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Enhances calcium absorption: Overview of Calcium – Dietary Reference Intakes for Calcium and Vitamin D

Overview of Calcium – Dietary Reference Intakes for Calcium and Vitamin D

Several key bone mass measures are commonly used in the context of calcium nutriture and related health outcomes. The accumulation and level of bone mass can be determined using the calcium balance method or, alternatively, the measurement of BMC or BMD based on DXA. The latter method relies on the assumption that about 32 percent of the measured bone mineral is calcium (Ellis et al., 1996; Ma et al., 1999). These methods are described below.

Calcium Balance

Calcium balance (positive, neutral, or negative) is the measure derived by taking the difference between the total intake and the sum of the urinary and endogenous fecal excretion. Balance studies embody a metabolic approach to examining the relationship between calcium intake and calcium retention and are based on the assumption that the body retains the amount of calcium that is needed. As such, measures of calcium balance (or of “calcium retention”) can reflect conditions of bone accretion, bone maintenance, or bone loss. Calcium balance analyses involve measuring as precisely as possible the intake and the output of calcium. Output is usually reflected by urine and fecal calcium; sweat calcium is not usually measured, but its inclusion adds to the precision of the estimates. Calcium balance studies are expensive and require considerable subject cooperation owing to the prolonged stays in metabolic wards. Measures of calcium balance have limitations and are generally cross–sectional in nature, and their precision is difficult to ascertain. However, if well conducted, they provide valuable information on calcium requirements relative to the typical intake of the population under study. Long-term balance studies for calcium are generally not carried out because of the difficult study protocol. Calcium balance can also be estimated by using stable isotopes to trace the amount of calcium absorbed, usually in infants from a single feeding (Abrams, 2006).

Calcium balance outcomes that are positive are indicative of calcium accretion and are sometimes referred to as net calcium retention; neutral balance suggests maintenance of bone, and negative balance indicates bone loss. The relevance of the calcium balance state varies depending upon developmental stage. Infancy through late adolescence are characterized by positive calcium balance. In female adolescents and adults, even within the normal menstrual cycle, there are measurable fluctuations in calcium balance owing to the effects of fluctuating sex steroid levels and other factors on the basal rates of bone formation and resorption. Later in life, menopause and age-related bone loss lead to a net loss as a result of calcium due to enhanced bone resorption.

In the 1997 IOM report that focused on calcium DRIs (IOM, 1997), metabolic studies of calcium balance were used to obtain data on the relationship between calcium intakes and retention, from which a non-linear regression model was developed; from this was derived an intake of calcium that would be adequate to attain a predetermined desirable calcium retention.4 The approach used in 1997 was a refinement of an earlier approach suggested to determine the point at which additional calcium does not significantly increase calcium retention, called the plateau intake (Spencer et al. , 1984; Matkovic and Heaney, 1992).

The balance studies included in the 1997 IOM report (IOM, 1997) met criteria that included the following: subjects had a wide range of calcium intakes, as variability in retention increases at higher intakes; the balance studies were initiated at least 7 days after starting the diet in order for subjects to approach a steady state, as observed by Dawson-Hughes et al. (1988); and, where possible, the adult balance studies included were only for subjects who were consuming calcium at their usual intakes, unless otherwise indicated. By selecting studies conducted on such subjects, the 1997 committee concluded that it obviated the concern about whether the bone remodeling transient (i.e., the temporary alteration in the balance between bone formation and bone resorption) might introduce bias in the calcium retentions observed (IOM, 1997). Such selection was not possible in studies in children who were randomized to one of two calcium intakes. However, in children, the impact of the bone remodeling transient related to changing intake is overshadowed by their rapid and constantly changing rates of calcium accretion (i.e., their modeling and remodeling rates are not in steady state, even without an intake change).

For the 1997 DRI development (IOM, 1997), the non-linear regression model describing the relationship between calcium intake and retention was solved to obtain a predetermined desirable calcium retention that was specific for each age group. According to the report, the major limitation of the data available was that bone mineral accretion during growth had not yet been studied over a wide range of calcium intakes. Overall, the committee expressed concern about the uncertainties in the methods inherent in balance studies.

Specifics about calcium balance studies that relate to DRI development are provided in Chapter 4, but, as background the recent work of Hunt and Johnson (2007) offers some remedy for the uncertainties surrounding the precision of balance studies. Hunt and Johnson (2007) examined data from 155 subjects—men and women between the ages of 20 and 75 years— who took part in 19 feeding studies conducted at one site (Grand Forks Human Nutrition Research Unit) between 1976 and 1995 in a metabolic unit under carefully controlled conditions.

In their overall analysis, the relationship between intake and output was examined by fitting random coefficient models. Rather than model calcium retention compared with calcium intake by using the Jackman et al. (1997) model, as was done in the 1997 DRI report (IOM, 1997), Hunt and Johnson (2007) modeled output rather than retention to avoid confounding in the precision of estimates that would be caused by including intake as a component of the dependent variable. In the Hunt and Johnson (2007) analysis, the data summary did not show non-linearity and therefore did not justify the use of a more complex non-linear model. The authors noted that the coefficients of the 1997 approach appeared to be greatly influenced by data points above the 99th percentile of daily calcium intake and pointed out that the data in their model reflected typical calcium intake between the 5th and approximately 95th percentiles for all boys and men 9 or more years of age, and between the approximately 25th and greater than 99th percentiles for all girls and women 9 or more years of age.

Hunt and Johnson (2007) also pointed out that most (but not all) studies with adults that indicate a positive influence of high total calcium in reducing the rate of bone remodeling were confounded by the presence of vitamin D as an experimental co-variable. In their study, the metabolic diets were similar to the estimated median intake of vitamin D by free-living young women. In short, the analysis may provide a reasonable approach for extracting meaningful data from calcium balance studies that are often confounded by multiple dietary factors. At this point, factorial methods should be briefly noted as the determination of calcium requirements has also made use of a factorial approach as noted in the 1997 DRI report (IOM, 1997). The factorial approach allows the estimate of an intake level that achieves the measured levels of calcium accretion/retention. The method combines estimates of losses of calcium via its main routes in apparently healthy individuals and then assumes that these losses represent the degree to which calcium intake, as corrected by estimated absorption, is required to balance these losses. The weakness in this method is that it is unusual for all of the necessary measurements to be obtained within a single study. Therefore, most calculations using the factorial approach are compiled from data in different studies and thus in different subjects; this can introduce considerable variation and confound the outcomes. This approach, as carried out in the 1997 IOM report on DRIs for calcium and vitamin D (IOM, 1997), where the interest was in desirable retention, is illustrated in .

TABLE 2-1

1997 DRI Factorial Approach for Determining Calcium Requirements During Peak Calcium Accretion in White Adolescents.

Bone Mineral Content and Bone Mineral Density

BMC is the amount of mineral at a particular skeletal site, such as the femoral neck, lumbar spine, or total body. BMC is correctly a three-dimensional measurement, but when it is commonly measured by DXA, a cross-section of bone is analyzed, and the two-dimensional output is a real BMD (i.e., BMC divided by the area of the scanned region). True measurements of BMC (volumetric BMD) can be determined non-invasively by computed tomography. Throughout this report, the term “BMD” generally means areal BMD unless specified as volumetric BMD. Most importantly, any of these measures are strong predictors of fracture risk (IOM, 1997). Bone density studies can be considered to reflect average intakes of calcium over a long period of time. When available, such data likely provide a better snapshot of long-term calcium intake than does the combination of accretion/retention data.

In children, change in BMC is a useful indicator of calcium retention; change in BMD is less suitable, because it overestimates mineral content as a result of changes in skeletal size from growth (IOM, 1997). In adults, with their generally stable skeletal size, changes in either BMD or BMC are useful measures. In the context of longitudinal calcium intervention trials that measure change in BMC, the measures can provide data on the long-term impact of calcium intake not only on the total skeleton, but also on skeletal sites that are subject to osteoporotic fracture (IOM, 1997). However, because DXA does not distinguish between calcium that is within bone and calcium on the surface (e.g., osteophytes, calcifications in other tissues) or within blood vessels (e.g., calcified aorta), an increase in BMC or BMD, particularly in the spine, may result in false positive readings suggesting high bone mass (Banks et al., 1994).

In DXA, fan beam dual-energy X-ray beams are used to measure bone mass, with correction for overlying soft tissue. Data are converted to BMC and the area represented is measured. The BMD measurement is annotated in grams of mineral per square centimeter. BMC represents the amount of mineral in a volume of bone without consideration of total body size. It is thus independent of growth. The DXA method is also limited by excessive soft tissue as present in massively obese individuals. Dual-energy computed tomography measurements, which are much more expensive and require larger X-ray doses can provide density as well as volumetric determinants and are useful for estimating the entire mineral component.

Direct estimation of calcium balance in older adults by BMD is highly dependent on other factors besides calcium intake, such as serum levels of estrogen and PTH, intake of other nutrients (e.g., phosphorus and sodium), as well as adequate intestinal absorption and normal kidney function. Indeed, bone remodeling is not directly regulated by calcium, although it can suppress PTH-induced increases in bone resorption under certain conditions. Circumstances that enhance bone resorption, such as estrogen deficiency, or glucocorticoid use, alter the organic matrix and reduce the thickness and density of trabeculae, independent of calcium intake. In short, density measurements do not directly reflect calcium stores.

Vitamin D supplementation increases calcium absorption without a threshold effect | The American Journal of Clinical Nutrition

ABSTRACT

Background: The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency.

Objective: The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase calcium absorption.

Design: This was a placebo-controlled, dose-response, randomized, double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women. Seventy-six healthy postmenopausal women were randomly assigned to placebo or 800 IU (20 μg), 2000 IU (50 μg), or 4000 IU (100 μg) vitamin D3 for 8 wk. The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk.

Results: Seventy-one women with a mean ± SD age of 58.8 ± 4.9 y completed the study. The mean calcium intake was 1142 ± 509 mg/d and serum 25(OH)D was 63 ± 14 nmol/L at baseline. A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D3 dose or serum 25(OH)D concentration was observed. A 6.7% absolute increase in calcium absorption was found in the highest vitamin D3 group (100 μg). No evidence of nonlinearity was observed in the dose-response curve.

Conclusions: No evidence of a threshold of calcium absorption was found with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin D. This trial was registered at clinicaltrials.gov as NCT01119378.

See corresponding editorial on page 429.

INTRODUCTION

It has been suggested that there is a vitamin D intake or a serum 25-hydroxyvitamin D [25(OH)D]4 concentration (the measure of vitamin D status) above which there is no further influence on calcium absorption. This purported “threshold” could be used as an indicator of vitamin D sufficiency; ie, once calcium absorption is maximized, there would be no rationale for increasing the vitamin D intake above the threshold for skeletal health (proposed to be as high as 80–90 nmol/L). Other investigators propose that a decreased calcium absorption occurs only when there is a substrate deficiency of 25(OH)D [<10 ng/mL (25 nmol/L)], resulting in a lack of calcitriol synthesis (1).

Hansen et al (2) carried out a study of 18 subjects, given 50,000 IU vitamin D2/d for 15 d. Calcium absorption was measured in the same subjects by using dual calcium isotopes. Calcium absorption efficiency (mean ± SD) increased only 3% (from 24 ± 7% to 27 ± 6%; P = 0.04). There was no evidence of a threshold. A single megadose of vitamin D2 was used in this uncontrolled study. Shapses et al (3), using a dual-isotope study with a single dose of vitamin D3 of 375 μg/wk and 10 μg/d, noted a 3.7% increase in calcium absorption. Gallagher et al (4) reported on a prolonged (1 y) dose-response, placebo-controlled study of 163 postmenopausal women with vitamin D insufficiency. They concluded that the increase in calcium absorption observed with supplementation of 4800 IU vitamin D3/d was only the equivalent of drinking a small glass of milk. Calcium absorption was measured by using a single-isotope technique and a low calcium carrier (100 mg). Other studies in children and elderly women have also not found an increase in calcium absorption with vitamin D supplementation (5, 6).

A double-isotope technique is preferable for measurement of calcium absorption because it corrects for calcium recycling (7, 8). We performed a dose-response, placebo-controlled, randomized double-blind study of the effect of vitamin D3 supplementation on intestinal calcium absorption We used the dual-isotope technique with a calcium intake of 300 mg to answer the question: Is there a serum 25(OH)D concentration or intake of vitamin D3 above which calcium absorption no longer increases?

SUBJECTS AND METHODS

Subjects

Recruitment was carried out during the winter months in consecutive years. Recruitment started in November 2010, and the study ended in March 2012. Letters were sent to our existing research patients who had expressed the desire to enroll their family members and friends into a clinical trial. Ads were placed in the local newspapers, and a direct mailing was used. Healthy postmenopausal women between the ages of 50 and 70 y were eligible for enrollment. Exclusion criteria included the following: 1) any chronic medical illness; 2) subjects with a BMI (in kg/m2) >35; 3) use of medication that influences vitamin D and bone metabolism; 4) significant deviation from normal in medical history, physical examination, or laboratory tests as evaluated by the primary investigator; 5) hypercalciuria (urine calcium:creatinine ratio >0.37, hypercalcemia (serum calcium >10.6, nephrolithiasis, and active sarcoidosis; 6) unexplained weight loss >15% during the previous year or history of anorexia nervosa; 7) participation in another investigational trial in the past 30 d before the screening evaluation; 8) alcohol intake reported by patient of >2 drinks/d; 9) baseline 25(OH)D concentration >70 nmol /L; 10) smoking of more than one pack per day; 11) dietary calcium intake >2000 mg; and 12) unwillingness to forego multivitamin and vitamin D supplements during the study. The study was approved by the Winthrop University Hospital Institutional Review Board. Subjects gave written informed consent.

Protocol

Subjects had a baseline visit for screening. If eligible, they returned for a randomization visit at week 2, at which time calcium absorption was measured and medication was dispensed. The subjects made a revisit after 8 wk of supplementation (week 10), at which time calcium absorption and the baseline laboratory studies were repeated. Total daily calcium intake was estimated by using a dietary recall (Short Calcium Questionnaire 2002; NIH Clinical Center) at the baseline and final visits. The subjects were randomly assigned to 1 of 4 groups with each receiving placebo, 800 IU (20 μg), 2000 IU (50 μg), or 4000 IU (100 μg) vitamin D3/d, respectively. A computer-generated block randomization was used (20 blocks of 4). The random allocation sequence was generated by the statistician, and the research pharmacist assigned participants. Investigators and participants were blinded to group assignment. Supplements and placebo appeared identical in size, shape, color, and weight.

Calcium absorption

Calcium absorption was performed at baseline and again after 8 wk of supplementation. A dual-tracer-isotope method was used to measure calcium absorption efficiency (7, 9–11). Subjects were given a breakfast that was a fixed meal providing 300 mg Ca. Toward the end of breakfast, the subjects were given a stable isotope of calcium, ~24.75 μg 46Ca that had been mixed with 240 mL Ca-fortified orange juice (7). After breakfast, a different calcium stable isotope (~1.75 mg 42Ca) was infused intravenously within 5 min, flushing the line with saline. The syringes were weighed before and after the infusion to determine the precision of the intravenous isotope doses. After administration of the calcium isotopes, a complete 24-h urine sample was collected by the patient and was handed over in person to the research team the next day.

The relative fraction of the oral, compared with the intravenous, dose in this 24-h urine pool was determined and represented the fraction of the oral tracer dose that was absorbed (7). Urine samples were prepared for mass spectrometric analysis by using the oxalate precipitation technique. Samples were analyzed for isotopic enrichment by using thermal ionization mass spectrometry as previously described (7). The analyses were performed in the laboratory of the USDA/Agricultural Research Service Children’s Nutrition Research Center.

Laboratory analyses

Serum 25(OH)D was measured by using a radioimmunoassay from DiaSorin Inc. The intraassay variability in our laboratory was 4.1%, and the interassay variability was 7.0%. Our laboratory participates in the Vitamin D External Quality Assessment Scheme—an external quality-control program—and uses the National Institute of Standards and Technology standard (12). Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was measured by using an enzyme immunoassay manufactured by Immuno Diagnostic System Ltd. The intraassay variability was 10.2%, and the interassay variability was 18.1%. Serum and urinary calcium were measured with O-cresolphthalein complex by using automated equipment (Dimension-RXL). Urinary creatinine was measured by Jaffe reaction with automated instrumentation (Dimension-RXL). The vitamin D tablets were assayed by HPLC [Waters Symmetry; C18, 3.9 × 150-mm column, mobile phase, acetonitrile:methanol (75:25)]. Serum parathyroid hormone (PTH) was measured with the Immulite 2000 Analyzer for the quantitative measurement of intact PTH (Diagnostic Products Corporation). Serum C-terminal telopeptides of type I collagen (CTX) was measured with a Serum Crosslaps ELISA kit made by Nordic Bioscience Diagnositics. Serum procollagen type 1 N-terminal propeptide was measured by using a UniQ P1NP RIA kit from Orion Diagnostica.

Adverse events

An adverse event was defined as any undesired change in the subject as indicated by signs, symptoms, or laboratory data that occurred in association with taking the study drug whether or not it is considered to be related to the medication.

Statistical analysis

Our main outcome variable was the comparison of groups with respect to changes in calcium absorption from baseline. We determined our sample size based on a previous study (13). As per that study’s design, a sample size of 25 patients per group achieved 90% power to detect a difference between groups of 7.2% (in absolute terms) in changes from baseline. Alpha was equal to 0.05.

Descriptive statistics (mean, median, and SD) of continuous clinical covariates and laboratory markers were generated to describe the sample of patients both overall and within each treatment arm. Differences in the mean levels of each covariate across treatment arm were examined via ANOVA. Similarly, categorical covariates such as race were summarized by using frequencies and percentages with differences between treatment arms assessed with chi-square tests. Relations between continuous covariates were examined via Pearson correlation coefficients. Scatterplots of continuous variables with nonparametric smoothed curves imposed were generated to examine the degree and nature of the specific relations. For the primary outcome of calcium absorption at follow-up, further exploration of the relation between absorption and treatment weight, BMI, baseline calcium absorption, 25(OH)D, and other laboratory markers was performed by using linear regression models. Multivariable models for calcium absorption were examined to adjust for potential confounders such as age, weight, and BMI. To arrive at the final multivariable model presented, an exhaustive search of the model space was conducted, and models were ranked on the basis of their adjusted R2 values. Because of likely colinearity between different variables, the final models presented were considered representative of other equally informative models. Model assumptions were checked via residual analysis and graphic summaries, and removal of outlying or influential observations was performed to observe the robustness of the main results.

The relation between vitamin D intake and calcium absorption at baseline and follow-up, and the change (delta) between follow-up and baseline, were each assessed via ANOVA, and statistical significance of the overall treatment effect was determined via the global F test. To examine the hypothesized piecewise linear or curvilinear relation between calcium absorption and 25(OH)D at follow-up, linear, quadratic, and cubic spline models with an a priori knot at 80 nmol/L were fitted. Model coefficients and R2 summary statistics were examined for each model to determine whether the hypothesized change point was supported by the data at hand and whether the model for calcium absorption was improved by the inclusion of more complex, nonlinear terms into the model. The SAS version 9.3 statistical program was used to analyze the data.

RESULTS

Baseline values

Baseline demographic characteristics and laboratory results are provided in Table 1. The study flow sheet is shown in Figure 1. No statistically significant interactions with treatment arm with respect to baseline variables were found. The declared race was predominantly white; 8% of the participants were black, 6% Hispanic, and 3% Asian. The mean (±SD) weight was 70 ± 5.1 kg, mean BMI was 26 ± 4, and mean age was 58.8 ± 4.9 y. Calcium intake was 1142 ± 509 mg/d. The distribution of BMI values was as follows: 29% <25, 31% from 25 to 29, and 16% ≥30. The mean serum 25(OH)D was 63 ± 14 nmol/L. The distribution of serum 25(OH)D was as follows: 30–49 nmol/L, 24%; 50–75 nmol/L, 54%; and >75 nmol/L, 22%. The baseline calcium absorption efficiency was 32 ± 14%. The dose-response curve for 10-wk calcium absorption showed no evidence of nonlinearity (P-quadratic term in the adjusted model = 0.16). The curve is depicted in Figure 2. This was also the case for serum 25(OH)D (Figure 3). Calcium absorption was also related to 24-h urine calcium excretion (P = 0. 002). Age and weight were considered potential confounders with respect to calcium absorption; all baseline factors were adjusted for these variables in the primary statistical model.

TABLE 1

Baseline characteristics by vitamin D dose1

Measurement  Control (n = 19)  800 IU (n = 19)  2000 IU (n = 20)  4000 IU (n = 18)  P value2 
Age (y)  60 ± 4.5  57 ± 4.5  59 ± 5.8  60 ± 4.7  0.4 0.6 
BMI (kg/m2 26.2 ± 3.8  26.4 ± 3.6  27.6 ± 4.9  26 ± 4   
Calcium intake (FFQ − dietary + supplement)  1156 ± 580  1027 ± 469  1160 ± 499  1196 ± 518  0.8 
Calcium absorption  0.4 ± 0.2  0.4 ± 0.2  0. 5 ± 0.2  0.5 ± 0.2  0.4 
Serum calcium (mg/dL)  9.6 ± 0.3  9.6 ± 0.3  9.5 ± 0.4  9.5 ± 0.4  0.95 
Serum creatinine (mg/dL)  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.89 
25(OH)D (nmol/L)  61.7 ± 15.3  64 ± 13.8  64.8 ± 15.1  62.1 ± 14.2  0.90 
1,25(OH)2D (pmol/L)  97.9 ± 27.7  104.6 ± 26.3  111.7 ± 38.1  117.3 ± 64.9  0.52 
Measurement  Control (n = 19)  800 IU (n = 19)  2000 IU (n = 20)  4000 IU (n = 18)  P value2 
Age (y)  60 ± 4.5  57 ± 4.5  59 ± 5.8  60 ± 4.7  0.4 0.6 
BMI (kg/m2 26. 2 ± 3.8  26.4 ± 3.6  27.6 ± 4.9  26 ± 4   
Calcium intake (FFQ − dietary + supplement)  1156 ± 580  1027 ± 469  1160 ± 499  1196 ± 518  0.8 
Calcium absorption  0.4 ± 0.2  0.4 ± 0.2  0.5 ± 0.2  0.5 ± 0.2  0.4 
Serum calcium (mg/dL)  9.6 ± 0.3  9.6 ± 0.3  9.5 ± 0.4  9.5 ± 0.4  0.95 
Serum creatinine (mg/dL)  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.89 
25(OH)D (nmol/L)  61.7 ± 15.3  64 ± 13.8  64.8 ± 15.1  62.1 ± 14.2  0.90 
1,25(OH)2D (pmol/L)  97.9 ± 27.7  104.6 ± 26.3  111.7 ± 38.1  117.3 ± 64.9  0.52 

TABLE 1

Baseline characteristics by vitamin D dose1

Measurement  Control (n = 19)  800 IU (n = 19)  2000 IU (n = 20)  4000 IU (n = 18)  P value2 
Age (y)  60 ± 4. 57 ± 4.5  59 ± 5.8  60 ± 4.7  0.4 0.6 
BMI (kg/m2 26.2 ± 3.8  26.4 ± 3.6  27.6 ± 4.9  26 ± 4   
Calcium intake (FFQ − dietary + supplement)  1156 ± 580  1027 ± 469  1160 ± 499  1196 ± 518  0.8 
Calcium absorption  0.4 ± 0.2  0.4 ± 0.2  0.5 ± 0.2  0.5 ± 0.2  0.4 
Serum calcium (mg/dL)  9.6 ± 0.3  9.6 ± 0.3  9.5 ± 0.4  9.5 ± 0.4  0.95 
Serum creatinine (mg/dL)  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.89 
25(OH)D (nmol/L)  61.7 ± 15.3  64 ± 13.8  64.8 ± 15.1  62.1 ± 14.2  0.90 
1,25(OH)2D (pmol/L)  97.9 ± 27.7  104.6 ± 26.3  111.7 ± 38.1  117. 3 ± 64.9  0.52 
Measurement  Control (n = 19)  800 IU (n = 19)  2000 IU (n = 20)  4000 IU (n = 18)  P value2 
Age (y)  60 ± 4.5  57 ± 4.5  59 ± 5.8  60 ± 4.7  0.4 0.6 
BMI (kg/m2 26.2 ± 3.8  26.4 ± 3.6  27.6 ± 4.9  26 ± 4   
Calcium intake (FFQ − dietary + supplement)  1156 ± 580  1027 ± 469  1160 ± 499  1196 ± 518  0.8 
Calcium absorption  0.4 ± 0.2  0.4 ± 0.2  0.5 ± 0.2  0.5 ± 0.2  0.4 
Serum calcium (mg/dL)  9.6 ± 0.3  9.6 ± 0.3  9.5 ± 0.4  9.5 ± 0.4  0.95 
Serum creatinine (mg/dL)  0.6 ± 0.1  0. 6 ± 0.1  0.6 ± 0.1  0.6 ± 0.1  0.89 
25(OH)D (nmol/L)  61.7 ± 15.3  64 ± 13.8  64.8 ± 15.1  62.1 ± 14.2  0.90 
1,25(OH)2D (pmol/L)  97.9 ± 27.7  104.6 ± 26.3  111.7 ± 38.1  117.3 ± 64.9  0.52 

FIGURE 1.

Flow chart of the study. IV, intravenous.

FIGURE 1.

Flow chart of the study. IV, intravenous.

FIGURE 2.

Calcium absorption rate at 10 wk (8 wk after randomization) by vitamin D dose group (n = 70; univariate P-trend = 0.18). A statistically significant linear dose effect was observed after adjustment for age, weight, and initial calcium absorption (P-trend = 0.03). No evidence of any nonlinear effect was found after examination of change points and higher order terms in the model. Final model: 10-wk calcium absorption = 34. 4 − 0.11 × age − 0.11 × weight + 0.65 × baseline calcium absorption + 2.2 × dose.

FIGURE 2.

Calcium absorption rate at 10 wk (8 wk after randomization) by vitamin D dose group (n = 70; univariate P-trend = 0.18). A statistically significant linear dose effect was observed after adjustment for age, weight, and initial calcium absorption (P-trend = 0.03). No evidence of any nonlinear effect was found after examination of change points and higher order terms in the model. Final model: 10-wk calcium absorption = 34.4 − 0.11 × age − 0.11 × weight + 0.65 × baseline calcium absorption + 2.2 × dose.

FIGURE 3.

Calcium absorption at 10 wk (8 wk after randomization) by 10-wk serum 25(OH)D (n = 70). A marginally significant linear effect (P = 0.05) was observed in a model adjusted for age, weight, and baseline calcium absorption. No evidence of any nonlinear effect was found after examination of change points and the presence of higher order terms in the model. Final model: 10-wk calcium absorption = 26.8 − 0.16 × age − 0.09 × weight + 0.66 × baseline calcium absorption + 0.14 × 10-wk serum 25(OH)D. 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3.

Calcium absorption at 10 wk (8 wk after randomization) by 10-wk serum 25(OH)D (n = 70). A marginally significant linear effect (P = 0.05) was observed in a model adjusted for age, weight, and baseline calcium absorption. No evidence of any nonlinear effect was found after examination of change points and the presence of higher order terms in the model. Final model: 10-wk calcium absorption = 26.8 − 0.16 × age − 0.09 × weight + 0.66 × baseline calcium absorption + 0.14 × 10-wk serum 25(OH)D. 25(OH)D, 25-hydroxyvitamin D.

Changes in calcium absorption

The changes in calcium absorption (mean ± SD) from baseline to follow-up were as follows: placebo, −2.6 ± 10.7%; 800 IU, 3.9 ± 10.4%; 2000 IU, 5.0 ± 18.7%; and 4000 IU, 6. 7 ± 12%. A multivariable model for 10-wk calcium absorption containing the predictor’s dose group, baseline calcium absorption, age, and weight (R2 of multivariable model = 0.41) yielded a statistically significant linear trend across vitamin D dose groups (Table 2; P = 0.03).

TABLE 2

Baseline predictors of 10-wk follow-up calcium absorption1

Factor  Model estimate  SE  P value 
Age (y)  −0.11  0.31  0.71 
Weight at baseline (lb)  −0.11  0.06  0.06 
Calcium absorption at baseline (%)  0.65  0.11  <0.0001 
Vitamin D dose group2  2.21  1.00  0.03 
Factor  Model estimate  SE  P value 
Age (y)  −0. 11  0.31  0.71 
Weight at baseline (lb)  −0.11  0.06  0.06 
Calcium absorption at baseline (%)  0.65  0.11  <0.0001 
Vitamin D dose group2  2.21  1.00  0.03 

TABLE 2

Baseline predictors of 10-wk follow-up calcium absorption1

Factor  Model estimate  SE  P value 
Age (y)  −0.11  0.31  0.71 
Weight at baseline (lb)  −0.11  0.06  0.06 
Calcium absorption at baseline (%)  0.65  0.11  <0.0001 
Vitamin D dose group2  2.21  1.00  0.03 
Factor  Model estimate  SE  P value 
Age (y)  −0. 11  0.31  0.71 
Weight at baseline (lb)  −0.11  0.06  0.06 
Calcium absorption at baseline (%)  0.65  0.11  <0.0001 
Vitamin D dose group2  2.21  1.00  0.03 

Examination of the relation between 10-wk calcium absorption and 10-wk serum 25(OH)D concentrations showed a similar linear trend, with no evidence of nonlinearity (P-quadratic effect = 0.35). A marginally significant linear effect (P = 0.05) due to 10-wk serum 25(OH)D was observed because serum 25(OH)D concentrations increased by 10 nmol/L and mean calcium absorption increased by 1.4%.

Changes in serum 25(OH)D

The response of serum 25(OH)D to increasing doses of vitamin D3 was linear, and no curvature was found (P-linear trend < 0.001). The only biochemical variable associated with 10-wk serum 25(OH)D was the baseline value for serum 25(OH)D (P < 0. 0001). Serum 25(OH)D concentrations increased from baseline to follow-up on average by 15.7 ± 20.4 nmol/L. Individuals with higher starting 25(OH)D concentrations had smaller changes in 25(OH)D at follow-up (P = 0.03). The variability of the 25(OH)D response differed by dose group (P = 0.002) and was highest in the 4000-IU/d group. BMI was also negatively correlated with 10-wk serum 25(OH)D (P = 0.04). The 10-wk serum 25(OH)D concentrations are depicted in Figure 4 with the estimated regression. Serum 25(OH)D is expected to increase by 10.6 nmol/L for each increased intake of 400 IU/d (10 μg/d).

FIGURE 4.

Serum 25(OH)D concentrations at 10 wk (8 wk after randomization) by vitamin D dose group (n = 70). A strong linear effect was observed in both the univariate model and after adjustment for age, weight, and initial calcium absorption (P < 0.0001). No evidence of any nonlinear effect was found after examination of change points and the presence of higher order terms in the model. Final model: 10-wk 25(OH)D = 24 + 0.19 × age − 0.11 × weight + 0.65 × baseline 25(OH)D absorption + 10.6 × dose. 25(OH)D, 25-hydroxyvitamin D.

FIGURE 4.

Serum 25(OH)D concentrations at 10 wk (8 wk after randomization) by vitamin D dose group (n = 70). A strong linear effect was observed in both the univariate model and after adjustment for age, weight, and initial calcium absorption (P < 0.0001). No evidence of any nonlinear effect was found after examination of change points and the presence of higher order terms in the model. Final model: 10-wk 25(OH)D = 24 + 0.19 × age − 0.11 × weight + 0.65 × baseline 25(OH)D absorption + 10.6 × dose. 25(OH)D, 25-hydroxyvitamin D.

Correlations between changes in variables

The correlations between changes (10-wk minus baseline) in key variables are presented in Table 3. Changes in PTH were inversely associated with changes in serum 25(OH)D (P = 0. 01). A significant increase in calcium absorption was observed with the increase in serum 1,25(OH)2D and a trend to increase with serum 25(OH)D (P = 0.07). The increase in serum 1,25OH2D was directly correlated with the increase in CTX.

TABLE 3

Correlations between changes (follow-up minus baseline) in key laboratory markers1

Spearman correlation coefficient 
  Serum 25(OH)D  Calcium absorption  Serum 1,25(OH)2 Serum PTH  Serum CTX  Serum P1NP 
Serum 25(OH)D  1.0           
Calcium absorption  0.22  1.0         
Serum 1,25(OH)2 0.232  0.03  1.0       
Serum PTH  −0. 302  0.04  −0.05  1.0     
Serum CTX  0.19  0.302  0.282  −0.001  1.0   
Serum P1NP  0.16  −0.12  0.01  −0.17  −0.06  1.0 
Spearman correlation coefficient 
  Serum 25(OH)D  Calcium absorption  Serum 1,25(OH)2 Serum PTH  Serum CTX  Serum P1NP 
Serum 25(OH)D  1.0           
Calcium absorption  0.22  1.0         
Serum 1,25(OH)2 0.232  0.03  1.0       
Serum PTH  −0. 302  0.04  −0.05  1.0     
Serum CTX  0.19  0.302  0.282  −0.001  1.0   
Serum P1NP  0.16  −0.12  0.01  −0.17  −0.06  1.0 

TABLE 3

Correlations between changes (follow-up minus baseline) in key laboratory markers1

Spearman correlation coefficient 
  Serum 25(OH)D  Calcium absorption  Serum 1,25(OH)2 Serum PTH  Serum CTX  Serum P1NP 
Serum 25(OH)D  1.0           
Calcium absorption  0.22  1.0         
Serum 1,25(OH)2 0.232  0. 03  1.0       
Serum PTH  −0.302  0.04  −0.05  1.0     
Serum CTX  0.19  0.302  0.282  −0.001  1.0   
Serum P1NP  0.16  −0.12  0.01  −0.17  −0.06  1.0 
Spearman correlation coefficient 
  Serum 25(OH)D  Calcium absorption  Serum 1,25(OH)2 Serum PTH  Serum CTX  Serum P1NP 
Serum 25(OH)D  1.0           
Calcium absorption  0.22  1.0         
Serum 1,25(OH)2 0.232  0. 03  1.0       
Serum PTH  −0.302  0.04  −0.05  1.0     
Serum CTX  0.19  0.302  0.282  −0.001  1.0   
Serum P1NP  0.16  −0.12  0.01  −0.17  −0.06  1.0 

Adverse events

No serious adverse events occurred. Three adverse events were reported: sinusitis, seasonal allergy, and jaw pain. None were judged to be related to the intervention. No instances of hypercalcemia or hypercalciuria occurred.

DISCUSSION

Our study showed that, at serum 25(OH)D concentrations of 40 to 130 nmol/L, no evidence of a “threshold” for calcium absorption was found. However, none of our participants had very low 25(OH)D concentrations, so we cannot comment on whether there is a “threshold” in the vitamin D deficiency range. On the basis of our results and those of the other studies cited, we conclude that there is no evidence in reference to calcium absorption that vitamin D should be increased above the Institute of Medicine (IOM) recommendation (Recommended Dietary Allowance) of a serum 25(OH)D concentration of 50 nmol/L (2–6). Gallagher et al (4) found no evidence of a calcium absorption threshold with serum 25(OH)D concentrations ranging from 25 to 165 nmol/L. They concluded that the additional 6% of calcium absorbed from the high dose of vitamin D could be achieved by increasing calcium intake with half a glass of milk. In a recent study in children, no increase in calcium absorption was noted from 1000 IU vitamin D3/d, despite a decrease in serum PTH (6).

Our study design differed from that of Gallagher et al (4) in that we used the more accurate method for calcium absorption, the dual-isotope technique. We also used a higher carrier. The low-carrier method is thought to better reflect transcellular calcium transport, whereas the method we used more accurately reflects the response to a calcium-rich meal. Despite the differences in the design or methods of the studies by Hansen et al (2), Shapses et al (3), and Gallagher et al (4) and our study, the results are consistent. Gallagher et al (4) noted an absolute increase in calcium absorption of 6% at a dose of 4800 IU/d compared with our increase of 6.7%. Hansen et al (2) observed an absolute increase of 3%, and Shapses et al (3) observed an increase of 3.7%.

Perhaps the most important finding from these studies is that there was a small linear response of calcium absorption to increasing vitamin D intakes. There was no evidence of a threshold at 50 or 80 nmol/L. It is likely that serum calcitriol and calcium absorption continue to increase with even higher intakes of vitamin D. We observed in this study that even when PTH declined in response to increased vitamin D intakes, serum calcitriol did not decrease. Vitamin D intoxication is thought to result from direct effects of 25(OH)D on bone, but elevated calcitriol concentrations may persist even in the case of severe hypercalcemia (14).

Although our study did not include a sufficient number of subjects with very low concentrations of serum 25(OH)D (<10 to 12 nmol/L), previous literature suggests that very low 25(OH)D leads to calcium malabsorption and osteoporosis (15). It is believed that the reduction in calcium absorption is caused by reduced levels of calcitriol that result from a substrate deficiency of 25(OH)D. It is calcitriol that regulates intestinal calcium absorption rather than 25(OH)D (4, 15–17).

The decrease in serum PTH in response to higher serum 25(OH)D concentrations is of interest particularly in this group, which is presumably calcium-sufficient (Table 3). The construct of a “threshold” has also been applied to a serum 25(OH)D concentration above which PTH is no longer suppressed to determine vitamin D sufficiency. Many statistical models have been applied to this conceptual “threshold,” with the most publicized articles suggesting a threshold >70–80 nmol/L (18–24). However, a review of the literature indicated a large heterogeneity of “thresholds” or no threshold (25). Most of these studies were cross-sectional in design. In our admittedly small prospective study, no evidence of nonlinearity of the decline in PTH with increasing 25(OH)D concentrations was found.

Another interesting finding in our study was the positive association between the increase in serum calcitriol and serum CTX (Table 3). As serum calcitriol rises with increasing vitamin D exposure, it may increase bone resorption independently of PTH. The actions of vitamin D on bone apparently differ with low, sufficient, and high vitamin D exposures (25). Osteoporosis is observed in sarcoidosis, for which the primary defect in the calcium economy is high calcitriol concentrations. Evaluations of the effects of high doses of vitamin D, which are recommended for prevention and treatment of a variety of disorders, should assess whether increased bone resorption occurs.

We and others have previously noted that the dose-response curve of the increment in serum 25(OH)D in response to increasing doses of vitamin D intake is curvilinear and is related to the baseline concentration. However, in this study we found only a linear relation. We observed a 0.6-nmol · L–1 · μg–1 vitamin D3 response in this study, which is similar to our previous reports (26).

We recognized several limitations of our study. Dietary calcium intake was not controlled, and the group was almost sufficient for calcium intake (and vitamin D status) according to IOM recommendations. Whereas no threshold for vitamin D was found, there were an insufficient number of vitamin D–deficient participants (<30 nmol/L) to confirm that there is indeed a decrease in calcium absorption at these very low levels, as previously reported. It can be questioned whether 8 wk is sufficient to reach a plateau in the vitamin D/25(OH)D dose-response curve. However, evidence from the available literature suggests that the plateau is reached before this time (27–30). Our findings are also confined to postmenopausal women, 83% of whom were white. Nevertheless, our study had many strengths. It was a randomized, double- blind, placebo-controlled, dose-response design that used vitamin D3. The dual-isotope method was used to measure calcium absorption. A physiologic calcium intake was used for the carrier. The dose-response design included the IOM recommended ranges of vitamin D intake, up to the upper limit.

In conclusion, the results of our study and those of previous isotopic studies make it clear that increasing concentrations of 25(OH)D may minimally increase intestinal calcium absorption, but there is no apparent threshold up to the upper limit of 4000 IU/d. The small increase in calcium absorption attained with vitamin D supplementation does not support increasing the Recommended Dietary Allowance above the recommendation of the IOM committee.

We thank the staff at the Bone Mineral Research Center at Winthrop University for their dedication to this study and Christopher Hall (our laboratory technician) and Shahidul Islam (our statistician) for their expertise and commitment to the study.

The authors’ responsibilities were as follows—JFA: designed the study, wrote the manuscript, and supervised the study; RD and AS: worked with JFA to draft the protocol; MM: supervised the study; LR: supervised the laboratory studies; SAA: performed the isotope studies; and MF: performed the statistical analyses, interpreted the data, and produced the tables and figures. All authors read and approved the final manuscript. None of the authors had a conflict of interest to declare.

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ABBREVIATIONS

     

  • CTX

    C-terminal telopeptides of type I collagen

  •  

  • IOM

  •  

  • PTH

  •  

  • 1,25(OH)2D

  •  

  • 25(OH)D

© 2014 American Society for Nutrition

Absorption of Minerals and Metals

Absorption of Minerals and Metals

The vast bulk of mineral absorption occurs in the small intestine. The best-studied mechanisms of absorption are clearly for calcium and iron, deficiencies of which are significant health problems throughout the world.

Minerals are clearly required for health, but most also are quite toxic when present at higher than normal concentrations. Thus, there is a physiologic challenge of supporting efficient but limited absorption. In many cases intestinal absorption is a key regulatory step in mineral homeostasis.

Calcium

Calcium is absorbed from the intestinal luman by two distinct mechanims, and their relative magnitude of importance is determined by the amount of free calcium available for absorption:

1. Active, transcellular absorption occurs only in the duodenum when calcium intake is low. This process involves import of calcium into the enterocyte, transport across the cell, and export into extracellular fluid and blood. Calcium enters the intestinal epithelial cells through voltage-insensitive (TRP) channels and is pumped out of the cell via a calcium-ATPase.

The rate limiting step in transcellular calcium absorption is transport across the epithelial cell, which is greatly enhanced by the carrier protein calbindin, the synthesis of which is totally dependent on vitamin D.

2. Passive, paracellular absorption occurs in the jejunum and ileum, and, to a much lesser extent, in the colon when dietary calcium levels are moderate or high. In this case, ionized calcium diffuses through tight junctions into the basolateral spaces around enterocytes, and hence into blood. When calcium availability is high, this pathway responsible for the bulk of calcium absorption, due to the very short time available for active transport in the duodenum.

Phosphorus

Phosphorus is predominantly absorbed as inorganic phosphate in the upper small intestine. Phosphate is transported into the epithelial cells by contransport with sodium, and expression of this (or these) transporters is enhanced by vitamin D.

Iron

Iron homeostasis is regulated at the level of intestinal absorption, and it is important that adequate but not excessive quantities of iron be absorbed from the diet. Inadequate absorption can lead to iron-deficiency disorders such as anemia. On the other hand, excessive iron is toxic because mammals do not have a physiologic pathway for its elimination.

Iron is absorbed by villus enterocytes in the proximal duodenum. Efficient absorption requires an acidic environment, and antacids or other conditions that interfere with gastric acid secretion can interfere with iron absorption.

Ferric iron (Fe+++) in the duodenal lumen is reduced to its ferrous form through the action of a brush border ferrireductase. Iron is the cotransported with a proton into the enterocyte via the divalent metal transporter DMT-1. This transporter is not specific for iron, and also transports many divalent metal ions.

Once inside the enterocyte, iron follows one of two major pathways. Which path is taken depends on a complex programming of the cell based on both dietary and systemic iron loads:

  • Iron abundance states: iron within the enterocyte is trapped by incorporation into ferritin and hence, not transported into blood. When the enterocyte dies and is shed, this iron is lost.
  • Iron limiting states: iron is exported out of the enterocyte via a transporter (ferroportin) located in the basolateral membrane. It then binds to the iron-carrier transferrin for transport throughout the body.

Iron in the form of heme, from ingestion of hemoglobin or myoglobin, is also readily absorbed. In this case, it appears that intact heme is take up by the small intestinal enterocyte by endocytosis. Once inside the enterocyte, iron is liberated and essentially follows the same pathway for export as absorbed inorganic iron. Some heme may be transported intact into the circulation.

Copper

There appear to be two processes responsible for copper absorption – a rapid, low capacity system and a slower, high capacity system, which may be similar to the two processes seen with calcium absorption. Many of the molecular details of copper absorption remain to be elucidated. Inactivating mutations in the gene encoding an intracellular copper ATPase have been shown responsible for the failure of intestinal copper absorption in Menkes disease.

A number of dietary factors have been shown to influence copper absorption. For example, excessive dietary intake of either zinc or molybdenum can induce secondary copper deficiency states.

Zinc

Zinc homeostasis is largely regulated by its uptake and loss through the small intestine. Although a number of zinc transporters and binding proteins have been identified in villus epithelial cells, a detailed picture of the molecules involved in zinc absorption is not yet in hand.

Intestinal excretion of zinc occurs via shedding of epithelial cells and in pancreatic and biliary secretions.

A number of nutritional factors have been identified that modulate zinc absorption. Certain animal proteins in the diet enhance zinc absorption. Phytates from dietary plant material (including cereal grains, corn, rice) chelate zinc and inhibit its absorption. Subsistance on phytate-rich diets is thought responsible for a considerable fraction of human zinc deficiencies.

References and Reviews
  • Andrews NC: Disorders of iron metabolism. New Eng J Med 341:1986, 1999.
  • Bronner F: Calcium absorption: A paraadigm for mineral absorption. J Nutrition 128:917-920, 1998.
  • Krebs NF: Overview of zinc absorption and excretion in the human gastrointestinal tract. J Nutrition 130:1374S-1377S, 2000.
  • Kuanal RC, Nemere I: Regulation of intestinal calcium transport. Annu Rev Nutr 28:179-196, 2008.
  • Lonnerdal B: Dietary factors influencing zinc absorption. J Nutrition 130:1378S-1385S, 2000.
  • Miret S, Simpson RJ, McKie AT: Physiology and molecular biology of iron absorption. Ann Rev Nutr 23:283-301, 2003.
  • Wessling-Resnick M: Iron transport. Annu Rev Nutr 20:129-151, 2000.

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Mechanism of Calcium Absorption in Infants Uncovered

A mechanism which enables infants to absorb large amounts of calcium has been identified in mice by a group of researchers at the University of Alberta. The findings are published in the journal Cellular and Molecular Gastroenterology and Hepatology.

Although the process of calcium absorption in adult mammals had been previously elucidated to take place in the upper part of the small intestines, the mechanism had not been understood in infants until now.

Calcium absorption is an important step in bone formation, with a lack of optimal bone mineralization resulting in diseases such as osteoporosis.

We interviewed Megan Beggs, Registered Dietician/PhD candidate and Dr Todd Alexander, Professor of Pediatrics at the University of Alberta and Stollery Science Lab Distinguished Researcher, to learn more about the study and the wider implications the findings could have on preventing and treating bone diseases.

Anna MacDonald (AM): What inspired the study of calcium absorption in infants? Were there any particular motivators that got the project started?

Dr Todd Alexander (TA):
Megan Beggs (first author) is a pediatric dietitian, and I (principle investigator) am a pediatric nephrologist. Clinically, we see and treat infants and children with poor bone mineralization and altered calcium homeostasis (i.e. altered blood calcium levels). In looking to the literature to better understand why this happens, we realized that almost nothing was known about how even healthy infants and children hold on to enough calcium to build bones. This is important as this happens only early in life enabling us to reach peak bone mineral density by early adulthood. Trying to understand how this process works was the motivation for Megan’s PhD work, which has ultimately led to the findings in the current study. We realized that we first must understand normal physiology before understanding why some people do not develop optimal bone mineralization and subsequently osteoporosis and fractures.

AM: Can you give us an overview of your findings?

Megan Beggs (MB):  In this study, we delineated specific molecular pathways of intestinal calcium absorption across different ages using a mouse model. We noted that in infants, a pathway of active calcium uptake was present in segments that make up about 90% of the length of the small intestine. We further identified two specific calcium channels, that are central to calcium absorption. When one of these proteins was genetically deleted, it lead to delayed bone mineralization in the pups.

AM: How does this compare to calcium absorption in adults?

TA: The pathways identified above were only present in infant mice that were still suckling, which is the mouse equivalent to breastfeeding. In the first segment of the small intestine (called the duodenum) which makes up the remaining 10% of small intestine length, a pathway of active calcium absorption is present only in the older mice but not in the infants. The infants and older mice therefore have a reciprocal pattern of intestinal calcium absorption. This is likely the same in human children and adults.

AM: What impact could these findings have on dietary guidelines for infants, such as weaning age?

MB: Bone health outcomes are used to derive dietary calcium requirements for ages 12 months and up. Such data for infants aged 0-12 months is sparse and therefore the requirement is based upon a calculated average intake. Infants 0-6 months require 200 mg of calcium daily and infants 6-12 months (the period of weaning) require 260 mg calcium per day. The findings of the current study provide us with an understanding of how this calcium is taken up from the diet but are not likely to change current recommendations. If further research leads us to find that these pathways are altered in some infants i.e. ones that are bottle fed, it may help to determine if increased requirements are needed for certain populations.

AM: Does formula see the same response as breastmilk?

MB: It is known that to promote normal growth, infant formula must contain double the concentration of calcium as what is found in breast milk. It is thought that this is due to decreased absorption of the calcium in formula. Our current study suggests that a bioactive compound in breastmilk enhances calcium absorption via the pathways we identified. Further research is needed to test this hypothesis and identify what the compound(s)/molecules may be.

AM: How could the findings be harnessed to develop treatments for bone diseases such as osteoporosis?

TA:
Osteoporosis is a disease that affects 1 in 3 women and 1 in 5 men with debilitating consequences on quality of life. If we can identify bioactive compounds in breast milk that contribute to a positive calcium balance early in life, one could potentially give them to adults/seniors to offset later bone mineral loss or even help provide a positive calcium balance and increased bone mineralization.

Todd Alexander and Megan Beggs were speaking to Anna MacDonald, Science Writer for Technology Networks.

Scientists pinpoint inulin’s calcium absorption site

The research, published in the October issue of The Journal of
Nutrition
​, improves our understanding of the ingredient, and
may aid the development of other products, suggested the
researchers, led by Steven Abrams.

“This study provided confirmation that the animal studies,
which had identified a benefit of [inulin-type fructan] ITF for
calcium absorption, accurately identified the principal mechanisms
as well,”
​ wrote the authors, from Baylor College of Medicine
(Houston), the USDA/Agricultural Research Service Clinical
Nutrition Research Center, and Texas Children’s Hospital.

“Furthermore, understanding the site of action may be helpful
in considering the effects of ITF and related products on the
absorption of other minerals or on the design of other ITF
products,”
​ they added.

The research appears to confirm the potential of the ingredient to
support bone health and prevent osteoporosis, estimated to affect
about 75m people in Europe, the USA and Japan.

Currently, two approaches are being pursued to prevent
osteoporosis: First, optimise bone mass acquisition during
adolescence, and secondly, minimise bone loss after the
menopause.

The majority of work with inulin and oligofructose to date in both
animals and humans has focussed on the first approach, with animal
studies in particular showing repeatedly over the last decade that
inulin/ oligofructose supplementation to a diet results in more
absorption of calcium.

“The mechanism of action in increasing absorption is unknown
but may be related to increased colonic calcium absorption,”

stated the authors.

Abrams and co-workers recruited 13 young adults (average age 23.8,
average BMI 21.9 kg per sq. m) and assigned them to eight weeks of
supplementation with eight grams of a inulin-type fructans (Beneo
Synergy 1, Orafti). The subjects underwent a calcium isotope study
(42Ca orally, and 46Ca intravenously) before and after starting the
prebiotic supplementation.

Eight of the subjects (average calcium intake of 900 mg/d) were
reported to have responded to prebiotic supplementation, with
increased calcium absorption of at least three per cent, from 22.7
to 31.0 per cent.

Seventy percent of the absorption increase was found to have
occurred in the colon, said the researchers. This is equivalent to
a 49 mg per day being absorbed in the colon.

“Given the multiple methods by which ITF acts, it is not
surprising that some human subjects have a much greater response
than others. Our results demonstrate that in those individuals who
respond to ITF, its effects primarily occur in the colon,”

they stated.

They added, however, that while increased solubility of calcium in
the colon appears to be the predominant mechanism for IFT, whole
gut mechanisms must not be ignored.

“In this regard, it is important to remember that in humans,
calcium absorption primarily occurs in the upper portion of the
small intestine compared with the large intestine in rats,”

stated Abrams and co-workers.

The study is in-line with studies with human adolescents, where
short-term supplementation with the synergistically active mixture
of oligofructose and long-chain inulin (SYN1) is reported to have a
higher calcium absorption (38 per cent), than the placebo group (32
per cent).

These increases in calcium absorption were subsequently repeated by
long-term supplementation studies of up to a year in length.

Indeed, one study reported that girls and boys aged between 9 and
12 supplemented with SYN1 had an additional net accretion of
calcium of 30 milligrams per day, compared to the controls who
received a placebo (American Journal of Clinical
Nutrition
​, 2005, Vol. 82, pp. 471-476).

Belgium’s Orafti has been influential in building the science
behind inulin and oligofructose, backing research into potential
benefits for a variety of health conditions ranging from bones to
colorectal cancer, from immunity to satiety and weight management.
The company co-funded the current study, along with the USDA
Agricultural Research Service and the National Institutes of
Health.

Source: Journal of Nutrition
Volume 137, Pages 2208-2212
“An Inulin-Type Fructan Enhances Calcium Absorption Primarily
via an Effect on Colonic Absorption in Humans”
​Authors:
S.A. Abrams, K.M. Hawthorne, O. Aliu, P.D. Hicks, Z. Chen, I.J.
Griffin

Overview of Disorders of Calcium Concentration – Endocrine and Metabolic Disorders

Parathyroid hormone is secreted by the parathyroid glands. It has several actions, but perhaps the most important is to defend against hypocalcemia. Parathyroid cells sense decreases in serum calcium and, in response, release preformed PTH into the circulation. PTH increases serum calcium within minutes by increasing renal and intestinal absorption of calcium and by rapidly mobilizing calcium and phosphate from bone (bone resorption). Renal calcium excretion generally parallels sodium excretion and is influenced by many of the same factors that govern sodium transport in the proximal tubule. However, PTH enhances distal tubular calcium reabsorption independently of sodium.

PTH also decreases renal phosphate reabsorption and thus increases renal phosphate losses. Renal phosphate loss prevents the solubility product of calcium and phosphate from being exceeded in plasma as calcium concentrations rise in response to PTH.

PTH also increases serum calcium by stimulating conversion of vitamin D to its most active form, calcitriol. This form of vitamin D increases the percentage of dietary calcium absorbed by the intestine. Despite increased calcium absorption, long-term increases in PTH secretion generally result in further bone resorption by inhibiting osteoblastic function and promoting osteoclastic activity. PTH and vitamin D both function as important regulators of bone growth and bone remodeling (see also Vitamin D Deficiency and Dependency).

Radioimmunoassays for the intact PTH molecule are still the recommended way to test for PTH. Second-generation assays for intact PTH are available. These tests measure bioavailable PTH or complete PTH. They give values equal to 50 to 60% of those obtained with the older assay. Both types of assays can be used for diagnosing primary hyperparathyroidism or monitoring hyperparathyroidism secondary to renal disease, as long as normal ranges are noted.

PTH increases urinary cAMP. Sometimes total or nephrogenous cAMP excretion is measured in diagnosis of pseudohypoparathyroidism.

Calcium and Bone Density – Scientific Research and Diet

Risk Factors for Osteoporosis and Osteopenia

  • Older age
  • Non-Hispanic, Caucasian and Asian ethnicity
  • Small bones – i.e. females
  • Family history of osteoporosis or osteopenia
  • Long-term estrogen hormone use
  • Cigarette smoking
  • Alcohol abuse
  • Sedentary lifestyle or bedridden
  • Low calcium intake
  • Low vitamin D blood level
  • Certain medications such as prednisone, excess thyroid, Dilantin and others

Gut Bacteria and Calcium

A remarkable new area of modern research is in the human colon.  Here, there are over 2000 species of bacteria and trillions upon trillions of bacteria.  They live and thrive in the colon and produce a large number of health benefits.  It is now known that when significant amounts of certain vegetable fibers or dietary supplements reach the colon that the very best bacteria grow vigorously.  These thriving bacteria, in turn, cause extra calcium to be absorbed through the colon wall. 

Soluble Prebiotic Fiber

All plant fiber arrives in the colon unchanged.  There, it is the soluble (meaning water soluble) fibers that are used by certain of the gut’s bacteria to enhance the absorption of calcium.  The two fibers that have been most studied are inulin and oligofructose.  In fact, when a group of young teenagers took this fiber supplement daily, they had a 20% increase in bone density (bone strength) after one year.

Vitamin D

Vitamin D is also essential to bone health. It encourages absorption of calcium. You get vitamin D from exposure of the skin to the sun, from a limited number of foods, and from dietary supplements. A remarkable recent finding is that there are receptors for vitamin D in many tissues other than the small intestine, where calcium from food is absorbed. These include muscles, brain, prostate, breast, colon, and immune cells. We have to believe that these vitamin D receptors serve a function since diseases in these organs have been associated with vitamin D deficiency.

Additionally, vitamin D levels have recently been found to be significantly low in many age groups. The previous recommendation of 400 IU per day is too low. The new recommendation is 800-1200 IU daily, especially for people who do not have significant skin sun exposure like the elderly or those who are inactive. Vitamin D is found in a limited number of foods such as cheese, butter, vitamin D fortified milk, oily fish, and eggs.

Vitamin D and calcium are intimately connected.  You need to have a good level of vitamin D in your blood to absorb and use calcium.  In Caucasian and light-skinned people, the sun’s rays will make vitamin D in the skin. Dark-skinned people and African-Americans need to get their vitamin D from foods and vitamin D pills.  This is important as vitamin D deficiency is very common.  For detailed information on vitamin D from the National Institutes of Health, Google search: Dietary Supplement Fact Sheet: Vitamin D.

Selected Foods High in Vitamin D

  • Cod liver oil
  • Salmon, Mackerel, Sardines, Tuna
  • Vitamin D enriched milk, fruit juices, yogurt

What To Do – The Good Things

  • Consume 1000-1500 mg of calcium per day in food and/or a supplement
  • Active lifestyle – walking, bicycling, gym
    workout, etc.  You want to stress your bones.  Weightlifting by itself
    does not do this very well.
  • Eat soluble plant fiber or take a prebiotic supplement.
  • No cigarettes
  • Moderate alcohol only
  • Check your medications with your physicians.
  • Moderate caffeine intake – coffee and sodas

Calcium Intake

By far, the most important consideration is to get enough calcium into your body every day.  A minimum of 1000 mg a day is recommended going up to 1500 mg a day when needs are high, such as in recovery from fractures, athletics, and pregnancy.  The chart below provides information on calcium content in various common foods.

Calcium Content of Foods

90,000 Calcium Myth – Avocado

Photo: @mija_mija

There are also factors that can negatively affect the level of calcium stores.

★ Caffeine, which is found in both tea and coffee, reduces the absorption of calcium in the intestines and through the kidneys. The compensation mechanism works as follows: when the level of calcium is low, the body increases the level of the hormone PTH (parathyroid hormone), which in turn increases the production and absorption of vitamin D, increases the absorption of calcium in the kidneys and releases calcium from bone reserves.It is enough to drink 9-12 cups of coffee or tea a week to start a cascade of events.

★ Phytic acid, which is found in nuts, seeds and legumes, blocks the absorption of minerals, including calcium. In order to avoid this, the listed foods should be soaked and, if possible, germinated.

★ Oxalates, found in spinach, Swiss chard, parsley, soy, quinoa, and chocolate, may reduce calcium absorption, but not completely. For example, 100 grams of spinach contains 99 mg of calcium, but due to the presence of more oxalates, which are grouped with calcium, only 30 percent will be absorbed.But the leaves of kale contain less oxalates, so up to half of the calcium from only one serving will be absorbed. In this case, it is best to eat young leaves and make sure you include different calcium resources in your diet.

There are several other factors that reduce calcium levels. These include diseases associated with hormonal imbalances. These include an overabundance of the stress hormone (cortisol), hypoparathyroidism, and hyperthyroidism. Celiac disease, smoking, and chronic alcoholism also reduce intestinal absorption of calcium.

To summarize, remember that a plant-based diet also has a large selection of calcium-rich foods. The most important thing is to diversify your diet and focus on getting enough protein. It is also important to provide the body with not only calcium, but also vitamins, which play an important role in its metabolism. Stay alert and don’t waste your calcium!

Author: Alexandra Efimova

90,000 Calcium (Ca). Minerals. Complivit

Diseases caused by deficiency of the mineral calcium (Ca)

Insufficient intake of calcium in the body can have serious consequences, one of the most dangerous is a decrease in the density and strength of bone tissue and the development of osteoporosis, which leads to an increased risk of fractures.In the Russian Federation, 14 million people (10% of the country’s population) suffer from osteoporosis, another 20 million have osteopenia. Other unpleasant consequences of calcium deficiency include deterioration of the condition of teeth, hair and nails, the appearance of cramps in the muscles and impaired contractility (decreased tone), and possible disorders of blood coagulation and the functioning of the immune system. Insufficient calcium intake in childhood is especially dangerous – this can lead to a delay in the growth and development of the child, deformation (curvature) of the limbs and spine, and the formation of improper posture.Currently, low bone mineral density is recorded in 29-59%, and a slowdown in skeletal maturation and insufficient bone mineralization in 70% of schoolchildren.

In addition to providing the body with a sufficient amount of calcium, it is necessary to take into account that many factors have a significant influence on its assimilation. Vitamin D is a key factor affecting calcium absorption – it provides active transport of calcium through the wall of the small intestine.It has been shown that in the absence of vitamin D, only 10-15% of the calcium taken with food is absorbed by passive absorption. Phosphorus plays an important role in the absorption of calcium. Protein foods, citric acid and lactose also contribute to calcium absorption.

Impede the absorption of calcium and disrupt its utilization; excess content in food of phytic acid (which is rich in cereals), inorganic phosphates, fatty and oxalic acids. Inflammatory diseases of the gastrointestinal tract can also lead to impaired absorption of calcium.

With excessive consumption of animal fats, during the digestion of which saturated fatty acids are released, calcium is able to bind with acids to form insoluble salts and be excreted in a significant amount with feces. This explains osteomalacia in people with impaired fat absorption. Bile acids, promoting the absorption of fatty acids, improve calcium utilization.

Science: Science and technology: Lenta.ru

Some combinations of products popular among Russians turned out to be harmful.Endocrinologist-nutritionist, Candidate of Medical Sciences Yekaterina Ivannikova told Komsomolskaya Pravda about this.

So, adding milk to cocoa will not bring the expected benefit to a healthy person: oxalic acid contained in cocoa beans blocks the absorption of calcium. At the same time, it is better for people with urolithiasis to completely abandon such a combination, since milk fat enhances the absorption of oxalate substances from cocoa, which lead to a worsening of the patient’s condition.

The doctor also recommends refraining from eating white bread with jam.Both products contain fast carbohydrates and, when ingested, provoke a sharp jump in blood sugar levels. Frequent consumption of sandwiches with jam can lead to the development of type 2 diabetes mellitus, obesity, and also cause inflammation in the organs of the gastrointestinal tract.

It is not recommended to eat bran with milk. Cereals contain phytic acid, which binds to calcium from milk to form insoluble compounds. Thus, useful minerals are not absorbed, and the digestion process is difficult.In addition, the expert advises against eating chicken and liver at the same time. The fact is that zinc contained in chicken and vitamin B9, which the liver is rich in, interfere with each other’s assimilation.

However, the nutritionist named pizza and soda the most harmful combination of products. “The combination of carbohydrates, proteins and trans fats, which are contained in such a set, requires a lot of energy from the body to digest. Sugar from soda inhibits stomach activity, ”explained Ivannikova. According to her, after such a meal, there is a feeling of heaviness, bloating, and blood sugar levels rise.In addition, due to the high content of refined carbohydrates, the false feeling of hunger increases, as the signal of satiety is suppressed.

Earlier, doctors told about the need to give up some products when using drugs. So, while taking aspirin or ibuprofen, it is worth giving up raspberries, since this berry contains natural salicylic acid. This combination often leads to internal bleeding. There have been cases where grapefruit juice, combined with drugs that lower cholesterol, led to the death of a patient.

It was also recommended not to consume spinach, broccoli and lettuce when taking blood-thinning medications (warfarin). Viburnum, chokeberry, strawberries and beets can significantly enhance the effect of blood pressure lowering drugs. And when taking psychotropic drugs, cheese can cause a hypertensive crisis and convulsions.

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Alcohol and cancer. | OBUZ Kursk City Clinical Emergency Hospital

Alcohol and oncological diseases.

Alcohol and cancer: is there a connection between them? Can excessive alcohol consumption trigger the development of cancer in the body? Yes maybe. Excessive systematic intake of alcohol significantly increases the risk of oncology.

Of course, not everyone who abuses alcohol will get cancer. But it has been scientifically proven that the appearance of malignant neoplasms is more common in drinkers. Continuous drinking increases the likelihood of cancer of the throat, liver, esophagus, mouth, breast, intestines .

A drinking person has a strong suppression of appetite, a decrease in digestive function, nutrition becomes unbalanced, a deficiency of microelements appears, there is a lack of antioxidants that protect against cancer. The body is exhausted and exhausted, which is just the right breeding ground for cancer.

People who drink, as a rule, have gastritis, there is a deterioration in the functioning of the pancreas, liver, and mental problems. When drinking alcohol, smoked meats or dried fish are often used as a snack, which further enhances the carcinogenic effect of alcohol and can lead to cancer of the esophagus.

Excessive drunkenness inevitably leads to cirrhosis of the liver, which, in turn, gives rise to malignant formations. Recent studies have shown that even small amounts of alcohol increase the chances of developing bowel cancer.

Those who drink alcohol are always deficient in vitamins, which promotes the conversion of ethanol into poison and negatively affects the central nervous system.

Excessive amount of alcohol reduces the absorption of calcium, and lack of calcium is a direct road to osteoporosis.Due to improper nutrition in the body, a deficiency of phosphorus and magnesium appears, and kidney function is disrupted. As a result, mental deviations appear: nervousness, loss of orientation, a feeling of goose bumps, inability to formulate thoughts.

Addiction to wine can provoke both a deficiency and an excess of micronutrients. Lack of zinc leads to impaired functioning of the testicles and ovaries, impaired night vision and decreased immunity, which makes a person defenseless against infections.Lack of selenium leads to the loss of antioxidants that fight free radicals. At the same time, the content of lead and iron in the blood goes off scale, which contributes to the fixation of free radicals, which are the main cause of cancer and aging of the body.

As you can see, we can confidently say that oncology is often a consequence of alcohol abuse.

Is alcohol in small doses good for you?

It is believed that small amounts of alcohol, such as red wine, are beneficial to health.But this is a misconception. It doesn’t matter what kind of alcohol is used: wine, beer, vodka or other alcoholic drinks, in the future they will remind of themselves.

If you significantly reduce the intake of alcohol or stop drinking it altogether, you can reduce the likelihood of cancer.

Having limited the amount of alcohol consumed, you should establish good nutrition and exercise regularly. Vegetables and fruits should always have a place on the table. They will protect from oncology, in particular from diseases of the stomach, throat, oral cavity, lung cancer.

90,000 Kidney stones come from calcium supplements?


4 February 2020

Are Kidney Stones From Calcium Supplements?

Calcium intake is the main preventive measure for osteoporosis, the spread of which has reached epidemic proportions. However, the presence of urolithiasis or the fear of acquiring it significantly limits the use of calcium supplements.Kidney stones occur in about 5% of the population, and the risk of their formation over a lifetime is as high as 10%. Fears are actively supported by numerous publications that “excess” calcium is deposited not only in the kidneys, but also in the vessels, tissues of internal organs and even the skin.

But in fact, the accusations against calcium are not supported by anything, because the regulation of calcium metabolism is much more complicated. According to the researchers, the formation of kidney stones is not due to excess, but from a lack of calcium and vitamin D.Moreover, the same mechanisms are involved in the development of osteoporosis and stone formation. Deficiency of calcium and vitamin D leads to an increase in the production of parathyroid hormone by the parathyroid (parathyroid) gland – hyperparathyroidism. It is this hormone, on the one hand, that enhances the destruction of bone tissue, and on the other hand, it prevents the excretion of calcium by the kidneys and promotes the formation of stones.

To prevent stone formation and osteoporosis, the main attention should be paid to the timely prevention and correction of deficiencies – the intake of vitamin D and a sufficient amount of calcium-containing foods in the diet.And this should be started not during the period of problems that have already appeared or upon reaching the “balzac” age, but from childhood. An important condition for proper absorption of calcium is an adequate amount of magnesium in the body. The optimal ratio of calcium and magnesium in the diet is 2: 1 or 3: 2. If there are kidney stones, then the possibility of using calcium supplements should be discussed with the attending physician.

90,000 Balanced feeding promotes healthy growth in dogs


Ludwig Maximilian University
Munich, Germany
Email: Dobenecker @ lmu.de

Abstract

This paper discusses the main factors affecting the healthy growth of dogs in terms of comparing the nutrient requirements of these animals on the one hand and humans on the other. These factors include the reserves of calcium and phosphorus in the body necessary for growth, as well as the energy supply required for growth and development. It also reviews published data on the effects of excess or inadequate supply of minerals to the body during periods of growth intensity.

Calcium and phosphorus

Dogs have higher requirements for minerals such as calcium (Ca) and phosphorus (P), therefore they are more sensitive to both insufficient and excessive intake of nutrients compared to other species of animals, including, and especially, – with a person. This observation is true for adult dogs, and it is even more true for young dogs during their active growth period. Different experts can give different recommendations for both humans and dogs regarding the consumption of minerals, their quality composition and their quantity, but one thing is always obvious: adult dogs need much more calcium than an adult.

The body’s need for calcium and its deficiency

Why do dogs need so much calcium?

It is known that the body of animals must maintain a sufficiently stable and certain level of calcium in the blood. Therefore, an accurate mechanism for regulating its content is needed in order to avoid significant hypo- or hypercalcemia, each of which can be life-threatening. Since it is usually difficult to increase the absorption of calcium in adult dogs, the lack of calcium in them can be eliminated using the reserves of the body itself, i.e.e. by activating bone resorption. It is currently not well established how long it takes for a dog to effectively activate bone resorption. It is also possible that the existing skeletal reservoirs for various purposes – for immediate single use or for long-term use – allow the dog to remain practically insensitive to daily fluctuations in the mineral composition in their diet. However, even adult dogs can develop osteomalacia as a result of prolonged calcium deficiency in the diet.

What happens to people with prolonged calcium deficiency in food?

It would not be such a big exaggeration if we say that in a number of Western countries, unbalanced and malnutrition is widespread, with a predominance of animal fats and carbohydrates, but low in vitamins and some minerals. For example, the 2008 nutrition report of the German Nutrition Society (Deutsche Gesellschaft für Ernährung) documented the lack of fiber, several vitamins, and calcium intake by most German children and adolescents.However, there are few reports of obvious clinically relevant developmental problems in children associated with their mineral-deficient diet. Perhaps this is partly because even Ca deficiency, combined with overweight and too steep a growth curve, does not often lead to orthopedic diseases in children, unlike in dogs.

If a puppy during the period of active growth consumes such an amount of calcium, which is considered sufficient for children of the same body weight, then he will develop severe clinical problems with the skeleton.Growing dogs may be more susceptible to calcium deficiency due to their higher growth rate and therefore higher tissue accretion requirements. Dogs are prolific and, therefore, reproducing females have higher requirements for Ca and P. If we compare the needs of an adult male, who, by the nature of his activity, needs proper or even enhanced nutrition, then these needs in terms of minerals will still be significantly lower than the needs of an adult male …The question, therefore, is not whether a dog provided with a human-calculated amount of Ca will develop health problems, but how quickly they will develop.

Table 1. Daily calcium requirement in dogs and humans at the same weight, calculated for the period of growth, development and the reproductive period.

Life Stage Adult dogs Adult men Factor
mg / d (70kg BW) * 3146 1000 3.1
Growth phase Puppies (<14 weeks) Children ~ 2 years old) Factor
mg / d (12kg BW) # 4384 600 7.3
Reproduction period Adult dogs Adult women Factor
mg / d (70kg BW) * 19844 1000 19.8
* Calculated for dogs weighing 70 kg and an average adult male weighing 70 kg 90 140
# The calculation was made for an actual weight of 12kg and an adult weight of 70kg

Recommendations developed by: Deutsche Gesellschaft für
Ernährung, (1) NRC (2) and FEDIAF.(3)

Do we have enough knowledge and evidence of such a huge difference between humans and dogs? If so, the question is, is this difference related to reduced Ca absorption in dogs? How about a mechanism to regulate and adapt to an appropriate diet and diet? And what are the sources of the data already available, that is, what tests were carried out to study digestion? Should we consider all these aspects?

First, we need to examine the existing requirements for the lower and upper limits for minerals in the diet.Despite the fact that a sufficient number of articles on this topic have been published, which can be a sign of an excellent (or at least sufficient) awareness of the scientific community in this area of ​​knowledge, from all these publications only the most general recommendations regarding the norms of calcium and phosphorus in the diet can be gleaned. nutrition. How could this have happened?

It is hypothesized that a number of factors may affect the bioavailability of key minerals, predominantly Ca and P, in dogs.This includes age, height, reproduction, body weight, breed of animal, conditions of its keeping. Consideration should also be given to factors such as the composition of the animal’s diet, the source of minerals, the concentration of the corresponding mineral in the diet, as well as the concentration of other minerals that are known to affect the digestibility of the mineral in question (interactions determined, for example, by the Ca / P ratio) , the digestibility of the entire diet and the duration of feeding a specific diet.The last of the listed factors seems to be very important. Nevertheless, it is he who is still very little studied. Thus, collecting reliable data on the bioavailability of Ca and P presupposes homogeneous testing or, better yet, knowledge and the ability to quantify all factors that could influence the results in any way.

A recent study by scientists, including a meta-analysis of the digestibility of foods containing calcium and phosphorus in dogs and cats, improves our understanding of the digestibility of these elements in these groups of animals.It has been established that Ca metabolism in adult cats and dogs is regulated by parathyroid hormone (PTH), calcitonin and vitamin D metabolites. food and, conversely, increase this amount in case of insufficient content in the diet in order to maintain the necessary balance of minerals in the body. However, the results of the above-mentioned meta-analysis refuted the existing view.The researchers presented the following explanations: 1. The duration of the tests usually carried out to determine the Ca balance is too short to initiate the regulation of absorption / excretion of this substance; 2. Dogs (at least in their particular conditions of keeping) are completely unable to adapt the digestibility of Ca in comparison with other species, such as horses and rabbits.

Let us explain the first position. The duration of the tests performed, and therefore the effect of the proposed diet on the test animals, may be too short to modulate nutrient absorption in dogs.The normal period for digestion testing should be 4 to 8 weeks. If during this period there is no adaptation of the absorption of Ca, as shown by Mack and colleagues, then the level of its content in the blood should be regulated by bone resorption in the case of insufficient intake or by excretion of Ca through urine in the event of an excess in the body. In this case, the data obtained during such “normal” tests turn out to be completely useless precisely in relation to the problem of absorption of Ca – simply because the test period is too short.

Let us explain the second position. Dogs are unable to adapt Ca absorption even after a longer period of feeding on diets with insufficient or excess Ca. This would deplete bone tissue and, sooner or later, lead to health problems in the animals. Using the wolf as the progenitor of all canines as an experimental model to study the background of Ca metabolism may help us understand that the presence of this element in the diet of this family is of great importance.All primitive, natural diets of carnivorous animals consisted of other animals they slaughtered. Therefore, they did not need to increase the efficiency of Ca assimilation: there was more than enough bone material in their access. Another to The greater requirement of dogs for Ca during the period of growth and reproduction can be confirmed by the historically established principle of dividing prey in the canine family. Traditionally, the leaders of the pack got the best parts of the killed game, followed by adult females, and then young growing dogs, who received mainly the bone part of the carcass of the killed animal, which increased their calcium intake.There is probably a similar historical explanation for the inability, and perhaps the lack of need for, in dogs and cats to synthesize vitamin D. Based on the existing knowledge of the factors affecting the bioavailability of calcium and phosphorus, it is necessary to establish the greatest possible uniformity in those tests to test their digestibility. animals, the results of which should be really taken into account (composition of subjects, uniformity of fed diets, test format and test organization).This must be done in order to obtain a reliable database necessary for the formation of sound recommendations on the content of Ca and P in the diet of animals. The question of whether it is possible to regulate Ca absorption in dogs, and if so, how long it might take, is still open, and therefore new research is needed in this area. The accumulated knowledge should form the basis for correct feeding of dogs and the possibility of eliminating both deficiency and excess of Ca in the diet.

Excess calcium in the body

By revising our understanding of the data presented in some scientific publications, as well as analyzing the clinical situations described by scientists related to diet-induced diseases of animal bone tissue during its formation, we can better understand the flow of complex and sometimes seemingly contradictory information. In the scientific literature there are many works that talk about the dangers of excess Ca for the formation of a healthy skeleton in dogs during the period of their active growth.What these works have in common is the results of most tests showing that overfeeding of calcium-rich diets to puppies without a corresponding increase in their phosphorus content leads to a change in the ratio of these elements: Ca: P> 2: 1. This shift leads to to the appearance of signs of the development of orthopedic diseases in growing dogs of certain breeds, mainly in Great Danes. It is well known that the amount of Ca in the diet influences the absorption of R. In addition, Mac et al.found that the excretion of phosphorus in feces strongly correlates with the excretion of calcium in the feces of dogs and cats. In other test trials, where Ca: P ratios were more balanced by increasing dietary P, very rare signs of orthopedic disease were observed in the test dogs. Therefore, not an excess of Ca itself seems to be the only and main problem for the formation of a healthy skeleton, but a shift in the Ca: P ratio and a possible clinical consequence of secondary phosphorus deficiency caused by an excess of calcium.This explanation is not new at all. It was first published in 1931 by Marek and Wellman. Summarizing their findings on the harmful effects of excess calcium in the body of dogs, they concluded that lameness and curvature of the limbs became especially pronounced in them if the phosphorus content did not increase in parallel in their diet. It has already been reported that two German Shepherd puppies developed severe clinical signs of bone disease, further confirmed by X-ray and histological examinations, as well as hypophosphatemia, after being regularly fed a diet high in calcium and normal phosphorus.Severe clinical signs of bone disease have also been observed in a fox terrier puppy after adding CaCO3 to its diet. Further, these signs disappeared after CaCO3 was replaced with bone meal, as this led to an increase in phosphorus intake and a balanced Ca: P ratio in the diet. Taking into account this information, it can be concluded that the combination of excess calcium with secondary phosphorus deficiency can cause bone diseases, especially in puppies of large and giant breeds.At the same time, in addition to the size factor, some breeds also have an increased sensitivity to excess calcium in the body. This is supported by practical observations showing that dogs of some breeds develop serious osteopathologies, while dogs of other breeds remain (clinically) healthy under the same conditions. This observation is supported by the results of a study of the effect of simultaneous excess in the body of Ca and P on skeletal development in two different breeds of dogs during the period of active growth.Measurements of the length and width of the forearm bones on radiographs of beagle dogs and hound dogs of 6 weeks of age, and then – in them at 27 weeks of age – after constantly feeding them a diet with a high calcium content, showed a tendency to slowdown in the growth of limbs only in beagles, and their bone tissue remained generally quite healthy.

The hypothesis that bone disease in growing dogs is associated with a phosphorus deficiency in the diet was supported by results from a study on the nutrition of beagle and hound puppies.Puppies received a diet that provided them with about 40-50% of the recommended phosphorus, while the calcium content in their diet fully corresponded to existing norms. Thus, there was a shift in the Ca: P ratio in the diet. In this experiment, some puppies of both breeds developed severe clinical signs of bone disease, manifested in severe curvature of all limbs. Further, when the feed was saturated with phosphorus, these signs disappeared.

That excess Ca is more dangerous for growing dogs when accompanied by low or marginal P intake by them can also be explained by an analysis of the natural diet of the modern dog’s ancestors.As mentioned above, in a pack of wild dogs or wolves, those of its members who occupy the lowest positions in the hierarchy are, of course, puppies and young dogs, feed exclusively on the remains of large prey, that is, mainly on connective tissue and bones … In this order, sensitivity to excess Ca would only make sense if the absorption of minerals from bones were rather low in dogs, or if dogs could excrete excessive amounts of calcium in the urine without more harm to the body (perhaps after a period of accumulation of the Ca reserve in the skeleton).It is hypothetically more likely that dogs, including puppies, are completely immune to excess Ca, which is why their natural diet contains high amounts of Ca and P. However, a certain amount of Ca excess over time can have a negative impact on healthy development. the skeleton of animals under the influence of such factors as the characteristics of the breed and the growth curve, microtrauma, intense training, the presence of calcium and phosphorus, as well as the supply of other nutrients in the diet, etc.On the other hand, dogs appear to have only a limited ability to improve the absorption of Ca and P and therefore may tend to show signs of disease if deficient. The last part of the hypothesis explains why dogs need much more Ca than humans. As in many other fields, it seems justified to warn scientists about transferring knowledge of human physiology to dogs. Dogs are not at all like people who can bark!

Providing the body with energy during the growth stage

Another important factor that must be taken into account when raising a healthy dog ​​is providing its body with the necessary supply of energy.It is well known that along with such factors as the age and weight of a dog, breed, activity, health, housing conditions and others also affect its energy requirements during the growth period. From the foregoing, the main conclusion can be drawn that the correct supply of energy to each individual puppy can only be monitored by monitoring its weight gain during the growth period. If the body weight is within the recommended range of the growth curve, the risk of overfeeding and obesity is minimal.In this context, it should be emphasized that there are significant problems with respect to the accepted systems for assessing the body of growing puppies. Not only does DEXA body fat not necessarily match the predicted BCS (Body Condition Assessment System), a low BCS score can easily be found in a puppy who is actually too obese for his age. This is because puppies of high growth potential breeds use excess energy to grow, not to store fat.In this case, the puppy may look skinny despite the fact that his body will experience the harmful effects of too high body weight on the growing skeleton. Because size is often mistaken for beauty, good health and strength, especially in large and giant breed dogs, puppies of these breeds are often overweight. These dogs require restrictive feeding in order for them to grow more slowly, but their health would be better. The NRC’s recommendations for replenishing the body’s energy resources during the growth period overestimate the actual needs of dogs, which can lead to incorrect recommendations for their feeding.Dog owners, following such feeding guidelines based on existing energy requirements calculations, can thus systematically overfeed their puppies. In addition, most owners add many treats to their puppy’s daily rations when training or to form a close bond with the owner. This can lead not only to excess energy supply and to accelerated growth rates of the animal with detrimental consequences for its health. If the average commercial food is formulated to meet all of the nutritional needs of an animal, but it has an overestimated energy intake, then the puppy may start eating less and lack nutrients.If, for example, a puppy needs only 70% of the average daily energy in the diet for proper growth, then he will consume 70% or less (depending on the amount of additional treats) of the expected amount of the diet, and therefore only 70% of the nutrients. For the same reason, it is not recommended to use diets intended for feeding adult dogs during the growth period of the animal. Most of these foods do not contain enough nutrients for puppies.The consequences of feeding these inappropriate diets to puppies, including signs of bone disease, is something we regularly see in our veterinary nutritional counselor practice.

Other nutrients affecting skeletal development

Both a deficiency and an excess of nutrients such as vitamins A and D, trace elements, including zinc, copper, etc., can also have a negative effect on dogs during growth, respectively, and therefore all of them should be especially strictly taken into account when drawing up diets for puppies.

The effect on puppies of other nutrients, such as protein, is clearly overestimated. It is often said that too much protein impairs healthy growth in puppies, which is why there are foods in the pet food market that are advertised as “healthy growth foods with limited protein concentration,” although this has not been found and demonstrated to exist. The above is also partly true for the alleged harmful effects of excess vitamin A on skeletal development.As we recently learned, the safe upper limit for this element is 26 times higher in puppies than previously thought. Based on all of the above factors, the recommendation for practical puppy feeding is to try to meet existing requirements as closely as possible, at least in terms of energy, calcium and phosphorus. In this regard, however, the question arises as to whether it is possible in principle to create a universal diet that would be ideal for all breeds, ages, activities, stages of life, etc.in such a way that some special requirements are also taken into account in the respective products. After all, careful selection of the right food is critical at such an important stage in a dog’s life as active growth.



Author of the translation: Anatoly Chernikov – Chief Veterinarian, 101 Dalmatians Clinic, Moscow


References


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Diets cause osteoprosis

Russian scientists examined a group of girls from 18 to 25 years old, especially zealous for their figure, and were amazed at the results.It turned out that the body of slender and attractive ladies is sorely lacking such an important element as calcium.

Reason – a lifestyle associated with constant diets and dietary restrictions. Doctors say that if urgent measures are not taken, then in a few years the beauties will turn into hunched over old women, with twisted limbs, dull sparse hair and dry, flaking nails. And the name of this disease is osteoporosis. It is noteworthy that it is difficult to trace the initial stage of osteoporosis, as experts say, the bones “ache in silence”.The diagnosis can be made using only special equipment. No wonder osteoporosis is called a “silent epidemic”. According to statistics, today almost every third adult woman suffers from osteoporosis.

UNDER THE THREAT OF RING DEFICIENCY

Modern girls in pursuit of a figure eat like birds. Peck some salad and enough. Meanwhile, even a full-fledged set meal does not satisfy the body’s need for calcium. And even with the “bird’s” way of nutrition, this vital element enters the body in a catastrophically small amount.The situation is aggravated by the fact that calcium is absorbed only in the presence of fat-soluble vitamin D. Therefore, low-fat diet food only increases calcium deficiency. And the “hungry” organism begins to draw calcium from bone tissue, nails and hair.

CHOOSING CALCIUM CORRECTLY

The inclusion of biologically active additives in the diet helps to compensate for the lack of calcium. But here it is necessary to understand that in order to effectively fight osteoporosis, it is required not only to saturate the body with calcium, but to deliver it to the right place – our bones.Therefore, at the forefront when choosing calcium drugs should be such indicators as:

Digestibility: regardless of the calcium content in the preparation, you may not get the required amount of the mineral, since different calcium salts are assimilated by the body in different ways.

Efficiency: the presence of synergistic components, the reception of which simultaneously with calcium enhances the effect of the drug (for example, vitamin D3) and the absence of obvious antagonists (for example, the simultaneous intake of iron or magnesium reduces the absorption of calcium by more than 2 times).

Safety: calcium should not accumulate in the kidneys in the form of stones, cause calcification of the walls of blood vessels and, as a result, increase the risk of developing cardiovascular pathologies.

UNDER EFFICIENCY MAGNES

When choosing a calcium preparation, be sure to pay attention to what is the source of calcium.

Calcium carbonate is an inorganic salt that is actively used by drug manufacturers due to its low price.However, you need to understand that when it gets into the stomach, calcium carbonate reacts with hydrochloric acid, the by-product of which is carbon dioxide. This causes gastrointestinal discomfort: bloating and belching. Moreover, in people with low stomach acidity, calcium from carbonate “leaves” extremely reluctantly.

Calcium Citrate is an organic salt that is an exceptional form of calcium in terms of its effectiveness and safety. First, calcium from calcium citrate is absorbed regardless of food intake and stomach acidity.Secondly, citrate is involved in the energy exchange of cells in our body. Third, the chemical properties of calcium citrate make it a particularly useful source of calcium for people with hypochloridia (including elderly patients and patients taking drugs that reduce gastric acid secretion).

Finally, calcium citrate is highly water soluble and is a form of calcium that does not increase the risk of kidney stones or vascular calcification. It is not surprising that experts advise giving preference to preparations containing precisely calcium citrate as a source of the mineral.Calcium-Active Citrate is one such drug.

THE RIGHT CHOICE

Due to the composition of CALCIUM-ACTIVE CITRATE, the developers call it a “smart” drug. It is absorbed 2.5 times better than other calcium-containing preparations. Taking CALCIUM CITRATE, you do not have to face a choice: slimness and attractiveness or a hunched back and fragile bones. Do not drive yourself to the point where your doctor will prescribe treatment and prescribe serious medications.