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1/27/17 1 Fortify Your Life: The Case for Dietary Supplements Tieraona Low Dog, MD Fellowship Director, Academy of Integrative Health & Medicine Financial Disclosures Tieraona Low Dog, MD has the following disclosures to make: President, Dr. Low Dog’s Apothecary Health Advisory Board, Pharmaca Spokesperson, FoodState Director, Scientific & Regulatory, Healthy Lifestyle Brands Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved. Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved. Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.
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Page 1: Fortify Your Life: The Case for Dietary Supplements Financial … · 2017. 1. 27. · Vitamin B12 • Found in animal and fortified foods. Key role in DNA synthesis, hematopoiesis

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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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

Copyright©2016IntegrativeMedicineConcepts,LLC.AllRightsReserved. Copyright©2009-2014IntegrativeMedicineConcepts,LLC.AllRightsReserved.Copyright©2016IntegrativeMedicineConcepts,LLC.AllRightsReserved.

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CentersforDiseaseControl

• Recentfindingshavedeterminedthatlessthanoptimalbiochemicallevelsofvitaminsandmineralsareassociatedwithrisksofadversehealtheffects.

• “Thesehealtheffectsincludecardiovasculardisease,stroke,impairedcognitivefunction,cancer,eyediseases,poorbonehealth,andotherconditions.”

CDC:2nd NationalReportonBiochemicalIndicatorsofDietandNutritionintheU.S.Population

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

FoodInsecurity

• Foodinsecurityisaseriouspublichealthproblemassociatedwithpoorcognitiveandemotionaldevelopmentinchildrenandwithdepressionandpoorhealthinadults.

• Prevalencerate30.2%foodinsecurityinfemale-headedhouseholds~3timesthenationalaverage,morethan12.4millionchildren.

• Evenmildestformoffoodinsecurityisassociatedwithriskofpoorcognitive,social,andemotionaldevelopmentofchildrenyoungerthan3years.

ChiltonM,etal.AmJPublicHealth2009;99(7):1203–1211

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

B-Vitamins

• TheB-vitaminsareimportantforthemetabolismofcarbohydrates,fatsandproteinsandplayavitalroleintheproductionoffuelandenergyforthebody.

• ThereareeightB-vitaminsthatpartnertogether,whichiswhyyoualmostalwayswanttotakethemtogetherinbalancedamounts.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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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)

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved. Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright©2016IntegrativeMedicineConcepts,LLC.AllRightsReserved.

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.

Copyright©2016IntegrativeMedicineConcepts,LLC.AllRightsReserved.

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.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

MetabolismofB12

• Entersstomach,HCLandpepsinseparateB12fromproteininanimalfood

• FreeB12joinedtoproteincalledintrinsicfactor(IF)madebyparietalcellsinstomach.

• B12-IFtravelstoileumwhere,ifcalciumisadequate,itisabsorbed.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

Warning:Iron• Peoplewhoarenotatriskofirondeficiency(teenageboys,adultmen,womenwithinfrequentmenstrualcycles,andpostmenopausalwomen)shouldNOT takemultivitaminsthatcontainironorironsupplementsunlessinstructedtodosobytheirhealthcareprovider.

• Whentakingsupplements:Lookforironbisglycinate,ferrousbisglycinate,orironglycinateonthelabel. TakewithvitaminCandNOTwithcalcium.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

• 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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Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

Deficiency

• Oneofthefirstsignsofcalciumdeficiencyismusclecramping.

• Muscleachesofthighsandarms,withminimalexertion,couldindicateadeficiencyofcalcium,vitaminD,and/ormagnesium.

• Longtermdeficiencyleadstopoorbonedevelopment/lossofbonemineraldensity.

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright©2016IntegrativeMedicineConcepts,LLC.AllRightsReserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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

Copyright © 2016 Integrative Medicine Concepts, LLC. All Rights Reserved.

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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