Gut Calcium Absorption Research Articles

Microbial Composition of a Traditional Fermented Wheat Preparation—Nishasta and Its Role in the Amelioration of Retinoic Acid-Induced Osteoporosis in Rats

Fermented foods have a long history of human use. The purpose of this study was to characterize the microbial composition of a traditional fermented wheat preparation—Nishasta— and to explore its effect in retinoic acid-induced osteoporosis in Wistar rats. The sample was suspended in sterile water (10% w/v), mixed thoroughly, filtered, and gradually diluted. Aliquots of dilutions were cultured in MRS (DeMan–Rogosa–Sharpe) medium, and colonies with similar morphologies were subjected to DNA extraction. The 16S rRNA gene of the isolates was amplified by polymerase chain reaction, checked by agarose gel electrophoresis, and finally identified by sequencing. Anti-osteoporosis screening of Nishasta was carried out in female Wistar rats using retinoic acid as an inducer (70 mg/kg, p.o. once a day for 14 days). Its effect on bone health parameters was determined. The bone metabolism markers such as hydroxyproline (HOP), tartrate-resistant acid phosphatase (TRACP), and alkaline phosphatase (ALP) were evaluated. The results of microbial characterization revealed the presence of ten clones of Lactobacillus plantarum in the fermented preparation with L. plantarum NF3 as the predominant strain. The average microbial count was 2.4 × 103 CFU/g. Retinoic acid administration led to a marked disorder of various bone health markers in rats. It also increased the levels of urine calcium and phosphorus, indicating increased bone destruction. Treatment with fermented wheat (at 200, 100, and 50 mg/kg doses, p.o. daily for 42 days after the induction of osteoporosis) improved bone mineral density in a dose-dependent manner. It also improved the bone microstructure and reduced the levels of ALP, TRACP, and HOP. Micro-CT revealed that it reduced trabecular separation and increased the percent bone volume, trabecular numbers, trabecular thickness, and bone mineral density in the rats. The results showed that the fermented wheat promoted bone formation and prevented bone resorption. Our findings clearly established the effectiveness of Nishasta against osteoporosis in Wistar rats that can be partly attributed to the improved gut calcium absorption and microbiota composition.

Vitamin D in Dialysis: Defining Deficiency and Rationale for Supplementation

Vitamin D status is determined by the serum concentration of one of its metabolites, 25-hydroxy-D. Defining vitamin D deficiency based on its classical roles in gut calcium absorption and bone mineralization is problematic in dialysis patients and, until recently, was ignored in the nephrology literature. The newly recognized nonclassical functions of vitamin D include effects on the immune system, cardiovascular disease, and cancer. The nonclassical effects are likely to be equally relevant in the dialysis population, but suffer from a lack of strong evidence on which to base therapeutic targets. Past medical opinion in the nondialysis population warned that higher dose vitamin D supplementation may be toxic and was unnecessary. This is because older supplementation recommendations were based on early twentieth century studies using cod-liver oil to treat rickets. The clinical resolution of rickets requires a relatively low dose of vitamin D. Current vitamin D guidelines generally target higher 25-hydroxy-D levels of 30 ng/ml, based on optimizing markers of bone health. This results in very high estimates of 50-100% for the prevalence of vitamin D deficiency in dialysis patients. This review examines the relevance of data on the classical and nonclassical effects of vitamin D in dialysis patients. An evidence-based dosing regimen for use in dialysis patients is suggested to safely and reliably achieve vitamin D sufficiency.

Endocrine and Bone Metabolic Complications in Chronic Liver Disease and After Liver Transplantation in Children

With improved survival of orthotopic liver transplantation (OLT) in children, prevention and treatment of pre- and posttransplant complications have become a major focus of care. End-stage liver failure can cause endocrine complications such as growth failure and hepatic osteodystrophy, and, like other chronic illnesses, also pubertal delay, relative adrenal insufficiency, and the sick euthyroid syndrome. Drug-induced diabetes mellitus post-OLT affects approximately 10% of children. Growth failure is found in 60% of children assessed for OLT. Despite optimisation of nutrition, rarely can further stunting of growth before OLT be prevented. Catch-up growth is usually observed after steroid weaning from 18 months post-OLT. Whether growth hormone treatment would benefit the 20% of children who fail to catch up in height requires testing in randomised controlled trials. Hepatic osteodystrophy in children comprises vitamin D deficiency rickets, low bone mass, and fractures caused by malnutrition and malabsorption. Vitamin D deficiency requires aggressive treatment with ergocalciferol (D2) or cholecalciferol (D3). The active vitamin D metabolites alphacalcidol or calcitriol increase gut calcium absorption but do not replace vitamin D stores. Prevalence of fractures is increased both before OLT (10%-28% of children) and after OLT (12%-38%). Most fractures are vertebral, are associated with low spine bone mineral density, and frequently occur asymptomatically, but they may also cause chronic pain. Fracture prediction in these children is limited. OLT in children is also associated with a greater risk of developing avascular bone necrosis (4%) and scoliosis (13%-38%). This article reviews the literature on endocrine and skeletal complications of liver disease and presents preventive screening recommendations and therapeutic strategies.

Cohesion of epithelial ion homeostasis: implementing calcium transport with sodium transporters?

THE ABILITY TO MOVE SOLUTES between the exterior and interior of an organism, between different extracellular compartments, between intracellular and extracellular space, and between organelles and cytoplasm involves a myriad of transport mechanisms; all of which are indispensible for life. Considering the wide variety of solutes that have to be translocated at each of these levels, the precise transport machineries devoted to each solute, and the host of regulatory mechanisms accompanying each of these ensembles, one ponders whether we have enough genes in our genome to achieve these homeostatic feats. The intuitive answer is of course “yes” since we have already succeeded in doing so. While the utilization of multiple proteins to serve the same means bestows redundancy and insurance, the evolution of one protein to execute multiple functions maximizes genetic economy. The fact that one gene product can serve multiple and diverse functions may be a well-known and foregone conclusion to all but is still a remarkable phenomenon to be marveled. Take as an example the most abundant protein in our circulation: hemoglobin. In addition to its known function of carrying O2, hemoglobin also regulates O2 offloading as a metabolic sensor of tissue oxygenation, couples CO2 and nitric oxide transport at the lung and periphery, buffers H, releases vasodilators to directly regulate local blood flow, regulates circadian rhythm of antioxidant, and may even participates in immune surveillance. It is unlikely that this multitasking coevolved completely contemporaneously but was more likely to have done so in tandem, or more likely in “overlapping tandems,” where the needs of one function modulate the evolution of the others. Inherent in this system of serving many masters exist inevitable conflicts that at some point mandate some degree of compromise.

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Idiopathic hypercalciuria (IH) is the most common metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is greater than 250 mg/d in women and 300 mg/d in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, a negative calcium balance is seen commonly in balance studies, especially on a low-calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered parathyroid hormone levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients.

Effects of vitamin D metabolites on intestinal calcium absorption and bone turnover in elderly women

The relative importance of vitamin D metabolites in the regulation of gut calcium absorption has not been well studied in elderly women living in an environment with abundant sunlight. The objective was to examine the determinants of active gut calcium absorption ( +/- SD: 42 +/- 11%) after an overnight fast with the use of a low (10 mg) calcium load. One hundred twenty elderly women aged 74.7 +/- 2.6 y underwent an active calcium absorption test with a radioactive calcium tracer, dietary analysis, and measurement of markers of bone turnover and calcium metabolism. The mean serum 25-hydroxyvitamin D [25(OH)D] concentration at the time of the calcium absorption test was 68 +/- 29 nmol/L. Gut calcium absorption was correlated with 25(OH)D but not 1,25-dihydroxyvitamin D (calcitriol), the free calcitriol index, or dietary calcium intake. After adjustment for age, calcitriol concentration, and dietary calcium intake, the significant determinant of fractional calcium absorption was the 25(OH)D concentration (r = 0.34, P = 0.001). When body weight was included in the regression, both 25(OH)D (beta = 1.20 x 10(-3)) and calcitriol (beta = 1.00 x 10(-3)) were significantly correlated with calcium absorption. Despite the strong relation between 25(OH)D and gut calcium absorption, there was no relation with other aspects of bone turnover or calcium metabolism. These data suggest that at low calcium loads, 25(OH)D is a more important determinant of gut calcium absorption than is calcitriol in elderly women exposed to abundant sunlight, but that this relation has little effect on overall calcium metabolism.

Correlates of intestinal calcium absorption in women 10 years past the menopause.

Because intestinal calcium absorption may be an important independent determinant of calcium balance and therefore bone mass, we have studied this factor and other potential predictors in 196 healthy postmenopausal women. Gut calcium absorption was measured in each subject by a stable strontium method and expressed as a fractional absorption. The fractional absorption was significantly negatively correlated with years since menopause (YSM) (r = -0.15 P < 0.05) and dietary calcium intake (r = -0.15 P < 0.05), and significantly positively correlated with 24-hour urine calcium excretion (r = 0.31 P < 0.001) and body mass index (r = 0.20 P < 0.01). Apart from YSM, these factors remained as correlates in multiple regression analysis; the standardized regression coefficient was largest for 24-hour urine calcium excretion (0.32). Fractional absorption of calcium was not correlated with vertebral bone density. Thus, intestinal calcium absorption, although falling with increasing menopausal age and increasing calcium intake, is best correlated with the urine calcium excretion. This indicates either that gut calcium absorption is regulated in response to the magnitude of the urine calcium excretion or that the kidney maintains calcium balance by excreting what is absorbed by the intestine. The mechanisms whereby gut and renal calcium handling are correlated are uncertain.

Recurrent kidney stones: causes and diagnostic criteria in patients from Campania (southern Italy).

A study was carried out on 180 recurrent kidney stone formers from the Campania region of southern Italy. The data showed that this hypercalciuric population was similar to that in previous studies; however, there was no difference in terms of parathyroid activity when compared with normal controls. The slightly depressed serum levels of vitamin D in hypercalciurics indicate that gut calcium absorption is not directly related to vitamin D levels. We found no difference in the prevalence of metabolic abnormalities associated with stone formation between the patients in this series and those in previous studies.

Altered kinetics of an intravenous calcium load in idiopathic hypercalciuria

Increased gut calcium absorption or reduced renal tubular calcium reabsorption have been alternatively reported in idiopathic hypercalciuria with kidney calculi. The present study aimed to investigate the handling of an exogenous calcium load in hypercalciuric stone formers to detect possible differences with regard to tissue calcium metabolism in vivo. A constant rate intravenous calcium infusion (0.2 mmol kg bodyweight per two hours) was carried out on six absorptives and six renals, defined according to the reported criteria, as well as on normal controls from clinical staff. Serum ionized calcium concentration were determined at regular intervals during the infusion and in the four hours after the end of calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections. Absorptive and renal hypercalciurics had lower serum ionized calcium levels compared with normal controls at all experimental times, a finding that suggests a faster disappearance of calcium from the circulation. The total body calcium clearance calculated from the area under the curve of the serum calcium concentrations was enhanced in hypercalciuric patients ( P < .001). Although renal calcium excretion was higher in hypercalciurics, renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels found in the hypercalciurics could not be explained by the renal calcium leak. The enhanced total body calcium clearance found in hypercalciuric subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of altered cell calcium handling in idiopathic hypercalciura with no difference between the so-called absorptives and renals in terms of the pathophysiologic mechanism.

Mechanism of dietary modulation of calcitonin levels in Fischer rats.

Aging caused an increase in serum calcitonin that was markedly suppressed by food restriction. Food restriction had no significant effect on gut calcium absorption, urinary calcium excretion, serum 1,25(OH)2 vitamin D, blood ionized calcium, the clearance of calcitonin from plasma, and its rate of inactivation in vitro by the kidney and liver. In contrast, food restriction modulated an increase with age in calcitonin secreting C-cells, thyroidal calcitonin and thyroidal calcitonin mRNA pools. We conclude that the lowering of age-related increase in serum calcitonin levels by food restriction is likely because of lowered thyroid calcitonin pools rather than changes in the metabolism of calcium, which is the primary stimulus for calcitonin secretion. Our findings also suggest that food restriction decreases age-related increase in calcitonin levels, at least in part, by modulating the expression of the calcitonin gene.

The effects of dietary calcium deprivation on serum calcitriol levels in premenopausal and postmenopausal women

The effect of the postmenopausal state on serum calcitriol levels was studied in 13 normal premenopausal women and 10 normal postmenopausal women under basal conditions and during seven days of dietary calcium deprivation. Calcitriol levels and the free calcitriol index were lower in the postmenopausal women, and this difference persisted during calcium deprivation. One of the major actions of calcitriol is to increase gut calcium absorption. Relative calcitriol deficiency, despite retained renal synthetic reserve, would in part explain the increased dietary calcium requirement to maintain calcium balance in postmenopausal women.