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Cited by 214Algal biology and biofuel productionFatty Acid Research and HealthAquaculture Nutrition and Growth

Microalgae n-3 PUFAs Production and Use in Food and Feed Industries

Open access
Remize, Marine, Brunel, Yves, Silva, Joana L., Berthon, Jean-Yves, Filaire, Edith·2021·Marine Drugs
DOI 10.3390/md19020113PMC PMC7922858
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Abstract

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes the health benefits, supply challenges, biosynthesis, and food/feed applications of microalgae-derived n-3 PUFAs, especially EPA and DHA. It argues that microalgae are a promising sustainable alternative to fish-derived n-3 PUFAs, but that synthesis pathways and regulatory/commercial constraints still need further work.

Key findings

  • Global consensus recommends 250–500 mg EPA+DHA per day; France recommends 500 mg/day (250 mg each), while fisheries are plateauing at about 90 million tons per annum and 33.1% of stocks were overfished in 2018.
  • Microalgae lipid content ranges from 1–40% depending on species and growth conditions; DHA can reach up to 40% of total fatty acids in some dinophytes, 30% in haptophytes, and around 60% of total fatty acids as triacylglycerides in *Aurantiochytrium* and *Schizochytrium*.
  • EPA production examples include diatoms at around 20% EPA, *Nannochloropsis oculata* at 15–30% EPA, and *Chlorella minutissima* at 31% EPA under photoautotrophic conditions or 45% w/w at low temperatures.
  • Microalgae biomass is predominantly used in the health food market, representing 75% of annual microalgal biomass production; aquaculture contributed 46% of world fish production in 2016–2018 versus 26% in 2000.

Methods

  • Narrative review synthesizing current knowledge on n-3 PUFA health effects, supply and demand, microalgal production, biosynthetic pathways, and food/feed industry uses.
  • No primary experimental data, sample, or statistical analysis are reported; evidence is drawn from cited literature, commercial examples, and prior studies.
  • Discusses conventional FAS, n-3/n-6 elongation-desaturation, and polyketide synthase pathways, including use of 14C- and 13C-labelling approaches for pathway elucidation.

Limitations

  • The paper states that microalgal EPA and DHA synthesis pathways remain under investigation and that more knowledge is needed to improve production sustainably.
  • It notes that clinical benefits of EPA/DHA in COVID-19 are anecdotal and need rigorous clinical trials, and that authorization proving safety limits the number of microalgae species used in food and feed.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy, inclusion criteria, or quantitative synthesis, and it draws on heterogeneous studies with varying designs and outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/md19020113

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 265 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Dietary intakes of n-3 PUFAs, particularly EPA and DHA, reduce the risk of developing cardiovascular problems.

    “Dietary intakes of n-3 PUFAs, particularly eicosapentaenoic acid (EPA—20:5n-3) and docosahexaenoic acid (DHA—22:6n-3) have long been known to reduce the risk of developing cardiovascular problems [19,20].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Rimm E.B. Appel L.J. Chiuve S.E. Djoussé L. Engler M.B. Kris-Etherton P.M. Mozaffarian D. Siscovick D.S. Lichtenstein A.H. A Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association Circulation 2018 138 e35 e47 10.1161/CIR.0000000000000574 29773586 PMC6903778 source

      Not checked in the free run.

    • cites [20] Colussi G. Catena C. Novello M. Bertin N. Sechi L.A. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes Nutr. Metab. Cardiovasc. Dis. 2017 27 191 200 10.1016/j.numecd.2016.07.011 27692558 source

      Not checked in the free run.

  • Premisecitation

    EPA and DHA come mainly from marine sources like fish or seaweed.

    “EPA and DHA come mainly from marine sources like fish or seaweed.”
    • Also stated in: § 3. Increasing Demand for n-3 Polyunsaturated Fatty Acids · plain
      “Supply of n-3 PUFA comes mainly from the ocean and the vast majority (almost 90%) from capture fisheries [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Tocher D.R. Betancor M.B. Sprague M. Olsen R.E. Napier J.A. Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand Nutrients 2019 11 89 10.3390/nu11010089 PMC6356973 30621155 source

      Not checked in the free run.

  • Interpretationreasoning

    Aquaculture appears insufficient to meet the increasing requirements of EPA and DHA for humans.

    “Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans.”
    • Also stated in: § 3. Increasing Demand for n-3 Polyunsaturated Fatty Acids · hedged
      “In the longer term, aquaculture thus appears not to be economically sustainable, especially since climate change already impacts the natural production of these oils.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Microalgae levels of compounds of interest are similar or even higher than in plants and animals.

    “The levels of these compounds of interest in microalgae are similar or even higher than they are in plants and animals [5,6].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Chacón-Lee T. González-Mariño G. Microalgae for “Healthy” Foods-Possibilities and Challenges Compr. Rev. Food Sci. Food Saf. 2010 9 655 675 10.1111/j.1541-4337.2010.00132.x 33467820 source

      Not checked in the free run.

    • cites [6] Barka A. Blecker C. Microalgae as a Potential Source of Single-Cell Proteins. A Review Biotechnol. Agron. Société Environ. 2016 10 10.25518/1780-4507.13132 source

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  • Premisecitation

    Microalgae chemical composition varies widely between species and culture conditions.

    “Microalgae chemical composition has been widely studied in the literature, with proportions varying widely between the different species and culture conditions used [1,12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Patras D. Moraru C.V. Socaciu C. Bioactive Ingredients from Microalgae: Food and Feed Applications BUASVMCN-FST 2019 76 1 9 10.15835/buasvmcn-fst:2018.0018 source

      Not checked in the free run.

    • cites [12] Bernaerts T.M. Gheysen L. Foubert I. Hendrickx M.E. Van Loey A.M. The potential of microalgae and their biopolymers as structuring ingredients in food: A review Biotechnol. Adv. 2019 37 107419 10.1016/j.biotechadv.2019.107419 31340183 source

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  • May combine two claims. 73
  • Classified as probably not a substantial claim. 42

  • May combine two claims.

    Premisecitation

    EPA and DHA have proven positive effects on a panel of diseases and anti-oxidative, anti-inflammatory or anti-cancer properties.

    “They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties.”
    • Also stated in: § 2. Polyunsaturated Fatty Acids and Human Health · boosted
      “Both fatty acids are known for their therapeutic properties with regard to cardiovascular diseases, hypertension, and autoimmune disorders [14,16].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Hamed I. Özogul F. Özogul Y. Regenstein J.M. Marine Bioactive Compounds and Their Health Benefits: A Review Compr. Rev. Food Sci. Food Saf. 2015 14 446 465 10.1111/1541-4337.12136 source

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    • cites [16] Dyall S.C. Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA Front. Aging Neurosci. 2015 7 52 10.3389/fnagi.2015.00052 25954194 PMC4404917 source

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  • May combine two claims.

    Premisecitation

    Humans do not possess the enzymes to produce EPA and DHA and are unable to produce them in sufficient quantities.

    “However, unlike these organisms, humans do not possess these enzymes and are unable to produce EPA and DHA in sufficient quantities [15].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Li D. Wahlqvist M.L. Sinclair A.J. Advances in n-3 polyunsaturated fatty acid nutrition Asia Pac. J. Clin. Nutr. 2019 28 1 5 30896407

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Microalgae have a very efficient photosynthetic system and continuous access to water, CO2, and nutrients, allowing effective conversion of energy to biomass.

    “Indeed, thanks to their aqueous environment and submerged nature, microalgae have continuous access to water, CO2, and nutrients that allow them to be very effective in converting energy to biomass [3,5].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Pinckney J.L. A Mini-Review of the Contribution of Benthic Microalgae to the Ecology of the Continental Shelf in the South Atlantic Bight Chesap. Sci. 2018 41 2070 2078 10.1007/s12237-018-0401-z

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    • cites [5] Chacón-Lee T. González-Mariño G. Microalgae for “Healthy” Foods-Possibilities and Challenges Compr. Rev. Food Sci. Food Saf. 2010 9 655 675 10.1111/j.1541-4337.2010.00132.x 33467820 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Early trials attested beneficial cardiovascular outcomes, but recent works are nuanced.

    “Indeed, while early trials attested to beneficial cardiovascular outcomes, recent works are nuanced [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Casula M. Olmastroni E. Gazzotti M. Galimberti F. Zambon A. Catapano A.L. Omega-3 polyunsaturated fatty acids supplementation and cardiovascular outcomes: Do formulation, dosage, and baseline cardiovascular risk matter? An updated meta-analysis of randomized controlled trials Pharmacol. Res. 2020 160 105060 10.1016/j.phrs.2020.105060 32634581 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Due to global warming, EPA and DHA are becoming scarce for humans because of overfishing and stock reduction.

    “Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction.”
    • Also stated in: § 3. Increasing Demand for n-3 Polyunsaturated Fatty Acids · plain
      “Global fisheries have reached a plateau following stock reduction (90 million tons per annum) [40,69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [40] Tocher D.R. Betancor M.B. Sprague M. Olsen R.E. Napier J.A. Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand Nutrients 2019 11 89 10.3390/nu11010089 PMC6356973 30621155 source

      Not checked in the free run.

    • cites [69] FAO Meeting the Sustainable Development Goals The State of World Fisheries and Aquaculture; FAO Rome, Italy 2018 978-92-5-130562-1

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only a few microalgae species are commercially produced due to strict food safety regulations and because industrial cultivation is only a few decades old.

    “Among the critical number of species known to date, only a few are commercially produced due to strict food safety regulations, namely in Europe, and because their cultivation in industrial quantities is only a few decades old [10,11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Gouveia L. Batista A.P. Sousa I. Raymundo A. Bandarra N. Microalgae in novel food products Food Chemistry Research Developments Papadopoulos K.N. Nova Science Publishers Hauppauge, NY, USA 2008 2 37 978-1-60456-262-0

      Not checked in the free run.

    • cites [11] Nova P. Martins A.P. Teixeira C. Abreu H. Silva J.G. Silva A.M. Freitas A.C. Gomes A.M. Foods with microalgae and seaweeds fostering consumers health: A review on scientific and market innovations Environ. Boil. Fishes 2020 32 1789 1802 10.1007/s10811-020-02129-w

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microalgae lipids can represent up to 74% of microalgae's total biochemical content according to species.

    “Indeed, they can represent up to 74% of microalgae’s total biochemical content according to species [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Bernaerts T.M. Gheysen L. Foubert I. Hendrickx M.E. Van Loey A.M. The potential of microalgae and their biopolymers as structuring ingredients in food: A review Biotechnol. Adv. 2019 37 107419 10.1016/j.biotechadv.2019.107419 31340183 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    N-3 PUFAs are characterized by health benefits for both animals and humans.

    “N-3 PUFAs, also called omega-3 fatty acids, are characterized by their health benefits for both animals and humans.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Increasing the ratio of n-3 to n-6 PUFAs decreases inflammation, as omega-6 is a precursor of pro-inflammatory molecules while eicosanoids from omega-3 have antagonist properties.

    “Increasing the ratio of n-3 to n-6 PUFAs decreases inflammation, as omega-6 is a precursor of pro-inflammatory molecules while eicosanoids issued from omega-3 have antagonist properties [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Hamed I. Özogul F. Özogul Y. Regenstein J.M. Marine Bioactive Compounds and Their Health Benefits: A Review Compr. Rev. Food Sci. Food Saf. 2015 14 446 465 10.1111/1541-4337.12136 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Available data support positive impact of dietary n-3 PUFAs on blood pressure and congestive heart failure, and supplementation >1 g/day seems effective in lowering risk of fatal cardiac events.

    “Generally, the available data seem to support the positive impact of dietary n-3 PUFAs on blood pressure [20], congestive heart failure [25], and supplementation of more than one g/day−1 of n-3 PUFAs seem effective in lowering the risk of fatal cardiac events [21].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [20] Colussi G. Catena C. Novello M. Bertin N. Sechi L.A. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes Nutr. Metab. Cardiovasc. Dis. 2017 27 191 200 10.1016/j.numecd.2016.07.011 27692558 source

      Not checked in the free run.

    • cites [25] Sakamoto A. Saotome M. Iguchi K. Maekawa Y. Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Heart Failure: Current Understanding for Basic to Clinical Relevance Int. J. Mol. Sci. 2019 20 4025 10.3390/ijms20164025 PMC6719114 31426560 source

      Not checked in the free run.

    • cites [21] Casula M. Olmastroni E. Gazzotti M. Galimberti F. Zambon A. Catapano A.L. Omega-3 polyunsaturated fatty acids supplementation and cardiovascular outcomes: Do formulation, dosage, and baseline cardiovascular risk matter? An updated meta-analysis of randomized controlled trials Pharmacol. Res. 2020 160 105060 10.1016/j.phrs.2020.105060 32634581 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DHA, as a component of photoreceptor cells, is indispensable for vision.

    “DHA, as a component of photoreceptor cells, is also indispensable for vision [44].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Garg P. Pejaver R.K. Sukhija M. Ahuja A. Role of DHA, ARA, & phospholipids in brain development: An Indian perspective Clin. Epidemiol. Glob. Heal. 2017 5 155 162 10.1016/j.cegh.2017.09.003 source

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  • May combine two claims.

    Premisecitation

    EPA and DHA prescription for Type 2 diabetes mellitus significantly reduces triglyceride levels, thereby reducing risk of hypertriglyceridemia.

    “EPA and DHA prescription for Type 2 diabetes mellitus significantly reduces the levels of triglyceride known to be responsible for fat accumulation, thereby reducing the risk of developing hypertriglyceridemia [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Avallone L. Shaikh A. Hassan A. Tajuddin N. Prescription omega-3 fatty acid products: Considerations for patients with diabetes mellitus Diabetes Metab. Syndr. Obesity Targets Ther. 2016 9 109 118 10.2147/DMSO.S97036 PMC4846047 27143943 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Gut microbiota composition is influenced by phenotype, age, gender, exercise frequency, dietary habits, antibiotics, drugs, probiotics, immune function, geographical location, environment, and host-specific factors in humans.

    “The composition of gut microbiota is influenced by phenotype, age, gender, exercise frequency, dietary habits, the use of antibiotics, drugs, probiotics, immune function, geographical location, environment, and host-specific in humans [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Rinninella E. Raoul P. Cintoni M. Franceschi F. Miggiano G.A.D. Gasbarrini A. Mele M.C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases Microorganism 2019 7 14 10.3390/microorganisms7010014 30634578 PMC6351938 source

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  • May combine two claims.

    Premisecitation

    EPA and DHA can improve drug delivery by modifying tumor vasculature with architectural remodeling and present antiangiogenic activities.

    “Indeed, EPA and DHA can improve drug delivery by modifying the tumor vasculature with architectural remodeling [57], and present antiangiogenic activities [58,59].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [57] Goupille C. Vibet S. Frank P.G. Mahéo K. EPA and DHA Fatty Acids Induce a Remodeling of Tumor Vasculature and Potentiate Docetaxel Activity Int. J. Mol. Sci. 2020 21 4965 10.3390/ijms21144965 PMC7404030 32674321 source

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    • cites [58] Elmasry K. Ibrahim A.S. Abdulmoneim S. Al-Shabrawey M. Bioactive lipids and pathological retinal angiogenesis Br. J. Pharmacol. 2019 176 93 109 10.1111/bph.14507 30276789 PMC6284336 source

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    • cites [59] Ma Y. Wang J. Li Q. Cao B. The Effect of Omega-3 Polyunsaturated Fatty Acid Supplementations on anti-Tumor Drugs in Triple Negative Breast Cancer Nutr. Cancer 2020 1 10 10.1080/01635581.2020.1743873 32223441 source

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  • May combine two claims.

    Premisecitation

    In animal models, omega-3 supplementation improved hepatic insulin sensitivity, production of adipocytokines, and direct and indirect anti-inflammatory effects.

    “In animal models, omega-3 supplementation improved hepatic insulin sensitivity, the production of adipocytokines and direct and indirect anti-inflammatory effects [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Itsiopoulos C. Marx W. Mayr H. Tatucu-Babet O. Dash S. George E. Trakman G. Kelly J. Thomas C. Brazionis L. The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review J. Nutr. Intermed. Metab. 2018 14 42 51 10.1016/j.jnim.2018.02.002 source

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    Premisecitation

    Arachidonic acid is involved in brain functioning and eases neuronal transmission and long-term potentiation.

    “Arachidonic acid (ARA—20:4n-6) is also involved in brain functioning and eases neuronal transmission and long-term potentiation [44].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Garg P. Pejaver R.K. Sukhija M. Ahuja A. Role of DHA, ARA, & phospholipids in brain development: An Indian perspective Clin. Epidemiol. Glob. Heal. 2017 5 155 162 10.1016/j.cegh.2017.09.003 source

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  • May combine two claims.

    Premisecitation

    EPA is a precursor of eicosanoids and can limit inflammatory developments related to chronic diseases.

    “EPA, 20:5n-3, is a precursor of eicosanoids and can limit inflammatory developments related to chronic diseases [16,30].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Dyall S.C. Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA Front. Aging Neurosci. 2015 7 52 10.3389/fnagi.2015.00052 25954194 PMC4404917 source

      Not checked in the free run.

    • cites [30] Calder P.C. n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases Am. J. Clin. Nutr. 2006 83 1505S 1519S 10.1093/ajcn/83.6.1505S 16841861 source

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    Premisecitation

    Cytokine storm is a very common manifestation in severe COVID-19 patients and often leads to exacerbation; anti-inflammation therapy may help prevent further injury.

    “As cytokine storm is a very common manifestation in severe patients and often leads to exacerbation, intervention with anti-inflammation therapy may help in preventing further injury [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Chang J.P.-C. Pariante C.M. Su K.-P. Omega-3 fatty acids in the psychological and physiological resilience against COVID-Prostaglandins Leukot Essent. Fat. Acids 2020 161 102177 10.1016/j.plefa.2020.102177 33031994 PMC7516470 source

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  • May combine two claims.

    Premisecitation

    Rodent and human models show that DHA supplementation could have a beneficial impact on brain functions including learning and memory, depressive and aggressive behaviors, audition, and olfaction.

    “Rodent and human models show that DHA supplementation could not only have a beneficial impact on brain functions, including learning and memory [46,47], depressive and aggressive behaviors [45,48] but also on audition [49,50], and olfaction [51,52].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [46] Sugasini D. Thomas R. Yalagala P.C.R. Tai L.M. Subbaiah P.V. Dietary Docosahexaenoic Acid (DHA) as Lysophospha-tidylcholine, but Not as Free Acid, Enriches Brain DHA and Improves Memory in Adult Mice Sci. Rep. 2017 7 1 11 10.1038/s41598-017-11766-0 28900242 PMC5596017 source

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    • cites [47] Liu J.-H. Wang Q. You Q.-L. Li Z.-L. Hu N.-Y. Wang Y. Jin Z.-L. Li S.-J. Li X.-W. Yang J.-M. Acute EPA-induced learning and memory impairment in mice is prevented by DHA Nat. Commun. 2020 11 1 15 10.1038/s41467-020-19255-1 33122660 PMC7596714

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    • cites [45] DiNicolantonio J.J. O’Keefe J.H. The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders Nutrients 2020 12 2333 10.3390/nu12082333 32759851 PMC7468918 source

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    • cites [49] Unay B. Sarıcı S.Ü. Ulaş Ü.H. Akın R. Alpay F. Gökçay E. Nutritional effects on auditory brainstem maturation in healthy term infants Arch. Dis. Child. Fetal Neonatal Ed. 2004 89 F177 F179 10.1136/adc.2002.021014 14977907 PMC1756035 source

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  • May combine two claims.

    Premisecitation

    N-3 PUFAs participate in synapse formation, neuronal proliferation, differentiation, and extension of nerve fibers.

    “N-3 PUFAs also participate in synapse formation, neuronal proliferation, and differentiation and extension of nerve fibers [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Zhang T.-T. Xu J. Wang Y.-M. Xue C.-H. Health benefits of dietary marine DHA/EPA-enriched glycerophospholipids Prog. Lipid Res. 2019 75 100997 10.1016/j.plipres.2019.100997 31442526 source

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  • May combine two claims.

    Premisecitation

    EPA and DHA used individually at 5 g/day seemed to diminish infarct size, while a combination at 5 g/kg did not.

    “EPA and DHA used individually (5 g × day−1) seemed to diminish infarct size, while a combination of both to a level of 5 g × kg−1 did not [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Madingou N. Gilbert K. Tomaro L. Touchette C.P. Trudeau F. Fortin S. Rousseau G. Comparison of the effects of EPA and DHA alone or in combination in a murine model of myocardial infarction Prostaglandins Leukot. Essent. Fat. Acids 2016 111 11 16 10.1016/j.plefa.2016.06.001 27499449 source

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    Premisecitation

    Dysbiosis might be responsible for metabolic or neurologic disease development.

    “Any alteration of the gut microbiota or imbalance between microbial communities, called dysbiosis, might be responsible for metabolic or neurologic disease development [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Rinninella E. Raoul P. Cintoni M. Franceschi F. Miggiano G.A.D. Gasbarrini A. Mele M.C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases Microorganism 2019 7 14 10.3390/microorganisms7010014 30634578 PMC6351938 source

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    Premisecitation

    EPA and DHA induce apoptosis, block the cell cycle resulting in stopping tumor development, and participate in lipid peroxidation-mediated endoplasmic-reticulum-stress which triggers deterioration of cancer cells.

    “They also induce apoptosis [60,61], block the cell cycle resulting in stopping tumor development [53], and participate in lipid peroxidation-mediated endoplasmic-reticulum-stress which triggers deterioration of cancer cells [62].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [60] Chen H. Sun S. Li J. Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells HPB 2016 18 e166 10.1016/j.hpb.2016.02.395 PMC3544235 23330014

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    • cites [61] Xue M. Ge Y. Yu C. Zheng Z. He X. Zhao J. Apoptosis is induced by docosahexaenoic acid in breast cancer cells via death receptor and mitochondria-mediated pathways Mol. Med. Rep. 2017 16 978 982 10.3892/mmr.2017.6678 28586001 source

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    • cites [53] Zhang T.-T. Xu J. Wang Y.-M. Xue C.-H. Health benefits of dietary marine DHA/EPA-enriched glycerophospholipids Prog. Lipid Res. 2019 75 100997 10.1016/j.plipres.2019.100997 31442526 source

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    • cites [62] Zhang J. Yang Y. Wang F. Yang W. Zou Z. MAG-DHA Induces Apoptosis and Autophagy in Breast Cancer Cells via Lipid Peroxidation-Mediated Endoplasmic Reticulum Stress Preprint 2020 10.21203/rs.3.rs-35529/v1 34494660 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The intestinal microbiota is involved in immune response and prevention of pathogenic invasions.

    “The intestinal microbiota is involved in immune response and prevention of pathogenic invasions [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Fung T.C. Olson C.A. Hsiao E.Y. Interactions between the microbiota, immune and nervous systems in health and disease Nat. Neurosci. 2017 20 145 155 10.1038/nn.4476 28092661 PMC6960010 source

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  • May combine two claims.

    Premisecitation

    EPA-only prescription seems slightly better than DHA-only because it does not increase LDL cholesterol, decreases total cholesterol, and results in fewer gastrointestinal effects.

    “However, the EPA-only prescription seems slightly better as it does not increase the concentration of low-density lipoprotein cholesterol, decreases total cholesterol levels, and results in fewer gastrointestinal effects than DHA-only prescription [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Avallone L. Shaikh A. Hassan A. Tajuddin N. Prescription omega-3 fatty acid products: Considerations for patients with diabetes mellitus Diabetes Metab. Syndr. Obesity Targets Ther. 2016 9 109 118 10.2147/DMSO.S97036 PMC4846047 27143943 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Research suggests that treatment including supplementation with EPA and/or DHA could decrease violence in schizophrenic patients.

    “and research suggests that treatment including supplementation with EPA and/or DHA could decrease violence in schizophrenic patients [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Qiao Y. Mei Y. Han H. Liu F. Yang X.M. Shao Y. Xie B. Long B. Effects of Omega-3 in the treatment of violent schizophrenia patients Schizophr. Res. 2018 195 283 285 10.1016/j.schres.2017.08.026 28830741 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DHA has been studied as a valuable compound to delay brain aging and protect against onset of Alzheimer's disease.

    “DHA had also been studied as a valuable compound to delay brain aging and protect against the onset of Alzheimer’s disease (AD) [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Mohajeri M.H. Troesch B. Weber P. Inadequate supply of vitamins and DHA in the elderly: Implications for brain aging and Alzheimer-type dementia Nutrition 2015 31 261 275 10.1016/j.nut.2014.06.016 25592004 source

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  • May combine two claims.

    Premisecitation

    DHA is one of the main structural components of nerve cells and helps transmit signaling messages to maintain brain plasticity.

    “DHA is one of the main structural components of nerve cells and helps transmit signaling messages to maintain the plasticity of the brain [44,45].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] Garg P. Pejaver R.K. Sukhija M. Ahuja A. Role of DHA, ARA, & phospholipids in brain development: An Indian perspective Clin. Epidemiol. Glob. Heal. 2017 5 155 162 10.1016/j.cegh.2017.09.003 source

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    • cites [45] DiNicolantonio J.J. O’Keefe J.H. The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders Nutrients 2020 12 2333 10.3390/nu12082333 32759851 PMC7468918 source

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  • May combine two claims.

    Premisecitation

    Mechanisms underlying anti-inflammatory actions of EPA and DHA involve inhibition of leukocyte chemotaxis, reduction of adhesion molecule expression and leukocyte-endothelial adhesive interactions, disruption of lipid rafts, inhibition of NF-κB activation, activation of anti-inflammatory transcription factors such as PPARγ, and binding to GPCR120.

    “More precisely, mechanisms underlying the anti-inflammatory actions of EPA and DHA involve inhibition of leukocyte chemotaxis, reduction of adhesion molecule expression and leukocyte-endothelial adhesive interactions, disruption of lipid rafts, inhibition of activation of NF-κB, activation of anti-inflammatory transcription factors, such as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ),”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Calder P.C. n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases Am. J. Clin. Nutr. 2006 83 1505S 1519S 10.1093/ajcn/83.6.1505S 16841861 source

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  • May combine two claims.

    Interpretationcitation

    The increase in water temperature may induce major shifts in global PUFA production by phytoplankton and microzooplankton, with reverberating effects on higher terrestrial and aquatic trophic levels.

    “The increase in water temperature may then induce major shifts in global PUFA production by phytoplankton and their first consumers, microzooplankton, which could then have reverberating effects on higher terrestrial and aquatic trophic levels [18,74].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Gladyshev M.I. Sushchik N.N. Makhutova O.N. Production of EPA and DHA in aquatic ecosystems and their transfer to the land Prostaglandins Other Lipid Mediat. 2013 107 117 126 10.1016/j.prostaglandins.2013.03.002 23500063 source

      Not checked in the free run.

    • cites [74] Hixson S.M. Arts M.T. Climate warming is predicted to reduce omega-3, long-chain, polyunsaturated fatty acid production in phytoplankton Glob. Chang. Biol. 2016 22 2744 2755 10.1111/gcb.13295 27070119 source

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  • May combine two claims.

    Premisecitation

    Omega-3 fatty acids including ALA have anti-inflammatory, anti-oxidative, and anti-angiogenic properties and are of immense interest in preventing diabetic retinopathy.

    “Thus, with the previously described effects of omega-3 fatty acids, including α-linolenic acid (anti-inflammatory, anti-oxidative or anti-angiogenic proprieties among others) on such disorders, they are of immense interest in preventing DR [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Suzumura A. Terao R. Kaneko H. Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases Antioxidants 2020 9 920 10.3390/antiox9100920 32993153 PMC7600094 source

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  • May combine two claims.

    Premisecitation

    Humans or top predators cannot synthesize de novo n-3 PUFAs or produce them from their precursors in large enough quantities and must obtain them from diet.

    “As already stated above, humans or top predators cannot synthesize de novo n-3 PUFAs or produce them from their precursors in large enough quantities. They thus have to obtain them from their diet [96,97].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [96] Gladyshev M.I. Sushchik N.N. Long-chain Omega-3 Polyunsaturated Fatty Acids in Natural Ecosystems and the Human Diet: Assumptions and Challenges Biomolecules 2019 9 485 10.3390/biom9090485 31547473 PMC6770104 source

      Not checked in the free run.

    • cites [97] Taipale S. Peltomaa E. Salmi P. Variation in ω-3 and ω-6 Polyunsaturated Fatty Acids Produced by Different Phytoplankton Taxa at Early and Late Growth Phase Biomolecules 2020 10 559 10.3390/biom10040559 32268552 PMC7226532 source

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  • May combine two claims.

    Premisecitation

    Supply of n-3 PUFA comes mainly from the ocean and almost 90% from capture fisheries.

    “Supply of n-3 PUFA comes mainly from the ocean and the vast majority (almost 90%) from capture fisheries [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Tocher D.R. Betancor M.B. Sprague M. Olsen R.E. Napier J.A. Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand Nutrients 2019 11 89 10.3390/nu11010089 PMC6356973 30621155 source

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  • May combine two claims.

    Premisecitation

    The percentage of 20:5n-3 and 22:6n-3 varies with microalgae species and depends on productivity rate and growth conditions.

    “The percentage of 20:5n-3 and 22:6n-3 varies with microalgae species and depends on the productivity rate and the growth conditions imposed [96].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Gladyshev M.I. Sushchik N.N. Long-chain Omega-3 Polyunsaturated Fatty Acids in Natural Ecosystems and the Human Diet: Assumptions and Challenges Biomolecules 2019 9 485 10.3390/biom9090485 31547473 PMC6770104 source

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  • May combine two claims.

    Premisecitation

    Hyperglycemia triggers pathological alterations such as oxidative stress, inflammation, angiogenesis, increased apoptosis of endothelial cells and neurons, and injury to retinal blood capillaries.

    “Hyperglycemia triggers various pathological alterations such as oxidative stress, inflammation, angiogenesis, increase of apoptosis of endothelial cells and neurons, and injury to the retinal blood capillaries [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Behl T. Kotwani A. Omega-3 fatty acids in prevention of diabetic retinopathy J. Pharm. Pharmacol. 2017 69 946 954 10.1111/jphp.12744 28481011 source

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  • May combine two claims.

    Premisecitation

    Utilization of higher plants as a substitute for aquaculture feed is conceivable, but since they cannot synthesize 20:5n-3 and 22:6n-3 due to absence of dedicated enzymes, they would only supply precursors and be difficult to promote for n-3 LC-PUFA production by aquacultured fish.

    “Utilization of higher plants as a substitute for aquaculture feed is conceivable [72,80], however since they are not able to synthesize 20:5n-3 and 22:6n-3 due to the absence of dedicated enzymes [78,81], they would only supply precursors (like 18:2n-6 or 18:3n-3) and be difficult to promote for n-3 long-chain PUFAs (LC-PUFA) production by aquacultured fish.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [72] Tocher D. Issues surrounding fish as a source of omega-3 long-chain polyunsaturated fatty acids Lipid Technol. 2009 21 13 16 10.1002/lite.200800079 source

      Not checked in the free run.

    • cites [80] Domergue F. Abbadi A. Heinz E. Relief for fish stocks: Oceanic fatty acids in transgenic oilseeds Trends Plant Sci. 2005 10 112 116 10.1016/j.tplants.2005.01.003 15749468 source

      Not checked in the free run.

    • cites [78] Adarme-Vega T.C. Thomas-Hall S.R. Schenk P.M. Towards sustainable sources for omega-3 fatty acids production Curr. Opin. Biotechnol. 2014 26 14 18 10.1016/j.copbio.2013.08.003 24607804 source

      Not checked in the free run.

    • cites [81] Robert S.S. Production of Eicosapentaenoic and Docosahexaenoic Acid-Containing Oils in Transgenic Land Plants for Human and Aquaculture Nutrition Mar. Biotechnol. 2006 8 103 109 10.1007/s10126-005-5142-x 16372159 source

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  • May combine two claims.

    Premisecitation

    Genetically modified plants are often negatively regarded by consumers as artificial and unnatural and are perceived to carry risks for health and the environment.

    “However, these genetically modified plants are often negatively regarded by consumers as artificial and unnatural and are perceived to carry risks for health and the environment [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Ribeiro T.G. Barone B. Behrens J.H. Genetically modified foods and their social representation Food Res. Int. 2016 84 120 127 10.1016/j.foodres.2016.03.029 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    There is increasing interest around EPA and DHA for their positive effects on health for both humans and animals, correlating to continually increasing demand.

    “Thus, there is increasing interest around EPA and DHA for their positive effects on health for both humans and animals. This correlates to a continually increasing demand for these two compounds in recent years.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In the longer term, aquaculture appears not to be economically sustainable, especially since climate change already impacts natural production of these oils.

    “In the longer term, aquaculture thus appears not to be economically sustainable, especially since climate change already impacts the natural production of these oils.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Algal biomasses are currently used and formulated for farmed fish feed and human consumption and are commercialized by different industries.

    “Algal biomasses are currently used and formulated for farmed fish feed and human consumption and are commercialized by different industries [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Tocher D.R. Betancor M.B. Sprague M. Olsen R.E. Napier J.A. Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand Nutrients 2019 11 89 10.3390/nu11010089 PMC6356973 30621155 source

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  • May combine two claims.

    Premisecitation

    Overfishing is responsible for stabilizing fish harvesting in recent decades, with 33.1% of stocks overfished in 2018.

    “Overfishing is also responsible for stabilizing fish harvesting in the last few decades (33.1% of stocks were overfished in 2018) [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] FAO Meeting the Sustainable Development Goals The State of World Fisheries and Aquaculture; FAO Rome, Italy 2018 978-92-5-130562-1

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  • May combine two claims.

    Premisecitation

    Due to anti-angiogenetic properties, n-3 PUFAs can reduce retinal stress in ROP; due to anti-oxidant capacities they can protect eye photoreceptors from oxidative stress.

    “Due to their anti-angiogenetic proprieties, they can reduce retinal stress in ROP [64], their anti-oxidant capacities they can protect eye photoreceptors from oxidative stress [65].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] Fu Z. Lofqvist C.A. Shao Z. Sun Y. Joyal J.-S. Hurst C.G. Cui R.Z. Evans L.P. Tian K. SanGiovanni J.P. Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose–endoplasmic reticulum stress reduction to increase adiponectin Am. J. Clin. Nutr. 2015 101 879 888 10.3945/ajcn.114.099291 25833984 PMC4381778 source

      Not checked in the free run.

    • cites [65] Simón M.V. Agnolazza D.L. German O.L. Garelli A. Politi L.E. Agbaga M. Anderson R.E. Rotstein N.P. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress J. Neurochem. 2015 136 931 946 10.1111/jnc.13487 PMC4755815 26662863

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  • May combine two claims.

    Premisecitation

    Generally, n-3 PUFAs decrease with increasing temperature, while n-6 PUFAs have antagonist dynamics with rising temperature.

    “Generally, n-3 PUFAs decrease with increasing temperature, while n-6 PUFAs have antagonist dynamics with rising temperature [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Hixson S.M. Arts M.T. Climate warming is predicted to reduce omega-3, long-chain, polyunsaturated fatty acid production in phytoplankton Glob. Chang. Biol. 2016 22 2744 2755 10.1111/gcb.13295 27070119 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In FAS, KSIII catalyzes the initial condensation between malonyl-CoA and acetyl-CoA, KSI is used during the six following iterative steps to produce 16:0-ACP, and KSII conducts the last elongation of 16:0-ACP to form 18:0-ACP.

    “KSIII is in charge of the initial condensation between malonyl-CoA and acetyl-CoA, KSI is used during the six following iterative steps to produce 16:0-ACP, and the last elongation reaction of 16:0-ACP is conducted by KSII to form 18:0-ACP [117].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Harwood J.L. Fatty acid biosynthesis Plant Lipids: Biology, Utilisation and Manipulation John Wiley & Sons Cardiff, Wales, UK 2009 27 66 978-1-4051-4812-2

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The first step of the fatty acid synthesis pathway is the reaction between acetyl-CoA and bicarbonate to form malonyl-CoA.

    “The first step of the fatty acid synthesis pathway is the reaction between acetyl-CoA and bicarbonate to form malonyl-CoA [116,117].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

      Not checked in the free run.

    • cites [117] Harwood J.L. Fatty acid biosynthesis Plant Lipids: Biology, Utilisation and Manipulation John Wiley & Sons Cardiff, Wales, UK 2009 27 66 978-1-4051-4812-2

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    16:0 and 18:0 are the major products of the FAS pathway in microalgae.

    “16:0 and 18:0 are the major products of the FAS pathway in microalgae [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Metazoan cells contain front-end desaturases such as Δ5 and Δ6 desaturases but do not possess methyl-end desaturases like ω6 (Δ12) or ω3 (Δ15).

    “Metazoan cells, for example, contain front-end desaturases such as Δ5 and Δ6 desaturases but do not possess methyl-end desaturases like ω6 (Δ12) or ω3 (Δ15).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Type I fatty acid synthase, present in mammal cytoplasms, consists of seven catalytic components linked together in a multifunctional megasynthase.

    “Type I fatty acid synthase, present in mammal cytoplasms, consists of seven catalytic components linked together in a multifunctional megasynthase [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In microalgae and higher plants, palmitic acid can follow three routes: it can be used in the plastid to form chloroplast lipids such as galactolipids, further elongated into 18:0 and more complex fatty acids, or converted into a free fatty-acid.

    “In microalgae and higher plants, at this point, palmitic acid can follow three different routes: (i) it can be used in the plastid to form chloroplast lipids such as the galactolipids, (ii), further elongated into 18:0 and then more complex fatty acids or (iii) converted into a free fatty-acid [121,122].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [121] Los D.A. Murata N. Structure and expression of fatty acid desaturases Biochim. Biophys. Acta (BBA) Lipids Lipid Metab. 1998 1394 3 15 10.1016/S0005-2760(98)00091-5 9767077 source

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    • cites [122] Li-Beisson Y. Beisson F. Riekhof W. Metabolism of acyl-lipids in Chlamydomonas reinhardtii Plant J. 2015 82 504 522 10.1111/tpj.12787 25660108 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In plants, fatty acids formed by FAS and from FAS-products following desaturases can remain in the plastid for synthesis of glycolipids or be released to the cytosol and transferred to the endoplasmic reticulum for extraplastidial lipid synthesis.

    “The fatty acids formed by FAS and from FAS-products following the action of desaturases have two possible fates in plants: (i) they can remain in the plastid and be involved in the synthesis of glycolipids especially galactolipids or (ii) they can be released to the cytosol and transfered to the endoplasmic reticulum to be used in extraplastidial lipid synthesis [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • May combine two claims.

    Premisenone given

    The conversion rate of 18:2n-6 and 18:3n-3 into essential C20-C22 PUFAs is generally insufficient and thus these PUFAs have to be supplied by the diet.

    “Nevertheless, as previously stated, the conversion rate of 18:2n-6 and 18:3n-3 into essential C20-C22 PUFAs is generally insufficient and thus has to be supplied by the diet.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    After FAS synthesis, 16:0 undergoes one last condensation, reduction, dehydration and reduction step and gives stearic acid (18:0).

    “After being synthesized by the FAS pathway, 16:0 encompass one last condensation, reduction, dehydration and reduction step, respectively, and gives a saturated two-carbon longer fatty acid: stearic acid (18:0).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    In microalgae, similar fatty acid trafficking to plants could exist, as studied in the diatom Chaetoceros muelleri with 13C-labelling.

    “In microalgae, similar fatty acid trafficking could exist as studied in the diatom Chaetoceros muelleri with 13C-labelling [124].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Remize M. Planchon F. Loh A.N. Le Grand F. Bideau A. Le Goic N. Fleury E. Miner P. Corvaisier R. Volety A. Study of Synthesis Pathways of the Essential Polyunsaturated Fatty Acid 20:5n-3 in the Diatom Chaetoceros Muelleri Using 13C-Isotope Labeling Biomolecules 2020 10 797 10.3390/biom10050797 PMC7277837 32455747 source

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  • May combine two claims.

    Premisecitation

    Taipale et al. studied 16 species belonging to six main groups of phytoplankton and showed that PUFA content can vary greatly within phytoplanktonic groups due to variation in cell size.

    “Taipale et al. [97] studied the influence of the growth stage on the production of n-3 and n-6 PUFAs in 16 species belonging to the six main groups of phytoplankton (Cryptophytes, Dinophytes, Chrysophytes, Diatoms, Chlorophytes and Cyanobacteria). They showed that PUFA content can vary greatly within phytoplanktonic groups to variation in cell size.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Taipale S. Peltomaa E. Salmi P. Variation in ω-3 and ω-6 Polyunsaturated Fatty Acids Produced by Different Phytoplankton Taxa at Early and Late Growth Phase Biomolecules 2020 10 559 10.3390/biom10040559 32268552 PMC7226532 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Putative FAS I enzymes have been identified in Nannochloropsis oceanica and Euglena gracilis.

    “putative FAS I enzymes have been identified in Nannochloropsis oceanica and Euglena gracilis [119,120].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [119] Vieler A. Wu G. Tsai C.-H. Bullard B. Cornish A.J. Harvey C. Reca I.-B. Thornburg C. Achawanantakun R. Buehl C.J. Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779 PLoS Genet. 2012 8 e1003064 10.1371/journal.pgen.1003064 23166516 PMC3499364 source

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    • cites [120] Hoffmeister M. Piotrowski M. Nowitzki U. Martin W. Mitochondrial trans-2-Enoyl-CoA Reductase of Wax Ester Fermentation from Euglena gracilis Defines a New Family of Enzymes Involved in Lipid Synthesis J. Biol. Chem. 2005 280 4329 4338 10.1074/jbc.M411010200 15569691 source

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  • May combine two claims.

    Premisecitation

    Diatoms can synthesize around 20% of EPA and a low proportion of DHA.

    “Diatoms can synthesize around 20% of EPA and a low proportion of DHA [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Liang Y. Maeda Y. Yoshino T. Matsumoto M. Tanaka T. Profiling of fatty acid methyl esters from the oleaginous diatom Fistulifera sp. strain JPCC DA0580 under nutrition-sufficient and -deficient conditions Environ. Boil. Fishes 2014 26 2295 2302 10.1007/s10811-014-0265-y

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The elucidation of fatty acid synthesis pathways in microalgae is still ongoing; some species such as diatoms are more extensively studied, but for other species the synthetic routes remain to be identified.

    “The elucidation of fatty acid synthesis pathways in microalgae is still ongoing. Even if a synthesis pathway of some species such as the diatoms are more extensively studied [107,125,126,127], for other species the synthetic routes remain to be identified.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [107] Arao T. Sakaki T. Yamada M. Biosynthesis of polyunsaturated lipids in the diatom, Phaeodactylum tricornutum Phytochemistry 1994 36 629 635 10.1016/S0031-9422(00)89787-3 source

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    • cites [125] Arao T. Yamada M. Biosynthesis of polyunsaturated fatty acids in the marine diatom, Phaeodactylum tricornutum Phytochemistry 1994 35 1177 1181 10.1016/S0031-9422(00)94817-9 source

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    • cites [126] Domergue F. Lerchl J. Zähringer U. Heinz E. Cloning and functional characterization of Phaeodactylum tricornutum front-end desaturases involved in eicosapentaenoic acid biosynthesis Eur. J. Biochem. 2002 269 4105 4113 10.1046/j.1432-1033.2002.03104.x 12180987 source

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    • cites [127] Domergue F. Spiekermann P. Lerchl J. Beckmann C. Kilian O. Kroth P.G. Boland W. Zähringer U. Heinz E. New Insight into Phaeodactylum tricornutum Fatty Acid Metabolism. Cloning and Functional Characterization of Plastidial and Microsomal Δ12-Fatty Acid Desaturases Plant Physiol. 2003 131 1648 1660 10.1104/pp.102.018317 12692324 PMC166921 source

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  • May combine two claims.

    Premisecitation

    Microalgae can modify their membrane fluidity in response to temperature variations, thus adapting their fatty acid composition.

    “Indeed, as stated earlier in this review, microalgae can modify their membrane fluidity in response to temperature variations, thus adapting their fatty acid composition [76,77].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [76] Renaud S.M. Thinh L.-V. Lambrinidis G. Parry D.L. Effect of temperature on growth, chemical composition and fatty acid composition of tropical Australian microalgae grown in batch cultures Aquaculture 2002 211 195 214 10.1016/S0044-8486(01)00875-4 source

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    • cites [77] Rousch J.M. Bingham S.E. Sommerfeld M.R. Changes in fatty acid profiles of thermo-intolerant and thermo-tolerant marine diatoms during temperature stress J. Exp. Mar. Biol. Ecol. 2003 295 145 156 10.1016/S0022-0981(03)00293-4 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lipid chains are created from malonyl-CoA by successive additions of two-carbon units involving four enzymatic steps: condensation, reduction, dehydration, and another reduction, consuming NADPH and releasing CO2.

    “Lipid chains are created from malonyl-CoA by successive additions of two-carbon units involving four enzymatic steps: condensation, reduction, dehydration, and another reduction and consuming NADPH while releasing CO2 [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Mammals can elongate and desaturate dietary 18:2n-6 and 18:3n-3 into C20-C22 PUFAs (20:4n-6, 20:5n-3, 22:6n-3) using their Δ4, Δ5 and Δ6 desaturase.

    “Mammals can elongate and desaturase dietary 18:2n-6 and 18:3n-3 into C20-C22 PUFAs (20:4n-6, 20:5n-3, 22:6n-3) using their Δ4, Δ5 and Δ6 desaturase.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The conventional elongation and desaturation pathway present in numerous eukaryotes is named the n-3 and n-6 pathways, and the polyketide synthase pathway (PKS pathway) also exists to produce polyunsaturated fatty acids.

    “The conventional elongation and desaturation pathway present in numerous eukaryotes names, hereafter n-3 and n-6 pathways and the polyketide synthase pathway (PKS pathway), also exist to produce polyunsaturated fatty acids.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Both n-3 and n-6 pathways are reported to be performed in the mitochondria and the endoplasmic reticulum and present a similar synthesis sequence to palmitate, involving specific enzymes acyl-CoA derivatives.

    “Both n-3 and n-6 pathways are reported to performed in the mitochondria and the endoplasmic reticulum (ER) and present a similar synthesis sequence as those of palmitate, and involve specific enzymes acyl-CoA derivatives (Figure 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    For Cyanobacteria or Chlorophytes, long chain n-3 PUFA production can be assumed negligible, and only certain levels of PUFAs such as ALA and stearidonic acid can be found and play a subsiding role in consumer development, namely Chlorella vulgaris.

    “For other taxa such as Cyanobacteria or Chlorophytes, long chain n-3 PUFA production can be assumed negligible [96], and only certain levels of PUFAs such as ALA and stearidonic acid (SDA—18:4n-3) can be found and play a subsiding role in consumer development, namely Chlorella vulgaris [97].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [96] Gladyshev M.I. Sushchik N.N. Long-chain Omega-3 Polyunsaturated Fatty Acids in Natural Ecosystems and the Human Diet: Assumptions and Challenges Biomolecules 2019 9 485 10.3390/biom9090485 31547473 PMC6770104 source

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    • cites [97] Taipale S. Peltomaa E. Salmi P. Variation in ω-3 and ω-6 Polyunsaturated Fatty Acids Produced by Different Phytoplankton Taxa at Early and Late Growth Phase Biomolecules 2020 10 559 10.3390/biom10040559 32268552 PMC7226532 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Malonyl-CoA has a central role as the initial precursor of de novo fatty acid synthesis and is useful in later elongation steps occurring in the endoplasmic reticulum.

    “Malonyl-CoA has a central role in this synthesis as the initial precursor of the de novo fatty acids synthesis, but also by being useful in the later elongation steps occurring in the endoplasmic reticulum (ER).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In microalgae, chain elongation and desaturation happen in the mitochondria and endoplasmic reticulum, desaturation steps in the endoplasmic reticulum, and de novo synthesis in the plastid.

    “In microalgae, chain elongation and desaturation happen in the mitochondria and endoplasmic reticulum, desaturation steps in the endoplasmic reticulum, and de novo synthesis in the plastid [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fatty acid biosynthesis is initiated by de novo synthesis of acetyl-CoA via the concerted action of acetyl-CoA carboxylase (ACCase) and fatty acid synthase.

    “It is initiated by de novo synthesis of acetyl-CoA via the concerted action of acetyl-CoA carboxylase (ACCase) and fatty acid synthase [115].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Watkins S.M. German B.J. Unsaturated fatty acids Food Lipid: Chemistry, Nutrition, and Biotechnology Food Science and Technology CRC Press/Taylor & Francis Group Boca Raton, CA, USA 2008 513 537

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The biosynthesis of fatty acids is similar among plants and animals.

    “The biosynthesis of fatty acids is similar among plants and animals.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Watkins S.M. German B.J. Unsaturated fatty acids Food Lipid: Chemistry, Nutrition, and Biotechnology Food Science and Technology CRC Press/Taylor & Francis Group Boca Raton, CA, USA 2008 513 537

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Several iteration steps of the FAS pathways allow for the formation of palmitic acid (16:0).

    “Several iteration steps of the FAS pathways allow for the formation of palmitic acid (16:0).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Differences in morphology and physiology of microalgae species, their cellular organization and carbon metabolism are expected to impact lipid trafficking and synthesis pathway.

    “Differences in morphology and physiology of microalgae species, their cellular organization and carbon metabolism is expected to impact lipid trafficking and synthesis pathway [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • May combine two claims.

    Premisecitation

    The conventional fatty acid synthesis pathway described in plants and microalgae is divided into three distinct pathways supported by three enzymatic systems: biosynthesis of palmitic acid and other saturated fatty acids via FAS, further chain elongations, and desaturations to produce more complex polyunsaturated fatty acids.

    “The conventional fatty acid synthesis pathway described in plants and microalgae is divided into three distinct pathways supported by three enzymatic systems: (i) first, the biosynthesis of palmitic acid (16:0) and other saturated fatty acids is completed from acetyl-CoA, following the Fatty Acid Synthase (FAS) pathway (Figure 1), (ii) then further chain elongations, and (iii) desaturations occur”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

      Not checked in the free run.

    • cites [117] Harwood J.L. Fatty acid biosynthesis Plant Lipids: Biology, Utilisation and Manipulation John Wiley & Sons Cardiff, Wales, UK 2009 27 66 978-1-4051-4812-2

      Not checked in the free run.

    • cites [118] Bell M.V. Tocher D.R. Biosynthesis of polyunsaturated fatty acids in aquatic ecosystems: General pathways and new direc-tions Lipids in Aquatic Ecosystems Kainz M. Brett M.T. Arts M.T. Springer New York, NY, USA 2009 211 236 978-0-387-88607-7 source

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  • May combine two claims.

    Interpretationreasoning

    Microalgae have both methyl-end and front-end desaturases and thus play an important role in providing higher trophic levels with essential C20-C22 PUFAs.

    “On the contrary, microalgae have both methyl-end and front-end desaturases and thus play an important role in providing higher trophic levels with these essential compounds.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The first reduction reaction by β-ketoacyl-ACP reductase (KR) is NADPH-dependent.

    “The first reduction reaction by β-ketoacyl-ACP reductase (KR) is NADPH-dependent.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Harwood J.L. Fatty acid biosynthesis Plant Lipids: Biology, Utilisation and Manipulation John Wiley & Sons Cardiff, Wales, UK 2009 27 66 978-1-4051-4812-2

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In microalgae, fatty acid biosynthesis is performed by stromal fatty acid synthase (type II), a multisubunit composed of four monofunctional enzymes ensuring four enzymatic reactions.

    “In microalgae, fatty acid biosynthesis is performed by stromal fatty acid synthase (type II) which consists of a multisubunit composed of four monofunctional enzymes ensuring the following four enzymatic reactions [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Khozin-Goldberg I. Lipid metabolism in microalgae The Physiology of Microalgae Borowitzka M.A. Beardall J. Raven J.A. Developments in Applied Phycology Springer International Publishing Cham, Switzerland 2016 413 484 978-3-319-24945-2 source

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  • May combine two claims.

    Premisenone given

    The PKS pathway and FAS pathway share functioning similarities and rely on the same four basic reactions-condensation, reduction, dehydration and reduction-by the same four enzymes: KS, KR, DH, and βER.

    “The PKS pathway and FAS pathway share functioning similarities and rely on the same four basic reactions, namely condensation, reduction, dehydration and reduction by the four same enzymes: β-ketoacyl-ACP synthase (KS), β-ketoacyl-ACP reductase (KR), β-hydroxyacyl-ACP dehydrase (DH), and β-enoyl-ACP reductase (βER).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Type I and Type II PKS need an acyl carrier protein (ACP) to activate the substrate, while Type III acts directly on acetyl-CoA independently of ACP.

    “Type I and Type II need an acyl carrier protein (ACP) to activate the substrate responsible for the channeling of the growing polyketide intermediates. In contrast, Type III acts directly on the acetyl-CoA independently of ACP [142].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [142] Shen B. Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms Curr. Opin. Chem. Biol. 2003 7 285 295 10.1016/S1367-5931(03)00020-6 12714063 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Type I PKS are large multifunctional enzymes with several catalytic domains on the same polypeptide; Type II PKS are complexes of monofunctional enzymes; Type III PKS are homodimeric enzymes involved in condensation reactions.

    “Type I PKS are large multifunctional enzymes with several catalytic domains located on the same polypeptide. Each module is responsible for a set of distinct, non-iteratively acting activities responsible for the catalysis of one cycle of polyketide chain elongation [142]. Type II PKS are complexes composed of monofunctional enzymes, where each enzyme carries one catalytic domain and a single set”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [142] Shen B. Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms Curr. Opin. Chem. Biol. 2003 7 285 295 10.1016/S1367-5931(03)00020-6 12714063 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The PKS pathway was first identified in the deep-sea bacteria Shewanella.

    “The PKS pathway was first identified in the deep-sea bacteria, Shewanella [133].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Metz J.G. Roessler P. Facciotti D. Levering C. Dittrich F. Lassner M. Valentine R. Lardizabal K. Domergue F. Yamada A. Production of Polyunsaturated Fatty Acids by Polyketide Synthases in Both Prokaryotes and Eukaryotes Science 2001 293 290 293 10.1126/science.1059593 11452122 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While FAS synthesis and elongation/desaturation pathways are very energy-consuming, the PKS pathway has fewer reduction and dehydration steps and can produce PUFAs more efficiently.

    “While FAS synthesis and elongation/desaturation pathways, involving numerous enzymatic activities and reactions are very energy-consuming [132], the PKS pathway, in constrat, has fewer reduction and dehydration steps and can produce PUFAs more efficiently [133].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [132] Wallis J.G. Watts J.L. Browse J. Polyunsaturated fatty acid synthesis: What will they think of next? Trends Biochem. Sci 2002 27 467 473 10.1016/S0968-0004(02)02168-0 12217522 source

      Not checked in the free run.

    • cites [133] Metz J.G. Roessler P. Facciotti D. Levering C. Dittrich F. Lassner M. Valentine R. Lardizabal K. Domergue F. Yamada A. Production of Polyunsaturated Fatty Acids by Polyketide Synthases in Both Prokaryotes and Eukaryotes Science 2001 293 290 293 10.1126/science.1059593 11452122 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microalgae are cultivated and concentrated as dispersible pastes or as freeze-dried cubes.

    “Microalgae are cultivated and concentrated in the form of dispersible pastes (which can be added directly in the water tank and dissolved in the liquid media) or as freeze-dried cubes [198].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Raja R. Coelho A. Hemaiswarya S. Kumar P. Carvalho I.S. Alagarsamy A. Applications of microalgal paste and powder as food and feed: An update using text mining tool Beni Suef Univ. J. Basic Appl. Sci. 2018 7 740 747 10.1016/j.bjbas.2018.10.004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Diatoms such as Chaetoceros sp. and Phaeodactylum sp. or the Eustigmatophyte Nannochloropsis oculata are generally more used to form microalgae pastes.

    “To form the microalgae pastes, diatoms such as Chaetoceros sp. and Phaeodactylum sp. or the Eustigmatophyte, Nannochloropsis oculata are generally more used [198].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Raja R. Coelho A. Hemaiswarya S. Kumar P. Carvalho I.S. Alagarsamy A. Applications of microalgal paste and powder as food and feed: An update using text mining tool Beni Suef Univ. J. Basic Appl. Sci. 2018 7 740 747 10.1016/j.bjbas.2018.10.004

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Type I PKS is mainstream of protist and has been identified in Haptophytes, Chlorophytes, Dinophytes, and Thraustochytrids.

    “Type I PKS is mainstream of protist and has been identified in Haptophytes [141,143], Chlorophytes [140], Dinophytes [137,144], and Thraustochytrids [145].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [141] John U. Beszteri S. Glöckner G. Singh R. Medlin L. Cembella A.D. Genomic characterisation of the ichthyotoxic prymnesiophyte Chrysochromulina polylepis,and the expression of polyketide synthase genes in synchronized cultures Eur. J. Phycol. 2010 45 215 229 10.1080/09670261003746193 source

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    • cites [143] Freitag M. Beszteri S. Vogel H. John U. Effects of physiological shock treatments on toxicity and polyketide synthase gene expression in Prymnesium parvum (Prymnesiophyceae) Eur. J. Phycol. 2011 46 193 201 10.1080/09670262.2011.591438 source

      Not checked in the free run.

    • cites [140] John U. Beszteri B. Derelle E. Van De Peer Y. Read B. Moreau H. Cembella A. Novel Insights into Evolution of Protistan Polyketide Synthases through Phylogenomic Analysis Protist 2008 159 21 30 10.1016/j.protis.2007.08.001 17931970 source

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    • cites [137] Murray S.A. Garby T. Hoppenrath M. Neilan B.A. Genetic Diversity, Morphological Uniformity and Polyketide Production in Dinoflagellates (Amphidinium, Dinoflagellata) PLoS ONE 2012 7 e38253 10.1371/journal.pone.0038253 22675531 PMC3366924 source

      Not checked in the free run.

    • cites [144] Eichholz K. Beszteri B. John U. Putative Monofunctional Type I Polyketide Synthase Units: A Dinoflagellate-Specific Feature? PLoS ONE 2012 7 e48624 10.1371/journal.pone.0048624 23139807 PMC3489724 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In Dinophytes, the multifunctional activities characteristic of Type I PKS are not always verified because some species like Karenia brevis, Alexandrium ostenfeldii, and Heterocapsa triquetra possess an atypical architecture for Type I PKS with only one catalytic module.

    “In Dinophytes, the multifunctional activities characteristic of Type I PKS is not always verified because some species like Karenia brevis, Alexandrium ostenfeldii, and Heterocapsa triquetra possess an atypical architecture for Type I PKS with only one catalytic module [144,146].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [144] Eichholz K. Beszteri B. John U. Putative Monofunctional Type I Polyketide Synthase Units: A Dinoflagellate-Specific Feature? PLoS ONE 2012 7 e48624 10.1371/journal.pone.0048624 23139807 PMC3489724 source

      Not checked in the free run.

    • cites [146] Monroe E.A. van Dolah F.M. The Toxic Dinoflagellate Karenia brevis Encodes Novel Type I-like Polyketide Synthases Con-taining Discrete Catalytic Domains Protist 2008 159 471 482 10.1016/j.protis.2008.02.004 18467171 source

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  • May combine two claims.

    Premisecitation

    Arthrospira platensis, Auxenochlorella protothecoides, Dunaliella bardawil, Dunaliella salina, Schizochytrium sp., and Ulkenia sp. are GRAS.

    “Other GRAS species are Arthrospira platensis, Auxenochlorella protothecoides, Dunaliella bardawil, Dunaliella salina, Schizochytrium sp., and Ulkenia sp. [194,208].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [194] Sidari R. Tofalo R. A Comprehensive Overview on Microalgal-Fortified/Based Food and Beverages Food Rev. Int. 2019 35 778 805 10.1080/87559129.2019.1608557 source

      Not checked in the free run.

    • cites [208] Torres-Tiji Y. Fields F.J. Mayfield S.P. Microalgae as a future food source Biotechnol. Adv. 2020 41 107536 10.1016/j.biotechadv.2020.107536 32194145 source

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  • May combine two claims.

    Premisecitation

    In 1999, 62% of the microalgae produced for aquaculture were used for mollusks, 21% for crustaceans (mainly shrimps), and 16% for fish.

    “As an example, in 1999, 62% of the microalgae produced for aquaculture were used for mollusks, while 21% were used for crustaceans (mainly shrimps) and only 16% for fish [168].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [168] Spolaore P. Joannis-Cassan C. Duran E. Isambert A. Commercial applications of microalgae J. Biosci. Bioeng. 2006 101 87 96 10.1263/jbb.101.87 16569602 source

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  • May combine two claims.

    Premisecitation

    Nannochloropsis sp. is characterized by high levels of PUFAs (37%) and is rich in EPA and DHA.

    “Indeed, species like Nannochloropsis sp. are characterized by high levels of PUFAs (37%) and are rich in EPA and DHA [217].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [217] Matos Â.P. Feller R. Moecke E.H.S. De Oliveira J.V. Junior A.F. Derner R.B. Sant’Anna E.S. Chemical Characterization of Six Microalgae with Potential Utility for Food Application J. Am. Oil Chem. Soc. 2016 93 963 972 10.1007/s11746-016-2849-y

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The PKS pathway, even if fundamentally anaerobic, can take place in aerobic conditions.

    “The PKS pathway, even if fundamentally anaerobic, can take place in aerobic conditions [134].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [134] Qiu X. Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): Two distinct pathways Prostaglandins Leukot. Essent. Fat. Acids 2003 68 181 186 10.1016/S0952-3278(02)00268-5 12538082 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    These microalgae are easily and efficiently filtered from the water where the shells grow.

    “They are easily and efficiently filtered from the water where the shells grow [179].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Packer M.A. Harris G.C. Adams S.L. Food and feed applications of algae Algae Biotechnology Bux F. Chisti Y. Green Energy and Technology Springer International Publishing Cham, Switzerland 2016 217 247 978-3-319-12333-2 source

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  • May combine two claims.

    Premisecitation

    Microalgae biomass can enhance animal physiology by improving immune response, disease resistance, antiviral and antibacterial protections, reproductive performance, feed conversion, and weight gain.

    “Microalgae biomass can enhance animal physiology by improving their immune response, disease resistance, antiviral and antibacterial protections, and better reproductive performance, feed conversion, and weight gain [219].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [219] Camacho F. Macedo A. Malcata F. Potential Industrial Applications and Commercialization of Microalgae in the Functional Food and Feed Industries: A Short Review Mar. Drugs 2019 17 312 10.3390/md17060312 31141887 PMC6628611 source

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  • May combine two claims.

    Premisecitation

    EPA and DHA have been credited with health benefits even when supplemented in small amounts and can positively affect immune system, lipid metabolism, stress resistance, appetite, reproductive performance, and cholesterol levels.

    “As for humans, EPA and DHA have been credited with health benefits even when supplemented in small amounts, and can have positive effects on the improvement of the immune system, lipid metabolism, stress resistance, increase in appetite, enhancing reproductive performance, or even the reduction of cholesterol levels [231].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [231] Kovač D.J. Simeunović J.B. Babić O.B. Mišan A.Č. Milovanović I.L. Algae in Food and Feed Food Feed Res. 2013 11 21 32

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    AlgaPrimeTM from Corbion is marketed for animal feed and consists of a DHA source from Schizochytrium sp.

    “AlgaPrimeTM from Corbion is also marketed for animal feed and consists of a DHA source from Schizochytrium sp. [239].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [239] Corbion Inc AlgaPrimeTM DHA Is the World’s Leading Source of Algae Omega-3 Feed Ingredient for Aquaculture, Production Animals and Companion Animals Available online: https://algaprime.com (accessed on 7 December 2020)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Nannochloropsis sp. and Isochrysis galbana are widely used for rotifer production and to enhance rotifer richness in EPA and DHA.

    “Nannochloropsis sp. and Isochrysis galbana are also widely used for rotifer production and to enhance their richness in EPA and DHA [226,227,228].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [226] Lubzens E. Raising rotifers for use in aquaculture Hydrobiologia 1987 147 245 255 10.1007/BF00025750 source

      Not checked in the free run.

    • cites [227] Ferreira M. Maseda A. Fabregas J. Otero A. Enriching Rotifers with “Premium” Microalgae Isochrysis aff. galbana Clone T-ISO Aquaculture 2008 279 126 130 10.1016/j.aquaculture.2008.03.044 source

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    • cites [228] Ferreira M. Coutinho P. Seixas P. Fábregas J. Otero A. Enriching Rotifers with “Premium” Microalgae Nannochloropsis gaditana. Mar. Biotechnol. 2009 11 585 595 10.1007/s10126-008-9174-x 19153793 source

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  • May combine two claims.

    Premisecitation

    Crypthecodinium cohnii has been marketed for its DHA production and used as a substitute for fisheries-derived oils for seabream (Sparus aurata) microdiets.

    “For example, the heterotrophic dinoflagellate Crypthecodinium cohnii has been marketed for its DHA production and used as a substitute for fisheries-derived oils for seabream (Sparus aurata) microdiets [225].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [225] Ganuza E. Benítez-Santana T. Atalah E. Vega-Orellana O. Ganga R. Izquierdo M. Crypthecodinium cohnii and Schizochytrium sp. as potential substitutes to fisheries-derived oils from seabream (Sparus aurata) microdiets Aquaculture 2008 277 109 116 10.1016/j.aquaculture.2008.02.005 source

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  • May combine two claims.

    Premisecitation

    DHA in dog diets can improve immune system, enhance palatability of food, increase digestibility, and enhance cognitive responses.

    “DHA in dog diets can improve their immune system, enhance the palatability of their food, increase digestibility, and enhance their cognitive responses [234,235].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [234] Souza C.M.M. De Lima D.C. Bastos T.S. De Oliveira S.G. Beirão B.C.B. Félix A.P. Microalgae Schizochytrium sp. as a source of docosahexaenoic acid (DHA): Effects on diet digestibility, oxidation and palatability and on immunity and inflammatory indices in dogs Anim. Sci. J. 2019 90 1567 1574 10.1111/asj.13294 31680401 source

      Not checked in the free run.

    • cites [235] Hadley K. Bauer J. Milgram N. The oil-rich alga Schizochytrium sp. as a dietary source of docosahexaenoic acid improves shape discrimination learning associated with visual processing in a canine model of senescence Prostaglandins Leukot. Essent. Fat. Acids 2017 118 10 18 10.1016/j.plefa.2017.01.011 28288702 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Crypthecodinium's elevated DHA production was particularly suitable for the high DHA requirement of seabream larvae and resulted in similar performances as classical fisheries-related diets.

    “The elevated DHA production of Crypthecodinium was particularly suitable for the high requirement for this essential PUFA of seabream larvae and resulted in similar performances as with classical fisheries-related diets [225].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [225] Ganuza E. Benítez-Santana T. Atalah E. Vega-Orellana O. Ganga R. Izquierdo M. Crypthecodinium cohnii and Schizochytrium sp. as potential substitutes to fisheries-derived oils from seabream (Sparus aurata) microdiets Aquaculture 2008 277 109 116 10.1016/j.aquaculture.2008.02.005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These microalgae increase rotifer survival, productivity, efficiency of feed assimilation, and biochemical composition.

    “Indeed, they increase their survival, productivity, efficiency of feed assimilation, and biochemical composition [227,228].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [227] Ferreira M. Maseda A. Fabregas J. Otero A. Enriching Rotifers with “Premium” Microalgae Isochrysis aff. galbana Clone T-ISO Aquaculture 2008 279 126 130 10.1016/j.aquaculture.2008.03.044 source

      Not checked in the free run.

    • cites [228] Ferreira M. Coutinho P. Seixas P. Fábregas J. Otero A. Enriching Rotifers with “Premium” Microalgae Nannochloropsis gaditana. Mar. Biotechnol. 2009 11 585 595 10.1007/s10126-008-9174-x 19153793 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nannochloropsis oceanica's thick cell walls protect EPA from metabolization by rumen microbiota, inducing full enrichment in EPA for better ruminant development and health without inhibiting growth and activity of rumen bacteria.

    “The algae’s thick cell walls protect the healthy compound from metabolization by rumen microbiota, inducing a full enrichment in the EPA for better ruminant development and health without inhibiting the growth and activity of rumen bacteria [232].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [232] Alves S.P. Mendonça S.H. Silva J.L. Bessa R.J.B. Nannochloropsis oceanica, a novel natural source of rumen-protected eicosapentaenoic acid (EPA) for ruminants Sci. Rep. 2018 8 10269 10.1038/s41598-018-28576-7 29980726 PMC6035222

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Arthrospira is highly used in terrestrial animal feed across cats, dogs, aquarium fish, ornamental birds, horses, cows, and breeding bulls because it affects their physiology to essential fatty acids.

    “Arthrospira is also highly used in this domain and touches all types of animals, such as cats, dogs, aquarium fish, ornamental birds, horses, cows, and breeding bulls, because it affects their physiology to essential fatty acids among other [168].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [168] Spolaore P. Joannis-Cassan C. Duran E. Isambert A. Commercial applications of microalgae J. Biosci. Bioeng. 2006 101 87 96 10.1263/jbb.101.87 16569602 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Providing n-3 PUFAs positively impacts atopic dermatitis, osteoarthritis, and modulation of immunity indicators in dogs.

    “Providing n-3 PUFAs has a positively impact on atopic dermatitis, osteoarthritis, and the modulation of immunity indicators in dogs [233].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [233] Beynen A.C. Microalgae in Petfood Creat. Companion 2019 40 7

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    These feeds enhance vital functions, heart conditions, cognitive development, or stimulate intestinal immunity.

    “These feeds enhance their vital functions, heart conditions, cognitive development, or stimulate their intestinal immunity [237].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [237] Allmicroalgae Natural Products Allvitae by Allmicroalgae Available online: https://www.allmicroalgae.com/en/feed-2/ (accessed on 7 December 2020)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    EPA and DHA have positive impact on human health due to antioxidant, anti-inflammatory, and anti-cancer properties.

    “EPA and DHA are receiving increasing interest for their positive impact on human health thanks to their antioxidant, anti-inflammatory and anti-cancer properties.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Rotifers supply consumers with macro- and micronutrients, vitamins, and even antibiotics.

    “They are in charge of supplying consumers with macro- and micronutrients, vitamins and even antibiotics [226].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [226] Lubzens E. Raising rotifers for use in aquaculture Hydrobiologia 1987 147 245 255 10.1007/BF00025750 source

      Not checked in the free run.

101 of 101

  • The paper relies on this without support.

    Global population and demand for n-3 PUFAs will continue to grow.

    “Consequently, considering the constant growth of the global population and the resulting demand for these compounds, aquaculture now appears to be one of the solutions for meeting future seafood needs and filling the gap between supply and demand [40,78].”

  • The paper relies on this without support.

    Microalgae can be cultivated at industrial scale sufficient to sustainably supply n-3 PUFAs for food and feed.

    “This translates into a high potential for the production and commercialization of these organisms in the coming years.”

  • The authors state this as an assumption.

    In microalgae, fatty acid biosynthesis is similar to that of higher plants, with acetyl-CoA and de novo fatty acid synthesis taking place in the plastid and requiring ATP and NADPH.

    “In microalgae, fatty acid biosynthesis is assumed to be similar to that of higher plants: acetyl-CoA and de novo fatty acid synthesis seem to take place in the plastid (chloroplast) and require energy (ATP) and reducing power (NADPH) [116].”

  • The authors state this as an assumption.

    In microalgae, acetyl-CoA has two origins: direct supply from the plastid by pyruvate dehydrogenase/decarboxylase or indirectly from mitochondrial pyruvate dehydrogenase where mitochondrial acetyl-CoA is transferred to the plastid after hydrolysis to be regenerated by ACCase.

    “like in plants, acetyl-CoA is assumed to have two origins: it can be provided by direct supply from plastid by pyruvate dehydrogenase/decarboxylase or indirectly from mitochondrial pyruvate dehydrogenase where the mitochondrial acetyl-CoA has to be transferred to the plastid after hydrolysis to be regenerated by ACCase [117].”

  • The authors state this as an assumption.

    The reactions catalyzed by plant FAS are identical for microalgae FAS.

    “The different reactions catalyzed by plant FAS and supposed to be identical for microalgae FAS as genes coding for these enzymes have been characterized for phytoplankton and were described earlier [116]”

  • The authors state this as an assumption.

    The polyunsaturated fatty acid synthesis pathway occurs in plants and microalgae as described in the following paragraph.

    “The following paragraph describes the polyunsaturated fatty acid synthesis pathway as it has been assumed to occur in plants and microalgae [116].”

  • The authors state this as an assumption.

    The precursors and fatty acids involved in the PKS pathway are as proposed by Bell and Tocher (2009).

    “The different precursors and fatty acids assumed to be involved in the PKS pathway and proposed by Bell and Tocher (2009) [118] are presented in Figure 3.”

  • The paper relies on this without support.

    The synthesis pathways leading to EPA and DHA production in microalgae remain incompletely elucidated.

    “Despite the extensive knowledge of the diverse species able to produce these two compounds, the synthesis pathways leading to the production of EPA and DHA are still under investigation.”

  • The paper relies on this without support.

    EPA and DHA face supply challenges due to current stock reduction and overfishing.

    “Originating mainly from marine sources such as fish, these two compounds face supply challenges due to current stock reduction and overfishing.”

  • The paper relies on this without support.

    Aquaculture is not sufficient for filling the gap between supply and demand for EPA and DHA.

    “Because of environmental stress and increased pressure on the natural stock, aquaculture is not sufficient for filling the gap between supply and demand.”

  • The paper relies on this without support.

    Authorization proving microalgae are safe for consumption is difficult to obtain.

    “as authorization proving they are safe for consumption is difficult to obtain.”

  • The paper relies on this without support.

    Microalgae are primary producers of EPA and DHA.

    “As primary producers of EPA and DHA, microalgae have been used in recent years to develop the future ingredients and foods.”
12 of 12

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Fatty-acid synthesis step is called both dehydration and hydration

    Minor

    The same four-step fatty-acid synthesis sequence is first described as including dehydration, but its subsequent step-by-step description calls that step hydration.

  • Cyanobacterial DHA production conflicts with negligible-production claim

    Minor

    The paper says long-chain n-3 PUFA production by Cyanobacteria can be assumed negligible, but later says Arthrospira, discussed as a cyanobacterium, can produce DHA at 9% of total fatty acids.

  • Recommended n-6:n-3 ratio conflicts with higher n-3 consumption

    Minor

    Higher n-3 consumption than n-6 would require an n-6:n-3 ratio below 1:1. The stated range, 2:1 to 1:1, instead specifies equal or higher n-6 consumption.

3 of 3

The citation lists haven’t been fetched yet

References 235 · Cited by 214

Research works printed but not linked: 5

  1. Harwood, J.L. (2009). Fatty acid biosynthesis. Plant Lipids: Biology, Utilisation and Manipulation, John Wiley & Sons.
  2. Kainz, M., Brett, M.T., and Arts, M.T. (2009). Biosynthesis of polyunsaturated fatty acids in aquatic ecosystems: General pathways and new direc-tions. Lipids in Aquatic Ecosystems, Springer. · DOI · Paper page
  3. Abdo, 2017, Microalgae Dunaliella salina for Use as Food Supplement to Improve Pasta Quality, Int. J. Pharm. Sci. Rev. Res., 46, 45
  4. 2013, Algae in Food and Feed, Food Feed Res., 11, 21
  5. Beynen, 2019, Microalgae in Petfood, Creat. Companion, 40, 7

Authors
Remize, M., Brunel, Y., Silva, J. L., Berthon, J.-Y., & Filaire, E.
Affiliations
  • GREENSEA, 3 Promenade du Sergent Jean-Louis Navarro, 34140 MÈZE, France
  • ALLMICROALGAE–Natural Products, Avenida 25 Abril, 2445-413 Pataias, Portugal
  • Greentech (France) (FR)
  • Université Clermont Auvergne (FR)
Corresponding author
Filaire, Edith
ORCID
Venue
Marine Drugs
Publisher
MDPI AG
Published
2021-02-18
Volume
19
Issue
2
Pages
113
ISSN
1660-3397 (ISSN-L)
DOI
10.3390/md19020113
PMC
PMC7922858
OpenAlex
W3130888280
Cited by
214
References
235
Citations by year
2026: 41 · 2025: 52 · 2024: 46 · 2023: 35 · 2022: 29 · 2021: 11
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Marine Drugs (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Elon University
Topics
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Algal biology and biofuel production
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
Keywords
omega-3 fatty acids, microalgae, eicosapentaenoic acid, docosahexaenoic acid, microalgae cultivation, seaweed, aquaculture
MeSH terms
Animals, Animal Feed, Docosahexaenoic Acids, Humans, Eicosapentaenoic Acid, Aquaculture, Food Industry, Microalgae

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

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