carrageenan 2018 sunset national organic standards board

18
Handling Subcommittee Carrageenan 2018 Sunset Comments Comments submitted in advance of the National Organic Standards Board Spring 2016 Meeting April 25 – 27 Washington, DC

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Page 1: Carrageenan 2018 Sunset National Organic Standards Board

HandlingSubcommittee

Carrageenan2018Sunset

Comments

Commentssubmittedinadvanceofthe

NationalOrganicStandardsBoardSpring2016MeetingApril25–27Washington,DC

Page 2: Carrageenan 2018 Sunset National Organic Standards Board

TheCornucopiaInstituteP.O.Box126Cornucopia,WI54827608-625-2000voice866-861-2214faxcultivate@cornucopia.orgwww.cornucopia.orgCopyright©2016,TheCornucopiaInstitute

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CONTENTSCARRAGEENAN–2018SUNSET.................................................................................................................1DISCUSSION...........................................................................................................................................................5HumanHealthConcernsReferencedinthe2016TechnicalReview........................................5Inaccuraciesinthe2016TechnicalReview.........................................................................................7MissingStudiesinthe2016TechnicalReview...................................................................................8PastNOSBActionsandDeliberations..................................................................................................11TheHandlingSubcommitteeisRepeatingIndustryPropaganda............................................12InReferencetoSpecificQuestionsPosedbytheHandlingSubcommittee.........................13CarrageenanisNotEssential...................................................................................................................14

CONCLUSION......................................................................................................................................................15

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HANDLINGSUBCOMMITTEE

Carrageenan–2018Sunset

SUMMARY

TheCornucopiaInstituteopposestherelistingofcarrageenanat205.605(a)Nonagricultural(Nonorganic)substancesallowedasingredientsinoronprocessedproductslabeledas‘‘organic’’or‘‘madewithorganic(specifiedingredientsorfoodgroup(s))”becauseofdecadesofpublicscientificresearchshowingbiologicalreactivityinhumancellscausingharmtohumanhealth.Carrageenanalsolacksessentiality.

Rationale:

! Carrageenanisnon-essential.Everyorganicproductcontainingcarrageenanhasanorganicalternative,beingproducedbyoneormorecompetitors.

! The2016TRfailstodiscusstheundisputedfactthatdegradedcarrageenanispresentwithinfood-gradecarrageenan.AttherequestofEuropeanregulators,theMarinalgWorkingGroupattemptedtoreliablymeasuretheamountofdegradedcarrageenaninfood-gradecarrageenan.Thelabresultswerepostedonlineandprovedthatbioactive,lowmolecularweightcarrageenans(poligeenan)werepresentinallsamplesoffood-gradecarrageenan.Fortunately,TheCornucopiaInstitutedownloadedthesedocumentsbeforetheyweresubsequentlyremovedfromtheinternetbytheindustrylobby.1

! Asaresult,the2005EuropeanCommission’srecommendationthatnomorethan5%offoodgradecarrageenanfractionsshouldhavemolecularweightbelow50kDa2hasnotbeenmetbytheindustry.3,4

! ThestatementmadebytheNOSBhandlingsubcommitteethattheyare“troubledthattheresearchshowinginflammationandglucoseintoleranceisallfromoneresearchteamandhasnotbeenreplicated,”issimplynottrue.

1 Marinalg International (2006) Technical Position on Measurements Related to Meeting the EC Molecular Weight 2 European Committee Scientific Committee on Food. Opinion on Carrageenan. Expressed on 5 March 2003. Available online: http://ec.europa.eu/food/fs/sc/scf/out164_en.pdf. Last accessed March 23, 2016. 3 www.coruncopia.org (reports tab) 4 Marinalg International (2006) Technical Position on Measurements Related to Meeting the EC Molecular Weight distribution Specification for Carrageenan and PES. (Formally available online, but later removed by the company. Appendix B in Cornucopia’s carrageenan report www.cornucopia.org).

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o Thereareanumberoflabsaroundtheworldthathavestudiedthe

inflammatoryeffectsofcarrageenan.Approximately10,000referencesinPubMedoccurwhen“inflammationandcarrageenan”issearched.IntheEuropeanCommissionreviewfrom2003,hundredsofstudiesthatdiscussedtheeffectsofcarrageenanonintestinalinflammationwerereviewed.AfewimportantreferencesthataremissingfromtheTRinclude:

1. Theclinicalimpactofcarrageenananddiabetes,currentlybeingstudied

inGermany(UniversityofTuebingen,Dr.RobertWagnerandDr.NorbertStefan).5

2. Theeffectsofcarrageenanoninsulinresistanceandinhibitionofinsulinsignaling,currentlybeingstudiedbyT.W.Jung,S.Y.Lee,andH.C.Hong.6

3. Theinductionofdiabetesbycarrageenaninananimalmodel,studiedbyH.S.BaekandJ.W.Yoon(1991).7

4. NIH-supportedMouseMetabolicPhenotypingCenteratVanderbilthasdemonstratedtheimpactofcarrageenanexposureonresponsestoinsulininhyperinsulinemic-euglycemicmousestudies.8

! Thepositionstakenbyregulatoryagencieshavebeeninfluencedbyaggressivelobbyingandindustry-fundedreportsaboutcarrageenan—bylawtheNOSBneedstotakeamorecriticalapproach.Thepositionstakenbytheregulatoryagenciesareoftenbasedonasinglestudyinwhichcriticalpointsareobfuscated.Asanexample,therecentinfantpigfeedingstudy9,onwhichtheJointFAO/WHOExpertCommitteeonFoodAdditives(JECFA)partiallybaseditsdecision,containedseveralcriticalflawsincluding(thisquestionable,industry-fundedresearchwasheavilyrelieduponbytheHS):1) Useofinfantpigsinwhichtheinnateimmuneresponsetocarrageenanis

expectedtobelessthaninhumans.

2) Onsetofthepigstudywasafteringestionofmaternalcolostrumandmaternal

5 https://clinicaltrials.gov/ct2/show/NCT02629705. Last accessed on March 23, 2016. 6 Jung TW, Lee SY, Hong HC, Choi HY, Yoo JH, Baik SH, and Choi KM (2014) AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes. Molecular and Cellular Endocrinology 382(1):66-73. 7 Baek HS and Yoon Jw (1991) Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice. Diabetes 40(12):1586-97. 8 Bhattacharyya S, Feferman L, Unterman T, Tobacman JK. (2015) Exposure to common food additive carrageenan alone leads to fasting hyperglycemia and in combination with high fat diet exacerbates glucose intolerance and hyperlipidemia without effect on weight. Journal of Diabetes Research:513429. doi: 10.1155/2015/513429. 9 Weiner ML et al (2015) An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract. Food and Chemical Toxicology 77:120-131.

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feedingforanunspecified,andvariablenumberofdays,unlikethecommonuseinhumaninfantformulafeedingatbirth.

3) Several“incidental”deathsoccurredduringthestudywithnoexplanation.

4) Wateryfeceswereincreasedinthecarrageenan-treatedanimals.

5) Glycosuria(theexcretionofexcessivewaterinurine)occurredin4outof12

animals.

6) Rectalweightwassignificantlyreducedinmalesthatreceivedcarrageenan.

7) Weightswerereportedwithoutrangesorstandarddeviations.

8) Animalsenteredthestudyclosetotheageofweaning,ratherthanimmediatelyafterbirth.

9) Histopathologyimagesdemonstratedifferencesbetweencontroland

carrageenan-treatedtissuesthatwerenotincludedinthetext.

10) Therewasanabsenceofanylong-termdata.[Tobacman,personalcommunication]

ThereweremanysimilarflawsincludingprolongedrecoveryperiodsfollowingexposuretocarrageenanintheBenitzfeedingstudiesalsousedbytheWorldHealthOrganizationtodeterminethatcarrageenanissafe10.Evenwiththisprolongedrecovery,thereweresignificantchangesintheendothelialcellsoftheliversofthemonkeystreatedwithcarrageenan.[Tobacman,personalcommunication]

! The2016TRstatesthat“carrageenancanbeavoidedbysensitiveindividualsasitisincludedinthelabel,therebymakingiteasytoavoid.”Thisisincorrect.Withthislogic,all“sensitive”consumerswouldhavetobeknowledgeableaboutcarrageenan'sinflammatorycharacteristics.Furthermore,whencarrageenanisa“secondary”ingredient,asincondensedmilk,beer,andcream,itisnotlistedonthelabel.

! ThestatementmadebytheNOSBsubcommitteethat“onlysomepeoplearesensitive”isinaccurate.Carrageenanisbioactiveandinflammatory(andapotentialcarcinogenduetolong-termexposure)inallindividuals,notjustthosewhoexhibitacutesymptoms.Itmightbetruethatonlyasubsetofthepopulationexhibitacutesymptoms.However,thespecificchemicalcompositionofcarrageenanisimmunogenicdueto

10 Benitz KF, Golberg L, and Coulston F. (1973) Intestinal effects of carrageenans in the Rhesus monkey (Macaca mulatta). Food and Cosmetics Toxicology 11:565-575.

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thepresenceofthegalactose-alpha-1,3-galactosebond,whichhumansdonotmake.Therefore,theeffectsofcarrageenanoccurinallindividualsandareindependentofthemolecularweight,althoughmoreharmfuleffectsareobservedwithlowermolecularweightcarrageenans(whicharepresentinallfood-gradecarrageenan).

! IndustryhasalsotriedtodiscountstudiesinhumancolonicepithelialcelllineNCM460,whichisroutinelyusedinmanycellculturestudies(notjustinvestigatingcarrageenan)becauseitenablessurvivalinculture.Thisisnotanissue,becauseallofthestudieshadcontrolsthatwerenotexposedtocarrageenanforcomparison,anddatawereanalyzedbyappropriatestatistics.

! Studieshavealsoshowninflammationinnormalhumancolonicepithelialcellsfromcolonsurgeryspecimens,fromotherestablishedrodentandhumanintestinalcelllines,andinmousemodels.11

! It'swidelyacceptedthatdegradedcarrageenanisdangeroustohumanhealth.Severalstudies,havedemonstratedthatfoodgradecarrageenan,whenexposedtostomachacid,degradesinthedigestivetrackposingsignificant,potentialrisk.12,13

! Studiesthatlookattheaveragemolecularweightofcarrageenan,manyofwhicharediscussedintheTR,arenotusefulbecausetheyobscurethepresenceoflowermolecularweightformsthatcontaminateallfoodgradecarrageenan.

! Thelackofmore“dose-response”studieshasbeenerroneouslycriticizedinreports

fundedbyindustry,butseveraldose-responsestudieshavebeenperformed.Theamountofcarrageenanexposureinmanyoftheexperimentsthatdemonstrateinflammationislessthanwhatisconsumedinthetypicaldiet(averagecarrageenanconsumptionof250mg/day.Levelsofdailyconsumptionofcarrageenaninthedietmaybemuchhigher,ontheorderof18-40mg/kg/d).

11 Borthakur A, Bhattacharyya S, Dudeja PK, and Tobacman JK (2007) Carrageenan induces interleukin-8 production through distinct Bc110 pathway in normal human colonic epithelial cells. American Journal of Gastrointestinal Liver Physiology 292: G829-G838. 12UnoY,OmotoT,GotoY,AsaiI,NakamuraM,andMaitaniT(2001)Molecularweightdistributionofcarrageenansstudiesbyacombinedgelpermeation/inductivelycoupledplasma(GPC/ICP)method.FoodAdditivesandContaminants18:763-772.13PittmanKA,GoldbergL,andCoulstonF(1976)Carrageenan:theeffectofmolecularweightandpolymertypeonitsuptake,excretionanddegradationinanimals.FoodandCosmeticsToxicology14(2):85-93.

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DISCUSSION

Carrageenanfunctionsasabulkingagent,carrier,emulsifier,gellingagent,glazingagent,humectant,stabilizer,orthickener.Itistypicallyusedataraterangingfrom0.03%to0.75%,anditsmostcommonusesareindairyproducts,non-dairy"milk"analogs,processedmeats,yogurts,chewablevitamins,pizzacrusts,toothpastes,wetpetfoodsanddrinkmixes.Itisadirectfoodadditivewithanaveragemolecularweightof200-800kDa,andmaybereferredtoas“undegraded”or“native”carrageenanintheliterature,howeverthismisrepresentsthesubstancebecauseallcarrageenancontainssomedetectablepercentageofdegradedcarrageenan(usedtoinducecancertostudyanti-inflammatorydrugs).Thekappa,iotaorlambdaformationofcarrageenanisdefinedbythenumberandpositionofsulfategroups,butalltypesareusedinfoods.TheEuropeanCommission’srecommendationthatnomorethan5%ofcarrageenanfractionsshouldhavemolecularweightbelow50kDa14hasbeenimpossiblefortheindustrytocomplywith,basedontheirownreports.15Carrageenanwithmolecularweightlessthan50kDaarethoughttocausethemostseverehealthproblems.

HumanHealthConcernsReferencedinthe2016TechnicalReview

Anumberofstudiesbymultipleresearchershaveidentifiedpotentialhumanhealthconcerns,including:• “Theliteratureisinagreementthatpoligeenancausesulcerationsofthececusand

proximalcoloninexperimentalanimals,leadingtoitsclassificationbytheInternationalAgencyforResearchonCancerasapossiblehumancarcinogen”(line27-29).

• “InanearlyinvivostudybyPittman,GolbergandCoulston(1975)16,carrageenanwasgiventoguineapigs,monkeysandratsviadrinkingwaterorinthediet.Fecalandliversampleswereexaminedquantitativelybygelelectrophoresistodeterminechangesinmolecularweightofcarrageenansafterpassingthroughthedigestivetract.Thestudydemonstratedthathighmolecularweightcarrageenansaredegradedtosomeextentasaresultoftheirpassagethroughtheintestinaltract.

14 European Committee Scientific Committee on Food. Opinion on Carrageenan. Expressed on 5 March 2003. Available online: http://ec.europa.eu/food/fs/sc/scf/out164_en.pdf. Last accessed March 23, 2016. 15 Marinalg International (2006) Technical Position on Measurements Related to Meeting the EC Molecular Weight distribution Specification for Carrageenan and PES. (Formally available online, but later removed by the company. Appendix B in Cornucopia’s carrageenan report www.cornucopia.org). 16 Pittman KA, Goldberg L, and Coulston F (1976) Carrageenan: the effect of molecular weight and polymer type on its uptake, excretion and degradation in animals. Food and Cosmetics Toxicology 14(2):85-93.

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• Polysaccharidessuchascarrageenanaredepolymerized(degraded)inacidsolution,andtherateofpolymerizationdependsonpHandtemperature(Capron,YvonandMuller1996)17.Thefindingsshowedthatafter2hoursinsimulatedgastricjuiceatpH1.2,almost90%ofthecarrageenanhadamassoflessthan100kDaand25%hadamassoflessthan20kDa.

• “Grassoetal.(1973)18identifiedmultiplepin-pointcaecalandcoloniculcerationsinguineapigsafterbeingfed5%dietofcarrageenanfor45days”(line116-117).

• “Aseriesofstudieshasshownthatcarrageenancaninduceacomplexinflammatorycascadeinhumanintestinalepithelialcellsthroughanimmune-mediatedmechanism(Borthakuretal.2012)19andareactiveoxygenspecies(ROS)-mediatedmechanism(Bhattacharyya,DudejaandTobacman2008)20,whichcontributetoaninflammatoryresponse.Afeedbackloopleadstoextendedinflammation...(Bhattacharyaetal.2010a21,Borthakuretal.200722;Bhattacharyyaetal.2010b23;Bhattacharyya,Feferman,andTobacman201524)”(lines147-155).

• “AreviewarticlebyTobacman(2001)ofanimalstudiesontheeffectsofcarrageenan

andpoligeenanongastrointestinalhealthconcludedthatundegradedcarrageenanisassociatedwithintestinalulcerationsandneoplasms.Thearticleattributedtheseissuestothecontaminationofundegradedcarrageenanbycomponentsoflowmolecularweight,thespontaneousmetabolismtolowermolecularweightbyacidhydrolysisunderconditionsofnormaldigestion,ortheinteractionswithintestinalbacteria.(NicklinandMiller198425;Rustia,ShubikandPatil198026;Pittman,Golberg

17 Capron IM, Yvon, and Muller G (1996) In-vitro gastric stability of carrageenan. Food Hydrocolloids 10(2):345. 18 Grasso PM, Sharrat MB, Carpanini, and Gangolli SD (1973). "Studies on Carrageenan and Large-bowel Ulceration in Mammals." Food Cosmetic Toxicology 11:555-564. 19 Borthakur A, Bhattacharyya S, Anbazhagan AN, Kumar A, Dudeja PK, Tobacman JK. (2012) Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NFκB-BCL10 loop. Biochimica Biophysica Acta 1822(8):1300-7. 20 Bhattacharyya S, Dudeja PK, Tobacman JK. (2008) Carrageenan-induced NFkappaB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10. Biochimica Biophysica Acta 1780(7-8):973-82. 21 Bhattacharya, Sumit, et al. (2010) B-cell CLL/Lymphoma 10 (BCL10) Is Required for NF-kB Production by Both 316 Canonicl and Noncanonical Pathways and for Nf-kB-inducing Kinase (NIK) Phosphorylation. Journal of Biological Chemistry 285(1): 522-530. 22 Borthakur A, Bhattacharyya S, Dudeja PK, and Tobacman JK (2007) Carrageenan induces interleukin-8 production through distinct Bc110 pathway in normal human colonic epithelial cells. American Journal of Gastrointestinal Liver Physiology 292:G829-G838. 23 Bhattacharya S et al. (2010) Carrageenan-induced innate immune response is modified by enzymes that hydrolyze distinct galactosidic bonds. Journal of Nutritional Biochemistry 21: 906-913. 24 Bhattachayra S, Feferman L, and Tobacman JK. (2015) Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(p)-ISR1 and through Inflammation-induced Increase in Ser(P)307-IRS1. Journal of Biological Chemistry 290(17): 10764-10774. 25 Nicklin S and Miller K (1984) Effect of orally administered food-grade carrageenans on antibody-mediated and cell-mediated immunity in the inbred rat. Food Chemical Toxicology 22(8): 615-621. 26 Rustia M, Shubik P, and Patil K (1980) Lifespan carcinogenicity tests with native carrageenan in rats and hamsters. Cancer Letters 11:1-10.

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andCoulston197527;EngsterandAbraham197628;Poulsen197329;Benitz,GolbergandCoulston197330;Grassoetal.197331)”(lines161-165).

• “Sincedifferentanimalspecies,differentanimalswithinthesamespecies,anddifferent

humanintestinalcelllineshaveproduceddifferentexperimentalresults,itisreasonabletoexpectthathumansmayalsoexperiencevaryingdegreesofsensitivitytocarrageenaninthediet”(lines177-180).

Inaccuraciesinthe2016TechnicalReview

• “Poligeenan,alsocalled“degradedcarrageenan”or“C16”intheliterature,isadistinctly

differentsubstancefromfoodgradecarrageenan…”(line19-20).Correction:Poligeenan(degradedcarrageenan)isfoundinfood-gradecarrageenan.

• “Poligeenan(CAS#53973-98-1)isanartificiallyformedpolymerproducedbysubjectingcarrageenantoextensiveacidhydrolysisatlowpH(0.9-1.3)andhightemperatures(>80ºC)foranextendedperiodoftime.”(line19-22)Correction:poligeenanisfoundnaturallyinallredseaweedsandinfood-gradecarrageenan.

• “Its[poligeenan]onlyapplicationtodayisasa25componentofx-rayimagingdiagnosticproducts”(line24-25).Correction:carrageenanisusedinresearchtoinduceinflammationandstudytheeffectofanti-inflammatorydrugs.

• “Itispossiblethatfood-gradecarrageenanmaycontainsomelowmolecularweightfractionsthatareequivalenttopoligeenan,althoughvalidatedanalyticalmethodstoaccuratelymeasurethelowmolecularweightdistributionsofcarrageenanarenotfullydevelopedoravailabletotheindustry”(lines31-33).Correction:reportsfrombothacademiaandindustryshowthatfood-gradecarrageenaniswelldocumentedtocontainpoligeenan.

27 Pittman KA, Goldberg L, and Coulston F (1976) Carrageenan: the effect of molecular weight and polymer type on its uptake, excretion and degradation in animals. Food and Cosmetics Toxicology 14(2):85-93. 28 Engster M and Abraham R (1976) Cecal response to different molecular weights and types of carrageenan in the guinea pig. Toxicology and Applied Pharmacology 38(2):265-282. 29 Poulsen E (1973) Short-term Peroral Toxicity of Undegraded Carrageenan in Pigs. Food Cosmetic Toxicology 11:219-227. 30 Benitz KF, Golberg L, and Coulston F (1973) Intestinal Effects of Carrageenans in the Rhesus Monkey (Macaca mulatta). Food Cosmetic Toxicology 11:565-575. 31 Grasso P, Sharrat M, Carpanini MB, and Gangolli SD (1973) Studies on Carrageenan and Large-bowel Ulceration in Mammals." Food Cosmetic Toxicology 11:555-564.

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MissingStudiesinthe2016TechnicalReview

• MarinalgInternational(2006)TechnicalPositiononMeasurementsRelatedtoMeeting

theECMolecularWeightdistributionSpecificationforCarrageenanandPES.(Formallyavailableonline,butlaterremovedbythecompany.AppendixBinCornucopia’scarrageenanreportwww.cornucopia.org).Summaryoffindings:Degradedcarrageenanwasfoundinallfood-gradecarrageenansamples,butthepercentagecouldnotbereplicatedacrossdifferentlabs.

• TobacmanJK(2015)TheCommonFoodAdditiveCarrageenanandthealpha-galepitope.JournalofAllergyandClinicalImmunology136(6):1708-9.Summaryoffindings:Thespecificchemicalcompositionofcarrageenanisimmunogenicduetothepresenceofthegalactose-alpha-1,3-galactosebond,whichhumansdonotmake.Therefore,theeffectsofcarrageenanoccurinallindividualsandareindependentofthemolecularweightofthecarrageenaningested,althoughmoreharmfuleffectsoccurfromlowmolecularweightcarrageenan.

• ColemanMRandColemanMT(2015)“Dairy-free”dietarysubstitute,abdominalpain,andweightloss.ClinicalMedicalReviewsandCaseReports2:8.Summaryoffindings:Eliminationofcarrageenan-containingalmondmilkfromthedietofapatientthathadsubstituteditforcow’smilkseveralmonthspriorresultedinstabilizationofweightandresolutionofabdominalpain.

• JungTW,LeeSY,HongHC,ChoiHY,YooJH,BaikSH,andChoiKM(2014)AMPKactivator-mediatedinhibitionofendoplasmicreticulumstressamelioratescarrageenan-inducedinsulinresistancethroughthesuppressionofselenoproteinPinHepG2hepatocytes.MolecularandCellularEndocrinology382(1):66-73.Summaryoffindings:Carrageenancausesinflammationthroughtoll-likereceptor4,whichplaysanimportantroleininsulinresistanceandtype2diabetesmellitus.Carrageenaninducesendoplasmicreticulum(ER)stressinatime-anddose-dependentmanner.

• BhattacharyyaS,FefermanL,andTobacmanJK(2014)RegulationofChondroitin-4-Sulfotransferase(CHST11)ExpressionbyOpposingEffectsofArylsulfataseBonBMP4andWnt9A.BiochimBiophysActa1849(3):342-352.Summaryoffindings:Exposuretothecommonfoodadditivecarrageenan,whichreducesARSBactivity,reducedexpressionofbonemorphogeneticprotein(BMP)-4incolonicepitheliumandincreasedWnt9AexpressionandWnt/β-cateninsignaling.

• BhattacharyyaS,FefermanL,andTobacmanJK(2014)IncreasedExpressionofColonicWnt9AthroughSp1-mediatedTranscriptionalEffectsinvolvingArylsulfataseB,Chondroitin4-Sulfate,andGalectin-3TheJournalofBiologicalChemistry289(25):17564-17575.Summaryoffindings:MechanismbywhichWntexpressionwasincreasedbycarrageenanexposurewasunknown.ExtracellulareventscanregulatetranscriptionthroughchangesinarylsulfataseBandchondroitin4-sulfation.

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• YangB,BhattacharyyaS,LinhardtRandTobacmanJK(2012)Exposuretocommon

foodadditivecarrageenanleadstoreducedsulfataseactivityandincreaseinsulfatedglycosaminoglycansinhumanepithelialcells.Biochimie94(6):1309-16.Summaryoffindings:Exposuretosmallamountsoffood-gradecarrageenanreducestheactivityofsulfataseenzymes,whicharecriticalformanyvitalcellularprocesses.

• BhattacharyyaS,DudejaPKandTobacmanJK(2010)Tumornecrosisfactoralpha-inducedinflammationisincreasedbutapoptosisisinhibitedbycommonfoodadditivecarrageenan.JournalofBiologicalChemistry285(50):39511-22.Summaryoffindings:Thisstudyexaminestheparticularmechanismsbywhichfood-gradecarrageenancauseinflammation.

• BhattacharyyaS,GillR,ChenML,ZhangF,LinhardtRJ,DudejaPKandTobacmanJK(2008)Toll-likereceptor4mediatesinductionoftheBcl10-NFkappaB-interleukin-8inflammatorypathwaybycarrageenaninhumanintestinalepithelialcells.JournalofBiologicalChemistry283(16):10550-8.Summaryoffindings:Exposureofhumancolonicepithelialcellsintissueculturetosmallquantitiesoffood-gradecarrageenanwasassociatedwithchangesinmolecularsignalingpathwaysthatresemblethechangesfoundinhumancolonicpolyps.Untreatedpolypscandevelopintocoloncancer.

• BhattacharyyaS,BorthakurA,DudejaPKandTobacmanJK(2008)Carrageenaninducescellcyclearrestinhumanintestinalepithelialcellsinvitro.JournalofNutrition138(3):469-75.Summaryoffindings:Exposureofhumancolonicepithelialcellsintissueculturetosmallquantitiesofundegraded(food-grade)carrageenanproducedanincreaseincelldeathwithcellcyclearrest,effectsthatcancontributetoulcerations.

• BhattacharyyaS,BorthakusA,DudejaPKandTobacmanJK(2007)Carrageenanreducesbonemorphogeneticprotein-4(BMP4)andactivatestheWnt/beta-cateninpathwayinnormalhumancolonocytes.DigestiveDiseasesandSciences52(10):2766-74.Summaryoffindings:Thisstudyidentifiedmechanismsbywhichfood-gradecarrageenaninfluencesthedevelopmentofhumanintestinalpolyps.Untreatedintestinalpolypscandevelopintocoloncancer.

• SuzukiJ,NaHK,UphamBL,ChangCCandTroskoJE(2000)Lambda-carrageenan-inducedinhibitionofgap-junctionalintercellularcommunicationinratliverepithelialcells.NutritionandCancer36(1):122-8.Summaryoffindings:Carrageenanfunctionsasatumor-promotingchemicalbyinhibitingGJIC(Gap-junctionalintercellularcommunicationisbelievedtohelphealthycellsfightcancer).ThedatarevealedinhibitionofGJICbycarrageenansimilartothatbythewell-documentedtumorpromoterphorbolester.

• CorpetDE,TachéS,andPréclaireM(1997)Carrageenangivenasajellydoesnotinitiate,butpromotesthegrowthofaberrantcryptfociintheratcolon.CancerLetters

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114:53–55.Summaryoffindings:Consumptionoffood-gradecarrageenanpromotesthegrowthofaberrantcryptfociintheratcolon.Aberrantcryptfociareabnormalglandsinthecolonthatareprecursorstopolypsandareoneoftheearliestchangesseeninthecolonthatmayleadtocancer.

• CalvertRJandReicksM(1988)Alterationsincolonicthymidinekinaseenzymeactivityinducedbyconsumptionofvariousdietaryfibers.ProceedingsoftheSocietyforExperimentalBiologyandMedicine189:45–51.Summaryoffindings:Researchersexaminedthereportedeffectsofvariousdietaryfibersonchemicallyinducedcoloncarcinogenesisinrats.Thisstudyfoundafour-foldincreaseinthymidinekinaseactivity(ameasureformalignantdisease)incolonicmucosafollowingexposuretofood-gradecarrageenan.Nodifferenceswerefoundfollowingexposuretoguargum,afoodadditiveusedasanalternativetocarrageenan.

• ArakaweS,OkumuaM,YamadaS,ItoM,TejimaS(1986)Enhancingeffectofcarrageenanontheinductionofratcolonictumorsby1,2-dimethylhydrazineanditsrelationtoß-glucuronidaseactivitiesinfecesandothertissues.JournalofNutritionalScienceandVitaminology32:481–485.Summaryoffindings:Higherratesoftumorswerefoundinratsfedundegradedcarrageenaninthediet.

• WattJandMarcusR(1981)Dangerofcarrageenaninfoodsandslimmingrecipes.TheLancet317(8215):338.LettertoTheLancet:ScientistsrepeattheirconcernwiththeuseofcarrageenaninfoodinalettertoTheLancet.

• WattJandMarcusR(1980)Potentialhazardsofcarrageenan.TheLancet315(8168):602-603.LettertoTheLancet:Theauthorsofpublishedresearchshowingincreasedratesofulcerativecolitis-likediseaseinlaboratoryanimalsgivenfood-gradecarrageenanwrotethelettertoTheLancet.Highlyrespected,TheLancetisoneoftheworld’sleadingmedicaljournals.Thescientistsexpresstheirconcernwiththesafetyofcarrageenaninfood.

• WatanabeK,ReddyBS,WongCQ,WeisburgerJH(1978)EffectofdietaryundegradedcarrageenanoncoloncarcinogenesisinF344ratstreatedwithazoxymethaneormethylnitrosourea.CancerResearch38:4427–4430.Summaryoffindings:Thisstudyfoundhigherratesoftumorsinratsfedundegradedcarrageenaninthediet.

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PastNOSBActionsandDeliberations

DuringthelastSunsetReviewin2012,theNOSBreceivedcommentsfromboththescientificcommunityandthepublicconcerningcarrageenan’simpactonhumanhealth.Industrycritiquedresearchmethodologyusedinpublicallyfundedstudiesandclaimedthatresultswerenotalwaysconsistentwithhowcarrageenanbehaveswheningestedinfood.TheNOSBstatedtheycouldnotthoroughlyinvestigatetheseissueswithintheshortperiodoftimebetweentheSunsetannouncementandthevotetorenew.Sincethistime,allofindustry’scriticismsofpublicallyfundedresearchhavebeenaddressedand,basedonindustrytalkingpoints,thehandlingsubcommitteehasattemptedtodiscreditthepublicresearch/researchers.TheHandlingSubcommitteecommissionedaLimitedScopeTechnicalReport,completedbyOMRIandreleasedtothepublicinMarch2016,howevertheauthorswerenotdisclosed.Thescientificcommunity’spreeminentpublicresearcheroncarrageenanwasnotconsultedforanyinformationinresearchingtheTR[Tobacman,personalcommunication].EvenaftertheTRwasreleasedtheHandlingSubcommitteeincorrectlystated“Wearetroubledthattheresearchshowinginflammationandglucoseintoleranceisallfromoneresearchteamandhasnotbeenreplicated.Wehopethatinthenextfewmonthsbeforewevotemoreconclusiveresearchreplicationorrebuttalwillhelpinformourdecision.”Thisstatementiswoefullyinaccurate.EventheTR(whichismissingsomepublishedresearch)sitesdozensofscientistsandarticlesshowingharmfromfood-gradecarrageenan.Yes,Dr.Tobacman’sgroupwasthefirsttoevaluatehowtheinflammatoryeffectsofcarrageenaninhibitinsulinsignalingandcauseinsulinresistance.However,otherinvestigatorshavepublishedeffectsofcarrageenanoninhibitionofinsulinsignaling(Jungetal,MolecularCellEndocrinology201432),andinvestigatorsintheNIH-supportedMouseMetabolicPhenotypingCenteratVanderbiltdemonstratedtheimpactofcarrageenanexposureonresponsestoinsulininhyperinsulinemic-euglycemicmousestudies(Bhattacharyya,JournalofDiabetesResearch,2015.)33

32 Jung TW, Lee SY, Hong HC, Choi HY, Yoo JH, Baik SH, and Choi KM (2014) AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes. Molecular and Cellular Endocrinology 382(1):66-73. 33 Bhattacharyya S, Feferman L, Unterman T, Tobacman JK. (2015) Exposure to common food additive carrageenan alone leads to fasting hyperglycemia and in combination with high fat diet exacerbates glucose intolerance and hyperlipidemia without effect on weight. Journal of Diabetes Research:513429. doi: 10.1155/2015/513429.

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TheHandlingSubcommitteeisRepeatingIndustryPropaganda

Inaddition,studiesofcarrageenanfeedingininfantpigsconductedbyindustryresearchersdetectedglycosuriain4outof12oftheanimals(Weineretal,FoodandChemicalToxicology,2015).34StudiesconducteddecadesagobyindustryscientistsatAlbanyMedicalCollegeshowedelevatedbloodsugarsandreducedhepaticglycogenstores,consistentwithdiabetes.35InvestigatorsinGermany(Drs.WagnerandStefanUniversityofTuebingen)arecurrentlyexaminingtheimpactofcarrageenanonglucosetoleranceandinsulinresistanceinanongoingclinicalstudy.36Tobacman’sgrouphasbeenfundedbytheAmericanDiabetesAssociationtodetecttheimpactoftheno-carrageenandietonglucosetoleranceinprediabeticpatients.Otherinvestigatorshavereportedinductionofdiabetesbycarrageenaninananimalmodel(Baek,Diabetes,1991).37TheHandlingSubcommitteealsostated“ItisalsoworthnotingthatinthetimesincethelastreviewtheWorldHealthOrganizationJECFAcommitteere-evaluatedcarrageenanforuseininfantformulaandchangedtheiropiniononrestrictingitsusetohaveanunrestrictedstatus.”Thisdeterminationwasbasedlargelyontheflawedindustrystudyofcarrageenanintakeininfantpigs(Weineretal,FoodChemicalToxicology,2015.)38Flawsinthisstudyinclude:1)useofinfantpigsinwhichtheinnateimmuneresponsetocarrageenanisexpectedtobelessthaninhumans,sincepigsmakethealpha-1,3-galactosyltransferaseenzymeandthegalactose-alpha-1,3-galactosebondofcarrageenanisnotimmunogenicinthepig;2)onsetofthestudywasafteringestionofmaternalcolostrumandmaternalfeedingforanunspecified,andvariablenumberofdaysinthestudyanimals;3)antibioticsandironsupplementsweregivenpriortoandthroughoutthe28-daycarrageenanfeeding;4)several“incidental”deathsoccurredwithnoexplanation;5)softand/orwateryfeceswereincreasedinthecarrageenan-treatedanimals;6)glycosuriaoccurredin4/12animals;7)rectalweightwassignificantlyreducedinmales;8)weights,whichwerereportedwithoutrangesorstandarddeviations,wereunusuallyhigh(allover10kg)atStudyDay28,suggestingthattheanimalswereatleast5weeksold,andthereforehadenteredthestudyclosertotheageofweaning,expectedtobeatday19.4afterbirth;9)histopathologydemonstratesdifferencesbetweencontrolandcarrageenan-treatedtissues,includingincreasedinflammatoryinfiltrateinthelaminapropriaandreducedcolonic

34 Weiner ML et al (2015) An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract. Food and Chemical Toxicology 77:120-131. 35 Abraham R, Benitz KF, Mankes R, and Rosenblum I (1985) Chronic and Subchronic Effects of Various Forms of Carrageenan in Rats. Ecotoxicology and Environmental Safety 10: 173-183. 36 https://clinicaltrials.gov/ct2/show/NCT02629705. Last accessed on March 23, 2016. 37 Baek HS and Yoon Jw (1991) Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice. Diabetes 40(12):1586-97. 38 Weiner ML et al (2015) An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract. Food and Chemical Toxicology 77:120-131.

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haustrations,and10)absenceofanylong-termdata.Theessentialchemicalstructureofcarrageenancontainstheimmuneepitopegalactose-alpha-1,3,-galactosewhichisnotmadebyhumancellsandstimulatesimmuneresponses,includingrejectionoftransplantedtissuefromothermammals,exceptOldWorldapes.Hence,thefeedingstudiesperformedinpigsbyindustryareirrelevantinthisregard,sincecarrageenanisnotanticipatedtostimulatetheinnateimmuneresponseinthepigs.The28-daypigfeedingstudywasnotconductedrigorously,andthereportobfuscatesdifferencesbetweenthecarrageenan-exposedandcontrolgroups.This28-daystudyisinadequatetojustifyprolongedfeedingofcarrageenan-containingformulatomillionsofbabies.Finally,aprevious,industry-supportedstudyininfantbaboonsdidnotexaminelong-termeffectsoreffectsonimmunity(McGill,Gastroenterology,1977).39Increasedcolonicpathologywasidentifiedinthecarrageenan-treatedanimals,includingincreasesincryptabscessesandhyperemiaofthecolonicmucosaafter112days.

InReferencetoSpecificQuestionsPosedbytheHandlingSubcommittee

1)Ifhumanshavevaryingdegreesofsensitivitytocarrageenaninthediet,isthatenoughreasontoprohibititinallorganicfoods?Humansarealsosensitivetogluten,dairy,legumes,andmanyotherfoods;isthatareasontokeepthemout?

• Theeffectsofcarrageenanonhumanhealthhavebeenstudiedindepthoverthepastseveraldecades.ThechemicalstructureofcarrageenanandtheinteractionwiththeTLR4receptorindicatethelikelihoodthatcarrageenan’seffectsareattributabletofundamentalbiologicalcharacteristicsof[all]humans.

• Industryhastriedfordecadestodifferentiatebetweenharmfuleffectsattributabletolowmolecularweightpoligeenanvs.highmolecularweightcarrageenan.Now,thereisanattemptbyindustrytodistinguishalowmolecularweighttailofcarrageenanfrompoligeenan.Thesedistinctionsareabsurd.Carrageenaniscomposedofdisaccharideunits,similartothestructureofchondroitinsulfateorheparin.Molecularweightmayvaryforthesesulfatedglycosaminoglycansdependingonthenumberofdisaccharideunits.Thedisaccharideunitsofpoligeenan,orcarrageenan,orthelowmolecularweighttailofcarrageenanarethesame.

• Food-gradecarrageenancontainssomelowermolecularweightformsnaturally,andtheamountincreasesduetoprocessing,heat,acid,intestinalbacteria,andmechanicalprocessing,suchaschewing.

39 McGill HC Jr., McMahan CA, Wigodsky HS, et al. (1977) Carrageenan in formula and infant baboon development. Gastroenterology 73:512-517.

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CarrageenanisNotEssential

Manybrandsarenowusingthelackofcarrageenanintheirformulationsasamarketingtool.Overthepastfiveyears,anumberofprominentcompanieshaveannouncedtheyhaveorwillsoonremovecarrageenanfromtheirproductlines.ThesecompaniesincludeWhiteWave,oneofthelargestmarketersoforganic/naturalfoodsinthecountry.However,asofApril2016,Whitewave’sHorizonorganiclow-fatsourcreamandcottagecheesestillhavecarrageenan.Theyhaveremoveditfrommanyoftheirotherproducts,includingTuberzyogurtforchildren,chocolatemilk,andwhippingcream.Inresponsetogrowingmarketplaceconcern,thefollowingcompanieshavecompletelyremovedcarrageenanfromtheirproductlines:AlmondBreeze®,AmazingGrassKidzSuperfood®,Annie’s®,CalifiaFarms®,andGoodKarma®.SoDelicious®(alsoownedbyWhiteWave)hasremoveditfromtheirrefrigeratedcoconutmilk,butnottheirshelf-stableselections.Inothercases,companiescontinuetodefenditssafety,frequentlypostingbiasedinformation,suppliedbylobbyiststothecarrageenanindustry,ontheirwebsites.OrganicValleyisworkingtoremoveitfromtheirproductlines.InNovember2012,theyreformulatedtheireggnogtobecarrageenan-free.Theyalsoremoveditfromtherechocolatemilk.AsofApril,2016,theonlyremainingOrganicValleyproductwithcarrageenanisheavywhippingcreamthatis“ultra-pasteurized”,whereasitsheavywhippingcreamthatislabeled“pasteurized”(standardhightemperatureshorttimepasteurization—HTST)doesnot.TheCornucopiaInstitute’swebpage(www.cornucopia.org),onthe“Reports”tab,hasthelatestresourcesoncarrageenaninproducts,includingabuyersguidetohelpfamilieschooseproductswithoutcarrageenan.

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CONCLUSION

TheCornucopiaInstituteopposestherelistingofcarrageenanat205.605(a)becauseofharmtohumanhealthandlackofessentiality.Thecarrageenanindustryhastriedfordecadestoretaintheuseofcarrageenaninfoodproducts,becauseofitscost-effectivebiologicalreactivitywithingredients.Thissamebiologicalreactivityiswhatmakescarrageenanharmful.Effortsbyindustrytocoveruptheharmfuleffectsofcarrageenanresemblesimilareffortsbythosewithothervestedinterests(tobacco,climatechange,fracking,etc.).Thesecover-upsmustnotgounchallenged.TheOrganicsectorexpectsbetter.ThereasonCongressestablishedthepoweroftheNOSB,toreviewsyntheticandnon-organicfoodingredientsandotherinputs,wasthatthebodyassumedthattherewouldbeahigher,morerigorousstandardsetfororganicfoodsincomparisontoconventionalprotocols.Sinceallindependentlyfundedpublicresearchillustratesthedangertohumanhealth,iningestingfood-gradecarrageenan,andmost,butnotall,industryfundedresearchsuggeststheopposite,itwouldbegeneroustosuggestthatthecurrentscientificliteratureis“mixed.”ItisincumbentupontheNOSBtoerronthesideofcaution,operatingunderthePrecautionaryPrinciple,byexcludingcarrageenanfromuseinorganicfoods.