An Evaluation of Liquid Vitamin-Mineral Supplement Technology
GERHARD N. SCHRAUZER, D.Sc. FACN, CNS

ABSTRACT

Liquid multivitamin-mineral preparations are gaining popularity among those who believe that liquid (or colloidal) nutrients are better absorbed from a liquid than when ingested in tablets or pills. Critics have argued that this claim is not supported by any studies-but is this really true? This article provides answers to this and other frequently asked questions about these products.

INTRODUCTION

ALTHOUGH VITAMINS AND MINERALS are cus­tomarily taken in solid (tabletted, cap­ suled, or chewable) forms, liquid preparations have recently become available and have rapidly found wide customer acceptance, based in part on the marketing argument that supplements in solution are better absorbed than those taken in solid form. Liquid supple­ments are as such are not new; the first were developed decades ago but were prescribed mainly for elderly persons, infants, and pa­tients with digestive problems. They were not in general use and did not become widely known. The recent upsurge of the popularity of liquid supplements started 10 years ago with the promotion of products designated as “plant-derived minerals” or “colloidal miner­als.” Unlike the conventional supplements, which as a rule use chemically defined com­pounds of single elements in solid form, the plant-derived minerals are offered in solution. They are promoted as being superior to con­ventional mineral supplements in that they contain not just the usual elements, such as iron or zinc, but instead virtually all elements, es­sential and nonessential, that are present in mineral-rich humic shale deposits. They con­tain iron and a number of essential trace ele­ments at nutritionally significant amounts, but many of the other elements listed on the labels are present at very low levels.

The popular acclaim of these preparations is difficult to rationalize on the basis of their min­eral content alone; if anecdotal reports are be­lieved, they appear to have additional healing or tonicizing effects and act somewhat like elixirs, the possible reasons for which will be discussed later. These liquid mineral extracts are also not new products; they were claimed to have been used as remedies by Native Amer­icans for centuries in regions of Utah where such humic shale deposits occur, and this is how they became known to white settlers in the region, one of whom started to market them some 75 years ago. Their continuing popular­ity among users is attributed primarily to the high bioavailability of the elements present in these extracts. However, it has been charged that this claim is unsupported by evidence; in addition, the chemical nature, composition, and safety of the extracts have been called into question (Schauss, 1997a, 1997b). Indeed, the various products that were being marketed ini­tially differed considerably in quality and com­position. After these criticisms, manufacturers standardized their products with respect to composition and purity, but the general uncer­tainty as to the nature and health value of these natural mineral extracts still persists. In a broader sense, this uncertainty extends to liq­uid vitamin-mineral supplements as a whole, and questions are still raised as to whether vi­tamins or minerals are indeed better absorbed from solutions than from tablets or whether any other advantages are offered by liquid preparations compared with conventional solid supplements.

The present account was prepared to address these questions without directly or indirectly promoting any specific line of products. At first, the bioavailability and absorption of liq­uid and solid vitamins and minerals is dis­cussed on general principles. Then, studies are reviewed in which liquid supplements were tested for against solid forms. Finally, the na­ture of the plant-derived mineral extracts is dis­closed and questions regarding their apparent efficacy, mechanism of action, and safety are addressed.

NUTRIENT BIOAVAILABILITY AND ABSORPTION

Bioavailability is defined as the proportion of a nutrient in food that can be absorbed and made available for use and storage; absorption is the physiological process that permits pas­sage of a dietary nutrient from the intestinal lumen to the body fluids and tissues (Bender, 1989). Because bioavailability is a prerequisite of absorption, solid supplements must be sol­uble in the stomach fluid. Most supplements are formulated to meet this requirement, but their increasing complexity makes solubility difficult to achieve.

The United States Pharmacopeial Conven­tion, Inc. (USP) has established manufacturing standards for vitamins and minerals with regard to quality, purity, potency, and the disso­lution and disintegration properties of supple­ments. However, only a few manufacturers state on the label that their products meet the USP requirements. It therefore has been sug­gested (Blonz, 1996) that consumers test ques­tionable pills themselves, by placing them in half a glass of vinegar, to simulate the acidic environment of the stomach. According to USP, calcium supplements should dissolve in 30 minutes, magnesium supplements in 45 min­utes; for vitamin E tablets, a 45-minute disin­tegration is acceptable, and for multivitamin and mineral combinations, a 60-minute disso­lution. However, for people with low stomach acid production, the in vitro dissolution tests may be of little value.

In the liquid supplements, the vitamins and 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, such as carbo­hydrates (glucose, lactose), 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.

Active transport

The vitamins and minerals in foods are nor­mally present at low concentrations. Accord­ingly, active transport systems have evolved to ensure their absorption. Active transport across the intestinal mucosa may require specific car­rier proteins and cofactors and is energy de­pendent (usually adenosine triphosphatase de­pendent) (Serfaty-Lacrosniere et aL, 1995). Carrier proteins are often highly substrate spe­cific, although in the case of metals the same carrier can bind several different metals with similar ionic radii and charges. Active trans­port is an important mechanism of homeosta­tic control and may be subject to adaptation­that is, it may increase in response to deficiency or decrease if a nutrient is supplied in excess. However, active transport mechanisms are subject to genetic damage and may change with age or in response to disease. It therefore is difficult to predict, on a case-to-case basis, to what extent a bioavailable nutrient is absorbed. As a general rule, the more of an actively trans­ported nutrient that is supplied, the less that is absorbed. This situation favors liquid supple­ments because, if taken as directed, they pro­vide the nutrients in lower concentrations than solid supplements do.

Facilitated absorption

The absorption of certain vitamins and min­erals is facilitated by endogenous carrier pro­teins or by exogenous factors acting as com­plexing agents. The endogenous carrier proteins are located on the two faces of the cell membrane and exist in two conformational states. Metal binding occurs first at one and then at the other site on the membrane (Serfaty­Lacrosniere et al., 1995; Stein, 1986). Facilitated absorption occurs mainly by diffusion and is not an energy-dependent process; the driving force is the concentration difference of the ion between the two sides of the membrane. In gen­eral, facilitated absorption is more rapid than simple diffusion, but it is limited by the carrier capacity and the amount of binding factor available. If a specific endogenous carrier or binding factor is not produced under patho­logical conditions, intestinal absorption of the nutrient may be negligible. In order not to over­whelm the available absorption capacity, vita­mins and minerals should be supplemented at low concentrations over a period of time rather than suddenly. These conditions are more eas­ily met with liquid than with solid supple­ments: The former are ingested in compara­tively high dilution, whereas the latter on ingestion may release the vitamins and miner­als at concentrations much higher than those normally encountered in foods and in excess of the available absorption capacity. Time-release supplements were developed to obviate this problem.

Absorption by passive diffusion

Simple or passive diffusion represents the simplest possible mechanism of absorption (Serfaty-Lacrosniere et al., 1995). It is an energy-independent process and occurs best from isotonic solutions. The degree of absorption de­pends on the concentration of the nutrient on both sides of the membrane and its relative sol­ubility in the lipid bilayer. Liquid supplements readied for ingestion are, or should be, near­isotonic solutions, so as to favor nutrient ab­sorption by passive diffusion. A solid supple­ment, in contrast, may dissolve in the stomach to yield an initially hypertonic solution. When this solution is passed into the small intestine, it is first diluted with body fluid, via osmosis through the intestinal membrane, until iso­tonicity is reached. Because of the attendant in­crease of intestinal content, peristalsis may be activated, resulting in gastric discomfort, diar­rhea, and diminution of absorption. In elderly subjects or patients with intestinal disorders, the normally spontaneous process of rendering an hypertonic solution isotonic may be gener­ally disturbed. For such subjects, special iso­tonic liquid feeding mixtures have been devel­oped.

Inhibitors of absorption

The ingestion of solid supplements with foods is sometimes recommended to increase bioavailability. However, foods may actually diminish the bioavailability or absorption of nutrients. For example, long-chain fatty acids from ingestion of lipids form insoluble calcium and magnesium salts, which are poorly ab­sorbed. In the liquid vitamin-mineral prepara­tions, the comparatively low solubility of the citrates of calcium and magnesium compounds results in the formation of suspensions. Bioavailability is not reduced, because these compounds readily dissolve when added to orange juice. Phytic acid (inositol hexakis­dihydrogen phosphate), a compound present in unprocessed whole grains and unleavened bread, forms insoluble complexes with iron, zinc, copper, calcium, and manganese and greatly reduces their bioavailability (Davies and Nightingale, 1975; Hallberg, et aI, 1987; Navert et al., 1985). Copper forms an insoluble sulfide when ingested with egg yolk (Schultze, et al., 1936). Dietary fiber, oxalic acid in veg­etables, and tannins in coffee and tea also in­hibit the absorption of iron and other minerals (Morck, 1983). Tannins form poorly absorbable, complexes with metals as well with vitamin Bl (thiamine) (Friedrich, 1987). Raw fermented fish contain an enzyme (thiaminase) that inac­tivates thiamine; thiamine absorption is also in­hibited by alcohol. Naturally occurring antag­onists of vitamin B2 (riboflavin), vitamin B6 (pyridoxal), and biotin are known. The uptake of vitamin K is inhibited by vitamin E (Friedrich,1987).

Adverse interactions in supplements

Solutions of the B vitamins are more stable in acidic rather than in neutral or alkaline so­lutions, which is one of the reasons why citric and ascorbic acids are added to the liquid vit­amin-mineral preparations. However, the re­sulting mixtures are extremely oxygen sensi­tive. To prevent loss of vitamins during manufacture and storage, liquid supplements must be protected from air as much as possi­ble; opened bottles should be kept refrigerated. Destructive oxidation reactions may also take place in powdered mixtures of minerals and vi­tamins and even in the finished tablets, thereby reducing the shelf-life of the products. Ac­cordingly, special precautions are taken during manufacture of the supplements, oxygen is ex­cluded where necessary, and reactive ingredi­ents either are not combined or are prevented from interacting through microencapsulation or the use of excipients. In some cases tablets with a layered structure are produced; the vit­amins typically form the central core, which is surrounded by mineral salts and a protective layer of calcium carbonate. Other manufactur­ers obviate this problem by offering packages of five or more tablets or capsules containing water-soluble vitamins, fat-soluble vitamins, and minerals separately.

BIOAVAILABILITY AND ABSORPTION OF VITAMINS

Many (but not all) of the water-soluble and fat-soluble vitamins are absorbed by passive diffusion when they are present at sufficiently high concentrations (Serfaty-Lacrosniere et al.,1995) (Table 1). At low, physiological levels the absorption of vitamins is often active, facili­tated, and cofactor dependent, which provides an argument against megadosing. As is well known, oral vitamin B12 is absorbed regardless of oral dose only to the extent that it is bound to intrinsic factor; impaired excretion of this factor by gastric mucosal cells results in B12 de­ficiency. The absorption of vitamin C (ascorbic acid) in humans is active and saturable. At dosages up to 180 mg/ day, 80-90% of the vi­tamin is absorbed; at 2,000 mg/ day, absorp­tion drops to 44%, and at 5,000 mg/ day, to 20.9% (Horning et al., 1980). The human or­ganism can maximally absorb 1,160 mg of ascorbic acid per day. Vitamin C is better ab­sorbed in a natural citrus extract containing bioflavonoids, proteins, and carbohydrates (Vinson and Bose, 1988). In therapeutic appli­cations, multiple smaller oral doses are in gen­eral preferable to single large doses. This was confirmed for vitamin C in a study wherein three divided doses per day caused a more sig­nificant increase of serum ascorbate levels than the same amount given in one daily dose (Vin­son et al., 1998).

Selenium is included in Table 1 because it oc­curs in foods, mainly in the form of seleno­methionine (Le., an organic rather than an in­organic form). Baker’s or Brewer’s yeast natu­rally converts selenium into selenomethionine and is widely used in supplements, although yeast-free selenomethionine-containing sup­plements are also available. Selenomethionine is absorbed like methionine, by active trans­port; its selenium is not immediately bioavail­able but becomes so after enzymatic degrada­tion. In some products, selenomethionine is replaced by sodium selenite or other inorganic selenium salts. Inorganic selenium salts are also added to yeast, which is then offered as “organic” even though it does not contain se­lenomethionine. Selenomethionine is compati­ble with vitamin C, but selenite is reduced by it to the bio-unavailable elemental selenium
(Schrauzer and McGinness, 1979). The use of selenite in solid or liquid nutritional supple­ments should therefore be discouraged; also, the need for accurate labeling of supplemental selenium products is apparent.

TABLE 1. INTESTINAL ABSORPTION OF VITAMINS AND OF, Fooo-FoRM ORGANIC SELENIUM (SELENOMETHIONINE)

Vitamin
A
D
D, E, and carotenes K1
K2 Thiamin
Riboflavin
Nicotinic acid Nicotinamide B6
Folic acid
Biotin
Pantothenic acid B12 (cobalamin)
C (ascorbic acid)
Se (selenomethionine)
Site of absorption
Proximal and distal
small intestine
Duodenum, jejunum
Duodenum, jejunum Proximal small
intestine Terminal ileum Jejunum
Duodenum
Proximal jejunum
Proximal jejunum
Not known
Jejunum
Proximal small
intestine
Ileum
Ileum
Small intestine

Mechanism of absorption

Facilitated (carrier-dependent) diffusion at low
concentrations, simple diffusion at higher concentrations
Absorption increases with fats; salts of bile acids increase
resorption Simple diffusion; fats and emulsification facilitate absorption Active transport; unsaturated fatty acids, vitamin E, inhibit
absorption Simple diffusion Synergistic absorption with sodium; conversion to
absorbable metabolites
Active transport at physiological concentrations, at higher levels by simple diffusion; thiamine at 10 times daily dose produces only minor increase of serum level because of rapid excretion
Absorption is probably regulated hormonally, with sodium acting synergistically (?) after conversion into coenzyme
form (flavine mononucleotide) in intestinal mucosa
Synergistic absorption with sodium (?), and simple diffusion Rapid intestinal absorption at all concentrations
Simple diffusion, facilitated by conversion into metabolites
(rat, hamster); pyridoxamine, pyridoxal and pyridoxine pass intestinal mucosal cells by passive diffusion; at low levels, a partial phosphorylation and dephosphorylation, transport by passive diffusion
Free folic acid is absorbed by simple diffusion at high
concentrations; tenfold daily dose is rapidly absorbed
Synergistic absorption with sodium; active absorption or by
diffusion (hamster) Probably primarily by simple diffusion Cobalamin complex with intrinsic factor (IF) is bound to specific receptors in ileum; the IF-cobalamin complex or free cobalamin is then transported into the mucosal cell
At physiological levels, active, carrier, and sodium­
dependent absorption that is saturable; in some
animals, absorption by diffusion
Active transport, similar to methionine

W. Friedrich, 1987, modified.

BIOA V AILABILITY AND ABSORPTION OF SELECTED MINERALS

Table 2 summarizes available data on the site and mechanism of absorption of essential min­erals and trace elements (Berthon, 1995). As may be seen, the absorption of metals is often subject to endocrine controL A separate dis­cussion of several selected mineral elements and of the so-called colloidal minerals follows.

Calcium

The most commonly prescribed calcium sup­plements contain calcium carbonate. Althoughcalcium carbonate is soluble in acids and there­fore should dissolve in the stomach, the solu­bilities of calcium carbonate-based supple­ments vary considerably (Blanchard, 1989). Because the failure to dissolve is in some cases caused by the compactness of the tablets, a dis­integration test in simulated gastric fluid under standardized conditions was introduced to as­sess calcium bioavailability (United States Pharmacopoeia, 1985). However, because this test measured only disintegration and not dissolution, it overestimated bioavailability. Therefore, since 1987, the official USP require­ment for labeling of calcium supplements has included a dissolution test, by which the tablets.

TABLE 2. INTESTINAL ABSORPTION OF ESSENTIAL MINERALS

 

Mineral	Site of absorption
Na,K	Small intestine
Ca	Small intestine
Mg	Small intestine
Fe	Duodenum and small intestine
Cu	Small intestine, duodenum
Zn	Jejunum, duodenum, colon
Mn	Duodenum
Cr	Jejunum, ileum, duodenum

Mechanism of absorption

Passive and associated with water absorption; regulation of sodium/
potassium balance in higher animals and humans occurs in the kidney
Uptake is regulated by parathyroid hormone, vitamin D, calcitonin,
phosphate; citrate, orotate, ascorbate increase Ca bioavailability; phytic
and oxalic acid decrease bioavailability.
Mechanism of absorption in animals and humans is probably related to
that of Ca, but in general less Mg is absorbed
Passive absorption facilitated by stomach hydrochloric acid, citric acid,
ascorbic acid, lactic acid, succinic acid, etc., inhibited by polyphenols,
phytic acid, coffee, tea, dietary calcium
Active transport with a diffusion component, facilitated under acidic
conditions, by citric and ascorbic acid; diminished by carbohydrates,
notably fructose, excess ascorbic acid, also by zinc
Active and carrier-mediated, inducible in rodents and humans
(metallothionein); absorption is increased by glucose, low-molecular­
weight compounds, inhibited by phytic acid, calcium, vitamin D
Absorption increased by low intestinal pH, but not specifically by
ascorbic acid; absorption inhibited by calcium
Facilitated diffusion, absorption very low; absorption is increased by
oxalate, amino acids, transferrin, albumin, starch, ascorbic acid;
absorption decreased by antacids, zinc, iron, vanadium must dissolve in 30 minutes to at least 75% in 0.10 mollL HCI at 37°C (Blanchard, 1989). An­other test, the vinegar disintegration test, has been developed to assess calcium bioavailabil­ity (United States Pharmacopoeia, 1987; Kobrin et a1., 1989). In this test, a single tablet is placed into an Erlenmeyer flask containing 150 ml of vinegar and is swirled vigorously every 5 min­utes until the tablet is completely disintegrated. In vinegar disintegration tests of seven com­mercial calcium carbonate tablets, three were found to have low calcium bioavailability. This result was confirmed by in vivo measurements of calcium absorption and excretion.

Because stomach acid production diminishes with age, elderly persons may be unable to uti­lize calcium as the carbonate. An effective car­rier for facilitated absorption of calcium is cit­ric acid, which may explain why calcium carbonate dissolved in orange juice shows gen­erally superior bioavailability (Whiting and Pluhator, 1992) and, under these conditions, does not interfere with iron absorption (Mehansho et a1., 1989). Other calcium com­pounds that are well soluble and provide bioavailable calcium include the orotate and the ascorbate. Calcium absorption and the in­corporation of calcium into bone are biochem­ically complex, hormonally controlled processes in which several additional trace elements and phosphate play contributory roles (Bucci, 1991). To this effect, more sophisticated liquid and solid calcium supplements have been for­mulated that contain calcium and magnesium as the citrates and orotates, microcrystalline hy­droxyapatite, and vitamin D, with boron and other trace elements believed to be working synergistically to improve calcium absorption and incorporation into bone.

Magnesium

Some studies indicate that soluble magne­sium compounds such as magnesium citrate are more bioavailable than magnesium oxide (Lindberg et a1., 1990). Magnesium absorption may be enhanced by the addition of a glucose polymer solution (Bei, et a1., 1986). Some stud­ies, however, indicate that the intestinal ab­sorption of magnesium is the same so long as it is free and in the ionized form (Lindberg et a1., 1990). Only about 21 % of the magnesium is normally absorbed through the intestine; ex­cesses after storage compartments are filled are excreted, about 70% via the intestine and 30% renally. The mechanism of intestinal absorp­tion of magnesium resembles that of calcium; physiological concentration and excretion are hormonally controlled. Excess magnesium stimulates calcium excretion, and excess cal­cium impairs absorption of magnesium. Min­eral waters containing magnesium and calcium as the bicarbonates provide good sources of both elements. In some liquid vitamin-mineral supplements, ocean-derived minerals, Dead Sea minerals, or minerals from the Great Salt Lake are added to increase the magnesium con­tent and to add additional naturally occurring trace elements. The magnesium is present in the form of the chloride, which is well absorbed from dilute solutions but acts as a cathartic if ingested in larger amounts.

Iron

Subclinical iron deficiency is widespread in the general population. In adults, migraine headaches, lack of appetite, aversion to eating meat, breathlessness on exertion, heart palpi­tations, brittle nails, constipation, cold sensi­tivity, sore tongue, and weak or fragile bones can be caused by iron deficiency. In children, growth retardation, pale complexion, un­healthy appearance, fatigue, depression, dizzi­ness, inability to concentrate or to think clearly, and irritability are caused by iron deficiency.

For the treatment of simple iron deficiency anemias, pills containing a high dose of iron, usually as the sulfate, are prescribed. Iron sul­fate taken in excess is toxic; in the home, it poses a serious health hazard, and accidental ingestion of an overdose, especially by infants, can be fata1. For some years, therefore, pow­dered elemental iron (Ferrum reductum) was used to treat iron deficiency anemias. Elemen­tal iron is less toxic than ferrous sulfate, but be­cause of its poor bioavailability 500 mg (ap­proximately 7.5 grains) must be taken three or four times daily after meals (The Dispensatory, 1995a). Even ferrous sulfate must be taken daily for months because so little of the iron is ab­sorbed. It may cause stomach upset and con­stipation, and patient compliance is often poor; children, especially, tend to refuse to take iron sulfate pills for any extended period. To obvi­ate the compliance problem in an experiment with preschool children aged 2-6 years, iron­fortified bread was given for 6 months; how­ever, this regimen failed to produce positive results. A significant increase of hemoglobin lev­els in the children resulted only when a small amount of iron (20 ppm Fe as ferrous sulfate) was added to the drinking water. At the con­clusion of the test, after 8 months of supple­mentation, hemoglobin levels increased from 10.6::!: 1.1 to 13.0::!: 1.1 g/dl, serum ferritin from 13.7 ::!: 8.9 to 25.6 ::!: 10.5 p,g/L (N = 31), and “no problems related to the (iron) salt ad­dition or to the children drinking the iron-en­riched water” occurred (Dutra de Oliveira et a1., 1994). Iron is discussed further in the sec­tion on colloidal minerals. Liquid vitamin-min­eral supplements contain vitamin C and vita­min A, which increase iron bioavailability and absorption, respectively.

Zinc, copper, manganese, chromium

The bioavailability and absorption of zinc, copper, manganese, and chromium are low­ered by dietary components (e.g., phytic acid, tannin, fiber, phosphate). Absorption is in­creased by certain amino acids, decreased by others. The bioavailabilities of ionic forms of these metals are mutually interdependent. Sup­plemental iron, for example, impairs the ab­sorption of zinc (Solomons and Jacob, 1981), copper (Haschke et a1., 1985), and manganese (Thomson et a1., 1971), whereas calcium may reduce chromium absorption (Seaborn and Stoecker, 1990). Ingestion of multiple minerals may provide assurance against imbalances in­duced by single elements. In solid supple­ments, the presence of calcium and magnesium may impair absorption of these metals. Vita­min C may decrease gastrointestinal absorp­tion of copper. More research is required on both solid and liquid supplements to establish the optimal concentration of these elements for supplementation.

Plant-derived liquid or colloidal minerals

Some of the liquid vitamin-mineral supple­ments contain aqueous extracts of minerals found in deposits in humic shales. The extracts contain predominantly the sulfates of iron, and aluminum; in addition, zinc, silicon, nickel, manganese, magnesium, lithium, calcium, boron, chromium, copper, and silicon and traces of 60 or more other elements are present, or claimed to be present, depending on the sen;­sitivity of the analytical method employed. In some extracts, traces of organic compounds such as humic or fulvic acids are detectable. The safety of these extracts became a concern after it was suggested that some could contain possibly radioactive or toxic elements such as strontium and aluminum (Schauss, 1997a, 1997b). These concerns have since proved to be unfounded with respect to radioactivity and the presence of unusually high levels of stron­tium. In our own tests, using a scintillation technique approved by the U.S. Environmen­tal Protection Agency, none of 10 extracts tested showed radioactivity above back­ground, and a previously quoted high value for strontium was actually that of sulfur.

The levels of aluminum in some of the ear­lier, more concentrated versions of extracts could exceed 4,000 ppm, but these have been lowered in most products to one third of that value or less. At current levels, 1 ounce of ex­tract provides 10-20 mg of aluminum, which is within the nutritional range. Aluminum is widely distributed in foods, from which a cer­tain amount is absorbed, and the absorption appears to occur in proportion with iron. Al­though iron is retained, excess aluminum is ex­creted, causing the adult human body invari­ably to contain only about 0.5 g of aluminum, compared with 4-5 g of iron. Several studies attest that aluminum may have beneficial or es­sential physiological functions in animals; past postulated links between oral aluminum intake and Alzheimer’s disease have been discredited (Watt, 1997).

Thus, recent comparisons of the levels of mineral elements in the subcortical region and the frontal cortex of the brains of AD patients give no evidence that Al is an etiological factor in AD. Instead, these studies revealed signifi­cant accumulations of calcium and zinc in the frontal cortex of AD brains, suggesting that mineral transport systems in the brain cells of AD patients are defective (Kienzl et a1., 1996).

Because the humic shale extracts contain sul­fates of iron and aluminum, they are weakly acidic and contain equilibrium amounts of free sulfuric acid and traces of colloidal metal hy­droxides. It was the presence of the latter that led to their marketing name, “colloidal minerals,” although most of the elements are actu­ally present in ionic forms. An extract may typ­ically contain 300 ppm of iron, predominantly as ferrous sulfate. One ounce of extract in 8 ounces of orange juice provides almost 10 mg of iron at a dilution that makes it both well tol­erable and highly bioavailable. This fact pro­vides a basis for the disputed promotional claim that the plant-derived minerals are 10-12 times more bioavailable than in their elemen­tal form. The fact that elemental iron has a low bioavailability is well known; the literature lists it as ranging from 0.5% to 2%. In contrast, the bioavailability of iron in the form of ferrous sul­fate is given as 12-16% (Auterhoff, 1968).

The presence of iron in the extracts could be responsible for some of their claimed beneficial effects: Iron supplementation in cases of sub­clinical iron deficiency often results in striking improvements of the general condition. How­ever, the extracts also provide nutritionally sig­nificant amounts of several other essential ele­ments. The extracts bear a close chemical resemblance to the iron sulfate-containing min­eral springs or “vitriol waters” found in Eu­rope. These have been described as possessing astringent, tonicizing, and antiseptic proper­ties. They were widely recommended at the turn of the 20th century for treatment of iron deficiency anemias and especially of chlorosis, the then common form of anemia occurring in young girls, because it was already known that dissolved iron is more bioavailable than that in conventional iron preparations (Tilenius, 1925). Vitriol waters were prescribed as tonics after acute diseases or blood loss; to treat exhaustion and fatigue; and for diseases of the spleen, liver, and kidneys, various chronic diseases, nervous disorders, “sciatica,” disorders of the thyroid gland, diseases of the mucous mem­branes, and so on (Tilenius, 1925). These claims may appear excessive or difficult to rationalize, but they were based on empirical observations made over the years by the local balneologists.

Today, similar claims are made by users of the “colloidal minerals” products. If one is will­ing to accept them as true, these apparent heal­ing effects cannot be attributed solely to the iron present. To rationalize them, it must be consid­ered that the preparations contain sulfates of iron and other metals, which causes them to be acidic as a result of the presence of equilibrium amounts of sulfuric acid. Dilute sulfuric acid, Acidum sulfuricum dilutum, was used for hun­dreds of years internally as a tonic and medi­cine for a wide variety of conditions-to pro­mote convalescence from protracted fevers, to reduce fatigue, to stimulate the appetite, to im­prove digestion, and to treat gastric hypoacid­ity, menopausal hot flashes, thyroid diseases, and so on. The administration of dilute sulfuric acid was recommended still relatively recently as a “constitutional agent” (Aschner, 1995). In U.S. pharmacies it was available in flavored al­cohol solution known as Elixir of vitriol or Acidum sulfuricum aromaticum (The Dispen­satory, 1995b), and in Europe as Elixir acidum halleri or Aqua rabelii (Schulz, 1903). The plant mineral extracts or colloidal mineral prepara­tions therefore may owe their apparent efficacy also to the presence of sulfuric acid. They could be regarded as natural versions of “elixirs of vit­riol.” Sulfuric acid, or sulfate, is the terminal product of the metabolism of sulfur amino acids. Sulfate is required for biosynthesis of the all-important chondroitin sulfates and for detoxification of physiological metabolites, nat­ural products, and pharmaceuticals, including adrenaline, thyroid hormones, phenols, and a wide variety of drugs. Sulfate may also detox­ify heavy metals such as lead and barium.

SUMMARY AND OUTLOOK

Because the industry is now offering both solid and liquid vitamin-mineral preparations, health professionals have a wider choice in searching for the right supplements for their patients. Solid vitamin and mineral prepara­tions have the obvious advantage that single or multiple nutrients can be prescribed and dis­pensed at accurate dosages. They are also eas­ier to ship and store, but, as we have seen, they may cause problems with respect to bioavail­ability and compliance. Liquid supplements contain the nutrients in a more highly bioavail­able form, are gentler to the stomach, and sometimes are more suitable than solid sup­plements, especially for children and elderly patients, as was shown specifically for iron. The liquid mixtures containing numerous vitamins and minerals are probably better suited for rou­tine general supplementation than for treat­ment of a defined deficiency. Those containing humic-shale or plant-derived minerals are ton­ics as well as supplements and therefore belong in a special category. In general, the prepara­tion of any supplement poses a challenge, and some of the newer liquid products need to be further refined and improved. However, the liquid technology is here to stay and offers op­portunities for numerous new products. It is hoped that further development of the liquid supplement technology will ultimately lead to a more balanced and economical use of vita­mins and minerals.

REFERENCES

Aschner, B. (1995). Technik der Konstitutionstherapie, ed 7.
(KF. Haug, Heidelberg) pp 52, 56, 120.
Auterhoff, H. (1968). Textbook of Pharmaceutical Chemistry,
ed 5. (Wiss. Verlagsges., Stuttgart) pp 85-86.
Bender, AE. (1989). Nutrient availability: Chemical and biological aspects. In Bioavailability “88.” D. Southgate, I. Johnson, G.A Fenwick, eds. (Royal Society of Chem­istry, Cambridge, UK) p. 3.
Bei, L., Wood, RJ., and Rosenberg, I.H. (1986). Glucose polymer increases jejunal calcium, magnesium and zinc absorption in humans. Am J Clin Nutr 44, 244-247.
Berthon, G. (1995). Handbook of Metal-Ligand Interactions in Biological Fluids Vol. 1. (Marcel Dekker, New York) Chapter 2.
Blanchard, J. (1989). Calcium and osteoporosis: Some caveats and pleas (editorial). Calcify. Tissue Int. 44, 67-68.
8Ionz, E. (1996). Food Section, The San Diego Union-Tri­
bune, Thursday, Dec. 5.
Bucci, L.R (1991). Osteoporosis treatment: Much more
than calcium. Today’s Chirop 20, 38.
Davies, N.T., and Nightingale, R (1975). The effects of phytate on intestinal absorption and secretion of zinc and whole body retention of zinc, copper, iron and manganese in rats. Br J Nutr 34, 243-258.
Dutra de Oliveira, J.E., Ferreira, J.B., Vasconsellos, V.P., and Marchini J.S. (1994). Drinking water as an iron car­rier to control anemia in preschool children in a day­care center. JAm Coll Nutr 13,198-202.
Friedrich, W. (1987). Handbuch d. Vitamine. (Urban and
Schwarzenberg, Baltimore).
Hallberg, L., Rossander, L., and Skanberg, AB. (1987).
Phytates and the inhibitory effect of bran on iron ab­
sorption in man. Am J Clin Nutr 45, 988-996.
Haschke, F., et al. (1985). Effect of iron fortification of in­
fant formula on trace mineral absorption. J Pediatr Gas­
troenterol Nutr 5, 768-773.
Homing, D., Vuilleumier, J.P., and Hartmann, D. (1980).
Int J Vitam Nutr Res 50, 818.
Kienzl, E., Jellinger, K., Wruss, W., Sorbager, S., and Puchinger, L. (1996). Distribution of individual ele­ments in Alzheimer disease brain tissue. In Metal Ions in Biology and Medicine Vol. 4. P. Collery, J. Corbella, J.L. Domingo, et aI., eds. Gohn Libbey Eurotext, Montrouge, France) pp. 617-619.
Kobrin, S.M., Goldstein, S.J., Shangraw, RF., and Raja, RM. (1989). Variable efficacy of calcium carbonate tablets. Am J Kidney Dis 14,461-465.
Lindberg, J.5., Zobitz, M.M., Poindexter, J.R, and Pak, c.Y. (1990). Magnesium bioavailability from magne­sium citrate and magnesium oxide. J Am Coli Nutr 9, 48-55.
Mehansho, H., Kanerva, RL., Hudepohl, G.R, and Smith, K.T. (1989). Calcium bioavailability and iron-calcium interaction in orange juice. J Am Coli Nutr 8, 61-68.
Morck, T.A (1983). Inhibition of food iron absorption by
coffee. Am J Clin Nutr 37, 416-420.
Navert, B., Sandstrom, B., and Cederblad, A (1985). Re­duction of the phytate content of bran by leavening in bread and its effect on zinc absorption in man. Br J Nutr 53, 47-53.
Schauss, AG. (1997a). Colloidal mienrals: Clinical impli­cations of clay suspension products sold as dietary sup­plements. Am J Nat Med 4, 3-10.
Schauss, AG. (1997b). An analysis of colloidal mineral
claims. Health Counselor 9, 60-62.
Schrauzer, G.N., and McGinness, J.E. (1979). Observations
on human selenium supplementation. Trace Substances
in Environmental Health 13, 64-67.
Schulz, H. (1903). Vorlesungen iiber die Wirkungen und An­
wendung der unorganischen Arzneistoffe, ed. (K.F. Haug,
Berlin) pp. 246-247.
Schultze, M.a., et al. (1936). Further studies on the bioavailability of copper from various sources as a sup­plement to iron in hemoglobin formation. J Bioi Chem 115, 453-457.
Seaborn, C. and Stoecker, B. (1990). Effects of antacid or ascorbic acid on tissue accumulation and urinary ex­cretion of chromium. Nutr Res 10, 1401-1407.
Serfaty-Lacrosniere, c., Rosenberg, I.H., and Wood, RJ.
(1995). The process of mineral absorption. In Handbook of Metal-Ligand Interactions in Biological Fluids, Vol. 1. (Marcel Dekker, New York) pp 322-330.
Solomons, N.W., and Jacob, RA (1981). Studies on the bioavailability of zinc in humans. Am J Clin Nutr 34, 475-482.
Stein, W.D. (1986). Transport and Diffusion Across Cell Mem­
branes. (Academic Press, New York).
The Dispensatory of the United States of America, ed 25.
(1955a). G.B. Lippincott, Philadelphia) p 721-722.
The Dispensatory of the United States of America, ed 25.
(1995b). G.B. Lippincott, Philadelphia) pp. 1373-1374.
Thomson, AB.R, et al. (1971). Interrelation of intestinal
transport system for manganese and iron. J Lab Clin Med
73, 6422.
Tilenius, O. (1925). Iron Springs etc. [German). In Biider
Almanach 1925. (Berlin). pp 203-205.
United States Pharmacopoeia. (1985). SXXl/NF XVI Sup­
plement 5. (U.S. Pharmacopoeial Convention,
Rockville, MD).
United States Pharmacopoeia. (1987). SXXl/NF XVI Sup­
plement 5. (U.S. Pharmacopoeia Convention, Rockville,
MD).
Vinson, J.A, and Bose, P. (1988). Comparative bioavail­
ability to humans of ascorbic acid alone or in a citrus
extract. Am J Clin Nutr 48,601-604.
Vinson, J.A, Roberts, K., Stonebrook, K., Jahner, D.K.W., and Berman, J.G. (1998). Comparative nutrient absorp­tion after daily supplementation with multivita­min/multimineral tablets in young adults. J Am Coli Nutr 17, 531.
Watt F. (1997). Berkeley Newsletter. June/July 1997.
Whiting S.J. and Pluhator, M.M. (1992). Comparison of in
vitro and in vivo tests for determination of availability of calcium from calcium carbonate tablets. J Am Coli Nutr 11, 553-560.

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