Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study.

BACKGROUND: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.

Comparative In Vitro Dissolution Assessment of Calcined and Uncalcined Hydroxyapatite Using Differences in Bioresorbability and Biomineralization.

This study reports the effect of the not-calcining process on the bioresorption and biomineralization of hydroxyapatite through in vitro dissolution assessment. The prepared calcined hydroxyapatite (c-HAp) and uncalcined hydroxyapatite (unc-HAp) have a particle size of 2 µm and 13 µm, surface areas of 4.47 m2/g and 108.08 m2/g, and a Ca/P ratio of 1.66 and 1.52, respectively. In vitro dissolution assessments of c-HAp and unc-HAp were performed for 20 days at 37 °C in a citric acid buffer according to ISO 10993-14. During the dissolution, the c-HAp and unc-HAp confirmed an increase in weight, and the calcium and phosphorous ions were rapidly released. The calcium ions released from c-HAp formed rod-shaped particles with a longer and thinner morphology, while in unc-HAp, they appeared thicker and shorter. In the ICP-OES results, the concentrations of calcium elements were initially increased and then decreased by this formation. The rod-shaped particles identified as calcium citrate (Ca-citrate) through the XRD pattern. The calcium content of Ca-citrate particles from unc-HAp was higher than that from c-HAp. The unc-HAp demonstrated non-toxic properties in a cytotoxicity evaluation. Therefore, due to its higher bioresorption and biomineralization, unc-HAp exhibits enhanced biocompatibility compared to c-HAp.

The Facile Production of p-Chloroaniline Facilitated by an Efficient and Chemoselective Metal-Free N/S Co-Doped Carbon Catalyst.

The catalytic hydrogenation of the toxic and harmful p-chloronitrobenzene to produce the value-added p-chloroaniline is an essential reaction for the sustainable chemical industry. Nevertheless, ensuring satisfactory control of its chemoselectivity is a great challenge. In this work, a N/S co-doped metal-free carbon catalyst has been fabricated by using cysteine as a source of C, N, and S. The presence of calcium citrate (porogen agent) in the mixture subjected to pyrolysis provided the carbon with porosity, which permitted us to overcome the issues associated with the loss of heteroatoms during an otherwise necessary activation thermal treatment. Full characterization was carried out and the catalytic performance of the metal-free carbon material was tested in the hydrogenation reaction of p-chloronitrobenzene to selectively produce p-chloroaniline. Full selectivity was obtained but conversion was highly dependent on the introduction of S due to the synergetic effect of S and N heteroatoms. The N/S co-doped carbon (CYSCIT) exhibits a mesoporous architecture which favors mass transfer and a higher doping level, with more exposed N and S doping atoms which act as catalytic sites for the hydrogenation of p-chloronitrobenzene, resulting in enhanced catalytic performance when compared to the N-doped carbon obtained from melamine and calcium citrate (MELCIT) used as a reference.

Calcium Citrate Amount and Gelatine Source Impact on Hydroxyapatite Formation in Bone Regeneration Material in Simulated Body Fluid.

Bone grafting is crucial for bone regeneration. Recent studies have proposed the use of calcium citrate (CC) as a potential graft material. Notably, citrate does not inhibit hydroxyapatite (HAp) formation at specific calcium-to-citrate molar ratios. Octacalcium phosphate (OCP)/gelatine (Gel) composites, which are commonly produced from porcine Gel, are valued for their biodegradability and bone replacement capability. This study introduces fish Gel as an alternative to porcine Gel because of its wide acceptance and eco-friendliness. This is the first study to examine the interaction effects between two osteogenic materials, OCP/CC, and the influence of different gelatine matrix components on HAp formation in an SBF. Samples with varying CC contents were immersed in an SBF for 7 d and analysed using various techniques, confirming that high CC doses prevent HAp formation, whereas lower doses facilitate it. Notably, small-sized OCP/CC/porcine Gel composites exhibit a high HAp generation rate. Porcine Gel composites form denser HAp clusters, whereas fish Gel composites form larger spherical HAps. This suggests that lower CC doses not only avoid inhibiting HAp formation but also enhance it with the OCP/Gel composite. Compared with porcine Gel, fish Gel composites show less nucleation but an increased crystal growth for HAp.

Biguanide-Based Synthesis of 1,3,5-Triazine Derivatives with Anticancer Activity and 1,3,5-Triazine Incorporated Calcium Citrate Nanoparticles.

Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines-HCT116 and SW620. 2c and 3c which are the derivatives containing o-hydroxyphenyl substituents exhibited the highest activity with IC50 against both cell lines in the range of 20-27 µM, which is comparable to the IC50 of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative 2a. Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, "CaCit-2a NPs" were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of 2a from the synthesised CaCit-2a NPs is pH-responsive, and 2a could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.

Effect of Collagen Peptide, Alone and in Combination with Calcium Citrate, on Bone Loss in Tail-Suspended Rats.

Oral administration of bovine collagen peptide (CP) combined with calcium citrate (CC) has been found to inhibit bone loss in ovariectomized rats. However, the protective effects of CP and CP-CC against bone loss have not been investigated in a tail-suspension simulated microgravity (SMG) rat model. Adult Sprague-Dawley rats (n = 40) were randomly divided into five groups (n = 8): a control group with normal gravity, a SMG control group, and three SMG groups that underwent once-daily gastric gavage with CP (750 mg/kg body weight), CC (75 mg/kg body weight) or CP-CC (750 and 75 mg/kg body weight, respectively) for 28 days. After sacrifice, the femurs were analyzed by dual-energy X-ray absorptiometry, three-point bending mechanical tests, microcomputed tomography, and serum bone metabolic markers. Neither CP nor CP-CC treatment significantly inhibited bone loss in SMG rats, as assessed by dual-energy X-ray absorptiometry and three-point bending mechanical tests. However, both CP and CP-CC treatment were associated with partial prevention of the hind limb unloading-induced deterioration of bone microarchitecture, as demonstrated by improvements in trabecular number and trabecular separation. CP-CC treatment increased serum osteocalcin levels. Dietary supplementation with CP or CP-CC may represent an adjunct strategy to reduce the risk of fracture in astronauts.

Effects of calcium citrate, chitosan and chitooligosaccharide addition on acrylamide and 5-hydroxymethylfurfural formation in dark brown sugar.

Calcium citrate, chitosan, and chitooligosaccharide were added to sugarcane juice to investigate their effect on color, pH, antioxidant activity, reducing sugar, acrylamide and HMF mitigation in dark brown sugar production. Results showed that the content of 52-67% acrylamide in the dark brown sugar was mitigated with 0.1-1.0% chitosan addition and the reducing power of dark brown sugar increased with 0.5-1.0% chitosan addition. Furthermore, the addition of 0.5-1.0% chitosan or chitooligosaccharide increased HMF formation. Only the pH of dark brown sugar with chitosan addition was lower than that of other dark brown sugars. This is due to the low pH condition in dark brown sugar mitigating Maillard reaction and acrylamide formation. When the pH of sugarcane juice with chitosan adjusted back to pH 7 again, the acrylamide content of dark brown sugars significant increased (p < 0.05). Acrylamide and HMF are both produced through the Maillard reaction, the lower pH will cause the hydrolysis of sucrose to produce more HMF and reducing sugar. The L values and white index of dark brown sugar with 0.5-1.0% added chitosan were lower than those of control dark brown sugar (p < 0.05). High negative correlation was observed between HMF and acrylamide in the present study.

Calcium lactate as an attractive compound to partly replace salt in blue-veined cheese.

In addition to their high sodium content, cheeses are thought to induce an acid load to the body, which is associated with deleterious effects on consumers' health. Our objective was to explore the use of alkalinizing salts in partial substitution of NaCl to reduce both the sodium content and the acid-forming potential of cheese, without altering its sensory properties. Blue-veined cheeses were produced under industrial conditions, using brine salting followed by dry salting with a 4:1 (wt/wt) mixture of calcium lactate:NaCl or calcium citrate:NaCl. Sodium chloride was used in 2 granulometries: coarse (control treatment) and fine, to obtain homogeneous mixtures with the organic salts. Cheeses were then ripened for 56 d. No major appearance defects were observed during ripening. Calcium lactate substitution decreased the Na content of the cheese core by 33%, and calcium citrate substitution increased the citrate content of the cheese core by 410%, respectively, compared with fine NaCl. This study highlighted the substantial role of salt granulometry in sodium content, with the use of the coarse salt reducing the sodium content by 21% compared with fine salt. Sensory profiles showed nonsignificant differences in bitter and salty perceptions of salt-substituted cheeses with calcium lactate and calcium citrate compared with control cheeses. The use of calcium lactate should be considered to reduce the sodium content and improve the nutritional quality of cheeses while maintaining the sensory quality of the products. Alkalinizing organic salts could replace the acidifying salts KCl or CaCl2, which are currently used in salt replacement and are not recommended for consumers with renal disease. The method described here should be considered by cheese-making producers to improve the nutritional quality of cheese. Additional nutritional optimization strategies are suggested.

Wheat bread enriched with organic calcium salts and inulin. A bread quality study.

The objective of this work was to study quality parameters of enriched wheat bread with calcium citrate (Ca3CI2) or lactate (CaLA2) and inulin (In), also to optimize bread formulation. Fermentation time (tf), specific volume (Vs), browning index of crust (BI) and crumb properties (moisture, alveolus, texture) were studied. Generally, tf and Vs decreased with prebiotic increment. Ca3CI2 did not change Vs at equal inulin quantity, whereas with CaLA2 smaller breads were obtained (at 6.5 % In). Moisture of crumbs decreased with an increase in Ca3CI2 (at ≤ 6.5 %); while for CaLA2 was more influenced by the prebiotic. Up to 6.5 % In, the addition of both salts decreased crumb firmness and increased cohesiveness. Using a desirability function, the optimum calcium-prebiotic bread obtained with Ca3CI2 contained 2.40 g/kg Ca and 7.49 % In and with CaLA2 presented 1.33 g/kg Ca and 4.68 % In. Breads of high-quality with higher calcium and prebiotic quantity were able to obtain with Ca3CI2.

Nutrition, Vitamin D, and Calcium in Elderly Patients before and after a Hip Fracture and Their Impact on the Musculoskeletal System: A Narrative Review.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Effects of body mass index on urinary lithogenic factors in urinary system stone patients.

AIM: Obesity and metabolic syndrome are becoming more prevalent these days. In addition, we know that urinary stone disease is also on the rise. In this study, we wanted to examine if body mass index (BMI) had a negative effect on the stone disease by evaluating 24-hour urinalysis in stone patients and recurrence rates in our region.

Improving calcium citrate food functions through spherulitic growth in reactive crystallization and a mechanism study.

Calcium citrate, a high-end daily calcium supplement, whose irregular particle morphology leads to poor powder properties, limited food functions, and paste-like suspension problems. This study prepared the spherical calcium citrate by investigating four aspects of this reactive process: side reaction, crystallization, agglomeration, and fragmentation. Consequently, a concentration-dependent spherulitic growth operating space was established, in which reactive crystallization followed the second-category spherulitic growth mechanism depending on supersaturation. Besides, the temperature, stirring rate, and residence time were critical parameters for regulating the spherulite shape and size. These spherulites exhibited improved flowability and tabletability as calcium fortification ingredient, it also had a smoother and more pleasant texture. Furthermore, the micronized spherical powder showed high suspension stability as a calcium supplement during brewing. These spherical particles did not form paste-like suspension. Finally, the success of the scale-up experiments in semi-batch mode raised the possibility of industrialization of spherical calcium citrate.

Comparison of Physicochemical Properties of Noodles Fortified with Commercial Calcium Salts versus Calcium Citrate from Oyster Shells.

This study examined the physicochemical effects of the fortification of noodles with 0.25-1.00% (w/w) calcium salts, viz. calcium acetate, calcium carbonate, calcium citrate, and calcium lactate. Fortification with calcium citrate, calcium acetate, and calcium carbonate increased the pH and breaking force of the dried noodles. However, the fortification of noodles with any concentration of calcium did not increase the extent of elongation of the control raw noodles. The L* and b* values of the raw and dried noodle color increased with increasing concentrations of calcium salts, except for noodles with added calcium citrate. Fortification with calcium citrate yielded no significant influence on color, texture, adhesiveness, springiness, flavor, and overall scores for cooked noodles. Noodles fortified with 0.5% calcium citrate made from oyster shells were compared with a control sample of noodles and noodles fortified with commercially available calcium citrate. The particle size of the calcium citrate made from oyster shells (258 nm) was smaller than that of the purchased calcium citrate (2631 nm). Noodles fortified with calcium citrate made from oyster shells showed no significantly difference compared to noodles fortified with commercially available calcium citrate. These results suggest that calcium citrate made from oyster shells may be used as the additive of choice for the manufacture of calcium-fortified noodles.

Effects of ATP on the Physicochemical Properties and Cytocompatibility of Calcium Sulfate/Calcium Citrate Composite Cement.

Adenosine triphosphate (ATP), acting as a source of energy, has effects on cellular activities, such as adhesion, proliferation, and differentiation. In this study, ATP-loaded calcium sulfate hemihydrate/calcium citrate tetrahydrate cement (ATP/CSH/CCT) was successfully prepared for the first time. The effect of different contents of ATP on the structure and physicochemical properties of ATP/CSH/CCT was also studied in detail. The results indicated that incorporating ATP into the cement did not significantly alter their structures. However, the addition ratio of ATP directly impacted the mechanical properties and in vitro degradation properties of the composite bone cement. The compressive strength of ATP/CSH/CCT gradually decreased with an increasing ATP content. The degradation rate of ATP/CSH/CCT did not significantly change at low concentrations of ATP, but it increased with a higher ATP content. The composite cement induced the deposition of a Ca-P layer in a phosphate buffer solution (PBS, pH = 7.4). Additionally, the release of ATP from the composite cement was controlled. The ATP was controlled releasing at the 0.5% and 1% ATP in cement by the diffusion of ATP and the degradation of the cement, whereas it was controlled by the diffusion process merely at the 0.1% ATP in cement. Furthermore, ATP/CSH/CCT demonstrated good cytoactivity with the addition of ATP and is expected to be used for the repair and regeneration of bone tissue.

Bioavailability of calcium in an enriched postbiotic system compared to calcium citrate in healthy postmenopausal females; A randomized, double-blind, comparator-controlled, crossover study.

Introduction: Bioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women. Methods: A total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively. Results: Ca-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study. Discussion: These findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial.

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Review of Analytical Methods for Calcium Salts and Cholecalciferol in Dietary Supplements.

Dietary supplements composed by the combination of a calcium salt with cholecalciferol (vitamin D3) are widely used for improving bone health in conditions caused by the deficiency of these compounds in the body. Historically, these supplements have been linked to quality and safety issues. In the case of calcium salts, the presence of potentially toxic contaminants such as lead (Pb) has already been alerted by health authorities from different countries. Meanwhile, cholecalciferol is very unstable under inadequate manufacturing and storage conditions. The content of both compounds in commercial dietary supplements is often found to be in disagreement with the label claims, which can lead to a deficient or excessive nutrient intake by consumers. In this scenario, analyzing these compounds is still a difficult and time-consuming task, which usually requires specific pretreatment procedures and multiple analytical methods due to the inorganic nature of calcium and the organic nature of cholecalciferol. Therefore, this article reviews the analytical methods, described in official compendia and scientific literature, for the determination of calcium salts and cholecalciferol in dietary supplement formulations. We also approached the sample preparation procedures highly required due to the matrix complexity of these materials.

Strontium increasing calcium accessibility from calcium citrate.

Strontium chloride added to aqueous suspensions of metastable calcium citrate tetrahydrate increased calcium ion activity measured electrochemically without transition of metastable tetrahydrate to stable calcium citrate hexahydrate as shown by DSC. Calcium activity increase was explained by lower solubility of strontium citrate pentahydrate formed (8.9 × 10-4 M at 25 °C) increasing with temperature compared to calcium citrate tetrahydrate (1.6 × 10-3 M) decreasing with temperature. Strontium binding to citrate was found endothermic, ΔH0 = 45 kJ∙mol-1 at 25 °C, while calcium binding shows variation from ΔH0 = 94 kJ∙mol-1 at 10 °C becoming exothermic above physiological temperature with ΔH0 = -9 kJ∙mol-1 at 45 °C as determined from temperature and concentration variation in electric conductivity. These differences in solution thermodynamics and pH effect on complex formation between calcium and strontium citrate are discussed in relation to biomineralization.

Hydrates of calcium citrate and their interconversion in relation to calcium bioaccessibility.

Calcium citrate tetrahydrate (CCT) and hexahydrate (CCH) precipitates from aqueous solutions of CaCl2 and sodium citrate above and below the transition temperature of 52 °C, respectively. The CCT, the dihydrate (CCD) and anhydrate (CCA) as obtained by a stepwise dehydration of solid CCH have enthalpy of dehydration of ΔH0CCH to CCT = 43.6, ΔH0CCT to CCD = 43.8, and ΔH0CCD to CCA = 88.1 kJ∙mol-1 as measured by DSC. WAXS measurements demonstrate a stepwise decrease in unit cell size upon dehydration, and a stronger binding of the two first water compared to additional. The increasing negative enthalpy of dissolution, as calculated from the temperature dependence of solubility (10-90 °C), +21 kJ∙mol-1 (CCH), -20 kJ∙mol-1 (CCT), -22 kJ∙mol-1 (CCD), and -40 kJ∙mol-1 (CCA) shows along the series of hydrates with increasing solubility, enthalpy-entropy compensation with an isoequilibrium temperature of 49 °C. Conversion of CCD and CCA in aqueous solutions yields the more soluble CCT, not the stable CCH in agreement with Ostwald's stage law, increasing calcium bioaccessibility under physiological conditions in intestines.

Calcium availability from whey mineral residues increased by hydrogen citrate.

Insoluble mineral residues from whey processing dominated by hydroxyapatite and calcium hydrogen phosphate were found to dissolve isothermally in aqueous sodium hydrogen citrate. Dissolution occurred spontaneously and the resultant homogeneous solutions were found to be supersaturated solutions in both calcium citrate and calcium hydrogen phosphate. Supersaturation was investigated by visual inspection combined with turbidity measurements and analyses of calcium and phosphorous by ICP. The maximal supersaturation was found to be proportional to total hydrogen citrate concentration. For 0.2 M hydrogen citrate, maximum calcium concentration was achieved in the first hours of dissolution resulting in the supersaturation of calcium hydrogen phosphate with a factor of 10. Calcium citrate rather than calcium hydrogen phosphate precipitated from the supersaturated solutions and the time elapsing before precipitation began, increased with increasing concentrations of excess of hydrogen citrate. This lag phase for precipitation ranged from several hours for 0.2 M hydrogen citrate to more than a day for higher hydrogen citrate concentrations, for which the solutions were saturated in calcium hydrogen phosphate and became supersaturated only in calcium citrate due to the strong binding of calcium by citrate. The appearance and decay of supersaturation was kinetically studied in order to provide the background for future exploration of whey minerals in functional foods for improved calcium nutrition.