Metabolic evidence that deficiencies of vitamin B−12 (cobalamin), folate, and vitamin B−6 occur commonly in elderly people

Abstract

Measurements of the serum concentrations of the metabolites homocysteine, cystathionine, methylmalonic acid, and 2-methylcitric acid, which accumulates when vitamin B-12-, folate-, and vitamin B-6-dependent enzymatic reactions are impaired, should provide a better indication of intracellular deficiency of these vitamins. We measured the serum concentration of these vitamins and the four metabolites in 99 healthy young people, 64 healthy elderly subjects, and 286 elderly hospitalized patients. A low serum vitamin B-12 concentration was found in 6% and 5%, low folate in 5% and 19%, and low vitamin B-6 in 9% and 51%, and one or more metabolites were elevated in 63% and 83% of healthy elderly subjects and elderly hospitalized patients, respectively. These results strongly suggest that the prevalence of tissue deficiencies of vitamin B-12, folate, and vitamin B-6 as demonstrated by the elevated metabolite concentrations is substantially higher than that estimated by measuring concentrations of the vitamins.

Iron, folate and vitamin B12 status of an elderly South African population

“…Folate and vitamin B 12 status, particularly in the elderly, is currently the subject of considerable debate, primarily Iron, folate and vitamin B 12 status KE Charlton et al because re®ned biochemical techniques estimate the prevalence of tissue de®ciency, without the presence of anaemia, to be higher than the prevalence detected by measuring serum or blood cell concentration of the vitamins (Joosten et al, 1993;Lindenbaum et al, 1994); such suboptimal status at the biochemical level has been associated with signi®cant neuropsychiatric damage including impairment in cognitive function Healton et al, 1991). Moreover, similar suboptimal status of both vitamins, together with vitamin B 6 , has been associated with elevated serum homocysteine concentration (Stabler et al, 1988), the latter being increasingly accepted as an independent and major risk factor for coronary, peripheral and cerebrovascular disease (Clarke et al, 1991;Kang et al, 1992).…”

“…In unison with these proposals, it is of interest that in the present study serum ferritin levels below 15mg/l were uncommon in men and found only in 5 of the women. Serum ferritin is an acute phase protein and is typically elevated in infection, in¯ammation and malignancy (Joosten et al, 1993;Bothwell et al, 1979;Worwood, 1986). When iron de®ciency therefore coexists with chronic disease serum ferritin may be falsely raised and iron de®ciency may remain undiagnosed.…”

“…Although the prevalence of iron de®ciency anaemia tends to decrease after the age of 65 y (Beal, 1980), especially in women, it can be present in up to 20 of elderly people seeking medical attention (Joosten et al, 1992;Kikerby et al, 1991). The prevalence of folic acid and vitamin B 12 de®ciencies, based on the determination of serum concentrations, varies (0±20) according to the population being studied; however, on the basis of the determination of abnormal intermediary metabolites, a substantially higher prevalence (39±68) of de®ciency has recently been reported (Joosten et al, 1993).…”

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

“…Estimates among the elderly vary widely; from 5% (based upon a low serum vitamin B 12 concentration) among institutionalized elderly adults in Germany, The Netherlands and Belgium (32) to 46% (based on multiple criteria including serum vitamin B 12 and methylmalonic acid (MMA)) among institutionalized elderly adults in the UK (33) . The impact on estimates of prevalence of using different criteria of deficiency can be illustrated by adapting data presented for a UK cohort of elderly adults (34) .…”

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.…”