Time course of calcium absorption in humans: Evidence for a colonic component

Summary We examined the time course of calcium absorption (CaAbs) in 155 studies, using a double isotope technique. The subjects were 118 healthy peri-menopausal women (mean age 53.3 years), studied as impatients under metabolic balance conditions. We measured the ratio of radiolabeled calcium (oral:IV) in serum and urine for 144 hours after the oral dose, and generated a composite CaAbs curve for all 155 studies using normalized data. Although CaAbs was 80.9% complete at 3 hours, it was still only 95.8% complete at 7 hours; the remaining 4.2% was absorbed in a slower late component, and did not reach completion until about 26 hours. The rapid initial component probably represents mainly small intestinal absorption and the late component, colonic. At the dietary intakes of our subjects, we estimate the size of the late component at about 6.8 mg/day. For fully accurate measurements of CaAbs, it is necessary to allow for this small late component.     

The effect of an oral calcium load on plasma ionized calcium and parathyroid hormone concentrations in osteoporotic postmenopausal women

Summary Plasma ionized calcium (IC) and parathyroid hormone (PTH) concentrations were measured in 31 osteoporotic postmenopausal women at hourly intervals for 5 hours after a 1 g oral calcium load. Fifteen subjects had normal radiocalcium absorption and 16 subjects were malabsorbers of calcium. IC rose and PTH fell after the calcium load in both groups with a plateau at 3–4 hours, and the rise in IC was greater (P<0.01) in the normal absorbers. There was a nonsignificant trend for the fall in PTH to be greater in the normal absorbers. In the group as a whole the mean increase in IC (above baseline) at 4 hours was directly related to calcium absorption (P<0.025) and the mean change in PTH was inversely related to calcium absorption (P<0.05). These results demonstrate that in subjects with postmenopausal osteoporosis the responses of IC and PTH to an oral calcium load are a function of calcium absorptive status.     

Calcium prescription by Indian orthopaedic surgeons: A survey and a review of literature

BackgroundOrthopaedic surgeons prefer calcium supplement for various pathologies like fracture, osteoporosis, chronic musculoskeletal pain, yet there is no proper evidence to support the benefits of taking them regularly. The average requirement for calcium is around 500–1000 mg/day for a healthy adult, this amount of calcium is not achieved by diet, especially in developing countries like India. Despite this, the serum calcium level remains unaltered, due to the well-controlled absorption and excretion of calcium by the human body. As there is no clarity over the dose, duration and the prefered calcium salts, we constructed a survey to find the preferred dose, duration, the preferred calcium salts among orthopaedic surgeons, and to give an in-depth review of literature about dose, duration, timing, preferred calcium salt and various other calcium-related queries.Materials and methodThe survey included 15 pre-structured questionnaires; these questions were formatted and validated by senior surgeons and other specialists after a through a review of calcium-related literature. These questionnaires were used in a pilot study conducted within the department and were later modified and separated into 7 sections. Data were collected by both online survey (google forms) and direct interviews.Result and conclusion128 Orthopedic surgeons responded. The total number of response obtained was 2355. Unanswered questions were 152. From the survey, it was found that most orthopaedic surgeons prefer to prescribe calcium routinely (55.46%). The commonly used calcium salt was calcium carbonate (47.65%), followed by citrate (32.8%). 42.18% were not aware of the efficiency of prescribing calcium in divided doses. Most responded that calcium is not to be given for patients with renal stones, but literature shows that calcium prescribed reduces the recurrence of commonest kidney stones, calcium oxalate stones.     

The acute metabolic effects of oral tricalcium phosphate and calcium carbonate

A double-blind study was performed to test the metabolic effects of tricalcium phosphate (TP) and calcium carbonate (CC) on serum calcium (SCa), serum phosphorus (SP), and immunoreactive intact serum parathyroid hormone (SPTH) levels in two groups of 24 subjects. The mean age of young subjects was 29.5 years, and elderly subjects, 65.9 years. These subjects fasted overnight for 12 hours, but with good hydration, before the tests. Following a 2-hour baseline-urine collection, 1200 mg elemental calcium (as CC or TP in tablet form) was chewed and ingested and 2-hour postload urines were collected. Blood was drawn immediately before and at 1, 2, and 4 hours after calcium load. The results showed that SCa and SP increased, whereas SPTH decreased with both preparations. The increment of SCa was similar after oral load of either calcium salt in both groups. The increment of SP after TP load was more than after CC. The urinary calcium/creatinine ratio (UCa/Cr) increased significantly after both preparations in the young group. The urinary phosphorus/creatinine ratio (UP/Cr) did not change significantly following TP, but decreased significantly after CC load in the young subjects. However, in the elderly individuals, the UP/Cr increased after TP load but did not change following CC, with statistical significance. The difference of urinary cyclic adenosine monophosphate/creatinine ratio (UcAMP/Cr) was not significant in both groups with either preparation. In summary, there was a similar rise in SCa and an equivalent fall in SPTH between TP and CC, in both young and elderly individuals.     

Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: A comparison with oral calcium tolerance test

Summary To test the accuracy of calcium tolerance test in estimating calcium absorption, we have measured the radioactive calcium absorption (expressed as Fx) in 27 patients with IH and renal calcium stones. The results of this test were compared with those of a standard oral calcium tolerance test. Although only seven of nine AH patients displayed normal fasting calcium excretion, they all displayed Fx values above normal and a normal parathyroid activity. Conversely, only 5 of our 18 RH patients demonstrated a hyperabsorption of radioactive calcium and an elevation in iPTH and cAMP above normal limits, yet all of them showed an increased calciuric response to an oral calcium challenge. Calcium absorption was inversely related to iPTH (r=−082;P<0.001) and cAMP (r=−064P<0.05) in AH, but directly proportional to these parameters (r=0.62P<0.001 andr=0.46P<0.05, respectively) in RH patients. In view of these results, two ratios, iPTH/Fx and cAMP/Fx were used to discriminate between the two groups of patients. Both ratios were over normal limits in all RH patients and within normal range in all but one AH patient. Furthermore, no overlap was found between the two groups. Conversely, we were unable to completely separate AH from RH subjects on the basis of the oral calcium tolerance test, since in both groups the fasting and the absolute (or percentage) changes in urinary calcium, cAMP and blood iPTH levels following oral calcium loading, overlapped in each instance. The result of this study indicates that two indices, iPTH/Fx and cAMP/Fx, may prove particularly useful in differentiating AH from RH patients. Furthermore, since only a subgroup of patients with an abnormal calciuric response to an oral calcium load manifest an increase in calcium absorption, it is concluded that the calcium tolerance test overestimates calcium absorption in IH. Supported in part by Grant No. 5T32 AM0703310     

Intestinal calcium absorption from different calcium preparations: Influence of anion and solubility

Not only is the calcium content of a preparation significant for providing adequate calcium supplementation for the prophylaxis and therapy of osteoporosis, but also its bioavailablity is of essential importance. In the present study, the bioavailability of calcium citrate and calcium lactogluconate/carbonate from a therapeutic dose (= 500 mg Ca²⁺) was compared in men aged between 45 and 60 years on an intra-individual basis. Calcium citrate was administered both as a solution and as a suspension to 18 healthy volunteers. Using a double-isotope method, the intestinal absorption from the three preparations was determined in randomized order at intervals of 2–4 weeks. The stable isotope⁴⁴Ca (20 mg), in highly enriched form, was added in each case to the ready-to-drink solutions and, at the same time, a sterile and pyrogen-free solution containing 5 mg of the stable isotope⁴²Ca was injected intravenously. The intestinal calcium absorption was then determined after 24 h on the basis of the ratio of the two isotopes in the plasma. There was a significantly higher absorption of 29% from the citrate solution than from the lactogluconate/carbonate solution (25%). Absorption from the citrate suspension was similar to that from the lactogluconate/carbonate solution. While no correlation was found between the measured values for calcium absorption from the three preparations and the plasma concentration of 1,25-dihydroxycholecalciferol, significant inverse correlations with the basal parathyroid hormone concentration were observed for the citrate and lactogluconate/carbonate solution. The results of this study show that quantitative data on intestinal calcium absorption can be obtained without employing radioactive isotopes in humans. Moreover, they show that calcium absorption is not determined only by the solubility and the degree of ionization of the calcium salt administered, but rather that it is of a complex nature.     

Comparison between the fractional isotopic calcium absorption and an oral calcium tolerance test

Summary In 27 subjects with several disorders of calcium metabolism, the fractional intestinal absorption of⁴⁷CaCl₂ was rather poorly correlated with the urinary output of calcium or with the maximal increase of serum calcium after an oral calcium load. Conversely, a good correlation was observed with the product of these parameters. We propose that this product be used as an estimate of intestinal calcium absorption when a radioisotopic method is not available.     

Effects of a cation exchange resin on intestinal calcium absorption and urinary calcium in calcium stone formers

Summary The effect on the urinary excretion of calcium of an oral cation exchange resin with-out phosphorus was studied in healthy control subjects and patients with recurrent calcium lithiasis under out-patient conditions. An immediate reduction of intestinal calcium absorption and urinary calcium excretion was found in five control subjects and in one patient after ingestion of resin, whereas calcium excretion remained unchanged in all other patients during long-term treatment. In addition, signs of mild transitory hyperparathyroidism together with an increase in intestinal calcium transport were observed during treatment. It is suggested that intraluminal binding of calcium ions to the resin leads to substantial changes in calcium metabolism with the result that urinary calcium excretion returns to pretreatment values.     

Caffeine and the calcium economy revisited

We report an analysis of data from 560 calcium balance studies carried out on 190 women aged 34.8–69.3 years at the time of study. The main purposes were to confirm a previously observed association between caffeine intake and calcium balance, and to attribute the association, if possible, to specific component(s) of balance. We found a caffeine relationship such that for every 6 fl oz (177.5 ml) serving of caffeine-containing coffee, calcium balance was more negative by 0.114 mmol/day (4.6 mg/day) (P<0.001). The relationship was localized to the input side of the balance equation, and both of its components (i.e. calcium intake and calcium absorption efficiency) were independently and inversely associated with caffeine intake. There was no evidence that the putative caffeine effect is confined to, or is greater among, subjects with low calcium intakes or those who are older or estrogen-deprived. The magnitude of the negative effect of caffeine on calcium balance suggests that it can be offset by increasing calcium intake by about 1 mmol (40 mg) for every 177.5 ml serving of caffeine-containing coffee.     

Oral calcium loading test and response to diuretics in normal taiwanese school children

To investigate possible mechanisms of increased urinary calcium excretion and increased prevalence of urolithiasis in 16- to 20-year-old children, oral calcium loading and diuretic tests were performed in 120 normal children in three age groups (7–8, 12–13, and 17–18 years of age). Urinary calcium/creatinine ratios and 24-h urinary calcium excretion were significantly increased following the oral calcium loading test in 17- to 18-year-olds compared with the two younger age groups. Oral furosemide resulted in increased urinary calcium excretion in the 17- to 18-year age group, while hydrochlorothiazide was less effective in reducing urinary calcium excretion in this age group. These results suggest that increased intestinal calcium absorption and decreased renal tubular reabsorption of calcium in 17- to 18-year-olds may be contributing factors in the increased prevalence of nephrolithiasis in older Taiwanese children.     

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.     

Calcium absorption measurements in normal subjects in determining calcium deposition during prolonged hypokinesia and with and without calcium loading

Measuring calcium (Ca) absorption, Ca balance and Ca level in serum,feces and urine during HK (hypokinesia) with and without Ca loading, the aim of this study was to disclose if prolonged HK could reduce Ca deposition more with or without Ca load contributing to greater Ca imbalance. Studies were conducted during 30-days pre-HK and 364-days HK. Forty male normal volunteers 23.7 ± 6.0 years of age were chosen as subjects. They were divided into four groups: unloaded active control subjects (UACS), unloaded hypokinetic subjects (UHKS), loaded active control subjects (LACS), loaded hypokinetic subjects (LHKS). All hypokinetic subjects were walking average distances of 0.5 ± 0.2 km day^–1, and active control subjects were running average distances of 6.6 ± 1.2 km day^–1. LACS and LHKS were loaded with 1.3 mmol calcium lactate/kg body wt. Before Ca load, fecal Ca loss, urinary Ca and phosphate (P) losses, Ca imbalance, serum ionized calcium (Ca_I), P and total Ca (Ca_t) levels increased significantly. (P < 0.05) with time, and serum intact parathyroid hormone (iPTH), 1.25 dihydroxyvitamin D (1.25(OH)₂D₃) levels and Ca absorption, decreased significantly (P < 0.05) with time in LHKS and UHKS compared with their pre-HK values and their respective active controls (LACS and UACS). After Ca load, however, Ca absorption, serum iPTH and 1.25 (OH)₂D₃ levels decreased significantly (P < 0.05) more with time, while fecal Ca loss, urinary Ca and P excretion and Ca imbalance increased significantly (P < 0.05) more with time in LHKS than UHKS. Conversely, before and after Ca load, fecal Ca excretion, urinary P and Ca loss, serum Ca_I, P, Ca, iPTH and 1.25 (OH)₂D₃ levels, Ca absorption and Ca balance did not change in LACS and UACS compared with their pre-HK values. The greater Ca losses with than without Ca load have shown that the more Ca is consumed the more Ca is eliminated during HK and Ca imbalance. The significant increase of Ca loss with Ca imbalance demonstrated reduced Ca deposition. Dissociation between Ca loss and Ca imbalance demonstrated reduced Ca deposition as the mechanism of Ca imbalance development during HK.     

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     

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.     

Effects on calcium and phosphate metabolism and on parathyroid function of acute administration of tricalcium phosphate

The effects of the ingestion of tricalcium phosphate on calcium and phosphate metabolism and on parathyroid function were evaluated in 10 young adults. Each subject was studied during a control period of two hours before and during an experimental period of four hours after ingestion of a single oral dose of tricalcium phosphate containing 1500 mg of calcium and 770 mg of phosphorus. Serum and urinary calcium and phosphate and the nephrogenous cAMP fraction were measured. Significant rises in serum (from 2.32 ± 0.05 to 2.44 ± 0.08 mmol/l) and urinary (from 1.08 ± 0.65 to 3.43 ± 1.38 μmol/l GF) calcium and in serum phosphate (from 1.05 ± 0.18 to 1.28 ± 0.14 mmol/l) occurred. Unexpectedly, the acute supply of calcium in the form of tricalcium phosphate did not provoke significant alteration of nephrogenous cAMP level. In order to assess the respective effects of calcium and of phosphate, similar tests with ingestion of similar amounts either of calcium (as a glucoheptogluconate salt) or of phosphate were subsequently performed in the same subjects. Significant increases in serum total calcium were observed after calcium glucoheptogluconate as after tricalcium phosphate. However, the effects on parathyroid function differed, since a significant (p < 0.001) decrease in nephrogenous cAMP followed the ingestion of calcium glucoheptogluconate. Otherwise, a stimulating effect of phosphate on parathyroid function was observed. These findings suggest that the respective effects of calcium and of phosphate are counterbalanced when administered as tricalcium phosphate, resulting in the absence of parathyroid suppression.     

Estimated levels of supersaturation with calcium phosphate and calcium oxalate in the distal tubule

Approximate estimates of the ion-acitivity products of calcium phosphate and calcium oxalate in distal tubular urine were derived from the 16-h urinary excretion of calcium, oxalate, citrate, magnesium and phosphate. Urine variables were obtained from 96 normal subjects and 277 calcium stone formers and the calculations were carried out with iterative approximation using the EQUIL2 program. With respect to other ions of importance for the ion-activity products, the urine was assumed to have a fixed composition with pH 6.45. Significantly higher ion-activity products of both calcium phosphate and calcium oxalate were recorded in stone formers. It was concluded that diurnal variations in urine composition and pH might result in peaks of calcium phosphate supersaturation in distal tubular urine whereby a crystallization can occur. In association with abnormalities in terms of promotion and inhibition of calcium salt crystallization, such a precipitation can be of importance for the subsequent formation of calcium renal stones.     

Bioavailability of oyster shell electrolysate

Balance studies were conducted on 4 normal elderly subjects, 2 males and 2 females, ranging in age between 66 and 86 years in order to compare the bioavailability of oyster shell electrolysate with that of calcium carbonate and calcium lactate, in a crossover design. In each subject, 600 mg oyster shell electrolysate was more effective than calcium carbonate or calcium lactate containing the same 600 mg calcium to restore the negative calcium balance found on 600 mg/day calcium intake, suggesting a better bioavailability of oyster shell electrolysate than the two kinds of calcium salts.     

Isotopic exchange of ingested calcium between labeled sources. Evidence that ingested calcium does not form a common absorptive pool

Summary We studied the extent of salt dissociation during absorption of calcium from sources of differing absorbability by measuring fractional absorption from loads in the range of 200–300 mg in healthy adult women. Sources were labeled both intrinsically and extrinsically with⁴⁵Ca and⁴⁷Ca, respectively, and were fed alone and in combination with one another. We first confirmed our previous observation of superior absorbability of calcium oxalate over spinach calcium in a randomized cross-over design in 20 women. Spinach calcium exhibited only half the absorbability of the same load of calcium presented as the oxalate. Then, in 14 women fed spinach with both an intrinsic and an extrinsic label, apparent absorption of the extrinsic label averaged 0.130±0.041 and of the intrinsic label, 0.029±0.023. Thus, the extrinsic tag was partially, but not completely, bound by the spinach. In the same 14 women, milk absorption averaged 0.331±0.092 when ingested alone. However, when coingested with spinach, apparent milk calcium absorption fell to 0.267±0.079 and apparent spinach calcium absorption rose to 0.111±0.039. Thus, there was significant but incomplete label exchange between the two sources, indicating that at least some of the calcium from both sources enters a common preabsorptive, ionic pool. By contrast, we had previously shown no tracer exchange when labeled oxalate was co-fed with labeled milk. We conclude that (1) the presence of calcium as the oxalate in spinach is not a sufficient explanation for the poor absorbability of spinach calcium; and (2) oxalate calcium and spinach calcium are absorbed by different mechanisms, one involving a common preabsorptive pool and the other not. We suggest that oxalate calcium absorption is by passive diffusion of the intact complex and spinach calcium absorption by active transport of the free cation.     

Peptic ulcer disease and calcium intake as risk factors of osteoporosis in women

Introduction: Low dietary intake and decreased absorption of calcium are known as important risk factors of osteoporosis. Peptic ulcer disease may be accompanied by dietary restrictions influencing negatively calcium intake. Inflammation of gastric and duodenal mucosa as well as alkali used may significantly decrease calcium absorption. Additionally, bone metabolism may be changed by inflammatory mediators released as a result of mucosal inflammation. Aims: Comparison of bone mineral density and calcium dietary intake in women with and without (control group) peptic ulcer disease. Methods: Two hundred and sixty-three women were studied: 143 (mean age 60.3 years) with peptic ulcer disease diagnosed by endoscopy and/or upper gastrointestinal X-ray, and 120 (mean age 58.4 years) as controls. History of alimentary tract diseases and presence of risk factors of osteoporosis, as well as history of hormone replacement therapy, were collected based on specially designed questionnaires. Women with present risk factors of secondary osteoporosis and with previously diagnosed osteoporosis were excluded. The calcium dietary intake was determined using a standard questionnaire assessing milk and milk products intake as well as calcium supplementation when used. Bone mineral density of the lumbar spine and femoral bone was determined by DXA. Results: Women with peptic ulcer disease not using hormone replacement therapy had lower bone mineral density in all studied regions as compared to control group without peptic ulcer disease. In the subgroup not using hormone replacement therapy all studied values differed significantly. In the smaller subgroup of women using hormone replacement therapy not all values were statistically significant. There was no statistical significance between studied groups in dietary calcium intake as milk, milk products, and calcium supplements. Conclusions: Calcium intake in women with ulcer disease is similar to healthy subjects. Peptic ulcer disease is an independent risk factor for osteoporosis in women.     

Calcium supplements: Practical considerations

The preferable source of calcium is a balanced diet, but medicinal supplements are sometimes necessary if patients are to reach desired intakes. A divided dose regimen (4×/d; i.e., with meals and at bedtime) results in substantially greater absorption of a supplement than does l×/d dosing. However, differences in chemical solubility between supplement preparations are of little importance, with calcium carbonate preparations, for example, being absorbed as well or better than some much more highly soluble salts. Gastric acid is not necessary for absorption of even poorly soluble preparations, so long as they are taken with meals. Because typical patients exhibit a wide range of absorption efficiencies, it is desirable to assess absorption fraction before beginning a supplement regimen. (Some patients will need three times as large a dose as others to absorb the same amount of calcium.) Calcium intakes up to at least 62.5 mmol (2500 mg) are safe for virtually all patients.