clinical interaction drug-supplement
TRANSCRIPT
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Interactions in Clinical Practice:
Drug-Supplement, Drug-Nutrient
Leo Galland, M.D.
Applied Nutrition, Inc.www.nutritionwors!op.com
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"#er#iew
"$ almost %&& drugs and $i'ed-drugcom(inations used in t!e ).S.:
* Almost +&& ma deplete speci$ic nutrients.* "#er +&& ma interact wit! $ood or $ood
components.
* "#er && !a#e (een s!own to interact wit!dietar supplements, wit! ad#erse and (ene$icial interactions euall common.
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/pes o$ Interactions
* Pharmacodynamic: two su(stances e'!i(it
p!armacologic actions t!at rein$orce or
inter$ere wit! eac! ot!er0s actions.
* Pharmacokinetic: t!e a(sorption,
distri(ution, e'cretion or en1matic
trans$ormation o$ one su(stance is altered ( anot!er. Most ad#erse interactions are o$
t!is tpe.
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P!armacoinetic Mec!anisms
* Alteration o$ gastrointestinal or urinar p2.
* Stimulation, induction or in!i(ition o$
en1mes in#ol#ed in (iotrans$ormation or
transport o$ drugs or nutrients .
* Displacement o$ a drug $rom (inding to
plasma proteins.
* Alteration o$ solu(ilit.
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3$$ects o$ Interactions
* Nutrient depletion: Indi#idual nutrients ma !a#e
t!eir dietar reuirement increased ( speci$ic
drugs 4or supplements5.* Ad#erse: A speci$ic supplement ma undesira(l
decrease or increase t!e e$$ect o$ a drug or
supplement (eing taen.
* 6ene$icial: Drugs 4or supplements5 ma !a#e t!eir
actions en!anced or side e$$ects diminis!ed (
speci$ic supplements.
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Drug-Induced Nutrient Depletion
* A(out !al$ t!e drugs used in clinical
practice !a#e documented nutrient
depleting e$$ects.
* Co-en1me 78&, $olic acid, 69, 6, Mg, ;n
are nutrients most liel to (e depleted.
* Mec!anisms include impaired a(sorption or
(ioacti#ation< increased e'cretion.
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Co-en1me 78& Depletion
* Statin-induced co-7 depletion impairs
mitoc!ondrial $unction, raising t!e serum
lactate=pru#ate ratio. Sim#astatin (ut notator#astatin depletes mo$i(rillar co-7.
* Supplemental co-7, 8&& mg=da, pre#ents t!e
decline in serum co-7 le#els wit!out impairment
o$ t!e lipid-lowering e$$ect o$ statins and mare#erse smptoms o$ statin mopat!.
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Co-en1me 78& Depletion
4cont0d5* Statin-induced Co-7 depletion is increased (
#itamin 3 4>&& I)=da5.
* Co-7 is consumed in reccling tocop!erluinones (ac to tocop!erols.
* /!ia1ides, some (eta-(locers and man older
psc!otropic drugs !a#e (een s!own to inter$ere
wit! co-7 dependent en1mes, creating a possi(le
need $or co-7 supplementation in patients
recei#ing t!em.
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Are reported ad#erse
cardio#ascular e$$ects o$ #itamin3 supplements related to co-7
depletion in patients taing drugs
t!at inter$ere wit! co-7
snt!esis or co-7 dependent
en1mes?
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@itamin 3 and Statins
* a-/ocop!erol pre#ents statin (ene$its in people wit! low 2DL-C and normal /C.
* elated to tocop!erol in!i(ition o$ statin-induced ele#ation o$ 2DL9-C.
* Selenium 48&& mcg=da5 and $is! oil !a#e
t!e opposite e$$ect.* a-/ocop!erol depletes gamma-tocop!erol
( competiti#e (inding to transport protein.
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Clinicall Signi$icant Depletions-8
* Adriamcin depletes co-en1me 78&.
Cardioto'icit is reduced ( co-7 and
proprionl-L-carnitine.* Cisplatin depletes Mg. Nep!troto'icit is
reduced ( i.#. and oral Mg 48& mg tid5.
* /!ia1ides and B-ASA deri#ati#es deplete$olate, raising !omocsteine concentration.
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Clinicall Signi$icant Depletions-9
* Loop diuretics increase e'cretion o$ , Ca,
Mg, ;n, 68, 6, C. Correcting 68 de$icit
impro#es cardiac $unction o$ C2 patients.
* Cep!alosporins 4parenteral5 can deplete
#itamin 9, causing !emorr!age.
* Steroids deplete Ca and Mg, causing (oneloss. e#ersi(le wit! calcium and #it D.
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Antiretro#iral Nutrient Depletion
* A;/ depletes muscle carnitine and
increases lmp!octe apoptosis. e#ersed
wit! carnitine supplementation.
* A;/ is associated wit! decreased serum
1inc and copper< 1inc 9&& mg=da reduced
Candida and Pneumocstis in$ections in patients taing A;/.
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P!entoin-induced Depletions
* P!entoin ma deplete (iotin, $olate,
t!iamine, #itamin D 4causing !pocalcemia
and osteomalacia and #itamin .
* Memor impairment is associated wit!
reduced 6C $olate. olic acid, 8 mg=da,
pre#ents de$icienc wit!out ad#ersela$$ecting p!entoin meta(olism.
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@alproic Acid Depletions
* @alproate depletes carnitine, raisingammonia< re#ersed wit! carnitine 9 g=da.
* @alproate acid lowers serum $olate and PBP,raising !omocsteine< re#ersed wit! +&&mcg $olate, 89& mg 6 and >B mg 69.
* @alproate in!i(its (iotinidase. 6iotin 8&mg=da re#erses #alproate-associated !airloss and dermatitis in c!ildren.
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C!elation and Drug A(sorption
* C!elation ( minerals impairs a(sorption o$
uinolone or tetraccline anti(iotics,
t!roid, (isp!osp!onates, L-D"PA, someAC3 in!i(itors.
* 3#en some !er(s lie dandelion and $ennel,
can (e so ric! in minerals t!at t!e in!i(ita(sorption o$ t!ese same drugs.
.
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/!e Ctoc!rome P+B& Sstem and
Drug-Supplement Interactions* 3'pressed c!ie$l in li#er, intestines, lungs
and idnes 4EP!ase 8 deto'icationF5.
* 9& di$$erent !uman CPs, grouped (
amino acid !omolog, not ( $unction.
* CP8A9, CP9C%, CP9C8%, CP9D,
CP938 and CPA+ most important $oro'idation o$ drugs, 'eno(iotics.
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CP8A9
* Li#er onl. Inacti#ates ca$$eine and
(ioacti#ates aromatic and !eterocclic
amines< large inter-indi#idual di$$erences4up to 8&&-$old5. Induced ( c!ar-(roiled
meat, cigarettes, pollutants, dio'ins and
cruci$erous #egeta(les.
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CP9: Drug-Drug Interactions
* CP9C% accounts $or &H o$ CP acti#it in!uman li#er. Ma (e modi$ied ( Gingo (ilo(a.
* CP9C8% is primaril !epatic. P!enotpe re$lectst!e interaction o$ gene alleles.
* CP9D is e'tra-!epatic. 6ioacti#atescodeine=codones. BB alleles.
* CP938 in li#er, lung, (rain meta(oli1es organic
sol#ents lie et!anol. Induced wit! c!ronic et!anoluse, $asting, o(esit. In!i(ited ( acute alco!olintae, tea, (roccoli, garlic, onion, watercress.
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CPA+
* Li#er and small intestine.
* /rans$orms a(out B&H o$ common drugs.
* Induced ( St. Jo!n0s wort 4li#er, intestine5and 3c!inacea 4li#er onl5.
* In!i(ited ( peppermint oil and piperine.
* Intestinal (ut not li#er CPA+ is in!i(ited ( grape$ruit Kuice, Se#ille orange Kuice and3c!inacea.
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CPA+ and St. Jo!n0s ort
* CPA+ stimulation ( St. Jo!n0s wort
reduces (lood le#els o$ (en1odia1epines,
calcium c!annel (locers, anti-retro#irals,estrogens 4including "CPs5, amitriptline,
cclosporine, met!adone, tacrolimus and
possi(l war$arin.
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Intestinal CPA+ In!i(ition
* Increases (lood le#els o$ amiodarone,
artemisinin, ator#astatin, (uspirone,
car(ema1epine, cclosporine, dia1epam,diltia1em, ert!romcin, estradiol,
$elodipine, $entanl, $luo'etine, lo#astatin,
met!l-prednisolone, ni$edipine,nimodipine, pra1iuantel, sauina#ir,
sertraline, sildena$il, sim#astatin, #erapamil
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P-glcoprotein /ransporter 4P-gp5
* 3Kects 'eno(iotics $rom cells and causes (ac$low o$ some drugs $rom intestinal
mucosa into t!e lumen.* Produces multi-drug resistance to cancer
c!emot!erap.
* In!i(ited ( piperine, mil t!istle andacutel ( St. Jo!n0s wort.
* Stimulated ( continued St. Jo!n0s wort.
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Alteration o$ Intestinal CPA+
and=or P-glcoprotein* "$ten in#ol#es t!e same su(strates.
* Primaril e$$ects drugs t!at pass slowl
t!roug! intestinal mucosa.
* Interactions in vivo ma not (e predicted (
interactions in vitro.
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Ad#erse P!armacodnamic
Interactions* B-2/P and SSI0s
* Licorice and !orsetail, diuretics or la'ati#es
* P!enlalanine or a#a and neuroleptics
* 6ee #enom and AC3 in!i(itors
* 6rewer0s east and MA" in!i(itors* Inter$eron-alp!a and (upleurum
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Antit!rom(otic Interactions
* B natural products in!i(it platelet $unction
in vivo $ollowing oral use. /!e ma
rein$orce eac! ot!er or interact wit!antit!rom(otic medication.
* Aspirin-#itamin 3 interaction: aspirin
in!i(its platelet aggregation< #itamin 3in!i(its platelet ad!esion to endot!elium.
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Aspirin-@itamin 3 Interactions
* a-/ocop!erol 4B& I)=da5 raised ris o$ gingi#al (leeding 9BH among ASA users.
* +&& I)=da a-tocop!erol added to 9B mg ASA=dareduced incidence o$ /IAs compared to aspirinalone.
* @it 3 B& I)=da, decreased isc!emic stroe ( &H
(ut increased !emorr!agic stroe ( 8+BH in!pertensi#e, non-dia(etic male smoers. India(etics, t!ere was no increase in !emorr!agicstroe and isc!emic stroe decreased ( >&H.
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ar$arin Interactions
* +% natural products ma inter$ere wit!war$arin< 98 con$irmed, 9 possi(le.
* 2er(al coumarins mig!t compete $or (inding to plasma protein, increasing plasma $ree war$arin concentration.
* Controlled studies $ound no e$$ect on#itamin 3 or coen1me 78& on IN o$ patients taing war$arin.
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6ene$icial Drug-Supplement
Interactions* e$lect additi#e=complementar e$$ects o$
supplements and drugs, or amelioration o$
to'ic drug e$$ects ( supplements.* is! oils en!ance anti-in$lammator,
antiarr!t!mic, anti-lipemic, antidepressant,
and neuroleptic drugs, (eta-(locers,lit!ium and insulin. 3PA and D2A ma
!a#e di$$erential e$$ects.
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Acetaminop!en /o'icit
* Protecti#e supplements:
N-acetl csteine 4clinical use5
L-met!ionine and SAMe
Mil t!istle
Andrograp!isSc!isandra
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ASA=NSAID Gastropat!
* Protecti#e supplements 4!uman trials5:
@it C 4B&&-8&&& mg (id5
SAMe B&& mg=da
Caenne 9& grams
Deglcrr!i1inated licorice B& mg tid
Colostrum 89B mg tid
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Neuroleptic Side 3$$ects
* Protecti#e supplements:
@itamin 3 89&&-8&& I)=da 4/.D.5
6ranc!ed c!ain amino acids 4/.D.5Gingo (ilo(a B& mg=da
Sarcosine 4N-C2-glcine5 9 gm=da
3icosapentaenoate 43PA5 9 gm=da
Glcine &.+-&. mg=g=da
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Cisplatin /o'icit
* Protecti#e supplements:
6ismut! 8B& mg=g=da 8&das
Gingo (ilom(a 8&& mg=g single dose
Glutat!ione B gm i.#.
MgS"+ gm i.#.= Mg 8& mg tid
Sili(inin 9&& mg=g i.#. single dose
N-acetl csteine gm=da
Selenium +&&& mcg=da das
@itamin C B&-9&& mg=g i.#. single dose
@itamin 3 && I)=da till mont!s post-c!emot!erap
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More Antineoplastic /o'icit
* Protecti#e supplements
@itamin 6 B& mg tid
Glutamine & gm=daMelatonin 9& mg 2S
Coriolus #ersicolor 8 gm tid
/!eanine 4in #itro5Inositol !e'ap!osp!ate 4IP5 4in #itro5
Calcium D-glucarate 4in #itro5
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is! oils, NSAIDs, ASA
* 9&& mg o$ 3PA D2A $or mont!s allow NSAID reduction in r!eumatoid art!ritis.
Plasma p!osp!olipid 3PA must reac! BH.* is! oil & ml=da re#ersed ASA0s increase
o$ L/6+ snt!esis< no !emorr!age.
* ASA increases snt!esis o$ anti-in$lammator resol#ins and protectins $romD2A in #itro ( acetlating C"-9.
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Conclusion
* Almost !al$ t!e drugs commonl used in t!e)S ma deplete speci$ic nutrients, creating a
need $or nutritional supplementation.* Ad#erse interactions !a#e recei#ed e'tensi#e
press co#erage.
* 6ene$icial drug-supplement interactions areat least as important and permit creati#enutritional t!erapies.