Amino acid chelation in human and animal nutrition

260 Pages·2012·10.62 MB·English

by  H DeWayne Ashmead

AMINO ACID
CHEL ATION
IN
HUMAN AND
ANIMAL
NUTRITION

AMINO ACID
CHEL ATION
IN
HUMAN AND
ANIMAL
NUTRITION
H. DeWAYNE ASHMEAD
Boca Raton London New York
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© 2012 by H. DeWayne Ashmead
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Contents
Foreword...................................................................................................................vii
Introduction................................................................................................................ix
About.the.Author.......................................................................................................xi
Chapter 1 The.Fundamentals.of.Mineral.Nutrition...............................................1
Chapter 2 The.Chemistry.of.Chelation................................................................19
Chapter 3 The.History.of.Nutritional.Chelates....................................................35
Chapter 4 The.Requirements.for.a.Nutritionally.Functional.Chelate..................49
Chapter 5 The.Development.of.Analytical.Methods.to.Prove.Amino.Acid.
Chelation.............................................................................................61
Chapter 6 Absorption.of.Amino.Acid.Chelates.from.the.Alimentary.Canal......81
Chapter 7 The.Pathways.for.Absorption.of.an.Amino.Acid.Chelate...................97
Chapter 8 The.Absorption.of.Amino.Acid.Chelates.by.Active.Transport........117
Chapter 9 The.Absorption.of.Amino.Acid.Chelates.by.Facilitated.Diffusion....135
Chapter 10 The.Fate.of.Amino.Acid.Chelates.in.the.Mucosal.Cell....................153
Chapter 11 The.Uptake.of.Amino.Acid.Chelates.into.and.out.of.the.Plasma.....171
Chapter 12 Tissue.Metabolism.of.Amino.Acid.Chelates....................................185
Chapter 13 Some.Metabolic.Responses.of.the.Body.to.Amino.Acid.Chelates.....201
v
vi Contents
Chapter 14 Toxicity.of.Amino.Acid.Chelates......................................................223
Chapter 15 The.Absorption.and.Metabolism.of.Amino.Acid.Chelates...............233
Foreword
Mineral.bioavailability.has.historically.been.“the.black.box”.of.micronutrient.metab-
olism..Dietary.intake.of.a.mineral.micronutrient.in.sufficient.quantities.to.meet.
dietary.reference.intakes.does.not.always.ensure.adequate.metabolizable.mineral.
at.the.tissue.level..Minerals.are.by.nature.ionic.and.form.complexes.and.chemical.
compounds.quite.readily..The.pathway.from.the.food.or.supplement.in.which.they.
are.contained.to.their.target.cells.in.the.body.provides.multitudinous.opportunities.
to.interact.with.their.immediate.chemical.environments..The.foodstuffs.with.which.
they.are.ingested,.the.acidic.and.chemical.milieu.of.the.digestive.tract,.the.absorptive.
surface.and.interface.of.the.gastrointestinal.tract,.the.ions.in.the.plasma,.and.ulti-
mately.the.cellular.matrix.to.which.they.are.delivered.can.interact.to.influence.the.
ultimate.efficacy.of.the.structural,.metabolic,.or.catalytic.roles.of.the.dietary.min-
eral..The.seemingly.large.doses.of.mineral.supplements.needed.to.correct.a.dietary.
mineral.deficiency.can.be.explained.in.terms.of.the.“inefficiency.of.absorption”.
or,.in.broader.terms,.the.lack.of.“bioavailability”.of.the.particular.mineral.supple-
ment..Mineral.nutritionists.have.long.sought.chemical.forms.of.minerals.that.evoke.
a.greater.or.more.positive.response.at.the.target.tissue..Two.important.historical.
examples.of.mineral.nutrition.research.that.continue.to.be.pursued.today.are.calcium.
supplementation.to.influence.bone.mineralization.and.iron.supplementation.to.influ-
ence.blood.hemoglobin.levels..Not.all.covalently.bound.minerals.ionize.sufficiently.
to.release.their.mineral.counterpart.optimally.at.the.sites.of.absorption.in.the.gut..
Mineral.absorption.from.the.gut.is.a.complex.topic,.considering.the.various.routes.
that.are.available.(e.g.,.passive.absorption,.facilitated.absorption,.active.transport).
to.account.for.the.disappearance.of.the.mineral.from.the.gut.and.its.appearance.in.
the.plasma.
Enter.the.concept.of.supplying.the.mineral.in.an.ionic.or.covalently.bound.pro-
tective.amino.acid.matrix.(chelate).with.a.stability.factor.that.helps.to.circumvent.
ionization.issues.and.delivers.the.mineral.to.sites.of.absorption.in.the.intestinal.brush.
border..Certain.amino.acids.form.soluble.complex.molecules.with.metal.ions,.thus.
“protecting”.the.ions.so.that.they.cannot.react.with.other.elements.or.ions.prior.to.
arriving.at.the.absorptive.site.in.the.gut..The.chelated.mineral.ligand.can.then.be.
either.passively.absorbed,.subsequently.released.to.its.transporter,.or.in.some.man-
ner.“escorted”.through.the.absorptive.surface.of.the.gut.to.permit.a.more.rapid.and.
quantitative.transfer.of.the.mineral.from.the.intestinal.contents,.across.the.intesti-
nal.villi.and.into.the.blood..The.principle.of.chelation.extends.well.beyond.amino.
acid.chelates.and.is.well.documented.in.organic.and.inorganic.chemistry..This.book.
explores.the.chelation.principles.as.applied.to.the.biochemistry.of.mineral.absorp-
tion.and.metabolism,.specifically.focusing.on.the.formation.and.absorption.of.amino.
acid.metal.chelates.
The.progress.and.development.of.amino.acid.mineral.chelates.has.not.been.with-
out.controversy..Although.the.improved.bioavailability.of.some.amino.acid.mineral.
chelates.is.generally.accepted,.it.has.not.been.clearly.understood.exactly.why.these.
vii
viii Foreword
chelates.provide.improved.absorption..Early.studies.of.the.nutritional.aspects.of.the.
bioavailability.of.mineral.chelates.occurred.during.the.1960s.and.1970s.when.ana-
lytical.techniques.suggested,.but.did.not.permit,.direct.implication.of.chelates.in.
improved.absorption.and.transfer.of.mineral.across.the.gut..Over.the.intervening.
years,.considerable.indirect.evidence.and.some.direct.evidence.of.enhanced.bioavail-
ability.was.gained.through.numerous.animal.and.a.few.human.feeding.trials..Much.
of.this.early.experimental.information.was.initially.studied.with.an.agricultural.
emphasis.and.published.in.related.animal.nutrition.venues.and.proprietary.in-house.
publications.sponsored.by.early.innovators.of.chelated.mineral.products.such.as.
Albion.Laboratories..Some.of.these.publications.were.not.widely.read.by.or.acces-
sible.to.mineral.researchers.due.to.the.early.emphasis.in.livestock.applications.and.
publication.venues.that.were.not.readily.available.or.read.by.those.in.the.human.min-
eral.nutrition.field..By.publishing.this.book,.Ashmead.makes.this.information.more.
readily.available.to.a.wide.audience.
In.this.book,.DeWayne.Ashmead.provides.a.historical.account.of.the.theory.and.
application.of.chelates.to.mineral.nutrition..Much.of.the.pioneering.early.work.was.
accomplished.by.DeWayne’s.father,.the.late.Harvey.Ashmead..Albion.Laboratories.
is.a.family-owned.and.operated.business,.and.at.first.glance,.one.might.imagine.that.
the.content.of.this.book.would.be.a.treatise.on.the.nutritional.superiorities.of.min-
eral.amino.acid.chelates..That.preconceived.notion.would.be.a.mistake..This.book.
is.a.scholarly.compendium.that.not.only.provides.the.historical.context.of.chelates.
but.also.explains.the.chemistry.of.chelation.and.the.formation.of.amino.acid.min-
eral.chelates.in.considerable.detail..The.book.contains.a.well-developed.introduc-
tion.and.discussion.to.the.complexities.of.mineral.bioavailability..Ashmead.then.
progresses.to.review.the.analytical.methodology.necessary.to.establish.that.one.is.
indeed.working.with.a.true.chelate.prior.to.engaging.in.direct.feeding.comparisons.
of.amino.acid.mineral.chelates.versus.inorganic.forms.of.the.mineral.in.question..
Tabular.and.graphical.data.from.feeding.trials.previously.published.in.the.literature.
as.well.as.some.extracted.from.some.difficult-to-access.publications.and.previously.
unpublished.work.are.presented.in.the.chapters.on.amino.acid.mineral.chelates..The.
concept.and.criteria.for.the.development.of.a.“nutritionally.functional”.metal.chelate.
are.presented.and.discussed.
Although.the.main.focus.of.this.book.is.on.the.ingestion.of.amino.acid.metal.
chelates.as.a.way.to.optimize.mineral.absorption,.the.book.also.provides.a.good.
fundamental.discussion.of.chelation.chemistry..Ashmead.provides.not.only.his.inter-
pretation.of.the.results.of.numerous.studies.of.animal.and.human.amino.acid.mineral.
chelate.digestion.and.absorption.but.also.alternative.interpretations..One.cannot.help.
but.admire.the.clarity.of.writing.and.the.logical.and.stepwise.development.of.the.
material.in.this.book..This.reference.should.be.invaluable.to.bioinorganic.mineral.
researchers.and.others.seeking.to.enhance.mineral.bioavailability.to.support.opti-
mal.health.and.productivity.
Wayne Askew, PhD
Professor, Division of Nutrition
University of Utah
Introduction
In.the.early.1960s,.a.study.was.conducted.in.which.gestating.rats.were.given.diets.
containing.the.same.mineral.content.of.mineral.salts.or.amino.acid.chelates..The.
young.from.the.group.that.was.given.amino.acid.chelates.had.a.much.higher.survival.
rate.and.grew.faster..This.type.of.study.was.then.extended.to.dairy.cows..Here,.it.was.
found.that.both.milk.and.butterfat.productions.were.higher.in.the.group.receiving.
amino.acid.chelates..This.type.of.study.was.then.extended.to.laying.hens;.greater.
production.and.fewer.broken.eggs.were.observed.from.the.group.receiving.amino.
acid.chelated.minerals..Other.researchers.conducted.a.study.with.gestating.sows..
This.study.showed.that.the.group.receiving.amino.acid.chelated.iron.had.higher.
birth.weights,.lower.mortality,.and.greater.weight.gains.than.those.given.the.normal.
iron.dextran.treatment..These.studies.initiated.many.others.on.the.absorption.of.
amino.acid.chelated.metals..The.studies.consistently.demonstrated.that.amino.acid.
chelates.were.absorbed.better.and.improved.some.aspect.of.health.in.humans.and.
other.treated.animals.
Although.chelation.was.first.observed.over.100.years.ago,.it.has.only.been.in.the.
last.50.years.that.scientists.discovered.the.nutritional.benefits.of.amino.acid.chelates..
This.book.examines.the.reasons.for.those.benefits,.the.chemistry.of.chelation,.the.
analytical.methods.that.have.been.used.to.prove.or.verify.chelation,.and.a.detailed.
discussion.of.the.absorption.and.metabolism.of.various.metal.amino.acid.chelates.
compared.to.mineral.salts..The.requirements.for.nutritionally.functional.chelates.and.
their.absorption.are.discussed.in.this.text..For.a.chelate.to.be.formed,.a.metal.must.
be.a.member.of.a.heterocyclic.ring..When.an.amino.acid.forms.a.chelate,.the.car-
boxylate.anion.forms.a.bond.with.a.positively.charged.metal..This.places.the.amine.
group.in.perfect.position.to.share.its.pair.of.electrons.with.the.metal.to.form.a.bond.
to.the.metal.and.create.a.heterocyclic.ring.or.chelate..Depending.on.the.charge.on.the.
metal,.this.process.can.be.repeated.one.or.more.times..The.structure.of.this.chelate.
can.be.proven.by.x-ray.crystallography.and.strongly.indicated.by.Fourier.transform.
infrared.(FT-IR).spectroscopy.
It.is.logical.to.conclude.that.the.amino.acids,.which.surround.the.metal,.protect.
the.metal.from.reactions.that.can.greatly.inhibit.its.absorption..Some.of.the.reac-
tions.that.produce.precipitation.of.the.metals.are.reactions.with.phosphates,.phytic.
acid,.and.other.substances.commonly.found.in.the.gut..This.protection.of.the.met-
als.is.related.to.the.stability.of.different.amino.acid.chelates..More.stable.amino.
acid.chelates.provide.better.protection.against.precipitation..It.is.also.logical.that.in.
lower.pH.environments.the.amine.portion.of.the.amino.acid.could.accept.a.proton..
The.pair.of.electrons.that.provided.the.bond.to.the.metal.is.now.used.to.bond.to.the.
proton..When.this.happens,.the.protonated.amine.carries.a.positive.charge.and.the.
chelate.ring.is.broken..This.produces.a.chelate/complex.rather.than.a.chelate,.but.
Dr..Ashmead.explains.how.this.allows.the.metal.amino.acid.chelate/complex.to.be.
attracted.to.negatively.charged.transport.molecules.and.thus.be.absorbed.through.
ix
x Introduction
active.transport..The.relationship.between.absorption.through.passive.diffusion,.
facilitated.diffusion,.as.well.as.active.transport.is.explained.
A.study.to.determine.the.fate.of.amino.acid.chelates.used.a.radioactive.isotope.
of.the.metal.and.another.radioactive.isotope.in.the.amino.acids..There.appeared.
to.be.some.division.of.the.metal.and.the.amino.acids.in.the.mucosal.tissue.due.to.
hydrolysis..Differences.in.the.amount.of.hydrolysis.of.the.amino.acid.chelates.in.the.
mucosal.tissue.are.explained.on.the.basis.of.the.stability.of.the.amino.acid.chelates..
Regardless.of.how.much.hydrolysis.occurs.in.the.mucosal.tissue,.some.of.the.amino.
acid.chelate.or.chelate/complex.appeared.to.be.transferred.to.the.plasma.intact..The.
metabolism.of.these.amino.acid.chelates.has.been.shown.to.produce.responses.in.
performance.or.production.of.the.animals.being.tested,.and.because.of.greater.tissue.
retention,.these.amino.acid.chelates.can.provide.long-term.positive.responses.
Increased.absorption.of.amino.acid.chelates.has.been.observed.many.times.in.
tests.where.a.radioactive.isotope.of.the.metal.is.given.to.the.animal.as.an.amino.acid.
chelate.or.as.a.mineral.salt..After.dosing,.the.amount.of.mineral.that.is.absorbed.by.
various.tissues.and.organs.can.be.accurately.determined..These.tests.demonstrate.
that.amino.acid.chelates.provide.better.mineral.absorption.than.when.these.minerals.
are.given.as.salts..Even.though.amino.acid.chelated.minerals.have.greater.absorption.
than.mineral.salts,.to.be.effective.these.amino.acid.chelates.must.be.bioavailable..A.
detailed.explanation.of.why.this.occurs.is.found.in.this.book.
Bioavailability.of.minerals.is.sometimes.more.difficult.to.determine,.but.this.is.
usually.done.by.comparing.some.aspect.of.health.or.production.when.different.types.
of.minerals.are.given..Many.studies.are.reviewed.that.range.from.improving.iron.
deficiency.anemia.in.human.infants,.to.milk.production.in.cows,.to.improved.sur-
vival.of.baby.pigs..These.studies.all.showed.that.when.amino.acid.chelated.minerals.
are.in.the.diet,.the.response.is.improved.health.or.production.
Although.introduction.of.amino.acid.chelates.in.mineral.nutrition.initially.met.
with.considerable.skepticism.and.controversy,.greater.absorption.and.bioavailabil-
ity.of.amino.acid.chelated.minerals.compared.to.nonchelated.minerals.has.been.
well.documented..This.book.reviews.many.of.the.studies.that.provided.information.
on.the.comparison.of.amino.acid.chelates.and.nonchelated.minerals..These.studies.
were.conducted.using.many.different.animals,.including.humans,.under.a.variety.of.
conditions,.and.amino.acid.chelates.consistently.provided.improved.responses.that.
resulted.from.better.absorption.and.bioavailability.of.the.minerals.being.tested.
Boyd R. Beck, PhD
Retired Professor of Chemistry
Snow College, Ephraim, Utah