British Journal of Nutrition

Full Papers

Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

Robert Clarkea1 c1, Paul Sherlikera1, Harold Hina2, Anne M. Molloya3, Ebba Nexoa4, Per M. Uelanda5, Kathleen Emmensa1, John M. Scotta3 and John Grimley Evansa6

a1 Clinical Trial Service Unit, University of Oxford, Oxford, UK

a2 Hightown Surgery, Hightown Gardens, Banbury, UK

a3 School of Biochemistry and Immunology, Trinity College, Dublin, Republic of Ireland

a4 Department of Clinical Biochemistry, AS, Aarhus University Hospital, Aarhus, Denmark

a5 Section for Pharmacology, Institute of Medicine, University of Bergen, Bergen, Norway

a6 Division of Clinical Geratology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK


Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd 14·7) nmol/l in 1995 to 31·1 (sd 26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46) v. 1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71) v. (1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

(Received August 08 2007)

(Revised January 31 2008)

(Accepted February 04 2008)

(Online publication March 17 2008)


c1 Corresponding author: Dr Robert Clarke, fax +44 1865 743985, email


Abbreviations: holoTC, holotranscobalamin; MMA, methylmalonic acid; OHAP, Oxford Healthy Aging Project; tHcy, homocysteine