RESUMO
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.
Assuntos
Acloridria , Doenças Autoimunes , Gastrite Atrófica , Gastrite , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicações , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Mucosa Gástrica , Compostos NitrososRESUMO
BACKGROUND: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. OBJECTIVES: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. METHODS: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. RESULTS: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG. CONCLUSIONS: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.
Assuntos
Alimentos Fortificados , Gastrite Atrófica/complicações , Estado Nutricional , Inibidores da Bomba de Prótons/efeitos adversos , Deficiência de Vitamina B 12/dietoterapia , Deficiência de Vitamina B 12/etiologia , Vitamina B 12 , Acloridria/complicações , Idoso , Envelhecimento , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pepsinogênios/sangue , Prevalência , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/sangue , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangue , Complexo Vitamínico B/uso terapêuticoRESUMO
La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)
Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Carbonato de Cálcio/farmacocinética , Osteoporose Pós-Menopausa/prevenção & controle , Cálcio/farmacocinética , Hormônio Paratireóideo/análise , Acloridria , Calcitriol/farmacocinética , Carbonato de Cálcio/administração & dosagem , Carbonato de Cálcio/uso terapêutico , Índice de Massa Corporal , Densidade Óssea , Avaliação Nutricional , Osteoporose Pós-Menopausa/dietoterapia , Osteoporose Pós-Menopausa/tratamento farmacológico , Programas de Rastreamento , Cálcio/deficiência , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/sangue , Colecalciferol/administração & dosagem , Colecalciferol/efeitos adversos , Estudos Cross-Over , Citrato de Cálcio/uso terapêutico , Fraturas Ósseas/prevenção & controle , Estrogênios/deficiência , Absorção Gastrointestinal/efeitos dos fármacos , Cooperação e Adesão ao Tratamento , Anabolizantes/uso terapêuticoRESUMO
Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.
Assuntos
Acloridria/complicações , Reabsorção Óssea/etiologia , Distúrbios do Metabolismo do Cálcio/fisiopatologia , Fraturas do Fêmur/complicações , Consolidação da Fratura , Animais , Cálcio/metabolismo , Cálcio/uso terapêutico , Distúrbios do Metabolismo do Cálcio/complicações , Suplementos Nutricionais , Feminino , Fraturas do Fêmur/metabolismo , Camundongos , Distribuição Aleatória , Receptor de Colecistocinina B/genéticaRESUMO
UNLABELLED: We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. INTRODUCTION: Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. METHODS: Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. RESULTS: Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. CONCLUSION: Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.
Assuntos
Gluconato de Cálcio/uso terapêutico , Gastrectomia/efeitos adversos , Hiperparatireoidismo Secundário/tratamento farmacológico , Osteoporose/tratamento farmacológico , Acloridria/tratamento farmacológico , Idoso , Animais , Biópsia , Densidade Óssea/efeitos dos fármacos , Cálcio/metabolismo , Gluconato de Cálcio/farmacologia , Carbamatos/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Homeostase/efeitos dos fármacos , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Ílio/patologia , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Osteoblastos/patologia , Osteoclastos/patologia , Osteoporose/etiologia , Osteoporose/patologia , Osteoporose/fisiopatologia , Estudos RetrospectivosRESUMO
The purpose of the present study is to investigate the effects of hypochlorhydria induced by proton pump inhibitor (PPI) administration and intake of a dairy product fermented by lactobacilli (DFL) on bone metabolism in growing rats. Male rats, aged 3 weeks, were divided into two groups: a control group fed a casein-based diet and a group fed a DFL-based diet. Each group was fed its respective experimental diets for 9 d. At day 5 of the feeding period, each group was divided into two subgroups: one that received a saline injection and one that received a PPI injection. Rats were subcutaneously administered saline or PPI for 5 d. Faecal Ca excretion was determined from day 6 to day 9. At the end of the experiment, plasma and femurs were collected. Administration of PPI significantly decreased bone mineral density (shown by X-ray computerised tomography) and bone strength (shown by a three-point bending test) in the control group. Plasma osteocalcin, type I collagen C-telopeptides, 1,25-dihydroxyvitamin D and parathyroid hormone concentrations were elevated by PPI administration in the control group. Faecal Ca excretion and urinary P excretion in the control group were remarkably increased by PPI administration. On the other hand, these adverse effects of PPI were not observed in the DFL group. These results suggest that hypochlorhydria-induced bone loss may result from high bone turnover induced by secondary hyperparathyroidism due to Ca malabsorption and that DFL intake cancels these adverse effects probably via improving Ca malabsorption in growing rats.
Assuntos
Acloridria/metabolismo , Osso e Ossos/metabolismo , Laticínios , Fermentação , Lactobacillus/metabolismo , Inibidores da Bomba de Prótons/farmacologia , Animais , Peso Corporal , Densidade Óssea , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Suco Gástrico/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Fósforo/metabolismo , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada por Raios XRESUMO
Malabsorption of dietary calcium is a cause of osteoporosis. Dissolution of calcium salts (e.g. calcium carbonate) in the stomach is one step in the proper active and passive absorption of calcium as a calcium ion (Ca(2+)) in the proximal small intestine. Stomach acid markedly increases dissolution and ionization of poorly soluble calcium salts. If acid is not properly secreted, calcium salts are minimally dissolved (ionized) and, subsequently, may not be properly and effectively absorbed. Atrophic gastritis, gastric surgery, and high-dose, long-term use of antisecretory drugs markedly reduce acid secretion and may, therefore, be risk conditions for malabsorption of dietary and supplementary calcium, and may thereby increase the risk of osteoporosis in the long term.
Assuntos
Acloridria/complicações , Distúrbios do Metabolismo do Cálcio/etiologia , Cálcio/metabolismo , Mucosa Gástrica/metabolismo , Osteoporose/etiologia , Acloridria/metabolismo , Suplementos Nutricionais , Gastrectomia/efeitos adversos , Ácido Gástrico/metabolismo , Gastrite Atrófica/complicações , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de RiscoRESUMO
The NHE4 Na+/H+ exchanger is abundantly expressed on the basolateral membrane of gastric parietal cells. To test the hypothesis that it is required for normal acid secretion, NHE4-null mutant (NHE4-/-) mice were prepared by targeted disruption of the NHE4 (Slc9a4) gene. NHE4-/- mice survived and appeared outwardly normal. Analysis of stomach contents revealed that NHE4-/- mice were hypochlorhydric. The reduction in acid secretion was similar in 18-day-old, 9-week-old, and 6-month-old mice, indicating that the hypochlorhydria phenotype did not progress over time, as was observed in mice lacking the NHE2 Na+/H+ exchanger. Histological abnormalities were observed in the gastric mucosa of 9-week-old NHE4-/- mice, including sharply reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells. NHE4-/- parietal cells exhibited limited development of canalicular membranes and a virtual absence of tubulovesicles, and some of the microvilli had centrally bundled actin. We conclude that NHE4, which may normally be coupled with the AE2 Cl-/HCO3- exchanger, is important for normal levels of gastric acid secretion, gastric epithelial cell differentiation, and development of secretory canalicular and tubulovesicular membranes.
Assuntos
Ácido Gástrico/metabolismo , Trocadores de Sódio-Hidrogênio/fisiologia , Acloridria/patologia , Alelos , Processamento Alternativo , Animais , Apoptose , Northern Blotting , Western Blotting , Diferenciação Celular , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Éxons , Gastrinas/metabolismo , Concentração de Íons de Hidrogênio , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Modelos Biológicos , Modelos Genéticos , Mutação , Necrose , Células Parietais Gástricas/citologia , Células Parietais Gástricas/ultraestrutura , Fenótipo , RNA/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trocadores de Sódio-Hidrogênio/metabolismo , Fatores de TempoRESUMO
Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.
Assuntos
Acloridria/genética , Antiácidos/efeitos adversos , Antioxidantes/uso terapêutico , Transformação Celular Neoplásica/efeitos dos fármacos , Dano ao DNA , Suplementos Nutricionais , Acloridria/metabolismo , Adulto , Idoso , Antioxidantes/farmacocinética , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/uso terapêutico , Esôfago de Barrett/genética , Esôfago de Barrett/metabolismo , Feminino , Determinação da Acidez Gástrica , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Inibidores da Bomba de Prótons , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Vitamina E/farmacocinética , Vitamina E/uso terapêuticoRESUMO
OBJECTIVE: Low gastric pH is generally believed to be an important factor in intestinal mineral absorption. Thus, hypochlorhydria could be an important risk factor for mineral malabsorption and the development of marginal mineral status. We studied whether the hypochlorhydria associated with treatment with the anti-ulcer medication omeprazole, a potent gastric proton pump inhibition, would affect intestinal calcium, phosphorus, magnesium, or zinc absorption from food. METHODS: Thirteen normal, healthy adults were assigned to either a control group (n = 5) receiving no drug treatment or an omeprazole treatment group (n = 8) to produce increased gastric pH. Omeprazole treatment of normal volunteers resulted in a significant change in postprandial gastric pH (pH 6.4 +/- 0.3 vs. 3.6 +/- 0.5 in control subjects, p < 0.01) and baseline fasting pH (pH 5.8 +/- 0.5 vs. pH 1.8 +/- 0.3 in controls, p < 0.01) after an overnight fast. Net mineral absorption from a standard test meal was measured using a whole gut lavage technique. Mineral absorption was measured twice in each subject, once with 120 mL of 0.1 mol/liter hydrochloric acid and a second time with 120 mL of distilled water alone. RESULTS: We found that despite marked changes in gastric pH due to drug treatment or administration of exogenous HCl, no change in the intestinal absorption of calcium, phosphorus, magnesium or zinc from a standard test meal was evident. CONCLUSIONS: These findings suggest that changing the gastric pH alone does not modify the net intestinal absorption of several minerals from food. Therefore, it is unlikely that moderate hypochlorhydria resulting from short-term omeprazole treatment substantially increases the risk for developing calcium, phosphorus, magnesium, or zinc deficiencies due to mineral malabsorption.
Assuntos
Acloridria/induzido quimicamente , Acloridria/metabolismo , Antiulcerosos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Metais/farmacocinética , Omeprazol/farmacologia , Fósforo/farmacocinética , Acloridria/fisiopatologia , Adulto , Idoso , Cálcio/análise , Cálcio/farmacocinética , Feminino , Análise de Alimentos , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Magnésio/análise , Magnésio/farmacocinética , Masculino , Metais/análise , Pessoa de Meia-Idade , Fósforo/análise , Estômago/fisiologia , Zinco/análise , Zinco/farmacocinéticaRESUMO
There are more than a dozen commonly prescribed calcium supplements and hundreds of different formulations commercially available. Numerous factors need to be considered when selecting a calcium preparation. Physical properties such as solubility, interference from coingested medications or foodstuffs, dosage, and timing can all affect the bioavailability of calcium. Medical conditions such as lactose intolerance, impaired gastric acid secretion, and high risk profile for kidney stone formation may impact on selection of a calcium supplement. This article will review the available literature and make general recommendations for the optimal use of calcium preparations.
Assuntos
Cálcio da Dieta/administração & dosagem , Cálcio/efeitos adversos , Acloridria/metabolismo , Disponibilidade Biológica , Desenvolvimento Ósseo/efeitos dos fármacos , Cálcio/economia , Cálcio/farmacocinética , Cálcio da Dieta/análise , Cálcio da Dieta/uso terapêutico , Alimentos Fortificados/efeitos adversos , Alimentos Fortificados/economia , Humanos , Absorção Intestinal , Cálculos Renais/etiologia , Lactase , Necessidades Nutricionais , beta-Galactosidase/deficiênciaRESUMO
Young infants and approximately 30% of the elderly have low secretion of hydrochloric acid by gastric parietal cells. It has been established that low hydrochloric acid secretion can lead to decreased absorption of ferric iron. Conflicting results have been obtained in clinical studies of the effects of intraluminal gastric pH values on calcium absorption. The results of an in vitro study suggest that the chemical form of the ingested calcium and the presence of protein may influence whether high intraluminal gastric pH values affect resultant calcium solubilities in the small intestine. The effects of low hydrochloric acid secretion on zinc absorption have not been ascertained. The results of an in vitro study indicate that high intraluminal gastric pH values would not affect resultant zinc solubilities in the small intestine following pancreatin digestion of soy protein isolate supplemented with calcium and/or zinc. Considering that the diets of many elderly contain primarily plant foods and that soy protein isolate formulas are commonly fed to infants, further research is especially needed to determine the effects of low hydrochloric acid secretion on mineral bioavailabilities from high fiber and phytate containing plant foods.
Assuntos
Acloridria/metabolismo , Ácido Gástrico/fisiologia , Minerais/farmacocinética , Adulto , Idoso , Envelhecimento/fisiologia , Disponibilidade Biológica , Cálcio da Dieta/farmacocinética , Fibras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Humanos , Recém-Nascido , Absorção Intestinal , Ferro/farmacocinética , Solubilidade , Zinco/farmacocinéticaRESUMO
Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 mumol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 mumol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250-500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secretion.
Assuntos
Ácido Gástrico/metabolismo , Hormônios Gastrointestinais/fisiologia , Acloridria/fisiopatologia , Animais , Gastrectomia , Fundo Gástrico/análise , Gastrinas/sangue , Gastrinas/fisiologia , Histocitoquímica , Omeprazol/farmacologia , Radioimunoensaio , Ranitidina/farmacologia , RatosRESUMO
Defective absorption of calcium has been thought to exist in patients with achlorhydria. I compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.
Assuntos
Acloridria/metabolismo , Cálcio/metabolismo , Absorção Intestinal , Adulto , Idoso , Carbonato de Cálcio/metabolismo , Radioisótopos de Cálcio , Citratos/metabolismo , Ácido Cítrico , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Ácido Gástrico/metabolismo , Gastrite Atrófica/terapia , Gastrite/terapia , Oxigenoterapia Hiperbárica , Úlcera Péptica/terapia , Acloridria/fisiopatologia , Acloridria/terapia , Adulto , Idoso , Doença Crônica , Estudos de Avaliação como Assunto , Feminino , Gastrite Atrófica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/fisiopatologiaRESUMO
Since calcium solubility is a prerequisite to calcium absorption, and since solubility of calcium is highly pH-dependent, it has been generally assumed that gastric acid secretion and gastric acidity play an important role in the intestinal absorption of calcium from ingested food or calcium salts such as CaCO3. To evaluate this hypothesis, we developed a method wherein net gastrointestinal absorption of calcium can be measured after ingestion of a single meal. A large dose of cimetidine, which markedly reduced gastric acid secretion, had no effect on calcium absorption in normal subjects, and an achlorhydric patient with pernicious anemia absorbed calcium normally. This was true regardless of the major source of dietary calcium (i.e., milk, insoluble calcium carbonate, or soluble calcium citrate). Moreover, calcium absorption after CaCO3 ingestion was the same when intragastric contents were maintained at pH 7.4 (by in vivo titration) as when intragastric pH was 3.0. On the basis of these results, we conclude that gastric acid secretion and gastric acidity do not normally play a role in the absorption of dietary calcium. Other possible mechanisms by which the gastrointestinal tract might solubilize ingested calcium complexes and salts are discussed.
Assuntos
Cálcio da Dieta/metabolismo , Ácido Gástrico/metabolismo , Absorção Intestinal , Acloridria/complicações , Acloridria/metabolismo , Adulto , Anemia Perniciosa/complicações , Carbonato de Cálcio/metabolismo , Cimetidina , Citratos/metabolismo , Ácido Cítrico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-IdadeRESUMO
In order to evaluate whether gastric inhibitory polypeptide (GIP) could be responsible for the postprandial fall in serum gastrin previously observed in patients with achlorhydria, 7 achlorhydric patients were given 100 ml Lipomul (66 g triglycerides) on one occasion, and 5 of these patients were later given a 30-min intravenous infusion of porcine GIP in a dose of 1 microgram/kg. Following the Lipomul ingestion, serum gastrin fell significantly, whereas no effect on serum gastrin was seen during the intravenous GIP infusion. A small, but significant release of serum insulin was seen shortly after starting the GIP infusion, together with a significant and more sustained release of plasma pancreatic polypeptide (PP). It is concluded that GIP does not lower the serum gastrin levels in achlorhydric patients, but that GIP might participate in the intestinal phase of the PP release.
Assuntos
Acloridria/metabolismo , Polipeptídeo Inibidor Gástrico , Hormônios Gastrointestinais , Polipeptídeo Pancreático/metabolismo , Adulto , Idoso , Óleo de Milho , Gorduras na Dieta/administração & dosagem , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Gastrinas/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Óleos/administração & dosagemRESUMO
A 72-year-old female gave a history of chronic gastrointestinal blood loss necessitating transfusion with over 90 units of blood despite continuous oral iron therapy over a period of 24 years. Gastroscopic appearances were very similar to those recently described by Lewis and by Wheeler in patients with submucosal angiomatous lesions and chronic gastrointestinal blood loss. Striking erythematous streaks radiated from the pylorus and were confined to the antrum. In our case complete achlorhydria to pentagastrin was associated with low serum and antral gastrin concentrations. The introduction of oral prednisolone was followed by a marked fall in the rate of gastrointestinal blood loss, removing the need for transfusion during the following year. Complete achlorhydria persisted and endoscopic appearances remained unchanged, but there was a marked rise in antral and serum gastrin concentrations. The possible modes of action of prednisolone in this case are discussed. The patient remains well in November 1979. The dose of prednisolone was reduced to 10 mg on alternate days in May 1979. Iron supplements have been continued but no transfusion has been required since the start of steroid therapy. The hemoglobin has gradually risen to 14.9 g/dl.
Assuntos
Acloridria/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Prednisolona/uso terapêutico , Acloridria/diagnóstico , Acloridria/patologia , Transfusão de Sangue , Resina de Colestiramina/uso terapêutico , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia , Humanos , Pessoa de Meia-IdadeRESUMO
Verner and Morrison, in 1958, reported non-insulin-secreting tumours of the pancreas that were associated with a syndrome of refractory diarrhea, achlorhydria and hypokalemia. Surgical resection of such tumours results in rebound acid hypersecretion and cessation of the watery diarrhea. The authors report the case of an 84-year-old man who had three of the four major criteria for diagnosis of the Verner Morrison syndrome. Hypokalemia was absent, but this was possibly due to the large doses of potassium chloride that he was taking in conjunction with diuretics. After resection of the tumour severe obstipation with resultant bowel obstruction developed in addition to rebound hypersecretion and relief of watery diarrhea. Treatment, consisting of bulk laxatives in appropriate amounts, alleviated the obstipation.