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FortifyYourLife:TheCaseforDietarySupplements
TieraonaLowDog,MD
FellowshipDirector,AcademyofIntegrativeHealth&Medicine
FinancialDisclosures
• TieraonaLowDog,MDhasthefollowingdisclosurestomake:– President,Dr.LowDog’sApothecary– HealthAdvisoryBoard,Pharmaca– Spokesperson,FoodState– Director,Scientific&Regulatory,HealthyLifestyleBrands
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CentersforDiseaseControl
• Recentfindingshavedeterminedthatlessthanoptimalbiochemicallevelsofvitaminsandmineralsareassociatedwithrisksofadversehealtheffects.
• “Thesehealtheffectsincludecardiovasculardisease,stroke,impairedcognitivefunction,cancer,eyediseases,poorbonehealth,andotherconditions.”
CDC:2nd NationalReportonBiochemicalIndicatorsofDietandNutritionintheU.S.Population
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AtRiskPopulations
• Obesity(B1,B6,B12,D)• Ethnic/racialminorities
– Hispanics(B3,folate,D,magnesium,iron)– AfricanAmericans(iron,zinc,B6,D)
• Thosewithchronicdisease• Chronicmedicationuse• Familieswithfoodinsecurity• Thoseonrestricteddiets
– Vegans- B6,B12,D,K,choline,iron,zinc,omega3s
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FoodInsecurity
• Foodinsecurityisaseriouspublichealthproblemassociatedwithpoorcognitiveandemotionaldevelopmentinchildrenandwithdepressionandpoorhealthinadults.
• Prevalencerate30.2%foodinsecurityinfemale-headedhouseholds~3timesthenationalaverage,morethan12.4millionchildren.
• Evenmildestformoffoodinsecurityisassociatedwithriskofpoorcognitive,social,andemotionaldevelopmentofchildrenyoungerthan3years.
ChiltonM,etal.AmJPublicHealth2009;99(7):1203–1211
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B-Vitamins
• TheB-vitaminsareimportantforthemetabolismofcarbohydrates,fatsandproteinsandplayavitalroleintheproductionoffuelandenergyforthebody.
• ThereareeightB-vitaminsthatpartnertogether,whichiswhyyoualmostalwayswanttotakethemtogetherinbalancedamounts.
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The“Stress”B- Vitamins
MTHFR
Folate 5-MTHF+Homocysteine 1-Met SAMe
DA
5-HT
NE
METHYIDONATION
Metsynthase Mat
Methylcobalamin(vitaminB-12)
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TheB-vitamins
• Vitallyimportantforproductionofenergy,maintenanceofahealthybrainandnervoussystemandhealthyfunctionofthecardiovascularsystem.
• LowlevelsofvitaminB6andB12increaseriskfordepressionandimpaircognition,attention,andmemory.
• SubsetofwomentakingbirthcontrolpillsshowntobelowinvitaminB6.
• 2/3rd ofthosewithB12deficiencyareoverage40.• Womenwhodonoteatfortifiedfoodsmaynotbegetting
sufficientfolate,significantifpregnancyoccurs.
Chitayat D,etal. JClin Pharmacol 2016Feb;56(2):170-5.Rios-AvilaL, etal.AmJClin Nutr 2015;Sep;102(3):616-25.
CDC2nd NationalReportonBiochemicalIndicatorsofDietandNutritionintheU.S.Population
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FoodFortification
• ManycerealsarefortifiedwithvitaminsB1,B2,B3,B5,B9,B12,andC,aswellasironandcalcium.
• Thishasbothanupsideanddownside(potentiallygettingtoomuchanutrient;forinstanceironinadultmen).
• Furthercomplicatingtheissue:mostnon-GMOand/ororganiccerealsarenotfortified.
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ToGet1.5mgB6inFood
• 2.5bananas• 12Tbsp.roastedsunflowerseeds• 8 ounceschickenbreast• 8 ouncessockeyesalmon• 3.5cupsrawdicedavocado• 3cupssweetpotatoes• 15cupsofmilkOR• 20Tbsp.peanutbutter
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MetforminWithProtonPumpInhibitors:APolypharmacy RecipeforNeuropathyvia
VitaminB12DepletionZdilla MJ.Clin Diabetes2015;33(2):90-5.
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MANYMEDICATIONSINTERFEREWITHNUTRIENTABSORPTIONANDUTILIZATION
• Studyof390patientswithtype2diabetesrandomizedtometformin(850mg)orplaceboTIDfor4.3years.
• Comparedwithplacebo,metformintreatmentwasassociatedwithameandecreaseinvitaminB-12concentrationof−19%.
DeJager,et al.BMJ2010;340:c2181
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VitaminB12
• Foundinanimalandfortifiedfoods.KeyroleinDNAsynthesis,hematopoiesisandneurologicalfunction.
• Deficiencydamagesmyelinsheathcoveringcranial,spinal,andperipheralnerves,resultinginneurologicaldamage.
• Myelinationprimarilyoccursduringfetaldevelopmentandearlyinfancy butcontinuesthroughearlyadulthood.
• Risk:inadequateintake,veganism,malabsorption,medications,obese,insulinresistantadolescents.
• MMAlevel>271nmol/Lismostreliablemeasureofdeficiency(aimforserumB12500-800pg/ml)
Niafar M,etal.InternEmerg Med2015;10(1):93-102.
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MetabolismofB12
• Entersstomach,HCLandpepsinseparateB12fromproteininanimalfood
• FreeB12joinedtoproteincalledintrinsicfactor(IF)madebyparietalcellsinstomach.
• B12-IFtravelstoileumwhere,ifcalciumisadequate,itisabsorbed.
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Choline• WatersolublenutrientintheB-vitaminfamilythatis
particularlycrucialduringpregnancyandthefirstthreeyearsofachild’slife.
• Deficiencymaybeassociatedwithpermanentchangesinbrainfunctionthatnegativelyimpactintelligence,memory,moodregulation,andstressresponse.
• Preclinicalstudiesshowcholinepartiallyamelioratesmemoryandlearningdeficitsfromprenatalalcoholexposure.
• RDA:450mgperdayBreastfeeding:550mgperday
JiangX,etal.TrendsEndocrinol Metab 2014;25(5):263-73.JiangX,etal.FASEBJ.2012;26(8):3563–3574.
WozniakJR,etal.Nutr Res2013;33(11):897-904
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CholineandCognition
• Prospectivestudyinvolving154healthymother-infantpairsconductedinVancouver,Canada (72%white,15%Asian).AllwomenweretakingPNV.
• Maternalbloodcollectedat16and36weeksgestationandinfantneurodevelopmentassessedat18monthsagefor154mother-infantpairs.Babieswereallsingletonsandfull-term.
• Significantpositiveassociationsfoundbetweeninfantcognitivetestscoresandmaternalplasmafreecholine andbetaine(p=0.009)andastrongtrendtowardsgrossmotordevelopment.
WuBT,etal.PLoS One2012;7(8):e43448.
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CholineinFoods:http://naldc.nal.usda.gov/download/47335/PDF
Iron• WHO:irondeficiencymostcommonnutrientdeficiencyinworld,affecting2billionpeople.– Irondeficiencyanemiaaccountsfor20%ofallglobalmaternaldeaths.
• Necessaryforgrowthanddevelopmentandessentialcomponentofhemoglobin.
• Meta-analysisfoundthatironsupplementationimprovedattention,concentration,andIQ.
• Irondeficiencyincreasestheriskofleadtoxicity
FalkinghamM,etal.Nutr J2010;25;9:4.Calarge C,etal.JChildAdolesc Psychopharmacol.
2010;20(6):495–502Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.
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ToGet18mgofIroninFood• 4cupsraisins• 3–5cupsinstantoatmeal• 3cupsSpecialKcereal• 3cupscookedlentils• 2.2cupscannedwhitebeans• 10ouncesbeefliver• 45ounceschickenbreast• 15cupsbroccoli• 3cupscookedspinach
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Warning:Iron• Peoplewhoarenotatriskofirondeficiency(teenageboys,adultmen,womenwithinfrequentmenstrualcycles,andpostmenopausalwomen)shouldNOT takemultivitaminsthatcontainironorironsupplementsunlessinstructedtodosobytheirhealthcareprovider.
• Whentakingsupplements:Lookforironbisglycinate,ferrousbisglycinate,orironglycinateonthelabel. TakewithvitaminCandNOTwithcalcium.
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VitaminC
• Playsaroleinactivatingfolicacid,assistsinconversionoftryptophantoserotonin,andisacofactorinsynthesisofcarnitine,thyroxin,norepinephrine,anddopamine.
• VitaminClevelsdeclinerapidlyduringperiodsofemotionalandphysicalstrain,andillness.
• Aslevelsfall,collagensynthesisisimpaired:bruisemoreeasily,skinbecomesthickanddry,woundstakelongertoheal,jointshurt,fatigue.
• 15.7millionAmericanshavevitaminCdeficiency.
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Zinc• Zincplaysavitalroleinourimmuneresponse.• NeedzinctoactivateT-lymphocytes,immunecells
responsiblefordestroyingcellsinfectedwithvirusesorbacteria,orcancerous.
• Marginalzincdeficiencycanalsodiminishtheactivityofotherimportantimmunecellssuchasmacrophages,neutrophils,andnaturalkillercells.
• WHOestimatesmarginalzincstatusresultsinthedeathsof>780,000childrenundertheagefiveeveryyearfromdiarrhealdiseases,pneumonia,andmalaria.
• Noteffectivelystored,mustbecontinuouslyreplacedinthediet.
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ZincinChildren• Meta-analysis concluded zinc supplementation
reduces frequency, severity, and duration of diarrheal episodes in children under five years of age.
• Zinc supplementation in children (2-59 months) reduced incidence and prevalence of pneumonia.
• When supplemented for at least five months, zinc reduces cold incidence, school absenteeism and prescription of antibiotics in children.
Aggarwal R, et al. Pediatrics. 2007;119(6):1120-1130Lassi ZS, et al. Cochrane Database Syst Rev 2010; 8;12:CD005978Singh M, et al. Cochrane Database Syst Rev 2011; 16;2:CD001364
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ZincinChildren
• Prevalence of zinc deficiency high in low-income minority children in the US, especially among African Americans and Hispanic adolescents, 28.4% (females) and 24.5% (males) had zinc deficiency.
BrownKH,etal.FoodNutr Bull2009;30(1S):S12-40ColeCR,etal.AmJClin Nutr 2010;91(4):1027-34.DelaCruz-Gongora V,etal.Salud Publica Mex 2012;54(2):135-45.
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ZincandtheSenses
• Zincisnecessaryforsenseofsmell,whichaccountsforabout80%ofyoursenseoftaste!
• Alsoimportantfororalhealth;onesignofzincdeficiencyisred,swollen,andtendergumsthatmaybleedafterbrushing.
• Zinchelpsprotectcellsthatlinethemouthinthoseundergoingchemotherapyorradiation.
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ZincandTaste
• Study found half of women undergoing chemotherapy for gynecological cancer experienced altered taste.
• Serum zinc level consistently below lower limit of normal.
• RDBPCT of adult patients with head and neck cancers received zinc sulfate (50 mg, three times a day) or placebo at start of radiation through one month post. Zinc prevented radiation induced taste alterations.
Nishijima S, et al. Gynecol Oncol 2013; 131(3):674-8. Najafizade N, et al. J Res Med Sci 2013; 18(2):123-6
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Zinc and Oral Health
• A review of clinical trials found “moderate quality evidence that zinc supplements improve overall taste improvement in patients with zinc deficiency/idiopathic taste disorders.”
• Zinc deficiency detected in 28% of recurrent aphthous stomatitis patients compared to controls.
Nagraj SK, et al. Cochrane Database Syst Rev 2014; 2014 Nov 26;11:CD010470. Ozler GS. J Laryngol Otol 2014; 128(6):531-3
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• Zinc deficiency: loss of appetite; lack of taste or smell; poor wound healing; acne; hair loss; lack of menstrual period; night blindness; and depression
• Vegetarians need as much as 50% more zinc due to lower absorption of zinc from plant foods. DV= 15 mg
• ACE inhibitors and thiazide diuretics deplete zinc
• Best absorbed on empty stomach. Do not take more than 40 mg per day for more than a few days without medical supervision. Take 2 hours apart from medication, especially quinolones and tetracycline antibiotics.
Zinc
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Deficiency
• Oneofthefirstsignsofcalciumdeficiencyismusclecramping.
• Muscleachesofthighsandarms,withminimalexertion,couldindicateadeficiencyofcalcium,vitaminD,and/ormagnesium.
• Longtermdeficiencyleadstopoorbonedevelopment/lossofbonemineraldensity.
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CalciumSupplements
• You need roughly 1000 mg per day of calcium from all sources, depending upon age.
• Chelated calcium (citrate, malate)• Best for those over 50 years old or
those taking drugs to suppress stomach acid
• Do not take at the same time as other medications (thyroid, bisphosphonates, phenytoin, tetracycline)
SpenceLA,etal.Nutr Rev2013;71(1):15-22
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DrugInducedOsteoporosis• Thesedrugsinclude:
– Glucocorticoids(steroids)– 1:5casesofosteoporosis– Aromataseinhibitors(breastcancer)– Anti-androgentherapy(prostatecancer)– Protonpumpinhibitors(heartburn)– Antiretroviraldrugs(HIV,hepatitis)– SSRIs(antidepressants)andantipsychotics– Anticonvulsants(epilepsy)– Loopdiuretics(e.g.lasix)– Heparinandoralanticoagulants
Mazziotti G,etal.AmJMed2010;123:877-84
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VitaminD• Vitamin D interacts with more than 1000 genes• Vitally important for calcium regulation (bones, heart, etc.)• Review of 30 studies show that high vitamin D status is
strongly associated with better breast cancer survival.• Review ~ 1,000,000 participants found 10 ng/mL
increment in blood 25(OH)D level conferred a 26% reduction in risk for colorectal cancer
• Obesity increases the risk of deficiency……..• Endocrine Society: serum 25(OH)D level:
– Insufficiency defined as 21-29 ng/mL– Deficiency defined as <20 ng/mL
Kim Y, et al. Br J Cancer 2014; 110(11):2772-84. Ma Y, et al. J Clin Oncol 2011; 29(28):3775-82
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EndocrineSocietyGuidelines
• Serum25(OH)Dlevelusedtoevaluatehigh-riskfolks– Insufficiencydefinedas21-29ng/mL– Deficiencydefinedas<20ng/mL
• 66.8millionAmericans1yearandolderhadvitaminDlevelsbetween12-20ng/ml
• 23millionAmericans1yearandolderhadserumlevelslessthan12ng/ml
• Mostatriskwerewomenandnon-Hispanicblacks.
CDC2nd NationalReportonBiochemicalIndicatorsofDietandNutritionintheU.S.PopulationHolick MF,etal.JClin Endocrinol Metab 2011;96(7):1911-30
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EndocrineSociety
“Forclinicalcare,itappearsthatallcurrent(testing)methodologiesareadequateifonetargetsa25(OH)Dvaluehigherthancurrentcutpoints;forexample,avalueof40ng/ml(100nmol/L)iswithouttoxicityandvirtuallyensuresthattheindividuals‘true’valueisgreaterthan30ng/ml(75nmol/L).”
Holick MF,etal.JClin Endocrinol Metab 2011;96(7):1911-30
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ToGet600IUVitaminDinFood
• 3–4ouncessockeyesalmon,cooked• 11.4ounceswater-packedtuna• 26oil-packedsardines• 15largeeggs• 5cupsfortifiedmilkOR• 30-45ouncesyogurt
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AmericanEndocrineSociety
• AlladultswhoarevitaminDdeficientshouldbetreatedwith50,000IUofvitaminD2/D3onceaweekfor8weeksoritsequivalentof6000IUofvitaminD2/D3dailytoachieveabloodlevelof25(OH)Dabove30ng/ml,followedbymaintenancetherapyof1500–2000IU/d.
Holick MF,etal.JClin Endocrinol Metab 2011;96(7):1911-30
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VitaminDDeficiencyandObesity
• Sample6-18yearoldsfrom2003-6NHANES– PrevalenceofvitaminDdeficiency(<20ng/mL):
• Healthy-weight(21%)• Overweight(29%)• Obese(34%)• Severelyobesechildren(49%)
– PrevalenceofvitaminDdeficiencyinseverelyobesewhite(27%),Latino(52%),andAfrican-American(87%)children.
Turer CB,etal.Pediatrics2013;131(1):e152-61
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EndocrineSocietyGuidelines
• ObesechildrenandadultsshouldbegivenatleasttwiceorthreetimesthevitaminDrequirementspreviouslyspecified,asshouldallindividualstakinganticonvulsantmedications,glucocorticoids,antifungalssuchasketoconazoleandmedicationsforHIV/AIDS.
Holick MF,etal.JClin Endocrinol Metab 2011;96(7):1911-30
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VitaminK
• TherearetwomainformsofvitaminK.– Phylloquinone,orvitaminK1,issynthesizedbyplantsandmakesup90%ofthevitaminKobtainedinthediet.Bestsourcesaregreenleafyvegetables.Fat-solublesoshouldbeeatenwithsomehealthyfat.
– Menaquinone,vitaminK2,isresultofbacterialactioninGItractconvertingK1toK2orobtaineddirectlyfromfoodsourcessuchasmeat,eggyolks,fermenteddairyandsoy(e.g.,miso,natto).
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Geleijnse JM,etal.JNutr.2004;134(11):3100-5.
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Magnesium• Lowmagnesiumintakesandlowbloodlevelshavebeenassociatedwithtype2diabetes,metabolicsyndrome,elevatedCRP,hypertension,atheroscleroticvasculardisease,suddencardiacdeath,osteoporosis,migraineheadache,asthma,andcoloncancer.
• 48%ofUSpopulationconsumeslessthantherequiredamountofdailymagnesium.
Rosanoff A,etal.Nutr Rev2010;70(3):153-64.
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MagnesiumandtheHeart• Low serum magnesium levels associated with higher all-
cause and cardiovascular mortality. • Review of 44 studies shows Mg supplements enhance
blood-pressure lowering effect of BP medications in stage 1 hypertension when given 230-460 mg/d.
• Nurses Health Study (88,375 women) found that for every 0.25-mg/dL increment in plasma magnesium –41% lower risk of sudden cardiac death. Women with lowest levels of magnesium also had significantly increased risk of stroke.
Reffelmann, et al. Atherosclerosis 2011 Nov;219(1):280-4. Rosanoff, et al. Magnes Res 2010 Mar;23(1):27-40. Chiuve, et al. Am J Clin Nutr. 2011;93(2):253-60.Akarolo-Anthony SN, et al. Stroke 2014; 45(10):2881-6
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Ulcer/GERDMedications
DrugClassification NutrientDepletion
Protonpumpinhibitors Magnesium,iron,calcium,vitaminB12,folicacid,zinc,vitaminC,vitaminD(?)
H2antagonists folicacid
• There were 118.5 million prescriptions for PPIs in 2010 with roughly $11.4 billion in sales. Thesenumbersdonotincludeover-the-countersalesforPPIs.
- esomeprazole magnesium (Nexium) - omeprazole (Prilosec)
- pantoprazole sodium (Protonix) - rabeprazole sodium (Aciphex)
- lansoprazole (Prevacid) - dexlansoprazole (Dexilant)
- omeprazole and sodium bicarbonate (Zegerid)
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FDASafetyAdvisory• FDA issued MedWatch warning and label change for
PPIs due to low magnesium levels associated with long-term use.
• “Those taking medications, generally more than one year, may end up with low magnesium, which can put them at risk for seizures, irregular heartbeats, and muscle spasms.”
• Review of nine studies (n=115,455) found that the odds of developing hypomagnesia increased by 75% if taking PPIs.
• FDA advises magnesium levels be checked before and periodically during treatment.
ParkCH,etal.PLoS One2014;Nov13;9(11):e112558.
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MagnesiumforMigraines
• Studiesshowthatmigraineurs havelowbrainMgduringmigraineattacksandmayhavesystemicMgdeficiency.
• Mgreducesrecurrentpediatricmigraineandtensionheadaches.
• CanadianHeadacheSocietygavemagnesiumcitrateastrongrecommendationforprophylaxisofmigraine.
• Dosegenerally300-400mg/d.Diarrheamostcommonsideeffect(glycinate andcitrateformslessGIcomplaintsthanoxide).
Sun-EdelsteinC,Mauskop A.Clin JPain.2009Jun;25(5):446-52.Pringsheim T,etal.CanJNeurol Sci 2012;39(2Suppl)S1-59
Mauskop A,etal.JNeuralTransm 2012;119(5):575-9.
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IodineinPregnancy
• ManyreproductiveagedwomeninUShavemarginaliodinestatus;saltinprocessedfoodsisnotiodized.
• Deficiencyassociatedwithpregnancylossandprematurity,cretinism,andneurocognitivedefectsinthefetus.
• MildtomoderateiodinedeficiencyassociatedwithhigherincidenceofADHDandlowerIQinthebaby.
• AmericanThyroidAssociationrecommendspregnant/lactatingwomensupplement:150mcg/dpotassiumiodide.
CouncilonEnvironmentalHealth,etal.Pediatrics 2014;133(6):1163-6.
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CDC2nd NationalReportonBiochemicalIndicatorsofDietAndNutrition.TheWHOrecommendsthatthemedianUIinpregnancybe150-249mcg/L.
Resources• FortifyYourLife,TieraonaLowDog,MDwithNational
Geographic• DietarySupplementLabelDatabase:dsld.nlm.nih.gov• NIHNationalCenterforComplementaryandIntegrative
Health(NCCIH):nccih.nih.gov• OfficeofDietarySupplements:ods.od.nih.gov• LinusPaulingInstitute:lpi.oregonstate.edu• ConsumerLabs:www.consumerlabs.com• NaturalMedicinesComprehensiveDatabase:
naturaldatabase.com
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