Absorbability of calcium sources: The limited role of solubility

Summary Fractional absorption of seven chemically defined calcium sources was measured in normal adult women under standardized load conditions. Solubility of the sources in water at neutral pH ranged from a low of 0.04 mM to a high of 1500 mM. The relationship of solubility to absorbability was weak. In the range from 0.1 to 10 mM, within which most calcium supplement sources fall, there was no detectable effect of solubility on absorption. Data from four food sources are presented for comparison. Absorbability of food calcium was not clearly related to absorbability of the dominant chemical form in the food concerned. These findings suggest that (1) even under controlled, chemically defined conditions, solubility of a source has very little influence on its absorbability; and (2) absorbability of calcium from food sources is determined mainly by other food components.     

Studies of dietary influence on urinary oxalate in calcium oxalate stone formers

In order to examine the effect of diet on the urinary excretion of oxalate, a spinach loading and milk loading experiment was performed in normal subjects and patients with single calcium oxalate stones and recurrent calcium oxalate stones after a rat experiment. When spinach (100 g, total oxalate 642.57 mg, insoluble oxalate 282.21 mg, taken oxalate 444.57 mg) was given with a low calcium diet to the patients, the increase of urinary oxalate was more prominent in those with recurrent stones; the mean urinary oxalate increased from 39.84 to 84.18 mg/day (P less than 0.01) in the group with recurrent stones, from 36.95 to 55.12 mg/day (P less than 0.05) in the group with single stones and from 33.99 to 42.78 mg/day in the control group. These increases in oxalate excretion could be ameliorated by the concurrent oral administration of milk (calcium 343 mg). Moreover, diurnal variation in oxalate excretion was observed. It was more evident under spinach load in the group with recurrent stones than in the control group. Urinary oxalate increased promptly, reaching peak levels between 4 and 6 hours after loading in the group with recurrent stones and single stones, and between 2 and 4 hours in the control group. The influence of the spinach load disappeared within 24 hours.     

Absorbability of the calcium in a high-calcium mineral water

The availability of the calcium contained in a high-calcium mineral water (Sangemini), popular in Italy, was compared in 18 healthy women with the availability of milk calcium ingested at the same calcium load, using⁴⁵Ca as the tracer in a randomized cross-over design. At an ingested calcium load of 2.5 mmol, absorption fraction averaged 0.433 for milk and 0.475 for Sangemini water. The mean quotient of the two (Sangemini/milk) was 1.129 (±0.056, SEM,P<0.05). The calcium of Sangemini water is thus highly bioavailable, and at least as bioavailable as milk calcium.     

Urinary response to an oxalic acid load is influenced by the timing of calcium loading in rats

PURPOSE: Dietary intake of calcium or dairy products has been shown to decrease urinary oxalate excretion by limiting its intestinal absorption. However, not enough attention has been given to whether there is any benefit from altering the schedule of ingesting calcium and oxalate. Therefore, we investigated the effects of changes in the timing of calcium and oxalate loading on urinary oxalate excretion. MATERIALS AND METHODS: Male Wistar rats weighing 180 to 200 gm were fasted and randomized into several groups. They were then administered normal saline or oxalic acid with or without calcium or milk. Calcium or milk was given immediately, or 5, 10, 15 or 30 minutes before or after the oxalate load. All treatments were given via gastrostomy. Urine samples were collected by bladder puncture just before administration and at hourly intervals up to 5 hours afterward. Urinary oxalate was measured by capillary electrophoresis. RESULTS: Urinary oxalate increased after the administration of oxalate alone, while it decreased when oxalate was combined with calcium or milk. Urinary oxalate showed a smaller increment when calcium or milk was given before than after oxalate loading, and it was much smaller when calcium or milk was given immediately before oxalate. CONCLUSIONS: Prior calcium loading appears to have a positive influence on decreasing oxalic acid absorption from the intestinal tract. Therefore, calcium or dairy products should always be ingested before a meal rich in oxalate to prevent oxalate absorption and decrease urinary oxalate excretion.     

Absorption of Calcium as the Carbonate and Citrate Salts, with Some Observations on Method

Calcium supplement use has increased and there is confusion about the relative absorbability of various sources. Absorbability of calcium from the carbonate and citrate salts was compared at 300 mg and 1000 mg calcium loads, ingested as part of a light breakfast meal. Absorption was measured at the high load both by tracer appearance in serum and by the absorptive increment in urinary calcium, and at the low load by the tracer method only. Subjects were 37 healthy adult men and women, studied as outpatients, and each tested on both salts at the same load. Mean tracer absorption (± SD) for both salts combined was 36.0% at the 300 mg load and 28.4% at the 1000 mg load. In both experiments the observed mean difference in absorption between salts was very small. By the tracer method the within-subject difference (carbonate less citrate) was +3.3%± 1.2% of the ingested dose (mean ± SEM; P <0.05) at the high load, and at the low load, 3.6%± 2.7% (NS). Combining the two experiments yielded zero difference between sources. By the urinary calcium increment method, the mean difference between salts at the 1000 mg load was 1.8 ± 4.1 mg (NS). Side-by-side comparisons of the two methods revealed that the tracer method was 3 times more sensitive than the urinary increment method. We conclude that, when taken with food, calcium from the carbonate salt is fully as absorbable as from the citrate, and that the urinary increment method is not sufficiently sensitive to be useful in comparing sources in free-living subjects. Received: 6 April 1998 / Accepted: 6 April 1998     

Increased Calcium Absorption From Synthetic Stable Amorphous Calcium Carbonate: Double‐Blind Randomized Crossover Clinical Trial in Postmenopausal Women

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with ⁴⁴Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl₂ labeled with ⁴²Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24‐hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.     

Chitosan does not reduce post-prandial urinary oxalate excretion

Chitosan is a positively charged non-absorbable cellulose-like fibrillar biopolymer derived from shellfish which forms films with negatively charged surfaces. We hypothesized that negatively charged oxalate in the intestinal lumen could attach to the positively charged tertiary amino group of chitosan. We studied the effects of chitosan on intestinal oxalate absorption by measuring urinary oxalate excretion following an oral oxalate load with and without accompanying oral chitosan. The subjects consumed a fixed diet and collected urine for 24 h, in divided periods, during control and experimental protocols. Urine was collected with HCl and thymol as a preservative. For the control period, the subjects consumed an oxalate load, 50 g of cooked spinach, with water for lunch; the post-prandial urine collection was divided into three periods of 2 h. For the experimental period, 1 week later, the subjects consumed the same diet as that during the control period, but added 2 g of chitosan to the oxalate load. Post-prandial urinary oxalate excretion was expressed as mg oxalate/g creatinine. The spinach load was associated with a significant post-prandial increase in urinary oxalate during the control period of 25.7±12.8 mg/g creatinine. Accompanying the oxalate load with chitosan was well tolerated. There was no decrease in post-prandial urinary oxalate excretion during the experimental period: oxalate excretion rose by 31.3±16.9 mg/g creatinine (P=0.57, NS). We conclude that chitosan does not reduce acute intestinal oxalate absorption and therefore does not affect post-prandial urinary oxalate excretion.     

Bioavailability of Calcium: Comparison of Calcium Carbonate and Milk and the Effect of Vitamin D, Age, and Sex Using 24-Hour Urine Calcium as a Method

The aim of the present study was to compare the bioavailability of calcium from calcium carbonate and milk and to investigate if 1,200 IU of cholecalciferol a day increased intestinal absorption of calcium. Both young women and a group of older persons of both sexes were included to study the influence of age and sex. In total, 53 healthy women and men were included: a group of 23 younger women (median age 30) and an older group of 15 women and 15 men (median age 66). The study period was 4 weeks; each participant completed four treatment regimens randomly: CaCO₃, CaCO₃ + 1,200 IU of cholecalciferol, milk, and placebo. All regimens were distributed three times a day and consisted of 1,200 mg of elementary calcium. The 24-hour urine calcium excretion was used as a method. Total urinary calcium excretion rates (mmol/day) were as follows (mean ± SD): placebo 4.41 ± 2.17, milk 5.17 ± 2.33, CaCO₃ 5.83 ± 2.03, and CaCO₃ + D 6.06 ± 2.46. All regimens compared to placebo were significant. Addition of cholecalciferol to the CaCO₃ regimen increased calcium excretion but insignificantly: 0.27 ± 2.84 mmol/day. The increase in calcium excretion during the milk regimen was significant only for the old group: 0.96 vs. 0.28 mmol/day. No other difference was found according to age and sex. The bioavailability of calcium carbonate and milk was demonstrated. Additional cholecalciferol (1,200 IU) to individuals in positive calcium balance with serum 25(OH)D levels >50 nmol/L only marginally increased calcium absorption in a short-term intervention.     

Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone formers than in healthy controls: measurements with the [(13)C2]oxalate absorption test

PURPOSE: We assessed the importance of oxalate hyperabsorption for idiopathic calcium oxalate urolithiasis, oxalate absorption in healthy volunteers and recurrent calcium oxalate stone formers was compared. MATERIALS AND METHODS: The [(13)C2]oxalate absorption test, a standardized, radioactivity-free test, was performed. On 2 days 24-hour urine was collected and an identical standard diet containing 800 mg Ca daily was maintained. On the morning of day 2 a capsule containing 0.37 mmol sodium [(13)C2]oxalate was ingested. A total of 120 healthy volunteers (60 women and 60 men) and 120 patients (30 women and 90 men) with idiopathic CaOx urolithiasis (60% or greater CaOx) were tested. RESULTS: Mean intestinal oxalate absorption in the volunteers was 8.0 +/- 4.4%, and in the patients was 10.2 +/- 5.2% (p <0.001). There was no significant difference in mean absorption values between men and women within both groups. A high overlap between the absorption values of volunteers and patients was found. Only in the patient group did absorption values greater than 20% occur. Oxalate absorption correlated with oxalate excretion in the patients, r = 0.529 (p <0.01) and in the volunteers, r = 0.307 (p <0.01). CONCLUSIONS: In high oxalate absorbers dietary oxalate has a significant role in oxalate excretion and, therefore, increases the risk of calcium oxalate stone formation.     

Effect of caseinphosphopeptide on absorbability of co-ingested calcium in normal postmenopausal women

Caseinphosphopeptide in a dose of 87.5 mg was administered to 35 normal post-menopausal women as a part of a standard test meal containing a calcium load of 250 mg. Absorption of calcium was tested both with and without caseinphosphopeptide, using an intrinsic⁴⁵Ca label in the calcium source. The mean quotient of absorption with/without caseinphosphopeptide was greater than 1.0, but nonsignificantly so. However, when analysis was confined to women with low absorption values, caseinphosphopeptide administration was associated with significantly better absorption of co-ingested calcium. Those findings suggest that caseinphosphopeptide supplementation is particularly useful, for persons with low basal absorptive performance.     

Plasma oxalate level in pediatric calcium stone formers with or without secondary hyperoxaluria

Plasma oxalate (POx) concentration is significantly elevated in primary hyperoxaluria, severe renal failure or ethylene glycol poisoning. In these conditions, the degree of hyperoxalemia correlates with the severity of systemic calcium oxalate (CaOx) deposition and should be therefore carefully monitored. Although secondary hyperoxaluria (secHyOx) is a common finding in pediatric patients with kidney stone disease, very little is known about POx in this condition. We therefore evaluated POx level in 59 children and adolescence with calcium urolithiasis (34 confirmed by CaOx stone analysis and 25 children with a strong clinical suspicion of this type of urolithiasis), with or without “mild” secHyOx. A control group consisted of 41 healthy sex- and age-matched children. We found that POx was significantly increased in children with calcium urolithiasis and secHyOx compared to healthy children (9.16 ± 3.60 vs. 6.42 ± 2.53 μmol/l), but that was not the case in children with calcium urolithiasis but with normal urinary oxalate excretion (7.12 ± 3.33 μmol/l). We conclude that POx may be slightly increased in some pediatric calcium stone formers with secHyOx, probably related to intestinal oxalate hyperabsorption.     

Association between calcium ingested from drinking water and femoral bone density in elderly women: evidence from the EPIDOS cohort.

Although the main source of dietary calcium is dairy products, the calcium contained in mineral water, which is as available as that of milk, could provide a valuable source of calcium. We analyzed the data from the EPIDOS multicenter study to evaluate the relationship between both dietary calcium and that supplied by drinking water and bone density measured at the femoral neck by dual-energy X-ray absorptiometry. The study included 4434 women over 75 years of age who had not received any treatment likely to interfere with calcium metabolism. A significant correlation was found between total calcium intake and bone density at the femoral neck (r = 0.10, p < 0. 001). After adjustment for the main variables influencing bone density, an increase of 100 mg/day in calcium from drinking water was associated to a 0.5% increase in femoral bone density, while a similar increase in dietary calcium from other sources only led to a 0.2% increase; however, this difference was not significant. The consumption of calcium-rich mineral water may be of interest, especially in older women who consume little calcium from dairy products.     

Oxalate loading test for outpatients with calcium oxalate stones

A spinach loading experiment was performed on 9 normal subjects, 25 outpatients who were single calcium oxalate stone formers and 25 recurrent calcium oxalate stone formers. The experimental diet contained 445 mg of total oxalate, 163 mg of soluble oxalate and 115 mg of calcium. Urinary oxalate excretion was observed 2 hrs before and 6 hrs after the experimental diet was consumed. There was no significant difference in urinary oxalate excretion in preloading urine of normal subjects and stone formers. However, urinary oxalate excretion in postloading urine was significantly elevated in stone formers. This loading test is recommended as a simple and valuable screening method of hyperabsorption of oxalate on outpatients with calcium oxalate stones.     

Estimation by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio

According to the theoretical expression for calibration curve as a function of the optical absorption ratio of two peaks and with the analysis of the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and synthesized calcium oxalate dihydrate, the following quadratic equation was obtained; Y = 1.79 X2 - 30.90 X + 107.04 in which Y is the percentage of the purity of calcium oxalate dihydrate and X is the ratio of the relative optical absorption at 660 cm.-1 (the wave number at a characteristic absorption peak of calcium oxalate monohydrate) to that at 610 cm.-1 (that of calcium oxalate dihydrate) by regarding the line as a base-line that links the absorption valley at around 700 cm.-1 with that at 550 cm.-1 The linear correlation coefficient of the actual purity to the estimated purity obtained from this formula of calcium oxalate dihydrate is 0.995. When this formula is applied to the results derived from the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and calcium oxalate dihydrate obtained from urinary stones in duplicate in each percentage, the linear correlation coefficient is 0.991. This estimation method by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio gave a very close correlation between actual and estimated purity of calcium oxalate dihydrate and seems useful in the study of calcium oxalate urolithiasis.     

Dependence of oxalate absorption on the daily calcium intake

Two to 20% of ingested oxalate is absorbed in the gastrointestinal tract of healthy humans with a daily 800 mg calcium intake. Calcium is the most potent modifier of the oxalate absorption. Although this has been found repeatedly, the exact correlation between calcium intake and oxalate absorption has not been assessed to date. Investigated was oxalate absorption in healthy volunteers applying 0.37 mmol of the soluble salt sodium [(13)C(2)]oxalate in the calcium intake range from 5 mmol (200 mg) calcium to 45 mmol (1800 mg) calcium. Within the range of 200 to 1200 mg calcium per day, oxalate absorption depended linearly on the calcium intake. With 200 mg calcium per day, the mean absorption (+/- SD) was 17% +/- 8.3%; with 1200 mg calcium per day, the mean absorption was 2.6% +/- 1.5%. Within this range, reduction of the calcium supply by 70 mg increased the oxalate absorption by 1% and vice versa. Calcium addition beyond 1200 mg/d reduced the oxalate absorption only one-tenth as effectively. With 1800 mg calcium per day, the mean absorption was 1.7% +/- 0.9%. The findings may explain why a low-calcium diet increases the risk of calcium oxalate stone formation.     

Risk of Calcium Oxalate Nephrolithiasis after Calcium or Combined Calcium and Calcitriol Supplementation in Postmenopausal Women

Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n= 28) or 750 mg of calcium carbonate plus 0.5 mg calcitriol (n= 25) daily. Mean ± SEM for age was 65.3 ± 1.1 years, body weight 53.5 ± 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ± 0.43 mmol/day; after treatment 3.58 ± 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ± 0.41 mmol/day; after treatment, 4.08 ± 0.57 mmol/day; p<0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ± 0.39; after treatment, 1.36 ± 0.28) or after calcium plus calcitriol (baseline, 1.09 ± 0.17; after treatment, 1.09 ± 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ± 0.74 for urinary calcium, 1.01 ± 0.19 for urinary oxalate, and 2.23 ± 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis. Received: 10 March 1999 / Accepted: 16 November 1999     

Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

Summary Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. Introduction and hypothesis Adult-type hypolactasia (HL) defined by the LCT_(−13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). Methods Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H₂ breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. Results LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 ± 629 μg/L vs. 2020 ± 1130 μg/L in lactose tolerant subjects, p = 0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. Conclusion Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.     

Intestinal absorption of oxalate and calcium in patients with jejunoileal bypass

Jejunoileal bypass (JIB) has been widely performed for treatment of excessive obesity. Formation of calcium oxalate stones is a common side effect. Since, under physiological conditions, the intestinal absorption of calcium and that of oxalate are interrelated, intestinal oxalate and calcium absorption were measured in the present study by isotope techniques in 19 JIB patients and 20 healthy controls. The JIB patients showed pronounced hyperoxaluria and markedly increased absorption of oxalate, with a urinary excretion of 14C-oxalate of 29 +/- 19% (controls 6.2 +/- 3.7%; p less than 0.001). There was a strong correlation between the intestinal absorption and urinary excretion of oxalate in the JIB patients (r = 0.72; p less than 0.001). Furthermore, their oxalate kinetics was altered, with continued urinary excretion of 14C-oxalate for up to 48 hours. The JIB patients also had reduced calcium absorption (36 +/- 9.1% vs. 47 +/- 9.0%; p less than 0.001) and patients with malabsorption of calcium and low urinary calcium had the highest intestinal absorption and urinary excretion of oxalate. It is concluded that hyperoxaluria in JIB patients is due to a significant extent to hyperabsorption of oxalate.     

Acute biochemical variations induced by two different calcium salts in healthy perimenopausal women

Despite the potential utility of calcium supplementation and the availability of many calcium supplements in the market, there are few data concerning the absorbability of different calcium salts in different conditions. We have compared the acute metabolic responses following oral administration of calcium citrate (CC) or calcium gluconolactate and carbonate (CGC) given to 20 healthy perimenopausal women (aged 48–55 years). Ten women received two effervescent tablets of CC (each containing 500 mg of calcium) and 10 women received two effervescent tablets of CGC (each containing 500 mg of calcium). Before and on an hourly basis for 6 hours, serum total and ionized calcium, phosphate, and immunoreactive parathyroid hormone (iPTH) were measured. Urinary calcium and creatinine were also measured. Both calcium salts induced significant increase in serum total and ionized calcium and in urinary calcium excretion; they also significantly reduced circulating levels of iPTH. The analysis of ionized calcium and iPTH response curves to CC and CGC administration revealed a significantly greater bioavailability of CC compared with CGC. Our data suggest that CC could be prefered to CGC for its characteristics of absorbability and bioavailability.