Effect of dietary calcium and lead status on intestinal calcium absorption

Dietary lead intake was demonstrated to result in two very different effects on intestinal calcium absorption and associated parameters, depending on dietary calcium status. Normal growing 14-day-old chicks were fed diets either low (0.05%) or adequate (1.2%) in calcium and containing varying levels of lead (0%-0.8%) for an additional 10 days. In chicks fed the low calcium diet, ingested lead inhibited intestinal 47Ca absorption, and intestinal calbindin D and alkaline phosphatase synthesis in a dose-dependent fashion. Even at the highest levels of lead, however, this inhibition was limited to the stimulation of these parameters by low dietary calcium. In chicks fed the normal calcium diet, lead exposure did not diminish intestinal 47Ca absorption, or calbindin D or alkaline phosphatase synthesis, but actually elevated the values of these parameters at the higher lead exposure levels. The results indicate that the primary effect of lead, in both cases, occurs at or prior to intestinal protein synthesis and most likely involves the cholecalciferol endocrine system rather than any direct interactions between lead and calcium at the intestinal level.     

Intestinal calcium absorption: mechanisms and applications

Calcium absorption from the intestine involves two sets of events. One, a saturable transcellular process is regulated by vitamin D via its molecular product, the calcium-binding protein (CaBP, MW = 8800). This transcellular movement is largely confined to the proximal portion of the intestine. The second process is nonsaturable, occurs throughout the length of the intestine and is paracellular. Evidence in support of these statements is discussed, with emphasis on kinetic considerations. It is proposed that CaBP acts as a ferry, amplifying the intracellular movement of calcium by a factor of about 60, thereby enabling transcellular calcium transport to reach the measured values of Vm = 22 mumol/h per gram (wet) duodenum, with Km = 3.9 mM. The transcellular process is subject to down-regulation and is influenced by functional or nutritional factors such as age or calcium intake. The nonsaturable process, on the other hand, is not directly influenced by these or related events. Vitamin D therapy alters active calcium transport, but may lead to undesirable effects at other target organs, e.g., kidney or bone. An increase in calcium intake is the simplest method for increasing the amount absorbed. Future research may show whether paracellular pathway alterations are a practical approach to changing the amount of calcium absorbed by the nonsaturable process.     

Intestinal calcium absorption: a vitamin D-hormone-mediated adaptive response

The process of intestinal calcium absorption represents the mechanism for dietary calcium to enter into the physiological processes that contribute both to the skeletal growth of the organism and to the maintenance of calcium homeostasis (both intracellular and extracellular). Because there is a large variation worldwide in the availability of dietary calcium (300-1500 g/d for man) and because there is a changing physiological need throughout life (growth, puberty, pregnancy, lactation, and menopause) for absorption of 50-500 mg/d of dietary calcium, it is essential that the process of intestinal calcium absorption be adaptable and responsive to both the dietary and physiological circumstances. This article reviews the evidence that this adaptation process is largely orchestrated by the vitamin D endocrine system. In this model the steroid hormone 1,25-dihydroxycholecalciferol has been shown to stimulate intestinal calcium absorption by both genomic (receptor mediated) and nongenomic (transcaltachia mediated) mechanisms.     

Intestinal iron absorption: regulation by dietary & systemic factors

Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.     

The influence of dietary amino acids on lead absorption

Dietary supplements of about 5 g/kg of a number of amino acids increased tissue lead concentrations in newly weaned rats but decreased them in older rats. The retention of both oral and intraperitoneal lead was affected. The uptake of ²⁰³Pb by tissues was reduced when methionine was given in the diet over a period of 5 weeks or when it or ethionine was given by mouth 24 hr before the activity was measured. In the liver the fraction of the total activity found in the nuclei and mitochondria was increased by methionine, but in the kidney only the fraction found in nuclei was increased.     

The effects of dietary calcium and phosphorus on the retention and excretion of lead in rats.

1. Rats were given diets containing different amounts of calcium, phosphorus and lead. 2. Pb retention was greatly increased when the diets contained less Ca or P than the minimum estimated requirement of the rat. 3. The release of Pb already incorporated into the skeleton was inhibited by diets low in Ca but was not affected by diets low in P. 4. The retention of Pb given intraperitoneally was not affected by dietary Ca or P. 5. It can be concluded that dietary Ca and P influence the absorption of Pb by the gut and dietary Ca influences the metabolism of Pb in the bone. 6. There were changes in the distribution of Pb among the tissues due to changes of dietary Ca. 7. At low body concentrations, Pb probably affected skeletal growth.     

Meal effects on calcium absorption

The effect of coingestion of a meal on calcium absorption efficiency was investigated using Ca carbonate, milk, and a new Ca delivery system, CCM. Six experiments with 168 rats and two experiments with 46 normal young women showed that coingestion of a light meal of varied composition enhanced absorption efficiency from all three sources by 10-30% above levels achieved when the test load was ingested without other foods. The differences taken as a whole were highly statistically significant.     

Intestinal absorption of free and protein-bound dietary methionine in the rat.

Intestinal absorption of radioactive free and protein-bound dietary methionine (Met) and changes in plasma amino acids were observed after feeding Met-supplemented test meals. Plasma and gastrointestinal contents were collected from 15 minutes to 16 hours after feeding. Plasma amino acids were determined after ad libitum ingestion of diets containing free Met. Protein-bound Met in fresh egg white and free Met left the stomach at the same rate, but protein-bound Met in dried egg white and free Met were emptied from the stomach at different rates. Free Met was absorbed from the intestine more rapidly than protein-bound Met. Concentrations and molar ratios of various free amino acids in plasma changed briefly in response to Met-supplemented single test meals. Long-term changes were observed when Met-supplemented diets were fed ad libitum. Prolonged ingestion of supplemented diets may cause sustained alterations in the plasma amino acid pattern.     

Effects of lead exposure before pregnancy and dietary calcium during pregnancy on fetal development and lead accumulation

Millions of women of child-bearing age have substantial bone lead stores due to lead exposure as children. Dietary calcium ingested simultaneously with lead exposure can reduce lead absorption and accumulation. However, the effects of dietary calcium on previously accumulated maternal lead stores and transfer to the fetus have not been investigated. We studied the effects of lead exposure of female rats at an early age on fetal development during a subsequent pregnancy. We gave 5-week-old female Sprague-Dawley rats lead as the acetate in their drinking water for 5 weeks; controls received equimolar sodium acetate. This was followed by a 1-month period without lead exposure before mating. We randomly assigned pregnant rats (n = 39) to diets with a deficient (0.1%) or normal (0.5%) calcium content during pregnancy. A total of 345 pups were delivered alive. Lead-exposed dams and their pups had significantly higher blood lead concentrations than controls, but the concentrations were in the range of those found in many pregnant women. Pups born to dams fed the calcium-deficient diet during pregnancy had higher blood and organ lead concentrations than pups born to dams fed the 0. 5% calcium diet. Pups born to lead-exposed dams had significantly (p<0.0001) lower mean birth weights and birth lengths than controls. There were significant inverse univariate associations between dam or pup organ lead concentrations and birth weight or length. The 0.5% calcium diet did not increase in utero growth. Stepwise regression analysis demonstrated that greater litter size and female sex were significantly associated with reduced pup birth weight and length. However, lead exposure that ended well before pregnancy was significantly (p<0.0001) associated with reduced birth weight and length, even after litter size, pup sex, and dam weight gain during pregnancy were included in the regression analysis. The data demonstrate that an increase in dietary calcium during pregnancy can reduce fetal lead accumulation but cannot prevent lead-induced decreases in birth weight and length. The results provide evidence that dietary nutrients can influence the transfer of toxins to the fetus during pregnancy. If these results are applicable to women, an increase in diet calcium during pregnancy could reduce the transfer of lead from prepregnancy maternal exposures to the fetus.     

The effects of dietary lead content and food restriction on lead retention in rats

The effects of restricted food intake and of various dietary lead contents on lead retention¹ were studied in young rats. In three experiments the rats were given either unrestricted or restricted access to diets providing 200 or 400 mg lead/kg for 3 or 6 weeks. At the end of the experiments a sample of blood was taken and the rats were ashed. Lead was determined in blood and ash from the carcass. Food restriction always increased the retention of lead but not always the lead content of blood or carcass. The retention of lead was similar when the diet was supplemented with 50, 200 or 400 mg lead/kg. Lead supplementation at 200 or 400 mg/kg reduced food intake and growth but did not affect food conversion ratios. Blood lead was related to the rate of ingestion of lead. The effect of food restriction in reducing lead retention should be taken into account in interpreting the effects of lead exposure accompanied by dietary conditions which reduce appetite or food supply.     

The effects of dietary lead on ethanol-reinforced responding.

Sixteen adult male rats were presented with a diet containing no added lead (Group Control) or a diet containing 500 ppm inorganic lead (Group Lead) for 60 days. Subsequently, all animals were trained to lever press on an FR 1 reinforcement schedule for an ethanol reinforcer using a food-induction procedure where 20 g of food were presented to deprived animals 1 hr prior to the training session. Gradually, the daily food allotment was shifted to 15 min post-session and the ethanol concentration maintained at 6% (v/v). On a subsequent dose/response test, serial presentations of 1, 2, 4, 8, 16, and 32% ethanol reinforcement (v/v) were presented to both groups of animals. The results from the initial self-administration test using 6% ethanol as the reward outcome showed that Group Lead lever pressed at a significantly lower rate than Group Control. In addition, on the dose/response test control animals increased responding at a lower concentration, and then as dose levels continued to increase, began to decrease responding earlier than lead-treated animals. Apparently, sensitivity to ethanol effects is decreased by lead toxicity. The importance of these data for understanding other metal/alcohol interactions is discussed.     

Bone and gastric bypass surgery: effects of dietary calcium and vitamin D

OBJECTIVE: To examine bone mass and metabolism in women who had previously undergone Roux-en-Y gastric bypass (RYGB) and determine the effect of supplementation with calcium (Ca) and vitamin D. RESEARCH METHODS AND PROCEDURES: Bone mineral density and bone mineral content (BMC) were examined in 44 RYGB women (> or = 3 years post-surgery; 31% weight loss; BMI, 34 kg/m(2)) and compared with age- and weight-matched control (CNT) women (n = 65). In a separate analysis, RYGB women who presented with low bone mass (n = 13) were supplemented to a total 1.2 g Ca/d and 8 microg vitamin D/d over 6 months and compared with an unsupplemented CNT group (n = 13). Bone mass and turnover and serum parathyroid hormone (PTH) and 25-hydroxyvitamin D were measured. RESULTS: Bone mass did not differ between premenopausal RYGB and CNT women (42 +/- 5 years), whereas postmenopausal RYGB women (55 +/- 7 years) had higher bone mineral density and BMC at the lumbar spine and lower BMC at the femoral neck. Before and after dietary supplementation, bone mass was similar, and serum PTH and markers of bone resorption were higher (p < 0.001) in RYGB compared with CNT women and did not change significantly after supplementation. DISCUSSION: Postmenopausal RYGB women show evidence of secondary hyperparathyroidism, elevated bone resorption, and patterns of bone loss (reduced femoral neck and higher lumbar spine) similar to other subjects with hyperparathyroidism. Although a modest increase in Ca or vitamin D does not suppress PTH or bone resorption, it is possible that greater dietary supplementation may be beneficial.     

The influence of high dietary calcium and phosphate on lead uptake and release.

The effects of calcium and phosphate supplements on the retention of dietary lead and the loss of lead from the body were studied in young rats. There were three experiments in which rats were given a diet containing 200 or 400 micrograms of lead/g for 3 or 6 weeks. The diet contained adequate calcium and phosphate. Calcium and phosphate supplements were given alone or together. Lead uptake after a period of lead feeding was measured by analysis of the whole gut-free carcass. Lead loss was measured by a similar analysis after the rats had received diets containing lead and then diets free of lead. The uptake of lead from the diet was reduced by about half when either dietary calcium or phosphate or both was doubled. The rate of release of body lead was decreased by calcium supplementation.