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SupplementationforHealth,WellnessandControl

Preparedby:M.WilliamsMay2018

Objectives

1. Toestablishtheroleofsupplementsforthe

preventionandmanagementofNCDs(HTN&

T2DM)

2. Toidentifykeymicronutrients/supplements

andtheirroleinthepreventionandmanagementofT2DM andHTN

3. Tooutlinecommondrug-nutrient/disease-

nutrientinteractionswithmicronutrients

4. Tosummarizeusingcaseexamplestheeffectsofdrug-nutrientandnutrient-disease interactionsin

T2DMandHTN

DietarySupplementsDietarysupplementsareproductsdesignedtoaugmentyour

dailyintakeofnutrients.

Vitamins Minerals Aminoacids Enzyme Herb

BenefitsofSupplementsinNCDs

Anti-oxidativeMicronutrientsandNCDs• Humanbeingsneedoxygentosurvive

• UtilizationofoxygenproducesROS

• FreeradicalsovertimeresultsindegenerativeCellularfunction

• DevelopmentofNon-CommunicableDiseases(NCDs)

Anti-oxidativeMicronutrientsandNCDs•ExcessiveproductionofreactiveoxygenspeciesisreflectedbyincreasedperoxidationoflipidandDNA,leadingtooxidativestress.

•Freeradicalsarealsoproducedfromexposuretocigarettesmoke,excessexposuretothesun,drinkingalcohol,exposuretolargeamountsofheavymetalsandduringanyinflammatoryresponse

•Thereactiveoxygenspecies(ROS)hasnowbeenidentifiedtoplayafundamentalroleinthepathogenesisofcellularfunctionincludingendothelialdysfunctionandatherosclerosis

•Glucoseauto- oxidation,monocytedysfunctionandnon-enzymaticglycationetc.

Anti-oxidativeMicronutrientsandNCDs•Oxidativestressiscurrentlysuggestedasthemechanismunderlyingallnon-communicablediseasesaschronicdiseaseswithslowerprogressioncausing38milliondeathsperyearglobally,withrisingprevalenceacrosstheworldparticularlyindevelopingcountries.

Anti-oxidants

NeutralizesROS

ReduceProductionofROS

Evert,A.B.andBoucher,J.L.etal;NutritionTherapyRecommendationsFortheManagementofAdultswithDiabetes,:PositionStatementbytheADA,DiabetesCare2013,36;3821-42.Franz,Jetal;Evidence-baseddiabetesnutritiontherapyrecommendationsareeffective:thekeyisindividualization.Diabetes, MetabolicSyndromeandObesity:TargetsandTherapy2014:765–72

Anti-oxidativeMicronutrientsandNCDs

•Thisantioxidantdefencemechanismcanbedividedintotwogroups:1. Anti-oxidativeenzymes,presentinsidethecellssuchassuperoxidedismutase;

catalaseandglutathioneperoxidasewhichpreventsformationoffreeradicals.


Anti-oxidativeMicronutrientsandNCDs

2. Certainvitaminsandmineralsandsomespecificphytochemicalshaveamajoranti-oxidativeeffectinthebody.


MicronutrientsSupportPhysiologicalProcesses

§Vitaminsandmineralsfunctioninthehumanbodyasmetabolicregulators,influencinganumberofphysiologicalprocesses.

§AllphysiologicalprocesseswithinthebodyaredirectedorinfluencedbyENZYMES


§Thebasictasksofenzymesaretobuildupandbreakdownvariouschemicalcompounds,usuallyproteins.

§Proteinsformour:§ Cellwalls§ Hormones§ neurotransmittersetc

§Micronutrientsarebiologicalcatalystsastheyserveasco-factorsorco-enzymes


Vitamins&Minerals

Vitamins&Minerals

FactorsLeadingtoNutrientDeficiencies

Suboptimalmicronutrient

intakecanleadtochronicdisease

Vitaminandmineral

deficienciesoftencanbedifficultto

identify

Malabsorptionofnutrients

Changesinfoodproduction;genetic

engineering,toxicpesticidescanimpactfood

quality

CommonNutrientDeficiencies

Themostcommonnutrientdeficienciesare:• VitaminD• Omega-3s•Magnesium• VitaminsA,EandB12• Iodine• Calcium• Iron• Zinc

BMCBioinformatics2012;13(Suppl14):S10

OsteoporosisInternationalSeptember2013:24(9);2499–2507

DietarySupplementsandDiabetes/HTN

Omega-3(ALA)– DM◦ Antioxidantproperties◦ Promotesglucoseuptakeinmuscles◦ Increasessensitivityofthebodytoinsulin◦ Positiveeffectondiabeticneuropathy◦ Helpswithweightloss

S/E

Hypoglycaemiaanddecreaseironlevels

Omega-3(ALA)- HTN◦ Antioxidantproperties◦ Hasthepotentialtoregulatebloodpressure

S/E

Maycausefluctuationinbloodpressurecontrol

BMCBioinformatics2012;13(Suppl14):S10


Omega-3(EPA/DHA)Fattyacids- DM◦ Increaselevelsofadiponectin◦ Increasesinsulinsensitivity◦ Decreaseinsulinresistance

Omega-3Fattyacids–HTN◦ Lower bloodpressure◦ Reduce triglycerides◦ Slowthedevelopmentofplaqueinthe arteries◦ Reducethechanceofabnormal heart rhythm

AmericanJournalofClinicalNutrition2010May;91(5):1255-60

AreOmega-3FatsGoodforDiabetes?,PublishedSeptember27,2017byDavidSpero,BSN,RN

RCTsfoundthatOmega-3decreasestheriskofcardiovasculardiseaseandeventssuchasheartattackandstroke.


CoenzymeQ10(Ubiquinone&Ubiquinol)-DM◦ Helpscellmakeenergyandactsasanantioxidant

◦ Improveshearthealthinpeoplewithdiabetes

S/E◦ Interactsnegativelywithbloodthinnersandbloodpressuremedications

CoenzymeQ10(Ubiquinone&Ubiquinol)-HTN◦ Bloodpressureloweringproperties

S/E◦ Increasesthehypertensiveeffectsofanti-hypertensivemedications.


PreventDiseaseJuly26,2016


Zinc(Protamine)– DM◦ Insulinhomeostasis◦ Reduceinsulinresistance◦ Prolongstheactionandhalflifeofinsulin◦ Promotesinsulinsecretion

S/E◦ Hypoglycaemia

Zinc(Protamine)– HTN◦ Positivelyimpactsarterialbloodpressure

◦ Zincinteractswithotherminerals;especiallycoppertomaintainbloodpressure(8:1)

S/E◦ Excesscancausehypertensionbyincreasingoxidativestressonarteries


Granados-SilvestreMAetal.Mineralsanddiabetes,2014;82:97-103


Magnesium– DM◦ Neededco-factorforcarryingout>300enzymaticreactions,specificallyintheprocessesofphosphorylationand,ingeneral,inthosewheretheuseoftransferenceofATPisnecessary

◦ Promotesuptakeofinsulinbycellsandmaintainsvasculartone.

◦ Intracellularmagnesiumregulatestheactionofinsulin

S/E

Highlevelscanleadtoirregularheartrate,muscleweakness,hypotensionanddifficultybreathing

Magnesium– HTN

ADA,2016◦ Peoplereceivingabout368mg/dayofmagnesiumforaboutthreemonthshadoverallreductionsinsystolicbloodpressureof2.00mmHganddiastolicbloodpressureof1.78mmHg.

◦ Magnesiummightonlybeeffectiveamongpeoplewithmagnesiumdeficiencyorinsufficiency.

S/E

Hypotension


NCCIHOngoingResearch§Chromiumeffectsonelevatedbloodglucoselevels

§TheuseofYogaonglucosecontrolinpeopleatriskforDM

§GinkoBilobaExtractondiabetesmedications


Nutrient-Drug/DiseaseInteractions§Interactionisaconsequenceofphysical,chemicalorpathophysiologicrelationshipbetweenadrugandnutrient

§Interactionscanoccurbetweenadrugandanutrient,multiplenutrients,dietarypatternorspecificfoods.

§Aninteractionisclinicallysignificantifitaltersthetherapeuticdrugresponseandorcompromisenutritionalstatus

Nutrient-Drug/DiseaseInteractions

§Supplementscontainalargevarietyofmicronutrientsandphytochemicalsthathavebeenassociatedwithhealthbenefits.

§MostsupplementshoweverconsistofcomplexphytochemicalsthatcaninhibitorinducetheactivityofcytochromeP450familyofenzymes

Nutrient-Drug/DiseaseInteractions§Theclinicalsignificanceofanyparticularinteractiondependsontheseriousnessofthedose-relateddrugtoxicityandtheextenttowhichthesystemicdrugconcentrationincreases.

§Thelatterreliesonmultiplefactorsthatinclude:§ Bioavailabilityoftheinteractingdrug

§ Theconcentrationoftheinteractingnutrient

§ Thevulnerabilityofthepatienttotheinteraction

Baileyetal.CMAJ2012.DOI:10.1503/cmaj.120951


§Theseinteractionscanresultindecreasedbioavailabilityofdrugcausingtreatmentfailureorincreasedbioavailabilitycausingtoxicityandadverseeffects.

§Thepatient’snutritionalstatusanddietarycomponentswithpharmacologicalactivitycanaffectdrugmetabolismtherebyalteringactionandfunction.


§Medicationscanplayasignificantroleindevelopingnutrientdeficiencies.

§ Druginducedmicronutrientdepletionmayberesponsiblefortheunexplainedsymptomsthataffectmedicationcompliance(forexamplezincandACEinhibitors/ARBs)

§Manymicronutrientsarepotentiallyvulnerabletotheeffectsofprescribedmedicineswhenconsumptionisregularandsustained.

Nutrient-Drug/DiseaseInteractions§Medicationscanaffectnutrientsby:

§ Decreasingfoodintake

§ Decreasenutrientabsorption

§ Slowingdownnutrientproduction

§ Interferingwithnutrientmetabolism

§ Increasingnutrientexcretion

CommonDrug-Nutrient/DiseaseInteractions– HTN/DMDrugCategory Interaction/Outcome Recommendations

Anti-hypertensives:ACEInhibitorsARBsCCBsBBsDiuretics

ACEinhibitorsandARBsdepletezincandincreasepotassiumlevels

CCBsandThiazidediureticsdepletepotassium

BBsdepletecoenzymeQ10andVitaminB3

ACEIs/ARBs– Zinc<30mg/day

CCBs/Thiazidediuretics–Potassium<100mg/day

BetaBlockers– CoQ10100-200mg/day,VitB3– 16-18mg/day


Diuretics:FurosemideHCTZSpiranolactoneAcetazolamide

Loopandthiazidediureticsdeplete;magnesium,potassiumandzinc

Potassiumsparingdiureticsdepletefolicacid

LoopandThiazidediuretics–Magnesium250mg/dayPotassium<100mg/dayZinc<30mg/day

Potassiumsparingdiuretics:Folicacid400mcg/day


OralHypoglycemics:MetforminGlimeperideGlipizidePioglitazoneSitagliptin

Insulin

DepletionofFolicacidandVitaminB12

Omega-3- synergism

VitaminB12– 25-400mcg/day

Folicacid– 400mcg/day

Omega-3 - <300mg/day

CaseActivities

Case#1A68-year-olddiabeticwomanvisitedthecardiologyclinicwiththechiefcomplaintofpalpitation

atrestandwithminimalexertion.ShehadahistoryoftypeIIdiabetesmellitusforaround9

yearstreatedwithMetformin1500mg/day,andPioglitazone45mg/day.

Herothermedicationswereasfollows:Aspirin81mg/day,Atorvastatin20mg/day,Losartan25

mg/dayandCalcium+VitaminD(500mg+200IU)/day.

Case#1Onphysicalexamination,shewastosomeextentpalewithsubicterus,otherwiseunremarkable.

12-leadelectrocardiographywasnormalwhiletrans-thoracicechocardiographyshowednormal

leftandrightventricularsizeandglobalsystolicfunctionwithmildtomoderatemitral

regurgitationandnormalpulmonaryarterialpressure.

Case#1Laboratoryexaminationrevealedseveremacrocyticanaemiawithhypochromia,anisocytosis

andteardropcellsonperipheralbloodsmeartable.

Thyroidandrenalfunctiontestswerenormal.Shehadneitherneuropsychiatricnorgastro-

entrologicsymptoms.

Shewasnottakingproton-pumpinhibitorsorotherantacidmedicationseither.

Case#11. Whatisthesuspecteddiagnosis?

Case#11. Whatisthesuspecteddiagnosis?

Ans:MegaloblasticanaemiarelatedtoMetformin-inducedvitaminB12

§Competitiveinhibitionofcalcium-dependentabsorptionintheileum.Althoughcalciumsupplementationdecreasesthemalabsorption,itdoesnotincreaseserumvitaminB12levels.

2. Whatothermicronutrient/swouldyoubeconcernedaboutandwhy?

Case#1Whatothermicronutrient/swouldyoubeconcernedaboutandwhy?

Ans:ZincandPotassium

Losartan(ARB)hasthepotentialtodepletezincandincreasepotassiumlevels

Case#2A65-year-oldwomanreferredtothepharmacyclinicwiththechiefcomplaintofpalpitationat

restandlowbloodpressure.Shehadahistoryofhypertensionforaround6yearstreatedwith

aninitialmanagementof:

§ HCTZ12.5mg/day,Nifedipine40mg/daythen

§ HCTZ25mg/day+Nifedipine40mg/daythen

§Nifedipine30mg/day+Hctz12.5mg+Losartan75mg/day

Withallthepharmacotherapyadjustmentsthepatient’sbloodpressurewasconsistently

unstableandcompliancebecameachallengeforthepatient.

Case#2Withfurtherinvestigationthepatientinformsthepharmacistatonerefillofhermedicinesthatshedoesnotliketakingprescriptionmedicinesandoftentimesubstitutethemforherbalmedicines.

Thepharmacistadvisedthepatienttostopthatpracticeasthismayaffectheroverallcare.

Case#2Thepatient’sdaughter(anursingstudent)didsomeresearchonlineandrecommendedthefollowingsupplements:

◦ Magnesium500mg/day,

◦ FishOil300mg/dayand

◦ Bcomplex

Afterapproximatelytwomonthsoftakingthesupplementsalongwiththemedicationsthepatientnotedverylowbloodpressurereadingwithhighheartrates.Shecomplaintoflightheadednessalongwithfatigue.

NotethatthepatientnowtakesNifedipine 40mg/day+Losartan50mg/dayalongwiththesupplements

Case#21. Whatdoyoususpectishappeningtothispatient?

Case#21. Whatdoyoususpecttotheproblem/problemswiththispatient?

Ans:

Non-Compliancetopharmacotherapyandconcomitantuseofherbalremedieswithprescribedpharmacotherapy.

DailyallowanceofMagnesiumasasupplementis250mg/daynotexceeding350mg/day.Above350mgMagnesiumcangreatlylowerbloodpressure.

2.Whatothermicronutrient/swouldyoubeconcernedaboutandwhy?

Case#2

2.Whatothermicronutrient/swouldyoubeconcernedaboutandwhy?

PotassiumandZinc– Thiazidediuretics,CCBsandARBsincreasestheexcretionofpotassiumandARBsalsodepleteszinc.

Case#3A55-year-oldmalewasadmittedinApril2011afterbeingfoundlyingnakedinthestreettalkingtohimselfand

cursingpassers-by.Hewastakentothehospitalbyhisrelatives.

Mentalstatusexaminationonadmissionfoundthatthepatientwasconsciousbutunabletoanswerquestions

correctly.Hecoveredhisheadwithaquiltduringtheexaminationfornoobviousreason.Helaughedtohimself,

manifestedinappropriateemotionsandappearedtolackinsightintohiscondition.Hehaddifficulty

concentrating,hadslowedreactions,andgotascoreof20ontheMini-MentalStatusExam(MMSE)—indicating

moderatecognitiveimpairment.

Othersymptomsincludeddiarrhoeaandscalyskin.

Case#3GivenanadmissiondiagnosisofPsychosisNotOtherwiseSpecifiedandwastreatedaccordingly.Afterx3/7oftreatmentthepatientcognitivefunctiondidnotimprove.

Uponfurtherprobingofhisrelativestheysharedthatthepatienthasheartandbloodpressureproblemsfor7yearsandwastakingseveralmedicinesforthatproblem.Includedinthepatient’smedicationwasabetablocker.

Case#3Whatdoyoususpectishappeningtothispatient?

Case#3Whatdoyoususpectishappeningtothispatient?

Ans:VitaminB-3deficiencyduetolongtermuseofbetablocker

WhatisthenameoftheconditionthatisassociatedwithVitaminB-3deficiency?

Case#3

WhatisthenameoftheconditionthatisassociatedwithVitaminB-3deficiency?

Pellagra– diarrhoea,dermatitis,mentaldisorderinducedbyVitaminB-3deficiency.

Conclusion§Supplementssuchasmicronutrientsplayanimportantroleinmetabolicandcellularprocesses.

§TheirdeficiencyduetoanincreaseclearanceordeficiencyiningestionmaycontributetosecondarycomplicationsinchronicdiseasessuchasHTNandDM

§Theiradministrationassupplementsareimportanttoachievinghealth,wellnessandcontrol.

§Administration,however,shouldbecarefullymonitoredtoreachadequatedosesinordertoachievetheexpectedeffects,avoidingreachingconcentrationsthatmayproduceadverseeffects.

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Evert,A.B.andBoucher,J.L.etal;NutritionTherapyRecommendationsFortheManagementofAdultswithDiabetes,:Position StatementbytheADA,DiabetesCare2013,363821-42.

StandardsofMedicalCareinDiabetes-2013DiabetesCare2013;36(Suppl.1):S11–S66

Evert,A.B.andBoucher,J.L.etal;NutritionTherapyRecommendationsFortheManagementofAdultswithDiabetes,:Position StatementbytheADA,DiabetesCare2013,363821-42.

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StandardsofMedicalCareinDiabetes-2013DiabetesCare2013;36(Suppl.1):S11–S66

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Evert,A.B.andBoucher,J.L.etal;NutritionTherapyRecommendationsFortheManagementofAdultswithDiabetes,:Position StatementbytheADA,DiabetesCare2013,36:3821-42...

Cozma AI,Sievenpiper JL,deSouzaRJ,et al.Effectoffructoseonglycemic controlindiabetes:asystematicreviewandmeta-analysisofcontrolledfeedingtrials.DiabetesCare2012;35:1611–1620

Evert,A.B.andBoucher,J.L.etal;NutritionTherapyRecommendationsFortheManagementofAdultswithDiabetes,:Position StatementbytheADA,DiabetesCare2013,36:3821-42..

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