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Molecular mechanisms underlying the potentially adverse effects of folate

  • Kyle C. Strickland , Natalia I. Krupenko und Sergey A. Krupenko EMAIL logo
Veröffentlicht/Copyright: 12. Dezember 2012
Clinical Chemistry and Laboratory Medicine
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine Band 51 Heft 3

Abstract

The importance of proper consumption of dietary folate for human health has been highlighted by an extensive number of publications over several decades. Fortification of grain products with folic acid was initiated with the specific intent to prevent neural tube defects, and the scope of this endeavor is unique in that its target population (women of the periconceptional period) is many times smaller than the population it affects (everyone who ingests fortified grain products). Folate fortification has been wildly successful in terms of its goal; since its inception, the incidence of neural tube defects has markedly decreased. In the wake of this public health triumph, it is important to catalog both the serendipitous benefits and potential side effects of folic acid supplementation. The vitamin is generally regarded as a harmless nutrient based on studies evaluating the safe upper limits of folate intake. In recent years, however, a concern has been raised with respect to a potential downside to folate supplementation; namely, its proposed ability to enhance proliferation of malignant tumors. The current review summarizes the available literature on the effects of folate supplementation and the molecular mechanisms by which high doses of folate may have negative consequences on human health, especially with regard to cancer.

Keywords: cancer; dietary supplementation; folate; folate enzymes; folic acid; metastasis; molecular mechanisms
Corresponding author: Sergey A. Krupenko, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA, Phone: +1 843 792–0845

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: This work was supported by the National Institutes of Heals grants DK54388 and CA095030 (to SAK). Kyle C. Strickland was supported by a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral MD/PhD Fellows F30DK083215.

Employment or leadership: Medical University of South Carolina.

Honorarium: None declared.

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Received: 2012-8-30
Accepted: 2012-11-9
Published Online: 2012-12-12
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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  15. Red cell or serum folate: what to do in clinical practice?
  16. Formate: an essential metabolite, a biomarker, or more?
  17. The role of homocysteine in bone remodeling
  18. Mini Reviews
  19. Neuroprotective actions of perinatal choline nutrition
  20. Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system
  21. Molecular mechanisms underlying the potentially adverse effects of folate
  22. Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver
  23. Hydrogen sulfide as an oxygen sensor
  24. Opinion Paper
  25. B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes
  26. Research Articles
  27. One year B and D vitamins supplementation improves metabolic bone markers
  28. Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects
  29. Aqueous humor glycation marker and plasma homocysteine in macular degeneration
  30. Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
  31. Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution
  32. Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)
  33. Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
  34. Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain
https://doi.org/10.1515/cclm-2012-0561
Schlagwörter für diesen Artikel
cancer; dietary supplementation; folate; folate enzymes; folic acid; metastasis; molecular mechanisms

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Editorial
  4. Special issue on advances and controversies in B vitamins and choline
  5. Reviews
  6. B-Vitamin dependent methionine metabolism and alcoholic liver disease
  7. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis
  8. Proteomics of vitamin B12 processing
  9. Unexpected high plasma cobalamin/Proposal for a diagnostic strategy
  10. Clinical recognition and aspects of the cerebral folate deficiency syndromes
  11. Choline-containing phospholipids: relevance to brain functional pathways
  12. The ‘golden age’ of DNA methylation in neurodegenerative diseases
  13. Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease
  14. The diagnostic utility of folate receptor autoantibodies in blood
  15. Red cell or serum folate: what to do in clinical practice?
  16. Formate: an essential metabolite, a biomarker, or more?
  17. The role of homocysteine in bone remodeling
  18. Mini Reviews
  19. Neuroprotective actions of perinatal choline nutrition
  20. Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system
  21. Molecular mechanisms underlying the potentially adverse effects of folate
  22. Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver
  23. Hydrogen sulfide as an oxygen sensor
  24. Opinion Paper
  25. B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes
  26. Research Articles
  27. One year B and D vitamins supplementation improves metabolic bone markers
  28. Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects
  29. Aqueous humor glycation marker and plasma homocysteine in macular degeneration
  30. Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
  31. Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution
  32. Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)
  33. Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
  34. Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain
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