Homocysteine and vitamin status in older people in Perth

To the Editor: Elevated levels of homocysteine (Hcy) have recently been associated with increased risk of vascular events1 and dementia.2 The clearance of Hcy is dependent on three vitamins — folate, B6, and B12. Vitamin B12 deficiency has been described in older people for over 40 years,3 and may have wide-ranging effects through this vitamin’s influence on Hcy. The aims of this study were to examine serum B12 and folate status, and their relationships with plasma Hcy concentrations, in community-dwelling healthy older people living in Perth.

Older men and women were recruited from two different sources: 299 men aged 75 years and over were recruited from a large population-based study of screening for abdominal aortic aneurysm,4 where 70% of those invited joined the project; and we recruited 273 community-dwelling women aged 70 years and over through advertisements. Exclusion criteria for both groups included significant cognitive impairment, severe physical illness and current use of B-group vitamin supplements. The Human Research Ethics Committee at the University of Western Australia approved the study, and all participants provided informed consent.

Fasting total plasma Hcy, serum B12 and folate concentrations were measured in all participants, and serum creatinine concentration was measured in the men only to calculate glomerular filtration rate (cGFR). For analyses, the variable plasma Hcy was heavily skewed to the right and natural logarithmic transformation was used. Pearson’s product moment correlations were calculated for univariate analyses of continuous variables.

Descriptive statistics are presented in Box 1. Fourteen per cent and 1% of the men, and 6% and 1% of the women, were deficient in B12 and folate, respectively. Hcy concentrations above upper reference limits (15 μmol/L for men and 13 μmol/L for women) were found in 24% of both men and women. There were significant (P < 0.001) positive correlations between age and log Hcy concentration for men (r = 0.23; 95% CI, 0.12–0.33) and women (r = 0.25; 95% CI, 0.13–0.36), inverse correlations between B12 and log Hcy concentrations for men (r = – 0.25; 95% CI, – 0.14 to – 0.35) and women (r = – 0.30; 95% CI, – 0.19 to – 0.41), and inverse correlations between folate and Hcy concentrations for men (r = – 0.43; 95% CI, – 0.33 to – 0.52) and women (r = – 0.28; 95% CI, – 0.16 to – 0.39). Plots of log Hcy against B12 and folate concentrations for all participants are presented in Box 2. Under multiple regression, the association of B12 and folate concentrations with log Hcy concentration remained after adjustment for age and cGFR in men only; beta values (SE) were:

• – 0.00060 (0.00011) for B12 concentration;

• – 0.0155 (0.0017) for folate concentration;

• – 0.0029 (0.0008) for cGFR; and

• 0.012 (0.005) for age.

In this sample there were high prevalences of B12 deficiency and hyperhomocysteinaemia. Although the prevalence of folate deficiency was substantially lower, there were still moderate inverse associations between serum folate and Hcy concentrations. Unfortunately, vitamin B12 deficiency of this kind may not be universally corrected with small doses of oral supplements,5 and this has intensified concerns about precipitating neurological complications by population-based folate supplementation.6 There is a need for intervention studies of B-group supplements to evaluate whether the risks associated with hyperhomocysteinaemia can be ameliorated.

2: Plot of serum B12 and folate concentration against log homocysteine concentration (with regression line for B12) in 299 older men and 273 older women