Clinical Nutrition xxx (2014) 1e2
Contents lists available at ScienceDirect
Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
Reply
The unresolved debate on lowering the recommended dietary intake for folate Keywords: Recommended Dietary Allowance (RDA) Folate
We would like to thank Strohm et al., for explaining their strategy to construct the population Recommended Dietary Allowance (RDA) for folate. We are certainly aware of the approach of using the Estimated Average Requirement (EAR) of a specific nutrient in an age- and sexspecific manner to estimate the RDA. The original report of the German Societies for Nutrition concluded that 200 DFEs/d were sufficient to reach the folate requirement, without explaining the rationale behind adapting this new value http://www.dge.de/pdf/ws/Referenzwerte2013-Folat.pdf. More confusion was caused by the fact that, folate intake data in the German National Intake Survey Study (National Verzehrstudie II, NVSII) has also been revised and showed lower values in 2012 compared to intakes data in the 2008 survey [1]. The new median intake in the NVSII study is approximately 200 mg DFEs/d, the same as the newly proposed EAR, and both now are 100 mg DFEs/d lower than the 2008 data [1]. Therefore, the arguments published in the opinion paper [2] remain all valid, with the exception that it is now clear that the 200 mg DFEs was the EAR and not an estimated average intake. The EAR represents the median (50th percentile) intake necessary to maintain criteria of adequacy, derived from a careful review of the scientific evidence. Using this value aims to exclusively answer the specific question “adequate for what?” There is no doubt that the RDA is higher than the EAR (50% of the population below this intake level), since the first is expected to cover the requirements of the majority of the population, not only 50% (Fig. 1). The depletion-repletion study by Sauberlich et al., on 10 women [3], was one of three studies used to justify a new EAR [3e5]. The repletion phase included; Group A (n ¼ 4) [80 mg folic acid plus 20 mg dietary folate (¼156 mg DFEs/d)]; Group B (n ¼ 3) [200 mg dietary folate ¼ 200 mg DFEs]; or Group C (n ¼ 3) [200 then 300 mg DFEs dietary folate] [3]. Because whole blood folate continued to decline under 200 mg DFEs/d dietary folate or 156 mg DFEs, but not under 300 mg DFEs/d dietary folate, the authors concluded that an intake of 300 mg DFEs of dietary folate would appear to have been adequate to meet the folate requirements of the women in that specific study [3]. Therefore, the EAR according to Sauberlich et al., may be 300 (rather than 200) mg DFEs. The data by Milne et al. [5], was judged equivocal because of the “non-measurable” underestimation of food folate contents, changing the diet during the study, consuming a normal diet for 10 days to 2 months by some participants, and the different duration of the study between participants [6]. Therefore, the evidence on which an EAR of 200 mg DFEs has DOI of original article: http://dx.doi.org/10.1016/j.clnu.2014.04.021.
been derived by the German Societies for Nutrition remains highly questionable. The Dietary Recommended Intakes (DRIs) (e.g., RDA, EAR, and upper tolerable limit) are estimates with a considerable degree of uncertainty. Therefore, in view of the limited scientific evidence, dietary adequacy on a population level should be assessed based on the totality of evidence (clinical, biochemical, diseases) as suggested by the U.S National Academy of Sciences and by our paper [2]. The revised RDA (300 mg DFEs/d) can probably be considered as “folate intake adequate for preventing megaloblastic anemia” in the population, but not for preventing age-associated diseases, cancer or birth defects, which have a high social and economic burden in Germany [7]. Folate intake has been estimated to be 50% of the German population, who have an intake below the median (estimated 35 million adults of both sexes) (Fig. 1). The fortification choice is a policy decision, since the scientific evidence regarding benefit and safety is unequivocal. In the light of the revised RDA and intake data [1] and the recommendation by Strohm et al., to increase folate intake in the population from dietary sources, Fig.1(B) shows that a theoretical mean intake of 400 mg/d may ensure that w98% of the population are not at risk for insufficient intake. This implies the need to increase folate intake by w200 mg/d (or supplement 100 mg folic acid/d) to bridge the gap between the observed and the optimal intakes. However, the NVSII study clearly showed that only supplement users (743 women and 438 men) had a median total folate intake of 500 mg DFEs/d [1]. In contrast, none of the healthy lifestyle patterns or social factors (e.g., sport, income, country of birth,
http://dx.doi.org/10.1016/j.clnu.2014.04.018 0261-5614/Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article in press as: Obeid R, et al., The unresolved debate on lowering the recommended dietary intake for folate, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.04.018
2
Reply / Clinical Nutrition xxx (2014) 1e2
Fig. 1. Distribution of population intakes and risk of inadequate intake in the light of the revised EAR and RDA for folate in Germany. The figure is based on a proposed EAR (200 mg DFEs/d), median intake in the German population of approximately 200 mg DFEs/d, and it assumes a normal distribution of the data and a reference value for adults of 300 mg DFEs/ d. The upper panel shows that approximately 50% of all adult Germans: [e.g., 65% of all women with a median intake 184 mg/d and 85% of young women (15e19 y) with a median intake of 153 mg/d [1]] are probably at risk of inadequate intake of folate. The figures are only for illustration. The distribution may be different according to age and sex.
good nutrition education, not smoking) explained a difference in median dietary folate intake of more than 30 mg DFE/d [1]. Therefore, we insist the urgent need to revise the EAR and the intake data in the population, explore folate biomarkers, relate the results to health outcomes including the most demanding subjects (young women, elderly) to draw conclusions on the RDA for adults in an age- and sex-specific manner. At this point, one main issue remains unsolved: what is the most effective/cost-effective way to improve folate status of at least 50% of adults in the German population (not only women who intend to get pregnant or those in the first trimester)? Obviously, polarizing the public opinion against industry does not deliver scientific evidence, or a constructive solution for the problem. We confirm that until the date of publication, the opinion paper [2] has been prepared and discussed entirely among the contributing authors. No fourth party (e.g., from the working group on folic acid or any industrial part) had any influence on the content of the article. Finally, we wish to emphasize that none of the authors received financial support related to this work. The authors have no conflict of interests to declare.
[5] Milne DB, Johnson LK, Mahalko JR, Sandstead HH. Folate status of adult males living in a metabolic unit: possible relationships with iron nutriture. Am J Clin Nutr 1983;37:768e73. [6] Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. USA: Washington, DC: National Academy Press; 1998. pp. 390e422. [7] Bowles D, Wasiak R, Kissner M, van NF, Engel S, Linder R, et al. Economic burden of neural tube defects in Germany. Public Health 2014;128:274e81. [8] Eisele L, Durig J, Broecker-Preuss M, Duhrsen U, Bokhof B, Erbel R, et al. Prevalence and incidence of anemia in the German Heinz Nixdorf Recall Study. Ann Hematol 2013;92:731e7.
References
* Corresponding author. Department of Clinical Chemistry and Laboratory Medicine, Medical School, Saarland University, Building 57, D-66421 Homburg, Germany. Tel.: þ49 68411630711; fax: þ49 68411630703. E-mail address: [email protected] (R. Obeid).
[1] Ernährungsbericht 12, Deutsche Gesellschaft für Ernährung e.V.; 2012. pp. 40e85. [2] Obeid R, Koletzko B, Pietrzik K. Critical evaluation of lowering the recommended dietary intake of folate. Clin Nutr 2014;33:252e9. [3] Sauberlich HE, Kretsch MJ, Skala JH, Johnson HL, Taylor PC. Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr 1987;46:1016e28. [4] Herbert V. Minimal daily adult folate requirement. Arch Intern Med 1962;110: 649e52.
Rima Obeid* Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, D-66421 Homburg, Germany Berthold Koletzko Division of Metabolic and Nutritional Medicine, Ludwig-MaximiliansUniversity of Munich, D-80337 Munich, Germany Klaus Pietrzik Department of Nutrition and Food Science, Rheinische FriedrichWilhelms University, D-53115 Bonn, Germany
7 April 2014
Please cite this article in press as: Obeid R, et al., The unresolved debate on lowering the recommended dietary intake for folate, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.04.018
Contents lists available at ScienceDirect
Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
Reply
The unresolved debate on lowering the recommended dietary intake for folate Keywords: Recommended Dietary Allowance (RDA) Folate
We would like to thank Strohm et al., for explaining their strategy to construct the population Recommended Dietary Allowance (RDA) for folate. We are certainly aware of the approach of using the Estimated Average Requirement (EAR) of a specific nutrient in an age- and sexspecific manner to estimate the RDA. The original report of the German Societies for Nutrition concluded that 200 DFEs/d were sufficient to reach the folate requirement, without explaining the rationale behind adapting this new value http://www.dge.de/pdf/ws/Referenzwerte2013-Folat.pdf. More confusion was caused by the fact that, folate intake data in the German National Intake Survey Study (National Verzehrstudie II, NVSII) has also been revised and showed lower values in 2012 compared to intakes data in the 2008 survey [1]. The new median intake in the NVSII study is approximately 200 mg DFEs/d, the same as the newly proposed EAR, and both now are 100 mg DFEs/d lower than the 2008 data [1]. Therefore, the arguments published in the opinion paper [2] remain all valid, with the exception that it is now clear that the 200 mg DFEs was the EAR and not an estimated average intake. The EAR represents the median (50th percentile) intake necessary to maintain criteria of adequacy, derived from a careful review of the scientific evidence. Using this value aims to exclusively answer the specific question “adequate for what?” There is no doubt that the RDA is higher than the EAR (50% of the population below this intake level), since the first is expected to cover the requirements of the majority of the population, not only 50% (Fig. 1). The depletion-repletion study by Sauberlich et al., on 10 women [3], was one of three studies used to justify a new EAR [3e5]. The repletion phase included; Group A (n ¼ 4) [80 mg folic acid plus 20 mg dietary folate (¼156 mg DFEs/d)]; Group B (n ¼ 3) [200 mg dietary folate ¼ 200 mg DFEs]; or Group C (n ¼ 3) [200 then 300 mg DFEs dietary folate] [3]. Because whole blood folate continued to decline under 200 mg DFEs/d dietary folate or 156 mg DFEs, but not under 300 mg DFEs/d dietary folate, the authors concluded that an intake of 300 mg DFEs of dietary folate would appear to have been adequate to meet the folate requirements of the women in that specific study [3]. Therefore, the EAR according to Sauberlich et al., may be 300 (rather than 200) mg DFEs. The data by Milne et al. [5], was judged equivocal because of the “non-measurable” underestimation of food folate contents, changing the diet during the study, consuming a normal diet for 10 days to 2 months by some participants, and the different duration of the study between participants [6]. Therefore, the evidence on which an EAR of 200 mg DFEs has DOI of original article: http://dx.doi.org/10.1016/j.clnu.2014.04.021.
been derived by the German Societies for Nutrition remains highly questionable. The Dietary Recommended Intakes (DRIs) (e.g., RDA, EAR, and upper tolerable limit) are estimates with a considerable degree of uncertainty. Therefore, in view of the limited scientific evidence, dietary adequacy on a population level should be assessed based on the totality of evidence (clinical, biochemical, diseases) as suggested by the U.S National Academy of Sciences and by our paper [2]. The revised RDA (300 mg DFEs/d) can probably be considered as “folate intake adequate for preventing megaloblastic anemia” in the population, but not for preventing age-associated diseases, cancer or birth defects, which have a high social and economic burden in Germany [7]. Folate intake has been estimated to be 50% of the German population, who have an intake below the median (estimated 35 million adults of both sexes) (Fig. 1). The fortification choice is a policy decision, since the scientific evidence regarding benefit and safety is unequivocal. In the light of the revised RDA and intake data [1] and the recommendation by Strohm et al., to increase folate intake in the population from dietary sources, Fig.1(B) shows that a theoretical mean intake of 400 mg/d may ensure that w98% of the population are not at risk for insufficient intake. This implies the need to increase folate intake by w200 mg/d (or supplement 100 mg folic acid/d) to bridge the gap between the observed and the optimal intakes. However, the NVSII study clearly showed that only supplement users (743 women and 438 men) had a median total folate intake of 500 mg DFEs/d [1]. In contrast, none of the healthy lifestyle patterns or social factors (e.g., sport, income, country of birth,
http://dx.doi.org/10.1016/j.clnu.2014.04.018 0261-5614/Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article in press as: Obeid R, et al., The unresolved debate on lowering the recommended dietary intake for folate, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.04.018
2
Reply / Clinical Nutrition xxx (2014) 1e2
Fig. 1. Distribution of population intakes and risk of inadequate intake in the light of the revised EAR and RDA for folate in Germany. The figure is based on a proposed EAR (200 mg DFEs/d), median intake in the German population of approximately 200 mg DFEs/d, and it assumes a normal distribution of the data and a reference value for adults of 300 mg DFEs/ d. The upper panel shows that approximately 50% of all adult Germans: [e.g., 65% of all women with a median intake 184 mg/d and 85% of young women (15e19 y) with a median intake of 153 mg/d [1]] are probably at risk of inadequate intake of folate. The figures are only for illustration. The distribution may be different according to age and sex.
good nutrition education, not smoking) explained a difference in median dietary folate intake of more than 30 mg DFE/d [1]. Therefore, we insist the urgent need to revise the EAR and the intake data in the population, explore folate biomarkers, relate the results to health outcomes including the most demanding subjects (young women, elderly) to draw conclusions on the RDA for adults in an age- and sex-specific manner. At this point, one main issue remains unsolved: what is the most effective/cost-effective way to improve folate status of at least 50% of adults in the German population (not only women who intend to get pregnant or those in the first trimester)? Obviously, polarizing the public opinion against industry does not deliver scientific evidence, or a constructive solution for the problem. We confirm that until the date of publication, the opinion paper [2] has been prepared and discussed entirely among the contributing authors. No fourth party (e.g., from the working group on folic acid or any industrial part) had any influence on the content of the article. Finally, we wish to emphasize that none of the authors received financial support related to this work. The authors have no conflict of interests to declare.
[5] Milne DB, Johnson LK, Mahalko JR, Sandstead HH. Folate status of adult males living in a metabolic unit: possible relationships with iron nutriture. Am J Clin Nutr 1983;37:768e73. [6] Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. USA: Washington, DC: National Academy Press; 1998. pp. 390e422. [7] Bowles D, Wasiak R, Kissner M, van NF, Engel S, Linder R, et al. Economic burden of neural tube defects in Germany. Public Health 2014;128:274e81. [8] Eisele L, Durig J, Broecker-Preuss M, Duhrsen U, Bokhof B, Erbel R, et al. Prevalence and incidence of anemia in the German Heinz Nixdorf Recall Study. Ann Hematol 2013;92:731e7.
References
* Corresponding author. Department of Clinical Chemistry and Laboratory Medicine, Medical School, Saarland University, Building 57, D-66421 Homburg, Germany. Tel.: þ49 68411630711; fax: þ49 68411630703. E-mail address: [email protected] (R. Obeid).
[1] Ernährungsbericht 12, Deutsche Gesellschaft für Ernährung e.V.; 2012. pp. 40e85. [2] Obeid R, Koletzko B, Pietrzik K. Critical evaluation of lowering the recommended dietary intake of folate. Clin Nutr 2014;33:252e9. [3] Sauberlich HE, Kretsch MJ, Skala JH, Johnson HL, Taylor PC. Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr 1987;46:1016e28. [4] Herbert V. Minimal daily adult folate requirement. Arch Intern Med 1962;110: 649e52.
Rima Obeid* Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, D-66421 Homburg, Germany Berthold Koletzko Division of Metabolic and Nutritional Medicine, Ludwig-MaximiliansUniversity of Munich, D-80337 Munich, Germany Klaus Pietrzik Department of Nutrition and Food Science, Rheinische FriedrichWilhelms University, D-53115 Bonn, Germany
7 April 2014
Please cite this article in press as: Obeid R, et al., The unresolved debate on lowering the recommended dietary intake for folate, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.04.018
