Efficiency Of Intestinal Calcium Absorption Research Articles

High Fiber Diets Slow Bone Turnover in Young Men but Have No Effect on Efficiency of Intestinal Calcium Absorption

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery.

During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ∼30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism.

Serum vitamin D metabolites and intestinal calcium absorption efficiency in women

Vitamin D sufficiency may be determined by the serum concentration of 25-hydroxyvitamin D [25(OH)D] that results in maximal intestinal calcium absorption efficiency. However, some investigators questioned whether 25(OH)D concentrations above the concentrations associated with rickets or osteomalacia influence calcium absorption. We determined whether calcium absorption efficiency is related to serum 25(OH)D or serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] concentrations. We measured calcium absorption efficiency in 492 black and white healthy women (age range: 20-80 y) by the single-isotope method with (45)Ca. Serum 25(OH)D concentrations were measured by a radioreceptor assay. Other relevant measurements included concentrations of serum 1,25(OH)(2)D, serum parathyroid hormone, serum creatinine, and serum estradiol, calcium intake, and bone mineral density. There was no relation between serum 25(OH)D concentrations and calcium absorption efficiency. In development of a multivariate model, the 4 major determinants of calcium absorption efficiency were menopausal status, calcium intake, and serum estradiol and serum 1,25(OH)(2)D concentrations. There was an interaction between serum 25(OH)D and 1,25(OH)(2)D concentrations on calcium absorption efficiency. The relation between calcium absorption and 1,25(OH)(2)D was positive, and this relation was stronger for lower concentrations of 25(OH)D than for higher concentrations of 25(OH)D. The relation of serum 25(OH)D to calcium absorption is not useful as an indicator of vitamin D sufficiency.

Defects in the synthesis and metabolism of vitamin D.

It is now recognized that it is casual exposure to sunlight that provides most humans with their vitamin D requirement. During exposure to sunlight, the high energy ultraviolet B photons (290-315 mm) photolyzes cutaneous stores of 7-dehydrocholesterol to previtamin D3. Once formed, previtamin D3 undergoes a thermal isomerization that results in the formation of vitamin D3. Vitamin D3 is biologically inert and requires successive hydroxylations in the liver and kidney to form its biologically active hormone 1,25-dihydroxyvitamin D3. The major physiologic function of 1,25-dihydroxy-vitamin D3 is to maintain blood calcium in the normal range. It accomplishes this by increasing the efficiency of intestinal calcium absorption and mobilizing stem cells to become osteoclasts which, in turn, remove calcium from the bone. It is now recognized that there are a variety of calcium metabolic disorders that are related to defects in the synthesis and metabolism of vitamin D. Chronic granulomatous disorders are often associated with hypercalciuria and hypercalcemia. The mechanism by which this occurs is that activated macrophages within granulomatous tissue, in an unregulated manner, convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Besides its calcemic activity 1,25-dihydroxyvitamin D3 is a potent antiproliferative factor for cells and tissues that possess its vitamin D receptor. This has clinical utility in that 1,25-dihydroxyvitamin D3 and its analogs have been successfully used for the treatment of the hyperproliferative skin disease psoriasis.

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50-97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l+/-35.0 nmol/l and 49.4 ng/l+/-23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels (p=0.04), and positively and independently associated with 25(OH)D levels (p=0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate (r=-0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.

Effects of Smoking on Bone and Mineral Metabolism

Many studies have confirmed Daniell’s observation in 1976 that postmenopausal women who smoke have more fractures and less bone than postmenopausal women who do not smoke. Comparison of the bone density of smokers with that of their nonsmoking twins perhaps makes the point most strongly. There are many potential causes of these differences, including less calcium and vitamin D intake and less physical activity in smokers compared with nonsmokers. There is also evidence for direct toxic effects of smoking on bone cells. Decreased new bone formation in smokers has been suggested by decreased biochemical bone marker levels in several studies. Impaired osteoblastic proliferation, differentiation, and function in vitro have also been described. A few studies found an increase in bone resorption but most did not. Several authors have reported decreased intestinal calcium absorption efficiency in smokers. This is most likely caused by low levels of serum calcitriol (1,25-dihydroxyvitamin D), the hormone that controls calcium absorption. Although many smokers also have low levels of the storage form of vitamin D, 25-hydroxyvitamin D [25(OH)D], this does not appear to be the cause of their low serum calcitriol. Most studies, but not all, indicate that serum parathyroid hormone (PTH) is suppressed in smokers, and this is most likely the cause of both the low serum calcitriol and decreased calcium absorption. Why PTH is decreased is not clear. It could be because of increased degradation or decreased production of PTH. Two studies report normal serum ionized calcium levels in smokers, but one suggests ionized calcium levels are increased, which might cause a secondary decrease in serum PTH. Management of the increased bone loss found in smokers will remain empirical until its causes are better understood.

Relationships between intestinal calcium absorption, serum vitamin D metabolites and smoking in postmenopausal women.

Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p = 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r = 0.38) and non-smokers (r = 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH-calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH-calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation.

1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line.

The active hormonal form of vitamin D (1,25-dihydroxyvitamin D) is the primary regulator of intestinal calcium absorption efficiency. In vitamin D deficiency, intestinal calcium absorption is low leading to an increased risk of developing negative calcium balance and bone loss. 1,25-dihydroxyvitamin D has been shown to stimulate calcium absorption in experimental animals and in human subjects. However, the molecular details of calcium transport across the enterocyte are not fully defined. Recently, two novel epithelial calcium channels (CaT1/ECaC2 and ECaC1/CaT2) have been cloned and suggested to be important in regulating intestinal calcium absorption. However, to date neither gene has been shown to be regulated by vitamin D status. We have previously shown that 1,25-dihydroxyvitamin stimulates transcellular calcium transport in Caco-2 cells, a human intestinal cell line. In the current study, we have demonstrated that Caco-2 cells express low but detectable levels of CaT1 mRNA in the absence of 1,25-dihydroxyvitamin D treatment. CaT1 mRNA expression is rapidly up regulated (4-fold increase at 4 h and 10-fold at 24 h) by treatment with 1,25-dihydroxyvitamin D (10(-7) moles/L). Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein. These observations are the first to demonstrate regulation of CaT1 expression by vitamin D and are consistent with a new model of intestinal calcium absorption wherein vitamin D-mediated changes in brush border membrane CaT1 levels could be the primary gatekeeper regulating homeostatic modulation of intestinal calcium absorption efficiency.

Hypothesis to explain the association between hypocalciuria and low circulating 1,25-dihydroxyvitamin D levels in preeclampsia.

Abstract A hypothesis is presented according to which the hypocalciuria in preeclamptic women is due to a decreased efficiency of intestinal calcium absorption as a consequence of diminished placental synthesis of 1,25-dihydroxyvitamin D related to lower circulating placental lactogen level and/or a possible reduction in the synthesis of insulin-like growth factor I.

The efficiency of intestinal calcium absorption is increased in late pregnancy but not in established lactation

The fractional absorption of calcium (FA-Ca) was measured using a dual non-radioactive Ca isotope technique in 26 control women, 49 women in the last trimester (36 weeks) of pregnancy and 31 of these women in established (20 weeks) lactation. The ratio of the two non-radioactive Ca isotopes was measured, by high precision thermal ionisation mass spectrometry, in urine 12-24 hours after administration and was used to calculate FA-Ca. This is the first study to clearly show that FA-Ca is significantly elevated in late pregnancy but not in established lactation, when compared with control women.

Effects of glucose and glucose polymers on calcium absorption in healthy subjects

Glucose polymers have been shown to enhance intestinal calcium absorption in normal subjects as well as in patients with gastrointestinal disease. Glucose polymers are widely used as an energy source in enteral nutritional supplements and infant formulas. In this study, eight normal subjects underwent 47Ca absorption tests to compare the effect on calcium absorption of carbohydrate given orally as a simple carbohydrate (glucose) or a more complex carbohydrate (glucose polymers). Oral coadministration of glucose with calcium increased the efficiency of intestinal calcium absorption by 20% and coadministration of glucose with glucose polymers increased calcium absorption by 27%. This suggests that glucose, derived from glucose polymers by hydrolysis, may be responsible for the positive effect of polymers on calcium absorption. The potential positive effect of coadministration of carbohydrate on calcium bioavailability deserves considerations in the design of calcium supplementation strategies.

Role of nutrition and exercise in osteoporosis

Both adequate nutrition and exercise are essential for development of peak adult bone mass and maintenance of bone during aging. The optimal dietary level of a nutrient may vary from individual to individual and may change with age, intake of other nutrients, disease, drug therapy, or sex hormone status. Effects on spinal trabecular bone may not parallel effects on axial cortical bone. Calcium nutrition is important in the prevention of osteoporosis, as calcium is a major constituent of bone. The intake of calcium among most American adults is below the levels recommended by public health agencies. There have been no adequate prospective studies to determine the optimal intake of calcium for preservation of bone mass in young or middle-aged adults, although calcium balance studies indicate that premenopausal women require approximately 1,000 mg of calcium per day. The negative calcium balance of early menopause may be ameliorated by 1,000 mg of calcium per day; however, there is no proof that greater intakes fully reverse the effects of estrogen deficiency. Calcium requirements of both elderly men and women are likely to be greater (between 1,000 and 1,500 mg per day) due to an age-related decrease in the efficiency of intestinal calcium absorption. The optimal level of weight-bearing exercise for maintenance of bone mass in old age is probably similar to that of an active young adult. Maintenance of this activity level in middle and old age improves bone mass. An exercise prescription for elderly individuals must include an appraisal of cardiovascular and muscular-skeletal health and be designed to minimize the risk of trauma during exercise.

Calcium Metabolism in Children Recovering from Severe Protein‐Energy Malnutrition

SummaryTwenty preschool children with severe edematous protein‐energy malnutrition (PEM) were studied during the first 45 days of recovery. All children received 4 g/kg/day of protein and 150 kcal/kg/day of energy from a milk‐based recovery formula, providing 130–140 mg/kg/ day of calcium (Ca). Children were randomized to two treatment groups, one receiving intact milk formula and the other a lactose‐free preparation. Both groups showed a high efficiency of intestinal calcium absorption, sustained even after the normalization of weight for height and lean body mass. The presence or absence of lactose in the diet did not affect intestinal calcium absorption, and increased stool volume in the early period of recovery in the children receiving intact milk was not associated with higher fecal Ca losses. Urinary Ca excretion was within the range reported for healthy children under a normal diet. These results suggest that therapeutic amounts of calcium should be delivered to children with PEM well beyond the normalization of body weight and lean body mass.

Hypophosphataemia and vitamin D metabolism in sheep.

The effect of dietary induced hypophosphataemia on vitamin D metabolism was studied in four conscious sheep. No change in the plasma concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were found during hypophosphataemia when compared with normophosphataemia. In addition both the metabolic clearance rate and the production rate of plasma 1,25(OH)2D3 were unaltered during hypophosphataemia. This suggests that changes in circulating levels of 1,25(OH)2D3 were not necessary for the increased efficiency of intestinal phosphorus absorption seen in phosphorus-depleted hypophosphataemic sheep, and may explain why there is no increase in efficiency of intestinal calcium absorption in phosphorus depleted sheep. Increases in phosphataemia induced acutely by intravenous phosphate infusion for 3 h also had no effect on plasma 1,25(OH)2D3 concentration. It is concluded that in the sheep, unlike non-ruminant animals, chronic hypophosphataemia does not increase plasma 1,25(OH)2D3 concentrations and plays no physiological role in regulating its production or metabolism.

Calcium nutrition and bone health in the elderly

The average elderly person is in negative calcium balance and accordingly is losing bone mass. While factors such as decreased mechanical loading of the skeleton undoubtedly figure in this age-related loss, a growing body of evidence suggests that inadequate calcium intake may contribute to this loss. On any given day men and women in the US 65 yr or older ingest about 600 and 480 mg calcium, respectively. Calcium intake in the elderly is less than in the young, and reduced absorption efficiency further lowers effective intake. Additionally, other nutrients such as protein and fiber, taken in excess, effectively increase the calcium requirement. Estrogen withdrawal at menopause leads to a decrease in intestinal calcium absorption efficiency and in renal calcium conservation, both effects equivalent to an effective increase in calcium intake requirement. Thus it is not surprising that all studies of mean requirements for zero balance performed in elderly subjects have yielded values above the current RDA for the US. The available evidence thus suggests that the RDA for adults should surely not be lowered below its current level (800 mg), but that, instead, it ought to be raised. It is not possible to say with certainty to exactly what level, but available evidence is compatible with allowances of at least 1200 to 1500 mg/day. Further, the evidence indicates that the mean requirement ought to be thought of as a complex function of age, sex, absorption efficiency, intake of protein, fiber, and probably other nutrients, estrogen status, and mechanical loading. Extensive experience with calcium supplements indicates that daily intakes up to at least 2.5 g of elemental calcium are quite safe in all persons except for certain subsets of the population uncommon among the elderly (eg, those with sarcoidosis, active tuberculosis, or other absorptive hypercalciuric syndromes). At the same time it must be said that osteoporosis is a complex, multifactorial disorder, and that factors unrelated to calcium nutrition undoubtedly play important, even dominant roles in many--perhaps most--osteoporotics. The available evidence, taken together, does not indicate that raising calcium intake will abolish the problem of osteoporosis. It does indicate, however, that calcium nutrition is considerably more important in the genesis of osteoporosis than has been commonly thought for the past 35 yr. As our listing of "important issues" indicates, the full extent of that importance, in both pathogenesis and prophylaxis, remains to be elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)