Literature DB >> 26862004

What is the safe upper intake level of folic acid for the nervous system? Implications for folic acid fortification policies.

E H Reynolds1.   

Abstract

Between 1945 and 1959 it was convincingly documented that folic acid can precipitate or aggravate the neurological and haematological consequences of vitamin B12 deficiency by increasing the demand for vitamin B12. Since then there has been much misunderstanding of the issues, mainly by advocates of folic acid fortification who have been inclined to minimise or even dismiss the risks by misinterpreting the evidence as only a 'masking' of the anaemia of pernicious anaemia. Recent studies in the era of fortification are rediscovering the risks to the nervous system, especially cognitive function, of excess folate in the presence of vitamin B12 deficiency. I have reviewed the Reports of four Expert Advisory Committees in Europe and the USA, which suggest that the safe upper tolerable limit (UL) for folic acid is 1 mg in adults. These reports are unsound and there is already evidence of neurological harm from long-term exposure to doses of folic acid between 0.5 and 1 mg in the presence of vitamin B12 deficiency. There is an urgent need to review the safe UL for folic acid and to consider the addition of vitamin B12 to folic acid fortification policies.

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Year:  2016        PMID: 26862004     DOI: 10.1038/ejcn.2015.231

Source DB:  PubMed          Journal:  Eur J Clin Nutr        ISSN: 0954-3007            Impact factor:   4.016


  40 in total

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Journal:  J Lab Clin Med       Date:  1958-05

2.  Supplemental folic acid therapy in pernicious anemia: the effect on erythropoiesis and serum vitamin B12 concentrations in selected cases.

Authors:  A A LEAR; W B CASTLE
Journal:  J Lab Clin Med       Date:  1956-01

3.  The long-term evaluation of folic acid in the treatment of pernicious anemia.

Authors:  S O SCHWARTZ; S R KAPLAN; B E ARMSTRONG
Journal:  J Lab Clin Med       Date:  1950-06

4.  Vitamin B-12 and folate status in relation to decline in scores on the mini-mental state examination in the framingham heart study.

Authors:  Martha Savaria Morris; Jacob Selhub; Paul F Jacques
Journal:  J Am Geriatr Soc       Date:  2012-07-12       Impact factor: 5.562

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Authors:  D P Agamanolis; E M Chester; M Victor; J A Kark; J D Hines; J W Harris
Journal:  Neurology       Date:  1976-10       Impact factor: 9.910

Review 6.  Staging vitamin B-12 (cobalamin) status in vegetarians.

Authors:  V Herbert
Journal:  Am J Clin Nutr       Date:  1994-05       Impact factor: 7.045

7.  Apparent prevention of neural tube defects by periconceptional vitamin supplementation.

Authors:  R W Smithells; S Sheppard; C J Schorah; M J Seller; N C Nevin; R Harris; A P Read; D W Fielding
Journal:  Arch Dis Child       Date:  1981-12       Impact factor: 3.791

8.  Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

Authors:  James F Toole; M René Malinow; Lloyd E Chambless; J David Spence; L Creed Pettigrew; Virginia J Howard; Elizabeth G Sides; Chin-Hua Wang; Meir Stampfer
Journal:  JAMA       Date:  2004-02-04       Impact factor: 56.272

Review 9.  Does folic acid harm people with vitamin B12 deficiency?

Authors:  C J Dickinson
Journal:  QJM       Date:  1995-05

10.  In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations.

Authors:  Jacob Selhub; Martha Savaria Morris; Paul F Jacques
Journal:  Proc Natl Acad Sci U S A       Date:  2007-12-04       Impact factor: 11.205

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  8 in total

Review 1.  Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review.

Authors:  Lindsay H Allen; Joshua W Miller; Lisette de Groot; Irwin H Rosenberg; A David Smith; Helga Refsum; Daniel J Raiten
Journal:  J Nutr       Date:  2018-12-01       Impact factor: 4.798

2.  Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

Authors:  Lundi Ly; Donovan Chan; Mahmoud Aarabi; Mylène Landry; Nathalie A Behan; Amanda J MacFarlane; Jacquetta Trasler
Journal:  Mol Hum Reprod       Date:  2017-07-01       Impact factor: 4.025

3.  Food matrix structure (from Biscuit to Custard) has an impact on folate bioavailability in healthy volunteers.

Authors:  Caroline Buffière; Manon Hiolle; Marie-Agnès Peyron; Ruddy Richard; Nathalie Meunier; Cindy Batisse; Didier Rémond; Didier Dupont; Françoise Nau; Bruno Pereira; Isabelle Savary-Auzeloux
Journal:  Eur J Nutr       Date:  2020-05-03       Impact factor: 5.614

4.  Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation.

Authors:  Mahmoud Aarabi; Karen E Christensen; Donovan Chan; Daniel Leclerc; Mylène Landry; Lundi Ly; Rima Rozen; Jacquetta Trasler
Journal:  Hum Mol Genet       Date:  2018-04-01       Impact factor: 6.150

5.  Do the benefits of folic acid fortification outweigh the risk of masking vitamin B12 deficiency?

Authors:  James L Mills; Anne M Molloy; Edward H Reynolds
Journal:  BMJ       Date:  2018-03-01

Review 6.  High Folate, Perturbed One-Carbon Metabolism and Gestational Diabetes Mellitus.

Authors:  Jessica M Williamson; Anya L Arthurs; Melanie D Smith; Claire T Roberts; Tanja Jankovic-Karasoulos
Journal:  Nutrients       Date:  2022-09-22       Impact factor: 6.706

Review 7.  Consequences of Inadequate Intakes of Vitamin A, Vitamin B12, Vitamin D, Calcium, Iron, and Folate in Older Persons.

Authors:  Jessica Watson; Marissa Lee; Maria Nieves Garcia-Casal
Journal:  Curr Geriatr Rep       Date:  2018-04-17

8.  Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset.

Authors:  Michaela E Murphy; Cara J Westmark
Journal:  Nutrients       Date:  2020-01-18       Impact factor: 5.717

  8 in total

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