Abstract
Introduction
Cobalamin deficiency is frequent in elderly patients and the main aetiologies are foodcobalamin malabsorption and pernicious anaemia. The aim of our retrospective study was to identify the causes and methods of management of cobalamin deficiency at Nice geriatric university hospital.
Methods
A retrospective monocentric study was conducted over 14 months at Nice geriatric hospital, which included patients with cobalamin deficiency having received supplementation. The clinical and paraclinical data, etiological diagnosis, treatment and follow-up modalities were analyzed retrospectively.
Results
We studied 125 elderly patients whose median age was 85.5 ± 7 years. The etiological diagnosis was food-cobalamin malabsorption for 72 patients (57.6 %), nutritional cobalamin deficiency for 15 patients (12 %), pernicious anaemia for 12 patients (9.6 %) and there was no etiological diagnosis for 26 patients (20.8 %). Concerning cobalamin therapy, 111 patients (88.8 %) received oral therapy and 14 (11.2 %) intramuscular therapy. Vitamin B12 levels increased significantly after supplementation (p<0.001) but cobalamin administration varied according to the diagnoses (p<0.001) and was less effective in patients with dementia (p=0.04) and food-cobalamin malabsorption.
Conclusion
Our study showed the importance of food-cobalamin malabsorption in etiological diagnosis in accordance with the literature, but also the non-negligible share of nutritional cobalamin deficiency. Mainly oral cobalamin supplementation was used in our study with a significant increase in vitamin B12 levels. An oral cobalamin regimen is proposed for elderly patients with cobalamin deficiency but with no severe neurological signs.
Key words: Cobalamin deficiency, elderly, food-cobalamin malabsorption, nutritional, cobalamin deficiency, cobalamin supplementation
Introduction
Cobalamin deficiency is frequent in elderly patients, with a prevalence of 15-40% in patients 65 years and older (1), but is often unrecognized because of non-specific, polymorphic clinical manifestations (2, 3).
Cobalamin deficiency is often diagnosed in elderly patients in the presence of macrocytic anaemia or dementia (4). The main causes of cobalamin deficiency in elderly patients are food-cobalamin malabsorption (5), pernicious anaemia, nutritional cobalamin deficiency and post-surgical malabsorption (6). Oral cobalamin therapy is effective, as shown in several studies (7, 8), but the modalities of oral cobalamin supplementation in elderly as well as in younger adults are not clearly defined. Doses and durations have been proposed, especially for food-cobalamin malabsorption (9), but clinicians usually decide on the basis of their own experience. Our retrospective study aims at finding the causes of cobalamin deficiency in the acute and subacute care units at Nice geriatric hospital, but also describing the features of cobalamin supplementation in these elderly patients.
Patients and methods
This retrospective monocentric analytical study was conducted over 14 months (between September 2010 and November 2011) at Nice geriatric university hospital. All patients with serum cobalamin levels below 200 pg/mL, confirmed in two serum samples, with clinical and/or biological signs of cobalamin deficiency or with serum cobalamin levels below 160 pg/ml and who had received oral or intramuscular cobalamin therapy in the acute and subacute care units were enrolled in the study.
Age, gender, type of stay (acute care or subacute care unit), history of gastric or ileal surgery, alcoholism, blood diseases, the use of drugs such as proton pump inhibitors or metformin that may interfere with vitamin B12 absorption, clinical signs such as glossitis, confusion, dementia with the Mini Mental state examination (MMSE) score (abnormal if < 27/30) (10), stage of dementia and clinical signs of neuropathy were recorded for each patient.
Biochemical data included serum vitamin B12 levels before and after cobalamin therapy, the time between the end of vitamin B12 supplementation and new serum level measurement, folate levels, total blood cell count, mean corpuscular volume, serum iron levels, ferritin levels, serum creatinine levels, creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) formula, albumin levels, C-reactive protein (CRP) levels, gastrin and total homocysteine levels, anti-intrinsic factor and antiparietal cell antibody levels. Other data included bone marrow examinations and results of gastroscopies and gastric biopsies when available.
A nutritional profile was established for each patient. The body mass index (BMI) and Mini Nutritional Assessment (MNA) score (11) were calculated and the prospective energy intake was recorded for each patient.
The causes of cobalamin deficiencies were obtained from the hospital records. Treatment data and vitamin B12 levels after cobalamin supplementation were analyzed when available.
Quantitative variables were expressed as the median or mean ± standard deviation (SD) and range, and results of qualitative variables were expressed in absolute values and as percentages. To compare groups, we used comparison tests for quantitative variables, and the chi-squared and Fisher exact tests for qualitative variables. For these tests p < 0.05 values were considered as significant.
Results
Clinical data
The population studied at Nice geriatric university hospital over 14 months included 125 patients of which 64 % were women. The median patient age was 85.5 ± 7 years (range: 64-102 years). Seventy-three patients (58.4 %) were from the acute-care unit and 52 patients (41.6 %) from the subacute care unit.
Regarding the patients’ medical history, 7 patients (5.6%) had undergone gastric surgery, 5 patients (4 %) had alcoholism and 9 patients (7.2 %) had a blood disease. Among the treatments, 16 patients (12.8 %) were on long-term metformin for diabetes mellitus, 6 patients (4.8 %) were on long-term ranitidine and 41 patients (32.8 %) were on long-term omeprazole therapy for gastric disease.
Concerning the clinical signs, no patients had glossitis, 38 patients (30.4 %) had clinical signs of asthenia, oedema on the legs and dyspnoea, 6 patients (4.8 %) had signs of neuropathy, 15 patients (12 %) had confusion and 53 patients (42.7 %) had dementia.
The median MMSE score was 20.4 ± 5.8. Fifty patients (40%) had malnutrition of which 11 severe (9.7 %). The mean MNA score was 18 ± 4 (73/125 patients had MNA).
The energy intake/weight ratio was less than 30 Kcal/kg/day in 90 patients (72 %), over 30 Kcal/kg/day in 23 patients (18.4%) and undetermined in 12 patients (9.6 %). When aetiology was nutritional cobalamin deficiency, 86.7 % of patients have less than 30 Kcal/kg/day.
Laboratory and endoscopy data
Serum vitamin B12 levels, folate, iron, ferritin, gastrin, homocysteine and creatinine levels, anti-intrinsic factor and anti-parietal cell antibodies for all patients and for 61 patients whose vitamin B12 levels were controlled after cobalamin therapy are summarized in Table 1.
Table 1.
Laboratory tests and gastroscopy in 125 patients
| Paraclinical tests | Patients (n=125) | Normal laboratory values |
|---|---|---|
| Mean serum vitamin B12 (pg/ml) | 144,7 ± 36,7 | 200-1000 |
| Mean serum folate (ng/ml) | 7,4 ± 4,4 | 3-18 |
| Hb (g/dl) | 11,5 ± 2 | 12-14,5 |
| Mean corpuscular volume (fl) | 90,9 ± 11,5 | 80-95 |
| Platelets (103/mm3) | 265,08 ± 105,56 | 150-400 |
| Leukocytes(103/mm3) | 7110,4 ± 2841,1 | 4000-10000 |
| Mean serum iron (µmol/l) | 10,1 ± 6,8 | 11-29 |
| MDRD clearance (ml/min) | 80,5 ± 33,6 | >60 |
| Mean serum albumin (g/l) | 34,4 ± 5,2 | 33-50 |
| Anti-parietal cell antibodies | n=84 | |
| -positive | 23 (27,4%) | |
| Anti-intrinsic factor antibodies | n=22 | |
| -positive | 5 (22,7%) | |
| Mean serum gastrin (ng/l) | n=61 | 20-80 |
| -increased | 24 (19,2%) | |
| Mean serum homocysteine (µmol/l) | n=23 | <12 |
| -increased | 22(95,7%) | |
| Gastroscopy | n=10 | |
| -atrophic gastritis | 4 | |
| -pernicious anemia | 6 | |
| Bone-marrow aspiration | n=8 | |
| -mégaloblastosis |
5 |
Haematological abnormalities were anaemia in 82 patients (65.6 %; Hb <11g/dl) with macrocytosis in 28 % of cases (mean corpuscular volume > 98 fl), thrombocytopenia in 11 patients (8.8 %; platelets <150000/mm3), and leucopoenia in 3 patients (2.4 %; leukocytes <4000/mm3).
Anti-parietal cell antibodies were positive in 23/84 patients (27.4 %) and anti-intrinsic factor antibodies were positive in 5/22 patients (22.7 %). Gastrin and homocysteine levels were higher in 24/61 patients (19.2 %) and 22/23 patients (95.7 %) respectively.
Gastroscopy showed pernicious anaemia in 6/10 patients and confirmed gastric atrophy in other cases. Bone marrow examinations confirmed the diagnosis of cobalamin deficiency with megaloblastosis in 5/8 patients.
According to the chi-squared test, anti-parietal cell antibodies were significantly more often positive in patients whose vitamin B12 levels were <149 pg/ml than in patients with vitamin B12 levels >150 pg/ml (p=0.001). Gastrin levels were significantly more often normal for vitamin B12 levels >150 pg/ml than for vitamin B12 levels <149 pg/ml (p=0.008). Patients with vitamin B12 levels <149 pg/ml were significantly less malnourished than patients with vitamin B12 levels >150 pg/ml (p=0.04).
Diagnostics
The causes of cobalamin deficiency were food-cobalamin malabsorption in 72 patients (57.6 %), of undetermined aetiology in 26 patients (20.8 %), nutritional cobalamin deficiency in 15 patients (12 %) and pernicious anaemia in 12 patients (9.6%) (Table 2).
Table 2.
Characteristics of elderly patients with cobalamin deficiency according to the diagnosis
| Pernicious anemia (n=12) | Food-cobalamin malabsorption (n=72) | Nutritional deficiency (n=15) | Undetermined (n=26) | p | |
|---|---|---|---|---|---|
| Age | 80,4 ± 8,1 | 86,3 ± 6,1 | 85,6 ± 7,8 | 85,4 ± 7,5 | N.S. |
| Gender | |||||
| - Female | 9 (75 %) | 45 (62,5 %) | 10 (66,7 %) | 16 (61,5 %) | N.S. |
| - Male | 3 (25 %) | 27 (37,5 %) | 5 (33,3 %) | 10 (38,5 %) | |
| Mean serum Vitamin B12 (pg/ml) | 121,4 ± 46,5 | 145,3 ± 34,1 | 155,3 ± 33,6 | 147,4 ± 38,4 | N.S. |
| Controlled mean serum vitamin B12 (pg/ml) | 356,1 ± 437,5 | 379,0 ± 388,0 | 280,6 ± 119,8 | 283,0 ± 152,0 | N.S. |
| Mean serum folate (ng/ml) | 10,4 ± 4,8 | 7,2 ± 4,1 | 6,6 ± 5,7 | 6,8 ± 3,8 | N.S. |
| Hb (g/dl) | 11,9 ± 1,7 | 11,6 ± 2,0 | 10,0 ± 1,6 | 11,9 ± 2,2 | 0,002 |
| Controlled Hb (g/dl) | 11,5 ± 1,0 | 10,9 ± 1,0 | 10,2 ± 0,7 | 10,7 ± 1,1 | N.S. |
| Mean corpuscular volume (fl) | 94,3 ± 11,9 | 90,1± 12,2 | 93,0 ± 4,4 | 90,6 ± 10,7 | N.S. |
| Mean serum iron (µmol/l) | 8,8 ± 4,9 | 10,0 ± 6,0 | 9,7 ± 9,2 | 11,1 ± 7,7 | N.S. |
| Clearance MDRD (ml/min) | 87,3 ± 28,9 | 81,3 ± 35,7 | 86,9 ± 34,6 | 71,6 ± 28,7 | N.S. |
| Mean serum albumin (g/l) | 38,3 ± 6,0 | 34,6 ± 4,6 | 29,2 ± 5,1 | 35,1 ± 4,4 | <0,001 |
| Severity of the deficiency (pg/ml) | |||||
| Between 200 and 150 | 3 (25 %) | 40 (55,6 %) | 10 (66,7 %) | 13 (50 %) | N.S. |
| Between 149 and 100 | 4 (33,3 %) | 24 (33,3 %) | 4 (26,7 %) | 10 (38,5 %) | |
| <99 | 5 (41,7 %) | 8 (11,1 %) | 1 (6,7 %) | 3 (11,5 %) | |
| Folate deficiency | |||||
| - Yes | 0 (0 %) | 4 (5,6 %) | 2 (13,3 %) | 0 (0 %) | N.S. |
| - No | 12 (100 %) | 66 (91,7 %) | 13 (86,7 %) | 23 (88,5 %) | |
| - Undetermined | 0 (0 %) | 2 (2,8 %) | 0 (0 %) | 3 (11,5 %) | |
| Iron eficiency | |||||
| - Yes | 2 (16,7 %) | 16 (22,2 %) | 8 (53,3 %) | 7 (26,9 %) | N.S. |
| - No | 5 (41,7 %) | 24 (33,3 %) | 4 (26,7 %) | 13 (50 %) | |
| - Undetermined | 5 (41,7 %) | 32 (44,4 %) | 3 (20 %) | 6 (23,1 %) | |
| BMI | 24,3 ± 5,9 | 23,3 ± 4,7 | 21,6 ± 4,7 | 23,4 ± 4,2 | N.S. |
| MNA | 19,4 ± 3,5 | 18,2 ± 4,2 | 16,3 ± 1,9 | 17,9 ± 4,7 | N.S. |
| Malnutrition | |||||
| - Yes | 2 (16,7 %) | 33 (45,8 %) | 6 (40 %) | 9 (34,6 %) | 0,001 |
| - No | 10 (83,3 %) | 37 (51,4 %) | 2 (13,3 %) | 14 (53,8 %) | |
| - Undetermined | 0 (0 %) | 2 (2,8 %) | 7 (46,7 %) | 3 (11,5 %) | |
| Energy intake/weight | |||||
| -<30 Kcal/kg/day | 8 (66,7 %) | 51 (70,8 %) | 13 (86,7 %) | 18 (69,2 %) | 0,007 |
| ->30 Kcal/kg/day | 2 (16,7 %) | 16 (22,2 %) | 0 (0 %) | 5 (19,2 %) | |
| -Undetermined | 2 (16,7 %) | 5 (6,9 %) | 2 (13,3 %) | 3 (11,5 %) | |
| MMSE | 20,0 ± 8,0 (n=4) | 20,4 ± 5,3 (n=37) | 21,2 ± 8,9 (n=5) | 20,3 ± 5,9 (n=15) | N.S. |
| Dementia | |||||
| - Yes | 4 (33,3 %) | 30 (41,7 %) | 5 (33,3 %) | 14 (53,8 %) | N.S. |
| - No | 7 (58,3 %) | 42 (58,3 %) | 10 (66,7 %) | 12 (46,2 %) | |
| - Undetermined | 1 (8,3 %) | 0 (0 %) | 0 (0 %) | 0 (0 %) | |
| Confusion | |||||
| - Yes | 0 (0 %) | 11 (15,3 %) | 1 (6,7 %) | 5 (19,2 %) | N.S. |
| - No | 12 (100 %) | 61 (84,7 %) | 14 (93,3 %) | 21 (80,8 %) | |
| Route of supplementation | |||||
| - Intramuscular | 6 (50 %) | 6 (8,3 %) | 0 (0 %) | 2 (7,7 %) | <0,001 |
| - Oral |
6 (50 %) |
66 (91,7 %) |
15 (100 %) |
24 (92,3 %) |
When the aetiology was food-cobalamin malabsorption, there were several associated conditions: 5.6 % patients had atrophic gastritis, 9.7 % had undergone gastric surgery, 5.6 % suffered from chronic alcohol consumption, 40.3 % were on long-term acid-suppressive drugs, 18.1 % were on long-term metformin and 26.4 % were idiopathic.
Hb levels differed significantly according to the diagnosis (p=0.002): Hb levels were lower in patients with nutritional cobalamin deficiency versus pernicious anaemia (p=0.007), food-cobalamin malabsorption (p=0.006) and undetermined aetiology (p=0.008).
Patients with vitamin B12 levels <149 pg/ml were less malnourished than patients with vitamin B12 levels >150 pg/ml (p=0.03).
Patients whose diagnosis was pernicious anaemia were significantly younger than patients with food-cobalamin malabsorption (p=0.03), were less malnourished (p=0.03) and had lower vitamin B12 levels (p=0.04).
Albumin levels differed significantly depending on the aetiology of the cobalamin deficiency (p<0.001), with lower albumin levels in patients with nutritional cobalamin deficiency (p<0.001), food-cobalamin malabsorption (p=0.002) and undetermined aetiology (p=0.001) (Table 2).
Energy intake/weight ratios differed significantly according to the diagnosis (p=0.007). The energy intake/weight ratio was lower in patients with nutritional cobalamin deficiency (p=0.001) versus others diagnoses.
Therapeutic modalities
One hundred and eleven patients (88.8 %) were treated with oral cyanocobalamin and 14 (11.2 %) were treated with intramuscular cyanocobalamin. In the case of intramuscular therapy, two regimens were used: regimen 1: 1000 µg/day for 1 week and then 1000 µg/month; regimen 2: 1000 µg three times/week for 1 month and then 1000 µg/month.
Oral regimens were: regimen 3: 1000 µg/day for 1 month; regimen 4: 1000 µg/day for 15 days, then 1000 µg/10 days for 1 month and then 1000 µg/month for 2 months; regimen 5: 1000 µg three times /week for 1 month; regimen 6: 1000 µg/day for 1 week and regimen 7: 1000 µg/week for 1 month.
Regimen 4 was used in 80,3 % of patients in this study.
The mean Hb level after therapy was 10.8 ± 1g/dl. The mean vitamin B12 level after therapy was 353.4 ± 343.7 pg/ml. When cobalamin therapy was intramuscular, vitamin B12 levels increased from 117.4 ± 49 to 730.9 ± 711.5 pg/ml and with oral cobalamin therapy vitamin B12 levels increased from 141.33 ± 35.1 to 279.4 ± 128.5 pg/ml. According to comparison tests, vitamin B12 levels after supplementation increased significantly (p<0.001) with intramuscular (p=0.02) and oral therapy (p<0.001).
According to comparison tests, vitamin B12 levels <149 pg/ml were treated much better by intramuscular administration than vitamin B12 levels >150 pg/ml (p=0.03).
When gastrin levels were normal, vitamin B12 levels significantly increased after supplementation (p=0.01).
The method of administration differed significantly according to the aetiology (p<0.001); intramuscular therapy was used more often with pernicious anaemia. When the aetiology was food-cobalamin malabsorption, supplementation was less effective when patients had dementia (p=0.04).
Discussion
Our retrospective study highlighted the various causes of cobalamin deficiency in the elderly with a high prevalence of food-cobalamin malabsorption (57.6 %) in accordance with the literature (12). This syndrome is characterized by the inability to release vitamin B12 from food and/or intestinal transport proteins, whereas the absorption of “free” vitamin B12 is normal. This disorder was first described by Dosherholmen et al (13) in the 1990s (14, 15). Food-cobalamin malabsorption is the main aetiology of cobalamin deficiency in elderly patients, as shown by the Strasbourg study by Andrès et al (12, 16) and the study by Carmel et al (17). In our work, food-cobalamin malabsorption was found in patients older than patients with pernicious anaemia (p=0.03) confirming that this is a disease of elderly patients. Some predisposing clinical conditions are frequently found in the geriatric population such as atrophic gastritis with or without Helicobacter Pylori infection, gastric or intestinal bacterial overgrowth, long-term treatment with acid-suppressive drugs or biguanides, chronic alcohol abuse, history of gastric surgery, pancreatic insufficiency and age (idiopathic) (16). Food-cobalamin malabsorption is defined according to specific criteria (16, 18), but these criteria include results of the Schilling test. However, this test is not carried out in clinical practice in France so food-cobalamin malabsorption is a diagnosis of exclusion in the presence of vitamin B12 levels <200 pg/ml, no nutritional deficiency and one or more of the above-mentioned clinical conditions.
In our study, only 10 out of 125 patients had undergone a gastroscopy, which explains the low rate of patients with atrophic gastritis compared to other studies. But, 37.6% of patients were on long-term acid-suppressive drugs and 12.8% were on long-term biguanides. These drugs were an important factor in the diagnosis of food-cobalamin malabsorption in this work because elderly patients in geriatric acute-care and subacute care units take numerous drugs and suffer from various pathologies.
Another significant aetiology was nutritional cobalamin deficiency in a malnourished, geriatric population (40 %). Energy intake/weight in this group was lower (p=0.001) than other diagnoses, with 86.7 % of patients having less than 30 Kcal/kg/day.
Vitamin B12 is provided by the diet with a daily intake of 2 to 5 µg and the body’s reserves, localized in the liver, are significant and sufficient for 3 to 4 years. So, nutritional cobalamin deficiency is rare in healthy adults but more common in institutionalized elderly patients (19). Patients with vitamin B12 levels <149 pg/ml were less malnourished than patients with vitamin B12 levels >150 pg/ml (p=0.03) in our study because nutritional cobalamin deficiencies cause a minimal decrease in vitamin B12 levels. Cobalamin deficiency appears late in malnutrition, which involves systematically measuring vitamin B12 levels in this syndrome to detect cobalamin deficiency at the beginning.
In our study, 12 patients (9.6 %) had pernicious anaemia. This rate is lower than in other studies in which rates of about 30 % were observed (6, 20). Different reasons are probably involved: the recruitment bias because in geriatric units patients are particularly older and have several diseases. In addition, inclusion in our study took into account cobalamin deficiency and not the existence of anaemia so the number of gastroscopies was lower. In our work, patients with pernicious anaemia were younger (p=0.03), less malnourished (p=0.03) and had lower vitamin B12 levels (p=0.04).
Our data showed that of the 125 patients who received cobalamin supplementation, 111 patients (88.8 %) received oral treatment and 14 (11.2 %) intramuscular therapy. The mean serum vitamin B12 value increased significantly after supplementation, from 137.4 pg/ml to 353.4 pg/ml (p<0.001). The route still varied according to the diagnosis and the severity of cobalamin deficiency with intramuscular therapy often being used with pernicious anaemia (p<0.001) and when vitamin B12 levels <149 pg/ml (p=0.03). Intramuscular administration is currently recommended in the case of pernicious anaemia and severe neurological manifestations (21). But, nearly 1 % of free vitamin B12 is absorbed passively along the digestive tract and therefore does not require the presence of the intrinsic factor and its receptor, cubulin (22); this explains the possibility of using oral cobalamin therapy in the case of pernicious anaemia (9). In food-cobalamin malabsorption, absorption of free cobalamin remains intact and therefore oral cobalamin supplementation is sufficient as shown by Kuzminski (7) and Bolaman studies (8). Oral cobalamin therapy is preferred in elderly patients with cobalamin deficiency (23), but intramuscular administration should be used for patients not responding to oral therapy and in the case of severe neurological signs. Cyanocobalamin may be administrated subcutaneously in case of difficulties with intramuscular administration (patients on anticoagulants); this route is already used in geriatric units for other treatments (antibiotics, analgesics, hypodermoclysis…).
The procedure for oral cobalamin therapy has not yet been fully validated, but some studies have proposed regimens such as cyanocobalamin 1000 µg/day for 1 week (24) or 250-1000 µg/day for 1 month (25) or 125-1000 µg/day for at least 1 week (26) or 1000 µg/day for at least 3 months (27). In clinical practice, regimen proposed by the Strasbourg study by Andrès et al is cyanocobalamin 1000 µg/day for 1 month and then maintenance therapy with 125 to 500 µg/day for food-cobalamin malabsorption and nutritional deficiency and 1000 µg/day in the case of pernicious anaemia (28). In our study, five different oral regimens were used but regimen 4 was most frequently used (80.3 % of patients) with 1000 µg/day oral cyanocobalamin for 15 days, then maintenance therapy with 1000 µg/10 days for 1 month and then 1000 µg/month. But the comparison of this regimen with other oral regimens is difficult because of the low number of controlled patients who received other oral regimens. This regimen can be proposed for oral supplementation of cobalamin deficiency in elderly patients because it was effective according to our results. However, a prospective study to analyze different supplementation regimens in the elderly should be organized. Concerning food-cobalamin malabsorption, associated factors such as Helicobacter Pylori infection must be treated or clinical conditions such as alcohol abuse or use of acid-suppressive drugs and biguanides must be stopped.
In our study, when food-cobalamin malabsorption was associated with dementia, supplementation was less effective (p=0.04) due to difficulties with compliance. Studies have shown the improvement in MMSE with cobalamin supplementation (6, 29, 30) but this therapy does not improve overall cognitive functioning in patients with underlying dementia and has little effect on language disorders and praxis (30, 31). Elderly patients suffering from dementia associated with cobalamin deficiency must receive supplementation to improve some cognitive functions and surveillance must be organized for taking the treatment.
Conclusion
Our single-centre retrospective study in elderly patients in a geriatric university hospital confirmed that the leading cause of cobalamin deficiency is food-cobalamin malabsorption. Nutritional cobalamin deficiency is an important aetiology in our study compared to the literature due to the aging, undernourished population studied. Pernicious anaemia was probably underdiagnosed because of the low number of endoscopies performed. Cobalamin deficiency supplementation was mostly oral (88.8%) in this fragile population often treated with antiaggregants or anticoagulants. The regimen used was cyanocobalamin 1000 µg/day for 15 days then maintenance therapy with 1000 µg/10 days for 1 month and then 1000 µg/month with an interesting increase in vitamin B12 levels. However, a prospective study with various modalities of treatment in terms of dose, frequency and duration should be proposed to standardize the management of cobalamin deficiency in elderly patients.
References
- 1.Lindenbaum J, Rosenberg IH, Wilson PWF, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60:2–11. doi: 10.1093/ajcn/60.1.2. PubMed PMID: 8017332. [DOI] [PubMed] [Google Scholar]
- 2.Andrès E, Affenberger S, Vinzio S, Noel E, Kaltenbach G, Schlienger JL. Cobalamin deficiencies in aldults: update of etiologies, clinical manifestations and treatment. Rev Med Interne. 2005;26:938–946. doi: 10.1016/j.revmed.2005.04.036. 10.1016/j.revmed.2005.04.036 PubMed PMID: 15951065. [DOI] [PubMed] [Google Scholar]
- 3.Pautas E, Chérin P, De Jaeger C, Godeau P. Vitamin B12 deficiency in the aged. Presse Med. 1999;28:1767–1770. PubMed PMID: 10566283. [PubMed] [Google Scholar]
- 4.Sellal F, Becker H. Potentially reversible dementia. Presse Med. 2007;36:289–298. doi: 10.1016/j.lpm.2006.11.005. 10.1016/j.lpm.2006.11.005 PubMed PMID: 17258677. [DOI] [PubMed] [Google Scholar]
- 5.Carmel R. Malabsorption of food cobalamin. Clin Haematol. 1995;8:639–655. doi: 10.1016/s0950-3536(05)80224-0. [DOI] [PubMed] [Google Scholar]
- 6.Andrès E, Affenberger S, Vinzio S, Kurtz JE, Noel E, Kaltenbach G, et al. Foodcobalamin malabsorption in elderly patients: clinical manifestations and treatment. Am J Med. 2005;118:1154–1159. doi: 10.1016/j.amjmed.2005.02.026. 10.1016/j.amjmed.2005.02.026 PubMed PMID: 16194648. [DOI] [PubMed] [Google Scholar]
- 7.Kuzminski AM, Del Giacco EI, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92:1191–1198. PubMed PMID: 9694707. [PubMed] [Google Scholar]
- 8.Bolaman Z, Kadikoylu G, Yukselen V, Yavasoglu I, Barutca S, Senturk T. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clin Ther. 2003;25:3124–3134. doi: 10.1016/s0149-2918(03)90096-8. 10.1016/S0149-2918(03)90096-8 PubMed PMID: 14749150. [DOI] [PubMed] [Google Scholar]
- 9.Troilo A, Mecili M, Ciobanu E, Boddi V, D'Elios MM, Andrès E. Oral vitamin B12: efficacy and safety data in 31 patients with pernicious anemia and food-cobalamin malabsorption. Presse Med. 2010;39:273–279. doi: 10.1016/j.lpm.2010.03.027. 10.1016/j.lpm.2010.03.027 [DOI] [PubMed] [Google Scholar]
- 10.Folstein MF, Folstein SE, McHugh PR. « Mini-mental State ». A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. 10.1016/0022-3956(75)90026-6 PubMed PMID: 1202204. [DOI] [PubMed] [Google Scholar]
- 11.Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition. 1999;15(2):116–122. doi: 10.1016/s0899-9007(98)00171-3. 10.1016/S0899-9007(98)00171-3 PubMed PMID: 9990575. [DOI] [PubMed] [Google Scholar]
- 12.Andrès E, Noel E, Kaltenbach G, Perrin AE, Vinzio S, Goichot B, et al. Foodcobalamin malabsorption in elderly patients: a study of 60 patients. Rev Med Interne. 2003;24:218–223. doi: 10.1016/s0248-8663(02)00016-4. 10.1016/S0248-8663(02)00016-4 PubMed PMID: 12706777. [DOI] [PubMed] [Google Scholar]
- 13.Doscherholmen A, Swaim WR. Impaired assimilation of egg CO 57 vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection. Gastroenterology. 1973;64:913–919. PubMed PMID: 4633664. [PubMed] [Google Scholar]
- 14.Carmel R, Sinow RM, Siegel ME, Samloff IM. Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels. Arch intern med. 1988;148:1715–1719. 10.1001/archinte.1988.00380080019008 PubMed PMID: 3401093. [PubMed] [Google Scholar]
- 15.Carmel R. Current concepts in cobalamin deficiency. Annual review of medicine. 2000;51:357–375. doi: 10.1146/annurev.med.51.1.357. 10.1146/annurev.med.51.1.357 PubMed PMID: 10774470. [DOI] [PubMed] [Google Scholar]
- 16.Andrès E, Perrin AE, Demangeat C, Kurtz JE, Vinzio S, Grunenberger F, et al. The syndrome of food-cobalamin malabsorption revisited in a Department of Internal Medicine. A monocentric cohort study of 80 patients. Eur J Intern Med. 2003;14:221–226. doi: 10.1016/s0953-6205(03)00074-8. 10.1016/S0953-6205(03)00074-8 PubMed PMID: 12919836. [DOI] [PubMed] [Google Scholar]
- 17.Carmel R, Gott PS, Waters CH, Cairo K, Green R, Bondareff W, et al. The frequency low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities. Eur J Haematol. 1995;54:245–253. doi: 10.1111/j.1600-0609.1995.tb00679.x. 10.1111/j.1600-0609.1995.tb00679.x PubMed PMID: 7789470. [DOI] [PubMed] [Google Scholar]
- 18.Andrès E, Kaltenbach G, Perrin AE, Kurtz JE, Schlienger JL. Food-cobalamin malabsorption in the elderly. Am J Med. 2002;113:351–352. doi: 10.1016/s0002-9343(02)01181-6. 10.1016/S0002-9343(02)01181-6 PubMed PMID: 12361832. [DOI] [PubMed] [Google Scholar]
- 19.Russel RM. Vitamin requirements in old age. Age Nutr. 1992;3:20–23. [Google Scholar]
- 20.Couderc AL. Etiology of megaloblastic anemias in an internal medicine department: report of 43 cases during one year. 2006 [Google Scholar]
- 21.Solomon LR. Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev. 2007;21:113–130. doi: 10.1016/j.blre.2006.05.001. 10.1016/j.blre.2006.05.001 PubMed PMID: 16814909. [DOI] [PubMed] [Google Scholar]
- 22.Andrès E, Federici L, Serraj K, Kaltenbach G. Update of nutritient-deficiency anemia in elderly patients. Eur J Intern Med. 2008;19:488–493. doi: 10.1016/j.ejim.2008.01.016. 10.1016/j.ejim.2008.01.016 PubMed PMID: 19013375. [DOI] [PubMed] [Google Scholar]
- 23.Seal EC, Metz J, Flicker L, Melny J. A randomized double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. JAGS. 2002;50:146–151. doi: 10.1046/j.1532-5415.2002.50020.x. 10.1046/j.1532-5415.2002.50020.x [DOI] [PubMed] [Google Scholar]
- 24.Kaltenbach G, Noblet-Dick M, Andrès E, Barnier-Figue G, Noel E, Vogel T, et al. Early response to oral cobalamin therapy in older patients with vitamin B12 deficiency. Ann Med Interne. 2003;154:91–95. [PubMed] [Google Scholar]
- 25.Andrès E, Kaltenbach G, Noblet-Dick M, Noel E, Perrin AE, Vinzio S, et al. Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients. J Nutr Health Aging. 2006;10:3–6. PubMed PMID: 16453051. [PubMed] [Google Scholar]
- 26.Andrès E, Loukili NH, Noel E, Maloisel F, Vinzio S, Kaltenbach G, et al. Oral cobalamin (daily dose of 1000 µg) therapy for the treatment of patients with pernicious anemia. An opel label study of 10 patients. Curr Ther Research. 2005;66:13–22. doi: 10.1016/j.curtheres.2005.02.001. 10.1016/j.curtheres.2005.02.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002;50:1789–1795. doi: 10.1046/j.1532-5415.2002.50506.x. 10.1046/j.1532-5415.2002.50506.x PubMed PMID: 12410896. [DOI] [PubMed] [Google Scholar]
- 28.Andrès E, Serraj K, Mecili M, Ciobanu E, Vogel T, Weitten T. Update of oral vitamin B12. Ann Endocrinol. 2009;70:455–461. doi: 10.1016/j.ando.2009.07.001. 10.1016/j.ando.2009.07.001 [DOI] [PubMed] [Google Scholar]
- 29.Kwok T, Tang C, Woo J, Lai WK, Law LK, Pang P. Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Int J Geriatr Psychiatry. 1998;13:611–616. doi: 10.1002/(sici)1099-1166(199809)13:9<611::aid-gps832>3.0.co;2-o. 10.1002/(SICI)1099-1166(199809)13:9<611::AID-GPS832>3.0.CO;2-O PubMed PMID: 9777425. [DOI] [PubMed] [Google Scholar]
- 30.Jehl C, Vogel T, Martin-Hunyadi C, Lang PO, Andrès E, Berthel M, et al. Effects of oral cobalamin supplementation on cognitive function in elderly persons with vitamin B12 deficiency. Ann Gerontol. 2009;2(3):175–181. [Google Scholar]
- 31.Osimani A, Berger A, Friedman J, Porat-Katz BS, Abarbanel JM. Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects. J Geriatr Psychiatry Neurol. 2005;18:33–38. doi: 10.1177/0891988704272308. 10.1177/0891988704272308 PubMed PMID: 15681626. [DOI] [PubMed] [Google Scholar]