Hong Kong Med J 2015 Apr;21(2):155–64 | Epub 10 Mar 2015
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
REVIEW ARTICLE CME
Vitamin B12 deficiency in the elderly: is it worth screening?
CW Wong, FHKCP, FHKAM (Medicine)
Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo, Hong Kong
Corresponding author: Dr CW Wong (email@example.com)Full paper in PDF
Vitamin B12 deficiency is common among the elderly. Elderly people are particularly at risk of vitamin B12 deficiency because of the high prevalence of atrophic gastritis–associated food-cobalamin (vitamin B12) malabsorption, and the increasing prevalence of pernicious anaemia with advancing age. The deficiency most often goes unrecognised because the clinical manifestations are highly variable, often subtle and non-specific, but if left undiagnosed the consequences can be serious. Diagnosis of vitamin B12 deficiency, however, is not straightforward as laboratory tests have certain limitations. Setting a cut-off level to define serum vitamin B12 deficiency is difficult; though homocysteine and methylmalonic acid are more sensitive for vitamin B12 deficiency, it may give false result in some conditions and the reference intervals are not standardised. At present, there is no consensus or guideline for diagnosis of this deficiency. It is most often based on the clinical symptoms together with laboratory assessment (low serum vitamin B12 level and elevated serum homocysteine or methylmalonic acid level) and the response to treatment to make definitive diagnosis. Treatment and replacement with oral vitamin B12 can be as effective as parenteral administration even in patients with pernicious anaemia. The suggested oral vitamin B12 dose is 1 mg daily for a month, and then maintenance dose of 125 to 250 µg for patients with dietary insufficiency and 1 mg daily for those with pernicious anaemia. Vitamin B12 replacement is safe and without side-effects, but prompt treatment is required to reverse the damage before it becomes extensive or irreversible. At present, there is no recommendation for mass screening for vitamin B12 in the elderly. Nevertheless, the higher prevalence with age, increasing risk of vitamin B12 deficiency in the elderly, symptoms being difficult to recognise, and availability of safe treatment options make screening a favourable option. However, the unavailability of reliable diagnostic tool or gold standard test makes screening difficult to carry out.
Vitamin B12 deficiency is a common condition affecting the elderly and tends to increase with age. Acquirement of vitamin B12 into our body for cell metabolism involves dietary intake of vitamin B12–enriched foods and the absorption of vitamin B12 into our body for utilisation. The main dietary sources of vitamin B12 are animal products because animals obtain vitamin B12 through microbial symbiosis. The subsequent release of vitamin B12 from food for absorption into the body is complex and requires intact function of stomach, pancreas, and ileum. Pathophysiological changes, multiple co-morbidities, coupled with multiple drug intake, and increasing dependency associated with ageing can lead to malnutrition due to inadequate intake and malabsorption of vitamin B12, resulting in deficiency. Vitamin B12 is essential for the normal metabolism and functioning of all cells in the body. Vitamin B12 deficiency can pose significant adverse effects to organ systems with high cell turnover and metabolism like the bone marrow, gastro-intestinal tract, and brain. Fortunately, vitamin B12 deficiency can be readily treated by vitamin B12 replacement. Nevertheless, prompt diagnosis and treatment are required to prevent extensive and irreversible damage to the body.
Prevalence of vitamin B12 deficiency among the elderly
In general, vitamin B12 level declines with age and therefore prevalence of vitamin B12 deficiency increases with age.1 Studies have shown that prevalence of vitamin B12 deficiency among elderly can range between 5% and 40% depending on the definition of vitamin B12 deficiency used.1 2 3 4 5 6 7 Many studies have used serum vitamin B12 level with or without additional tests for its metabolites like homocysteine and methylmalonic acid (MMA) to estimate the prevalence of vitamin B12 in the population. The most frequent serum vitamin B12 cut-off to diagnose vitamin B12 deficiency is 150 pmol/L (203 pg/mL). Using this serum vitamin B12 cut-off alone, the prevalence of vitamin B12 deficiency is estimated to be in the range of 5% to 15%.3 4 5 6 However, when higher serum vitamin B12 cut-off at 258 pmol/L (350 pg/mL) or using elevated serum homocysteine or MMA level in addition to a low or low-to-normal serum vitamin B12 level to diagnose vitamin B12 deficiency, the prevalence of deficiency increases to 40.5%.1 3 Also, the prevalence of vitamin B12 deficiency appears to increase with age among the elderly population.4 5 Furthermore, reports have indicated that institutionalised elderly with multiple co-morbidities and with increasing dependency are more prone to vitamin B12 deficiency than non-institutionalised (free-living) elderly. In such individuals, the prevalence of vitamin B12 deficiency has been reported to reach 30% to 40%.8 9 In our unpublished study on 2096 institutionalised elderly residents aged >65 years, the prevalence of serum vitamin B12 level of <150 pmol/L was 34.9%, whilst in another local study conducted on non-institutionalised (free-living) elderly residents aged over 70 years, the prevalence of vitamin B12 level of <140 pmol/L was only 6.6%.7
Diagnosis of vitamin B12 deficiency
There is no precise or ‘gold standard’ test to diagnose vitamin B12 deficiency. The diagnosis is usually based on identifying a low level of serum vitamin B12 with clinical evidence of deficiency, which responds to vitamin B12 replacement therapy. When there is a clinical suspicion of vitamin B12 deficiency, the initial laboratory assessment includes serum vitamin B12 levels, complete blood count, and blood film examination.10 11 12 Although the blood picture and classical finding of vitamin B12 is megaloblastic anaemia, often times this is not seen especially in mild cases of vitamin B12 deficiency. The investigations for vitamin B12 deficiency are traditionally recommended for patients with macrocytosis, but macrocytosis with or without anaemia is neither specific nor sensitive to confirm the diagnosis.10 11 12 The reason for this is that macrocytosis can also be found in other conditions like folate deficiency and myelodysplastic disorders, and up to 84% of cases would be missed if macrocytosis is used as the only parameter to screen for vitamin B12 deficiency.13
Tests to measure and quantify serum vitamin B12 levels in the body are readily available and inexpensive. However, the screening test has some limitations and drawbacks. The main drawback is that there is no universally accepted serum vitamin B12 cut-off to define deficiency although the value of <150 pmol/L (200 pg/mL) is often used, and at this serum vitamin B12 level or below, metabolites like serum homocysteine, serum and urine MMA, become elevated. The World Health Organization has suggested to use this cut-off to define vitamin B12 deficiency since the year 2008.14 However, some have argued that the cut-off value of 150 pmol/L is too low and inevitably does not reflect a sufficient level of vitamin B12 in the body, and more so the clinical symptoms of vitamin B12 deficiency like neurological symptoms can occur even if serum vitamin B12 is above 150 pmol/L. Thus, a higher cut-off value of 220 to 258 pmol/L (298-350 pg/mL) based on more sensitive indicators of vitamin B12 status like elevated serum homocysteine and MMA levels has been suggested.3 15 It should be noted that not all the vitamin B12 circulating in the blood is in metabolically active form and a low serum vitamin B12 level is not necessarily equivalent to tissue deficiency. The falsely low vitamin B12 level can be related to the disturbance in vitamin B12 metabolism but may not be associated with any tissue vitamin B12 deficiency. Such situations can occur in people with folate deficiency, multiple myeloma, and transcobalamin I deficiency.10 11 12 On the other hand, falsely normal serum vitamin B12 level may occur in the presence of liver disease, myeloproliferative disorder, congenital transcobalamin II deficiency, and intestinal bacterial overgrowth.10 11 12
When serum vitamin B12 results are normal but still the clinical suspicion of deficiency exists, additional ‘confirmatory testing’ may help to identify vitamin B12 deficiency. There is compensatory elevation of homocysteine and MMA levels preceding the drop in serum vitamin B12 level and these are regarded as more sensitive indicators of vitamin B12 deficiency than just low serum vitamin B12 level.11 12 16 17 Elevated serum homocysteine and MMA level (>3 standard deviations above the mean in normal subjects) has a sensitivity of 95.9% and 98.4%, respectively to diagnose vitamin B12 deficiency.16 However, the reference intervals for serum MMA and homocysteine are variable among different laboratories. Serum MMA of 100 to 750 nmol/L, urine MMA of 1 to 4 nmol/L, and serum homocysteine of 6 to 29 µmol/L are the reference ranges for most methods.10 If the normalisation of elevated serum homocysteine and MMA levels in response to vitamin B12 replacement therapy is used as a diagnosis of deficiency, up to 50% of patients may be missed when the diagnosis is based on low vitamin B12 level (150 pmol/L) alone.18 19 Rise in homocysteine level before increase in MMA is an early indicator of vitamin B12 deficiency. However, this is less specific than elevated MMA level for vitamin B12 deficiency, since such elevated homocysteine levels can occur even in vitamin B6 and folate deficiency states. Both homocysteine and MMA levels can be elevated in renal insufficiency, hypovolaemia, and inherited metabolic defects.12 Although elevated homocysteine and MMA levels can aid in the diagnosis of vitamin B12 deficiency in people with ‘normal’ serum vitamin B12 levels, there are concerns about these metabolite assays. Some have reported that serum MMA and homocysteine levels increase with age and the prevalence of elevated MMA and homocysteine levels is higher than the prevalence of low vitamin B12 or clinically evident vitamin B12 deficiency in the elderly.19 20 21 22 In this regard, using the assay for metabolites alone may result in overdiagnosis and overtreatment. The rationale for these findings is uncertain and some have suggested that it may be related to the increased prevalence of subclinical vitamin B12 deficiency in the elderly. Moreover, these add to the controversies about whether to use metabolite estimation as the initial test to diagnose vitamin B12 deficiency. Besides, other important considerations are that they are more expensive, not readily available, and reference intervals are not standardised. Currently, the initial test for vitamin B12 deficiency is to assess serum vitamin B12 levels, and only when there is low normal vitamin B12 level, metabolite assay is most often suggested.11 12 However, the consensus for vitamin B12 threshold levels for ordering the additional tests has not yet been reached.
In addition to elevation in homocysteine and MMA levels, a decrease in serum holotranscobalamin level is also considered an early marker for vitamin B12 deficiency. Holotranscobalamin is composed of vitamin B12 attached to a transport protein, transcobalamin II. It is a biologically active fraction of vitamin B12 that can be readily taken up by all cells and represents only 6% to 20% of total serum vitamin B12.23 In vitamin B12 deficiency, serum level of holotranscobalamin decreases even before elevation in homocysteine and MMA levels occurs.24 It has been shown that holotranscobalamin is the most sensitive marker for vitamin B12 deficiency, followed by MMA.23 25 Like homocysteine and MMA, holotranscobalamin cannot be tested in renal patients as its level increases in renal impairment.23 Furthermore, higher cost and lesser availability than homocysteine and MMA testing make it difficult to acquire wide clinical acceptance.
Causes of vitamin B12 deficiency in the elderly
As we know elderly people are particularly at risk of vitamin B12 deficiency. The main aetiologies can be divided under two main categories: inadequate dietary intake and impaired absorption of vitamin B12 (Table 1).
It is believed that in developed countries, the most common cause for vitamin B12 deficiency in the elderly is inadequate dietary intake.1 15 However, studies have shown that this is far from real. A French study showed that among 172 elderly patients with vitamin B12 deficiency, only 2% accounted for inadequate intake,26 while in a hospital-based Chinese study on 52 patients, only 3.8% (median age, 73.5 years) with megaloblastic anaemia (98% had vitamin B12 deficiency) had inadequate dietary intake.27 However, this can be a problem in strict vegans because animal products are the only dietary source of vitamin B12. Usually, 2 to 3 mg of vitamin B12 reserves are stored in the body primarily in the liver, and our daily requirement of vitamin B12 is only about 2 to 3 µg. Thus, even with vegan diets, deficiency generally takes several years to develop. According to a local study on 119 older Chinese vegetarian women, the prevalence of deficiency was 42%.28 Besides, factors like poor health conditions, especially in those living in institutions, lead to inadequate nutritional intake and vitamin B12 deficiency.
Often, vitamin B12 deficiency can be seen even among the elderly consuming meat and animal proteins and this is because of malabsorption. Vitamin B12 in animal food is bound to a protein, and after ingestion, it is broken down in the stomach by pepsin and hydrochloric acid to release free vitamin B12 (Fig 129). The free vitamin B12 is then bound to R-protein (transcobalamin I) found in saliva and gastric juice. The vitamin B12-R-protein complex is also secreted in bile from the enterohepatic circulation. These complexes are then degraded by pancreatic enzyme to release free vitamin B12 in the duodenum. The free vitamin B12 is then bound to intrinsic factor secreted by the gastric parietal cells, and then they travel undisturbed until the distal 80 cm of ileum where they bind to mucosal cell receptors. Subsequently, vitamin B12 is carried by transport protein, transcobalamin, via the portal system to all cells in the body for utilisation. About 60% of vitamin B12 from food is absorbed through this pathway, and any pathophysiological changes in stomach, pancreas, and intestine result in disturbance of vitamin B12 absorption. Food-cobalamin (vitamin B12) malabsorption, first described by Carmel in 1995,30 is the most common cause of vitamin B12 deficiency in the elderly and accounts for about 40% to 70% of cases.26 29 31 It is characterised by the inability to release vitamin B12 from food or from its binding protein and thus, preventing vitamin B12 from being taken up by intrinsic factor for absorption. It is defined by vitamin B12 deficiency in the presence of sufficient dietary vitamin B12 intake, negative Schilling test, and lack of anti-intrinsic factor antibodies.30 Clinically, it is diagnosed by exclusion of other disorders or factors causing vitamin B12 deficiency. It can be corrected simply with oral vitamin B12 supplement since free vitamin B12 absorption is not affected.31 Any process that interferes with the release of free vitamin B12, such as decreased production of gastric acid and pepsin for releasing vitamin B12 from food, and impaired secretion of pancreatic enzyme for releasing vitamin B12 from vitamin B12-R-protein complex, can lead to malabsorption. Atrophic gastritis is the main cause of food-cobalamin malabsorption in the elderly. In the stomach, hypochlorhydria associated with atrophic gastritis interferes with vitamin B12 release from the food and causes intestinal bacterial overgrowth to compete for vitamin B12 uptake, resulting in a decline in vitamin B12 in the body. The prevalence of atrophic gastritis in the elderly ranges from 20% to 50% and generally increases with age.26 32 According to Framingham Heart Study, the prevalence in age-group of 60 to 69 years was 24% and increased to 37% in people aged >80 years.33 Chronic Helicobacter pylori infection is strongly associated with atrophic gastritis,34 35 and a study reported that H pylori was found in 56% of people with vitamin B12 deficiency.35 Other causes of food-cobalamin malabsorption include long-term consumption of proton pump inhibitors,36 histamine H2 blockers,36 chronic alcohol consumption, gastric bypass surgery, and pancreatic insufficiency in patients with alcohol abuse and cystic fibrosis. Food-cobalamin malabsorption often produces a slow, progressive depletion of vitamin B12. Clinical manifestations tend to be subtle and mild,2 although progression to more severe form, like pernicious anaemia (PA), can still occur in a minority of patients.26
Pernicious anaemia, a result of autoimmune atrophic gastritis (type A atrophic gastritis), is most often diagnosed in the elderly. Earlier studies suggested that PA was restricted to Northern Europeans, but subsequent studies indicate that PA affects virtually all ethnic groups.37 Pernicious anaemia was considered a classical cause of vitamin B12 deficiency before food-cobalamin malabsorption was described, and accounted for 15% to 25% of vitamin B12 deficiency in the elderly in studies.9 In a local study on 296 Chinese patients, definite PA was diagnosed in 61% of patients having megaloblastic anaemia with vitamin B12 or folate deficiency.38 Pernicious anaemia is characterised by destruction of gastric mucosa, especially fundal mucosa, primarily by a cell-mediated mechanism.39 There is progressive destruction and eventual loss of intrinsic factor producing gastric parietal cells. Moreover, auto-antibodies in gastric juices bind and block the vitamin B12–binding site of intrinsic factor and prevents the uptake of vitamin B12. The end result is gastric atrophy and depletion of intrinsic factor leading to poor absorption of food-bound, free, and biliary vitamin B12.2 Malabsorption is more complete and severe in PA compared to food-cobalamin malabsorption which is more partial in nature,2 and so the manifestations are more overt and severe in PA. Two antibodies, anti-parietal cell antibody and anti-intrinsic factor antibody, have been described in PA. Anti-parietal cell antibody is more sensitive (90%) but less specific (50%) for diagnosis of PA as it can also be found in other autoimmune diseases.29 39 On the other hand, anti-intrinsic factor antibody is less sensitive (50%) but more specific (98%), and its presence is almost diagnostic of PA.29 39 Schilling test, traditionally used to diagnose intrinsic factor–related malabsorption, is now rarely performed. Although PA is associated with excess risk of gastric carcinoma and gastric carcinoid tumour,40 the benefit of endoscopic surveillance has still not been established. Once the patient is diagnosed with PA, single endoscopic screening for gastric cancer or carcinoid tumours is recommended, but subsequent routine endoscopic surveillance recommendation is inconclusive.41
In the elderly, long-term use of medications for co-morbidities can interfere or reduce vitamin B12 absorption. These include proton pump inhibitors and histamine H2 blockers, which suppress gastric acid secretion and prevent release of vitamin B12 from food.42 Other drugs like metformin reduces intestinal availability of free calcium ions for vitamin B12–intrinsic factor complex uptake by ileal cell membrane receptors,43 and cholestyramine interferes with vitamin B12 absorption from intestine.44
Clinical manifestations of vitamin B12 deficiency
Vitamin B12 is essential for metabolism of all cells in our body. In humans, two enzymatic reactions are dependent on vitamin B12—methylmalonyl coenzyme A mutase (MUT) reaction and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) reaction (Fig 2). The MUT reaction is an important step in the extraction of energy from protein and fat in the mitochondrial citric acid cycle. In the MTR reaction, vitamin B12 and folic acid are required for the conversion of homocysteine to methionine that is important for maintaining the integrity of nervous system. Tetrahydrofolate is also regenerated via the MTR reaction for DNA synthesis. Hence, in vitamin B12 deficiency, multi-organ systems can be affected and hence associated with wide spectrum of clinical manifestations. However, clinically overt vitamin B12 deficiency with classical feature of macrocytic anaemia and neuropathy is infrequently seen in the elderly.2 Very often they have mild, subclinical deficiency, which are usually asymptomatic.2
Clinical manifestations of vitamin B12 deficiency are usually non-specific and are highly variable according to severity or organ systems involved.9 There is no one clinical feature unique to all patients with vitamin B12 deficiency. Non-specific symptoms and signs are loss of appetite, diarrhoea, fatigue and weakness, shortness of breath, low blood pressure, confusion, and change in mental states.9 29 Classical manifestations include Hunter’s glossitis, megaloblastic anaemia, and subacute combined degeneration of spinal cord (Table 29).
Vitamin B12 deficiency and atherosclerotic vascular disease
Hyperhomocysteinaemia, as an independent risk factor for cardiovascular disease, has been receiving increased attention. Elevated homocysteine level is associated with an increased risk for atherosclerotic and thrombotic events.45 Meta-analysis of 30 studies involving 5073 ischaemic heart disease (IHD) events suggested that elevated homocysteine level was at most a modest independent predictor of IHD and stroke risk in healthy populations, and a 25% reduction in homocysteine levels was associated with 11% and 19% reduction in IHD and stroke, respectively.46 Another meta-analysis also provided a strong evidence of the causal association between homocysteine and cardiovascular disease, and showed that lowering homocysteine level by 3 µmol/L could reduce the risk of IHD by 16% and stroke by 24%.47
Vitamin B12, folic acid, and vitamin B6 are required for homocysteine metabolism, and often nutritional deficiency of these vitamins can cause hyperhomocysteinaemia. In contrast to severe hyperhomocysteinaemia associated with genetic disorders, hyperhomocysteinaemia resulted from nutritional deficiency is mild but is still associated with increased risk of atherothrombosis. The proposed mechanism for hyperhomocysteinaemia on inducing endothelial dysfunction and thus atherosclerosis includes homocysteine-induced endoplasmic reticulum stress, oxidative stress, and proinflammatory response.48 Animal models of hyperhomocysteinaemia have confirmed the causal relationship between hyperhomocysteinaemia and the development of endothelial dysfunction and accelerated atherosclerosis.48
Although meta-analyses have shown reduction of cardiovascular risk with reduction of homocysteine levels,46 47 vitamin supplementation (with vitamin B6, vitamin B12, and folic acid) to lower homocysteine in the body may not be transformed into clinically beneficial vascular outcomes. In a double-blind, randomised controlled trial of 3680 adults with non-disabling cerebral infarction, subjects who received a combination of vitamin B6, vitamin B12, and folic acid showed moderate reduction in total homocysteine levels, but there was no effect on vascular outcomes (recurrent ischaemic stroke and coronary heart disease) during 2 years of follow-up.49 Probably a longer duration of treatment may be necessary or there may be other factors governing the clinical response. Therefore, we need more controlled trials to explore the vascular benefits of vitamin supplementation.
Vitamin B12 deficiency and neuropsychiatric illness
Neuropsychiatric manifestations in the absence of haematological abnormalities are commonly seen in the elderly.2 50 These include paraesthesia, weakness, gait abnormalities, and cognitive or behavioural changes. Although the exact mechanism of how vitamin B12 deficiency causes neuropsychiatric disorder is unclear, the disruption of both MUT and MTR vitamin B12–dependent reactions seem to play a role. Vitamin B12 deficiency disrupts MUT reaction with accumulation of MMA; MMA is a myelin destabiliser and can affect normal myelin formation. Besides, disruption of MTR reaction leads to insufficient supply of methionine and S-adenosylmethionine (SAM), which is essential for the myelination of myelin sheath, phospholipids and neurotransmitter synthesis, for maintaining brain and nervous system function.51 Furthermore, high levels of homocysteine due to vitamin B12 deficiency are associated with an increased risk of atherosclerotic vascular disease, and this in turn may increase the risk of cognitive impairment or dementia. It has been shown that low serum vitamin B12 is associated with a 2- to 4-fold higher risk of cognitive impairment.50 The prevalence of low serum vitamin B12 has been reported to be significantly higher in the people with Alzheimer’s disease (AD).52 However, the causal relationship between vitamin B12 deficiency and the development of AD remains controversial. Amyloid deposition and hyperphosphorylation of tau protein are believed to be involved in the mechanism of AD. The SAM-dependent methylation is involved in the regulation of mechanism of presenilin I expression, γ-secretase activity, and thus amyloid levels; SAM is also involved in the regulation of tau phosphorylation.51 Moreover, hyperhomocysteinaemia has been shown to be associated with a significant increase in amyloid level and amyloid deposition on cortex and hippocampus in mouse models of AD.53 Overall, vitamin B12 deficiency may have implications in the neuropathological process of AD.
Depression is a common psychiatric manifestation of vitamin B12 deficiency. Involved in the synthesis of neurotransmitters, SAM may be implicated in mood disorders. In a population-based study of 3884 elderly people, deficiency of vitamin B12 was associated with almost 70% more likelihood of having a depressive disorder.54 In another cross-sectional study of 700 community-dwelling, physically disabled women aged ≥65 years, vitamin B12–deficient women were twice more likely to have severe depressive symptoms.55 Although controlled studies to show response to vitamin B12 replacement therapy in depression are lacking, it is recommended that all patients with vitamin B12 deficiency should be managed as part of depression treatment. Psychosis, including delusion and hallucination, has also been reported in vitamin B12–deficient patients. Although the exact mechanism is unknown, vitamin B12 replacement even after a prolonged period (at least up to 2 years) has shown good outcomes in patients with psychosis.56
In general, vitamin B12 replacement therapy helps to reverse the haematological abnormalities and psychiatric disorders. However, even after correcting serum vitamin B12 and its metabolite levels, or haematological abnormalities, the ability to reverse cognitive impairment (dementia) and neurological disorders is not promising.50 51 52 The longer the time the neurological disorder or cognitive impairment presents before treatment, the less likely it can be reversed. It is suggested that prompt correction of deficiency should be done within 6 to 12 months of cognitive impairment in order to obtain maximum response.57 Nevertheless, continuous replacement therapy may still help to prevent symptoms from deteriorating. Treatment for subtle or subclinical deficiency is still debatable although prompt diagnosis and treatment might prevent the progress to clinically overt deficiency.
Classical treatment for vitamin B12 deficiency is parenteral administration, usually intramuscular injection, to correct the deficiency and build up tissue storage. There are two forms of vitamin B12 for parenteral administration: cyanocobalamin and hydroxocobalamin. It is believed that hydroxocobalamin is converted to active enzyme more easily and retained in the body for a longer period of time than cyanocobalamin, and therefore be administered in intervals of 3 months. The regimen for vitamin B12 therapy varies across countries and between individual practices. Generally, the schedule for vitamin B12 replacement is 1 mg daily for a week or 1 mg 3 times a week for 2 weeks, followed by 1 mg per week for 1 month, and then 1 mg per month as maintenance dose.9
Around 1% to 5% of free vitamin B12 can be absorbed along the entire intestine by passive diffusion. Oral vitamin B12 replacement is theoretically as effective as parenteral administration even in patients with PA or ileal disease, provided that the dosage is high. However, the unpredictable absorption by passive diffusion makes recommendation of a standard dose difficult. A Cochrane review supports the use of high-dose vitamin B12 (1 mg and 2 mg daily) in elevating serum vitamin B12 level and achieving haematological and neurological responses, even in patients with PA or with ileal resection.58 The recommendation for oral replacement is 1 mg daily for a month, and then 125 to 250 µg daily as maintenance dose for patients with dietary insufficiency and food-cobalamin malabsorption, while for PA the maintenance dose is 1 mg daily.29
Vitamin B12 does not have side-effects even when prescribed in large doses.59 However, hypokalaemia, resulting from uptake of circulating potassium by newly growing and dividing haematopoietic cells, can be severe or sometimes life-threatening. Transient potassium replacement at the initial stage of vitamin B12 replacement, especially in those with low-normal serum potassium, can prevent subsequent hypokalaemia.
Correction of risk factors associated with vitamin B12 deficiency, like antibiotics for H pylori infection and intestinal bacterial overgrowth, stopping or replacing offending medications are also important in the management and prevention of vitamin B12 deficiency. Some institutions have even recommended universal vitamin B12 supplement for people aged ≥60 years in view of the high prevalence of vitamin B12 deficiency among this popualation.15
Vitamin B12 deficiency is prevalent among the elderly. Elderly people are particularly at risk of deficiency because of the increasing prevalence with increasing age of atrophic gastritis–associated food-cobalamin malabsorption, PA, and due to drug intake for co-morbidities. Symptoms and signs of vitamin B12 deficiency are usually vague and unrecognised. Treatment may always be useful to correct clinical abnormalities like vitamin B12–related haematological abnormalities, psychiatric and depressive symptoms. For neurological disease and dementia, prompt vitamin replacement is necessary before it becomes irreversible or permanent. Both oral and parenteral administration of vitamin B12 are effective and without untoward side-effects. Overall, we are in support of screening for vitamin B12 deficiency in the elderly. However, accurate diagnosis of vitamin B12 deficiency remains controversial. To diagnose vitamin B12 deficiency, laboratory tests have their limitations, and this makes it difficult to choose a reliable and easily available tool for screening. Although there is no formal recommendation for screening for vitamin B12 deficiency in asymptomatic elderly people, the high prevalence, higher risk of deficiency in the elderly, easy and safe treatment availability warrant more liberal testing and vitamin supplementation in the elderly.
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