Factors with mechanism to promote calcium absorption
  • Bone is not only the important pillar of the body, but also the biological activities of organism. it is where calcium stores and metabolizes and plays a main role in maintaining the internal environment stability and balance.

    Calcium is the most abundant and active mineral elements in mammal (including cats and dogs) and the essential biological macro-elements.

    Puppies are born with calcium content close to 6g/kg of body weight while it increases to about 12g/kg when turns to adult. The calcium content in the kitten remains the same with the puppy when born but the weight would hit up to 15g/kg when step into adult. From the perspective of the demand of calcium, bones and teeth bear the predominant requirement in active period.

    Bone is not only the important pillar of the body, but also the tissue of physiological activities. it is the place where calcium stores and metabolizes and plays a main role in maintaining the internal environment stability and balance. Nutrition problems such as calcium deficiency easily occur due to long-term captivity feeding which violated pet growth and development regularity and way of foraging. Inadequate intake of calcium, not only affect the growth and development of young dogs and cats, but also affect bone health of adult dogs and cats, calcium absorption as well as calcium transportation. This paper expounds the mechanism of calcium absorption and the main factors to promote calcium absorption, thus to improve the pet calcium absorption conditions, which are afforded as theoretical basis and reference

    1. Calcium Absorption
    The calcium in the digestive tract is absorbed in the form of passive or active transport in the small intestine and then flows into the blood stream through the intestinal mucosa epithelial cells. Dietary calcium remains in the form of combination whereas the way being absorbed by body that calcium ionizes though gastric acid. Generally, calcium absorption is reckoned to happen in duodenum and upper jejunum in high acid environment. 
    1.1 Active transport
    Active transport of calcium follows by inverse electrochemical gradient, which reflects on the fact that calcium ion moves in direction from low concentration to high concentration, which requires consuming energy and involvement of carrier system and related enzymes. If the cell energy metabolism is restrained, the active transport of calcium will be suppressed. Active absorption of calcium is realized mainly by transcellular pathway and is completed by asymmetry columnar cells in the intestinal mucosa. After Calcium passes into the small intestine, vitamin D acts on the cavity surface membrane, causing calcium ion channels to open and leading calcium ions to diffuse across the brush border into cell sap and then under help of CaBP, vitamin D, on one hand, is absorbed and stored by mitochondria, on the other, is pumped into blood by basolateral membrane.

    1.2 Passive transport
    Passive transport of calcium is realized by liquid pressure difference, concentration and potential difference on both sides of the membrane in the form of diffusion and permeation. Unlike active transport, there is no energy consumption in the process of passive absorption, with its infiltration rate is directly proportional to the concentration difference, potential difference on both sides membrane liquid. Calcium passive transport mainly is realized by cells alternative pathway. When calcium ion concentration in enteric cavity is high, the ion will enter into blood by diffusion while passing paracellular with the absorption site being ileum. When concentration is low, calcium is mainly absorbed by transcellular pathway. Additionally, when enteric cavity calcium concentration increases, passive diffusion of transcellular pathway is activated too. transcellular pathway where Calcium ions are absorbed in intestinal tract is saturated, but paracellular route is unsaturated, which is explained that the higher the calcium concentration in the lumen is, the faster the calcium absorption of intestine relatively becomes.

    2. Main influence factors and its mechanism 
    2.1 Vitamin D
    As a precursor of the hormone - vitamin D2 and vitamin D3, catalyzed by hydroxylase by liver and kidney, transforms into active metabolites like 1, 25 (OH) 2 d2 and 1, 25 (OH) 2 d3 and become vitamin D with bioactivity. What’s more, 1, 25 (OH) 2 d3 is the highest active form of vitamin D, and is crucial hormone to adjust calcium and phosphorus together with parathyroid hormone (PTH) and calcitonin (CT), which directly participate in the bone metabolism. 
    VitD can promote CaBP generation in intestinal mucosal epithelial cells. Numerous researches illustrate that CaBP carrier may play a role in the process of intestinal calcium absorption and 1,25(OH)2D3 increases the synthesis of CaBP, which therefore verify that VitD could facilitate intestinal calcium absorption. The 1,25(OH)2D3 generated by kidney combining with VitD transport protein of plasma is carried to epithelial cell of intestinal mucosa, following the diffusion process to enter cells and then constitute a complex with cytosol receptor. Whenever it reaches to cell nucleus, it unites nuclear receptor together to relatively improve RNA polymerase activity, induce production of mRNA and generate CaBP and Ca-ATP enzymes via acting on nuclear chromatin. Moreover, VitD could boost the kidney tubules capability to resorb calcium and phosphorus and minimize their output, which benefit remaining of calcium and phosphorus in the body. Additionally, VitD promotes citric acid and calcium chelation to form compound, which then is transported to new bones to motivate bone formation and mineralization. It also stimulates osteoblast to synthesize and secrete osteocalcin as to participate in the regulation of calcium metabolism. Under engagement of PTH, 1,25(OH)2D3 stimulates osteoclast so as to enhance its activity and osteolysis, thus to free calcium and phosphorus from bone to release into the blood, hence improving the concentration of serum calcium, phosphorus and maintaining its metabolic balance through coordination of related hormone. VitD has dual nature on the skeleton, it can promote the new bone formation and calcification, and has the effect of boosting bone resorption enabling bone to constantly regenerate, which plays a very important role in the process of the unity of opposites of bone salt dissolution and deposition. VitD shortage is bound to affect the absorption and transfer of calcium and phosphorus in intestinal tract, and release of bone salt, which accordingly result in metabolic error of calcium and phosphorus and then generate immature ossein that does harm to mineralization of bone and hinder osteogenesis growth to cause skeletal lesion.
    2.2 Vitamin A
    VitA enrolling in Mucopolysaccharides synthesis in bone cell matrix, is basic substance to maintain normal function of osteoblast and osteoclast and ensure the normal metabolism of bone cells. Animals that lack in VitA manifest in ways of reduction the content of calcium in bone, obstruction of biosynthesis of mucopolysaccharides, dysfunction of bone generation, absorption and reconstruction as well as developmental bone malformation. Another important function of VitA is to maintain the health of the epithelial tissue. Lacking of VitA could cause renal tubular epithelial tissue damage and affect calcium absorption.
    2.3 Magnesium 
    Magnesium is important cation in the cell with extensive physiological function. As activator of enzyme system, magnesium involves in many important biochemical reactions in the body and plays key role in energy metabolism and substance metabolism. 50% of magnesium content in adult animal harbors in bone, which forms bone salts with calcium and phosphorus. Magnesium is the essential mineral element that promote bone growth and maintain bone cell structure and function. Deficiency or overabundance of serum magnesium could directly or indirectly influence calcium balance and bone metabolism. Magnesium lacking could lead to magnesium content decrease in bone, which, as a consequence, cause slow bone growth, decline of bone density and bone moisture and descending of bone intensity and bone stress. 
    Magnesium has a synergistic action with calcium but with inter-competition inlaid. When calcium is insufficient, magnesium could appreciably alternate calcium; when calcium is excessive in amount, magnesium absorption rate decreases, whereas organism requests increased demand of magnesium. However, when serum magnesium is excessive in amount, it would weaken calcium active transport and hold back the transformation from calcium phosphate to hydroxyapatite, delay its deposition speed, prevent from combining hydroxyapatite with bone protein and influence normal calcification of bone.
    2.4 Casein Phosphopeptides (CPP)
    In acidity condition, calcium salt solubility is relatively high, but reaching the end of small bowel, intraluminal condition may appear neutral or weakly alkaline, with calcium ions integrating anions of some macromolecules to create insoluble salt, which stops calcium absorption and utilization. CPP is a kind of polypeptide containing amino acid molecule which holds strong affinity with Ca2+ and could form soluble clathrate with Ca2+ under PH 7~8 thus to promote calcium absorption. Experiment indicates that CPP not only improves solubility of calcium outside the body and maintain stability of calcium solution, but also increase calcium deposition on thighbone to facilitate thighbone growth and prevent rickets. In addition, CPP could improve calcium storage in bones, strengthen calcium absorption and utilization of bones, weaken osteoclasts effects and inhibit resorption. Meanwhile, it could promote passive transport and absorption of unsaturated calcium in lower small tract while vitamin D only affects active transport and absorption of saturated calcium in upper small tract. 
    2.5 Proportion of Ca to P
    Calcium and phosphorus are important components of animal bones and teeth. Phosphorus is the constituents of ATP and creatine phosphate, involving in energy metabolism in the body; Phosphorus in the form of phospholipids promote absorption of lipid and fat-soluble vitamins; Phosphorus in the form of phosphate radical interlinks with metabolism of carbohydrate, fat and protein, etc.; The phosphate in the blood is also the important buffer substance in animal, which maintains acid-base balance in the body.
    Excessive phosphorus in the diet can facilitate calcium-phosphate compound deposition in enteric cavity. Animal model test evidenced that calcium-phosphorus ratio in the diet correlates bone loss. Intaking excessive phosphorus for long term could damage balance mechanism, change calcium metabolism as well as cause hypocalcemia and hyperthyroidisme secondaire. Animal absorbing calcium and phosphorus not only depends on their contents, but relates the proportion. Animals fed with high calcium and low phosphorus content feed or inverse proportion feed will consequently result in calcium and phosphorus deficiency, which leads to metabolic disorders. According to the feeding test, healthy intestinal tract of each animal usually embraces a premium calcium-phosphorus ratio. When calcium-phosphorus ratio in the daily ration is bigger or smaller than the optimum ratio, it could bring about calcium and phosphorus metabolic disorders. It is ideal and reasonable that calcium-phosphorus ratio should be 1.8:1 in dog food while 0.5~1.5:1 in cat food.
    2.6 Probiotics 
    Prebiotics, is also called bifidogenic factors, with its main function of optimizing balance of intestinal flora by promoting reproduction of intestinal probiotics. Numerous research has found that taking probiotics contained food could improve calcium, magnesium, iron and copper absorption capacity of animal under the mechanism that probiotics may be fertilized to generate organic acid, which results in pH value decrease and dissolve the compound constituted by intestinal calcium, phosphate and magnesium and thus to absorb. There is assumption believing that calcium is modified into calcium-hydrogen compound with low quantity of electric charge.

    In conclusion, appropriate and reasonable collocation of above substances could improve calcium and phosphorus absorption in intestinal tract and enhance bioavailability; the above substances could also facilitate regeneration of cartilage, protect health of bones and teeth, motivate skeletal growth, increase bone density and tenacity, adjust body calcium level and maintain normal serum calcium concentration respectively.
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