gastrins and Vitamin-B-12-Deficiency

The classic workup of a patient for possible PA is revisited in light of the vanishing Schilling test. The vagaries of testing for B12 and blocking antibodies are reexamined. The advantages and disadvantages of newer tests such as MMA and serum gastrin levels are catalogued. At this juncture in the evolution of new test strategies, there is a considerable controversy regarding the significance of high MMA levels in the face of normal B12 levels, particularly in the elderly. Hopefully, this controversy will soon be resolved and the newer crop of tests will be proven and accepted in the workplace. Still, the words of Alexander Pope spring to mind: "Be not the first by whom the new are tried, Nor yet the last to lay the old aside."

Topics: Anemia, Pernicious; Antibodies, Blocking; Gastrins; Humans; Intrinsic Factor; Methylmalonic Acid; Pathology, Clinical; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori - antibodies assayed from a blood sample it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The test enables the identification of patients whose risk of gastric cancer, of the consequences of vitamin B12 deficiency (e.g. elevated levels of homocysteine) or of peptic ulcer is considerably increased and who can then undergo gastroscopy. It also facilitates the diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Topics: Finland; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A; Peptic Ulcer; Stomach Neoplasms; Vitamin B 12 Deficiency

Cobalamin deficiency must be suspected in all patients with unexplained neuropsychiatric symptoms or unexplained anemia. Special attention should be paid to patients at risk of developing cobalamin deficiency such as elderly people, vegetarians, HIV-infected patients, patients with gastrointestinal diseases and patients with autoimmunity or a family history of pernicious anemia. The assays aimed to answer the question: does this patient suffer from cobalamin deficiency, include analysis of P--cobalamins and analyses of the metabolites that accumulate upon cellular cobalamin deficiency, P--methylmalonate and P--homocysteine. P--cobalamins or especially a fraction of P--cobalamins, P--TC cobalamins are markers for latent cobalamin deficiency. An increased concentration of P--methylmalonate that decreases upon injection of cobalamin indicates overt metabolic cobalamin deficiency. The same holds for P--homocysteine but this analysis is less specific than P--methylmalonate. We suggest that either assay of P--cobalamins or P--methylmalonate is employed as screening test for cobalamin deficiency, and that further tests are performed only if the initial test in combination with the clinical picture gives an unclear answer. Once cobalamin deficiency has been diagnosed, the cause for the deficiency should be sought and the patient should be treated for life. Cobalamin absorption tests such as the Schilling test are considered of limited use. Gastric atrophy is likely to be present in patients with increased P--gastrin or decreased P--pepsinogen A. However, this condition can be diagnosed also by upper gastrointestinal endoscopy.

Topics: Gastrins; History, 19th Century; History, 20th Century; Homocysteine; Humans; Methylmalonic Acid; Pepsinogens; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adrenal Cortex Hormones; Anemia, Pernicious; Animals; Antigen-Antibody Complex; Antigens; Autoantibodies; Autoimmune Diseases; Chronic Disease; Dogs; Female; Gastric Mucosa; Gastrins; Gastritis; Guinea Pigs; Haplorhini; Humans; Immunity, Cellular; Intrinsic Factor; Male; Rabbits; Rats; Vitamin B 12 Deficiency

Topics: Age Factors; Anemia, Pernicious; Antibodies; Atrophy; Bethanechol Compounds; Carbachol; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Insulin; Intrinsic Factor; Methacholine Compounds; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Female; Gastrins; Humans; Male; Pepsinogens; Prevalence; Random Allocation; Sweden; Vitamin B 12; Vitamin B 12 Deficiency

Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children.. We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded.. The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia.. Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Topics: Adolescent; Anemia, Iron-Deficiency; Autoimmune Diseases; Child; Child, Preschool; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Parietal Cells, Gastric; Retrospective Studies; Stomach; Vitamin B 12 Deficiency

Prevalence of cobalamin deficiency is high especially in older patients and an immediate therapy start is necessary to prevent irreversible neurological damages. Unfortunately, the diagnosis of cobalamin deficiency is difficult and at present, there is no consensus for diagnosis of this deficiency. Therefore, we aim to elucidate a meaningful diagnostic pathway by a case report with an initially misleading medical history.. A 57 year-old Caucasian man suffering from dramatic myelosis of the cervical posterior columns. Apart from associated neurological symptoms (tactile hypaesthesia, reduced vibration sensation, loss of stereognosis and of two-point-discrimination) there were no further complaints; especially no gastrointestinal, haematological or psychiatric disorders were provable. Cobalamin (vitamin B12) serum level was normal. The diagnosis of subacute combined degeneration of spinal cord was confirmed by an elevated methylmalonic acid, and hyperhomocysteinemia. Cobalamin deficiency was caused by asymptomatic chronic atrophic inflammation of the stomach with a lack of intrinsic factor producing gland cells. This was revealed by increased gastrin and parietal cell antibodies and finally confirmed by gastroscopy. Parenteral substitution of cobalamin rapidly initiated regeneration.. This case demonstrates that normal cobalamin serum levels do not rule out a cobalamin deficiency. In contrast, path-breaking results can be achieved by determining homocysteine, holotranscobalamin, and methylmalonic acid.

Topics: Antibodies; Gastrins; Gastroscopy; Homocysteine; Humans; Inflammation; Male; Methylmalonic Acid; Middle Aged; Parietal Cells, Gastric; Spinal Cord; Subacute Combined Degeneration; Transcobalamins; Vitamin B 12 Deficiency

Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B(12) deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG.. 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B(12), antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated.. The mean age of the patients was 53.06 ± 12.7 years (range 24-81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B(12) deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA.. In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B(12) deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B(12) deficiency should be investigated for the presence of AIG.

Topics: Adenomatous Polyps; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Autoimmune Diseases; Carcinoid Tumor; Diarrhea; Female; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Iron; Iron Deficiencies; Male; Middle Aged; Parietal Cells, Gastric; Polyps; Sex Factors; Stomach Neoplasms; Vitamin B 12 Deficiency; Young Adult

Proton pump inhibitors (PPI) remain the leading therapy for acid-related disorders. Long-term PPI use increases the risk of pneumonia and enteric bacterial infections and of nosocomial Clostridium difficile-associated diarrhoea. PPIs do not lead to vitamin B12 or iron deficiencies and do not induce malignancies or increase the risk of major birth defects. Prolonged PPI use may be a weak risk factor for certain fractures and results in hypergastrinaemia and parietal cell hyperplasia leading to rebound acid hypersecretion, which may induce symptoms on withdrawal of therapy.

Topics: Anti-Ulcer Agents; Bacterial Infections; Congenital Abnormalities; Dyspepsia; Fractures, Bone; Gastrins; Gastroenteritis; Gastroesophageal Reflux; Heartburn; Humans; Neoplasms; Omeprazole; Pneumonia; Proton Pump Inhibitors; Risk Factors; Time Factors; Vitamin B 12 Deficiency

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Pernicious; Anemia, Sickle Cell; Autoantibodies; Depression; Female; Folic Acid; Gastrins; Hemoglobin SC Disease; Humans; Hydroxyurea; Hyperhomocysteinemia; Intrinsic Factor; Iron Overload; Male; Methylmalonic Acid; Pneumonia; Transcobalamins; Transfusion Reaction; Treatment Refusal; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Proton pump inhibitors (PPIs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders including gastroesophageal reflux disease and peptic ulcer disease. Alltough these medications are generally accepted as safe, the long-term clinical consequences of the inducing hypochlorhydria are not completely clear. Gastric acid production is mainly controlled by the hormone gastrin through a negative feedback in which hypochlorhydria induces an increase in serum gastrin. PPIs have been shown to increase serum gastrin levels. Gastric endocrine cell hyperplasia can occur in 10 to 30% of patients without carcinoid tumors. Recent studies indicate no association between PPI use and the risk of colorectal and gastric cancers. Proton pump inhibitor-associated gastric polyps are totally benign tumors that should not be followed. There is an association between PPIs-induced acid suppression and an increased risk of enteric infection. PPIs do not inhibit intestinal absorption of lipids, iron, phosphorus, magnesium or zinc from food but can affect vitamin B12 status in older patients. Despite the undoubted benefits of PPIs, the practitioner always needs to consider risks and benefits before initiating them.

Topics: Bacterial Infections; Colonic Neoplasms; Gastric Acid; Gastrins; Humans; Polyps; Proton Pump Inhibitors; Vitamin B 12 Deficiency

Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases.. To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients.. Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied.. Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication.. Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment.. The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Topics: Aged; Aged, 80 and over; Autoantibodies; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prospective Studies; Vitamin B 12 Deficiency

Patients with autoimmune thyroid disease (AITD) have a higher prevalence of pernicious anemia compared with the general population. Clinical signs of B12 deficiency may be subtle and missed, particularly in patients with known autoimmune disease. We assessed the prevalence of vitamin B12 deficiency in patients with AITD and whether their evaluation may be simplified by measuring fasting gastrin levels.. Serum B12 levels was measured in 115 patients with AITD (7 men and 108 women), with a mean age of 47 +/- 15 years. In patients with low serum B12 levels (< or =133 pmol/L), fasting serum gastrin and parietal cell antibodies (PCA) were measured.. Thirty-two patients (28%) with AITD had low B12 levels. Fasting serum gastrin was measured in 26 and was higher than normal in 8 patients. PCA were also measured in 27 patients with B12 deficiency and were positive in 8 patients. Five patients with high gastrin levels underwent gastroscopy with biopsy, and atrophic gastritis was diagnosed in all. The prevalence of pernicious anemia as assessed by high serum gastrin levels in patients with low B12 was 31%.. Patients with AITD have a high prevalence of B12 deficiency and particularly of pernicious anemia. The evaluation of B12 deficiency can be simplified by measuring fasting serum gastrin and, if elevated, referring the patient for gastroscopy.

Topics: Adolescent; Adult; Aged; Female; Gastrins; Graves Disease; Hashimoto Disease; Humans; Male; Middle Aged; Prevalence; Thyroiditis, Autoimmune; Vitamin B 12 Deficiency

Pernicious anemia (PA), as many other autoimmune disorders, has a trend to appear in other members of the family of the affected patients. Although this fact has been recognized since some decades ago, less is known about the frequency with which the abnormalities detected in the patients appear also in their relatives, the correlations that exist among these abnormalities and to what extent these markers of the disease relate to serum cobalamin concentration.. For these reasons we studied the values of some markers of PA in a group of 79 first-degree relatives and we detected that the most frequent abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40 (23.4% of cases). From a functional point of view, a decrease in hydrogen excretion in a magnesium breath test, indicative of achlorhydria, is also frequent (29.1%). The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases.. These findings emphasize the need for searching for the presence of occult or latent PA in relatives of patients with this diagnosis, not only to prevent the development of anemia but also to avoid other undesirable consequences of cobalamin deficiency.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Breath Tests; Family Health; Female; Gastrins; Humans; Hydrogen; Male; Middle Aged; Pepsinogen A; Risk; Vitamin B 12 Deficiency

Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation.. Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test).. The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months.. The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anemia, Iron-Deficiency; Antibodies, Bacterial; Autoantibodies; Autoimmune Diseases; Bacterial Proteins; Breath Tests; Celiac Disease; Child; Clarithromycin; Comorbidity; Drug Therapy, Combination; Female; Ferrous Compounds; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Omeprazole; Parietal Cells, Gastric; Prospective Studies; Urease; Vitamin B 12 Deficiency

This observation recalls that gastric phytobezoar should lead to a search for an underlying disease and that a iron deficiency can be associated and hide macrocytosis related to a vitamin B12 deficiency.. A 19 year-old woman consulted for asthenia. Microcyte anaemia associated with iron deficiency was diagnosed. Upper digestive endoscopy revealed severe, totally asymptomatic phytobezoar. Biological investigations revealed a vitamin B12 deficiency, high serum gastrin level and strong positivity for gastric antiparietal anti-cell antibodies, suggestive of an autoimmune gastritis. Total immunoglobulin A deficiency was also noted.. Autoimmune gastritis is responsible for megaloblastic anaemia (vitamin B12 deficiency) but can also provoke microcytic (iron-deficiency) anaemia due to insufficient absorption of the latter and related to gastric achlorhydria. Phytobezoar might also be related to achlorhydria and/or gastroparesia associated with autoimmune gastritis. Hence, autoimmune gastritis should be searched for when confronted with unexplained gastric bezoar or iron-deficiency anaemia.

Topics: Adult; Anemia, Iron-Deficiency; Autoimmune Diseases; Bezoars; Female; Gastrins; Gastritis; Humans; Plants; Vitamin B 12 Deficiency

The authors investigated whether low vitamin B12 intake, impaired gastric function, infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children.. The plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and and bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests, respectively.. infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin.. The specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Topics: Analysis of Variance; Breath Tests; Child; Diet; Female; Gastrins; Guatemala; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Male; Methylmalonic Acid; Pepsinogen A; Risk Factors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The prevalence of vitamin B-12 deficiency increases with age, probably resulting from malabsorption of food-bound B-12 secondary to gastric atrophy. On the basis of this assumption, the Institute of Medicine (IOM) recommends those aged >50 y consume crystalline vitamin B-12. There is limited information on the prevalence of gastric atrophy in the elderly and whether the IOM recommendation would be effective. The objective of this study was to assess predictors of vitamin B-12 status and their interactions in free-living elderly. Individuals (n = 57) with deficient plasma vitamin B-12 (p-B12 < 148 pmol/L) were compared with 68 individuals with marginal p-B12 (148-221 pmol/L) and 52 with normal p-B12 (>221 pmol/L) in a cross-sectional sample (n = 1546) of elderly (>60 y) Latinos in California. Associations were examined among p-B12 and serum gastrin, vitamin B-12 intake from food and crystalline sources, and medications that putatively affect vitamin B-12 absorption. Serum gastrin was elevated, indicating gastric atrophy, in 48% of participants with deficient p-B12, 23% with marginal p-B12 and 21% of normal p-B12 participants, and was a significant predictor of deficient p-B12 and high plasma homocysteine (p-tHcy). Median total vitamin B-12 intake exceeded recommendations and was similar among status groups. Crystalline vitamin B-12 intake in the normal p-B12 group was higher than in the deficient p-B12 group (P < 0.01), and tended to be higher than the marginal group (P = 0.07). When serum gastrin was elevated, p-B12 was predicted by crystalline vitamin B-12, but not by intake of vitamin B-12 from food. Elevated serum gastrin was highly prevalent and predicted vitamin B-12 depletion. Crystalline vitamin B-12 intake predicted p-B12 in individuals with elevated serum gastrin, supporting IOM recommendations to increase consumption of crystalline vitamin B-12.

Topics: Aged; Aging; Crystallization; Dietary Supplements; Female; Folic Acid; Food; Gastrins; Humans; Male; Middle Aged; Osmolar Concentration; Vitamin B 12; Vitamin B 12 Deficiency

The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria.. To conduct a systematic comparative examination of gastric histology and function.. Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status.. All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection.. The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics.. Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

Topics: Achlorhydria; Adult; Aged; Aged, 80 and over; Biopsy; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter pylori; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Prospective Studies; Schilling Test; Vitamin B 12 Deficiency

This study was undertaken to determine whether measurements of serum total homocysteine (Hcys) and bound B12 absorption are useful in determining which patients with low- or low-normal levels of serum B12 are B12 deficient. In 40 patients with low or borderline serum levels of B12, food-bound B12 absorptions were determined using a body counter in an iron room, and were related to serum total Hcys levels. Food-bound B12 absorption was decreased in 16 patients and in an additional four, absorption of the free vitamin was also decreased. Homocysteine levels were elevated in four of the 16; in three of the four who had both decreased bound and free B12 absorptions, Hcys was elevated. If elevation of the Hcys level indicates tissue deficiency of B12, the 75% incidence of normal levels of Hcys in these patients with low food-bound B12 absorptions suggests the existence of a cohort of patients who may be at risk to develop, but have not yet developed, B12 deficiency. Only long term follow-up will reveal how many ultimately will become B12 deficient.

Topics: Adult; Aged; Aged, 80 and over; Blood Cell Count; Female; Folic Acid; Food; Gastrins; Homocysteine; Humans; Intestinal Absorption; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency.. Clinical study of consecutive patients.. The catchment area of Sahlgrenska University Hospital, Göteborg.. A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery.. Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin.. Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin.. About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests.. Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.

Topics: Adult; Aged; Algorithms; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Homocysteine; Humans; Male; Methylmalonic Acid; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Vitamin B 12 Deficiency

In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5.5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was < or = 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Erythrocyte Indices; Female; Folic Acid; Folic Acid Deficiency; Gastrins; Hemoglobins; Homocysteine; Humans; Methylmalonic Acid; Nervous System Diseases; Neutrophils; Vitamin B 12 Deficiency; Zimbabwe

Two entities of considerable recent interest, Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody to H. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT < 1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0-1.99%) and 42% of 59 subjects with normal absorption (EYCAT > or = 2.0%) (chi 2 = 9.52, P < 0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03 +/- 1.83% vs 3.11 +/- 2.13%, t = 2.913, P = 0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence of H. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced by H. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.

Topics: Adult; Aged; Antibodies, Bacterial; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Malabsorption Syndromes; Male; Middle Aged; Serologic Tests; Vitamin B 12 Deficiency

C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins.. Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis.. Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity.. The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.

Topics: Anemia, Pernicious; Ascorbic Acid; Copper; Eating; Enzyme Activation; Freezing; Gastrins; Humans; Mixed Function Oxygenases; Multienzyme Complexes; Multiple Endocrine Neoplasia; Vitamin B 12 Deficiency

Serum concentrations of group I pepsinogens (pepsinogen-I) and gastrin were determined in patients with dementia disorders in order to assess the relationship, if any, between these indices of gastric mucosal function and serum cobalamin (vitamin B12) levels. A significant positive correlation between pepsinogen-I and B12 and, as expected, an inverse relationship between gastrin and pepsinogen-I concentrations was found, indicating that vitamin B12 deficiency was mainly determined by gastric mucosal atrophy (atrophic gastritis) in this West-Swedish sample of patients with dementia disorders. Patients with low B12 but normal gastrin and pepsinogen-I concentrations should, therefore, be further evaluated for possible nutritional deficiency, as well as nongastric causes of poor B12 assimilation from the diet.

Topics: Aged; Aged, 80 and over; Dementia; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Intestinal Absorption; Male; Pepsinogens; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency develops over a slowly progressive continuum. Early manifestations may be generalized weakness or fatigue, indigestion, diarrhea, or depression. Pernicious anemia is considered the classic cause, but others include malabsorption because of achlorhydria or other gastric dysfunction, fish tapeworm infection, and strict vegetarianism. Iron deficiency often coexists. Because presentation is often atypical, vitamin B12 deficiency is a diagnostic consideration whenever neuropsychiatric signs or symptoms are unexplained.

Topics: Anemia, Pernicious; Gastrins; Humans; Insurance, Health, Reimbursement; Intestinal Absorption; Medicare; United States; Vitamin B 12; Vitamin B 12 Deficiency

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Topics: Bilirubin; Female; Folic Acid; Gastrins; Hematocrit; Homocysteine; Humans; L-Lactate Dehydrogenase; Male; Methylmalonic Acid; Prospective Studies; Reference Values; Vitamin B 12; Vitamin B 12 Deficiency

The reported incidence of low serum vitamin B12 levels in patients ranges from 4% to 8%. In only a small percentage can this be ascribed to readily diagnosed pernicious anemia, malabsorption syndrome, or to gastrointestinal surgery. This leaves a number of patients in whom the meaning of the low serum B12 is not immediately apparent. In 71 patients with intact gastrointestinal tracts, hematological indices did not adequately separate patients with decreased absorption of unbound B12 from those with normal absorption. A low absorption of B12, either unbound or food-bound, was found, however, when the level of serum gastrin was elevated. In contrast, a normal absorption of unbound B12 was likely (95% of 44 patients) when the serum gastrin was normal.

Topics: Absorption; Cobalt Radioisotopes; Cooking; Egg Yolk; Gastrins; Hematologic Tests; Humans; Vitamin B 12; Vitamin B 12 Deficiency

The ratio of pepsinogen I to pepsinogen II in the circulation decreases progressively with increasing severity of atrophic gastritis of the fundic gland mucosa. Fasting blood was obtained from 359 free-living and institutionalized elderly people (age range, 60 to 99 years). A pepsinogen I/pepsinogen II ratio less than 2.9, indicating atrophic gastritis, was found in 113 (31.5%) subjects. The prevalence of atrophic gastritis increased significantly with advancing age (P less than .05). Within the atrophic gastritis group, 84 had a pepsinogen I level greater than or equal to 20 micrograms/L, indicating mild to moderate atrophic gastritis, and 29 had a pepsinogen I level less than 20 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. A significant increase in the prevalences of elevated serum gastrin levels (P less than .005), low serum vitamin B12 levels (P less than .005), circulating intrinsic factor antibody (P less than .005), and anemia (P less than .025) was observed with stepwise increases in severity of atrophic gastritis. Subjects with atrophic gastritis exhibited a lower mean serum vitamin B12 level (P less than .05) and a higher mean folate level (P less than .05), but no difference was detected in mean hemoglobin levels or serum levels of iron, ferritin, retinol or alpha-tocopherol. It is concluded that serum pepsinogen I and pepsinogen II levels can be used to determine the prevalence and severity of atrophic gastritis, that atrophic gastritis is common in an elderly population, and that atrophic gastritis is associated with vitamin B12 deficiency and anemia. Further, higher folate levels in atrophic gastritis may be related to an accumulation of 5-methyl tetrahydrofolate in serum due to vitamin B12 deficiency and/or greater folate synthesis by the intestinal flora resulting from bacterial overgrowth secondary to hypo- or achlorhydria.

Topics: Aged; Aged, 80 and over; Aging; Boston; Female; Gastrins; Gastritis; Gastritis, Atrophic; Hemoglobins; Humans; Intrinsic Factor; Male; Middle Aged; Nutritional Status; Pepsinogens; Vitamin B 12 Deficiency

A middle-aged woman developed a postgastric bypass megaloblastic anemia which responded to treatment. She eventually had the bypass reversed 6 1/2 yr after it had been performed. Gastric parietal cell function has remained abnormal almost 3 yr after reversal of the bypass, as demonstrated by abnormal Schilling tests and high serum gastrin levels. Parietal cell antibodies in high titer, but no intrinsic factor antibodies, were demonstrated in her blood. These observations are interpreted as indicating the development of irreversible chronic atrophic gastritis probably related to reflux of bile into the bypassed stomach.

Topics: Adult; Anemia, Megaloblastic; Female; Gastric Acid; Gastrins; Humans; Intrinsic Factor; Parietal Cells, Gastric; Postoperative Complications; Stomach; Vitamin B 12 Deficiency

Elevated levels of serum gastrin as a consequence of gastric achlorhydria are characteristic of clinical pernicious anemia. In a largely male hospitalized population with an average age of 64 years, 7.7% had low levels of serum B12 (less than 170 pg/mL); only 2.5% of these had frank pernicious anemia. In an attempt to separate a subgroup with low levels of serum B12 in whom pernicious anemia may later develop, their serum gastrin levels were determined. Twenty-two percent had high values and, of these, 70% had low B12 absorptions. In patients with low serum B12 levels, serum gastrin assays may be useful in determining those in whom clinical pernicious anemia seems likely to develop.

Topics: Anemia, Pernicious; Gastrins; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Afferent Loop Syndrome; Anemia, Macrocytic; Diarrhea; Dumping Syndrome; Folic Acid Deficiency; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Absorption; Intrinsic Factor; Mucus; Osteoporosis; Postgastrectomy Syndromes; Stomach Neoplasms; Vitamin B 12 Deficiency; Vomiting