Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

A combination of high folate with low vitamin B12plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72–74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12in relation to cognitive performance. Plasma vitamin B12concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

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Folate and vitamin B12status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

British Journal Of Nutrition ◽

10.1017/s0007114508958001 ◽

2008 ◽

Vol 100 (5) ◽

pp. 1054-1059 ◽

Cited By ~ 38

Author(s):

Robert Clarke ◽

Paul Sherliker ◽

Harold Hin ◽

Anne M. Molloy ◽

Ebba Nexo ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Older People ◽

Serum Folate ◽

Vitamin B ◽

Cross Sectional ◽

Folic Acid Fortification ◽

Folate Status ◽

Cross Sectional Studies ◽

The Uk

Concerns about risks for older people with vitamin B12deficiency 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 B12and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12status (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 (sd14·7) nmol/l in 1995 to 31·1 (sd26·2) 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 B12status was unaffected by highv.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 B12status 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 B12with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

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