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Effect of folic acid supplementation on mood and serotonin response in healthy males

  • Emma Williams (a1), Barbara Stewart-Knox (a1), Ian Bradbury (a2), Ian Rowland (a1), Kristina Pentieva (a1), Anders Helander (a3) and Helene McNulty (a1)
  • DOI:
  • Published online: 01 March 2007

Evidence suggests that low folate status may be detrimental to mood and associated with depleted cerebrospinal fluid levels of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). A placebo-controlled trial was carried out to determine the effect of folic acid supplementation (100 μg for 6 weeks followed by 200 μg for a further 6 weeks) upon subjective mood (Positive and Negative Affect Schedule) and biochemical markers of mood (5-HT) in healthy males (n 23). Blood samples were obtained at baseline (week 0) and during the intervention at week 6 and week 12. Subjective mood assessments were obtained at week 0 and week 12. The results showed an increase in serum and erythrocyte folate concentrations (P=0·02 and P=0·003, respectively) and a corresponding decrease in plasma homocysteine (P=0·015) in response to the folic acid intervention. Neither subjective mood nor 5-HT levels, however, were significantly altered in response to the change in folate status. Folic acid given at physiological doses did not appear to improve the mood of healthy folate-replete individuals over a 12-week period. Further research is needed to address the effect of folic acid supplementation or of longer duration or increased dose, particularly in the face of sub-optimal folate status.

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*Corresponding author: Dr Barbara Stewart-Knox, fax +44 28 70324965, email
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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