Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

Folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs. Clinicaltrials.gov identifier: NCT00110604.

Background: Very-long-chain nҀ3 polyunsaturated fatty acids (nҀ3 PUFAs) are suggested to be related to cognitive performance in older adults. However, limited data exist on the association between nҀ3 PUFAs and performance in specific cognitive domains. Objective: We evaluated the association between plasma nҀ3 PUFA proportions and cognitive performance in 5 cognitive domains and determined whether plasma nҀ3 PUFA proportions predict cognitive change over 3 y. Design: We used data from the FACIT trial, in which participants received folic acid or placebo capsules for 3 y. Fatty acid proportions in plasma cholesteryl esters at baseline were measured in 807 men and women aged 50 -70 y. Cognitive performance for memory, sensorimotor speed, complex speed, information-processing speed, and word fluency was assessed at baseline and after 3 y. The crosssectional analyses were based on all 807 participants; the longitudinal analyses were based only on 404 participants in the placebo group. Results: Higher plasma nҀ3 PUFA proportions predicted less decline in sensorimotor speed (multiple linear regression coefficient, z score ҃ 0.31; 95% CI: 0.06, 0.57) and complex speed (0.40; 95% CI: 0.10, 0.70) over 3 y. Plasma nҀ3 PUFA proportions did not predict 3-y changes in memory, information-processing speed, or word fluency. The cross-sectional analyses showed no association between plasma nҀ3 PUFA proportions and performance in any of the 5 cognitive domains. Conclusions: In this population, plasma nҀ3 PUFA proportions were associated with less decline in the speed-related cognitive domains over 3 y. These results need to be confirmed in randomized controlled trials.Am J Clin Nutr 2007;86:1479 -85. KEY WORDSCognitive performance, nҀ3 polyunsaturated fatty acids, nҀ3 fatty acids, cognitive decline, older adults

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A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = −0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.ClinicalTrials.gov NCT00110604

Although iron homeostasis is essential for brain functioning, the effects of iron levels on cognitive performance in older individuals have scarcely been investigated. In the present study, serum iron parameters and hemochromatosis (HFE) C282Y genotype were determined in 818 older individuals who participated in a 3-year randomized, placebo-controlled double-blind trial examining the effects of folic acid on carotid intima-media thickness. All participants had slightly elevated homocysteine levels and were vitamin B12 replete. Cognitive functioning was assessed at baseline and after 3 years by means of a neuropsychological test battery. At baseline, increased serum ferritin was associated with decreased sensorimotor speed, complex speed, and information-processing speed and increased serum iron was associated with decreased sensorimotor speed. Cognitive performance over 3 years was not associated with HFE C282Y genotype or iron parameters. In conclusion, serum iron parameters do not show a straightforward relationship with cognitive functioning, although elevated iron levels may decrease cognitive speed in older individuals susceptible to cognitive impairment.

Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by means of 1-year folic acid supplementation does not influence inflammatory responses involving C-reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density lipoprotein, and autoantibodies against oxidized low-density lipoprotein.