title: Safety and benefits of interventions to increase folate status in malaria-endemic areas.
abstract: For decades, folic acid has routinely been given to prevent or treat anaemia in children, pregnant women and people with sickle cell disease. However, there is no conclusive evidence that folate deficiency anaemia constitutes a public health problem in any of these groups. Industrial flour fortification is recommended and implemented in many countries to combat neural tube defects. Dietary folates or folic acid can antagonise the action of antifolate drugs that play a critical role in the prevention and treatment of malaria. Randomised trials have shown that folic acid supplementation increases the rate of treatment failures with sulfadoxine-pyrimethamine. The efficacy of antifolate drugs against Plasmodium is maximized in the absence of exogenous folic acid, suggesting that there is no safe minimum dose of ingested folic acid. We here review the safety and benefits of interventions to increase folate status in malaria-endemic countries. We conclude that formal cost-benefit analyses are required.
authors.affiliation: London School of Hygiene and Tropical Medicine, MRC International Nutrition Group, London, UK.|Nutrition Theme, MRC Unit The Gambia, Banjul, Gambia.|Cell Biology and Immunology Group, & Research, Wageningen, The Netherlands.|Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands.
authors.forename: Hans
authors.identifier: 0000-0002-9346-9689
authors.initials: H
authors.lastname: Verhoef
authors.affiliation: Laboratory for Microbiology and Immunology, Admiral de Ruyter Hospital, Goes, The Netherlands.|Laboratory for Microbiology and Infection Control, Amphia Hospital, Breda, The Netherlands.
authors.forename: Jacobien
authors.initials: J
authors.lastname: Veenemans
authors.affiliation: Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands.
authors.forename: Martin N
authors.identifier: 0000-0002-8358-4448
authors.initials: MN
authors.lastname: Mwangi
authors.affiliation: London School of Hygiene and Tropical Medicine, MRC International Nutrition Group, London, UK.|Nutrition Theme, MRC Unit The Gambia, Banjul, Gambia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use; D019587:Dietary Supplements / Q000009:adverse effects; D004347:Drug Interactions; D004351:Drug Resistance; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use*; D005493:Folic Acid Antagonists / Q000627:therapeutic use; D005494:Folic Acid Deficiency / Q000517:prevention & control; D006801:Humans; D008288:Malaria / Q000517:prevention & control*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D005492:Folic Acid
keywords: folic acid; folic acid antagonists; malaria; neural tube defects; sulfadoxine-pyrimethamine