A Review of Mineral Absorption with Special

Consideration of Chelation as a Method to Improve

Bioavailability of Mineral Supplements
by James Gerber, MD

Mineral absorption from supplements has been a hotly contested issue in the supplement
industry. Companies naturally desire to provide the best products and gain market share by
promoting them as the best. This has led many companies to claim superior absorption from
particular formulations of mineral supplements. Understanding and validating some of these
claims has often been difficult, due to insufficient or conflicting research. This white paper will
attempt to shed some light on the controversy and establish the state of scientific knowledge
about mineral absorption from supplements.

Physiology of Mineral Digestion and Absorption

In order to understand the ability of different mineral supplements to enhance mineral

bioavailability, a brief review of the physiology of digestion and absorption as it impacts minerals
would be useful. Since most research on mineral absorption has been done on iron, calcium and
zinc, our understanding of this topic is limited primarily to these minerals.

Stomach digestion

The first significant stage of digestion occurs in the stomach, wherein hydrochloric acid (HCL) and
the protein-digesting enzyme pepsin are secreted. This stage of digestion impacts mineral
absorption in more ways than one.

1. Many minerals (as well as some vitamins) in the diet are bound to proteins, and protein
digestion in the stomach is a necessary step in releasing the minerals from the proteins they
are bound to. HCL assists protein digestion by causing protein molecules to unfold and
separate from other food components, and by activating the digestive activity of pepsin.
2. HCL also directly affects minerals by helping the separation process called dissociation,
wherein the positively charged mineral ion (e.g. Mg++, Ca++, Fe++, etc) becomes free from the
food component or supplement compound (e.g. MgO, CaCO3, FeSO4) that it was part of.

Low HCL levels in the stomach occur frequently in the elderly, in people with some types of
stomach disorders, and when any of several types of antacid drugs are used. This low HCL can
prevent minerals from separating from food or supplements. If mineral separation has already
occurred, low HCL can allow the minerals to recombine into compounds that are difficult to
absorb (more about this in another paragraph below).

Not all mineral compounds are similarly affected by low HCL, however.

1. Iron has two possible ion states, ferrous and ferric, and ferric compounds are much less
well absorbed when HCL is low compared to ferrous compounds.1 For this reason, most iron
supplements are made with ferrous iron (e.g. ferrous sulfate, ferrous fumarate, amino acid
chelates, etc).
2. HCL-blocking drugs can affect the absorption of iron, 2 and zinc, 3 but no information
about the effect of these drugs on other minerals is available.
3. Calcium absorption is lower in people with low HCL levels only when a calcium
supplement is taken without food, calcium taken with a meal is absorbed normally even in
these HCL-deficient individuals.4 5 6

So it appears that adequate HCL is often, but not always, required for optimum mineral
absorption.

Intestinal digestion and absorption

After food or dissolved supplements leave the stomach, additional digestive juices are secreted
into the mix by the pancreas and gallbladder. The pancreas mainly secretes digestive enzymes
that further break down proteins, starches and fats, and secretes bicarbonate that neutralizes the
stomach acid so that these enzymes will function optimally. Whereas HCL may have an important
role in mineral absorption, it is unclear whether pancreatic enzymes play any significant part in
this process.

The neutralization of stomach acid by pancreatic secretions into the intestine could have negative
consequences on mineral absorption because without the influence of acid, some minerals may
not remain dissociated and may bind with other components present in the intestinal contents,
rendering them unavailable for absorption.7 8 9 10 11 One way this problem can be avoided is for the
mineral to be surrounded by “ligands,” or weak binding agents, which will protect the mineral from
stronger binding agents, even in the absence of acid, yet allow normal absorption to occur. Table
1 summarizes the effects of known binding agents found in the diet.

Table 1. Dietary ligands (weak binding agents) and their affect on mineral absorption12

Improve absorption (minerals affected) Impair mineral absorption (minerals

affected)

Citrate (iron, zinc, copper, manganese) Phytate* (calcium, magnesium, iron, zinc,
selenium, chromium, manganese)

Ascorbate (iron) Oxalate** (calcium, iron, zinc, manganese)

Other organic food acids (iron, copper) Tannate*** (iron, zinc)

Cysteine-containing peptides (iron, zinc, Fatty acids (calcium, magnesium)

copper)

Histidine and other amino acids (zinc,

copper, chromium, manganese)

Heme (iron)
* Found in whole grains, legumes and nuts

** Found in spinach and some other vegetables, berries, nuts, tea, and chocolate

*** Found in tea and coffee

As the above table implies, dietary binding agents do not similarly affect all minerals. Notably,
several binding agents may impair calcium or magnesium absorption, but agents that improve
absorption of these two minerals have not been identified. To reiterate, binding agents that
improve mineral absorption do so usually because they protect the mineral from making stronger
attachments to other binding agents that would impair absorption, yet their weaker binding energy
allows the mineral to free itself when absorption is imminent.

In addition to helpful ligands typically present in the diet, others may be secreted in digestive
juices. Picolinic acid (picolinate) is a ligand found in pancreatic secretions that appears to
facilitate zinc absorption, and has become a popular ingredient in some mineral formulations for
this reason.13 14

The body limits mineral absorption

The body often controls mineral absorption into the intestinal wall and from there into the blood
circulation. This is done in order to allow increased absorption in times of deficiency or greater
need, but also to limit absorption to prevent overloading the body with minerals that can be toxic
or might disturb carefully regulated blood concentrations. This control exerted by the body often
places absolute limits on the percentage absorption that is possible for different minerals. For
example, growing children can absorb up to 60% of their dietary calcium, whereas adults average
only about 30% calcium absorption. The ability to increase supplemental mineral absorption by
designing “optimal” formulations can only succeed within the limits set by these body controls.
The following table shows typical mineral absorption levels at usual intakes by non-deficient
people, and formulation factors that may help optimize absorption.

Table 2. Typical mineral absorption and optimizing factors12 15 16

Mineral Absorption Optimizing factors

Calcium 25-35% Vitamin D

Magnesium 21-27% Vitamin D

Iron (non-heme) 5-10% Vitamin C, ligands

Zinc 33-41% Ligands

 Copper 30-50% Ligands

Selenium 50-80% Incorporation into

selenomethionine

Chromium 0.4-2.5% Vitamin C, ligands

Manganese 1-3.5% ??

Supplement Formulation Effects on Mineral Absorption

In the nutritional supplement industry, many claims are made for the superior absorption of
certain, sometimes proprietary, mineral formulations. To understand the issues debated
concerning these claims, it is necessary to answer the question, “What is necessary for optimum
mineral absorption from a supplement?”

1. At a minimum the tablet or capsule must disintegrate properly to release the mineral
compound in time for proper digestion and absorption. Studies of enteric-coated (timed-
release) supplements that have delayed disintegration suggest they are more poorly absorbed
compared to immediate release formulations.17 18 19 20 Solubility of the mineral compound is
usually assumed to be essential to absorption. However, solubility is typically measured
outside of the complex gastrointestinal environment (this is called an ex vivo measurement),
often by simply testing the compound in plain water or slightly acidic solutions. These
simplified methods may have little relevance to what occurs during gastrointestinal processing
of mineral compounds; while some studies find a correlation between solubility and
absorbability of some mineral supplements, 21 others do not.22 23
2. Ionization, or dissociation, which is the separation of the mineral ion from the mineral
compound (e.g. Fe+2 from FeSO4 or Ca+2 from CaCitrate), may or may not occur when a
soluble mineral compound dissolves in the digestive tract. In fact, it may not be desirable for
 such ionization to occur. This is because a free mineral ion is vulnerable to binding with
ligands, such as phytate or oxalate, that may impair absorption of the mineral, as described
above (see Table 1, right column). On the other hand, if a mineral was compounded with a
weak dietary ligand known to improve absorption of that mineral (see Table 1, left column),
presumably by protecting it from stronger binding agents, then it would be advantageous for
this compound to remain intact until the absorptive region of the intestine was reached.
Unfortunately, whether mineral compounds in supplements remain non-ionized through the
stomach phase of digestion has not been adequately investigated. One existing ex vivo study
determined that magnesium citrate, tested in acidic conditions resembling stomach digestion,
remained 65% intact as a non-ionized complex after dissolving.21 So it may be that certain
mineral compounds, such as citrates, have improved absorption in part due to their ability to
remain in the form of soluble complexes until absorption occurs, but more research is needed
to confirm this.

The question of chelates

“Chelated” minerals are among the mineral supplements touted for their improved absorption.
Before exploring the validity of such claims, the inconsistent use of the term chelate must be
addressed.

Science defines chelation more precisely than does the supplement industry. The scientific
definition of chelate is "organic chemicals that form two or more coordination bonds with a central
metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some
biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and
the magnesium-binding chlorophyll of plants." 24

Below is an illustration of chelates, the most relevant of which is [Fe(edta)],2- a chelate of two
molecules of edta surrounding a single atom of iron.

The National Nutritional Foods Association (NNFA) adopted a similar definition in 1996,
specifically to establish a standard for chelated minerals using amino acids as the organic binding
agents: “Metal Amino Acid Chelate is the product resulting from the reaction of a metal ion from a
soluble metal salt with amino acids with a mole ratio of one mole of metal to one to three
 (preferably two) moles of amino acids to form coordinate covalent bonds. The average molecular
weight of the hydrolyzed amino acids must be about 150 AMU (Atomic Mass Units) and the
resulting chelate must not exceed 800 AMU. The minimum elemental metal content must be
declared. It will be declared as a METAL amino acid chelate: e.g. Copper amino acid chelate 25

Below is an example of a reaction that results in a chelate of one atom of copper with two
molecules of glycine:

In contrast to the definitions above, dietary supplement industry often uses the term chelate to
refer merely to any mineral compound formulated with amino acids or other organic acids,
whether or not the compounds have been proven with special analytical tests to possess the
scientific properties of a chelate.

Assuming that a mineral supplement is a true chelate, what is the evidence that this form is
superior to other mineral supplements? The foremost proponent of the superiority of true mineral
amino acid chelates, is Albion Laboratories of Clearfield, Utah, which develops, patents, and
markets these chelates as ingredients for dietary supplements and fortified foods.26 Albion claims
that the superiority of mineral amino acid chelates lies primarily in the improved absorption of
such molecular configurations over other mineral compounds. This improved absorption is
thought to occur by one or more theoretical mechanisms:27

1. Mineral amino acid chelates might not dissociate into free mineral ions in the stomach or
intestine, preventing interactions with inhibitory dietary ligands and binding agents such as
phytate and oxalate. Also, an undissociated compound may be less likely to cause
gastrointestinal irritation in sensitive people.
2. Mineral amino acid chelates might be absorbed intact by amino acid absorption
pathways, which allow higher percentages of absorption than the usual mineral absorption
pathways.

Either or both of the mechanisms described above could help minimize the competition for
absorption known to occur between certain pairs of minerals when they are both present in the
intestine.

Research on iron amino acid chelate

The absorption and nutritional value of mineral amino acid chelates has not been scientifically
studied in humans, with one exception – Ferrochel – a patented Albion product with the chemical
name iron bis-glycine chelate. The handful of published human studies on Ferrochel gives some
indication of the potential for chelated minerals to deliver benefits not possible with other mineral
compounds.

Most tests of Ferrochel absorption have compared it to ferrous sulfate, the most common dietary
iron supplement. Moreover, these absorption studies were typically carried out by mixing the iron
compounds with various foods, in order to test the value of the compounds as ingredients of
fortified grain products, infant formulas, etc. According to unpublished research reports by Albion,
Ferrochel was absorbed up to five times better than ferrous sulfate when given to adult males in a
cornmeal porridge, and 59% better when given to adults as tablets.27 Published research has
reported Ferrochel to be about two times better absorbed than ferrous sulfate when given in
bread to adults, some of whom were iron-deficient,28 and about four times better absorbed when
given to adult males in a cornmeal porridge.29 However, no difference between these iron sources
were found when used in weaning foods for 9-month old infants,30and no difference in absorption
between Ferrochel and ferrous ascorbate was found when the compounds were given in water to
adult women.31

Albion claims that chelated iron is absorbed by a pathway different from how other forms of iron
are absorbed. However, a recent study showed that iron bis-glycine chelate (not identified as
Ferrochel) influenced the absorption of ferrous sulfate in a way suggesting that iron chelates are
absorbed by typical non-heme iron pathways.32 The investigators concluded that iron chelates are
more bioavailable than other iron forms because they are protected from absorption inhibitors that
are typically present in the intestine when iron compounds are mixed with food.

From the above evidence, it appears that the primary benefit of mineral amino acid chelates may
be to improve absorption when these compounds are used in or taken with foods containing
absorption inhibitors. Used in water, no advantage of chelates was found, but unfortunately no
absorption research involving tablets or capsules taken away from meals has been published.
However, another avenue of human research has examined the treatment of iron-deficiency
anemia with chelated iron versus ferrous sulfate supplements. Anemic and malnourished infants
and young children given Ferrochel in syrup for four weeks had similar improvements in
hemoglobin levels but better improvements in levels of stored iron compared to infants receiving
ferrous sulfate.33 Apparently, Ferrochel allowed more rapid restoration of iron stores during the
short four-week treatment. In another trial, anemic adolescents were given tablets to supply 30,
60, or 120 mg/day of iron from Ferrochel or 120 mg of iron from ferrous sulfate.34 These tablets
were to be taken either with breakfast or supper. At the end of four weeks, hemoglobin was
similarly improved in all groups while ferritin improved in all but the group receiving the lowest
amount of Ferrochel. These investigators concluded that lower doses of Ferrochel obtained
similar results to higher doses of ferrous sulfate over the short-term treatment. While these
studies suggest anemic people may respond faster to chelated iron than to ferrous sulfate, there
remains no evidence that chelated iron is superior to forms of iron other than the sulfate, or that
chelated iron would perform better when taken in tablets or capsules away from food.

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