Cobalamin Deficiency in the Elderly

Abstract

Older people are at risk for cobalamin (vitamin B12) deficiency because of a number of common disorders (e.g. autoimmune gastritis) and drugs (e.g. antacids) that may alter its absorption and utilization. The prevalence of cobalamin deficiency increases with age, resulting particularly elevated in frail and institutionalized subjects. At variance with common sense, the diagnosis is far from simple and requires a high degree of suspicion, due to heterogeneity and non-specificity of the signs and symptoms, ranging from macrocytosis (with or without anemia) to neuropsychiatric manifestations, that characterize several other aging-related disorders, like hematological malignancies, diabetes, hypothyroidism or vasculopathies. Furthermore, the detection of low levels of serum vitamin B12 appears poorly sensitive and specific. Other biomarkers, like serum homocysteine or methylmalonic acid, have improved the diagnostic possibilities but are expensive, not widely available and may be influenced by some confounders (e.g. folate deficiency, or chronic renal failure). Early recognition and treatment are crucial, since a proportion of patients develop severe complications, such as bone marrow failure and irreversible neurological impairment. High-dose oral treatment has proven to be as effective as the parenteral route even in subjects with malabsorption, ensuring the complete resolution in the majority of cases. In this review, we trace the essential role of cobalamin in humans, the possible causes and impact of deficiency, the diagnostic challenges and the therapeutic options, between old and emerging concepts, with a particular focus on the elderly.

Perspective: Practical Approach to Preventing Subclinical B12 Deficiency in Elderly Population

“…It is known that B12 levels tend to decline with age, but there are conflicting data about the real prevalence of deficiency in this population due to limitations, including: (i) the vast differences among subjects included in epidemiological studies, (ii) studies conducted in different age rages and ethnicity, (iii) food consumption (e.g., fortified food or not), (iv) presence or absence of morbidities, (v) absence of a gold standard test for measurement, and (vi) different biomarkers and cut-off levels considered by different authors [20,28]. Indeed, many studies considered only serum B12 levels alone (with different cut-offs), while others used vitamin B12 combination with additional serum biomarkers, like Hcy and/or MMA [27].…”

“…B12 can be administered orally and parenterally (intramuscularly). Other methods include subcutaneous, transdermal, sublingual and nasal formulations [28], although their role in clinical practice appears marginal, because of their variable effectiveness and higher costs [131]. As reported in a Cochrane review [27], oral vitamin B12 or vitamin B12 administered intramuscularly might have similar effects in normalizing B12 serum levels, but oral treatment costs less [27].…”

“…Oral B12 supplementation represents an easy route of administration, more comfortable for end users and effective in mild-moderate deficiency [131]. Furthermore, it is also more appropriate in patients on anticoagulant treatment, in whom intramuscular injections may be contraindicated [28]. Despite all benefits, it should be mentioned that severe clinical deficiencies (e.g., neurological symptom, critically low B12 levels) should be treated aggressively with injections, to promptly provide a fast restoration of B12 stores [131].…”

“…Holotranscobalamin (HoloTC) is considered a better biomarker for early changes in B12 status than serum cobalamin concentration [4], although it can be affected by inborn errors altering intracellular vitamin B12 metabolism [141]. On the other hand, Homocysteine (Hcy) plasma concentration is affected by many confounding factors especially in the elderly, including folate deficiency, B6 deficiency, sarcopenia and renal impairment [2,4,28,142]. Methylmalonic acid (MMA), is considered the most specific and sensitive measure of B12 status, yet such analysis is more costly and this reduces its clinical availability [2].…”

The influence of anaemia on pressure ulcer healing in elderly patients

“…There are other significant nutritional deficiencies which may cause anaemia such as a vitamin B12 (cobalamin) and a vitamin B9 (folate). Both are common nutritional disorders in the elderly caused by malnutrition, malabsorption, some chronic conditions and medication and may lead to macrocytic anaemia associated with an increased value of MCV and an impaired development of abnormally large erythrocytes -megaloblasts (Thomas, 2017;Marchi et al, 2020;Vadakattu et al, 2019;Watson, Lee & Garcia-Casal, 2018;Nagao & Hirokawa, 2017 ). However, macrocytic anaemia may also be non-megaloblastic if caused by specific conditions such as liver dysfunction, hypothyroidism or myelodysplastic syndrome but not by cobalamin or folate deficiency (Nagao & Hirokawa, 2017).…”