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    Neurotoxicity of Folic Acid

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    Authors
    van Amsterdam JGC
    Jansen EHJM
    Opperhuizen A
    Type
    Report
    Language
    en
    
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    Title
    Neurotoxicity of Folic Acid
    Translated Title
    Neurotoxiciteit van Foliumzuur
    Publiekssamenvatting
    Het huidige literatuuroverzicht vat de neurotoxische effecten van foliumzuur samen. Enkele dierexperimentele studies gaven aan dat foliumzuur, indien direct toegediend in de hersenen, neurotoxisch en epileptogeen is. In 1970 maakte een, overigens slecht gecontroleerde en niet gereproduceerde, studie melding van neurotoxische symptomen, zoals malaise, slaapverstoring en mentale stoornissen in veertien gezonde vrijwilligers, die een maand lang dagelijks 15 mg foliumzuur oraal kregen toegediend. Vijf jaar later werden convulsies gemeld na hoge intraveneuze toediening van foliumzuur aan een patient met een slecht gecontroleerde epilepsie. Overigens zijn er geen gegevens, die duiden op een direct neurotoxisch effect in de mens bij oraal foliumzuurgebruik. Klinische studies, waarbij patienten langdurig (tot 3 jaar lang) 5 tot 15 mg per dag kregen toegediend gaven geen aanwijzing voor aan foliumzuur gerelateerde neurotoxiciteit. Tenslotte wordt uiteen gezet, dat een deficientie in foliumzuur, die de synthese van S-adenosylhomocysteine remt en stapeling van homocysteine veroorzaakt, wel kan leiden tot neurotoxische schade.

    The present review summarises the neurotoxicological effects of folic acid. Some studies in animals have shown that folic acid is neurotoxic and epileptogenic when applied directly to the brain. One poorly controlled and not further reproduced study from 1970 reported neurotoxic symptoms like malaise, sleep disturbances, and mental changes in 14 healthy volunteers who took daily 15 mg of folic acid for one month. Five years later seizures were reported in a patient with poorly controlled epilepsy after high intravenous doses of folic acid. There are no further data that indicate that oral folic acid is directly neurotoxic in humans. Clinical studies, where daily doses of 5 to 15 for up to 3 years were applied, did not shown any evidence of folate associated neurotoxicity. It is outlined that rather a deficiency in folic acid, that induces a decrease in the synthesis of S-adenosyl-homocysteine and accumulation of homocysteine, may lead to neurotoxicological damage.
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    Rijksinstituut voor Volksgezondheid en Milieu RIVM
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