British Journal of Nutrition

Research Article

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

Emma Williamsa1, Barbara Stewart-Knoxa1 c1, Ian Bradburya2, Ian Rowlanda1, Kristina Pentievaa1, Anders Helandera3 and Helene McNultya1

a1 Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland

a2 School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland

a3 Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden


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.

(Received October 15 2004)

(Revised March 02 2005)

(Accepted April 07 2005)


c1 *Corresponding author: Dr Barbara Stewart-Knox, fax +44 28 70324965, email