Detoxifi cation and Drainage

ATheoreticalandPracticalApproach

21stEnglishedition,June20072007byBiologischeHeilmittelHeelGmbH,Baden-Baden,Germany.

PrintedinGermany

6490006/07DinnerDruck

BiologischeHeilmittelHeelGmbHDr.-Reckeweg-Strae2-476532Baden-Baden,GermanyPhone+497221501-00Fax+497221501-450www.heel.com

Contents

Part I / Classes of Homotoxins ...5

1 Introduction 52 EffectsofToxinsinGeneral 63 MeasurementofToxicity 64 ClassesofToxins 7 4.1 Pollutants 4.2 Metals 4.3 AgriculturalChemicals(Pesticides) IncludingWoodPreservatives 4.4 PlasticizersandPBBEs 4.5 TherapeuticDrugsandDrugs ofAbuse 4.6 FoodAdditivesandPreservatives 4.7 EndogenousToxins

Part II / The Physiology of Detoxification ...13

1 Absorption 142 Transport 143 DistributionandStorage 154 MetabolismofToxins 16 4.1 PhaseIReactions 4.2 PhaseIIReactions5 Elimination 17

Part III / The Organs of Detoxification and Elimination ...21

1 TheLiver 212 ExcretioninBile 223 Entero-hepaticCirculation 224 TheKidneys 225 TheMatrixandLymph 23 5.1 TheMatrix 5.2 TheLymphSystem6 TheLungs 267 TheMucosalMembranes 268 TheSkin 279 Sweat 2810 Hair 2811 OtherRoutesofElimination 28

Part IV / Tools for Detoxification ...30

1 WhyDoesaPersonNeed 30 toDetoxifyandEliminate2 ToolsforDetoxificationandDrainage 31 2.1 TheGeneralBasicDetoxification 2.2 TheGeneralAdvanced Detoxification 2.3 TheCatalysts

Part V / Practical Detoxification ...38

1 ClinicalGroups 38 1.1 TheDetoxificationPointScale 1.2 TheClinicalAssessment ofthePatient2 HowLongShouldthePatientDetox? 393 BlockedExcretion 394 TheDecisionTree 40

Part VI / The Organ-specific Treatment ..42

1 TheLiver 42 1.1 TherapySchemeforDetoxification inChronicViralInfectionlike HepatitisC 1.2 DetoxificationoftheGallbladder andtheBile 1.3 TherapySchemeforFattyInfiltration oftheLiverinTypeIIDiabetics: So-calledNASH(NonAlcoholic SteatoticHepatitisSyndrome)2 TheKidneys 46 2.1 TherapySchemeforKidneyStones 2.2 TherapySchemefor ChronicRecurrentUTIs 2.3 InterstitialCystitis3 TheLymphoidSystem 49 3.1 TherapySchemefor ChronicRecurrentTonsillitis4 TheSkin 51 4.1 TherapySchemeforAcneVulgaris

Part VII / References ...53

4NoteSincethisisaninternationalpublication,namesandformulasoftheproductsmentionedinthisbookletmayvaryfromonecountrytoanother.

Classes of Homotoxins

Part I / Classes of Homotoxins

1 Introduction

TobetterunderstandtherationaleandmethodsforDetoxificationandDrainage,itisusefultodefinewhatare toxins, theiroriginandnature,howtheyreachthebodycellsandtissues,andhowtheyeven-tuallyinfluencehomeostasisandbecomeeventuallyetiologicalfactorsforinducingdiseaseprocesses.

Anyagent (physical, chemical,microbial, etc.) thatadverselymodifiesordamagesabalancedbiologicalsystemisconsideredatoxin.Toxinsmayenterthebody from theexternal environment (exogenousalsocalledtoxicantsorxenobiotics)throughthegas-trointestinalsystembyingestion,therespiratorysys-tembyinhalation,andtheskinbypassiveabsorptionorbyinjection.Toxinsmayalsooriginatewithinthebody itself (endogenous toxins) as by-products ofphysiologicalmetabolism(bilirubin,creatinine,lacticacid,etc.)orasmetabolitesunderabnormalmeta-bolicconditions(excessproduction/degradationsofneurotransmittersand/orhormones,excessfreerad-icalformation,etc.).

Modernmedicine isquite successful indiagnosingandtreatingacuteintoxicationsasmedicalemergen-ciesforheavymetals,drugpoisoning,etc.aswellassymptomaticsub-acutepoisoningsfromavarietyoftoxins (chemical, drugs and/or other xenobiotics),butonlyifsomelaboratoryevidenceofintoxicationisfound.Unfortunatelyforthepatient,sub-clinicalorsubtlestatesofchronicintoxicationsarenotrec-ognized,exceptforthefactthattheappearanceofany symptomatology is treated with suppressivemedicationsindependentlyofitsetiology.

Biologicaleffectsofchronicsubtlestatesofintoxica-tionsareofgreatimportancetobiologicalmedicine.Paracelsusisoftenparaphrasedasstatingthatthedosemakes thepoison.Often, if thedose is nothigh enough to produce immediate acute effectsand/orcannotbedetectedwithourpresenttechno-logical limitations,thenthetoxinisseenasnotre-sponsibleandthequestion is justdismissedasnotbeingresponsibleforthebiologicaleffectsandinflu-encesuponthehealthoftheindividual.

Another very important consideration to bear inmindistheindividualstolerabilityorsusceptibilitytospecifictoxins.Thetolerabilityofbiologicalsystemsto a toxin is inpart genetically determinedand inpart acquired on the basis of enzymatic inductionan/orinhibitions,thedegreeoffunctionalityofthetargetorgan,andfunctionalreservecapacityofspe-cific organ-systems. The clinical manifestations ofbiologicaleffectsof toxinsdependon thephysicalandchemicalpropertiesofthetoxinitself,butalsoonthedurationandrouteofexposure, itsmecha-nismofaction,andobviouslyontheindividualsus-ceptibility,aspreviouslydescribed.

Chemicalcompounds,whichcompromisethebulkofenvironmentaltoxins,arecurrentlyspreadallovertheworld,evenifthechemicalwasnotusedinthatarea.Thisisduetospreadviathegroundwater,sur-facerainandwinds.

Bioaccumulationofthesecompoundscausediseaseinlivingbeings,andinhumans,theimmunesystem,endocrine system and neurological system is themostaffected.(Crinnion,2005)

Theeffectsoftoxinsaredocumentedinanumberofdiseases,rangingfromasthma,allergies,autoimmu-nity,cancers,cognitivedeficit,andobesity.

Newdiagnoses also include so-called sick buildingsyndrome,andmultiplechemicalsensitivity.Sickbuil-ding syndrome (SBS) is a combination of ailmentsassociatedwithan individualsplaceofwork(typi-cally, but not always, an office building), thoughtherehavealsobeeninstancesofSBSinresidentialbuildings.A1984WorldHealthOrganisationreportintothesyndromesuggestedupto30%ofnewandremodelled buildings worldwidemay be linked tosymptomsofSBS.Multiplechemicalsensitivity isaconditionevenmoredifficulttotreat,andisrecog-nizedinsomeindividualswhodevelopchemicalsen-sitivitytoahostofenvironmentalchemicals.

2 Effects of Toxins in General

Toxinscanhaveseveraleffectsontheirenvironment/hostnamely:

Acutelethality Sublethaleffectsonnon-mammalianspecies Sublethaleffectsonplants Sublethaleffectsonmammals Teratogenicity Genotoxicity/mutagenicity Carcinogenicity

Wewillonlyconsidertheeffectonmammalsespe-ciallyonman.Here theeffectof the toxinon thehostwillbedeterminedby several factors,namelythesubstanceanditsconcentration,therateofin-toxicationandthehost.Toxinscancausetemporarydysfunctioninthebody,leadtopermanentdamageinthecaseofchronicintoxication,oreventodeathinthecaseofacuteintoxication.Inrealityalltoxinscanbedetrimentaltothebodyinthecorrectdose.InthewordsofParacelsus,onlythedosemakesthepoison.

Thetoxicity,orrathertheeffectofthetoxinonthebodyinrelationshiptothedoseisdependentonsev-eralfactors:

1. Thegalenic formof the toxin.For instance,or- ganicmercury ismuchmoretoxic inagaseous formthanasinliquidform.

2. Whenatoxinismixedwithothertoxins,thetox- icitymaygoup,as toxinsoftenpotentizeeach other. For instance, two environmental toxins maybepresentinasub-toxicconcentration,but together with another toxin becomes severely toxic.

3. Thetimeinwhichitistakenin,thusacute,sub- acuteorchronicintoxication.

If someone would drink 10 liters of water atonce,itwillcausehyponatraemiaanddeath,forinstance.

Oftenintoxicationinminuteamountsovertimehave a different effect on the organism, e.g.cause cancer, or affect the immune system,whereasanacuteintoxicationwillhaveatotallydifferenteffect.

4. Thepatient: a Theabilityofthepatienttoregulateinview oftheintoxication. b Thegenderofthepatient. c Thebodyweight. d Apossibletolerancetothesubstance, especiallyifitisgiveninlowdosesorally overtime.

Thelatter(a-d)hasimportantimplicationsfortreat-mentstrategiesandwillbediscussedmoreindepthlater.

3 Measurement of Toxicity

Tocomparethetoxicityoftoxinswitheachother,itis testedunder strictly controlled laboratory condi-tions,mainlyonanimals.Thisisexpressedastheso-called LD 50which determines inwhich dose de-pending on the body weight, half of the testpopulationwilldie.LDthusstandsfor lethaldose.Thedoseresponsecurveofsuchintoxicationislinearorsigmoidal.However,recentlytheinteresthasbeenrevived in toxic exposure at doses below the so-calledNOAL(noobservedadverseeffectlevel)overtime.It is now known that many environmental toxinsovertimewillexertastimulatoryoraninhibitoryef-fect on processes in the body in the so-called U-shaped responsecurves, suchas seen inhormesis.Thismeansthatatoxinmayonlyexertacertainef-fectinaspecificlowdosagerange.Iftheconcentra-tiongoesbelowthisverylowdose,ithasnoeffect,and if the substanceoccurs in full strength itmayalsohavenoeffectoranothereffect.Atoxinthusmaybehighlytoxicwhengiveninahighdose,loosethis toxicity in a lower dose, but then still have adetrimentaleffectoverlongtermexposureinmin-uteconcentrations.Especiallyforchemicalcarcino-

Part I / Classes of Homotoxins

gensactingbyagenotoxiceffect this isof impor-tance.(Calabrese,2001)

Recently,apublicationinSciencebroughttolightanevenmorefrighteningfactconcerningtheeffectofenvironmentaltoxins.Thisconcernstheareaofepi-genetics,wheregeneticmaterialisdamagedbytox-insinonegenerationandthedamageistransferredtothenext,wheretheeffectsareseenforthefirsttime.(Skinneretal.,2005)

The effects on reproduction correlatewith alteredDNAmethylationpatternsinthegermline.Theabil-ity of an environmental factor (for example endo-crinedisruptor)toreprogramthegermlineandtopromotea transgenerational disease statehas sig-nificant implications for evolutionary biology anddiseaseetiology.

4 Classes of Toxins

Giventhelargeamountoftoxinsitisdifficulttoclas-sifythemchemically,eitherbyfunctionorbymodeofaction,sincemanyofthemwillfallintomorethanoneclass.Toxinscanenterthebodythroughair,wa-ter,soilpollution(intermsofaccumulationintofoodsources).Othersenterthebodythroughdeliberateuse,suchasdrugsofabuse,therapeuticdrugs,cos-metics,foodadditivesandcontaminants.Anumberofthesetoxinscanbeclassifiedasso-calledanthro-pogenictoxins,astheyareconnectedtotheactionsofman,forexampleby

Industrialprocesses Mininganddrilling Combustionoffossilfuelforheatingandpower andexhaustfumesfromtransportationvehicles

4.1 Pollutants

Gaseous pollutantsThesesubstancesaregasesatnormal temperatureand pressure. Amongst the pollutants of greatestconcernare:

Carbonmonoxide(CO) Hydrocarbons Hydrogensulphide(H2S2) Nitrogenoxides(NO) Ozone(O3)andotheroxidants Sulfuroxides Carbondioxide(CO2)

Particulate pollutants Dust Fumes Mist Smoke Aerosols

The effects of the pollutants are numerous, butamongthemostimportantarethedamagingeffectonthelungandtherespiratorymucosa,whichcon-tributetoallergy,asthmaandcancer.

4.2 Metals

Metalsarenaturallyoccurringbutaccumulateduetotheirusesinouractivitiesofcivilization.Thesein-cludearsenic,lead,mercury,cadmiumandchromi-um.Metalshaveawiderangeofdetrimentalactionsonthebody,andsharecommontoxicmechanismsandsitesofaction.

Enzymeinhibition/activation.Especiallyenzymescontaining sulfhydryl (SH) groups, which bindcertainmetalsinthebodyasaco-factormaybeaffectedasthetoxicmetalcoulddisplacetheco-factor.

Sub-cellularorganelles.Toxicmetalsdisrupt thestructureandfunctionofanumberoforganelles,suchastheendoplasmicreticulum,thelysosomesand the mitochondria. Metal inclusion bodiesmayforminthenucleus.

Carcinogenicity: Arsenic, chromium, nickel, aswellascadmium,andcis-platinarehumancar-cinogens. This isdue to the interactionsof themetallicionswiththeDNA.

8 Kidney:Thisisduetothefactthatthemainex-cretoryorganinthebodyformetalsisthekidney.Cadmium and mercury especially are nephro-toxic.

Nervoussystem:Especiallythelipidsolublemet-als,suchasmethylmercuryandorganicleadcom-poundsareneurotoxicas they readily cross thebloodbrainbarrier.

Endocrineandreproductiveeffects:Becausethemaleandfemalereproductivesystemsareundercomplexneuroendocrinecontrol,anytoxininter-feringwithanyoftheseprocessescanaffectthereproductivesystem.

Respiratory system: Acute exposure to metalsleadstoirritationandinflammationoftherespi-ratorytract,whereaschronicexposuremayresultinfibrosis(aluminium)ortocarcinogenesis(arse-nic,lead,nickel).

Metalbindingproteins:Thetoxicityofmanyofthemetals,suchascadmium,leadandmercurydependsontheirtransportandintracellularbio-availability.This isregulatedbythehighaffinitytocertaincytosolicproteins.Theseproteinstypi-callyarerichinthiol(SH)groups.Theseintracel-lularsinksareparticularlyimportanttoseques-termetalsawayfromvitalorganelles.Theroleoftheextracellularmatrixmustalsobementionedhere,asitwillbeanimportantstorageplaceformetalsbeforetheyreachthecellasitisalsorichinthiolgroups.

4.3 agricultural Chemicals (Pesticides)

Including Wood Preservatives

Theuseofchemicalstocontrolpestsgoesbackcen-turiestotheancientChineseandtheRomans.How-ever,inthe1900s,compoundswhichwenowiden-tifyaspesticidescameintobeing.Ideallypesticidesshouldbehighlyspecific,andonlyharmtheintend-ed target, but subsequently many health hazardshavebeenrecognizedcomingfromthesesubstanc-es.Amajorriskistheenvironmentalcontamination,especiallywheretheymayenterthefoodchainandthenaturalwaterresources.Ofcourseaveryserious

concernisthelonghalflifeofcertainofthesecom-pounds, as well as their lipophilic nature, whichmakesbioaccumulationandespeciallyaccumulationinthehumanbodyarealthreat.ManyoftheseareclassifiedasPersistentOrganicPesticides(POPs).

TheGloballyHarmonizedSystem(GHS)fortheclas-sificationandlabelingofhazardouschemicalsisaninitiativetopromotecommon,consistentcriteriaforclassifyingchemicalsaccordingtotheirhealth,phys-ical and environmental hazards, and to developcompatiblelabeling,safetydatasheetsforworkers,andotherinformationbasedontheresultingclassi-fications.ThisisanongoinginitiativeoftheEnviron-mentalProtectionAgency(EPA)intheUSA.

The primary classes of pesticides produced todayare: fumigants, fungicides, herbicides, and insecti-cides.

IntheUSAalone,thetotalproductionperyearis1.2billionpoundsofsuchchemicals.Producedarealsosome665millionpoundsofwoodpreservatives.

Organochloride pesticides are probably the bestknownclassofpesticides.Thesesubstances, intro-ducedinthe1940sand1950sincludefamiliarpes-ticidessuchasDDT,Chlordane,andDieldrin(devel-opedlaterasanalternativetoDDT).

Inacuteintoxication,organochloridesactasneuro-toxins.Thepersistenceofthisgroupofpesticidesforinstanceisamajorconcern,andtheywerebannedintheUSAin1972afterthebookbyRachelCarson:TheSilentSpringin1962.(Carson,1962)

However,groundwaterinmanypartsoftheworldstillremainscontaminated.

Somebiologicaleffectsofpesticidesandwoodpre-servativesinclude: DirectdamagetoDNAandthuscarcinogenic Interferencewithimmunefunction InductionoftheP-450enzymedetoxification system Endocrinedisruptors

9Part I / Classes of Homotoxins

4.4 Plasticizers and PBBEs

Plasticizers, most commonly, phthalates, alkylphe-nols, bisphenol A are additives, which soften thematerials towhichtheyareadded,e.g. thosethatgivehardplastics likePVC itsflexibilityandPBBEs(flameretardants),whichalso includetheso-calledphthalates occurring in softeners of plastics, oilysubstances inperfumes,additivestohairsprays, lu-bricants, paint and wood finishers is of particularconcernhere.Flameretardants,suchasPolybromat-edbiphenylethers(PBBEs)arematerialsthatinhibitorresistthespreadoffire.

Whilehighdosesofphthalatesdoconstituterisksinthe sense of traditional toxicology, low doses alsochangethestakesdramatically.Researchrevealsthatmale reproductivedevelopment is acutely sensitivetosomephthalates.Forexample,thephthalatesdi-butyl phthalate (DBP) and diethylhexyl phthalate(DEHP) produceddramatic changes inmale sexualcharacteristicswhenexposuretookplaceinutero,atlevels far beneath those of previous toxicologicalconcern. These changes included increases in therates of hypospadias and other indications of de-masculinization.(Clarketal.,1999)

Bisphenolalsohasbeenimplicatedinthedevelop-mentofcancer.(Welshonsetal.,2003)

4.5 Therapeutic Drugs

and Drugs of abuse

Thisisahugegroupofchemicalswhichwillnotbediscussedin-depthhere.Apartfromtheknownsideeffectsofthisgroup,manywillalsodisrupttheself-regulatoryprocessesofthebodyandwillcausede-regulationandotherdisease.Many,whowill treatonecondition,willputthepatientatriskforanoth-er.For instance,many immunosuppressantagents,usedinauto-immunediseasesareknowntobecar-cinogenic.

4.6 food additives and Preservatives

Additivesareaddedtofoodsaspreservatives(suchas metyl-p-benzoic acid, propionates) but also tochange the physical characteristics, such as color(tartrazine) odor and taste (Saccharin and Aspar-tame,Piperonalaswellasnitratesandnitrites).Cer-tainlyhundreds,andpossiblythousands,offoodad-ditivesareinuseworldwide,manywithinadequatetesting.Someofthesewereintroducedwhentoxic-ity testingwasnot sophisticatedand subsequentlywereshowedtobetoxic.Thequestionofsynergisticinteractions between all of these has not beenlookedatadequately.Manyofthesearecarcinogen-icormutagenic.

4.7 Endogenous Toxins

Theseareproductsofnormal regulatoryprocessesin the body,which accumulate, either through anoverproduction,orduetothefactthattheyarenotadequately metabolized or excreted. Examples ofthese are substances such as adrenalin and hista-mine.

Itisimportanttonotethatthesesubstancesarealsometabolizedbythesameprocesseswhichmetabo-lizeexternaltoxins.Whentheseenzymesystemsareoverloadedbyexternaltoxins,itcanleadtotheac-cumulationoftheseinternaltoxins.Thisiswhyforinstance toxicpatientswilloftensuffer frompanicattacks,asthemetabolismofadrenalinwillbeim-paired.Psychotoxinswillcauseanimbalanceintheneurotransmitterstatus,andwilldisturbthenormalhomeostasis. Furthermore, the chronic stress hor-mone,cortisol,playsaveryimportantroleintheme-tabolismandtheresultantdetoxificationoftheex-tracellularmatrix, so that chronic stresswill impairtherenewalofthematrixandpromoteanaccumu-lationoftoxinsinthematrix.

10

P R a C T I C a l C l a s s I f I C a T I O n O f T O x I n s

(Thereisnoplaceinwhichwedontencountertoxins,butbybecomingawareoftheexposurepossibilities,wemaybetterplantoavoidthem,andifnotpossible,atleastlimitthemand/orlearntodetoxify.)

E x O G E n O u s (Toxicants or xenobiotics)

InGEsTIOn

ThemucosalsurfaceoftheGItractisabout200xthatoftheskinsur-face.Inapersonslifetimeover25tonsoffoodisprocessedbytheGIsystem,thusanenormousloadofpossibletoxins(antigens,xenobiotics,microbesetc.).

InHalaTIOn(Environmental)

Thelungshavethegreatestexposureofanyorgantotheenvironment.Theairwebreathecontainsdust,chemicals,pollutants,gases,microbes,smallparticlesandliquidaerosols.

fOOD OuTDOORWaTER DRuGs InDOOR

Chemical Contamination

Chemicals

1 ToxicMetals Arsenic,Lead,Cadmium,Hg,etc.

2 PolycyclicAromatic Hydrocarbons fromincompletecombustion ofhydrocarbons

3 IndustrialChemicals

PCBs Chloroform Trichloroethylene

etc.

4 Hormones&Drugs inAnimals

5 Fertilizers

6 Pesticides

1 Solvents

2 Phosphates

3 Nitrates

4 Herbicides

5 Pesticides

6 Fertilizers

7 Industrialwastes etcWaterisusuallyanalyzed forlessthan60ofover700 chemicalsfoundregularlyin drinkingwater.

By Products of Microbes

1 Bacteria e.g.E.Coli

2 Viruses e.g.Hepatitisvirus

3 Parasites e.g.Giardia

4 Algae &theirtoxins

Prescription

Recreational

Airqualitystandardsmeasure6pollutants:

1 Suspendedparticulates

2 Carbondioxide

3 Nitrogenoxides

4 Sulphurdioxide

5 Photochemicaloxidants e.g.ozone,aldehydes

6 Lead

Microbes

1 Bacteria viruses

2 Protozoa e.g.Giardia

Indoorairpollutantsmaycomefromoutdoor,frommaterialsinthebuilding,orfromhumanactivities.

Chemicals & Minerals

1 Asbestos2 Formaldehyde3 Volatileorganicchemicals(VOCs)4 Radongas5 Nitrogenoxide6 Carbondioxide

furniture & Renovations

1 Wood(phenols&formaldehydefromplywood,paelling,etc.)2 VOCS(fromglues,fillers,paints,stains,varnishes,etc.)3 Paints(withvolatilefungicides,pesticides,mildew-cides)4 Fiberglass(frominsulations)5 Plasticizers(flexiblevinylfloors)6 Upholsteryfabrics&carpets (dye,formaldehyde,plasticizers,fungicides)7 Newcarpets(containmorethan20chemicalstokillbacteria, holdcolors,bindfibersandalsoreleaseacetone,benzene, styrene,xylene,tolueneandformaldehyde...inadditiontodust, chemicalandmicrobesthatitcanharbor)

Household Products

1 Personalcareproducts2 Laundryproducts&fabricsoftenerscontain numeroustoxicchemicalssuchas: Carcinogenics(chloroform,benzylacetate,limonene) S.N.C.toxins(camphor,ethylacetate,benzylalcohol, linalool,pentane)3 Householdcleaningproducts4 Pesticides(usedfrequently)

Microbes, Molds, Dust, Pets

1 Molds&mildewsinhumidareas2 Dust&dustmites3 Bacteria,viruses,fungi,etc.4 Petsincreasetoxins(dander,fleas,useof fleapowder&collarsthathavetoxicchemicals,etc.)

Human activities

1 Transmissionofmicrobes2 Tobaccosmoke&fireplaces3 Recreationaldrugsetc.Air-conditioning&heatingsystemstogetherwithbettersealingsfromwindows/doorshavedrasticallyreducednaturalventilationsthenumberofairexchangeshavebeenpracticallyeliminated(toxinsremainandfurtheraccumulateinside)

natural sources of air Pollutants

1 Volcanoes(ashes)

2 Naturalgas

3 Terpenes(plants)

4 Ammonia (frombiologicaldecomposition)

5 Smoke(fires)

6 Dust(soil)

7 Plants/pollens

8 Microbes

Human-Causedair Pollutants

1 Chemicaldumps

2 Wastedisposal

3 Fuelcombustion

4 Transportation

5 Industrial

6 Farmspraying

etc.

Mycotoxins

1 ToxinsProducedbyMolds e.g.Aflatoxinsproduced bytheAspergillusmolds

Heavy Metals

1 Mercury

2 Lead

3 Arsenic

etc.

Others

1 Asbestos

2 Radioactiveelements radon,radium,uranium

3 Gasoline

etc.

food additives

1 Coloration

2 Preservatives

etc.

11

Part I / Classes of Homotoxins

P R a C T I C a l C l a s s I f I C a T I O n O f T O x I n s

(Thereisnoplaceinwhichwedontencountertoxins,butbybecomingawareoftheexposurepossibilities,wemaybetterplantoavoidthem,andifnotpossible,atleastlimitthemand/orlearntodetoxify.)

E x O G E n O u s (Toxicants or xenobiotics) E n D O G E n O u s (Toxins)

InHalaTIOn(Environmental)

Thelungshavethegreatestexposureofanyorgantotheenvironment.Theairwebreathecontainsdust,chemicals,pollutants,gases,microbes,smallparticlesandliquidaerosols.

DERMal(Skin)

InDOOR

Indoorairpollutantsmaycomefromoutdoor,frommaterialsinthebuilding,orfromhumanactivities.

Chemicals & Minerals

1 Asbestos2 Formaldehyde3 Volatileorganicchemicals(VOCs)4 Radongas5 Nitrogenoxide6 Carbondioxide

furniture & Renovations

1 Wood(phenols&formaldehydefromplywood,paelling,etc.)2 VOCS(fromglues,fillers,paints,stains,varnishes,etc.)3 Paints(withvolatilefungicides,pesticides,mildew-cides)4 Fiberglass(frominsulations)5 Plasticizers(flexiblevinylfloors)6 Upholsteryfabrics&carpets (dye,formaldehyde,plasticizers,fungicides)7 Newcarpets(containmorethan20chemicalstokillbacteria, holdcolors,bindfibersandalsoreleaseacetone,benzene, styrene,xylene,tolueneandformaldehyde...inadditiontodust, chemicalandmicrobesthatitcanharbor)

Household Products

1 Personalcareproducts2 Laundryproducts&fabricsoftenerscontain numeroustoxicchemicalssuchas: Carcinogenics(chloroform,benzylacetate,limonene) S.N.C.toxins(camphor,ethylacetate,benzylalcohol, linalool,pentane)3 Householdcleaningproducts4 Pesticides(usedfrequently)

Microbes, Molds, Dust, Pets

1 Molds&mildewsinhumidareas2 Dust&dustmites3 Bacteria,viruses,fungi,etc.4 Petsincreasetoxins(dander,fleas,useof fleapowder&collarsthathavetoxicchemicals,etc.)

Human activities

1 Transmissionofmicrobes2 Tobaccosmoke&fireplaces3 Recreationaldrugsetc.Air-conditioning&heatingsystemstogetherwithbettersealingsfromwindows/doorshavedrasticallyreducednaturalventilationsthenumberofairexchangeshavebeenpracticallyeliminated(toxinsremainandfurtheraccumulateinside)

active(Injections)

1 Prescriptiondrugs

2 Recreationaldrugs

3 Animaltoxins bitesorpuncturebyfish,arthropods, parasites,etc.

Passive

Substancesthatarebothwater&fatsolublearemoreeasilyabsorbedthroughtheepidermisespeciallyifnotintegralandthroughthehairfollicles:

1 Drugs

2 Cosmetics

3 Chemicals especiallyfromtheairandfrom waters.showers,bathing,etc.)

4 Radiations

Produced in the Body

1 Physiologically

- Bilirubin

- Ammonia

- Uricacid

- Lacticacid

- Creatinine

etc.

Becometoxicifinexcessfor:

- production

- detoxificationandexcretion

2 UnderAbnormalConditions

- productionofwasteproducts (CO2,H2O2,freeradicals,etc.)

- hormonesand/orneurotransmitters

- microbialdebris

- pHimbalances

etc.

stored in the Body

Originallyfromexternaloriginbutintroducedintothebodywheretheyarestoredandbecomeacontinuoussourceoftoxicrelease

(Watersolublechemicalsareeasilyexcreted,butfatsolublechemicalsaccumulateinfatcellsandcellmembranes)

1 Dentalmaterials

2 Medicalimplants

3 Microbes(foci)

etc.

Conclusion

Toxinsareubiquitousinourenvironmentandcanaccumulateforyearsinthegroundwater,aswellascovervastdistancesduetoclimaticphenom-ena.

Different classes of toxins exist, such as pollut-ants,metals,agricultural chemicals,plasticizers,food additives, therapeutic drugs and endoge-nous toxinswhichare formed in thebodyandnotadequatelyexcreted.

Manytoxinsoccurintheso-calledNOAL(noob-servedadverseeffectlevel),butstillcauselong-termproblemssuchascarcinogenesisifpresentatminuteconcentrations.

Epigeneticeffectsoftoxinsarenowrecognized,where one generation is exposed to the toxin,buttheeffectisonlyseenintheoffspring.

Thetoxicityoftoxinsrangefromlethalitytotera-togenicity to genotoxicity aswell as carcinoge-nicity.

Toxins canalso impair the immune system, theintracellularorganellesandcauseenzymeinhibi-tion or activation, or mimic endogenous hor-mones, when they are called hormone disrup-tors.

12

1

The Physiology of Detoxification

Part lI / The Physiology of Detoxification

Inthepreviouschapterwesawthatthebodyisex-posedtoawidevarietytoxinspresentintheair,wa-ter,soilandfood.Thebodyhasseveralinherentde-fensemechanismsandmembranebarrierstopreventthe absorption anddistribution of the toxinwhentheintoxicationhasoccurred.Onceinsidethebody,the internaldefensesystem,orBasicBioregulatorySystemwill bemobilized inorder to eliminate thetoxinoratleasttrytocompensateforit.

In this chapter, wewill look at theway the bodydealswiththesetoxins.

Beforeatoxincanhaveadetrimentaleffectonthebody, itneedstoreachthetargetorganorcell. Inprinciplefourstepsarenecessaryforthis:

Absorption Transport Metabolism Distributionandstorage Elimination

Toxicokinetics studies the absorption, distribution,elimination,metabolismand/orclearancethattakeplaceinthebodyafterexposuretothetoxin.Toxico-dynamicsontheotherhandstudiesthebiochemicalandphysiologicaleffectsofdrugsandtoxicantsanddeterminestheirmechanismofaction.Toxicokinet-icscanalsobeseeninthediagrambelow.

Exposure

Absorptionattheportalsofentry

Distributiontothebody

Metabolismtolesstoxicmetabolites

Metabolismtomoretoxicmetabolites

Metabolismtoconjugationmetabolites

Excretion

Interactionwithmacromolecules(proteins,DNA,receptors)

Toxiceffects:geneticcarcinogenic,immunologic

Turnoverandrepair

Fig. II,1: Toxicokinetics

14

1 absorption

Toxinscanenter thebody throughall thesurfaceswhichareincontactwiththeoutsideworld.These comprise the skin, the mucous membranesand also the gastrointestinal tract. In general, theabsorptionovertherespiratorymucosaisthequick-est,whereasitistheslowestoverthedermalroute.Theoverallentrydependsontheamountoftoxinspresent,butalsoonthesaturabilityofthetransportprocess.

The mucosal surfaces have several barriers whichwillpreventtoxinsfromenteringthebody,suchasamucosalbarrier, thephysicalpresenceofsymbioticbacteriaaswellastheso-calledtightjunction.The skin alsohasbarriers in the formof a certainlevelofpH,etc.

2 Transport

Oncethetoxicantisabsorbedintothebodyitmovesaroundintwoways,eitherbybulktransferviathebloodorlymph,butalsolocallythroughdiffusionaltransferovershortdistances.ThepathwhichatoxintakesafterabsorptionisillustratedinFig.II,2.

During absorption, distribution and elimination, atoxinwillencountervariouscellmembranesbeforeinteractingwiththetargettissue.Thesemembranebarrierswilldifferfromrelativelythickareasoftheskin to relatively thin lungmembranes, inallcasesthoughthecompositionisrelativelysimilar.

Thecellmembranecanbeseenasalipidmatrix.Itcontainsbothphospholipids(hydrophobic)portionsaswellashydrophilicheads.Intra-andextracellularproteinstransversethemembrane.

Fig. II,2: Toxin path after absorption

Environment Interstitialuid Plasma Interstitialuid

Mucosaoforganofelimination,skin

Capillarymembrane

Targetcellmembrane

Capillarymembrane

Intracellularuid

Subcellularorganellemembrane

Intra-organelleuid(mitochondria,liposome,nucleus)

Environment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma Interstitialuid

1

Thiswilldiffer fromorgantoorgan.Themyelin inthebrainconsistsof100%lipidbilayerwhereasmi-tochondria have only a 40% lipid bilayer. This, ofcoursehasimplicationforthedistributionoffatsol-uble toxins.Dependingon the fat solubilityof thetoxin, it will thus transverse the cell membrane.Manyoftheproteinswhichtranversethemembraneareactiveintransportoftoxinsoverthecellmem-branes.

Thedistributionof theabsorbedtoxinwilldependonvariousfactors,suchasphysiologicalfactors,butalsothephysiochemicalpropertiesofthedrug.ThisprocessisthusaREVERSIBLEmovementofthetoxi-cant between the blood and tissues and betweentheextracellularandintracellularcompartment.Thevelocity at which this movement is reversible be-comesimportantwhenweaddressthemobilizationanddrainageoftoxinslateron.

Factorswhich can complicate thedistributionof atoxincanbethefollowing:

PerfusionoftheorganThewell perfused tissues include the liver, kid-neysandbrain;whereasthelowperfusedtissuesinclude the bone and fat tissuewhere there issloweliminationfromthesetissues.

ProteinBindingThere also may be significant protein bindingwhichcouldaffectthedeliveryofthedrugtothetissuesandviceversa.Especiallybindingoftoxinsto the matrix structures may trap these toxinsthereforyearsandpreventelimination.

Proteinbinding alsoplays a very important role inthetransportoftoxins.Therearemanyplasmapro-teinsinvolvedinsuchatransport,butmostlyinvol-vedarealbumin, alpha-acid-glycoprotein, the lipo-proteins,andglobulins.Thelipoproteins,suchasHDL,LDLandVLDLareveryimportanthere,assomanytoxinsarelipophilic,andthereforetheywillcarryanumberoftoxins.Ironandcopperwill again be carried by themetal bindingglobulins,transferrinandcereluplasmin.

3 Distribution and storage

Plasma protein binding is not selective and toxinscan thus competewith each other and evenwithendogenoussubstancesforbinding.Covalentbindingtotheproteinformsaminorpart,butthedissociationisextremelydifficultandthecar-riermoleculeischanged,andmayeventuallyplayaroleincarcinogenesis.Noncovalent binding is more common. The toxincan dissociate easier from this bond. However, insomecasesthebondmaybesostrongthatthetox-inremainsboundforweeks,monthsoryears.Cer-tainmetalshavehighassociationconstantsandtheirdissociationisextremelyslow.

Iftheaffinityforanorganislarge,thetoxinwillac-cumulateorformadepotforyears.Ingeneral,lipidinsolubletoxicantsstayintheplasmaandinterstitialfluids, while lipid soluble contaminants reach allcompartments,andmayaccumulateinfat.

Sometoxinshavespecificaffinityforcertaintissues.Tetracyclineshaveahighaffinityforthecalciumcon-tainingtissues,whichisseeninthediscolorationofteethifitisgivenundertheageof14years.Simi-larly, the anti-malarial, chloroquine has an affinityforthemelanin,andcanbetakenupbytissuesliketheretina,causingaretinitis.Thisdrugisoftenusedinlupusandotherconnectivetissuediseases,whichmakes an ophthalmic check up every six monthsmandatory.

Bonewillalsoconcentratecertaintoxicantssuchasleadwhereasuddenlossofbonecanleadtoacutereleaseofthetoxinandhavedireconsequences,es-peciallyaftermenopausewhentheremaybeasud-denboneloss.Thiswillbediscussedlaterwhenwelookattheide-alratesofdetoxification.

Lipophilic pesticides, such as the organochlorinesandPCBscanbeexpectedtoaccumulateinfattis-sues.TheaffinityofmetalstoSHgroupshavealsobeenaddressedinthepreviouschapters.

Part lI / The Physiology of Detoxification

1

Thebindingofthesemetalstothenumerousthiolgroups intheextracellularmatrix isofspecialcon-cern.

Certainareaswillbenaturallylesspenetrabletotox-ins.Thebrain,whichisprotectedbythebloodbrainbarrier, issuchanexample.Diseaseprocessessuchas meningitis and other inflammatory or infectiveprocessescandisruptthisbarrierandthuscausetox-instoenterthebraintissue.

Other tissue blood barriers include the prostate/bloodbarrierandthetestis/bloodbarrier.

Unfortunately,otherthanwhatisgenerallybelieved,theplacentaisapoorbarrierandthefetus isthusexposedtoallthetoxinstowhichthemotherisex-posed.ThishasbeenseeninfattissuebiopsieswhichwereperformedonnewbornsandfoundnumeroustoxinssuchasPCBs,dioxinandothersinthetissues.Weneed thus to assume in todays environmentalpollution, that our newborns are already contami-natedwithtoxins.

4 Metabolism of Toxins

Oneofthemostimportantdeterminantsoftheper-sistenceoftoxinsinthebodyistheextenttowhichtheycanbemetabolizedandexcreted.Several familiesofmetabolicenzymesareactive inmetabolismofendogenousandexogenoustoxins.

Theseincludeoneofthemostimportant,theP450system,butalsotheflavincontainingmonooxidases(FMOs),thealcoholandaldehydedehydrogenases,amineoxidasescyclooxygenases,reductases,hydro-lasesandtheconjugatingenzymessuchastheme-thyltransferasesaswellastheglutathionetransfer-asestonameafew.

Mostofthemetabolismtakesplaceintheliver,andasmostofthetoxinsenteringthebodyarelipophil-ic,theyneedtobecomewatersolubleforexcretion.Afterentrancetotheliverandotherorgans,xenobi-oticsmayundergotwophasesofmetabolism.ThisisdemonstratedinFigII,3.

Xenobiotic

Cysteine, Glucoronic Acid,

Alcohol

GSH

Aldehyde

Glutathione

Acid

Phase I

Phase II

Free RadicalNitric Oxide

Tissue destruction

e

P450

Vit C, Mg, Fe

Selenium, Mg, B3

Zn, NADH Fe, Mo, B2

ExcretionConjugationFig II,3: Liver metabolism pathways

1

Part lI / The Physiology of Detoxification

4.1 Phase I Reactions

PhaseImetabolisminvolvesmainlytheCYP(P450)system,theFMOsandthehydrolases.Followingtheadditionofapolargroup,conjugatingenzymestyp-icallyaddmoreconstituents,suchassugars,sulfate-sor amino acidswhichmake the compoundmorewatersoluble.

Inthisprocess,howeversometimesmoretoxicinter-mediate metabolites are formed, these then willhavetobedetoxifiedagain.Theseintermediateme-tabolites are likely to react with nuclear parts ofmacromoleculesunless theyare furtherdetoxified.Anexampleisthebreakdownofalcoholtoacetalde-hyde,whichismuchmoretoxicthatthealcohol.

TheCYPsystemorP450playsaveryimportantroleinthephaseIreactions.TheCYPswhichconstitutesthe carbonmonoxide-bindingpigmentof the livermicrosomesarehemeproteins.Anomenclaturehasbeen developed for the different types and iso-forms.

Althoughmammalsareknowntohave18CYPfam-ilies,onlythreearereponsibleforxenobioticmetab-olism.Theremainingareinvolvedinsteroidhormoneproduction. They are classified according to thegene, subfamily and lastly the isoform (arabic nu-meral,letter,arabicnumeral).

ThusCYP3A4isresponsibleforthemetabolismofmanydrugsaswellasendogenoustoxinsandexog-enoustoxins.

Itsactivitycanalsobeinfluencedbyahostofdrugsandchemicals,anditcaneitherbeinduced,whichwill have the result that certain drugs are broken

downtooquickly,e.g.,warfarin,whereasgrapefruitjuiceinlargequantitiesisknowninfacttodamagethissystemirrevocablyandthusmayleadtoanac-cumulationofdrugs.

ThePhaseIdetoxifyingpathwaytakescareofenvi-ronmentaltoxinssuchaspesticides,pollutantsandfoodadditivesaswellasdrugsandalcohol.Theendproductsofourownmetabolismarealsoprocessedhereforexcretion.Fatsolubletoxinsarechangedbywayofoxidation,reductionandhydrolysistomakethemmorewatersoluble forexcretionvia thebileandthekidney.

Itisimportanttonotethattheseenzymesneedcer-tainco-factorstofulfilltheiraction.Thesearetraceelements,vitamins,aminoacidsandsubstanceslikeNADH.(seeFigII,3)

PhaseIproducessignificantamountsoffreeradicalsduringthisdetoxificationprocess,andiftheantioxi-dant status of the patient is not adequate tissuedamagemayoccuriftheP450isoverloaded,orin-duced.Somesubstances,suchascaffeine,alcohol,certain drugs, dioxin and organophosphates (usedaspesticides),andpaintfumescaninducethispath-way. Sometimes intermediate substances like theacetaldehydeformedduringthemetabolismofcer-tain toxins, like alcohol, can bemore toxic to thebody than the original substance. Certain people,called fast acetylators,will thenbemoreprone todamageoftheliver,asthetoxinisfastmetabolizedto thisdangerous intermediate, and then thepro-cessisslowagain.Theseindividualsareathigherriskfor liver damage during ingestion of toxinswhichwilluse thealcoholdehydrogenasepathwaytobedetoxified,forexamplewhenparacetamoloverdoseoccurs.

18

4.2 Phase II Reactions

ThePhaseIIpathwayorconjugationpathwayusessubstances rich in sulfhydryl groups tometabolizetoxins.Anumberofthesesubstances,likecysteineandtaurineaswellasglutathionewhichareformedfrom glycine, glutamine and cysteine under influ-enceofaseleniumdependentenzyme,alsoactasfree radical scavengers andheavymetal chelators.During conjugation of toxins they are lost to thebody forever, as they are excretedwith the toxin,whereasasfreeradicalstheycanberegenerated.SomesubstanceswillonlyusephaseIorphaseIItobedetoxified,otherswilluseboth. It is thusclear,thatifthephaseIIpathwayisoverloaded,thefreeradicalscavengingabilitywillbegivenupinfavoroftheconjugationfunctionandfurtherdamagetotheliver parenchymamay occur. Also if the patient isdeficient inseleniumfor instance,glutathionepro-ductionwillbeimpaired,withtheresultantoftoxic-ityandfreeradicaldamage.

5 Elimination

Afterthetoxinshavegonethroughthesetwophas-es,theyarereadytobeeliminated.However,iftheintermediarytoxinisnotbrokendown,orthetoxinloadistoohightherewillbebioaccumulationofthetoxin.

Theabilitytodetoxifyandeliminatetoxins ispara-mount to themaintenanceofhealth in anorgan-ism.Forunicellularorganismsasimpleprocessofdiffu-sion isenoughtoeliminatetoxins,however,multi-cellularorganisms,especiallyiftherehasbeenanin-crease in complexity, needs to find other ways toeliminatetoxins.

Environment Interstitialuid Plasma Interstitialuid

Mucosaoforganofelimination,skin

Capillarymembrane

Targetcellmembrane

Capillarymembrane

Intracellularuid

Subcellularorganellemembrane

Intra-organelleuid(mitochondria,liposome,nucleus)

Environment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma InterstitialuidEnvironment Interstitialuid Plasma Interstitialuid

Fig II,4: Toxin path for excretion

Withanincreaseincomplexity,organismshavede-veloped an increase in size, a decrease in surfacearea to bodymass ratio, compartmentalization ofcellsandorgans,aswellasanincreaseinlipidcon-tent.Togetherwiththefactthatorganismsneedtoprotectthemselvesfromtheenvironmentwithbarri-erssuchasscalesandskin,meansthatthereislesspossibilityfortoxinstodiffuseoutofthebody.Thiswas solved, by developing specializedmethods ofmetabolismfortoxinsandspecializedroutesofelim-ination.Wehavethusmajorandminoreliminationroutes

Themajorroutes involvethe liver, thekidneys,themucousmembranes and the lungs as well as theskin, whilst the minor routes involve the saliva,sweat, milk, hair, and secretion from reproductiveorgans.

To eliminate the toxin, itmust go through the re-verserouteaswasdescribed insection II fromtheplaceof storageback to theexternalenvironment(FigII,4).

Chemicalsaretransportedfromtheplaceofstoragemainlyviathebloodstream.Asthecirculatorysys-temleansitselftowardthetransportofwatersolu-ble substances, themore lipophilic substancesare,thelesslikelytheyaretofreelydiffuseintothebloodandthusthemobilizationofthesetoxinsfromtheirplaceofstorageismoredifficult.ThesameprocessaswasdiscussedinsectionII,wherebindingoftox-ins to carrier proteins and lipoproteins is the waythesetoxinswillenterthebloodstream.

Thetoxinsarethustransportedbacktotheorgansofelimination,butiftheseorgansaredysfunctional,overloaded or damaged, the toxins cannot be ex-creted.Thismeansthatsuchtoxinswillcirculatefur-therinthebloodstreamandthroughdiffusionentersomecompartmentsagain,e.g.a fatsolubletoxinmay nowbe stored in the brain,with dire conse-quences.Thestimulationoftoxinsoutoftheircom-partments should thus be a slow and careful pro-cess.

Herewedistinguishtwogroupsofcompartments:

1 Therapid-exchange system in these compartments, tissue concentrationof

toxicantissimilartothatoftheblood

2 Theslow-exchange system in these compartments, tissue concentrationof

toxicant ishigher than inbloodduetobindingand accumulation-adipose tissue, skeleton andkidneyscantemporarilyretainsometoxins,e.g.arsenicandzinc.

TheimportantfactisthatDetoxificationandDrain-ageshouldcarryonso longtill theslowexchangesystemisgivenachancetogiveupallthetoxins.Theorgans involved intheDetoxificationandDrainageofthetoxinswillbediscussedinthenextsection.

19

Part lI / The Physiology of Detoxification

Conclusion

Toxins have to cross severalmembranes in thebodytobeabsorbed,andtoeventuallybestored,oreliminatedviatheorgansofelimination.

Toxinsfollowsimplekinetics,andobservethedif-fusion over semi-permeable membranes till asteadystateisachievedonbothsideofthemem-brane.

Thesebasickineticsaredifferentfortoxinswhohasahighassociationco-efficientwithproteinsandcellularstructures,beitinthebloodorintheorganofstorage.

These kinetics affect both the storage and themobilizationoftoxins inandoutofthesecom-partmentsandneedstoformthebasisonwhichthepracticalDetoxificationandDrainageisexe-cuted.

Two groups of compartments can be distin-guished,dependingontheperfusionoftheor-ganandtheamountoftoxinboundtoprotein.

Therapid-exchange system. Inthesecompartments,tissueconcentration

oftoxinissimilartothatoftheblood.

Theslow-exchange system In these compartments tissue concentration

oftoxinishigherthaninbloodduetobindingandaccumulation.

Manytoxinsaremetabolizedbeforetheycanget

excreted.Oneofthemainpurposesofthisistorenderfatsolubletoxinswatersolubleforexcre-tioninthebileandkidneys.

TheP450systemofenzymesplaysamajorrolehere, especially in the liver,where it comprisesthephaseIreactions.This isaugmentedbythephaseIIreactions.

OrgansareatdangerduringtheactofDetoxifi-cationandDrainage,duetothehighconcentra-tionoftoxinsmovingthroughtheorganatthetime,andthroughthegenerationoffreeradicalsduringthedetoxificationprocess.

Supportof thesesorgans is thusofutmost im-portanceduringdetoxificationand theelimina-tionofthetoxin.

20

Aswasseen in thepreviouschapter,manyorgansandtissuesareinvolvedintheabsorption,thetrans-port,themetabolism,thestorageandtheelimina-tion of toxins. These highly complex processes re-quire special properties of the organ to fulfill thisfunction.Often,theorganitselfmaybeendangeredbydiseaseduetotheexcretion,storageandmove-mentoftoxinsthroughit.Weshallnowconsidertheseorgansinmoredepth.

1 The liver Theliverisoneofthemostim-portantdetoxifyingandelimi-nation organs in the body,and metabolically the mostcomplex.Theliverisamajororganofchemicaleliminationinthatittakesupchemicalsfromblood,metabolizeschemicals, andensures thebiliary and renal secre-tion of toxins. The liver detoxifies a large array ofexternalandinternaltoxins.Italsoplaysaroleinthecholesterolmetabolism,glycolysisandgluconeogen-esis,providingmanyoftheplasmaproteinsneces-

sary forcarryinghormones, fatsandprovidesclot-ting factors, to name a few of its numerousfunctions.Theprincipalcellintheliverresponsibleforthede-toxifying action is the hepatocytewhich facilitatesthetwopathwaysdiscussedinsectionII indealingwith mainly fat soluble toxins in order to renderthemhydrophilicorwatersoluble.We have seen that most toxins reach the organsofeliminationviathebloodstream.Theliverisverywellperfused,andgetsitsbloodfromtwosources:the arterial oxygen rich blood which is deliveredthrough the hepatic artery, and the venous bloodthroughtheportalveinfromwhichthelivergetsallthebloodthatisshuntedfromthecapillariesofthegutandspleen.Hepatocytesarepracticallybathed inbloodas thisbloodtransversesasystemofsinusoids.Thisprovi-desavery largesurfaceforchemicalstoeasilydif-fuseintothelivercellsorhepatocytes(seeFigIII,1).Duetothehighlipophiliccharacterofmanyofthechemicalswhicharemetabolizedbytheliver,tobeabletoenterthewatersolublearea,theywillneedcarrierproteins.Severalintracellularcarrierproteinsarepresentinhepatocytes.

The Organs of Detoxification and Elimination

21

Part lll / The Organs of Detoxification and Elimination

Fig. III,1: The liver as detoxification organ

CanalicularMembraneBileduct

HepaticPortalVein

HepaticArtery Hepatocytes Sinosoid

ToCentralVein

WatersolubleToxin

22

Onceinsidethehepatocytethechemicalcaninter-facewiththephaseIandIIenzymestoundergobio-transformationandbecomewatersoluble.Anum-berof thesesubstances thendiffuseback into theblood,wheretheywillbetransportedtothekidneysforelimination.

2 Excretion in Bile

These bio-transformed molecules can also diffuseover the membranes of the bile canalilculus, andthereforeflowintothebileduct.Thisisthenfurtherdelivered with the other constituents to the gall-bladderwhichexcretesthebileintotheintestineforfecalelimination.(SeeFig.III,1)

In many instances we also want to facilitate thedrainageofbile.Thegallbladdersprimaryfunctionis to secrete bile and release it through the cysticduct.Thisductjoinsthehepaticductfromthelivertocreatethecommonbileduct,whichthenemptiesintotheupperpartofthesmallintestine,thusintotheduodenum.Bilenotonlycarriesawayandneu-tralizestoxins,but itstimulatesandaidsdigestionsbyemulsifyingfats,stimulatingperistalsis,andact-ingasanaturallaxative.

3 Entero-hepatic Circulation

Thisisaprocesswherebyalreadyconjugatedchemi-calswhicharewatersolubleisdeconjugatedbyhy-drolyticenzymesinthegut,andthenrenderedlipo-philicagain,andareoncemorereabsorbedbythegut.The liver is thusexposed toanother roundofthesametoxintoreprocessitagainandagain.Thisincreasetheretentiontimefortoxicchemicalsinthe

liver,andmayincreaselivertoxicity.Someofthesemetabolitesaremoredangerousthantheiroriginalsubstanceandaswesawabove,theP450isalsoasourceoffreeradicalswhichwillthusfurtherdam-agethelivercell.

ItisthusimperativetoprotecttheliveraswellduringtheprocessofDetoxificationandDrainage.Thiswillbe furtherdiscussed in the sectiononmethodsofdetoxification.

4 The KidneysThekidneysareorgansspecialized intheexcretionofnumerouswatersolubletoxinsandmetabolites,maintainingho-meostasis of the organism. Thekidneysdetoxify

Drugs Heavymetals Othertoxins

Eachkidneypossessesaboutonemillionnephronsabletoperformexcretion. Renal excretion repre-sentsaverycomplexeventencompassingthreedif-ferentmechanisms:

GlomerularfiltrationbyBowmanscapsule Activetransportintheproximaltubule Passivetransportinthedistaltubule

Bloodisdeliveredtothekidneysviatherenalarteryandabout625mlofplasmamovethroughthekid-neys per minute, and of that 125 ml is filteredthroughtheglomelularmembrane.Mostofthewa-teristhenreabsorbedagainintheproximalanddis-tal tubule, so thatonly approximately 1-2 liters ofurineisformedperday.(SeefigureIII,2)tal tubule, so thatonly approximately 1-2 liters ofurineisformedperday.(SeefigureIII,2)

2

Fig. III,2: Filtration in the kidney

Somefilteredsubstances,suchasglucosewillalsobetotallyreabsorbed,sothat innormalconditionsthere isnoglucose intheurine.Othersubstances,manyofwhichareharmfultothebodyarefiltered,secretedandthenminimallyreabsorbed.Creatinineissuchasubstance,andcanthusbeusedtotesttheefficiency of the kidneys in clearing harmful sub-stances. Itaccumulatesinthebloodwhenthekid-neysaredysfunctional. Ifthekidneysaredamagedthrough disease or toxins (drugs and chemicals),theirabilitytoexcretedrugsisreduced,andincon-ventionalmedicine,thedoseofdrugsinneedstobeadjustedaccordingly.It is important for the urine to be on the alkalineside,as it facilitates thesecretionofcertaindrugs,likebarbituratesforinstance,andalkalineurinewillpreventurinarytractinfections.

Thekidneyscommonlybear thebruntofchemicaltoxicitysincethenephrontendstoconcentratethetoxin and thus increase levels of toxic exposure inthetubules.

ThekidneysthusalsoneedprotectionandsupportthroughouttheDetoxificationandDrainagestages.

5 The Matrix and lymph

5.1 The Matrix

This forms the final biophysical layer between thecellandtheregulatoryorgans.Thissystemwaslar-gelyforgottensinceVirchow,aphysicianwhowor-kedinViennaandacontemporaryofFreud,sawacell through amicroscope and postulated that alldiseasesoriginatedonacellularlevel.Anotherphy-sicianworkingthereatthetime,Rokitansky,wantedtostillbringinthehumeraltheory,butwaslargelyignored.

Pischinger and Heine, two modern researchers,broughtthisbackintobalance,andthenewermo-lecularbiologytexts increasinglyrecognizetheroleofthematrix.

Thecellonitsownisactuallyanabstraction.Thecelldoes not come in contactwith the blood vessels,nerves,veinsandlymphvesselswhichdelivernutri-entsandmessengersandremovetoxins.Itreliesforthisonthebiophysicallayermadeupofhighlypo-lymerizedsugarproteincomplexescalledGlycoami-noglycans (GAGs) likehyaluronicacid, chondroitin

Fig. III,3: The extra-cellular matrix

Part lll / The Organs of Detoxification and Elimination

GlomerularCapsule ProximalTubes

TotheUrinary

Bladder

CapillaryBedVein

LoopofVein

Glomerulus

Artery

24

sulphateandheparinorwhentheyare linkedtoaprotein backbone, they are called proteoglycans(PGs).Thismolecularsievemustbecrossedbytheentirearrayofmetabolicproducts.

Sugar protein complexes are phylogenetically con-sideredthebestcarriersof information.HeineandPischingercouldshowthatifthematrixisdisturbedbyapinprickinoneplace,thedisturbanceiscom-municatedtothewholematrixinseconds.Thisma-kesitanidealsystemthroughwhichtogiveanyin-formationtothebody.Theacupuncturepointisananatomicalstructureoriginatinginthematrix,abelllike structure, and it offers a wonderful windowintothissystem.

Unfortunately,becauseofthechemicalandelectri-cal charges on theGAGs and PGs, they also be-cometheplacewheretoxinsarestoredfora longtime.

Thematrixisalsooneofthetissueswithaslowper-fusion,andthuswillhavepatternofslowturnover.Thematrixhasitsownbiorhythm,andisdependentforinstanceoncortisolandthyroidhormonetobeactivated. During the early hours of themorning,thebodygoesintoanebbphasewithalowcortisol,and it isduringthisebbphasethatthematrixwillpurge itself fromtoxicmaterials.Stressedpatients,or patients who through a change in their sleep-wake cycle have lifted or disturbed the diurnalrhythmof cortisol,will not be able to detoxify, astheremaybeamisfiringbetweenthematrixandtheliver.Cortisoneinhighdosesasmedicationwillalsodisturbtheinnaterhythmofthebody,andre-sult inmatrix toxicity.We can see that in patientswhohasbeenoncortisonetherapy,astheybecomeswollen and puffy in thematrix. Patientswho arehypothyroidhavebeendescribedashavingmyxo-edema in the older textbooks. The same swellingwillbeapparentinthematrixifthematrixbiorhythmis disturbed. Many toxins are hydrophilic and willdrawfluidintothematrix.Theresultisedema,whichweinclinicalmedicineseeascyclicaledemainfe-malesorascellulite.

Itisclearfromtheabovethatifthemolecularsieveof thebiophysical layer fails, ispolluted that therewillbedistortionofinformationtoandfromthecell.Ifthedisturbanceissevereenough,cellulardiseasewillensue.

Newermolecularbiologicalresearchshowsthatthematrixisthesiteformanymessengerswhichcodesforintracellularphenomena,which,ifdisturbed,cancontribute tomany disease phenomena, includingcancer.(LukashevME,WerbZ,1998)

5.2 The lymph systemApartfromitsroleintheimmunesystem,thelymphsystemalsoacts as a detoxifying organanddrainsmostof the toxinsfromthematrixorconnectivetissueviathelymphvessels,which finally drain into thesuperiorvenacava.Thelymphsystemismadeupofamyriadoflittlelymphvesselswhichthenaggre-gateintolargervessels.Theselargerves-sels are interspersed by aggregations of lymphoidtissue,which aremade up of immune competentcells. These lymph nodes, as the aggregations arecalled,reallyfunctionassuperdetectioncentersforantigens,but it isalsoherewheretosensitized im-munecellswillmigrateinordertoproducemillionsof similarclonesof that sensitizedcell.Themigra-tioniscalledhominginimmunologyandthemul-tiplication, cloning. The swelling we see in theselymphnodesduringaninfectionisduetotheactiva-tionoftheimmunecascadebythesesensitizedcells.Thiswillcauseaninflammationofthelymphnode.

Amajorportionofourimmunesystemislocatedinthese lymph aggregations, and in fact the largestpartofourimmunesystemisfoundinthegutlin-ingsso-calledPeyerspatches.Thisisthereasonwhywecanmanipulatethewholeoftheimmunesystembyinterveningonthelevelofthegutlining.

2

Physiological considerations

Thelymphsystemisaslowdrainagesystem,andthepropulsionoflymphtowardstheheartisdependenton a number of factors. Firstly, the lymph vesselshave no valves, but depend on a sort of negativesuctionactionofthetruncalvessels,whichissimilartothatofanamphibianheart.Thelymphflowsrela-tivelyslowlyatarateof1-2ml/min,againstahighresistance, whereas the venous flow is rapid at2-3l/minagainstalowresistance.Twothirdsofthebodyfluidislocatedintheintracellularspace,whilstathirdislocatedintheextra-cellularspace.Ofthis,75%isintheinterstitialspaceorconnectivetissueandabout25%circulatesasplasma.Thelymphandvenousflowisresponsibleforcirculatingmostoftheextra-cellular fluid, and the interstitial fluid in par-ticularisdrainedmainlybythelymphsystem.

Fromtheaboveitisclearthatthefactorswhichwillcontrolthefluidinterchangewillbe:

Oncotic pressureoftheplasmaandthelymphisdeterminedbytheamountofmacromoleculessuchasprotein,andtheelectrolytecontentsuchas sodium,potassium,etc. in the solution.Sol-utesexertacertainpressureinanyfluid,astheydrawwatersotospeakandthemorethereisoftheminasolution,thehigherthepressure.Whenapatientisproteindeficientforinstance,throughmalnutritionordisease,weseethattherearenotenoughmacromoleculestokeepthefluidinthevascularcompartment,andthefluidwillleakoutinto the interstitium,with edemaas the result.Kidneyfailureontheotherhandresultsinanac-cumulationofelectrolytesandothermacromol-ecules in the interstitium.The result is that theoncotic pressure in the interstitiumwill exceedthatoftheplasma,andagainedemawillensue.

Thehydrostatic pressureisamechanicalpres-sure,whichcanbecomparedtoahosepipecon-nectedtoanopentap.Thesmallerthediameterof the hose pipe, the higher the pressure, themore open the tap is, the higher the pressure,and if there isanobstruction likeakink in thehose, the higher the pressure before the kink,andthe lowerthepressureafterthekink.Fluidalwaystendstodrainfromahigh-pressureareato a low-pressure area over a semi permeablemembrane,which isrepresentedbythevenouscapillaryorthelymphcapillary,untilthepressureisequalonbothsides.Thusifthereisobstructionin the venous system, similar to a kink in thehose, therewill beahighpressure in the vein,andthebodywilltrytoequalizethepressurebe-tween the vein and the interstitium, thus thefluidwillalsoaccumulateintheinterstitium.

If there is for instancecardiac failure,weseeaback pressure into the venous system,andinourhosemodelabove,thiswillrepresentawideopentap,withmorepressureinthevenoussys-tem,andthenmorefluidintheinterstitium.

Lastlyifthereisanobstructionofthelymphflow,wewillseeaback pressure in the lymph sys-tem andedemawillagainbetheresult.WeseethisindiseasesofthelymphvesselslikeElephan-tiasis,wherethelymphvesselisscarredbyapar-asiteforinstance.

The lymph system as a detoxifying organ

Thelymphsystemhasaspecialrelationshipwiththematrix.Itissotosayastheonlywayoutfortoxinswhicharestoredinthematrixisviathelymphsys-tem. Italsomeans that if thematrix isoverloadedwith toxins, the lymph system will be overloadedwithtoxinsaswell,asthelymphsystemhastore-move the toxic debris out of the interstitium, andat a certainpointwill alsobe cloggedwith these.The stimulation of lymph flow is thus one of themostimportantstepstoachievewhencleaningthematrix.

Part lll / The Organs of Detoxification and Elimination

The stimulation of lymph flow is thus one of themostimportantstepstoachievewhencleaningthe

2

6 The lungs

Notonlydoesthemucosaoftherespiratory tract plays an im-portant role as a barrier totoxinsaswasdiscussedear-lier, the lungs are also oneofthemainpointsofexcre-tionofgaseousandvolatiledrugs such as anestheticsandevenalcohol.Elimination via the lungs is typical for toxins withhighvolatility(e.g.organicsolvents).Gasesandva-pours with low solubility in blood will be quicklyeliminatedthisway,whereastoxinswithhighbloodsolubilitywillbeeliminatedbyotherroutes.

OrganicsolventsabsorbedbytheGITorskinareex-creted partially by exhaled air in each passage ofblood through the lungs, if they have a sufficientvapourpressure.Thebreathalysertestusedforsus-pecteddrunkdriversisbasedonthisfact.Thecon-centrationofCO2inexhaledairisinequilibriumwiththeCO2-Hbbloodcontent.Anotherexampleistheradioactivegasradonwhichappears inexhaledairduetothedecayofradiumaccumulatedintheskel-eton.

Anumberoftoxinsandbacteriaarealsosecretedinthemucousoftherespiratorytract,andexpectora-tionisthuswelcomedandsupported.

7 The Mucosal Membranes

Mucosal membranes form the largest part of ourbodiesincontactwiththeoutsideworld,andtheyarethereforeveryspecialized.Amucosalsurfaceislikeamicrocosmosinitself,andagoodexampleofall the components of the auto regulatory systemactiveinoneorgan.Withalmost80%of the immune system formingthe mucosal associated lym-phoid tissue (MALT), somehormoneshavingreceptorsonthemucosalcells,afullcomplementofnervesme-diatedbytheautonomicner-voussystem,anactive lymphaticdrainage,andthelargecomplementofextra-cellularmatrix,themucosalmembranecompri-seoneofthemostimportantregulatoryorgans.Notonly does it form a very selective barrierwith thetightjunctioninbetweentheepithelialcellandad-hesionmoleculesplayinganimportantroleindecid-ingwhatwillenterthebody,mucosalsurfacescanalso letsomeof the immunecells, likeneutrophilsthroughthetightjunctiontoingesttoxicmaterialinthe lumen. It furtherprotectsagainst toxinsbyse-creting chloride and other solutes into the lumenwhichwillosmoticallydrawwaterinordertowashawaytheoffender,afactthatweseeasdiarrheainthegutforinstance.

Theintegrityofthesesurfacesisthusofmajor im-portanceinthedefenseagainsttoxins.

The symbiotic gut bacteria also need mentioninghereasabarrierfunction.Notonlydotheyformapassivebarrieragainsttoxinscomingincontactwiththeepithelialsurface,theyalsocontributetothede-fense against toxinsbyproducing certainmetabo-liteswhichwillserveasfuelforthegutlining,andassuchwillthenhelpthemucosalcelltokeepthein-tegrity of the tight junction. However, due to thehydrolyticenzymesproducedbythem,theycanalsocontributetothedangerousentero-hepaticcircula-tionmentionedabove.

2

absorption via gastrointestinal tract

Toxinscanbeingestedinthecaseofaccidentalswal-lowing,intakeofcontaminatedfoodanddrinks,orswallowingofparticlesclearedfromtherespiratorytract.

Inthecaseoftoxinsbiotransformed inthe livertoless toxic or non-toxic metabolites, ingestion mayrepresentalessdangerousportalofentry.Afterab-sorptionintheGITthesetoxinswillbetransportedbytheportalveintotheliver,andtheretheycanbepartiallydetoxifiedbybiotransformation.The active area for absorption in the intestines isabout100m2.

Some toxic metal ions use specialized transportsystemsforessentialelements:Thallium,cobaltandmanganeseusetheironsystem,whileleadappearstousethecalciumsystem.

Manyfactorsinfluencetherateofabsorptionoftox-insinvariouspartsoftheGIT:

Physico-chemicalpropertiesoftoxins,forexam-ple,particlesizeisimportant,thesmallerthesize,thehigherthesolubility.

Quantityoffoodpresentinthegut(dilutingef-fect).

Residence time ineachpartof theGIT (fromafewminutes in themouth to one hour in thestomachtomanyhoursintheintestines).

Theabsorptionareaandabsorptioncapacityoftheepithelium.

LocalpH,whichgovernsabsorptionofdissociat-edtoxins;intheacidpHofthestomach,non-dis-sociatedacidiccompoundswillbemorequicklyabsorbed.

Peristalsis (movement of intestines by muscles)andlocalbloodflow.

Gastricandintestinalsecretionstransformtoxinsinto more or less soluble products; bile is anemulsifyingagentproducingmoresolublecom-plexes(hydrotrophy).

Combinedexposure toother toxins,which canproducesynergisticorantagonisticeffectsinab-sorptionprocesses.

Presenceofcomplexing/chelatingagents. Theactionofmicrofloraofthegutcomprising

about1.5kgmadeupof60differentbacterialspecieswhichcanperformbiotransformationoftoxins.

Whenwethusdetoxifyanddrain,itisalsoimpera-tive to support theactionsof thegut,but also tosupport the integrityof thebarrier function in thegut.

8 The skin

The skin forms the second largest surface of ourbodyafterthemucosawhichisinconstantcontactwiththeoutsideworld.Apartfromthebarrierfunc-tion,itisalsoamajordetoxifyingorgan,andhasthesameP450systemseenintheliver,aswellasgluta-thionetotakecareofpolycyclicaromatichydrocar-bons. The skin can absorbmany substances (likepesti-cides and chemicals in cos-meticproducts),andhastobe able to detoxify them.Another important func-tionoftheskinistopro-tectusagainsttheharm-fulUVraysfromthesun.The glutathione and other freeradicalscavengerslikecatalaseandsuperoxidedis-mutaseareofimportance,astheyscavengethefreeradicalsformedbytheUVrayexposure.Likeintheliverthough,inductionofthedetoxifyingP450path-waywill also generate free radicals so that in thepresenceoftoxinstheskin ismoreexposedtotheeffectsoffreeradicals,whichleadstoimmunotoxic-ity,tissuedestructionandeventuallyskinageingaswellascancer.Conversely,UVraysdamagethede-toxifyingabilityoftheskin(theP450),andsundam-agedskinisthuslessabletodealwithtoxins.

Part lll / The Organs of Detoxification and Elimination

28

Due to its role indetoxification, andbeingoneofourmostimportantexcretoryorgans(throughsweatandevaporation),wealsoseetheskinoftenbearingthe brunt when other detoxifying organs like theliver are overloaded. Eczema, drug induced rashesandincreasedsweatingareexamplesofthis.Inthesecases it is thus important to support other organslike the liver fordetoxification in skindisease. TheliverandskinforinstancebreakdownhistamineinthebodythroughtheP450.Ifthesystemsareover-loaded,allergywillensue.Histamineandotherami-nes are also formed during the inflammatory pro-cess,andmanyenvironmentaltoxins,likealcoholicdrinks, especially red wine can contain a largeamountofhistamine.

9 sweat

Manynon-electrolytescanbepartiallyeliminatedviaskinbysweat:ethylalcohol,acetone,phenols,car-bondisulphideandchlorinatedhydrocarbons.

10 Hair

Analysisofhaircanbeusedasanindicatorofho-meostasis of some physiological substances. Alsoexposure to some toxins, especially heavy metals,canbeevaluatedbythiskindofbioassay.

11 Other Routes of Elimination

Milk Many metals, organic solvents and some organo-chlorinepesticides(DDT)aresecretedviathemam-maryglandinmothersmilk.Thispathwaycanrep-resentadangerfornursinginfants.

saliva Some drugs and metallic ions can be excretedthroughthemucosaofthemouthbysaliva,forex-ample, lead(lead line),mercury,arsenic,copper,aswellasbromides,iodides,ethylalcohol,alkaloids,andsoon.Thetoxinsarethenswallowed,reachingtheGIT,wheretheycanbereabsorbedoreliminatedbyfeces.

Part lll / The Organs of Detoxification and Elimination

Conclusion

Manyorgansareinvolvedinthestorage,metab-olismandeliminationoftoxinsoncethetoxinisabsorbedintothebody.

The liver is one of themajor detoxification or-gans, and plays an especially important role intheprocessingoftoxinsbeingabsorbedviatheoralroute.

Theliveriswellperfusedandalsoequippedwithenzymes to render fat soluble toxins to watersoluble toxins tobeexcreted in thekidneyandbile.

Thekidneydealswiththeabovementionedwa-tersolubletoxins,butisalsothemajororganofeliminationdealingwithheavymetals and sev-eraldrugs.

Thelungplaysamajorroleintheeliminationofvolatile gases, e.g. organic solvents and gasesandvapourswithhighsolubilityintheblood.

Themucousmembranesactasabarrier,butalsocontaintheP450systemofenzymesandcanac-tivelymetabolizeandexcretetoxins.

Thesymbioticmicrofloraplaysaspecial impor-

tantrolehere.

Sweat,hair,milkandsalivaareminoreliminationorgans,andcanbeusedtotesttheeliminationoftoxinssuchasheavymetalsandothertoxins.

Excretionoftoxinsinmilkposearisktothein-fant.

The matrix and also with it the adipose tissueform amajor site of deposition of bothwaterandfatsolubletoxins,andduetothefactthatthisisaslowexchangecompartmentandincloseassociationwiththecell,isamajorareaofcon-cerninchronicintoxication.

Thelymphsystemistheonlysignificantwaytox-ins canbedrained from this compartmentandtherefore needs special attention during thedrainageprocess.

29

0

Tools for Detoxification

In the previous sections we looked at the varioustoxinswhichcanaffect theorganismaswellasatthe way the organism deals with the toxin undernormalphysiologicalconditions.Inthisandthenextsectionwewillexplorehowtosupportthisprocessinwellpersonsbutmostly inpatientswithmildorseriousdisease.

Wehaveseenintheprevioussectionsthat:

1 Wearesurroundedbytoxins,andthatthereisnoplaceonearththatissafeanymore.

2 Thatthesetoxinscanenterthebody,andifnotmetabolizedandeliminatedcanstayinthebodyfor years, in compartments that are relativelypoorlyperfused,likethefattissueandthecon-nectivetissue.

3 Thatthesetoxinscanhavedetrimentaleffectsinthebody,evenifpresentinminuteamountsovermanyyears.

4 Thatthehumanbodybeingacomplexorganismhasdevelopedsophisticatedmechanisms to se-questrate, metabolize and eliminate these tox-ins.

5 That theorgansofeliminationcanbe lesseffi-cient throughdiseaseandoverloador, throughthelackofvitalco-factorsneededfortheproperfunctioningofenzymes.

6 Thosetoxinsfollowsimpletoxicokineticsinthattheydiffuseover severalmembranesaswellasbindtoplasmaproteins.Thiswilldeterminetheratethattheyenterthebodyandcertaintissuecompartments,butalsotheratethattheyarere-movedfromthesecompartments.

1 Why Does a Person need

to Detoxify and Eliminate?

Itshouldbeclearfromtheabovethattoxinsstoredinthebodyornoteliminated,willbedetrimentalforvariousreasons.Toxinscanhaveawiderangeofef-fects,suchasfatigue,brainfog,concentrationloss,but also other not such apparent manifestationssuchastheso-calledchloracnewhichiscausedbyhalogenatedtoxins.

Aswesawabove,sometoxinscanbeendocrinedis-ruptors,causeimmunedysfunction,andintheworstscenarioactascarcinogenicsubstances.Duetothewidedistributionoftoxins,andourfastlifestylewithmodernmalnutritionandtoxicfood,aswellastheincreaseinpsychologicalstress,theneedfor Detoxification and Drainage exist in every pa-tient.Detoxificationanddrainagerequirements,however,willbedifferentindifferentpopulations.

Theaimsofdetoxificationcanbesummarizedastheso-called4-Streatment:

sTOP externalsupplyoftoxins.

suPPORT theorgansof DetoxificationandDrainage.

sTIMulaTE eliminationoftoxins.

sEnsITIZE thepatientfor furtherdetoxification.

We saw in part II of this booklet that toxins havebasic kinetics. Toxins need to diffuse over severalmembranes,toreachdifferentcompartments.Mosttoxinsreachtheothercompartmentbypassivedif-fusionover semipermeablemembranes. Toxins arecarriedtoandfromcompartmentsintheblood,andthereforeitmeansthatwewouldliketoreducetheconcentrationoftoxinsinthebloodsothatthetox-inscanstart todiffuseback intothebloodstreamagain.For this reasonweput thepatient on anon-toxicdiet,givealotoffluidsduringthedetoxificationpe-riod,andalsopro-activelystopthesupplyoftoxins,suchas inhalants,alcoholandother toxins.This isthefirstS:STOP.

Inothercases,thetoxinsareboundtoproteinsandalsotoSHgroupsinthecellandinthematrix.Weoftenthenhavetostimulatethereleaseofthetoxinfromthesemolecules.Thisisanactiveprocessandneedssupport.Togetthebodytofreeitselfoftoxinsweneedtodotwothings:Supporttheorganswhich

1

Part IV / Tools for Detoxification

metabolize harmful substances, support the func-tionof theorganswhich store toxins, suchas thematrix,andlastlywealsohavetostimulateelimina-tionfromtheseorgans.

It is important tonote thatonce stored toxinsarereleased they often have not completed theirme-tabolism,andthereforestillneedtobemadewatersolubleintheliverbeforegettingexcretedinthekid-neyandotherorgans.If the stored toxins are released too rapidly all atonce,ortheliverandothermetabolizingandelimi-nation organs are overloaded or not functioningproperly, the released toxins will diffuse into theblood,butcannotbeexcreted.Theywillthuscircu-late inthebloodstreamtilltheyfoundacompart-ment where the concentration is less than in thebloodandthendiffuseintothiscompartment.ThecruxisthatinthiswaytoxinsaremerelyshiftedfrompointAtoB.Thisisnotsuchaprobleminwellper-sons or patientswithmild toxicity, but in patientswithseveretoxicityitmayhaverepercussions,suchasheavymetalsnowenteringthebrainwhereitisextremelydifficulttoremovethem.Especially inpatientswhere theorgansofelimina-tionarenotfunctioningproperlyorburdenedbydis-easeorwithothertoxins(suchasseeninpatientsonchemotherapy),thisneedstobeconsidered.Inthesepatientsweneedtosupporttheorgansofdetoxifi-

cationandeliminationfirstbeforeweactuallydrainthetissues.It isalsoimportanttonotethattheprocessofDe-toxificationandDrainageputsa severeburdenonthebody,andthusintheveryfrailandsickpatientsitcanputanotherburdenonthebodyandinthesepatients detoxification should be done as a laterevent,whenthepatienthasreceivedothermedica-tionstosupportthebody.Detoxificationanddrain-agealsoneedsenergy, and therefore the catalystsareastandardadditiontomorestrenuousdetoxifi-cationprograms.Apartfromthefactthattheyalsoplayaroleincellulardetoxification.(Seebelow)

2 Tools for

Detoxification and Drainage

Foreachorganthereisaproductwhichwillsupportthetissues.Thesearemostlytheso-calledcompositapreparationswhichalsocontaintissueextractsandoften catalysts. And there are basic preparationswhicharecombinationsofplantmaterialsandalsomineralsontheotherhandaremostly(butnotonly)usedtostimulateelimination.Weshallnowdiscussthevariousmedicationsavailablefordetoxification.Firstly the basic regimens, which can be generallyappliedinalldiseases,andthenanumberofdiseaseprocesseswillbediscussedseparately.

Mildtomoderatetoxicity Organs Moderatetoseveretoxicity

Detox-Kit Liver Heparcompositum

contains +

Nux-vomicaHomaccord, Kidney Solidagocompositum

Berberis-Homaccordand +

Lymphomyosot Matrix Pulsatillacompositum/Thyreoideacompositum

+

Coenzymecompositum Cell Ubichinoncompositum/Glyoxalcompositum

Useatleastfor6weeks Usefirstforsixweeks,thenDetox-Kitforanother6weeks

Fig. IV,1: General Detoxification and Drainage

2

2.1 The General Basic Detoxification

This regimen isoftenused initially inpatientswithmildtomoderatetoxicity.Withthisbasic regimen,wewant tosupport the liverandgut, thekidneysanddrain thematrix of toxins aswell as help theexcretion.

Thesepreparationscomeindropformand30dropsofeachcanbeaddedtoa1.5literbottleofwatertobe taken over the day. This is thus a convenientmethodtodeliverthemedications.

nux vomica-Homaccordsupportstheliverandthegut.LikewithmostHomaccordsthismedication isalsofunctiotropictotheliverandgut,whichmeansthatitwillimprovethefunctionoftheseorgans.

Nuxvomica-Homaccord

LiverNuxvomica,Lycopodium

GutBryonia,Colocynthis

Fig. IV,2: Nux vomica-Homaccord

Fig. IV,3: Berberis-Homaccord

Berberis-Homaccord

UrinarytractBerberis

LiverandgutColocynthis,Veratrum

SkinBerberis

Part IV / Tools for Detoxification

Berberis-Homaccordhasthesameeffectasabove,butismorefunctiotropicforthekidneys,however,italsohasanactionontheliverandgallbladder.

lymphomysothasbeendesignedtobeadrainageremedy,andshouldnotbeusedinitiallyinthecaseofseveretoxicity,oriftheliverandkidneysareover-loaded.Ithasseveralcomponentswhichhelpsdrainthetis-sues of the various organs. It is thus a universaldrainageremedyandcanalsobeusedinthecaseofdiseaseofthelymphoidorgans.lymphomysothasbeenstudiedincasesofdiabeticneuropathywhereitwasseentobeaseffectiveasalphalipoicacidin-fusions,whicharecurrentlythetreatmentofchoicefordiabeticpolyneuropathy.Thepostulationwasthatlymphomyosotwilldraintheso-calledAdvancedGlycosylationEndproducts(AGEs) inthematrixofthesepatientsandtherebyreduce the inflammatory potential around thenerves.(Dietzetal.,2004)Theactionsofthevariousconstituentsoflympho-myosotaredepictedinthefigurebelow.

In some countries, nux vomica-Homaccord, Berberis-Homaccord aswell as lymphomyosotarecombined intoonepack, theso-calledDetox-Kit.InmostpatientswithmildtomoderatetoxicitythethreeproductscanbegiventogetherasDetox-Kit.

Often Coenzyme compositum is given togetherwiththesethreeproducts.Thecatalystswillbedis-cussedseparatelybelow,but this ismainly tosup-porttheKrebscycle,andalsotodetoxifythecellularstructures.ThismakestheDetoxificationandDrain-agequitecomplete.

The symptomsofDetoxification andDrainage canvaryfrompatienttopatient.Mostpatientsstartwithadiuresis, or losingwater,whileothersmaydrainpreliminarilyover thegut,withslightdiarrheaandloosestools.Thecoloroftheurineandstoolsmayalsochange.Somepatientswillusetheskinandthelungstodetoxify,whichmanifestsasanincreaseinsweatwithodororwithatachypnea.

Lymphomyosot

RespiratorytractMyosotisTeucriumNatriumsulfuricumNasturtium

LymphaticsystemandtheMatrixPinussilvestrisScrophulariaLevothyroxineCalciumphosph.JuglansFerrumjodatum

Fig. IV,4: Lymphomyosot

LiverandgutFumaria,Geranium,Gentiana

UrinarytractSarsaparilla,Equisetum

4

2.2 The General

advanced Detoxifi cation

The purpose of this advanced detoxification is tosupport the organs of detoxification, especially inpatients with a high toxic burden, or in patientswheretheorgansofDetoxificationandDrainagearenot functioning optimally. This is also true for pa-tientswhoaredebilitated.

Inthesepatientsitisveryimportantnottoincreasetheloadoftoxinstooearly,asthesepatientsoftenalready have genotoxic effects of toxins or activecancer.Forinstance,ifapatientwithbreastcancerishighly contaminatedwith DDT, which is an estro-geniclikesubstance,itcanactasapromoterforthecancer.Experimentswithovarectomizedmicehaveshown that themice can develop breast cancer iftheyare intoxicatedwithDDT,thenovarectomizedsothatthereisnointernalsourceofestrogens.ThemicethendevelopedbreastcancerfromthereleaseofDDTfromthetissues.(Bigsbyetal.,1997)

Itisthuswisetogoslowlyinpatientswithdecreaseddetox ability, or high loads of toxins aswell as inobesepatientswhichcouldstoreanumberoflipo-

philictoxins.Fastingshouldbeavoidedinmostpa-tientsforthisreason,asfastingcausesaveryquickrelease of toxins from the storage compartmentsintothebloodstreamduetothefactthattherearenoimmediatetoxinscominginfromthefood,andtheeliminationanddetoxorganswillthenturntheirattentiontoolderstoredtoxinsandthesemaythenbereleasedinlargeamountsandatonce.

The advanced detoxification products aim to sup-portthemajororgansofDetoxificationandDrain-age(seeFigIV,5).Theseproductsaremostlycom-positapreparations,whichimpliesthattheyhaveaspecialformulationwithplantandmineralmaterial,butthenalsocontainorganextractsofthespecifictargetorgans,ortissuewhichwillsupportthetargetorgans,aswellascatalystsandsometimesvitaminsindilution.

Theplantmaterialisinalowdilutionandhasaho-meophytotherapeutic effect, whilst the minerals,catalystsandorganextractsoccurinconcentrationswhicharethoughttobestimulatory.Theseconcen-trationsarethesameasthoseinwhichmanyofthebodys internalmessengers such as neurotransmit-tersandcytokinesarepresent.

Fig. IV,5: Advanced detoxifi cation products

Liver Urinarytract/ Lymph Skin Gut Gallbladder Connective Respiratory Kidney tissue tract

Basic Detox-Kit Detox-Kit Detox-Kit - Detox-Kit Chelidonium- Detox-Kit Bronchalis-Heeldetoxification/ Homaccorddrainage

Advanced Heparcomp. Solidagocomp. Tonsillacomp. Cutiscomp. Mucosacomp. Heparcomp. Thyreoideacomp. Mucosacomp.detox1

Advanced Hepeel ReneelH Galium-Heel/ Schwef-Heel Nuxvomica- Leber-Galle Pulsatillacomp.detox2 Lymphomyosot Homaccord Tropfen(new)

Advanced Injeel-Chol Galium-Heel/detox3 Lymphomyosot

Forcellular Coenzymecomp./ Coenzymecomp./ Coenzymecomp./ Coenzymecomp./ Coenzymecomp./ Coenzymecomp./ Coenzymecomp./ Coenzymecomp./detoxification Ubichinoncomp. Ubichinoncomp. Ubichinoncomp. Ubichinoncomp. Ubichinoncomp. Ubichinoncomp. Ubichinoncomp. Ubichinoncomp.inaddition

Part IV / Tools for Detoxification

ThesupportmedicationfortheliverisHepar com-positum.Thisproducthasthetypicalcompositumconfiguration, and will also support other tissuessuchasthepancreasandthecolon.Itisdesignedtosupportthedetoxifyingabilityoftheliverandgall-bladder.

Forthekidney,themedicationofchoiceissolidago compositum.Againthistypicalcompositumprod-uct combines organ extracts with plant materialsand minerals as well as with some catalysts. Thisproduct has a strengthening and toning effect ontherenaltract.

The lastpartoftheadvanceddetox is thesupportandactivationoftheextracellularmatrix.Itisimpor-tanttorealizethatfattissue,bone,andalsocarti-lageare all part of the extra cellularmatrix, albeit

withdifferencesindensityandtypesoffibres.How-ever, thesecompartmentsare relativelypoorlyper-fusedandalldrainedbythelymphsystem.Theyallalso share the high concentration of negativelychargedaminoacidsandSHgroupswhichwill allbindtoxinstightlyandwillkeepthesetoxinsseques-tratedforyears.Furthermore,adiposetissueoffersalargereservoirforfatsolubletoxins.

Thematrixisinconstantrenewalthroughabalancedprocessofcontrolleddegradationandcontrolledre-pair.Thedegradationismediatedviatheproinflam-matorycytokineswhichinturnwillmobilizetheso-called matrix metalloproteinases (MMPs) whichdissolves the tissueof thematrixand through thismethodalsogetridoftoxiccomplexes.(SeeFigureIV,6)

Interleukin-1

Interleukin-6

TumorNecrosis

Factor

Metalloproteinases

T I S S U E I N F L AMMAT I O NA N D D E G R A DAT I O N

(Freeradicals)

Osteoarthritis

Atherosclerosis

Cancer

Transforming

GrowthFactor

Anti-Metalloproteinases

T I S S U E R E P A I R

Tissuehealing

Fig. IV,6: Degradation and repair in the matrix

Thisprocessisundercontrolofseveralphysiologicalsubstances, like cortisol and thyroid hormone tonameafew. Ifpatients for instance loosethebio-rhythmofcortisolwhichweneedtocontrolthisre-pair process in thematrix, thepatientwill endupwithatoxicandedematousmatrix,suchasseeninpatientsonlong-termcortisoltherapy.

In such cases and in cases where the patient hasbeenunderseverepsychologicalstress,weneedtoactivatethematrixasanorganagain.

Thisisbestachievedbyproductscontainingthefac-torsneededfortheactivationandstrengtheningofthematrix,andthereforeweuseproductssuchasThyreoidea compositum, as it has a number ofsuis embryological and stem tissues in it, such asFuniculus umbilicalis made from Whartons jelly.Thesehaveastrengtheningandactivatingeffectonthemesenchyme,ofwhichthematrixispartof.

Oneothermedicationusedintheactivationofthematrix isPulsatilla compositum. Thismedicationcontainsaplant,Pulsatilla,themineralsulfurinho-meopathic formand lastlyalsocortisone inahighdilution.Thishighdilutionwillhaveahomeopathi-callyreversaleffect ifapatienthadahighdoseofcortisoneovertime.Thesulfuristhoughttoactivatethesulfurcontainingsubstancesofthematrix.

2.3 The Catalysts

Thisgroupofsubstancesareusedindetoxificationintwoways,namelyassupportfortheKrebscycleandsecondlyascellulardetoxifiers.

Therearethreeofthem,thefirstbeingCoenzyme compositum,thesecondubichinon compositum,andlastlyGlyoxal compositum.

Coenzyme compositumhasallthefactors intheKrebscycleandmanyoftheco-factors involved intheKrebscycle.Thevitaminsindilutionarethoughtto have a detoxifying effect on the cellular struc-tures.

ubichinon compositumhasanumberofquinonesinandapart fromsupporting theelectron transferchainduringcellular respiration, theyarealsoem-piricallyusedincancerpatients.

Glyoxal compositumwhichisamixturebetweenGlyoxalandMethylglyoxalwillhaveastimulatingef-fectonthecellularrespiration.Thelatteristhoughtto have themost stimulatory effect, although thishasnotbeenstudied.Currentstudiesarebeinginiti-ated to scientifically prove the actionof theseho-meopathically prepared catalysts which has beenempiricallyusedsince1976.

Thecatalystsplayaspecificallyimportantroleinde-toxification,andareaddedtodetoxifycellularstruc-tures.TheactionofGlyoxal compositumisthoughttobedeeperthanthatofubichinon compositum.andCoenzyme compositum.Glyoxal composi-tum isused inpatientswhohaveaseverecellulartoxicity,suchascancerpatients.Glyoxal composi-tumisusedinlongerintervals,togetherwithubi-chinon compositum and Coenzyme composi-tum. For instance, Glyoxal compositum can begiven1x perweek for 4weeks togetherwith theothercatalystswithabreakofseveralmonthsinbetweenandthenusedagain.

Coenzyme compos

itum

Ubichinoncompos

itu

m

compositumG lyoxal

Fig. IV,7: Action of catalysts

Conclusion

Mostpeopleneedtodetoxifyanddrainduetotheenvironmentalloadoftoxins.

Toxinsaccumulatethroughacombinationofin-creaseloadaswellasmodernmalnutritionandpsychologicalstress,whichimpactsontheabilityofthebodytodetoxifyanddrain.

The4-Sregimen isapracticalwaytoapproachtheproblemoftoxinaccumulation:

sTOP externalsupplyoftoxins. suPPORT theorgansofdetoxification

anddrainage. sTIMulaTE eliminationoftoxins. sEnsITIZE thepatientforfurther

detoxification.

AntihomotoxictoolsforDetoxificationandDrain-agecanbeusedintworegimens,thebasicandtheadvanced.

Generalsupportof regulation isalsoneeded intheformofvitalco-factorstothedetoxificationsystems(minerals,vitamins,traceelements,ami-noacids).

Thebasicdetoxificationproductsnux vomica-Homaccord, Berberis-Homaccord as well aslymphomyosotformatriotosupportthefunc-tionoftheliver,thekidneysandfinallytodrainthetissuesviathelymphsystem.

Theadvanceddetoxificationoffersacomprehen-sivesupportoftheorgansofdetoxificationandeliminationandisusedasapreparationphaseinpatientswheredetoxificationneedstobedoneataslowerpace,orwheretheorgansofDetoxi-fication andDrainage have beenweakened bydiseaseoroverload.

Special considerations need to be observed incertain clinical groups, such as obese patients,patientsonchemotherapy,theelderlyaswellaspatientswithahistoryofdrugabuseinthepast.Thepreparationphaseintheadvanceddetoxismandatoryinthesegroups.

Part IV / Tools for Detoxification

8

Practical Detoxification

ThissectionwilldealwiththewayweapproachDe-toxificationandDrainageinthedifferentpatients.

1 Clinical Groups

Theassessmentonwheretostartwiththedetoxifi-cationprocessismadewithtwotools:

The detoxification point scale

The clinical assessment of the patient

1.1 The Detoxification Point scale

This isbuiltuptoincorporateallthemajortoxicitysymptoms. Patients evaluate their symptoms on ascaleof0to4:

Point count

0=Neveroralmostneverhavethesymptom

1=Occasionallyhaveit,effectisnotsevere

2=Occasionallyhaveit,effectissevere

3=Frequentlyhaveit,effectinnotsevere

4=Frequentlyhaveit,effectissevere

Points are then totaled, yielding a score that indi-catestheseverityofthepatientstoxicburden:

Total points < 100: Patientwithmildtomoderatetoxicity

Total points > 100: Patientwithmoderatetoseveretoxicity

1.2 The Clinical assessment of

the Patient

Group 1Point count < 100: mild to moderate toxicity

Mostlythewell/healthypersonwhowantstocleanherorhisbodyandoptimizethedrainageoftoxinsaswellasthepatientwithmilddiseasesuchasskinconditions, fatigue,acne, irritablebowelsyndromeandothersignsofmildtoxicity.

D Basic Detoxification and Drainage with Detox-Kit

Group 2Point count > 100: severe toxicity

Mostly the patient with some diagnosed diseaseprocess,includingautoimmunityandpre-cancerousconditionsaswellasthepatientwithseveretoxicity.Butalsoallthefollowingpatientsmustberegardedas special groups andwill need advanced supportfirst:

Thecancerpatientonactivetreatmentsuchaschemotherapyandradiationtherapy

Theolderpatient Theobesepatientwithmetabolicdisease Thepatientwithimpairmentofthe

eliminationorgans,suchastheliverorthekidney

Thepatientwhohadsignificantdrugaddictioninthepast,evenifthiswasalongtimeago

D advanced Detoxification and Drainage

note: Patients in the special groups are always classified into group 2 regardless of their point count.

9

Wealsousethepointscaletofollowourtreatmentsandtodecidewhenapatientwithinitialseveretox-icity should switch to the basic regimen. (See Fig.V,1:TheDecisionTree)

2 How long should

the Patient Detox?

Fromourdiscussionabove,weseethatthereareingeneraltwowavesofdrainagewhenwestarttoap-plythe4-Sregimen:

sTOP externalsupplyoftoxins.

suPPORT theorgansof DetoxificationandDrainage.

sTIMulaTE eliminationoftoxins.

sEnsITIZE thepatientforfurtherdetoxifi- cationandlifestylechanges.

Firstweseeafairlyfastdrainageoftoxinsthroughthewellperfusedcompartments.Thiswill result inanincreaseinurinaryflow,loosestools,andincreaseinsweatingandmildheadache.

Afterafewdaysthepatientwillfeelbetter,butoneshouldnotstoptheDetoxificationandDrainage,asa secondwaveofDetoxificationandDrainagewillfollowfromthelowerperfusedcompartments,suchasthefattissuesandtheconnectivetissues.Itisthusimportanttoclearthesecompartmentstotally,overweeks.Inpatientswithseveretoxicity(group2)itiseven good to continue the drainage process withlymphomyosot up to 12 weeks or even longer,whilst in others, the patient can go on lympho- mysotfor4-6weeks(group1).

Note:Ifthepatienthasapointscoreof