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Risk groups for vitamin B12 deficiency

The prevalence of subclinical functional B12 deficiency is higher than assumed when sensitive and relatively specific markers are used, such as MMA, holoTC, and tHcy. Risk groups for B12 deficiency include: patients with unexplained anemia, patients with unexplained neuropsychiatric symptoms, patients with gastrointestinal manifestations (including stomatitis, anorexia, and diarrhea), elderly people (1), vegetarians (2), alcoholics, patients with gastrointestinal disorders (such as Crohn's disease or infection with Helicobacter pylori), or patients with stomach resection.

The number of people with subclinical deficiency who may develop clinical symptoms has thus far not been studied systematically. In the general population, the prevalence of B12 deficiency in younger people is about 5 – 7% (3). Functional B12 deficiency (that is high MMA and low holoTC) has been found in 10 – 30% of patients older than 65 years of age (1). A high prevalence of a slightly abnormal B12 status has been reported in elderly people, despite intake of the recommended daily dose (> 2.4 µg/d). In most cases, the deficiency is related to B12 malabsorption.

Persons with an increased vitamin requirement are a further risk group for B12 deficiency for example, pregnant and breast feeding women, patients with autoimmune disorders, or persons with HIV infection. Persons who regularly take proton pump inhibitors can also develop B12 deficiency.

Dietary vitamin B12 deficiency

The recommended dietary intake (RDI) of B12 of 2.4 μg can be met from a typical western diet. Vitamin B12 is conserved in human through the enterohepatic circulation and via an active reabsorption in the proximal tubule (4). In case of an intact absorption of the vitamin, the depletion takes years to be manifested as a metabolic or a clinical dysfunction. Natural sources of B12 in human diet are restricted to foods of animal origin. On the contrary, subjects ingesting mainly or exclusively plant-based diet may develop a deficiency (5). A strict vegetarian individual, also called vegan, consumes theoretically no B12 unless this micronutrient is supplied as crystalline B12 from fortified foods or vitamin pills.

Vegetarians are at high risk of developing B12 deficiency. A functional B12 deficiency (lowered holoTC, elevated MMA and tHcy) is common in vegetarians and depends on the strictness and the duration of the vegetarian diet. A study of lacto-vegetarians (LV) and lacto-ovo-vegetarians (LOV) found raised MMA (> 271 nmol/L) in 63% of subjects, lowered holoTC concentrations (< 35 pmol/L) in 73%, and HHCY (> 12 μmol/L) in 33%. In vegans, raised MMA was found in 86%, lowered holoTC in 90%, and HHCY in 55%. Vegan subjects, followed by LOV, had significantly lower B12 status compared to the omnivores. Vegetarians who had been consuming multivitamins that contain B12 had a slightly better metabolic profile than those who were not taking vitamins (2). However, low doses of B12 such as the one usually found in the multivitamin preparations were not likely to prevent the depletion of the vitamin in individuals who ingest little or no animal products (2).

Vitamin B12 deficiency and food malabsorption

Malabsorption of B12 is the most common cause for vitamin B12 deficiency in elderly people. B12 deficiency is typically observed in the presence of sufficient food B12 intake. This condition is characterized by failure to release B12 from food or from B12 binding proteins, particularly in the presence of hypochlorhydria where the absorption of ‘unbound’ B12 is normal. Sixty – 70% of elderly subjects with B12 deficiency suffer from food B12 malabsorption that is primarily seen in gastric atrophy. More than 40% of people over 80 years of age are affected by gastric atrophy that can be related to H. pylori infection. Factors which contribute to food B12 malabsorption in elderly subjects are as follows: chronic carriage of H. pylori and intestinal microbial proliferation after long-term antibiotic treatment, H2-receptor antagonists and proton pump inhibitors, chronic alcoholism, gastric surgery, partial pancreatic exocrine failure, and Sjögren’s syndrome. Type B chronic atrophic gastritis is related to H. pylori infection and is known to cause B12 malabsorption. This disease results in a low acid-pepsin production and food B12 malabsorption. The release of B12 from food protein is decreased in the case of lowered gastric acidity (6). Subjects with type B atrophic gastritis could benefit from crystalline B12, because the synthesis of IF is not affected. It has been reported that oral B12 therapy (3 – 5 mg/week) was effective in treatment of food B12 malabsorption (7). Celiac disease and tropical sprue are also associated with B12 deficiency because recurrent diarrhea causes severe damage to the gastrointestinal tract and interferes with B12 absorption by the enterocytes. Metformin treatment has been related to lower serum B12 (8). However, there is no evidence that metformin caused intracellular B12 deficiency or elevated concentrations of tHcy or MMA.

Vitamin B12 deficiency in elderly people

Vitamin B12 deficiency is common in elderly people and has gained a particular importance in recent years (1;9). The incidence of B12 deficiency in the elderly ranges between 10 – 40%, depending on the marker used to rule out the deficiency (10). Several age-related physiological factors could negatively influence the absorption of the vitamin from the intestine.

Causes of B12 deficiency in elderly people are usually not related to low intake of the vitamin, but to other physiological or pathophysiological conditions associated with aging. The bioavailability of B12 is affected by food matrices and co-administered compound like alcohol and medications. Moreover, the processing and absorption of the protein-bound B12 (food B12) is affected by many conditions in the gastrointestinal tract. For example, gastrointestinal pH, H. pylori infection, and malabsorption syndromes are common conditions causing B12 deficiency. In accordance with this, low dietary intake of B12 (< 2 μg) was recorded in only 1.7% in a study on elderly people (11). In contrast, elevated serum concentrations of MMA combined with lowered holoTC occur in a high proportion of older adults from industrial countries (1;12). This deficiency is presumed to be associated malabsorption. Fifty-three percent of elderly individuals from the Strasbourg study who had B12 deficiency had malabsorption problems, 33% had pernicious anemia (PA), and in only 2% B12 deficiency was related to insufficient dietary intake, and in 11% the etiology of the B12 deficiency remained unexplained (13). Approximately 2 – 3% of free living elderly people (> 60 years) had undiagnosed PA. Ethnic differences in the incidence of PA and the age of onset have been reported (14). Increasing the RDA for B12 for elderly people can reduce the incidence of B12-deficiency related to malabsorption. The relation between holoTC and MMA has been examined in relation to age and renal function (1). In general, elderly people display higher MMA concentrations in ranges of holoTC comparable with that in younger subjects. The latter findings suggest that cellular B12-delivery could be challenged in elderly with renal insufficiency, leading to MMA increment and holoTC retention.

There is currently no firm evidence showing that individuals expressing metabolic signs of B12 deficiency will transfer to severe deficient states. However, metabolic abnormalities related to B12 deficiency can be corrected by B12 supplementation. Diet modifications are less effective and reinforce the importance of metabolic maintenance on regular basis. Using synthetic B12 preparations can correct metabolic abnormalities in elderly persons.

References

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3.     Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med 2003;41:1478-88.
4.     Moestrup SK, Birn H, Fischer PB, Petersen CM, Verroust PJ, Sim RB et al. Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis
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