Glycated walnut meal peptide­calcium chelates (COS-MMGGED-Ca): Preparation, characterization, and calcium absorption-promoting.

This study isolated a novel peptide MMGGED with strong calcium-binding capacity from defatted walnut meal and synthesized a novel peptide­calcium chelate COS-MMGGED-Ca with high stability via glycation. Structural characterization and computer simulation identified binding sites, while in vitro digestion stability and calcium transport experiments explored the chelate's properties. Results showed that after glycation, COS-MMGGED bound Ca2+ with 88.75 ± 1.75 %, mainly via aspartic and glutamic acids. COS-MMGGED-Ca released Ca2+ steadily (60.27 %), with thermal denaturation temperature increased by 18 °C and 37 °C compared to MMGGED-Ca, indicating good processing performance. Furthermore, COS-MMGGED significantly enhanced Ca2+ transport across Caco-2 monolayers, 1.13-fold and 1.62-fold higher than CaCl2 and MMGGED, respectively, at 240 h. These findings prove glycation enhances structural properties, stability, calcium loading, and transport of peptide­calcium chelates, providing a scientific basis for developing novel efficient calcium supplements and high-value utilization of walnut meal.

Fibroblast growth factor-21 potentiates the stimulatory effects of 1,25-dihydroxyvitamin D3 on transepithelial calcium transport and TRPV6 Ca2+ channel expression.

Fibroblast growth factor (FGF)-21 is a salient liver-derived endocrine regulator for metabolism of glucose and triglyceride as well as bone remodeling. Previously, certain peptides in the FGF family have been shown to modulate calcium absorption across the intestinal epithelia. Since FGF21 receptor, i.e., FGF receptor-1, is abundantly expressed in the enterocytes, there was a possibility that FGF21 might exert direct actions on the intestine. Herein, a large-scale production of recombinant FGF21 at the multi-gram level was developed in order to minimize variations among various batches. In the oral glucose tolerance test, recombinant FGF21 was found to reduce plasma glucose levels in mice fed high-fat diet. A series of experiments applying radioactive tracer 45Ca in Ussing chamber showed that FGF21 potentiated the stimulatory effect of low-dose 1,25-dihydroxyvitamin D3 [10 nM 1,25(OH)2D3] on the transepithelial calcium transport across intestinal epithelium-like Caco-2 monolayer. FGF21 + 1,25(OH)2D3 also decreased transepithelial resistance, but had no effect on epithelial potential difference or short-circuit current. Furthermore, 1,25(OH)2D3 alone upregulated the Caco-2 mRNA expression of the major apical calcium channels, i.e., transient receptor potential vanilloid subfamily member 6 (TRPV6), which was further elevated by a combination of FGF21 and 1,25(OH)2D3, consistent with the upregulated TRPV6 protein expression in enterocytes of FGF21-treated mice. However, FGF21 was without effects on the mRNA expression of voltage-gated calcium channel 1.3, calbindin-D9k, plasma membrane Ca2+-ATPase 1b, claudin-12 or claudin-15. In conclusion, FGF21 did exert a direct action on the intestinal epithelial cells by potentiating the 1,25(OH)2D3-enhanced calcium transport, presumably through the upregulation of TRPV6 expression.

Lactobacilli and Their Fermented Foods as a Promising Strategy for Enhancing Bone Mineral Density: A Review.

Lactobacilli fermentation possesses special nutritional and health values to food, especially in improving diseases related to the gut microbiota such as osteoporosis risk. Previous research indicates that lactobacilli-fermented foods have the potential to enhance the bone mineral density (BMD), as suggested by some clinical studies. Nonetheless, there is currently a lack of comprehensive summaries of the effects and potential mechanisms of lactobacilli-fermented foods on BMD. This review summarizes findings from preclinical and clinical studies, revealing that lactobacilli possess the potential to mitigate age-related and secondary factor-induced bone loss. Furthermore, these findings imply that lactobacilli are likely mediated through the modulation of bone remodeling via gut inflammation-related pathways. Additionally, lactobacilli fermentation may augment calcium accessibility through directly promoting calcium absorption or modifying food constituents. Considering the escalating global health challenge of bone-related issues among the elderly population, this review may offer a valuable reference for the development of food strategies aimed at preventing osteoporosis.

Lactobacillus helveticus-Derived Whey-Calcium Chelate Promotes Calcium Absorption and Bone Health of Rats Fed a Low-Calcium Diet.

This study investigated the characteristics of Lactobacillus helveticus-derived whey-calcium chelate (LHWCC) and its effect on the calcium absorption and bone health of rats. Fourier-transform infrared spectroscopy showed that carboxyl oxygen atoms, amino nitrogen atoms, and phosphate ions were the major binding sites with calcium in LHWCC, which has a sustained release effect in simulated in vitro digestion. LHWCC had beneficial effects on serum biochemical parameters, bone biomechanics, and the morphological indexes of the bones of calcium-deficient rats when fed at a dose of 40 mg Ca/kg BW for 7 weeks. In contrast to the inorganic calcium supplement, LHWCC significantly upregulated the gene expression of transient receptor potential cation V5 (TRPV5), TRPV6, PepT1, calcium-binding protein-D9k (Calbindin-D9k), and a calcium pump (plasma membrane Ca-ATPase, PMCA1b), leading to promotion of the calcium absorption rate, whereas Ca3(PO4)2 only upregulated the TRPV6 channel in vivo. These findings illustrate the potential of LHWCC as an organic calcium supplement.

Characterization and Mechanism of a Novel Rice Protein Peptide (AHVGMSGEEPE) Calcium Chelate in Enhancing Calcium Absorption in Caco-2 Cells.

Rice protein peptides (RPP) are a potentially valuable source of high-quality calcium chelating properties. However, there is a lack of information regarding the calcium-absorption-promoting effect of RPP and its underlying mechanism. The present study adopted molecular docking methodologies to analyze the 10 most potent peptide segments from RPP. Results revealed that the peptide AHVGMSGEEPE (AHV) displayed optimal calcium binding properties (calcium-chelating capacity 55.69 ± 0.66 mg/g). Quantum chemistry analysis revealed that the AHV peptide effectively binds and forms stable complexes with calcium via the carbonyl oxygen atoms in valine at position 3 and the carbonyl of the C-terminal carboxyl group of glutamate at position 11. The spectral analysis results indicated that AHV may bind to calcium through carboxyl oxygen atoms, resulting in a transition from a smooth surface block-like structure to a dense granular structure. Furthermore, this study demonstrated that the 4 mmol/L AHV-Ca chelate (61.75 ± 13.23 µg/well) significantly increases calcium absorption compared to 1 mM CaCl2 (28.57 ± 8.59 µg/well) in the Caco-2 cell monolayer. In terms of mechanisms, the novel peptide-calcium chelate AHV-Ca derived from RPP exerts a cell-level effect by upregulating the expression of TRPV6 calcium-ion-channel-related genes and proteins (TRPV6 and Calbindin-D9k). This study provides a theoretical basis for developing functional foods with the AHV peptide as ingredients to improve calcium absorption.

Load carriage exercise increases calcium absorption and retention in healthy young women.

Aerobic exercise reduces circulating ionized Ca (iCa) and increases parathyroid hormone (PTH), but the cause and consequences on Ca handling are unknown. The objective of this study was to determine the effects of strenuous exercise on Ca kinetics using dual stable Ca isotopes. Twenty-one healthy women (26.4 ± 6.7 yr) completed a randomized, crossover study entailing two 6-d iterations consisting of either 60 min of treadmill walking at 65% VO2max wearing a vest weighing 30% body weight on study days 1, 3, and 5 (exercise [EX]), or a rest iteration (rest [REST]). On day 1, participants received intravenous 42Ca and oral 44Ca. Isotope ratios were determined by thermal ionization mass spectrometry. Kinetic modeling determined fractional Ca absorption (FCA), Ca deposition (Vo+), resorption (Vo-) from bone, and balance (Vbal). Circulating PTH and iCa were measured before, during, and after each exercise/rest session. Data were analyzed by paired t-test or linear mixed models using SPSS. iCa decreased and PTH increased (P < .001) during each EX session and were unchanged during REST. On day 1, urinary Ca was lower in the EX pool (25 ± 11 mg) compared to REST (38 ± 16 mg, P = .001), but did not differ over the full 24-h collection (P > .05). FCA was greater during EX (26.6 ± 8.1%) compared to REST (23.9 ± 8.3%, P < .05). Vbal was less negative during EX (-61.3 ± 111 mg) vs REST (-108 ± 23.5 mg, P < .05), but VO+ (574 ± 241 vs 583 ± 260 mg) and VO- (-636 ± 243 vs -692 ± 252 mg) were not different (P > .05). The rapid reduction in circulating iCa may be due to a change in the miscible Ca pool, resulting in increased PTH and changes in intestinal absorption and renal Ca handling that support a more positive Ca balance.

Identifying Gut Microbiome Features that Predict Responsiveness Toward a Prebiotic Capable of Increasing Calcium Absorption: A Pilot Study.

Previously, we demonstrated that prebiotics may provide a complementary strategy for increasing calcium (Ca) absorption in adolescents which may improve long-term bone health. However, not all children responded to prebiotic intervention. We determine if certain baseline characteristics of gut microbiome composition predict prebiotic responsiveness. In this secondary analysis, we compared differences in relative microbiota taxa abundance between responders (greater than or equal to 3% increase in Ca absorption) and non-responders (less than 3% increase). Dual stable isotope methodologies were used to assess fractional Ca absorption at the end of crossover treatments with placebo, 10, and 20 g/day of soluble corn fiber (SCF). Microbial DNA was obtained from stool samples collected before and after each intervention. Sequencing of the 16S rRNA gene was used to taxonomically characterize the gut microbiome. Machine learning techniques were used to build a predictive model for identifying responders based on baseline relative taxa abundances. Model output was used to infer which features contributed most to prediction accuracy. We identified 19 microbial features out of the 221 observed that predicted responsiveness with 96.0% average accuracy. The results suggest a simplified prescreening can be performed to determine if a subject's bone health may benefit from a prebiotic. Additionally, the findings provide insight and prompt further investigation into the metabolic and genetic underpinnings affecting calcium absorption during pubertal bone development.

Identification of calcium chelating peptides from peanut protein hydrolysate and absorption activity of peptide-calcium complex.

BACKGROUND: Peanut peptides have good chelating ability with metal ions. However, there are few studies on the chelation mechanism of peanut peptides with calcium and absorption properties of peptide-calcium complex. RESULTS: Peptides with high calcium chelating rate were isolated and purified from peanut protein hydrolysate (PPH), and the chelation rate of component F21 was higher (81.4 ± 0.8%). Six peptides were identified from component F21 by liquid chromatography-tandem mass spectrometry, and the frequency of acidic amino acids and arginine in the amino acid sequence was higher in all six peptides. Peanut peptide-calcium complex (PPH21-Ca) was prepared by selecting component F21 (PPH21). Ultraviolet analysis indicated that the chelate reaction occurred between peanut peptide and calcium ions. Fourier transform infrared analysis showed that the chelating sites were carboxyl and amino groups on the amino acid residues of peptides. Scanning electron microscopy revealed that the surface of peanut peptide had a smooth block structure, but the surface of the complex had a granular morphology. Caco-2 cell model tests revealed that the bioavailability of PPH21-Ca was 58.4 ± 0.5%, which was significantly higher than that of inorganic calcium at 37.0 ± 0.4%. CONCLUSION: Peanut peptides can chelate calcium ions by carboxyl and amino groups, and the peptide-calcium complex had higher bioavailability. This study provides a theoretical basis for the development of new calcium supplement products that are absorbed easily. © 2024 Society of Chemical Industry.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Dietary 25-Hydroxycholecalciferol Supplementation as a Vitamin D3 Substitute Improves Performance, Egg Quality, Blood Indexes, Jejunal Morphology, and Tibia Quality in Late-Phase Laying Hens.

This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn-soybean meal diet supplementation of 4000 IU/kg VD3 (control group), 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 (experimental group 1), or 50 µg/kg 25-OHD3 and 4000 IU/kg VD3 (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD3 caused a significant increase in the laying rate, especially in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD3 addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD3, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 µg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group increased markedly, and the MDA level decreased significantly in the 50 µg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group (p < 0.05). Dietary 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD3 addition, dietary supplementation of 25-OHD3 supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD3 as a substitute forVD3.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Calcium restriction for 28 days markedly and negatively influences bone mineral density of the femur and lumbar vertebrae regardless of the high-fat diet ingestion in young adult male rats.

Calcium (Ca) is necessary for bone calcification, and Ca deficiency leads to decreased bone mineral density (BMD). Epidemiological studies have reported a correlation between Ca intake and BMD. Although the influences of Ca deficiency on BMD have been reported, the effects of Ca restriction on bone during high-fat diet ingestion remain unclear. Therefore, we hypothesized that high-fat diet ingestion would potentiate the negative effects of Ca restriction on bone. Sprague-Dawley strain male rats (aged 11 weeks) were divided into 4 groups: basic control diet (Cont.) (11% lipid energy rate, 0.5% calcium), basic control diet with Ca restriction (CaR) (11% lipid energy rate, 0.02% calcium), high-fat diet (HF) (40% lipid energy rate, 0.5% calcium), and high-fat diet with Ca restriction (HFCaR) (40% lipid energy rate, 0.02% calcium). At 28 days after starting the experimental diets, body weights were higher in the high-fat diet groups (HF and HFCaR) than in the standard-fat diet groups (Cont. and CaR) on 2-way analysis of variance. The apparent Ca absorption rate in the Ca-restricted groups (CaR and HFCaR) was higher than in the Ca-sufficient groups (Cont. and HF). BMD and bone strength parameters of the femur and lumbar vertebrae in the Ca-restricted groups were markedly lower than in the Ca-sufficient groups, whereas there were no significant differences between the standard-fat diet and HF diet groups. These results suggest that 28 days of Ca restriction increases the risk of bone fracture and osteoporosis.

A Short-Term Zinc-Deficient Diet Maintains Serum Calcium Concentrations through Ca Absorption-Related Gene Expression in Rats.

We investigated the effects of short-term dietary zinc deficiency on zinc and calcium metabolism. Four-week-old male Wistar rats were divided into two pair-fed groups for a 1-wk treatment: zinc-deficient group (ZD, 1 ppm); control group (PF, 30 ppm). The mRNA expression of zinc transporters, such as Slc39a (Zip) 4, Zip5, Zip10, and Slc30a (ZnT) 1, in various tissues (liver, kidney, and duodenum) quickly responded to dietary zinc deficiency. Although there was no significant difference in serum calcium concentrations between the PF and ZD groups, serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3) was higher in the ZD group than in the PF group. Moreover, short-term zinc deficiency significantly increased mRNA expression of transient receptor potential (TRP) cation channel subfamily vanilloid (V) member 6, S100 calcium binding protein G (S100g), and ATPase plasma membrane Ca2+ transporting 1 (Atp2b1) in the duodenum. Furthermore, short-term zinc deficiency increased vitamin D receptor (VDR) and cytochrome P450 family 24 subfamily A member 1 (Cyp24a1) mRNA expression in the kidney. These findings suggested that short-term zinc deficiency maintains serum calcium concentrations through Ca absorption-related gene expression in the duodenum, and that short-term zinc deficiency induced the expression of Cyp24a1 in kidney in response to an increase in the serum 1,25(OH)2D3 level.

Vitamin D Deficiency in Children and Adolescents in Saudi Arabia: A Systematic Review.

Vitamin D deficiency is a globally recognized health concern, with particular prominence in specific geographies and demographics. Saudi Arabia, with its unique climatic conditions and cultural practices, has been under scrutiny regarding the prevalence of this deficiency, especially among children and adolescents. This systematic review aimed to assess the prevalence of vitamin D deficiency among children and adolescents in Saudi Arabia by compiling and analyzing various studies to offer a comprehensive view of the situation. The comprehensive web search encompassed a range of databases, including Google Scholar and PubMed, to gather studies published between 2012 and 2023. An analysis was conducted on seven studies, totaling 2,429 participants, with each study focusing on various aspects, regions, and cohorts within Saudi Arabia. These studies employed different methodologies, ranging from cross-sectional surveys to randomized clinical trials. The review unveiled an alarming prevalence of vitamin D deficiency in the studied population. On average, around 81.1% of children and adolescents showcased inadequate vitamin D levels. Specific vulnerable groups, such as those with Type 1 diabetes mellitus or asthma, had pronounced deficiencies. Factors influencing these levels ranged from dietary habits, sun exposure, physical activity, and socioeconomic parameters. The compelling evidence from the studies underscores a consistent health issue among the pediatric population in Saudi Arabia that the overwhelming majority of Saudi children and adolescents lack adequate vitamin D. Addressing this widespread deficiency needs a multifaceted approach. Implementing policies that support vitamin D food fortification, encouraging routine screenings, and launching public awareness campaigns about safe sun exposure and diet can play a transformative role in this health crisis.

An Algorithm to Assess Calcium Bioavailability from Foods.

BACKGROUND: The recommended calcium intakes to meet calcium requirements at various ages are based on average population absorption values. Absorption is altered by physiology, the calcium load, and type of food. The calcium intake necessary, therefore, to meet requirements depends upon diet composition, through bioavailability. OBJECTIVE: The objectives of this study was to improve predictions of calcium bioavailability on the basis of the food matrix. METHODS: We modeled calcium absorption data from individual foods, beverages, and fortified foods that were determined with calcium isotopic tracers and compared with milk as a referent to adjust for physiologic differences of the host. RESULTS: Data from 496 observations were modeled to develop a predictive algorithm for calcium bioavailability in adults on the basis of calcium load and oxalate and phytate loads, which represent the 2 main inhibitors of calcium absorption. CONCLUSIONS: This algorithm will be helpful in assessing calcium availability from the food supply, for developing diets for individuals and research cohorts, and for designing policies and interventions to address inadequate calcium intake for populations.

Pectin Modulates Calcium Absorption in Polarized Caco-2 Cells via a Pathway Distinct from Vitamin D Stimulation.

Pectin, a type of soluble fiber, promotes morphological changes in the small intestinal villi. Although its physiological significance is unknown, we hypothesized that changes in villus morphology enhance the efficiency of nutrient absorption in the small intestine and investigated the effect of pectin derived from persimmon on calcium absorption using polarized Caco-2 cells. In polarized Caco-2 cells, pectin altered the mRNA expression levels of substances involved in calcium absorption and the regulation of intracellular calcium concentration and significantly reduced calcium absorption. Although this was comparable to the results of absorption and permeability associated with the addition of active vitamin D, the simultaneous action of pectin and active vitamin D did not show any additive effects. Furthermore, as active vitamin D significantly increases the activity of intestinal alkaline phosphatase (ALP), which is known to be involved in the regulation of intestinal absorption of calcium and lipids, we also investigated the effect of pectin on intestinal ALP activity. As a result, it was found that, unlike the effect of active vitamin D, pectin significantly reduced intestinal ALP activity. These results suggest that pectin stimulates polarized Caco-2 cells through a mechanism distinct from the regulation of calcium absorption by vitamin D, modulating total calcium absorption from the elongated villi through morphological changes in the small intestine by suppressing it at the cellular level.

The Postprandial Calcium Absorption of a Milk-Derived Calcium Permeate - The Acute RENEW Double-Blinded Randomized Controlled Cross-Over Study.

BACKGROUND: Studies suggest that dairy-derived calcium supplements have additional beneficial properties compared with other calcium supplements in relation to bone health. OBJECTIVES: We investigated the postprandial calcium absorption from a milk-derived calcium permeate (CP) compared with calcium carbonate (CC). METHODS: In this randomized double-blinded cross-over study, 10 healthy postmenopausal females (age 50-65 y) received maltodextrin (placebo), 800 mg calcium from CP or from CC provided in 6 capsules on separate days. A fasting blood sample was collected at baseline, 60, 120, 240, and 360 min after ingestion. At baseline and 360 min, spot-urine samples were collected. Serum-ionized calcium, intact parathyroid hormone, phosphorus, and magnesium were analyzed, as were urinary calcium, phosphorus, and magnesium. A linear mixed model was applied. RESULTS: Serum-ionized calcium concentration after the CC supplement was higher at 240 min compared with the CP supplement [between-group difference; 95% confidence interval (CI): 0.039 mmol/L; 95% CI: 0.017-0.061; P = 0.00078]. Serum-ionized calcium concentration after the CC supplement was significantly higher than placebo at all postprandial time points except at 60 min. Urinary calcium concentration in 360 min spot urine was higher after intake of CC compared with CP [between-group difference; 95% CI: 2.47 mmol/L; 95% CI: 1.90-3.03; P = 0.0042]. CONCLUSIONS: Postprandial calcium absorption from CP was lower than that of CC, and concurrently, urinary concentration reflected increased serum appearance by CC compared with CP, highlighting different metabolic responses. The long-term and clinical implications should be studied further.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

Effect of circadian clock and claudin regulations on inulin-induced calcium absorption in the mouse intestinal tract.

Dietary calcium supplementation has been shown to be an effective adjunct therapy in an inflammatory bowel disease model. Soluble dietary fiber reduces intestinal pH and is known to enhance calcium absorption. Although many circadian clock regulations of nutrient absorption in the intestinal tract have been reported, the effects of clock regulation on calcium absorption have yet to be understood. In this study, we investigated the timing of efficient calcium intake by measuring urinary calcium excretion in mice. The diurnal variations in channel-forming tight junctions (claudins) were detected in both the jejunum and ileum. Following 2 days of feeding with a Ca2+-free diet, Ca2+-containing diets with or without soluble fiber (inulin) were fed at specific timings, and urine was subsequently examined every 4 hr. There was an evident increase in urinary calcium concentration when the inulin diet was fed at the beginning of the resting period. The Claudin 2 (Cldn2) expression level also showed a significant day-night change, which seemed to be a mechanism for the increased calcium excretion after inulin intake. This diurnal rhythm and enhanced Cldn2 expression were abolished by disruption of the suprachiasmatic nucleus, the central clock in the hypothalamus. This study suggests that intestinal calcium absorption might be modulated by the circadian clock and that the intake of inulin is more effective at the beginning of the resting period in mice.

Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.

TRPV6 is a Transient Receptor Potential Vanilloid (TRPV) cation channel with high selectivity for Ca2+ ions. First identified in 1999 in a search for the gene which mediates intestinal Ca2+ absorption, its far more extensive repertoire as a guardian of intracellular Ca2+ has since become apparent. Studies on TRPV6-deficient mice demonstrated additional important roles in placental Ca2+ transport, fetal bone development and male fertility. The first reports of inherited deficiency in newborn babies appeared in 2018, revealing its physiological importance in humans. There is currently strong evidence that TRPV6 also contributes to the pathogenesis of some common cancers. The recently reported association of TRPV6 deficiency with non-alcoholic chronic pancreatitis suggests a role in normal pancreatic function. Over time and with greater awareness of TRPV6, other disease-associations are likely to emerge. Powerful analytical tools have provided invaluable insights into the structure and operation of TRPV6. Its roles in Ca2+ signaling and carcinogenesis, and the use of channel inhibitors in cancer treatment are being intensively investigated. This review first briefly describes the biochemistry and physiology of the channel, and analytical methods used to investigate these. The focus subsequently shifts to the clinical disorders associated with abnormal expression and the underlying pathophysiology. The aims of this review are to increase awareness of this channel, and to draw together findings from a wide range of sources which may help to formulate new ideas for further studies.