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

Published online by Cambridge University Press:  08 March 2007

Emma Williams ,
Barbara Stewart-Knox ,
Ian Bradbury ,
Ian Rowland ,
Kristina Pentieva ,
Anders Helander  and
Helene McNulty
Emma Williams
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland
Barbara Stewart-Knox*
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland
Ian Bradbury
Affiliation:
School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland
Ian Rowland
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland
Kristina Pentieva
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland
Anders Helander
Affiliation:
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
Helene McNulty
Affiliation:
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland
*
*Corresponding author: Dr Barbara Stewart-Knox, fax +44 28 70324965, email [email protected]
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Abstract

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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.

Keywords

FolateFolic acidMoodPositive and Negative Affect ScheduleSerotoninHomocysteine
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 4 , October 2005 , pp. 602 - 608
Copyright
Copyright © The Nutrition Society 2005

References

Agnoli, A, Ruggieri, S & Cerrone, GG (1977) The dopamine hypotheses of depression: results of treatment with dopaminergic drugs. In Depressive Disorders, pp. 447–458 [Grattini, S, editors]. Stuttgart: FK Schatauer Verlag.Google Scholar
Alpert, JE & Fava, M (1997) Nutrition and depression: the role of folate. Nutr Rev 55, 145–149.CrossRefGoogle ScholarPubMed
Benton, D, Haller, J & Fordy, J (1995) Vitamin supplementation for 1 year improves mood. Neuropsychobiology 32, 98–105.CrossRefGoogle ScholarPubMed
Botez, MI, Botez, T, Levielle, J, Bielmann, T & Cadotte, M (1979 a) Neuropsychological correlates of folic acid deficiency: facts and hypotheses. In Folic Acid in Neurology, Psychiatry, and Internal Medicine. pp. 425–461 [Botez, MI, Reynolds, EH, editors]. New York: Raven Press.Google Scholar
Botez, MI, Young, SN, Bachevalier, J & Gauthier, S (1979 b) Folate deficiency and decreased brain 5-hydroxytryptamine synthesis in man and rat. Nature 278, 182–183.CrossRefGoogle Scholar
Botez, MI, Young, SN, Bachevalier, J & Gauthier, S (1982) Effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid. Am Neurol Assoc 12, 479–484.CrossRefGoogle ScholarPubMed
Bottiglieri, T, Hyland, K & Reynolds, EH (1994) The clinical potential of ademethionine ( S -adenosylmethionine) in neurological disorders. Drugs 48, 137–152.CrossRefGoogle Scholar
Bottiglieri, T, Laundy, M, Crellin, R & Toone, BK (2000) Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 69, 228–234.CrossRefGoogle ScholarPubMed
Brattstrom, L, Israellson, B, Jeppson, J & Hultberg, B (1998) Folic acid – an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 48, 215–221.CrossRefGoogle Scholar
Brewerton, TD, Flament, MF, Rapoport, JL & Murphy, DL (1993) Seasonal effects on platelet 5HT content in patients with OCD and controls. Arch Gen Psychiatry 50, 409.Google ScholarPubMed
Bryan, J, Calvaresi, E & Hughes, D (2002) Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr 132, 1345–1356.CrossRefGoogle Scholar
Cantoni, GL (1953) S -Adenosylmethionine: a new intermediate formed enzymatically from l -methionine and adenosine triphosphate. J Biol Chem 204, 403–416.CrossRefGoogle Scholar
Carney, MWP (1967) Serum folate values in 423 psychiatric patients. Br Med J 4, 512.CrossRefGoogle ScholarPubMed
Carney, MWP, Martin, R, Bottiglieri, T, Reynolds, EH, Nissenbaum, H, Toone, BK & Sheffield, BN (1983) The switch mechanism in affective illness and S -adenosylmethionine. Lancet 1, 820–821.CrossRefGoogle ScholarPubMed
Coppen, A & Bailey, J (2000) Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord 60, 121–130.CrossRefGoogle ScholarPubMed
Coppen, A, Turner, P, Rowsell, AR & Padgham, C (1976) 5-Hydroxytryptamine (5-HT) in the whole-blood of patients with depressive illness. Postgrad Med J 52, 156–158.CrossRefGoogle ScholarPubMed
Coppen, A, Chaudhry, S & Swade, C (1986) Folic acid enhances lithium prophylaxis. J Affect Disord 10, 9–13.CrossRefGoogle ScholarPubMed
Costello, J, Benjamin, R, Angold, A & Silver, D (1991) Mood variability in adolescents. A study of depressed, nondepressed and comorbid patients. J Affect Disord 23, 199–212.CrossRefGoogle ScholarPubMed
Crawley, H (1988) Food Portion Sizes 3rd ed. London: HMSO.Google Scholar
Fava, M, Borus, JS, Alpert, JE, Nierenberg, AA, Rosenbaum, JF & Bottiglieri, T (1997) Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 154, 426–428.Google ScholarPubMed
Ghadirian, AM, Anath, J & Engelsmann, F (1980) Folic acid deficiency in depression. Psychosomatics 21, 926–929.CrossRefGoogle ScholarPubMed
Godfrey, PSA, Toone, BK, Carney, MWP, Flynn, TG, Bottiglieri, T, Laundy, M, Chanarin, I & Reynolds, EH (1990) Enhancement of recovery from psychiatric illness by methylfolate. Lancet 336, 392–395.CrossRefGoogle ScholarPubMed
Guaraldi, G, Fava, M, Mazzi, F & LaGreca, P (1993) An open trial of methyltetrahydrofolate (MTHF) in elderly depressed patients. Ann Clin Psychiatry 5, 101–106.CrossRefGoogle ScholarPubMed
Harris, S & Dawson-Hughes, B (1993) Seasonal mood changes in 250 normal women. Psychiatry Res 49, 77–87.CrossRefGoogle ScholarPubMed
Herbert, V (1962) Experimental nutritional folate deficiency in man. Trans Assoc Am Physicians 75, 307–320.Google ScholarPubMed
Jensen, E, Dehlin, O, Erfurth, EM, Hagberg, B, Samuelsson, B, Svensson, T & Hultberg, B (1998) Plasma homocysteine in 80-year-olds: relationships to medical, psychological and social variables. Arch Gerontol Geriatr 26, 215–226.CrossRefGoogle ScholarPubMed
Jung, RE, Yeo, RA, Love, TM, Petropoulos, H, Sibbitt, TL & Brooks, WM (2002) Biochemical markers of mood: a proton magnetic resonance spectroscopy study of normal human brain. Biol Psychiatry 51, 224–229.CrossRefGoogle Scholar
Kang, SSWong, PWK & Malinow, MR (1992) Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 12, 279–298.CrossRefGoogle ScholarPubMed
Kema, IP, Schellings, AMJ, Melmorg, G, Hoppenbrouwers, CJM & Muskiet, FAJ (1992) Influence of a serotonin- and dopamine-rich diet on platelet serotonin content and urinary excretion of biogenic amines and their metabolites. Clin Chem 38, 1730–1736.CrossRefGoogle ScholarPubMed
Lapin, IP & Oxenkrug, GF (1969) Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect. Lancet 1, 132–136.CrossRefGoogle Scholar
Leino, A (1999) Fully automated measurement of total homocysteine in plasma and serum on the Abbott IMx Analyzer. Clin Chem 45, 569–571.CrossRefGoogle ScholarPubMed
Le Quan-Bui, KH, Plaisant, O, Leboyer, M, Gay, C, Kamal, L, Devynck, M & Meyer, P (1984) Reduced platelet serotonin in depression. Psychiatry Res 13, 129–139.CrossRefGoogle ScholarPubMed
McConville, C & Cooper, C (1992) Mood variability and personality. Pers Individ Dif 13, 1213–1221.CrossRefGoogle Scholar
McConville, C & Cooper, C (1996) Mood variability and the intensity of depressive states. Curr Psychol 14, 329–338.CrossRefGoogle Scholar
McConville, C & Cooper, C (1999) Personality correlates of variable moods. Pers Individ Dif 26, 65–78.CrossRefGoogle Scholar
McNair, DM, Lorr, M & Dropplemann, F (1971) Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service.Google Scholar
Molloy, AM & Scott, JM (1997) Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method. Methods Enzymol 281, 43–53.CrossRefGoogle ScholarPubMed
Morris, MS, Fava, M, Jacques, PF & Selhub, J (2003) Depression and folate status in the US population. Psychother Psychosom 72, 80–87.CrossRefGoogle ScholarPubMed
National Statistics Socio-Economic Classification (2002) National Statistics Socio-Economic Classification User Manual London: HMSO, Office for National Statistics.Google Scholar
Ordonez, LA & Wurtman, RJ (1974) Folic acid deficiency and methyl group metabolism in rat brain: effects of l -Dopa. Arch Biochem Biophys 160, 372–376.CrossRefGoogle ScholarPubMed
Quintana, J (1992) Platelet serotonin and plasma tryptophan in endogenous depression. Clinical, therapeutic, and biological correlations. Affect Disord 24, 55–62.CrossRefGoogle ScholarPubMed
Reynolds, EH & Carney, MWP (1984) Methylation and mood. Lancet 28, 196–198.CrossRefGoogle Scholar
Reynolds, EH & Stramentinoli, G (1983) S -Adenosylmethionine and affective disorder. Psychol Med 13, 705–710.CrossRefGoogle ScholarPubMed
Reynolds, EH, Preece, JM, Bailey, J & Coppen, A (1970) Folate deficiency in depressive illness. Br J Psychiatry 117, 287–292.CrossRefGoogle ScholarPubMed
Sarrias, MJ, Artigas, M, Martinez, A & Gelpi, E (1989) Seasonal changes of plasma serotonin and related parameters: correlations with environmental measures. Biol Psychiatry 26, 695–706.CrossRefGoogle ScholarPubMed
Ward, M, McNulty, H, McPartlin, J, Strain, JJ, Weir, DG & Scott, JM (1997) Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. Q J Med 90, 519–524.CrossRefGoogle ScholarPubMed
Watson, D (2000) Mood and Temperament New York: The Guilford Press.Google Scholar
Watson, D & Clark, LA (1997) Measurement and mismeasurement of mood; recurrent and emergent issues. J Pers Assess 66, 267–296.CrossRefGoogle Scholar
Watson, D & Clark, LA (1994) The PANAS-X Manual for the Positive and Negative Affect Schedule – Expanded Form Ames, IA: University of Iowa.CrossRefGoogle Scholar
Watson, D, Clark, LA & Tellegen, A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54, 1063–1070.CrossRefGoogle ScholarPubMed
Wesson, VA, Levitt, AJ & Joffe, RT (1994) Change in folate status with antidepressant treatment. Psychiatry Res 53 313–322.CrossRefGoogle ScholarPubMed
Xiao, R, Beck, O & Hjemdahl, P (1998) On the accurate measurement of serotonin in whole blood. Scand J Clin Lab Invest 58, 505–510.CrossRefGoogle ScholarPubMed
Zald, DH & Depue, RA (2001) Serotonergic functioning correlates with positive and negative affect in psychiatrically healthy males. Pers Individ Dif 30, 71–86.CrossRefGoogle Scholar