carrageenan 2018 sunset national organic standards board
TRANSCRIPT
HandlingSubcommittee
Carrageenan2018Sunset
Comments
Commentssubmittedinadvanceofthe
NationalOrganicStandardsBoardSpring2016MeetingApril25–27Washington,DC
TheCornucopiaInstituteP.O.Box126Cornucopia,WI54827608-625-2000voice866-861-2214faxcultivate@cornucopia.orgwww.cornucopia.orgCopyright©2016,TheCornucopiaInstitute
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.