with folic acid.