Current Concepts in Cobalamin Deficiency

Abstract

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.

Cross-sectional and longitudinal association between homocysteine, vitamin B12 and physical performance in older persons

“…Older age and male gender are associated with higher homocysteine levels (Jacques et al, 1999;Carmel, 2000;Refsum et al, 2004;Dhonukshe-Rutten et al, 2005). Female gender is associated with lower vitamin B12 levels (Dhonukshe-Rutten et al, 2005).…”

Folate and vitamin B12: friendly or enemy nutrients for the elderly

“…Other factors that contribute to malabsorption of food cobalamin in the elderly include chronic carriage of H. pylori and intestinal microbial proliferation, which can be caused by antibiotic treatment (18) , long-term ingestion of biguandies (metformin) (19,20) and antacids, including H 2 -receptor antagonists and proton pump inhibitors (21,22) ; the latter being particularly prevalent among patients with Zollinger-Ellison syndrome (23) , chronic alcoholism, surgery or gastric reconstruction (e.g. bypass surgery for obesity) and partial pancreatic exocrine failure (14,24) . PA is a classic cause of cobalamin deficiency and one of the most frequent among elderly patients; 20-50 % of cases according to two studies (25,26) and > 15% in another patient series (12)(13)(14)(15) .…”

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over

“…Following the early studies that demonstrated the basic relationship between vitamin B 12 and MMA in man (Gompertz et al, 1967;Chanarin et al, 1973;Norman et al, 1982;Carmel, 2000), and which established reliable assay techniques for MMA (Stabler et al, 1986), were a number of key studies showing a surprisingly high prevalence of raised MMA levels in the plasma of older people, where it appeared to provide a more reliable indicator of functional vitamin B 12 status than serum or plasma vitamin B 12 concentrations per se (Lindenbaum et al, 1988;Rasmussen et al, 1989;Moelby et al, 1990;Joosten et al, 1993;Allen & Casterline, 1994;Lindenbaum et al, 1994;Koehler et al, 1996;Baik & Russell, 1999;Bjorkegren & Svardsudd, 1999;Herrmann et al, 2000). Clearly, the ageing process in itself, and the increasing prevalence of age-related medical conditions that impair vitamin B 12 absorption, both increase the probability that people will become vitamin B 12 -deficient as they grow older.…”