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Krill oil – are there alternatives?

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Authors:

Clarissa Gödde, Institute for Alternative and Sustainable Nutrition

Dr. Markus Keller, Fachhochschule des Mittelstands (University of Applied Sciences)

Giessen/Bielefeld, 07.02.2018

Krill oil – are there alternatives?

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19 1

2

Index

IndexofTables..........................................................................................................................3

IndexofAbbreviations..............................................................................................................3

1 Introduction......................................................................................................................5

2 PhysiologicalroleofLCn-3PUFAs....................................................................................5

3 Recommendedintakeoflongchainomega-3fattyacids.................................................6

4 EffectsofLCn-3PUFAsonhumanhealth.........................................................................8

4.1 Cardiovasculardiseases..............................................................................................9

4.2 Inflammatorydiseases................................................................................................9

4.3 Neurologicaldevelopmentanddegeneration..........................................................10

4.4 Other.........................................................................................................................10

4.5 HealthclaimsforEPAandDHA.................................................................................10

5 Sourcesofn-3PUFAs:krillandplant-basedalternatives................................................11

5.1 Krilloil.......................................................................................................................11

5.2 Plant-basedLCn-3PUFAsources.............................................................................12

5.2.1 Microalgaeoil....................................................................................................12

5.2.2 Transgenicland-basedplantcrops....................................................................13

5.3 Comparisonofkrillwithmicroalgaeoil....................................................................13

5.3.1 Bioavailabilityofmicroalgaeoilversuskrilloil..................................................13

5.3.2 Safetyofmicroalgaeoilversuskrilloil..............................................................14

6 Conclusion.......................................................................................................................15

References...............................................................................................................................16

3

Index of Tables

Table1: Recommendationsforn-3PUFAintake1

Table2: TransgenicplantswithEPA/DHAcontent2

Index of Abbreviations

AA Arachidonicacid

AAP AmericanAcademyofPediatrics

AFFSA French Agency for Food, Environmental and Occupational

HealthandSafety

AHA AmericanHeartAssociation

ALA α-linolenicacid

AND AcademyofNutritionandDietetics

CVD Cardiovasculardisease(s)

DDT Dichlorodiphenyltrichloroethane

DHA Docosahexaenoicacid

EE Ethylester

EFSA EuropeanFoodSafetyAuthority

EPA Eicosapentaenoicacid

EU EuropeanUnion

FAO TheFoodandAgricultureOrganizationoftheUnitedNations

FFA Freefattyacid

GL Glycolipid

GMO Geneticallymodifiedorganism

GOED GlobalOrganizationforEPAandDHAOmega-3s

HDL High-densitylipoprotein

ISSFAL InternationalSocietyfortheStudyofFattyAcidsandLipids

LA Linoleicacid

LCn-3PUFA Longchainomega-3polyunsaturatedfattyacid

LDL Low-densitylipoprotein

n-6PUFA Omega-6polyunsaturatedfattyacid

PCB Polychlorinatedbiphenyl

4

PL Phospholipid

SCAN ScientificAdvisoryCommitteeonNutrition

TAG Triacylglycerol

VITAL VitaminDandOmega-3Trial

WHO WorldHealthOrganization

5

Introduction

Krill are shrimp-like marine crustaceans of the order Euphausiacea. Krill oil is primarily

obtainedfromAntarctickrill(Euphausiasuperba).Duetoitshighcontentofthelongchain

omega-3 polyunsaturated fatty acids (LC n-3 PUFA) eicosapentaenoic acid (EPA) and

docosahexaenoicacid(DHA)krilloiliswidelyusedasaLCn-3PUFAsupplement,inaddition

toLCn-3PUFAsupplementsderivedfromfishormicroalgae.Incontrasttoterrestrialplants,

marinemicroalgaearenotonlyabletosynthesizeLCn-3PUFAs,butarethemainprimary

producersofthesefattyacids inthemarineenvironment.3Thus,bytrophicupgradingEPA

andDHAaccumulatealongthemarine foodchain inkrilland fish. InkrilloilEPAandDHA

occur in phospholipid (PL) and free fatty acid (FFA) form, while in fish oil they are

predominantlypresentintriacylglycerol(TAG)form.Basedonthesebiochemicalvariationsa

reviewhasdiscussedahigherbioavailabilityofEPAandDHAfromkrilloilthanfishoil,but

concludedtheavailablehumanstudiesareinconclusive4.

1 Physiological role of LC n-3 PUFAs

Whilesaturatedfattyacidspredominantlyareutilizedtoprovideandstoreenergy,PUFAs,

likeEPAandDHA,havestructuralandregulatoryfunctions.Thus,theydeterminethefluidity

ofbio-membranes,altertheinflammatorycapacityoftissuehormonesandinfluencecellular

signallingpathwaysandgeneexpression.5HighconcentrationsofDHAareespeciallyfound

inbraintissueandtheretina.ThereisscientificevidencethataPUFA-richdietisassociated

with a reduced risk for cardiovascular diseases (CVD)6, inflammatory conditions, like

arthritis7, and neurodegenerative diseases8. It iswell known that DHA is essential for the

neurological and visual development of infants.9 The health effects of LC n-3 PUFAs are

discussedindetailinchapter3.

EPA and DHA are considered as conditionally essential for humans because they can be

synthesizedfromtheessentialfattyacidα-linolenicacid(ALA).10However,theconversionof

ALA to EPA andDHA in the humanbody is limited by the set of enzymes responsible for

elongationanddesaturation,whichtheysharewiththeomega-6fattyacids(n-6PUFA),i.e.

theconversionoflinoleicacid(LA)toarachidonicacid(AA).Modernhumannutritionisrich

inn-6PUFAslikeLA,therefore,theconversionofALAintolongchainn-3PUFAsisverylow

6

(ALA toEPA~8-12%;ALA toDHA<1%).Women seem tohavehigher conversions rates

(ALAtoEPAupto21%;ALAtoDHAupto9%)thanmen(ALAtoEPA0.3-8%;ALAtoDHA<

1%).5 The International Society for theStudyof FattyAcidsandLipids (ISSFAL) concluded

thattheconversionofALAtoDHAininfantsamountsto1%andis“considerablylower”in

adults.11

2 Recommended intake of long chain omega-3 fatty acids

Many international and national authorities and scientific organizations have published

recommendationsforthedaily intakeofn-3PUFAs.TheWorldHealthOrganization(WHO)

proposesan-3PUFA(allformscombined)intakeof1-2%ofthetotalenergyintake.12The

Food and Agriculture Organization (FAO) and the European Food Safety Authority (EFSA)

assessaminimumdietaryrequirement/adequateintakeforALAof0.5%oftotalenergyto

be sufficient to prevent deficiency symptoms in adults.13,14 Recommendations for the

combinedintakeofEPAandDHAforthegeneraladultpopulationmostlyvarybetween250

mg/day (EFSA13) and500mg/day (ISSFAL15) (Table1). These recommendations aremainly

basedonconsiderationsconcerningcardiovascularhealth.Duetoinsufficientdata,itisnot

possible to derive an average requirement for EPA and/or DHA. To date, LC n-3 PUFA

deficiencysymptomsarenotknown.13Inaddition,themajorityofinternationalandnational

organizations recommend a minimum intake of 200 mg DHA per day for pregnant and

lactating women, taking into account the role of LC n-3 PUFAs in visual and cognitive

developmentoftheinfants.16

Table 2: Recommendations of international and national authorities and scientificorganizationsforthen-3PUFAintakeofadults

Region Organization TargetPopulation RecommendationGlobal Foodand

AgricultureOrganizationoftheUnitedNations(FAO)14

Generaladultpopulation 0.5-0.6%ALAoftotaldietaryenergy250mgEPA+DHA/day

Pregnantandlactatingwomen

300mgEPA+DHA/day,ofwhich≥200mg/dayshouldbeDHA

7

InternationalSocietyfortheStudyofFattyAcidsandLipids(ISSFAL)17

Generaladultpopulation ≥500mgEPA+DHA/day

USA AcademyofNutritionandDietetics(AND)18

Generaladultpopulation 500mgEPA+DHA/day

AmericanHeartAssociation(AHA)19

Generaladultpopulation 500mgEPA+DHA/day

AmericanAcademyofPediatrics(AAP)20

Pregnantandlactatingwomen

200-300mgDHA/day

Canada DietitiansofCanada21

Generaladultpopulation 300-450mgEPA+DHA/day

Australia&NewZealand

DepartmentofHealth&Ageing,NationalHealth&MedicalResearchCouncil22

Generaladultpopulation Men:160mgEPA+DPA+DHA/dayWomen:90mgEPA+DPA+DHA/day

Europe EuropeanFoodSafetyAuthority(EFSA)13

Generaladultpopulation 0.5%ALAoftotaldietaryenergy250mgEPA+DHA/day

Pregnantandlactatingwomen

Additional100-200mgDHA/day

UnitedKingdom

ScientificAdvisoryCommitteeonNutrition(SACN)23

Generaladultpopulation 450mgEPA+DHA/day

Germany,Austria,Switzerland

GermanNutritionSociety,AustrianNutritionSocietyand

Generaladultpopulation 0.5%ALAoftotaldietaryenergy

Pregnantandlactatingwomen

≥200mgDHA/day

8

SwissSocietyforNutrition24

France FrenchAgencyforFood,EnvironmentalandOccupationalHealthandSafety(AFFSA)25

Generaladultpopulation 250mgDHA/day500mgEPA+DHA/day

Pregnantandlactatingwomen

250mgDHA/day500mgEPA+DHA/day

3 Effects of LC n-3 PUFAs on human health

There is growing evidence that EPA and DHA have positive effects on several health

outcomes. Especially the improvement of cardiovascular health is convincing (see below).

Most studies which explore the association between LC n-3 PUFAs and health outcomes

concentrate on secondary prevention (e. g. patients after a first cardiovascular event).

Primaryprevention trials in thegeneralpopulationarecurrently rare, raising thequestion

whetherhealthy individualswouldbenefit fromahigherLCn-3PUFA intake.Forexample,

vegetariansandespeciallyveganstendtohavelowbloodlevelsofEPAandDHA,duetothe

absence of LC n-3 PUFAs in plant foods.26However, vegetarians and vegans show a good

long term health with a reduced prevalence for obesity and hypertension27 (both are

establishedcardiovascularriskfactors),andalowerriskforischaemicheartdisease.28These

positiveoutcomescanbeexplainedtoagreatextentbythehealth-promotingfoodchoices

of vegetarians and vegans, e.g. higher consumption of vegetables, fruit and whole grain

products, and no consumption of red meat and meat products, but also by an overall

healthierlifestyle.Itisunclearifandtowhatextendvegetariansandvegansbenefitfroman

improvedLCn-3PUFAstatus,e. g. ina furtherdecreaseofCVD risk.29 TheongoingVITAL

(VITaminDandOmegA-3TriaL)trialaimstoinvestigatethepotentialeffectsofamarineLC

n-3PUFAsupplementationontheprimarypreventionofcancerandcardiovasculardisease

inamulti-ethnicpopulationof20.000men(>50yearsold)andwomen(>55yearsold) in

theUSA.30

9

3.1 Cardiovasculardiseases

The influence of LC n-3 PUFAs on health outcomes, especially CVD, has been extensively

studied.Thestorybeganinthe1970s,whenDanishresearchershadbeeninformedthatthe

GreenlandEskimoshada lowprevalenceof coronaryheartdiseases (CHD).Theirdietwas

richinsealblubberandfishandthereforeinLCn-3PUFAs,whichledtheresearcherstothe

suggestion that this so called “Eskimo diet” was a key factor in the alleged low CHD

incidence(meanwhile,the“Eskimodiettheory”hasbeendisproven:moststudiesconducted

duringthelast40yearsfoundthattheGreenlandEskimos,aswellasCanadianandAlaskan

Inuit,haveCHDasoftenasthenon-Eskimopopulations).31,32

Nevertheless,subsequentstudiesfoundthatEPAandDHAdecreaseelevatedTAGlevels33,

reducehypertension34andexertothercardioprotectivefunctions35,likereductionofplatelet

aggregation. In line with these findings, epidemiological studies reported an association

betweenhighintakesandbloodlevelsofLCn-3PUFAs,and(slightly)reducedcardiovascular

events.6,36However, in recent trials lowdose LCn-3PUFA supplementation in addition to

state-of-the-arttherapydidnotreducetherateofcardiovascularevents.37Thisissupported

by a recent systematic review of clinical trials which concluded that LC n-3 PUFA

supplementationdoesnotseemtoshowanybenefitforthetreatmentofCVDorassociated

complications.Nevertheless,italsostatedthatasupplementationof≥1gLCn-3PUFAsper

day (through supplements or marine products) reduces cardiovascular risk factors and

therefore can be recommended to improve cardiovascular health.38 Amost recentmeta-

analysis(10trials)foundnosupportfortherecommendationtouseapproximately1gLCn-

3 PUFAs per day in people with a history of CHD for the prevention of cardiovascular

events.39

3.2 Inflammatorydiseases

LC n-3 PUFAs influence inflammatory cells, for instance by changing the fatty acid

composition of their membranes and by altering the eicosanoid-pattern. The regulatory

potential of LC n-3 PUFAs with regard to inflammatory processes suggests that a

supplementation may be beneficial in inflammatory diseases, e. g. rheumatoid arthritis,

inflammatoryboweldisease,chronicobstructivepulmonarydisease,psoriasis,andasthma.40

Studies confirm this assumption for rheumatoid arthritis41, but are not consistent for

10

inflammatory bowel disease42 and asthma40. For themajority of inflammatory conditions

evidenceisnotsufficient.40BesidestheabsoluteamountofLCn-3PUFAintakethen-6:n-3

PUFA ratio seems important. An increased n-6:n-3 PUFA ratio was found to act pro-

inflammatoryandpro-thrombotic (by theprimary formationofn-6serieseicosanoids, like

prostaglandinE2andthromboxaneA2)and,therefore,promoteinflammatorydiseases.43

3.3 Neurologicaldevelopmentanddegeneration

PUFAsarecrucialforbrainfunctioning,includingbraindevelopmentandcognitivefunction.

DHA,whichmakesupabout40%ofbrainPUFAs,forexampleincreasesinthegreymatter

andretinaPLduringearlydevelopment.44,45SomestudiesreportthatDHAsupplementation

duringgestationleadstohighercognitiveoutcomesandvisualacuityininfantsandchildren,

whereasotherscouldnotfindadifferenceincomparisontoplacebocontrols.44Asystematic

review and meta-analysis concluded that cognitive outcomes had not been improved by

DHAinterventionsandthatthetopicwarrantsfurtherinvestigation.46Theresultsconcerning

neurodegenerative disorders, like Alzheimer’s disease and Parkinson’s disease, are also

inconclusive.Some,butnotall,studiesobservedlowerDHAconcentrationsinbrainand/or

livertissueofindividualswithAlzheimer’sdisease.47Sofar,interventiontrialswhichsupport

thehypothesisthatLCn-3PUFAsdelaytheprogressionofneurodegenerativediseasesare

lacking.

3.4 Other

Abeneficial roleofLCn-3PUFAs incancer47anddiabetes36prevention isbeingdiscussed,

butthereisnosufficientevidenceyet.

3.5 HealthclaimsforEPAandDHA

BasedonthescientificevidencetheEFSAhasapprovedseveralhealthclaimsforDHAand

EPAwhichallfocusonnormalphysiologicalfunctions:

• DHAandEPAcontributetothenormalfunctionoftheheart(0.25gperday)

• DHAandEPAcontributetothemaintenanceofnormalbloodpressure(3gperday)

11

• DHAandEPAcontributetothemaintenanceofnormalbloodtriglyceridelevels(2g

perday)

• DHAcontributes tomaintenanceofnormalblood triglyceride levels (2gperday in

combinationwithEPA)

• DHAcontributestomaintenanceofnormalbrainfunction(0.25gperday)

• DHAcontributestothemaintenanceofnormalvision(0.25gperday)

• DHAmaternalintakecontributestothenormalbraindevelopmentofthefoetusand

breastfed infants (0.2 g DHA plus the daily recommended intake of omega-3 fatty

acids(EPA+DHAforadultswhichis0.25gperday).

• DHAmaternalintakecontributestothenormaldevelopmentoftheeyeofthefoetus

andbreastfedinfants(0.2gDHAplusthedailyrecommendedintakeofomega-3fatty

acids(EPA+DHA)foradultswhichis0.25gperday).48

4 Sources of n-3 PUFAs: krill and plant-based alternatives

4.1 Krilloil

Trials investigating the association between LC n-3 PUFA intake and health outcomes are

typicallyconductedwithfishoilsupplementsoranincreasedintakeoffattyfish.Someofthe

supposedhealth-promotingeffectsofEPAandDHAhavealsobeentestedwithsupplements

derived from krill oil. As expected, the intake of krill oil supplements increased plasma

concentrations of EPA and DHA.49,50 A systematic review and meta-analysis on the lipid-

modifying effect of krill oil concluded that krill oil has a TAG and low-density lipoprotein

(LDL)loweringeffect,whileitelevateshigh-densitylipoprotein(HDL).51Thesemodifications

of blood lipids are known to be cardioprotective. Furthermore, one randomized, double-

blind, cross-over trial found improved endothelial function in individuals with type 2

diabetesmellitus after krill oil supplementation.52 In a randomized controlled trial krill oil

intakefor30daysimprovedmildkneepaininpatients.53Anotherrandomized,double-blind,

placebo controlled study indicates that krill oil intake (300mg/day) reduces inflammation

andarthriticsymptoms.54

12

4.2 Plant-basedLCn-3PUFAsources

TherisingrecognitionofLCn-3PUFAsasbeneficial tohumanhealthemphasizestheneed

for sustainable EPA and DHA sources, especially in consideration of the globally growing

population.Thereisanincreasingriskofexcessharvestingofnaturalmarinesourceslikeoily

fishesandkrill.Furthermore,conventionalsupplementsderivedfromfishoilorkrilloilare

notsuitableforthegrowingpopulationofvegetariansandvegans,forwhomLCn-3PUFAs

are considered critical nutrients.55 There are several alternative LC n-3 PUFA sources. The

two most prominent are: 1. single-cell oils extracted from several microalgae, and 2.

transgenic oilseeds and other plants (e. g. Camelina). Further options like EPA and DHA

producingtransgenicEscherichiacoliandtransgenicmicroalgaealsoarebeingexplored.56

4.2.1 Microalgaeoil

Asdiscussedearlier,severalmicroalgae, incontrasttoterrestrialplants,arecapableofde-

novosynthesisofLCn-3PUFAsandthereforearerichinEPAandDHA.Almostatthebottom

ofthemarinefoodchain,microalgaesupplythosefattyacidsformarineanimalslikefishand

krill. In photoautotrophic microalgae (e. g.Nannochloropsis oculata) EPA and DHA occur

partly in form of glycolipids (GL), which are bound to chloroplast membranes.57 Some

speciesproducehighamountsofEPAandonly littleDHA.Duetohighergrowthratesand

easier handling, heterotrophic microalgae (e. g. Schizochytrium sp.) are currently being

preferred as a source of EPA and DHA supplementation.56 They contain EPA and DHA

predominantly inTAGandPLform.Onerandomized,doubleblind,controlledtrialwith93

hypertriglyceridaemicparticipantsfoundthesameTAGloweringeffectsformicroalgaeoilas

forfishoil.58

CommerciallyavailableEPAand/orDHAcontainingoilsderivedfromcultivatedmicroalgae

contain10-95%EPAand/or20-45%DHA.59 Theseoilsusually areoffered in formofnon-

gelatinegelcapsules.Besides,thereareseveralplantoilsavailablethathavebeenfortified

withEPAand/orDHAofmicroalgalorigin,e.g.linseedoroliveoilwithEPA/DHA.60,61

13

4.2.2 Transgenicland-basedplantcrops

Amongotherplantscamelina(Camelinasativa)andcanola(BrassicanapusL.)areviewedas

potential hosts for the introduction of microalgal genes to facilitate LC n-3 PUFA

production.62In2014researchersproducedacamelinaoilwithupto24%EPAandasecond

versionwith11%EPAand8%DHA.63Table2showsexamplesofgeneticallymodifiedplant

oils.However,duetothe lowacceptanceofgeneticallymodifiedorganisms(GMOs) inthe

public, especially in Europe, these oils are intended to be used in aquacultures.62

Furthermore, risks regarding the long term usage of GMO for human nutrition are not

assessed.64Currently,theyarenotavailableforhumannutrition.

Table2:TransgenicplantswithEPA/DHAcontent2

Plant(company) EPA/DHA(g/100g)Oilseeds(CSIRO) 5.0gEPA

1.0gDHAMustard(BASF) 15.0gEPA

1.5gDHASoyabean(Dupont) 20.0gEPA

3.0gDHA

4.3 Comparisonofkrillwithmicroalgaeoil

4.3.1 Bioavailabilityofmicroalgaeoilversuskrilloil

Ingeneral,theFFAformofLCn-3PUFAsisconsideredtohavethehighestandtheethyl

ester(EE)formthelowestbioavailability,whilethePLandTAGformseemtohaveamedium

bioavailability.ThePLformappearstobebetterbioavailablethantheTAGform,but

conclusiveevidencefromhumanstudiesismissing.4Furthermore,thereisnodataavailable

torankfattyacidsinGLformintothisorder.Intheory,LCn-3PUFAsderivedfromkrilloilin

FFAandPLformmighthaveahigherbioavailabilitythanfromheterotrophicmicroalgaeoil

inTAGandPLform.BioavailabilityofLCn-3PUFAsfromphotoautotrophicmicroalgae

cannotbeestimatedbasedontheoreticalconsiderations.Studiestoconfirmthese

conclusionsarerare.

Sofar,onetrialcomparedthebioavailabilityofLCn-3PUFAs(1.5gEPA,noDHA)derived

fromthephotoautotrophicmicroalgaeNannochloropsisoculatawithLCn-3PUFAs(1.0g

14

EPA,0.5gDHA)derivedfromkrilloil.Afterconsumptionofasingledosetheincreaseof

plasmaconcentrationsofEPAwassignificantlyhigherwiththemicroalgaesupplement

comparedtothekrillsupplement.DHAplasmaconcentrationsalsoincreasedwithboth

supplements,buttherewasnodifferencebetweenthemicroalgaeandkrilloil.In

conclusion,theauthorssuggestabetterEPAbioavailabilityfromthealgaloilsupplement

comparedtothekrilloilsupplement,eventakinginaccountthedifferentEPA

concentrationsofthetwooils.Onepossibleexplanationforthehigherbioavailabilitymight

bethepresenceofGLinthemicroalgaeoil.65

NumerousstudiescomparedtheLCn-3PUFAbioavailabilityofkrilloilandfishoil.One

reviewsuggestsahigherbioavailabilityofEPAandDHAfromkrilloilthanfishoil,but

concludesthatfurtherstudiesareneededtoconfirmthisassumption.66Studiescomparing

krilloilandmicroalgaeoil,apartfromthementionedstudy,andmicroalgaeoilandfishoil

arenotavailable.

4.3.2 Safetyofmicroalgaeoilversuskrilloil

Persistentorganicpollutants,likeDDT(dichlorodiphenyltrichloroethane),chlordaneandPCB

(polychlorinatedbiphenyl),accumulatepreferablyinthemarineecosystemandareamajor

healthconcernforthepublic.Arecentreviewcomparedthetoxicologicalprofileofavailable

krilloilandfishoilsupplementsandrankedthekrilloilsupplementsintermediateregarding

the persistent organic pollutant content. Hexachlorocyclohexane, pentachlorobenzene,

hexachlorobenzeneandavarietyofPBCswerefoundinbothanalysedkrilloilproducts.DDT

occurred inoneproductandchlordanewasnot found in the twokrilloil supplements.All

analysedproductswere,attheirhighestrecommendeddosage,farbelowthetolerabledaily

intakeforallanalysedpollutants.67

Microalgaeareregardedasanon-pollutedresourceofLCn-3PUFAsupplementssincethey

areculturedundercontrolledconditions.56

15

5 Conclusion

AsevidenceofthebeneficialeffectsofLCn-3PUFAsonhumanhealthincreasesandseveral

international and national authorities and organizations recommend the dietary intake of

EPAandDHA,thedemandforLCn-3PUFAsupplementswillriseinthefuture.Inlightofthis

development,thesustainabilityofLCn-3PUFAsourcesshouldbetakenintoaccount.Froma

healthpointofview,fish,krillandmicroalgaeareconsideredtobesafesourcesofEPAand

DHAforhumannutrition.Currently,microalgaeseemtobetheonlysustainableandplant-

based alternative to fish and krill oil, since transgenic terrestrial plants raise ecological

questionsandarenotacceptedforhumannutritionbythepublic.

16

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