Omega-3 fedtsyrer (tang, krill og n-3/n-6 ratio) og sundhedseffekter

Omega-3 fedtsyrer (tang, krill og n-3/n-6 ratio) og sundhedseffekter Charlotte Jacobsen Professor mso Forskningsgruppen for bioaktive stoffer analyse og anvendelse Afdeling for Fødevareteknologi chja@food.dtu.dk

Dagsorden Intro til lipider Hvor kan vi få omega-3 fedtsyrer fra Anbefalet indtag og omega-6 vs omega-3 Sundhedseffekter af omega-3 fedtsyrer Konklusion 2 DTU Food, Technical University of Denmark

Important PUFA Omega-3, n-3, ω-3 - all cis ALA, C18:3 n-3 α-linolenic Acid EPA, C20:5 n-3 Eicosa-Pentanoic-Acid DHA, C22:6 n-3 Docosa-Hexanoic-Acid COOH essential COOH COOH Omega-6, n-6, ω-6 - all cis LA, C18:2 n-6 Linoleic Acid COOH essential ARA, C20:4 n-6 Arachidonic Acid COOH 3 DTU Food, Technical University of Denmark

Enzymatic pathway and synthesis of PUFA Omega-6 Omega-3 Linoleic acid, LA 18:2 n-6 18:3 n-3 α-linolenic acid, ALA Δ-6 desaturase γ-linolenic acid 18:3 n-6 18:4 n-3 GLA elongase 20:3 n-6 20:4 n-3 Δ-5 desaturase ARA 20:4 n-6 20:5 n-3 EPA elongase Δ-6 desaturase 4 DTU Food, Technical University of Denmark 22:4 n-6 22:5 n-3 24:5 n-3 DHA Δ-6 desaturase elongase 22:5 n-6 22:6 n-3 24:6 n-3

Lipid Classes 5 DTU Food, Technical University of Denmark

Introduktion til omega-3 fedtsyre kilder Verdens befolkning ventes at stige fra 7 mia i 2012 til 9.2 mia i 2050 Middelklassen vokser i lande med den kraftigste befolkningstilvækst (Indien og Kina) Stigende global efterspørgsel efter fisk Hvordan kan denne efterspørgsel efter fisk imødekommes? Voksende fokus på omega-3 fedtsyrernes sundhedseffekter Derfor stigende global efterspørgsel efter omega-3 olier Hvor skal omega-3 olierne komme fra er der nok? 6 DTU Food, Technical University of Denmark

Globalt fiskeri vs akvakultur-produktion 90 80 70 60 Millioner tons. Kun fisk Foto: Line Reeh 50 40 30 20 10 Foto:www.hvilested.dk/dambrugDK.htm Kilde: FAO 2012 0 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 2055 Capture Aquaculture 7 DTU Food, Technical University of Denmark

Hvad spiser opdrætsfisk? Foder til opdrætsfisk er traditionelt blevet fremstillet af fiskemel og fiskeolie Fiskeolien produceres fra industrifisk (f.eks. tobis), bifangster og biprodukter (afskær fra konsumfisk) Fangsten af industrifisk til fiskemel-og olieindustrien udgør 15-20 % af den samlede fiskefangst ~ 20 mio tons 8 DTU Food, Technical University of Denmark

Ændringer i afsætning af fiskeolie pga stigende efterspørgsel til akvakultur mm. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1990 1995 1998 2000 2005 2010 2015 Pharmaceutical Aquaculture Animal Feeds Industrial Hydrogenation Source: Bimbo 2007 9 DTU Food, Technical University of Denmark

Stigende konkurrence om fiskeolie Voksende akvakultur- og kosttilskudsmarked stigende efterspørgsel efter fiskeolie stigende priser Derfor erstattes noget af fiskeolien med planteolie i fiskefoder Hvad betyder det for omega-3 fedtsyre-indholdet i opdrætsfisk? 10 DTU Food, Technical University of Denmark

Hvor meget ørred skal man spise for at få omega-3 behovet dækket? Ugentligt omega-3 fedtsyre behov: ca. 3.5 g (ISSFAL) Fisk fodret med 100 % marin olie/protein i foder indeholder: 1,75 g omega-3/100 g fisk 200 g fisk/uge Fisk fodret med 60 % marin olie/protein i foder indeholder: 1,10 g omega-3/100 g fisk 318 g fisk/ uge Fisk fodret med 15 % marin olie/protein i foder indeholder: 0,55 g omega-3/100 g fisk 636 g fisk/uge Til sammenligning indeholder: Torsk 0,3-0,4 g omega-3/100 g fisk (ref. DTU Fødevareinstituttet) Sild 2-3 g omega-3/100 g fisk (Jensen et al. 2007) 11 DTU Food, Technical University of Denmark

Fiskeolie til kosttilskud og funktionelle fødevarer Markedet for omega-3 olier til kosttilskud og funktionelle fødevarer vokser med 10-15 % om året Fiskeolie til kosttilskud og funktionelle fødevarer raffineres og kan afsættes til en høj pris Nogle fiskeolier til kosttilskud opkoncentreres til f.eks. 60 % EPA og DHA (de 2 marine omega-3 fedtsyrer) Men hvilke fisk bruges til fiskeolieproduktionen, og kan der fanges flere af dem? 12 DTU Food, Technical University of Denmark

Markedsfordeling inkl. andre omega-3 olier Yeast Krill Algae Tuna Salmon Fish Livers Anchovy/Sardine 0,115 0,46 4,6 6,67 3,45 7,82 Source: Bimbo 2012 91,31 0 10 20 30 40 50 60 70 80 90 100 1000 METRIC TONS 13 DTU Food, Technical University of Denmark

Er der nok fiskeolie til at dække behovet for oparbejdet fiskeolie? Fangst af industrifisk er stagneret og produktionen af fiskeolie herfra ligeså I 2025 forventes, at behovet for rå fiskeolie til kosttilskud og fødevarer alene vil nå min. 450,000 tons Nej, der er ikke nok med den nuværende produktion og udnyttelsesgrad Hvad kan gøres? Foto: Line Reeh 14 DTU Food, Technical University of Denmark

Bedre udnyttelse af restprodukter Industrifisk udnyttes 100 % ved fiskeolieproduktion Konsumfisk udnyttes kun 50 %. Resten udgøres af: 14 % fiskehoved 14 % skelet 4 % skind 17 % indvolde Restprodukter udnyttes i nogle tilfælde Foto: Mie Weirum Engkebølle 42-44 million tons uudnyttet materiale som potentielt kan udnyttes til fiskeolieproduktion 15 DTU Food, Technical University of Denmark

Produktion af omega-3 fedtsyrer fra krill Krill er en underudnyttet ressource Krillolie indeholder ca. 25 % EPA og DHA Foto: Wikipedia Phospholipidfraktionen kan indeholde mere end 50 % EPA og DHA (phospholipider er membranlipider) Krill biomass estimeres til 400-600 million tons Ulemper: Fanges ved Antarktis, d.v.s. dyr og besværlig transport Kræves en del procesudvikling for at forbedre kvaliteten 16 DTU Food, Technical University of Denmark

Hvad er alger? Simpel plante Fleste lever i vand Photosyntese Bruger olie og fedt til at flyde i vand Stor variation fra små enkeltcellede organismer til komplekse flercellede arter som store tangplanter 17 DTU Food, Technical University of Denmark

18 DTU Food, Technical University of Denmark

Produktion of omega-3 fedtsyrer fra mikroalger Flere arter er i stand til at producere fedtsyrer med over 30 % EPA og DHA Foto: hielscher.com/da/algae_reactor_cleaning_01.htm Ulemper: Høje udviklings- og etableringsomkostninger Skal godkendes som novel food Der er en del patenter på området Foto: Allaboutalgae.com 19 DTU Food, Technical University of Denmark

Fatty acid composition in cultivations N.salina 45,00 40,00 35,00 30,00 %TFA 25,00 20,00 15,00 10,00 17/4 2015 23/4 2015 27/4 2015 5,00 0,00 14;0 15:00 16;0 16;1 (n-7)? 16;2(n-4) 16:3(n-4) 17;0 16:4(n-1) 18;0 18;1 (n-9) 18;1 (n-7) 18;2 (n-6) 18:2(n-4) 18;3(n-3) 18;4 (n-3) 20:00 20;1 (n-9) 20;1(n-7) 20;2 (n-6) 20;4 (n-6) 20:3 (n-6) 20:3(n-3) 20:4(n-3) 20;5 (n-3) 22:1(n-11) 21:5(n-3 22;5 (n-3) 22;6 (n-3) 24;1 (n-9) Fatty acid 07-09-2015 DTU Food, Technical University of Denmark DTU-Food 20

21 DTU Food, Technical University of Denmark

Omega-3 fedtsyrer fra tang Tang har et lavt lipidindhold (max 5 %) Men fedtsyresammensætningen er god højt indhold af omega-3 fedtsyrer Tang kan tilsættes til fiskefoder Ekstraktion af fedtfraktionen er også en mulighed Foto: Farvin & Holdt Ulempe: Kræver en del udvikling Dyrt 22 DTU Food, Technical University of Denmark

EPA og DHA fra genmodificerede planter Stor aktivitet på dette område Bl.a. arbejdes der på at genmodificere flg. planter: Rapsfrø Bomuldsfrø Sennepsfrø Sojabønne Tidsel Foto:da.wikipedia.rorg De første olier forventes på markedet inden for 5-7 år Ulemper: Store udviklingsomkostninger svær teknologi Forbrugerskepsis (specielt i Europa) Godkendelsesprocedure 23 DTU Food, Technical University of Denmark

Hvorfor er fiskeolie sundt? Fiskeolie indeholder 2 langkædede omega-3 fedtsyrer, EPA og DHA, som ikke findes i planter EPA DHA Vigtige biologiske funktioner i cellemembranerne og i vores immunsystem Vigtig rolle for vores hjertesundhed og for vores mentale sundhed 24 DTU Food, Technical University of Denmark

Anbefalede mængder og ratioer? Total mængde (eksempler på anbefalinger): ISSFAL: ca. 500 mg EPA + DHA pr dag EFSA: 250 mg EPA + DHA pr dag Men det optimale indtag af EPA og DHA afhænger sandsynligvis af baggrundskosten: Hvis højt indhold af omega-6 fedtsyrer i maden kræves højere indtag af omega-3 Beregninger på USA kost foreslår: ca. 2 g EPA og DHA/dag Ca. 0.8 g/dag krævet i DK Ratio mellem omega-6 og omega-3: De fleste anbefalinger siger 4-5:1 25 DTU Food, Technical University of Denmark

Suggested effects of LC omega-3 PUFA Disease Disease burden potentially modifiable by n-3 HUFAs Percent vulnerable population protected from illness (%) Model advice for n-3 HUFA intake 0.22 en% (500 mg/d) Heart disease 41.8 % 87.6 mortality M+F All cause mortality M 20.8 % 97.7 All cause mortality F 31.5 % 87.3 Homicide mortality 28.4 % >99.9 Postpartum 65.5 % 91.3 depression Major depression 98.5 % 83.2 Bipolar disorder 99.9 % 92.3 Hibbeln et al. Am J Clin Nutri 2006, 83, 1483S-93S 26 DTU Food, Technical University of Denmark

Consequences of low intake of LC omega-3 PUFA EPA DHA Deaths in USA due to low intake of fruits and vegetables: 58.000/year Heart deaths in USA due to low intake of EPA and DHA: 84.000/year Costs of low omega-3 intake: 10.000 Euro/employee/year Danaei et al. PLOS Med, 2010, 6(4):e1000058 27 DTU Food, Technical University of Denmark

Cardiovascular diseases Strong evidence that they are of benefit for cardiovascular disease outcomes Evidence is stronger in secondary than primary prevention not many studies on primary prevention Randomised control trials indicate that for secondary prevention < 1 g/day LC omega-3 PUFA is protective 28 DTU Food, Technical University of Denmark

29 DTU Food, Technical University of Denmark Dias fra Lotte Lauritzen, KU-LIFE

Cardiovascular diseases Results from Gissi study 11,324 patients with myocardial infarction (heart attack) +/- 885 mg EPA + DHA/day and/or vitamin E 3.5 years follow up EPA + DHA significantly lowered by 15 % risk of combined primary and secondary outcome of death and non-fatal cardiovascular events Mainly due to decreased mortality (20 % reduction in total deaths, 30 % in cardiovascular dealths and 45 % in sudden deaths) 30 DTU Food, Technical University of Denmark

Risk markers for cardiovascular diseases Strong evidence that omega-3 PUFA lower triglyceride levels in the blood EFSA: effect when > 2 g/day are consumed. Health claims allowed with the following wording: 1. DHA contributes to the maintenance of normal blood triglyceride levels. 2. DHA and EPA contribute to the maintenance of normal blood triglyceride concentrations. In both cases foods should provide an intake of DHA or EPA plus DHA above 2 g/day. Warning that intake should not exceed maximum 5 g/day 31 DTU Food, Technical University of Denmark

Risk markers for cardiovascular diseases EPA and DHA has been shown to lower blood pressure (1-2 mm Hg) EFSA: has recognized this Health claim allowed: EPA and DHA contribute to the maintenance of normal blood pressure. Daily intake of 3 g DHA-EPA required. Same warning about the 5g limit as for triglyceride levels. 32 DTU Food, Technical University of Denmark

Omega-3 index The red blood cell (RBC) fatty acid composition has been found to reflect the cardiac omega-3 content Omega-3 index is a risk marker for coronary heart diseases Block et al. Atherosclerosis 197 (2008), 821-828 33 DTU Food, Technical University of Denmark

Mechanism of action Many actions require incorporation of EPA and DHA into cell membrane In the membrane they can influence: Physical properties of membrane The assembly of signalling platforms (lipid rafts) Intracellular signalling cascades leading to gene expression Formation of various lipid mediators incl. prostaglandins, leukotrienes, resolvins and endocannabinoids 34 DTU Food, Technical University of Denmark

Mechanism of action Actions are slow but longlasting and underlie effects on: Lowering blood TAG Decreased blood pressure Reduced heart rate and increased heart rate variability Decreased platelet aggregation 35 DTU Food, Technical University of Denmark

Eicosanoid production from PUFA Omega-6 Omega-3 Linoleic acid, LA 18:2 n-6 18:3 n-3 α-linolenic acid, ALA Proinflammatory prostaglandins, tromboxaner Proinflammatoriske leucotrins ARA 20:4 n-6 20:5 n-3 EPA ANTIinflammatory prostaglandins tromboxanes ANTIinflammatory Leucotrins Structural lipids 22:6 n-3 DHA 36 DTU Food, Technical University of Denmark

Mechanisms continued 1.4 g EPA + DHA/day reduced the inflammatory burden in advanced athereosclerotic plaques greater stability of them Antiinflammatory effect in advanced plaques may be key action of marine omega-3 in reducing CV events and mortality. 885 mg EPA/DHA in patients with CHD: Increased fibrin clot permeability (larger pores in fibrin network) Decreased clot lysis time (= increased susceptibility to fibrinolysis) Decreased thrombin concentration and generation Decreased platelet reactivity All the above will result in in reduced risk of thrombosis 37 DTU Food, Technical University of Denmark

Other effects of omega-3 fatty acids Alleviates symptoms from rheumatoid arthritis Less well documented: Reduce pre-term birth Reduces weight loss and improves health in cancer patients Normalising immune response 38 DTU Food, Technical University of Denmark

Dias fra Lotte Lauritzen, KU-LIFE 39 DTU Food, Technical University of Denmark

Other effects of omega-3 fatty acids Not documented (as evaluated by EFSA panel): DHA suggested to protect blood lipids from oxidation (LDL cholesterol oxidation), but cause and effect relationship not established DHA suggested to contribute to weight management, but cause and effect relationship not established 40 DTU Food, Technical University of Denmark

Brain function Some indications that they improve the clinical outcome of early-stage schizophrenia Studies have also suggested a role in Alzheimers, depressions Well established role of DHA in brain function and a cause and effect relationship has been established (EFSA panel: Foods should contain 250 mg DHA in one or more servings to bear the claim) 41 DTU Food, Technical University of Denmark

Mechanisms of action brain function DHA major structural lipid in brain tissue and central nervous system Brain DHA predominantly found in PE and PS with saturated long chain fatty acids in the sn-1 position. This assymetri may be an underlying mechanism for proper interaction of the cell with its environment and is essential asset of biological membrane DHA provides fluidity and flexibility to the membrane may be important for signal transduction Deficiency of ALA results in neurological abnormalities, poor growth and decrease in plasma and tissue DHA concentrations 42 DTU Food, Technical University of Denmark

Mechanisms of action brain function Adequate Levels of ALA in maternal rat feed Deprivation of ALA from maternal diet during pregnancy and lactation disrupted cell migration in neonatal brain Too low levels of ALA in maternal rat feed Brand et al. (2010) J Neurochemistry, 114, 1393-1404 43 DTU Food, Technical University of Denmark

Omega-3 and Vitamin D Vitamin D and omega-3 could work together to improve cognitive function and social behaviour with particular relevance for battling ADHD, schizophrenia and bipolar disorder Synergy in maintaining healthy levels of serotonin in the brain http://www.nutraingredients.com/research/vitamin-d-and-omega-3- together-may-help-mental-illness 44 DTU Food, Technical University of Denmark

Vision Good evidence that they improve the visual development in preterm infants (born <wk 37) Well established role of DHA in maintaining normal vision and a cause and effect relationship has been established (EFSA panel: Foods should contain 250 mg DHA in one or more servings to bear the claim) DHA major structural lipid in retina and plays a role for its function 45 DTU Food, Technical University of Denmark

Omega-3 and schizophrenia (August 2015) 81 teenagers and young adults who were at high risk of developing fullblown psychosis within a year: had some of the earliest symptoms of schizophrenia (hearing voices or hallucinating, delusions that someone was trying to harm) About 30 percent of adolescents and young adults with such symptoms will go onto develop clinical schizophrenia or psychosis Half of the group took an omega-3-rich fish oil supplement for 12 weeks, the other half took placebo The team followed the study participants for seven years. 10 percent of the patients who took the fish oil supplement developed schizophrenia 40 percent of the patients in the control group developed schizophrenia 46 DTU Food, Technical University of Denmark

Konklusioner Nye kilder til omega-3 fedtsyrer er nødvendige for at kunne forsyne verdens befolkning fremover Omega-3 fedtsyrer har veldokumenterede effekter på hjertekarsygdomme, leddegigt og hjernefunktion Omega-3 fedtsyrernes rolle i forhold til at forebygge schizofreni, depressioner, demens og alzheimers er stadig ikke fuldt afklaret Nyere forskning tyder også på en vigtig rolle i forhold til mavetarmsystemet 47 DTU Food, Technical University of Denmark