Long-term effects of folic acid fortification and B-vitamin supplementation on total folate, homocysteine, methylmalonic acid and cobalamin in older adults.

OBJECTIVE: To investigate the long-term effects of the Canadian folic acid fortification program in older adults' whole blood cell folate (folate) and cobalamin (Cbl) status, including homocysteine (tHcy) and methylmalonic acid (MMA), with and without voluntary B-vitamin intake, from 1997 to 2004. METHODS: Cohort of community-dwelling volunteer older adults. Clinical and biochemical data, including intake of B-vitamin supplements, were obtained at 2- to 2.5-year intervals and divided in 4 periods. Random coefficients (mixed effects) models were used to estimate the linear trend in folate and to compare levels of biochemical parameters between periods. All models were estimated by restricted maximum likelihood as implemented in PROC MIXED of SAS V8.2. RESULTS: Folate levels increased continuously at a yearly rate of 234 ng/mL (95% CI 213-254; p < 0.001) and had not plateaued by the last period when 84% of subjects without B-vitamins had elevated folate. Homocysteine did not remain suppressed. Elevated tHcy was as prevalent in the last study period as in the first. No significant deficits of Cbl or increases of MMA were observed, but MMA levels tended to increase with time in subjects without B-vitamins. B-vitamin supplements significantly affected all results, reducing tHcy and MMA levels. CONCLUSION: In this population, fortification with folic acid has resulted in cumulative increases of folate with no long-term reduction in tHcy or changes in Cbl or MMA. Possible deleterious effects of cumulative increases of folate, and beneficial effects of B-vitamin supplements in reducing tHcy and MMA, should be investigated.

Metabolic markers of cobalamin deficiency and cognitive function in normal older adults.

OBJECTIVES: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. DESIGN: Cross-sectional study. SETTING: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. PARTICIPANTS: Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older. MEASUREMENTS: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). RESULTS: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (beta=-0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores. CONCLUSION: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.