Effects of inulin on calcium metabolism and bone health.

Inulin, a dietary fibre found in the roots of many plants, has positive effects on health. It is particularly noteworthy due to its positive impact on calcium metabolism. Inulin has significant functions, such as improving calcium absorption through passive diffusion, bolstering calcium absorption via ion exchange and expanding the absorption surface of the colon by stimulating cell growth. In addition, inulin boosts calcium absorption by increasing calcium solubility, stimulating levels of calcium-binding protein expression and increasing useful microorganisms. It increases calbindin levels and stimulates transcellular active calcium transport. An inulin intake of least 8-10 g/day supports calcium absorption and total body bone mineral content/density in adolescents through its known mechanisms of action. It also significantly enhances calcium absorption and improves bone health in postmenopausal women and adult men. Sustained and sufficient inulin supplementation in adults has a positive effect on calcium metabolism and bone mineral density.

Calcium status assessment at the population level: Candidate approaches and challenges.

Inadequate dietary calcium intake is a global public health problem that disproportionately affects low- and middle-income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high-risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium-rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population-level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population-based surveys.

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. AIM OF THE STUDY: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. MATERIALS AND METHODS: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. RESULTS: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. CONCLUSIONS: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.

A comparison of the release of phosphorus by a phytase enzyme in pigs fed diets deficient or adequate in phosphorus content.

Previous research indicated that phytase may release less phosphorus (P) from phytate when it is evaluated using diets with P levels above requirement as compared with diets below requirement. The objectives of this experiment were to further test the hypothesis that the P release values determined for phytase are higher when pigs are fed diets that are deficient (DE) in P compared with when they are fed diets that are adequate (AD) in P, and that phytase will increase the digestibility of dry matter (DM), gross energy (GE), nitrogen (N), and calcium (Ca) independent of dietary P status. Twenty-four barrows (body weight: 23.2 ± 1.8 kg) were randomly assigned to one of eight dietary treatments and housed in individual pens for 21 d and then moved to metabolism crates for 9 d, with the collection of urine and feces occurring on the final 5 d. A basal corn-soybean meal diet (P-AD) was formulated at 0.36% standardized total tract digestible (STTD) P and total calcium:STTD P (Ca:STTD P) of 2:1. A P-DE diet was also formulated to maintain a constant Ca:STTD P of 2:1 in both basal diets. Phytase was added to AD and DE diets at 350, 600, 1,000 phytase units (FYT)/kg. Pig was the experimental unit; diet (P-AD or P-DE), phytase level, and replicate were fixed effects. Orthogonal polynomial contrasts were used to test linear and quadratic effects of phytase within P-AD and P-DE diets. Phytase improved apparent total tract digestibility (ATTD) and STTD of P in both P-AD (linear P < 0.001) and P-DE diets (quadratic P < 0.001). Estimates for STTD P release were 0.07%, 0.09%, and 0.09% for 350, 600, and 1,000 phytase units (FYT)/kg in P-DE diets, and 0.02%, 0.03%, and 0.05% in P-AD diets, respectively. In P-DE diets, phytase improved absorption and retention of P and increased urinary excretion of P (quadratic P < 0.001). In P-AD diets, phytase improved absorption of P (linear P = 0.066), tended to improve retention (linear P = 0.066), and increased urinary excretion of P (quadratic P = 0.021). Phytase improved ATTD of Ca in P-DE diets (quadratic P = 0.002) but not in P-AD diets (P > 0.1). In conclusion, the release of P by phytase is lower in diets that are AD in P than those which are DE. Phytase increased the availability of Ca only in the diets DE in P. Finally, phytase increased the ATTD of DM and tended to increase the ATTD of energy, independent of dietary P status.

Calcium and Bone.

The maintenance of extracellular calcium levels within a narrow range is necessary for normal function of the nervous system, muscle, and coagulation, to maintain mineralization of the skeleton but to avoid calcification of soft tissues. Accordingly, absorption and excretion of calcium is closely regulated, and adult humans can adapt to a wide range of calcium intakes from 300 to 2,000 mg/day. The evidence that low calcium intakes contribute to osteoporosis development is weak, as is evidence that increasing these intakes significantly changes fracture risk. Consistent with this view, the United States Preventive Services Task Force does not support the use of calcium supplements in healthy community-dwelling adults. While some groups continue to recommend that supplements of calcium and vitamin D are given with drug treatments for osteoporosis, this view is not supported by clinical trials which demonstrate anti-fracture efficacy of estrogens and bisphosphonates in the absence of such supplementation. Thus, calcium supplements have only a minor place in contemporary medical practice.

Associations of Calcium from Food Sources Versus Phosphate Binders with Serum Calcium and FGF23 in Hemodialysis Patients.

BACKGROUND: Dysregulated serum calcium and FGF23 are associated with increased mortality and morbidity rates in patients receiving hemodialysis. Preliminary data suggest serum calcium regulates FGF23 secretion independently of serum phosphate, parathyroid hormone, and 25-OH vitamin D. It is unclear to what extent dietary and prescription sources of calcium influence calcium and FGF23 levels, and whether they confound this relationship. In this cross-sectional analysis of a multi-ethnic cohort of prevalent hemodialysis patients, association of dietary calcium and prescribed calcium were examined against serum calcium and FGF23. Bi- and multivariable linear regression was used for all analyses. RESULTS: 81 patients (mean age 58 years, dialysis vintage 2 years, 51 men) participated. Dietary calcium was inversely associated with FGF23 (p = 0.04) however association of FGF23 with prescribed calcium did not reach statistical significance (0.08). In multivariable models, dietary calcium and prescribed calcium were associated in opposing directions with serum calcium (prescribed calcium; ß-coefficient = -0.35, p = 0.005 versus dietary calcium; ß-coefficient = 0.35, p = 0.03). FGF23 was independently associated with serum calcium (p = 0.007). CONCLUSIONS: We found differing, sometimes opposing, associations between serum calcium and FGF23 levels when considering prescribed versus dietary sources of calcium. Serum calcium and FGF23 were strongly correlated regardless of possible confounders examined in this hemodialysis cohort. Dietary calcium was associated with higher serum calcium and lower FGF23 concentrations, while prescribed calcium was only inversely associated with serum calcium. Further studies are required to confirm these associations and determine causality.

Administration of Inulin-Supplemented Gluten-Free Diet Modified Calcium Absorption and Caecal Microbiota in Rats in a Calcium-Dependent Manner.

In coeliac disease (CD), the risk of adverse calcium balance and reduced bone density is induced mainly by the disease, but also by a gluten-free diet (GFD), the only accepted CD therapy. Prebiotics through the beneficial impact on intestinal microbiota may stimulate calcium (Ca) absorption. In the present study, we hypothesised that the dietary inulin in GFD would influence positively the intestinal microbiota, and by that will stimulate the absorption of calcium (Ca), especially in the conditions of Ca malnutrition. In a six-weeks nutritional experiment on growing a significant (p < 0.05) luminal acidification, decrease in ammonia concentration and stimulation of short chain fatty acids formation indicated inulin-mediated beneficial effects on the caecal microbiota. However, the effect of inulin on characteristics of intestinal microbiota and mineral utilization depended on the dietary Ca intake from GFDs. Inulin stimulated bifidobacteria, in particular B. animalis species, only if a recommended amount of Ca was provided. Most benefits to mineral utilization from inulin consumption were seen in rats fed Ca-restricted GFD where it increased the relative Ca absorption. Administration of inulin to a GFDs could be a promising dietary strategy for beneficial modulation of intestinal ecosystem and by that for the improvement the Ca absorption.

Calcium Balance in Chronic Kidney Disease.

PURPOSE OF REVIEW: The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. RECENT FINDINGS: Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Calcium supplements: benefits and risks.

Calcium is an essential element in the diet, but there is continuing controversy regarding its optimal intake, and its role in the pathogenesis of osteoporosis. Most studies show little evidence of a relationship between calcium intake and bone density, or the rate of bone loss. Re-analysis of data from the placebo group from the Auckland Calcium Study demonstrates no relationship between dietary calcium intake and rate of bone loss over 5 years in healthy older women with intakes varying from <400 to >1500 mg day(-1) . Thus, supplements are not needed within this range of intakes to compensate for a demonstrable dietary deficiency, but might be acting as weak anti-resorptive agents via effects on parathyroid hormone and calcitonin. Consistent with this, supplements do acutely reduce bone resorption and produce small short-term effects on bone density, without evidence of a cumulative density benefit. As a result, anti-fracture efficacy remains unproven, with no evidence to support hip fracture prevention (other than in a cohort with severe vitamin D deficiency) and total fracture numbers are reduced by 0-10%, depending on which meta-analysis is considered. Five recent large studies have failed to demonstrate fracture prevention in their primary analyses. This must be balanced against an increase in gastrointestinal side effects (including a doubling of hospital admissions for these problems), a 17% increase in renal calculi and a 20-40% increase in risk of myocardial infarction. Each of these adverse events alone neutralizes any possible benefit in fracture prevention. Thus, calcium supplements appear to have a negative risk-benefit effect, and so should not be used routinely in the prevention or treatment of osteoporosis.

Calcium balance and negative impact of calcium load in peritoneal dialysis patients.

Like hemodialysis patients, peritoneal dialysis (PD) patients are facing an excessively increased burden of vascular and valvular calcification. According to some surveys, more than 80% of prevalent PD patients are complicated with vascular calcification, and more than one third have heart valve calcification. Dysregulated phosphate metabolism is well recognized to play an important role in inducing vascular calcification, but increasing evidence is suggesting that dysregulated calcium metabolism also promotes vascular calcification and might in fact be more potent than phosphate in inducing that calcification. Growing evidence from randomized controlled trials shows more progression of vascular calcification and higher mortality among chronic kidney disease (CKD) patients receiving calcium-based phosphate binders than among those receiving non-calcium-containing phosphate binders. Those results raise important safety concern about the use of high-dose calcium-based phosphate binders in the CKD population, including both non-dialysis and dialysis patients (especially anuric dialysis patients), who have markedly reduced urinary calcium excretion. To prevent calcium overload, this review recommends restricting the dose of calcium-based phosphate binders in CKD patients, especially those who are elderly, who have increased cardiovascular risk, who already have baseline vascular or valvular calcification, or who have low intact parathyroid hormone and adynamic bone disease.

The Effects of Manganese Supplementation on Bone Status and Calcium Balance in Ovariectomized Rats according to the Calcium Intake Levels

The purpose of this study was to investigate the effect of manganese (Mn) supplementation on bone status and calcium balance in ovariectomized rats according to the calcium intake levels. Total of 50 Sprague Dawley female rats (6 weeks) were divided into 5 groups and bred for 12 weeks: sham operated control group (SACa), OVX Ca deficiency group (OLCa) with Ca deficiency diet (0.1% Ca modified AIN-93N diet), OVX Ca deficiency & Mn supplement group (OLCaMn), OVX adequate Ca group (OACa; 0.5% Ca AIN-93N diet) and OVX adequate Ca & Mn supplement group (OACaMn). BMD (bone mineral density) of the femur was increased by Mn supplementation in OVX adequate Ca group. However, BMDs of spine, femur and tibia were lowered in OLCa compared to the OLCaMn group. Bone strength of tibia in OLCaMn group was significantly lower than OLCa group. Serum ALP (alkaline phosphatase) and CTx (C-telopeptide of collagen cross-links) levels were significantly higher in ovariectomized rats than those in the sham group, but they were not changed by Mn supplementation. Ca retention rate and Ca absorption rate did not differ among the experimental groups. Urinary Ca excretion was increased by Mn supplementation in Ca deficiency rats. In summary, Mn supplementation resulted in positive effects on bone mineral density ovariectomized rats with which intake adequate Ca. However, Mn supplementation on Ca deficiency ovariectomized rats resulted in decrement of BMD and bone strength by increasing Ca excretion. Therefore, it is encouraged to consider calcium intake levels in supplementation of manganese in order to prevent postmenopausal osteoporosis and to keep bone healthy.