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PEER:MikeAllan&AdrienneLindbladDeptofFamilyMedicine,UofAEvidence&CPDProgram,ACFP

Vitamins:PerfectHealthorPerfectHoax?

Faculty/PresenterDisclosure

•  Faculty/Presenter:G.MichaelAllan,AdrienneLindblad

•  RelaKonshipswithcommercialinterests:–  Grants/ResearchSupport: Notapplicable–  SpeakersBureau/Honoraria:Notapplicable–  ConsulKngFees:Notapplicable–  Other:

–  EmployedbyUniversityofAlberta,AlbertaHealth(GMA)andACFP(AL)–  Non-profitsourcesincludingAlbertaCollegeofFamilyPhysicians,TOP,IHE,

CADTH,etc.

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VitaminD1.  Falls:Ifreal,~15%RRR.NNT~11over1year.2.  Fractures:At≥800IUwithCa+,~10%RRR.

•  If10yrfracturerisk~15%,NNT45-67

3.  Mortality:Ifreal,~5%RRR.•  If10yrmortalityrisk~10%,NNT200

4.  Mood:2+veof11RCTs(manyflaws).5.  RespiratoryInfec]ons:3of6meta-analysis+ve

JGenInternMed.2016;31(7):780-91.

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VitaminD6.  Rheumatoid:1+veof3RCTs

•  Study40+yearsold,megadose(100,000IU/d),“beder”

7.  MS:6RCTs,nothingonpreven]on•  Mul]pleoutcomes,1surrogate&1clinical.

8.  Cancer:4SysRev:Noeffectincidence•  Ifreal,12%RRRmortality(NNT334x6yrs).

9.  Regulartes]ng:Targetsfalse•  Testvariance10-20%(similarchangewith800IUdose)

10. Dose:Holdyourbreath

JGenInternMed.2016Jul;31(7):780-91.8.(Mortality)BrJCancer.2014;111(5):976-80.CochraneDatabaseSystRev.2014;6:CD007469

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VitaminDCouncilresponsetoourar]cle

1.  Thereviewignoresseveralimportantfindingswhilevoicingabiasedinterpreta]onofscien]ficliterature.

2.  Thereviewneglectedscien]ficevidencetopushtheircontroversialopinionintothemedia.

3.  Addresssomeofthesetopicsandtoputanendtospreadingmisleadinginforma]on.Let’stakealookatafewofthetopicsthatwefoundmostdecepKve.

4.  ButDr.Allandecidedtoignoretheseweakness,illustra]nghisunderlyingbias.

5.  Thereview’sconclusioncontradictsthefindingsfromeverystudythatwasincludedinthereview.Onceagain,theauthor’sopinionoverruledlogicandscien]ficevidence.

6.  Toneglecttheavailableresearchduetotrivialstudylimita]ons,whicharefoundwithinthemajorityofstudies,issimplyignorant.

hdps://www.vitamindcouncil.org/should-vitamin-d-enthusiasm-be-tempered/?mc_cid=a20e159f0e&mc_eid=40364f8b9b

•  Doses(1000IU),…tooconserva]ve•  “influencethelevelofoligedendritecells”•  “thishormoneregulatesgeneac]vity”.•  “controlgenetranscrip]on”.•  “‘missing’part,…dehydroepiandrosterone(DHEA)andtestosterone”&“VDRgenepredictssynthesisand/ormetabolismofsexualsteroidprecursorDHEA,…”

SpecialPleading

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Itjustmakessense,…

TheBeguilingPowerofaBeauKful

Mechanism

NewEvidence=MoreConfusion

WhatdidtheEditorialSay:Heterogeneousandnotsufficientlyapplicabletothegeneralpopula]on.

CurrentevidencedoesnotsupporttheuseofvitaminDsupplementa]ontopreventdisease,exceptforthoseathighriskofosteomalacia

Media:“ThereiscompellingevidencevitaminDhelpspreventcolds&flu”

Media:Don'tbelievethehype:vitaminDsupplementsunlikelytopreventchestinfec]ons

WhatdotheAuthorsConclude:VitaminDsupplementa]onwassafeanditprotectedagainstacuterespiratorytractinfec]onoverall.Pa]entswhowereveryvitaminDdeficientandthosenotreceivingbolusdosesexperiencedthemostbenefit.

BMJ2017;356:j456BMJ2017;356:j456

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BMJ.2017Feb15;356:i6583.

1stMeta-analysisOddsRa]o0.88(0.81-0.96)

53%,p=0.001Substan]alHeterogeneity

RedoMetaasRela]veRisk0.96(0.91-1.00)

Ifreal,anyURTI40.3%vs42.2%NNT53

Mongolian10y.o.,AnyRTI(VitDlvl17.5)

USAHealthy59y.o,anyRTI

Afghanistan,poor,0-3y.o.pneumonia

NewZealandHealthy47y.o.Colds

Afghanistan,poor,0-1y.o.pneumonia

WhoMightVitDbeeffecKveFor:Dailylow(~800IU)dosesinpeoplewithVitaminDlevel<25nmol/L.

VitaminD10. Mega-Dose:4+veof4RCTsforHarm.

•  Fracture:2+veof4RCTs,NNTnoneto32over3yrs•  Falls:3+veof4RCTs,NNTnoneto6-  Someevidencethatcertainindividualspar]cularly

suscep]ble(morefallersbutforthosethatfall,lotsmorefalls).IncidentRateRa]o2.33

-  Meannumberoffalls0.94versus1.47inoneyear

Ginde2016 Bischoff2016 Sanders2010 Smith2007Dose 100,000IU/

monthoral60,000IU/month

oral500,000IU/year

oral300,000IU/yearIMshot

Levels ~83nmol/L ~100nmol/L 120-75nmol/L Notgiven

JGenInternMed.2016;31:780-91.JAmGeriatrSoc.2016Nov16.doi:10.1111/jgs.14679.JAMAInternMed.2016;176:175-83.

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Whatlevelsdoweneed?OurLabprintoutsays,…•  <25nmol/Lsevere

deficiency•  25-80moderatetomild

deficiency•  80-200op]mumlevels•  >200toxicitypossible

InsKtuteofMedicine•  ≤30nmol/Latriskrela]veto

bonehealth•  30-50nmol/Lsome,butnot

all,arepoten]allyatriskforinadequacy

•  ≥50nmol/Lprac]callyallpersonsaresufficient

•  >75nmol/Lnotconsistentlyassociatedwithincreasedbenefit.

•  >125nmol/Lmaybereasonforconcern

DietaryReferenceIntakesforCalciumandVitaminD.Ins]tuteofmedicine2011.(page13-14)

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DietaryRecommenda]ons

•  TheEARandRDAassumeminimaltonosunexposure.•  Mul]plesmallcaveats:Example,…

–  Obesity:Associatedwithlowercircula]ngVitDbutunclearifthatmaderstobonehealth.

Age1-70 Age>70 SerumLevel

EsKmatedAverageRequirement

400IU 600IU 40nmol/L

RecommendedDailyAllowance

600IU 800IU 50nmol/L

NEnglJMed375;19:1817-20.

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AreyourpaKentsbuying/takingVitamins•  In2009:40%tookvitamins/mineralsinpastmonth

– Useassociatedwithea]ngwell,exercising,beingwelleducatedandwealthy.

•  FromMedia,varyingquotes:–  40%-73%takesomevitamins/supplements– Wespend:$370millionto$3billionperyear.

•  “Butbasedonourlifestyletoday,thequalityofthefoodsthat'soutthere,itisimpossibletogetallofyouressen]alnutrientsfromyourdiet.”– GaryLeong,chiefscien]ficofficerforJamiesonLabs4

CanJPublicHealth.2009Sep-Oct;100(5):357-601)hdp://www.theglobeandmail.com/life/health-and-fitness/fitness/3-reasons-to-reconsider-vitamin-pills/ar]cle4103389/2)hdp://news.na]onalpost.com/health/vitamins-minerals-health-benefits?__lsa=bb00-5aac3)hdps://www.thestar.com/business/2015/02/09/supplement-industry-under-fire.html4)hdp://www.cbc.ca/news/health/vitamin-pills-should-be-avoided-journal-editors-say-1.2466351

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Someratesof“serumdeficiency”inCanada

•  VitaminCdeficiency:3%(<11umol/L)

•  FolateDeficiency:<1%(RBCfolate<305nmol/L)

•  IronDef:~3%in1st]meblooddonors(<25ug/Lferri]n)

•  B-12Def:~4%(<148pmol/L).

•  VitaminD:<40nmol/L≈13%(Rickets0.003%)

•  Boeom-Line:Ratesofbiochemical(notclinical)deficiencygenerallylessthan4%.

1)HealthRep.2016May18;27(5):3-10.2)CMAJ.2011Feb8;183(2):E100-6.3)Transfusion.2016Dec9.doi:10.1111/trf.13956.4)AmJClinNutr.2011;94:1079-87.5)hdp://www.statcan.gc.ca/pub/82-625-x/2012001/ar]cle/11731-eng.htm

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1.Everything:Mul]vitamins•  Meta-analysis21RCTswith91,074pa]ents(54%males)mul]vitaminsvsplacebox3.5yrs.Primarypreven]onstudies,EuropeorNorthAmerica.– OverallmortalityRR=0.98(0.94-1.02).– Cancermortality:RR=0.96(0.88-1.04).– CVDmortality:RR=1.01(0.93-1.09).

•  Boeom-Line:Tonsstudied,noeffect!

TFP#87,August5,2016.

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2.CVD:NiacinorFolate•  Niacin(B3):35,301studied

–  NoeffectonMortality,CVDoverall,StrokeorMI– Maybe31%RRRonnon-fatalMIfromCoronaryDrugProjectbutnothingonceotherdrugs(Sta]n,ASA,ACE,etc).

•  Folate(B9):58,804studied– Noeffectonmortality,CVDoverall,strokeorMI–  Strokewasborderline(RR0.93,0.86-1.00)

•  Iffolateingrain(RR1.07,0.92-1.25)butifnot(RR0.88,0.81-0.96)

•  Boeom-Line:Nomeaningfuleffect.

BMJ.2014Jul18;349:g4379.TFP#65April10,2012.EurJInternMed.2012Dec;23(8):745-54.

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3.CVDandCancer:An]-Oxidants

•  VitaminA&E(primarily)–  Increasemortality:RR1.04(1.01-1.07),NNH=238.– Beta-carotene(pro-vitaminA):RR1.05(1.01-1.09).– VitaminA,alldoses:RR1.07(0.97-1.18).

•  High-dose(>5000IU)vitaminAincreasesmortality.

– VitaminE:RR1.03(1.00-1.05).

•  VitaminCandSelenium:Noeffect.•  Boeom-Line:Nothelpful,possiblyharmful.

TFP#10,UpdatedAugust21,2016

4. Neural Tube Defects: Folate •  RCT 1817 women with history NTD, Folic acid 4mg/day

–  Folic acid RR 0.28, NNT = 40 •  RCT 4753 women, Folic acid 0.8mg/day (multivitamin),

1° prevention2

–  RR 0.08 (0.00 - 1.33) no cases folic acid group, NNT* = 399

•  Sys Rev, 5 RCTs, (most 2° prevention), 6105 women3 –  Significant ê Neural Tube Defects: RR 0.28 (0.15-0.52)

•  Bottom Line: decreased risk of NTD, particularly with history of NTD.

1) Lancet. 1991 Jul 20;338(8760):131-7. 2) Arch Gynecol Obstet (1994) 255:131-139 3) Cochrane Database Syst Rev. 2010 Oct 6;(10):CD007950.

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5.Headaches:Riboflavin(B2)•  Adults:3RCTs,primaryoutcomeposi]vein1of3.

–  N=130(+Mg&Q10).0.5lessheadaches/month(ns)•  Maxpainintensity0.17/3beder,fewothersposi]ve(ss)

–  N=55:2lessheadaches/month(ss)(about½)•  Responder(50%reduc]on):19%vs56%,NNT=3at3months.

–  N=49(+Mg&feverfew).50%reduc]on42%vs44%(ns)

•  Children:2RCTs–  N=42(50mg)&N=48(200mg):Noeffect.

•  Boeom-Line:Ifreal,riboflavinmayhavesomebenefitsinreducingmigrainefrequencybutnotconsistently(atbestNNT=3at3monthsfor50%reduc]on,butlikelyless).1)JHeadachePain.2015;16:32.2)Neurology.1998;50:466-70.3)Headache2004;44:885-90.4)Cephalalgia30(12)1426–1434.5)Neurology.1998Feb;50(2):466-70.

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6.VitaminCforColds

•  VitaminC,≥0.2g/d(most~1g/day)–  Incidence(10,708pa]ents):RR0.97(0.94-1.00)

•  Highstress:(598pa]ents):RR0.48(0.35-0.64)– Dura]on(9,745pa]ents):shorter9.4%(5.9-12.9%)

•  Others0.1to0.9ofaday(dependingonwho’sanalyzing)– Severity:SMD0.12(0.07-0.17),Clinicallymeaningless

•  Boeom-Line:Nomeaningfuleffectinthegeneralpopula]on.

CochraneDatabaseSystRev.2013Jan31;(1):CD000980

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7.ZincforColds•  Zinc:Lotsofissues(heterogeneity55-95%)

– Preven]on:10or15mgOD,400children(age2-10yr)2RCTs:coldsreducedRR0.64,(0.47-0.88);

•  about0.5–1.4fewercoldsover5–7“winter”months

– Treatment:2121pa]ent,symptoms1.65daysless.•  Noeffectinpediatric•  Harm(e.g.badtaste):NNH11

– Don’tusezincspray,casesofpersistentlossofsmell

•  Boeom-Line:Maybe,…

CMAJ.2014Feb18;186(3):190-9.CMAJ.2012Jul10;184(10):E551-61

8.MacularDegenera]on:OcularVitamins

•  OcularVitamins:An]oxidants/zincvsplacebo.Incategory3&4(moreadvanced),over6.3yrs.– Preven]ng15ledervisualloss:an]oxidants/zinc(23%)vsplacebo(29%),NNT17.

– Preven]ngprogression:NNT13– Newerformula]onEqualplacebo.

•  Boeom-Line:Forpa]entswithmoreadvancedage-relatedmaculardegenera]on,ocularvitaminsreduceprogression&visualwithNNT~15over6years.

TFP#85updatedAugust10,2016.

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9.Non-AnemicFa]gue:Iron•  Women(~mid-30s)“unexplained”fa]gue&normalHgb.– Changes4-10%onscales– “improvedfa]gue”(pa]entreportedor≥50%improve):NNT4-6

–  NoAEsta]s]caldifferent.•  Boeom-Line:Ifferri]n<50μg/Linreproduc]veagefemales,canofferatrialofiron(ferrousgluconate325mgBIDgivesaround80ofelementaliron).

TFP#79UpdatedAugust3,2016

10.ElderlyAnemia:IronDoses•  AnemicElderly:90pa]ents(age~85yrs)on15mg,50mg,or150mgofelementaliron/d.At2months– Alldosesgot14g/LincreaseinHgb.–  150mgvs15mg:abdominalcrampsNNH=2;nauseaorvomi]ngNNH=2;cons]pa]onNNH=5;anddropoutduetoadverseeventsNNH=5.

•  Boeom-Line:Inves]gateasappropriate.Givelowdoselike½ferrousgluconate300mgor2.5mlofFerrousSulphate(fer-in-sol)syrup.

CanFamPhysician.2015Feb;61(2):159.

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Summary

•  VitaminDmayreducefallsandfractures.– MAYBE:slightdecreasemortality.

•  Othervitaminsthatmightwork:– Folateforpreven]onneuraltubedefects.– Riboflavinformigrainepreven]on.– OcularvitaminsforadvancedAMD*.–  Ironfornon-anemicfa]gue.– Lowirondosesworkaswellashighdosesintheelderly.

5StepstogetthemostoutofyourVitamins1)  Takethevitaminstoafriends’house~5kmfromyourhouse.Ifyou

wanttotakeyourvitamin,walktotheirhouse,popthepill,walkhome.2)  Ifyoubelieveinhigherdosevitamins,chooseahome10kmfromyour

house,runthereatacomfortablepace,taketwopills,andrunhome.•  Note:Youcanjusttakeoneandgetthesameeffect•  Note2:Youcanalsotakenone

3)  Placeyourvitaminsonyourdinnerplate.Surroundthemwithfreshandwellseasoned/flavoredvegetables,fruit,grainsandfish/poultry.Ifcompelledtotryavitamin,pickitup,lickit.Doesitcomparetofood?

4)  Yourbodyisequippedwithatremendousfilteringsystemcalled“kidneys.”Sowhenyouingestmorethanthesmallamountofvitaminsrequiredforhealth,youpeeouttheexcess.Toavoidpossiblestrainonyourkidneys,placeyourvitaminsdirectlyintothetoiletandflush.

5)  Finally,ifyoureallywantyourvitaminstowork,packagethemupandsendthemtocountrieswherevitamindeficiencyareaserioushealthconcern.Theeffectgenerositymaybetheonlysupplementyouneed.