Here's my question then:
Many companies make Cal/Mag/Zinc tablets...
why? Doesn't the Cal interfere with the Zinc?
That's a good question and that's why I wouldn't use a combination supplement like that. Vitamins A & D however, are known to help with calcium absorption. Like I said before, it's very complex and there are a lot of variables and that's why we can't get all anal about it. Maybe some of this will help explain (or confuse):MINERAL ABSORPTION:
Absorption
Absorption is the rate at which and the process by which molecules and atoms from the environment enter the interior of the organism via passage across (or around) the lining cells of the gastro-intestinal tract. Absorption can occur all the way from the stomach to the rectum, although the small intestine is the organ most importantly involved in absorption.
Absorptive efficiency for many nutrients, notably iron, calcium and zinc, is governed by homeostatic feedback regulation. When the body stores are too low, the intestine up-regulates the avidity with which the intestine takes up the nutrient. When the body reserves are adequate or increased, the gut down-regulates the nutrient's uptake. At a molecular level, this regulation can be expressed by the control of intraluminal binding ligands, cell surface receptors, intracellular carrier proteins, intracellular storage proteins, or the energetics of the transmembrane transport.
Bioavailability
Bioavailability refers to the extent to which a nutrient reaches its site of pharmacologic action. For practical purposes, this definition includes the extent to which the nutrient reaches a fluid (e.g. blood) that bathes the site of action and via which the nutrient can readily reach the site of action. The bioavailability of a mineral depends directly on the extent to which the mineral is absorbed and distributed to the site of action and depends inversely on the extent to which it is metabolized and excreted prior to arriving at the site of action. (1620). It is necessary to consider the factors that affect absorption in order to determine the relative bioavailability of nutrients in different forms.
Factors Affecting AbsorptionCurrent knowledge on intestinal absorption of nutrients includes multiple factors that can affect absorption. Physiochemical processes that influence both the extent and the rate at which minerals cross the mucosal barrier and enter the bloodstream influence absorption. The following table lists factors that specifically enhance absorption of an orally administered nutrient:
Factors That Enhance the Extent and Rate of Absorption of an Orally Administered Nutrient[xiii][13]
Lack of complex formation with diet ingredients
Maintenance of chemical stability at stomach/small intestine pH
Presence of a specific transporter
Small size for transportation with bulk water flow
Lipid solubility-nonionized at local pH
High circulation to the site of absorption, to maintain concentration gradient
Appropriate stomach-emptying rate
Low small intestinal motility
Moreover,
the clinical study of absorption is complex and potentially misleading. For example, a
bsorption data derived from giving pulse doses of a miniscule quantity of an element in fasting subjects may not accurately reflect the real life situation in which individuals consume larger amounts in diets full of inhibitory and/or accelerating factors (i.e., phytates[xiv][14], fiber[xv][15], ascorbic acid[xvi][16], tannins[xvii][17], and other minerals[xviii][18]).[1][a] In contrast, mineral absorption may be understood through basic principles of biochemistry and physical chemistry. [xix][19]
Mechanisms of Absorption
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. Intestinal absorption is a key regulatory step in mineral homeostasis. Mineral homeostasis is the body's physiologic efficiency in absorbing the level of minerals the body requires from those minerals that are available to it.
Active transport of minerals is an important mechanism of homeostatic control. The minerals in foods are normally present at low concentrations. Active transport mechanisms have evolved to ensure their absorption. In general, there is an inverse relationship between mineral availability and absorption. Active transport of minerals increases in response to a mineral deficiency or decreases if a mineral is in excess. [xx][20]Thus, the more of an actively transported nutrient is supplied, the less that is absorbed. For example, feeding a diet low in calcium results in an increase in intestinal calcium absorption. This adaptive mechanism is caused by a PTH-mediated stimulation of 1,25-dihydroxyvitamin D synthesis, the active vitamin D metabolite that increases the rate of transcellular active calcium transport in the intestine.[xxi][21]
III. EVIDENCE THAT MINERALS IN COLLOIDAL FORM ARE MORE ABSORBABLE THAN MINERALS IN SOLID FORMS
A. Colloidal Minerals
Liquid preparations of minerals are known as "colloidal minerals." A "colloid" is a substance dispersed in particle size large enough to prevent or delay passage through a semipermeable membrane, but small enough to remain in suspension in a liquid or gas.[xxii][22] Colloids consist of very tiny particles that are usually between 1 nanometer and 1000 nanometers in diameter and that are suspended in a continuous medium, such as a liquid, a solid, or a gaseous substance.[xxiii][23]
The surface area of colloidal particles is very large. Particles may be electrically charged and have stabilizing agents added to prevent precipitation. Most are negatively charged but this varies between different colloid types.[2] The charges are particularly important for attracting water molecules and cations. The enormous surface area and charged sites on colloids attract and bind many biologically active substances. Another advantage of minerals in colloidal form is that the bound substances are able to withstand enzymatic attack.[xxiv][24]
The ionic form of minerals is important for mineral absorbability. Colloidal minerals from humic shale extracts predominantly contain sulfates of iron and aluminum and traces of metal hydroxides. Many of the minerals in humic shale extracts are present in ionic forms. This may make it easier for them to cross cellular membranes. Mineral bioavailability is facilitated by the way in which metals cross the intestinal mucosa. A variety of conditions may affect metal transport across the intestinal mucosa. These factors can act at the brush border membrane, within the cytosol, and at the basolateral membrane. Metal ions, probably bound to intracellular ligands, cross the cytosol and are extruded across the basolateral membrane into the portal circulation. Once a metal ion enters the enterocyte, it may be used by the cell for its own metabolic needs or released in the circulation for the metabolic needs of other tissues. Because colloidal minerals do not have to undergo disintegration and dissolution, in contrast with minerals taken in the form of tablets and capsules, under applicable principles of biochemistry they are said to have enhanced-absorption capability, i.e. absorbability.[xxv][25]
This absorbability is evident in solubility. For example, small-molecular weight ligands, such as amino acids and other organic acids, can increase solubility and facilitate absorption; In liquid supplements, minerals are already dissolved and therefore are immediately bioavailable. Furthermore, the liquid supplements usually are acidic; specifically, they are formulated to contain citric acid, ascorbic acid, and other substances that increase the bioavailability of minerals,[xxvi][26] such as carbohydrates (glucose,[xxvii][27] lactose[xxviii][28]), polyols (sorbitol), amino acids (arginine, lysine), vegetable gums, peptides, and emulsifying agents.
Solid vitamin-mineral preparations instead contain inert excipients and are usually buffered so as not to cause gastric discomfort on ingestion, although this may reduce mineral bioavailability.[xxix][29]
The bioavailability of a mineral in the body is governed by multiple factors, including body stores, hormonal regulation, the chemical form of the nutrient, and concomitant nutrient intake. There are few controlled clinical studies that examine the composition, efficacy, absorbability, or other properties of mineral supplements. There are, however, biochemical reviews of the properties of colloidal minerals that conclude that they are more bioavailable than minerals in other forms. [xxx][30] That conclusion is consistent with the applicable principles of biochemistry discussed above.
B. The Form of a Mineral Affects Absorption
The chemical form of a mineral is an important factor in its absorption. Although few studies have been done comparing absorption differences among mineral supplements, there is biologically plausible evidence that the form in which minerals are ingested affects absorption.[3][c] ,[xxxi][31]For example, in one study of bioavailability, when glucose polymer was perfused on a 30-cm segment of jejunum for 60 minutes, net calcium absorption increased by fourfold (95 vs. 488 mumol/30 cm/h), and net jejunal uptake of magnesium (393 mumol/30 cm/h) was observed. In addition, co administration of glucose polymer doubled net zinc absorption (13 vs 29 mumol/30 cm/h). These results suggest that glucose polymer may have potential as an agent to significantly enhance mineral absorption.[xxxii][32]
In contrast, the properties of minerals in solid forms have an impact on their bioavailability. For example, the particle size, surface area and solubility of a substance affect its dissolution rate.[xxxiii][33] A number of studies involving solid dosage forms of drugs have demonstrated that the gastrointestinal absorption of these forms is often dissolution rate limited.[xxxiv][34] Thus,
the dissolution rate is important for measuring the absorbability of a mineral. There are a number of manufacturing variables that may also affect the release characteristics of minerals in a tablet, including tablet compression force, the type and amount of excipients, and coating materials.[xxxv][35] Thus, the availability of a mineral in a solid dosage form is a function of its dissolution in the body into a liquid form.[xxxvi][36] Once dissolved, the minerals from a solid dosage are only then available for absorption. Thus, the liquid form is in this sense superior.
The bioavailability and absorbability of minerals in foods is similarly complicated as minerals in solid dosage form.
The composition of foods and beverages determines the chemical form of a mineral component.
In many solid foods, elements are not free, but firmly bound in the food matrix. They can be in covalent association with a protein, as in metalloenzymes, or in electrochemical chelation arrangements to a non-specific binder. Chelated forms of minerals may interact with other minerals to reduce absorbability.[xxxvii][37] For example, metallic iron in food is poorly assimilated because it must be oxidized to Fe (III) and then reduced to Fe (II) while still in the upper small intestine, before it is absorbed. Whatever fraction of the metallic iron becomes oxidized , at any level of the intestinal tract, is likely to be chelated by phytate in cereal and thus be rendered nonabsorbable.[xxxviii][38]
Absorption of supplements is improved when they are taken with food, perhaps by slowing gastric emptying and thereby extending the time in which the mineral-containing chyme is in contact with the absorptive surface.
However, some foods may actually diminish the bioavailability or absorption of nutrients. For example, several plant constituents form indigestible salts with calcium, thereby decreasing absorption of calcium. In addition, long-chain fatty acids from ingestion of lipids form insoluble calcium and magnesium salts, which are poorly absorbed. Protein rich foods also contain phosphorus, which reduces calcium absorption.
Commercial supplements of minerals are available in a wide variety of forms. The time required for absorption affects their absorbability. These include isolated compounds such as inorganic salts, organic salts, amino acid chelates and a yeast form. Bioavailability of trace elements has been studied in long-term animal supplementation (3-4 weeks) studies by measuring the trace element in liver, blood, serum or plasma and comparing the slope of the dose-concentration plots. A preliminary depletion is usually performed using trace element deficient food. In short-term experiments, the area under the blood, serum or plasma concentration-time curve is used to compare bioavailabilities after a single dose of the test substance is given. In laboratory studies, examination of the blood concentration-time curves for short-term human experiments involving selenium, zinc and copper revealed that the yeast form was more slowly absorbed, i.e., took longer to reach its maximum concentration, and was thus more bioavailable.[xxxix][39]
This is analogous to the situation of trace elements in foods that have been shown to be more slowly absorbed than the isolated salts of the trace elements. Thus, because minerals in colloidal form are at lower concentration than isolated salts of trace elements, they may be more slowly absorbed. Since low concentration and slower absorption rates enhance absorption, the bioavailablity of colloidal minerals can be expected to be superior to that of minerals in other forms.
Furthermore, because minerals in colloidal form do not have to go through dissolution or disintegration as solid tablets do, and have particles that are small in size with a large surface area, the colloidal mineral ingested can be expected to be more available for absorption.
C. Clinical Evidence That Mineral Supplementation in Colloidal or Liquid Form Are More Absorbable Than Minerals in Solid Form
Further evidence that a liquid medium may be a superior vehicle for mineral absorption comes from clinical studies of calcium and magnesium supplementation and their deficiency.
The efficacy of commercially available brands of calcium carbonate tablets on mineral metabolism has been studied.[xl][40] Formal investigation of the bioavailability of this product revealed it to have impaired disintegration and dissolution and a lack of clinical efficacy.[xli][41] Solubility of minerals is an important consideration in absorption. Most people absorb calcium better from calcium citrate than from carbonate because calcium citrate is soluble in water. The citrate form is also considered safer and better tolerated.
Preparing salt forms with improved water solubility can enhance the bioavailability of calcium.[xlii][42] Presumably this occurs because the dissolution and ultimately the rate and/or extent of absorption are increased. Because calcium is reported to be absorbed in its ionic form the potential impact of the salt form on bioavailability is obvious. [xliii][43] The problem of absorbability has led to the development of other forms of mineral supplements that seek to avoid the disadvantages associated with solid tablets.
Therapies to correct calcium deficiency recommend a liquid medium for greater absorbability. Of the therapies approved for the prevention or treatment of postmenopausal osteoporosis in the United States (which include hormone-replacement therapy, the selective estrogen-receptor modulator raloxifene, calcitonin, and the oral bisphosphonates alendronate and risedronate), the bisphosphonates are the only medications that have been shown in large randomized trials to reduce the risk of hip fracture. Bisphosphonates have low oral bioavailability and can cause esophageal inflammation or, rarely, ulceration. Thus, when taking alendronate or risedronate, the patient must be upright, have an empty stomach, drink a full glass of water, and remain sitting or standing and eat nothing for 30 minutes.[xliv][44] This therapy recommends that oral ingestion of a liquid medium, as in colloidal minerals, increases absorbability of minerals.
Another study found that the mineral form with the greater solubility had the greater bioavailability. This study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. The solubility of 25 mmol magnesium citrate and magnesium oxide was examined in vitro in solutions containing varying amounts of hydrochloric acid (0-24.2 mEq) in 300 ml distilled water intended to mimic achlorhydric to peak acid secretory states found in the small intestine. Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion (24.2 mEq hydrochloric acid/300 ml). Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Reprecipitation of magnesium citrate and magnesium oxide did not occur when the filtrates from the solubility studies were titrated to pH 6 and 7 to stimulate pancreatic bicarbonate secretion. Approximately 65% of magnesium citrate was complexed as soluble magnesium citrate, whereas magnesium complexation was not present in the magnesium oxide system. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load. The increment in urinary magnesium following magnesium citrate load (25 mmol) was significantly higher than that obtained from magnesium oxide load (during 4 hours post-load, 0.22 vs 0.006 mg/mg creatinine, p < 0.05; during second 2 hours post-load, 0.035 vs 0.008 mg/mg creatinine, p less than 0.05). Thus, magnesium citrate was more soluble and bioavailable than magnesium oxide. [xlv][45]
Conclusion
While the ultimate absorption of minerals by the human body is dependent upon numerous factors including homeostasis, body stores, and hormonal regulation, the absorbability of minerals (their availability for absorption) is also affected by the form in which the minerals are ingested. Minerals in solid forms such as in solid dosage supplements and in foods must be dissolved and disintegrated prior to being available for absorption. Principles of biochemistry show that minerals in a liquid medium, or in soluble acids, i.e. colloidal minerals, can be expected to be more absorbable due to their smaller size, larger surface area and relative charge. The solubility of a mineral has been shown to enhance its bioavailability. Thus, there is scientific evidence that colloidal minerals may be more efficient, a preferred vehicle for absorption, than minerals in solid forms.
