GSE
Choosing Oral Magnesium Supplement / Magnesium Bioavailability
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?
Dr. Mirkin post entitled,
Chelated Minerals Not Better ,
https://www.wattagnet.com/articles/410-chelates-clarity-in-the-confusion
FIRST, to clarify the term "chelate" - sometimes used incorrectly
in the world of nutrition supplements:
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 (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 . 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
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 vitamin B12 haemoglobin cytochrome
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
The stability constant of the comple x 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 iron triglycinate
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.
Absorption of Amino Acid Chelates
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 /
In organic saltsWILL 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'smagnesium 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 - 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 -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 absorption rate via facilitated diffusion active transport
Mineral supplement tables
AMINO ACID CHELATES
Magnesium bonded to an amino acid (C,H,O,N; E.g. glycine
is C4H8N3O2); STRONG chelators; rely on
amino aid pathways rather than their solubility. Theoretically
these may have advantageous absorption over other supplements due to (1)
Not dissociating in the stomach, preventing the still bonded mg ions from
otherwise forming less separable bonds with phytic acid and/or (2) being
absorbed intact via amino acid pathways in the gut lining
Magnesium AMINO ACID CHELATE
Elem. Mg %
Comments
Magnesium glycinate
11-14%
3.45 aka magnesium bisglycinate; glycine is a small,
calming amino acid
Magnesium lysinate
Magnesium taurinate
8.8%
Both magnesium and the amino acid taurine:
Magnesium glutamate
***AVOID: Glutamate is an excitory neurotransmitter; Neurotoxic
(see below)
Magnesium aspartate
7%
***AVOID: Aspartate is an excitory neurotransmitter; Neurotoxic
(see below)
Magnesium L-Threonate
8.1%
Passes BBB; improve memory and brain function.
Slutsky I, Abumaria N, Wu LJ, et al. Enhancement
of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77 Superior ability to penetrate the mitochondrial membrane,
Magnesium Arginate
### 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.
PMID 14596323
***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
