Vitamins: Perfect Health or Perfect Hoax? · Ginde 2016 Bischoff 2016 Sanders 2010 Smith 2007 Dose...
Transcript of Vitamins: Perfect Health or Perfect Hoax? · Ginde 2016 Bischoff 2016 Sanders 2010 Smith 2007 Dose...
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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.