Chelated minerals

Some chelated minerals tend not to break apart during digestion, forcing the metal mineral ion to go where its chelating "partner" goes

What is a chelated mineral?

Reference: https://www.wattagnet.com/articles/410-chelates-clarity-in-the-confusion

What is a "chelate" in simple terms: A chelate means to create a ring-like complex where a metal ion grabs and bonds to another ion or organic molecule. Chelated mineral supplements, usually with the mineral bonded to an amino acid, are touted for their improved absorption since the  mineral tends not to break off from its "partner" until it is absorbed across the intestinal wall.

• A COMPLEX is formed when a metal ion reacts with a molecule or ion (usually an anion), called a LIGAND (Latin:ligare - to bind), that contains at least ONE DONOR ATOM (nearly all non-metallic elements, such as carbon, oxygen, nitrogen, hydrogen or sulfur) DONATING BOTH OF THE ELECTRONS OF A BONDING ELECTRON PAIR to the metal ion (called a COORDINATE COVALENT bond since both of the shared electrons are donated from the same atom; note that in a normal covalent bond, each atom in the bond donates an electron ). With only ONE DONOR ATOM, the ligand is called a MONOdentate ligand, having only a single pair of electrons to donate to a metal ion. MONOdentate ligands include: hydroxide (OH^-), Ammonia (NH₃), water, carbon monoxide, chloride, fluoride, iodide, and bromide ions.
• A complex is called a CHELATE (Greek: chele - a lobster claw) when the metal ion bonds to an ion or ORGANIC molecule ligand via TWO OR MORE DONOR ATOMS forming a "RING STRUCTURE" (called a heterocyclic ring) - with each atom "grasping" the metal ion. Having more than one bond to the metal, the ligand is called a POLYdentate ligand, which, depending on the specific metal and ligand, can produce a molecule with enough STABILITY to protect the mineral against being separated from its bonding "partner" in the digestive process, by making it harder for hydrochloric acid in the stomach and/or pancreatic enzymes to break down (dissociate) the chelated molecule. Note that a chelate complex can have a positve, negative or neutral charge depending on the charges of the central metal ion and the coordinated ligands.

Complexes resulting from coordinate bonds with a chelating ligand are usually more thermodynamically stable than complexes with NON-chelating ligands

ORGANIC ACIDS (including AMINO ACIDS), SMALL PEPTIDES (and some other organic molecules, such as polysaccharides) can form CHELATES with their heterocyclic rings  (noting that some chelations have more stability than others - see below) - amino acids form chelates by forming a ring structure via multiple coordinate covalent bonds Eg. Attaching the two ends of an amino acid (an oxygen atom of its carboxylic group end and the nitrogen atom of the amino group end) to the metal mineral ion. Small peptides from protein digestion also have at least two functional groups (amino and hydroxyl) to form a ring with a metal mineral ion.

• A stable heterocyclic ring formed by amino acid or small peptide ligands (as in food) is likely to be bioavailable  - since the molecule can be absorbed intact via an amino acid transport channel (thereby promoting optimal mineral absorption during digestion).
• Too many covalent bonds in a chelated molecule can prevent the digestive system from accessing specific minerals  - Eg. phytic acid (an organic acid) has 6 covalent bonds, which the digestive system is unable to break down, and these molecules and their minerals will be eliminated from the body as waste.

Example chelated minerals - in the diagram below, "M" represents a metal mineral. Gluconate, citrate and tartrate are organic acids, glycine is an amino acid (a specific organic acid - the building block of proteins).

Chelated minerals found in nature.   Some examples are magnesium-binding chlorophyll  (a plant can synthesize chlorophyll using the amino acid glycine), vitamin B12 (contains cobalt), iron-binding haemoglobin and cytochrome (contains iron); upon entering a plant from the soil, a metal mineral will form chelates with organic acids, such as citrate, malonic and gluconic acids and some amino acids.

Chelates can also be produced under controlled conditions - by reacting inorganic mineral salts with, for example, an enzymatically prepared mixture of amino acids and small peptides;  the transition metals (Eg zinc, copper, iron, manganese) can best form stable coordinate covalent bonds with amino acids and peptides, but non-transition metals (Eg. magnesium, calcium}  can also form complexes with suitable ligands; Examples of amino acid chelates include: magnesium glycinate, zinc methionate, zinc glycinate; The advantage of metal-amino acid chelated supplements are that they can be recognized and absorbed as food. 

Factors for producing a chelated metal/mineral are:

• It must be steroically possible to chelate the metal - meaning that the spatial arrangement of the molecule must be possible.
• The ratio of the ligand to the mineral must meet minimum requirements for stability - usually 1 mole of metal to 2 moles of ligand
• Chelates have the "ring structure" formed by the coordinate covalent bonds between the ligand and the metal ion.

Effective chelated mineral supplements survive GI tract mostly intact

Benefits of an effective chelated mineral

• Reduction of antagonism, interferences and competition among minerals -  minimize any competition for absorption  between pairs of minerals when they are both present in the small intestine.
• Counteract anti-nutrients - prevent interactions of its  mineral with dietary absorption inhibitors, such as phytates, oxalates and fiber
• Improve bioavailability

Which chelates break down in GI tract, which do not?

So-called "true" chelates contain coordinate bonds stable enough to endure the journey through GI tract (which includes the HCl in the stomach) without breaking down - which would otherwise increase the chance of negative reactions with other substances in the GI tract before the chelated molecule is transported from the intestines. The "Stability Constant" between the specific metal and specific ligand in the complex determines the likelihood of the mineral staying with its chelating ligand:

• The stability constant of the complex is a measure of the strength of the reaction between the specific metal with the specific ligand in solution - Values range from 0-20 - the lower the number, the weaker the strength of the reaction, and the more likely the metal will separate / dissociate from its ligand in solution.

More technical details for those who seek the nitty-gritty :)

PEPTIDE LIGANDS (organic)

Peptide complexes make up proteins, and are the mineral forms naturally found in food

WILL LIKELY STAY INTACT -  HCl unfolds amino acids in proteins and activates pepsin enzymes, which break them down into shorter amino acid chains, called peptides. Peptides enter the intestines intact, where pancreatic enymes will further break them down into amino acids, which can be transported intact through the intestinal wall and into the bloodstream.

Amino acid ligands (organic)

• SOME WILL BREAK DOWN, SOME WILL LIKELY STAY INTACT
• Includes: glycine, lysine, taurine;
• Example amino acid chelate supplements: magnesium glycinate, magnesium taurinate, zinc glycinate.
• A "true" metal amino acid chelate has its metal mineral ion attached to 1-3 individual amino acids - with at least two coordinate bonds from each amino acid attaching to the mineral. The number of amino acids depends on the valence of the metal ion and size of the bonded ligand. Eg. sodium and potassium do not form strong chelated bonds with amino acids;
• An effective chelated mineral-amino acid supplement molecule needs to be NON-soluble in water - in addition to being chelated, an amino acid chelate molecule specifically needs to have no available sites to bind a water molecule via a coordinate covalent bond - Eg Ferrous bisglycinate is chelated to two glycine molecules, but is quite soluble (1 chelate molecule per 10 molecules of water) compared to iron triglycinate (ferric ion chelated to 3 glycine molecules), which is very insoluble (1 chelate molecule per 10,000 molecules of water).

A non-soluble amino acid chelate with its strong bonds and insolubility are considered more bioavailable than inorganic or organic mineral salts, since they do not rely on solubilty (whereby the mineral ion and its partner ligand separate into ions), and the mineral is transported through dedicated amino acid transport sytems.

Organic acid LIGANDS: (Non amino acid) (organic)

• MOST WILL BREAK DOWN IN GI tract - most organic acids are weak acids, which can be dissolved by HCl

• Includes: picolinic acid, citratic acid,  malic acid,  ascorbic acid, lactic acid, tartric acid, succinic acid, orotic acid;

• Example supplemental salt forms: magnesium malate, zinc citrate, calcium citrate, magnesium orotate, zinc picolinate, zinc gluconate

IMPORTANT EXCEPTIONS:

• Phytic acid - certain metallic mineral ions (calcium, magnesium, iron, zinc, selenium, chromium, and manganese) bonded to phytic acids can not  easily be separated and usually end up being expelled as waste. Phytate (its minerally chelated form) is found particularly in the husks of grains, nuts, seeds and legumes, which must be properly prepared by soaking, souring or sprouting before consumption to release their chelated mineral

• Oxalic acid - can irreversibly bind certain minerals in foods such as rhubard and spinach

OTHER Organic CHELATE LIGANDS (Eg. Polysaccharides)

• WILL LIKELY BREAK DOWN IN GI tract - Eg. polysaccharides (complexes of a soluble salt with simple sugars) are larger molecules, which lack stability

NON-chelated supplements / Inorganic salts

• WILL BREAK DOWN IN GI tract - Eg. zinc oxide, sodium chloride, magnesium carbonate, magnesium oxide, magnesium chloride, ;

Absorption of amino acid Chelates

• Serum magnesium tests measure short-term intake variations, but do not reflect the body's magnesium store, which is primarily in bone and muscle cells.
• Absorption of magnesium is negatively affected by low protein intake, high dietary fat, body's magnesium status;
• Mineral absorption can occur by passive diffusion, or via saturable, carrier-mediated (facilitated) passive diffusion
•  increased magnesium absorption is largely balanced by iincreased urinary excretion.
• The epithelial cells (aka. mucosal cells) lining the intestinal lumen ensure adequate containment of undesirable intestinal contents while preserving the ability to absorb nutrients into the body. Amino acid symporters, specific to amino acid pH and types, carry amino acids into intestinal mucosal cells; process requires energy, and transport systems are carrier mediated and/or ATP-Na+ dependent symport systems (driven by Na gradient established by Na+/K+ pump);
• Small peptides enter epithelial /mucosal cell by energy-dependent H+ - Na+ symporters, where they are broken down into individual amino acids by intracellular peptidase enzymes.
• Amino acids exit epthelial cell via various passive carriers (ie. facilitated diffusion), enter capillaries of intestinal villi via simple diffusion and are carried through the hepatic portal vein to the liver.

Neutral amino acids (Ala, Val, Leu, Met, Phe, Tyr, Ile);Basic amino acids (Lys, Arg) and Cys; Imino acids and Glycine; Acidic amino acids (Asp, Glu) ;  Beta amino acids ( beta Ala)

• Solubility of the chelate afects absorption and rate of facilitated diffusion into mucosal cell

To be absorbed, a chelated molecule must first be moved from the intestinal lumen and enter an intestinal mucosal cell, which is acieved via either:

•  At least one active transport system - likely to occur if lumen pH is low i.e. acidic) enough to dissociate the mineral ion from its chelated amino acid
•  Several facilitated diffusion transport systems -These pathways include different types of pores, different enzyme systems as part of an integral protein, or even facilitating absorption directly through the lipid bilayer of the mucosal cell membrane."

A summary of Professor D.S. Parsons, the chair at a 1976 international conference on intestinal permeation is given by Dr. H. Dewayne Ashmead, current president of Albion Laboratories, in his book, Amino Acid Chelation in Human and Animal Nutrition

Any of several carrier molecules  (including water) must be attached to an amino acid chelate to transport it intact across the luminal mucosal membrane into the mucosal cell. The carrier can be water if the amino acid chelate is dissolved in that water. Study data on amino acid chelate absorption generally demonstrates a regulatory mechanism to control the chelate's rate and amount of absorption into the mucosal cell in facilitated diffusion (transport via a protein channel without using energy, as a substance moves from a higher to lower concentration i.e. down a concentration gradient) but not in simple diffusion. i.e in facilitated diffusion the rate of absorption decreases as the concentration in the mucosal cell increases; until the concentration tends towards equalization on either side of the membrane.

The more soluble amino acid ligands have higher absorption rates via facilitated diffusion - A 1991 Albion Laboratory study using rats comparing uptake of amino acid chelated minerals zinc methionine to zinc glycinate in the small intestine concluded that absorption into blood was largely by facilitated diffusion of the intact chelates. Just as significant, the more soluble amino acid chelate (which is zinc glycinate, because the ligand glycine is more soluble than methionine), was absorbed at a greater rate into the blood, and differences were also reflected in organ tissues. It is emphasized that this study only shows that absorption rate via facilitated diffusion is increased with a chelate ligand with higher solubility, and does not address absorption differences by any active transport (which is likely to occur if lumen pH is low enough to dissociate the mineral ion from its chelated amino acid).

Mineral supplement tables

### a href="http://en.wikipedia.org/wiki/Magnesium_citrate" title="Magnesium citrate"> Magnesium citrate has been reported as more bioavailable than oxide or amino-acid chelates: glycinate, aspartate (neurotoxic), taurinate,  lysinate, arginate, or organic acid chelates: orotate or succinate forms.

Walker AF, Marakis G, Christie S, Byng M (2003). "Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study". Magnes Res 16(3): 183-91. PMID14596323

***Both magnesium aspartate and magnesium glutamate break down into neurotransmitters that, when not bound with other amino acids, are neurotoxic.

References

https://www.wattagnet.com/articles/410-chelates-clarity-in-the-confusion

https://books.google.com/books?id=7ud8CAAAQBAJ&pg=PA177&lpg=PA177&dq=mineral+chemical+form+in+food&source=bl&ots=ZlznAP7yQW&sig=o2kqx_u_vpi9S1VdJ81LNPZErWU&hl=en&sa=X&ved=0ahUKEwjQ1o-VyoLZAhUHSK0KHbHlBew4ChDoAQgvMAE#v=onepage&q=mineral%20chemical%20form%20in%20food&f=false