Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects
Introduction
Elevated plasma concentrations for the sulphur-containing amino-acid homocysteine and reduced concentrations of the B-vitamin folic acid, two common abnormalities in elderly subjects, have been associated with poor memory and cognitive performance as well as Alzheimer's and other forms of dementia (Rosenberg, 2001, Seshadri et al., 2002, Morris, 2003, Ellinson et al., 2004, Nilsson et al., 2004). There is an inverse relationship between folic acid and homocysteine concentrations through the methionine cycle, which is an essential part of methylation reactions in the brain (Rosenberg, 2001). Folic acid supplementation reduces homocysteine levels and homocysteine levels rise in states of folic acid deficiency (Mangoni and Jackson, 2002).
Elevated plasma homocysteine levels may be a more sensitive marker of functional folic acid deficiency in elderly subjects, in whom normal levels of serum folic acid may not always correspond to adequate cerebrospinal fluid concentrations (Selhub and Miller, 1992, Bottiglieri et al., 2000). Apart from its relationship with vitamin B deficiencies, homocysteine may exert detrimental effects on cognitive function through endothelial dysfunction, arteriosclerosis, thrombosis, and cellular damage (Rosenberg, 2001, Mangoni and Jackson, 2002).
Recent reports have shown that the neuro-psychological impairment of subjects with mild dementia and folic acid deficiency can be improved by folic acid replacement (Nilsson et al., 2001, Sommer et al., 2003). In subjects without vitamin deficiency, lowering homocysteine with short-term folic acid supplementation has been shown to improve endothelial function and reduce pro-thrombotic activity (Undas et al., 1999, Chambers et al., 2000, Mangoni et al., 2002). Therefore, lowering homocysteine concentrations with folic acid even in the absence of overt folic acid deficiency might have a beneficial effect on psychomotor performance. This may be particularly true of the healthy elderly subjects in whom there may be a degree of psychomotor impairment as a result of higher homocysteine levels and perhaps functional folic acid deficiency.
Hematocrit and blood viscosity rise with age and are independently associated with cognitive impairment (Elwood et al., 2001). Studies have also linked blood viscosity and fibrinogen with homocysteine (VonEckardstein et al., 1994). Moreover, folic acid has been shown to reduce fibrinogen, a major determinant of blood viscosity (VonEckardstein et al., 1994, Mangoni et al., 2003). In polycythemic patients the reduction of hematocrit by venesection improves cognitive performance (Wade, 1981). Therefore, it is possible that changes in folic acid and homocysteine blood levels have a positive effect on blood rheology and demonstrate a relationship with psychomotor performance.
The aim of this study was to test the hypothesis that lowering homocysteine levels by folic acid replacement could improve psychomotor performance in healthy elderly subjects with normal serum folic acid levels. The secondary aim was to study the effect of folic acid supplementation on blood rheology.
Section snippets
Subjects
Twenty-four subjects received folic acid or placebo in a randomized, double-blind, parallel-group study. Subjects were recruited from our volunteers’ database. Written consent was obtained in accordance with approval from the local research ethics committee. The subjects were aged ≥65 years; had no previous history of vascular disease, hypertension, diabetes, or smoking; a Mini Mental State Examination (MMSE) score >27/30 (Folstein et al., 1975); were not deficient in folic acid or vitamin B12;
Results
The groups receiving folic acid or placebo were matched for age, gender, systolic, diastolic and mean BP, cholesterol, hemoglobin, platelet count, and MPV (Table 1). Baseline homocysteine, folic acid, and vitamin B12 levels were also comparable (Table 2). Taking all subjects at baseline, folic acid, and homocysteine levels were negatively correlated (r = −0.53, p = 0.008). There was no significant correlation between baseline levels of folic acid, vitamin B12, or homocysteine, and baseline
Discussion
Short-term supplementation with folic acid reduced serum homocysteine concentrations but did not enhance the psychomotor performance of healthy elderly subjects. Similarly, no significant effect on hemorheology was observed. This is the first study to evaluate the effects of folic acid on psychomotor performance of subjects with normal folic acid levels and normal cognitive function. Previous studies showing beneficial effects of folic acid on psychomotor performance have studied subjects with
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