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.

Acute effects of calcium supplements on blood pressure: randomised, crossover trial in postmenopausal women.

Calcium supplements appear to increase cardiovascular risk, but the mechanism is unknown. We investigated the acute effects of calcium supplements on blood pressure in postmenopausal women. The reduction in systolic blood pressure was smaller after calcium compared with the placebo in the hours following dosing. INTRODUCTION: Calcium supplements appear to be associated with increased cardiovascular risk; however, the mechanism of this is uncertain. We previously reported that blood pressure declined over a day in older women, and that this reduction was smaller following a calcium supplement. To confirm this finding, we investigated the acute effects of calcium supplements on blood pressure. METHODS: This was a randomised controlled crossover trial in 40 healthy postmenopausal women (mean age 71 years and BMI 27.2 kg/m2). Women attended on two occasions, with visits separated by ≥7 days. At each visit, they received either 1 g of calcium as citrate, or placebo. Blood pressure and serum calcium concentrations were measured immediately before, and 2, 4 and 6 h after each intervention. RESULTS: Ionised and total calcium concentrations increased after calcium (p < 0.0001 versus placebo). Systolic blood pressure decreased after both calcium and placebo, but significantly less so after calcium (p = 0.02). The reduction in systolic blood pressure from baseline was smaller after calcium compared with placebo by 6 mmHg at 4 h (p = 0.036) and by 9 mmHg at 6 h (p = 0.002). The reduction in diastolic blood pressure was similar after calcium and placebo. CONCLUSIONS: These findings are consistent with those of our previous trial and indicate that the use of calcium supplements in postmenopausal women attenuates the post-breakfast reduction in systolic blood pressure by around 6-9 mmHg. Whether these changes in blood pressure influence cardiovascular risk requires further study.

Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

Enhancement of bone formation with a synthetic matrix containing bone morphogenetic protein-2 by the addition of calcium citrate.

PURPOSE: The aim of the study was to test whether calcium citrate combined with rhBMP-2 was able to enhance bone regeneration compared with a matrix containing only rhBMP-2. METHODS: In each of experimental mice, one cylinder of calcium citrate-rhBMP-2 or rhBMP-2 alone was implanted into the thigh muscle pouches of the mouse. The following two treatment modalities were randomly allocated: (1) empty control with rhBMP-2 alone in a gelatin matrix and (2) a gelatin matrix including both calcium citrate and BMP-2. After several weeks, bone granules were obtained by histological analysis. RESULTS: Histomorphometric analysis showed the greatest amount of newly formed bone was observed in the group that contained 10.0 mg calcium citrate with 2.0 mg rhBMP-2 (p < 0.05). Quantitative histomorphometry revealed in the calcium citrate-rhBMP-2 group an obvious increase in the fractional area and the average new bone mineral density of newly formed bone at 2, 4 and 6 weeks than in the rhBMP-2 group (p < 0.05). At 2 weeks time-point, the mature cancellous bone had formed in the calcium citrate-rhBMP-2 group. CONCLUSIONS: From this study, it can be concluded that calcium citrate combined with rhBMP-2 significantly enhances bone regeneration in muscle. This synthetic gelatin matrix containing calcium citrate/gelatin granules fulfils a number of criteria required for an ideal carrier system for rhBMP-2. The calcium ions that calcium citrate releases into the surrounding environment can activate bone formation when used as part of a combination of calcium citrate and BMP-2.

Characterization and antivibrio activity of chitosan-citral Schiff base calcium complex for a calcium citrate sustained release antibacterial agent.

Vibrio parahemolyticus is the "Number one killer" of seafood products. Anti-vibrio agents having low cost and high-safety are urgently needed to supplement the application needs. This work attempted to prepare CS-CT-CCa complex with citral (CT), chitosan (CS) and calcium citrate (CCa) as raw material by microwave-assisted high-pressure homogenization. Additionally the coordination structure and morphology of Bridge-CS-CT-Schiff base/OH-CCa were verified. The prepared CS-CT-CCa had a well-dispersed property (the size: 3.55~9.33 µm and the zeta potential: +38.7~+67.5 mV) and an excellent sustained released ability (sustained release up to 180 min). MIC, Glucose assay, MDA assay, biofilm formation inhibition assay, SEM, swimming and swarming motility assay demonstrated that CS-CT-CCa had strong (MIC of 128 µg/mL) and sustained (more than 12 h) inhibitory effects against V. parahaemolyticus. Meanwhile, CS-CT-CCa could increase the membrane permeability of V. parahaemolyticus and inhibit their biofilm-forming ability in a dose-dependent manner. It could be inferred that the antibacterial activities against V. parahaemolyticus caused inhibition of biofilm formation, swimming and swarming motilities. This study provided necessary data for the further design and development of chitosan antibacterial agents, food and feed additives.

Urate-lowering effect of calcium supplementation: Analyses of a randomized controlled trial.

OBJECTIVE: To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium. METHODS: This is a placebo-controlled trial in which thirty-five adult (aged 18-42 years) female low-calcium consumers (<800 mg/d) were randomized to one of three treatment groups: low calcium breakfast (control, ∼70 mg of calcium/d) -C or high-calcium breakfast (∼770 mg/d) from calcium citrate - CIT or from skim milk - SM, during 45 consecutive days. Breakfasts were matched for potential confounders and were provided as part of an energy-restricted normoprotein diet containing an additional 800 mg of calcium/d. Dual-energy X-ray absorptiometry measurements (body fat assessment) and fasting blood samples (urate, ionic calcium, PTH, and 1,25-(OH)2-D3) were taken at baseline and the end of the experiment. CLINICAL TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br/ (RBR-7Q2N33). RESULTS: Despite no significant changes in total body weight/fat, CIT and SM led to a significant reduction in serum urate and ionic calcium, but did not affect PTH and vitamin D concentrations compared to C. CIT and SM reduced baseline serum urate by ∼14% and ∼17%, respectively. There was a trend to a positive correlation between changes in serum urate and changes in ionic calcium on day 45 (r = 0.327, P = 0.055). CONCLUSIONS: Calcium supplementation (770 mg/d from dairy or calcium citrate) reduced serum urate concentrations, suggesting that the gout-protective effect of low-fat dairy consumption is at least partly due to a urate-lowering effect of calcium.

Cell wall stabilization and calcium absorption on mango fruit treated with a quarantine hot water treatment combined with calcium salts and stored at chilling temperature.

Hot water treatment (HT) induces chilling injury (CI) tolerance in mango, but prolonged exposure to HT causes softening. In this sense, calcium salts stabilize the cell wall. Nevertheless, there is little information on the effect of HT combined with calcium salts (HT-Ca) on calcium absorption and cell wall stability during storage of mango at CI temperature. We evaluated the effect of quarantine HT in combination with calcium chloride (CaCl2 ), calcium citrate (CaCit), or calcium lactate (CaLac) on calcium absorption, CI tolerance, and cell wall stabilization. HT and HT-CaCl2 had the lowest CI development. HT increased firmness loss and electrolyte leakage, and HT-Ca counteracted this effect. Overall, HT-Ca treatments had a similar effect on the cell wall degrading enzymes. HT-CaCl2 was the best treatment and did not present alterations on the epicuticular wax as observed on HT. HT-CaCl2 is a useful technology to stabilize cell wall and preserve mango during chilling storage. PRACTICAL APPLICATIONS: The addition of calcium salts in an established hot water quarantine procedure for mango exportation represents a viable alternative to counteract the negative effects of this thermal treatment upon cell microstructure, maintaining its positive effect of tolerance to chilling injury. In this sense, mango producers and packers can use a HT-CaCl2 treatment to reduce the presence of chilling injury and extent the fruit shelf life and improve its commercialization. Furthermore, technical and infrastructure changes are not necessary for the packaging chain.

Comparative effects of a novel plant-based calcium supplement with two common calcium salts on proliferation and mineralization in human osteoblast cells.

Calcium is an essential mineral to support bone health and serves as a major therapeutic intervention to prevent and delay the incidence of osteoporosis. Many individuals do not obtain the optimum amount of calcium from diets and depend on bioavailable calcium supplements. The present study was conducted to examine the effect of a novel plant-based calcium supplement, derived from marine algae, and contains high levels of calcium, magnesium, and other bone supporting minerals [commercially known as AlgaeCal (AC)], on proliferation, mineralization, and oxidative stress in cultured human osteoblast cells, and compared with inorganic calcium carbonate and calcium citrate salts. Cultured human fetal osteoblast cells (hFOB 1.19) were treated with AC (0.5 mg/ml, fixed by MTT assay), calcium carbonate, or calcium citrate. These cells were harvested after 4 days of treatment for ALP activity, PCNA expression, and DNA synthesis, and 2 days for Ca(2+) deposition in the presence and absence of vitamin D3 (5 nM). The ability of AC to reduce H(2)O(2) (0.3 mM)-induced oxidative stress was assessed after 24 h of treatment. ALP activity was significantly increased with AC treatment when compared to control, calcium carbonate, or calcium citrate (4.0-, 2.0-, and 2.5-fold, respectively). PCNA expression (immunocytochemical analysis), DNA synthesis (4.0-, 3.0-, and 4.0-fold, respectively), and Ca(2+) deposition (2.0-, 1.0-, and 4.0-fold, respectively) were significantly increased in AC-treated cells when compared with control, calcium carbonate, or calcium citrate treatment. These markers were further enhanced following additional supplementation of vitamin D3 in the AC-treated group cells. AC treatment significantly reduced the H(2)O(2)-induced oxidative stress when compared to calcium carbonate or calcium citrate (1.5- and 1.4-fold, respectively). These findings suggest that AC may serve as a superior calcium supplement as compared to other calcium salts tested in the present study. Hence, AC may be developed as a novel anti-osteoporotic supplement in the near future.

Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model.

Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg(-1) body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study.

AIMS: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates. METHODS: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment. RESULTS: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D. CONCLUSIONS: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

Citrate anticoagulation and the dynamics of thrombin generation.

BACKGROUND: Sodium citrate has been used as an anticoagulant to stabilize blood and blood products for over 100 years, presumably by sequestering Ca(++) ions in vitro. Anticoagulation of blood without chelation can be achieved by inhibition of the contact pathway by corn trypsin inhibitor (CTI). OBJECTIVE: To evaluate the influence of citrate anticoagulation on the performance of blood, platelet-rich and platelet-poor plasma assays. METHODS: Blood was anticoagulated in three ways: by collection into citrate, CTI and citrate with CTI. Plasma was prepared using each anticoagulation regimen. Functional analyses included calibrated automated thrombography, thromboelastography, plasma clotting, the synthetic coagulation proteome and platelet aggregation. Coagulation reactions were initiated with tissue factor-phospholipid and Ca(++) (when indicated). RESULTS: In all cases, citrate anticoagulation resulted in reaction dynamics significantly altered relative to blood or plasma stabilized with CTI alone. Subsequent experiments showed that calcium citrate itself impairs coagulation dynamics. CONCLUSION: Coagulation analyses using blood that has been exposed to citrate and recalcified do not yield reliable depictions of the natural dynamics of blood coagulation processes.

Anabolic effects of fluoride on bone.

Fluoride exerts a biphasic action at the level of osteoblasts, on bone mineral, on bone structure and function, and in the treatment of osteoporosis. At low circulating concentrations, skeletal uptake of fluoride is limited and the effects are beneficial. At higher concentrations and greater skeletal uptake, fluoride may cause the formation of abnormally mineralized bone of impaired quality. A new treatment program entailing intermittent slow release sodium fluoride (SR-NaF) with continuous calcium citrate may capture desirable qualities of fluoride without toxic effects, and be therapeutically efficacious in postmenopausal osteoporosis.

Anti-inflammatory effects of calcium citrate in RAW 264.7cells via suppression of NF-κB activation.

Here we aimed to investigate the anti-inflammatory effects of calcium citrate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The anti-inflammatory effects of calcium citrate were investigated by assessing pro-inflammatory factors (NO, ROS, NF-κB, iNOS, and COX-2) and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Treatment of cells with calcium citrate (10-100µM) significantly reduced the generation of intracellular reactive oxygen species and increased the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in LPS-stimulated macrophages. Calcium citrate was further shown to inhibit NO production in LPS-stimulated RAW 264.7cells. The expression levels of iNOS, COX-2, and NF-κB were also suppressed by treatment with calcium citrate. Calcium citrate was furthermore found to significantly inhibit the production of IL-1ß, IL-6, and TNF-α in response to LPS-stimulation. These findings demonstrate that calcium citrate may be an effective anti-inflammatory agent.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

PURPOSE: Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. METHODS: Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. RESULTS: OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. CONCLUSIONS: Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women.

This randomized crossover study compared the single-dose bioavailability and effects on parathyroid function of two commercially formulated calcium supplements containing 500 mg of elemental calcium. Twenty-five postmenopausal women underwent three phases of study wherein they each took a single dose of calcium citrate with a standard breakfast (as Citracal 250 mg + D), calcium carbonate (as Os-Cal 500 mg + D), or placebo at 8 a.m. Blood samples were drawn at baseline and hourly for 4 or 6 hours after each dose. Fasting and postload urine samples were also collected. Compared with calcium carbonate, calcium citrate provided a 46% greater peak-basal variation and 94% higher change in area under the curve for serum calcium and a 41% greater increment in urinary calcium. Moreover, the decrement in serum parathyroid hormone concentration from baseline was greater after calcium citrate. In conclusion, calcium citrate is more bioavailable than calcium carbonate when given with a meal.

Acute biochemical variations induced by calcium citrate and calcium carbonate in Type 2 diabetic patients: impaired calcium absorption in Type 2 diabetic patients with prolonged gastric emptying time.

Calcium supplementation is important in the treatment of osteoporosis, a disease that may also occur in diabetic patients. The acute effects of calcium supplementation and their relationship to gastric emptying time, however, have rarely been studied in type 2 diabetic patients. We evaluated the acute biochemical variations induced by the administration of two different calcium preparations, calcium citrate and calcium carbonate, in 16 (male/female: 13/3) Chinese diabetic patients. Serum free calcium, intact parathyroid hormone (i-PTH), and amount of urinary excretion of calcium (uCal/uCr) were evaluated after a single dose of 1200 mg of elemental calcium in each preparation. The free calcium levels did not change significantly in either group. However, significant suppression of i-PTH after calcium citrate administration at 1 h (17.1+/-2.0 pg/ml, P=.023), and after calcium carbonate administration at 2 h (14.2+/-2.5 pg/ml, P=.000), was noted when compared with individual basal level (21.2+/-2.5 and 19.3+/-2.4 pg/ml, respectively). The suppressive effect on i-PTH lasted for 6 h after calcium citrate and 5 h after calcium carbonate preparation of the 6-h study period. After administration of calcium citrate, the uCal/uCr of 2-to-4-h collection was significantly higher than that of the basal and 0-to-2-h collections: 0.25+/-0.04 vs. 0.19+/-0.03, P=.025; and 0.25+/-0.04 vs. 0.19+/-0.02, P=.014, respectively. A similar finding was observed for calcium carbonate: 0.23+/-0.03 vs. 0.18+/-0.02, P=.019; and 0.23+/-0.03 vs. 0.18+/-0.02, P=.011, respectively. We conclude that, in this group of Chinese type 2 diabetic patients in our study, the oral administration of 1200 mg elemental calcium in either calcium citrate or calcium carbonate preparation can induce a significant suppression of i-PTH. This may be helpful in preventing or treating osteoporosis. A prolonged gastric emptying time in these diabetic subjects may contribute to the non-significant alteration in free calcium levels after the administration of either calcium preparation.

Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine.

The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile.

Acute effect of calcium citrate on serum calcium and cardiovascular function.

Calcium supplements have been associated with an increased risk of cardiovascular events. However, the validity of these findings has been questioned. A major concern is that the mechanism underlying an increase in cardiovascular events has not been demonstrated. Calcium initiates cardiac and vascular contraction following influx of calcium into cardiac and smooth muscle from extracellular fluid. We have investigated whether the acute rise in serum calcium following calcium supplement administration is associated with adverse changes in cardiovascular function. In an open interventional study, we recruited 25 volunteers (16 female, age 60.3 ± 6.5 years, body mass index 25.7 ± 2.7 kg/m2) from the community who were not taking calcium supplements. Participants were studied before and 3 hours after a single oral dose of 1000 mg calcium citrate. We assessed well-validated markers of arterial stiffness (pulse wave velocity [PWV]), arterial wave reflection (augmentation index [AIx]), and myocardial perfusion (subendocardial viability ratio [SEVR]) by pulse wave analysis and endothelial function (reactive hyperemia index [RHI]) by peripheral arterial tonometry. Total and ionized serum calcium were acutely increased by 0.10 ± 0.07 and 0.06 ± 0.03 mmol/L, respectively, 3 hours after calcium citrate administration (p < 0.0001 for both comparisons). Following administration of calcium citrate there was a fall in AIx from a median of 29.7% (23.8% to 34.0%) to 26.4% (22.7% to 34.0%, p = 0.03) and an increase in SEVR from 163% (148% to 174%) to 170% (149% to 185%, p = 0.007). PWV and RHI were not significantly altered. The change in total calcium was negatively correlated with the change in AIx (r = -0.48, p = 0.02). In summary, the acute increase in serum calcium following calcium supplement administration is associated with reduced arterial wave reflection and a marker of increased myocardial perfusion. If maintained long-term, these changes would be expected to reduce cardiovascular risk. Acute serum calcium-mediated changes in these parameters of cardiovascular function are unlikely to underlie an association between calcium supplementation and cardiovascular events.

In vitro enamel remineralization by low-fluoride toothpaste with calcium citrate and sodium trimetaphosphate.

The objective of this study was to evaluate in vitro the effect of a low fluoride toothpaste (450 µgF/g, NaF) combined with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel remineralization. Bovine enamel blocks had the enamel surface polished sequentially to determine the surface hardness. After production of artificial carious lesions, the blocks selected by their surface hardness were submitted to remineralization pH cycling and daily treatment with dentifrice suspensions (diluted in deionized water or artificial saliva): placebo, 275, 450, 550 and 1,100 µgF/g and commercial dentifrice (positive control, 1,100 µgF/g). Finally, the surface and cross-section hardness was determined for calculating the change of surface hardness (%SH) and mineral content (%∆Z). Fluoride in enamel was also determined. The data from %SH, %∆Z and fluoride were subjected to two-way analysis of variance followed by Student-Newman-Keuls's test (p<0.05). The mineral gain (%SH and %∆Z) was higher for toothpastes diluted in saliva (p<0.05), except for the 450 µgF/g dentifrice with Cacit/TMP (p>0.05). The 450 Cacit/TMP toothpaste and the positive control showed similar results (p>0.05) when diluted in water. A dose-response was observed between fluoride concentration in toothpastes and fluoride present in enamel, regardless of dilution. It was concluded that it is possible to enhance the remineralization capacity of low F concentration toothpaste by of organic (Cacit) and inorganic (TMP) compounds with affinity to hydroxyapatite.