B12 Malabsorption Research Articles

A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test.

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976-1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5-95 years with 45.5% over 60 years. The referring specialties were Gastroenterology (47.6%), Haematology (11.3%), Paediatrics (2.1%) and all others (39.0%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B12 malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio greater than or equal to 1.3 and 127 (73.8%) a ratio greater than or equal to 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).

Megaloblastic Anemia Characterized by Microcytosis: Imerslund-Grasbeck Syndrome With Coexistent α-Thalassemia

Imerslund-Grasbeck syndrome is a hereditary autosomal recessive condition of selective vitamin B12 malabsorption in the terminal ileum, resulting in chronic megaloblastic anemia.1,2 The purpose of this report is to describe a child with coincident Imerslund-Grasbeck syndrome and α-thalassemia, who also had a vitamin B12-sensitive microcytic anemia. CASE REPORT When R.S. was 15 months of age his mother reported that progressive anorexia and lethargy had developed. There was no history of chronic diarrhea, vomiting, frequent infections, or pica; there was no family history for blood dyscrasias. R.S. was a black boy who weighed 8.3 kg (less than the fifth percentile); his length was 74 cm (less than the fifth percentile), and his head circumference was 45 cm (second percentile).

Is vitamin B12 malabsorption in bile fistula rats due to bacterial overgrowth? A study of bacterial metabolic activity in the small bowel.

To investigate whether vitamin B12 malabsorption in rats with choledochocolic fistulae is caused by bacterial overgrowth, we studied intestinal bacterial metabolic activity in choledochocolic fistula-operated rats, self-filling blind-loop-operated rats, and sham-operated rats. Fistula-operated rats had a moderate indicanuria compared with sham-operated ones, whereas the faecal excretion of nitrogen was unchanged. There was no difference in the amounts of radioactivity recovered in sediments of intestinal contents after an oral dose of 57CoB12, indicating unaltered bacterial uptake of vitamin B12 in fistula rats. The 14C-xylose breath test showed bacterial overgrowth in blind-loop rats only. Neomycin treatment of fistula rats diminished the excretion of indican but did not alter the absorption of vitamin B12. The results suggest moderately increased activity of indole-producing bacteria in fistula rats, but they do not support the hypothesis that vitamin B12 malabsorption is caused by bacterial overgrowth.

Incidence and clinical significance of protein-bound vitamin B12 malabsorption.

Patient records from January 1975 to December 1984 were analysed to assess the possible incidence of protein-bound vitamin B12 malabsorption. This condition is characterised by a low serum vitamin B12 level and a normal Schilling test but impaired absorption of vitamin B12 bound to protein. We found that 48 (25%) patients with a low serum cobalamin level unexplained by other causes had a normal Schilling test. Megaloblastic haemopoiesis was found in 25 of these. From this group, all 10 patients who had a test of protein-bound vitamin B12 absorption showed impaired absorption. Protein-bound vitamin B12 malabsorption may represent an early phase of pernicious anaemia when hypochlorhydria precedes intrinsic factor deficiency and should be tested for when the serum vitamin B12 level is decreased and the Schilling test is normal.

Intestinal absorption and unmediated permeation of sugars in post-infective tropical malabsorption (tropical sprue).

Differential absorption of D-xylose and 3-O-methyl-D-glucose, and unmediated intestinal permeation of lactulose and L-rhamnose has been investigated in 14 patients with diarrhoea following tropical exposure and in 16 healthy control subjects. Five had malabsorption of fat, D-xylose and B12 ('tropical malabsorption' (TM) group), and that was absent or minimal in the others ('tropical diarrhoea' (TD) group). After combined ingestion of the four test sugars in iso-osmolar solution a marked depression in plasma D-xylose concentration (with a slow rise) occurred in all of the TM group; the TD group did not differ significantly from the controls. In contrast, 3-O-methyl-D-glucose absorption was similar in all three groups. Urine analysis demonstrated that intestinal permeation of lactulose was increased and that of rhamnose decreased in the TM group compared with the controls. Ingestion as a hyperosmotic solution further enhanced abnormal lactulose permeation in the TM group. Although some of the TD group showed one or the other of these changes, discrimination of the TM group from the TD and control groups was improved when results were expressed as lactulose/rhamnose differential permeation ratios, especially when using a hyperosmotic stress. Similar abnormalities have previously been demonstrated in untreated gluten-induced enteropathy (coeliac disease). The magnitude of the absorption defects demonstrated in TM are more severe than would be anticipated from the jejunal mucosal abnormalities alone; this suggests that there is probably significant pathology in the distal small intestine (including the ileum) in TM.

Causes of malabsorption in the elderly.

The pathogenesis of malabsorption has been studied in 70 patients who presented over the age of 65 years and who were referred to a special investigative unit. Often more than one cause was apparent. Fourteen patients had pancreatic insufficiency, most of whom had no history of pain, alcoholism or gallstones. Twenty-three patients had the postgastrectomy syndrome or small-bowel diverticulosis or both. There were eight coeliacs aged 65-72 years at diagnosis. Fifteen patients had an anatomically normal small bowel; eight of these were over 80 years old, and 10 had vitamin B12 deficiency of whom five had confirmed pernicious anaemia. Enterobacterial overgrowth was a feature of all diagnostic groups except pancreatic and coeliac disease. Vitamin B12 deficiency may be an effect of malabsorption, but can also be a cause through impairment of enterocyte function. The association of pernicious anaemia and B12 deficiency with otherwise unexplained malabsorption and bacterial overgrowth suggests that gastric atrophy is a major causal factor in this syndrome, combined in some cases with a 'vicious circle' of B12 malabsorption and deficiency.

The pathogenesis of post-irradiation chronic diarrhoea: Measurement of SeHCAT and B 12 absorption for differential diagnosis determines treatment

The absorption of vitamin B12 and of a synthetic bile acid analogue 75SeHCAT was measured simultaneously in 26 patients presenting with persistent diarrhoea following pelvic irradiation for treatment of carcinoma of the cervix. Four groups were identified, namely patients with isolated bile acid malabsorption, patients with isolated B12 malabsorption, patients with malabsorption of both and those with malabsorption of neither compound. The therapeutic implications are different for each. Measurement of B12 and bile acid absorption comprises an important new test for the management of patients with this disabling and unpleasant complication of radiotherapy.

Vitamin B12 absorption after necrotizing enterocolitis.

Resection of the terminal ileum for necrotizing enterocolitis is not uncommon in neonates requiring intensive care in the first weeks of life. They may therefore be at risk of vitamin B12 malabsorption, and later of vitamin B12 deficiency. A method of measuring B12 absorption is described and the results are given. This assessment should be part of the follow up for all these children.

Biochemistry and clinical chemistry of vitamin B 12 transport and the related diseases

This review focusses on research performed by the author and coworkers. The absorption, turnover and excretion of cobalamin and the pathogenesis of cobalamin deficiency states are described and the laboratory tests used to diagnose these states are discussed. Topics dealt with in detail include: overall turnover, daily need, enterohepatic circulation and excretion of cobalamin and other corrins . The soluble proteins mediating cobalamin transport and their cellular receptors are described and their nomenclature, isolation, structure and mode of action, the role of calcium in the membrane transport, the evolution of these systems and the analogies with transport systems for other substrates are discussed together with deficiency states, especially fish tapeworm anemia and familial selective vitamin B12 malabsorption with proteinuria. Folate deficiency is a relatively rare cause of megaloblastic anemia in Scandinavia but common in North America and explanations for this difference are suggested. The methods of assaying cobalamin in serum and plasma and the performance of radiovitamin B12 absorption tests are critically evaluated. The measurement of intrinsic factor in gastric juice, serum, amniotic fluid and urine is described.

Prevalence and Incidence of Pernicious Anemia

To evaluate the feasibility of gastroscopic screening for gastric malignancy in patients with pernicious anemia, all individuals treated with vitamin B12 in a well-defined population were identified. Individuals treated for an uncertain diagnosis were submitted to supplementary examinations. Of all individuals treated with vitamin B12 41% had unequivocal pernicious anemia, 13% possible pernicious anemia, 26% vitamin B12 malabsorption other than pernicious anemia, and 20% no verified vitamin B12 deficiency. The maximum crude prevalence of pernicious anemia was 1.98 per mile and the crude maximum incidence 16.7 x 10(-5) x year-1. The estimated annual cost of endoscopic gastric screening at 3-year intervals in patients with pernicious anemia younger than 75 years of age would be SEK 15,000/100,000 inhabitants, a cost that to a great extent could be financed by a more adequate prescription of vitamin B12 treatment.

The changing pattern of megaloblastic anemia: megaloblastic anemia in Israel

The causes of megaloblastic anemia were studied in a survey of patients admitted to six Israeli hospitals over a period of 15 yr. Among the 203 patients identified, 69% had pernicious anemia, 12% had gastrointestinal disease, 9% had primary nutritional deficiency of whom only 1% were associated with pregnancy, and 7% had selective vitamin B12 malabsorption with albuminuria. Comparison with previously published surveys showed, that in contrast with earlier studies where primary nutritional deficiency was the cause of megaloblastic anemia in about 70% of cases and pernicious anemia in only 20%, in more recent studies the proportion of cases with primary nutritional anemia in general and those associated with pregnancy in particular was much lower. This is most probably the result of improved standards of living and a national program of preventive folate supplementation at maternity clinics. A potential hazard of such preventive programs is the aggravation of neurological complications in patients with undiagnosed vitamin B12 deficiency. Early recognition of pernicious anemia and other forms of selective B12 malabsorption is a new challenge created by the changing pattern of megaloblastic anemias.

Serum and red cell folate and serum vitamin B12 levels in horses.

Vitamin B12 and folate concentrations were determined by radioimmunoassay in groups of horses in Queensland. Highest serum vitamin B12 levels were found in supplemented performance horses. These, together with pastured horses that included pregnant and lactating mares, had significantly greater serum folate activity than permanently stabled animals. The range of red cell folate concentrations was much narrower in horses in training than from any other group. Red cell folate may be a better indicator of a horse's folate status than the serum folate value. Vitamin B12 and folate concentrations were highest in spring and summer. Small intestinal dysfunction in 2 horses was not associated with vitamin B12 or folate malabsorption. Serum folate levels returned to normal 24 h after intramuscular injections of 75 to 150 mg folic acid, whereas serum vitamin B12 values remained elevated for at least one week following injections of 8 to 10 mg to non-supplemented horses. None of the horses in this survey had evidence of vitamin B12 or folate deficiency, or showed significant haematological changes. Nevertheless, permanently stabled horses and some horses in training may require additional folic acid, preferably on a daily basis by the oral route. However, exogenous vitamin B12 administration does not appear to be justified.

A fast method of measuring vitamin B12 absorption using a whole-body counter.

The conventional method of measuring vitamin B12 absorption using a whole-body counter normally involves a delay of fourteen days before complete faecal excretion of unabsorbed B12 tracer can be assumed. A modified technique has been used which reduces the delay to four days. A non-absorbable tracer, 51Cr-chromic chloride, was administered firstly with 58Co-labelled vitamin B12 and then three hours later with 57Co-labelled vitamin B12 and then three hours later with 57Co-labelled vitamin B12 plus 50 mg hog intrinsic factor which normalises B12 malabsorption in patients with pernicious anaemia. Three days later, the residual whole-body activities of the three radionuclides were measured. The retention of 51Cr indicated the efficiency of faecal excretion of unabsorbed B12 tracer and could be used to quantify vitamin B12 absorption before complete excretion of unabsorbed B12 tracer. Vitamin B12 absorption values were measured at four days by this technique and compared with the corresponding values at fourteen days in 38 tests on 33 subjects, 16 of whom had pernicious anaemia. Excellent correlations between the results obtained at four and 14 days were obtained for both B12 tracers.

Imerslund症候群(selective vitamin B12 malabsorption with proteinuria)の1例:腎組織所見を中心に

Imerslund症候群(selective vitamin B12 malabsorption with proteinuria)の1例:腎組織所見を中心に

Effect of folate deficiency on vitamin B12 absorption.

In three different groups of patients presenting severe folate deficiency (purely nutritional folate deficiency, chronic alcoholism or various intestinal diseases), vitamin B12 absorption has been tested by Schilling test in order to investigate the possible effect of folate deficiency on B12 absorption. Following this study, it appears that folate deficiency in itself, even severe, cannot induce vitamin B12 malabsorption, since in the first group, consisting of malnourished old people, the Schilling test was always normal even in those who presented a lowered B12 serum level; in the group of patients with intestinal disease, the Schilling test was abnormal as expected in some patients; 3 alcoholics out of 12 presented a malabsorption of B12 on the Schilling test; the follow-up of 2 of them exhibited complete correction after normal diet and alcohol suppression. Consequently, folate deficiency does not seem responsible for a secondary B12 malabsorption unless another etiological factor is present, such as alcohol or ileopathy.

Homocystinuria.

The term “homocystinuria”, the abnormal appearanee of homocyst(e)ine in the urine, is often used synonymously with the metabolic disturbances related to cystathionine β-synthase deficiency, but is a feature of at least two other defects as well, 5-methyltetrahydrofolate: homocysteine methyltransferase deficiency, due to defective production of methylcobalmin, or due to 5,10-methylenetetrahydrofolate reductase deficiency. Homocystinuria has, moreover, been observed in the vitamin B12 malabsorption syndrome (Imerslund-Gräsbeck syndrome) (120), in vitamin B6 depletion in man (205), in patients treated with 6-azauridine (126), together with cystathioninuria in a patient with neuroblastoma (183) and as an artefact due to bacterial contamination in cystathioninuria (155).Key wordsHomocystinuriamethionine degradationmethionine synthesisvitamin B12 vitamin B6 folic acidcystathionine β-synthase deficiencymethylene THF reductase deficiencymethylmalonic aciduria

Effect of cimetidine on the absorption of vitamin B12.

The effect of cimetidine on the absorption of orally administered crystalline or food (egg yolk-bound) vitamin B12 (B12) was studied in 13 patients. Absorption or crystalline B12 was normal and not significantly changed by cimetidine. In contrast, the uptake of food-bound B12 decreased in all patients, from a mean of 5.3% without the drug to 2.5% after it, a fall of 53% (p less than 0.0001). This impairment of B12 absorption raises the possibility that long-term, full-dose therapy with cimetidine may produce B12 deficiency similar to that seen in other hypochlorhydric states. Our data indicate that cimetidine-induced B12 malabsorption would not be detected by the standard Schilling test.

Restorative proctocolectomy with ileal reservoir: a pathophysiological assessment.

A metabolic and physiological assessment was carried out in 14 patients who had undergone restorative proctocolectomy with ileal reservoir more than six months previously. The haemoglobin was normal in all but one and plasma electrolytes and serum albumin, calcium, phosphorus, and red cell folate estimations were normal in all. Five patients had low serum iron levels of whom one had an iron deficiency anaemia. The 24 hour faecal fat output was normal in all patients and there was no case of vitamin B12 malabsorption as judged by the Schilling test, although four patients had marginally low values. These were not associated with increased bacterial counts in the faeces within the reservoir and there was no evidence to support a diagnosis of stagnant loop syndrome. Inflammation of the reservoir mucosa was, however, associated with higher counts of aerobic bacteria than in cases where inflammation was absent. Subtotal villous atrophy or inflammation was seen in biopsies of the reservoir in six patients. The mean faecal output per 24 hours was 659 +/- 259 g and the mean reservoir volume was 330 +/- 78 ml. Mean resting anal canal pressure was significantly lower in patients with a mucous leakage per anum than in those without, while manometry of the reservoir showed no alteration of pressure over a period of one hour before and after a meal. A positive rectosphincteric reflex was observed in nine patients.

Vitamin B12 absorption and exocrine pancreatic insufficiency in childhood.

The absorption of vitamin B12, labelled with radioactive 58Co, was measured in 19 patients with cystic fibrosis and one child with the Shwachman-Diamond syndrome using the whole body counting technique. We found vitamin B12 absorption reduced to 7.97 on average, compared to 59.2% for the control group. The low vitamin B12 absorption correlated well with the reduced fat retention coefficients. After adding 0.212 pancreatin to the radioactive vitamin B12 test dose, the absorption quotas improved in all cases, the average being 61%. A meal poor in vitamin B12 tended to increase the absorption of the radioactive test dose to 23% on average. As yet there is no satisfactory explanation for the effect of the diet on the absorption of vitamin B12 in exocrine pancreatic insufficiency. This could be the reason why the malabsorption of vitamin B12 in patients with EPI can go unnoticed for many years and could possibly explain why vitamin B12 malabsorption in exocrine pancreatic insufficiency does not cause symptoms and signs of vitamin B12 deficiency for many years.

The metabolic consequences of jejunoileal bypass for obesity.

Twenty-one female patients studied between six and 12 months following a jejunoileal bypass procedure for obesity were found to have a wide variety of metabolic disturbances. Hepatic histological abnormalities were common and included liver cell necrosis and inflammation in nine patients and hepatic fibrosis in five. Liver function tests were no guide to the degree of hepatic impairment. Vitamin B12 malabsorption occurred in seven patients, in six probably as a result of bacterial intestinal overgrowth; three of these six patients had the most serious hepatic morphological changes. Malabsorption rather than poor oral intake of food appeared to account for continued postoperative weight loss in the majority of patients.