Can oils derived from genetically-modified plants replace fish oil as a source of long chain n-3 polyunsaturated fatty acids in the human diet?

Lead Research Organisation: University of Southampton
Department Name: Human Development and Health

Abstract

Omega-3 fats called EPA and DHA are known to be beneficial to human health. They lower the chance of getting heart disease and can control the symptoms of conditions that involve inflammation such as arthritis. The main food source of EPA and DHA is fatty fish like salmon and sardines. EPA and DHA are also found in fish oil supplements. The UK government recommends that people consume EPA and DHA regularly in order to stay healthy, particularly during ageing. However, many people do not follow these recommendations, partly because they do not like to eat fatty fish or find it too expensive. Also, there are not enough fish in in the sea to provide everyone in the world with enough EPA and DHA to stay healthy, and fish stocks are declining. Therefore, there is a need to find a sustainable source of EPA and DHA that can be increased in order to meet the need for these healthy fats.

Research sponsored by the BBSRC has led to the development of plants that can make EPA and DHA. This has been achieved by inserting the genes needed for making EPA and DHA into plants that do not normally have those genes. The oil produced in the seeds of these so-called transgenic plants contains similar amounts of EPA and DHA to fish oils. Therefore, it is possible that this seed oil could be used to replace fatty fish and fish oil supplements as a sustainable and inexpensive source of EPA and DHA. However, the structure of the oil produced by the plants is different from that of fish oils, and it is not known whether this difference would result in the plant oil being a better or worse source of EPA and DHA for people. It is important to know this, because if the plant oil was less effective than fish oil in increasing the amount of EPA and DHA in people's blood and tissues, and in benefiting health, then it may be less attractive as a source of EPA and DHA in the diet.

This project will determine whether the plant oil is as effective as fish oil in changing the amounts of EPA and DHA in the blood and in modifying some processes that are related to health. In the latter regard, we plan to study the concentrations of fats like cholesterol in the blood and the ability of immune cells taken from the blood to respond when stimulated in the laboratory. We will address our aims in two ways. First, we will recruit healthy men and women in two age groups (18 to 30 years or 50 to 65 years) to take part in a study that involves consuming a single meal containing either fish oil or new plant oil. We will then take a series of blood samples over the following 8 hours. This will allow us to assess whether EPA and DHA derived from the plant oil are absorbed as efficiently by the gut as when they are provided as fish oil. We will also compare the effect of the two oils on the levels of fat and on substances involved in immune function in blood. Second, we will recruit another group of healthy volunteers as above, and provide them with fish oil or plant oil as a dietary supplement to take over 8 weeks. We will take blood samples after 4 and 8 weeks and compare the effect of the different oils on the levels of EPA and DHA in blood and in blood cells. We will also compare the effect of these oils on immune function, the levels of fat in blood, and on the activity of genes in white blood cells. The findings will show whether the plant oil is as effective as fish oil in raising the levels of EPA and DHA in blood and in changing immune function.

We expect that the findings of this project will provide strong evidence for or against using the plant oil as a replacement for fish oil. Furthermore, these results will contribute to the continuing debate about the introduction of transgenic crops into agricultural practice. Ultimately, we hope that a positive outcome will lead to the use of the plant oil as a major source of EPA and DHA in the UK diet as this would have important positive implications for marine ecology and for health of the UK population.

Technical Summary

Omega-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), obtained from oily fish have established health benefits. Marine fish stocks cannot meet increasing global demands for EPA and DHA. Transgenic plant oils (TPO) enriched in EPA+DHA are a potential sustainable and scaleable alternative to oily fish. However, their effectiveness as a replacement for oily fish and fish oil (FO) supplements has not been tested in humans. The project will determine the bioavailability and effect on health-related outcomes of EPA and DHA provided as TPO compared to FO. The project comprises two human studies.

Study 1: Do differences in positional isomerisation of EPA and DHA in TPO and FO affect their acute relative bioavailability? Men and women aged 18 to 30 years or 50 to 65 years (n=10/group) will take part in a randomised, double blind, crossover (RDBC) 8 hour postprandial study. They will consume EPA+DHA (450 mg) as TPO or FO. The primary outcomes will be plasma EPA+DHA, inflammatory cytokine concentrations, and lipoprotein size and concentration during the 8 hour postprandial period.

Study 2: Characterisation of the longer-term accumulation of EPA+DHA. Men and women as above will take part in a RDBC supplementation study. Subjects will take EPA+DHA (450 mg/day) as either TPO or FO for 8 weeks, and then take the other oil after 6 weeks washout. Blood samples will be collected at the start and end of each period. The primary outcomes will be EPA+DHA concentrations in blood, leukocytes and erythrocytes, lipoprotein size and concentration, plasma inflammatory cytokine concentrations, leukocyte activation in vitro and expression of the T cell transcriptome.

This project will provide robust information that will inform government policy on transgenic crops and on the marine environment, and will have important implications for the dietary supplement and pharmaceutical industries, and for UK nutritional recommendations.

Planned Impact

The findings of this project will have important implications for capacity to meet national and global recommendations for consumption of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenic acid (DHA), in order to deliver the health benefits that are associated with these fatty acids. Thus, this project will benefit stakeholders and interested groups in both the public and commercial sectors.
UK Government: The UK government has made recommendations for oily fish consumption in order to ensure adequate EPA and DHA intake by the general population. Currently these recommendations cannot be met because the fish stocks on which supply of EPA and DHA depends are declining and so supply of these fatty acids is unsustainable. Furthermore, consumption of oily fish in the UK is relatively low. This project will deliver key evidence as to whether transgenic technology in which the UK government has invested can provide adequate EPA and DHA for the UK population in a form that is sustainable, scalable and overcomes the concerns about palatability that limit consumption of oily fish. This project will also inform debate about the use of GM crops and hence be of importance to policy makers both within the UK and the European Union.
Biotechnology Industry: Plant biotechnology has transformed agriculture across the globe, and currently 17% of the total annual harvest is GM. However, there is a strong need for new traits which have a consumer-benefit, both in terms of public acceptance and also fiscal value. This novel omega-3 trait represents the vanguard of such second-generation GM crops, and will reinvigorate the entire sector.
Pharmaceutical Industry: The pharmaceutical industry is the major growth sector for the use of fish oil products. The availability of EPA+DHA-based pharmaceuticals is likely to become limited as fish stock decline. Demonstration that oil from transgenic plants can replace fish oil can provide an alternative, sustainable source of EPA+DHA to fish will facilitate the continued use and development of omega-3-based pharmaceuticals.
Dietary Supplements Industry: Omega-3 containing dietary supplements are widely used (annual UK sales of over £110 million) but the industry relies largely upon the diminishing supply of fish-derived oils. The availability of EPA+DHA-containing oils of plant origin that have demonstrated ability to increase omega-3 status in humans will provide an alternative, sustainable source of EPA+DHA to fish which will assure the continued supply of omega-3-based supplements.
UK economy: The findings of this project are likely to benefit the UK economy through positive impacts on the key industries listed above. Such benefits are likely to be sustainable and will place the UK in a globally advantageous position by being first to show that EPA+DHA from transgenic plants can replace fish oil in the human diet. Production of this transgenic oil on a commercial scale will also generate employment for the UK workforce.
UK Population: Chronic disease is major challenge to healthily ageing, in particular conditions associated with inflammation as well as cardiovascular disease. EPA and DHA have been shown consistently to ameliorate such conditions and so are potentially important in promoting health during ageing. However, perceived unpalatability and cost limit EPA and DHA consumption and so constrain their use to promote healthy ageing. Transgenic plant oil containing EPA and DHA is not associated with the palatability concerns attributed to oily fish and, if produced in sufficient quantities, is likely to be a cheaper source of EPA+DHA than fish oil. Thus if this project shows that EPA+DHA-containing transgenic oil is at least as effective as fish oil in raising EPA and DHA status and in changing markers associated with cardiovascular inflammatory disease, then it is likely to be a more acceptable means of improving the health of the UK population.

Publications

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Description Omega-3 polyunsaturated fatty acids, termed EPA and DHA, found in oily fish are important for health. However, consumption of fish sources of EPA and DHA in the UK are below recommenced levels, primarily because of dietary choices, and global provision of these fats by marine fish stocks is unsustainable. The purpose of this project was to test whether an oil that contains EPA and DHA from a genetically modified can replace fish sources of EPA and DHA in the human diet. The findings of the first part of this project show that uptake of EPA and DHA from a meal when provided as genetically modified plant oil was indistinguishable from that when consumed as fish oil. There were no differences between men and women or between young and middle aged participants, and no adverse effects of the genetically modified oil were reported. A second study compared the effectiveness of dietary supplementation with the genetically modified oil to those of fish oil on EPA and DHA status and on immune function. Ths findings showed that consuming the genetically modified oil for eight weeks increased the EPA and DHA concentrations to the same extent to fish oil. Again, there was no reported adverse effects of consuming the genetically modified oil. Together the findings of the project strongly support the suggestion that an oil from a genetically modified plant that contains EPA and DHA could replace oily fish as a sustainable and scabable source of these fatty acids in humans.
Exploitation Route These findings have implications for ensuring adequate nutrition of people in the UK as the genetically modified oil does not incur concerns about palatability, consumption of animal-derived products or environmental pollutants and environmental sustainability associated with oils form marine fish. Consequently, there are potential opportunities for the development of developing functional or fortified foods. There are also potential opportunities for the dietary supplements industry. Similarly, because of the reduced processing, there is potential for the transgenic oil being a more economical and sustainable source of EPA and DHA for the production of omega-3 pharmaceuticals. Importantly, current EU legislation notwithstanding, the genetically modified plant represents an internationally unique crop and thus is a globally unique opportunity for UK agriculture.
Sectors Agriculture, Food and Drink,Environment,Manufacturing, including Industrial Biotechology

 
Description A poster presentation at an international conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This output was a poster entitled' Similar postprandial incorporation of eicosapentaenoic and docosahexaenoic acid from fish oil and genetically modified Camelina oil into plasma lipids in young women' that was presented at the 13th Conference of the International Society for the study of fatty acids and lipids, 27-31st May 2018, Las Vegas, USA. The aim of the presentation was to share the preliminary findings of the project with the international fatty acid nutrition community and with commercial organisations that produce Omega-3 polyunsaturated fatty acid products (primarily food and dietary supplements industries).
Year(s) Of Engagement Activity 2018
URL https://www.issfalcongress.com/s/ISSFAL_AbstractsPosters_5-22-18.xlsx
 
Description An article in a community magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact An article describing the purpose and outcomes of the project written by the project team was published in a community magazine which is delivered to 3200 households, Valley Park Voice' in April 2019. This accompanied an advertisement for volunteers to participate in the project.
Year(s) Of Engagement Activity 2019
URL https://valleyparkcommunitycentre.wordpress.com/valley-park-voice/
 
Description European Federation for the Science and Technology of Lipids 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The activity was an oral presentation entitled "Postprandial incorporation of eicosapentaenoic acid and docosahexaenoic acid from transgenic Camelina sativa oil into blood lipid is equivalent to fish oil in healthy humans" delivered by Dr Annette West (PDRA). The audience was a mixture of international academics and representatives of the food oil industry.
Year(s) Of Engagement Activity 2019
URL http://www.eurofedlipid.org/pages/sevilla.html
 
Description Faculty open day for A level students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The activity was an faculty open day aimed at introducing university biomedical research to 16 - 18 year old students. The project team, represented by Dr Annette West (PDRA) mentored small groups of students during the day engaging with them in discussions about the project
Year(s) Of Engagement Activity 2019
 
Description New Forest & Hampshire County Show 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The activity was part of a University of Southampton/Wessex Medical Research outreach activity to the public at the New Forest show. The activity was based on exhibits from a range of research groups in a tent which the public explored. One member of the research team activity engaged members of the public to explain the purpose of the present project and handed out a Newsletter.
Year(s) Of Engagement Activity 2018
 
Description Panel discussion at symposium for policy makers and industry leaders in UK agriculture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact An ad hoc contribution to a panel-led discussion on the potential for use of genetically modified crops as an innovation in British agriculture at the Westminster Food & Nutrition Forum Keynote Seminar 'The future of science and innovation in UK agriculture - agri-tech, data and increasing productivity' 5th December 2018. The purpose of the contribution was to inform the debate by providing evidence from this project of the efficacy of a product from a transgenic plant as a means of addressing global nutritional and environmental challenges, and to explain the potential for a world leading opportunity for UK agriculture if it became possible to grow the transgenic crop commercially. The discussion is captured in the published transcript of the meeting which also contains a synopsis of the project.
Year(s) Of Engagement Activity 2018
URL http://www.westminsterforumprojects.co.uk/publication/science-and-innovation-in-UK-agriculture-18
 
Description Poster presentation at a STEM event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact A poster presentation entitled 'Genetically modified Camelina sativa oil would make a good alternative source of omega-3 polyunsaturated fatty acids compared to fish oil: a human postprandial meal study' as part of a competition for early-career researchers at STEM for Britain 2019, 13th March 2019, House of Commons, London, UK. The purpose of the presentation was to bring the initial findings of this project to the attention of MP and other policy makers.
Year(s) Of Engagement Activity 2019
URL http://www.stemforbritain.org.uk/
 
Description Presentation at a food manufacturer symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A Keynote talk entitled 'Fatty acids and and epigenetics: A new approach to improving health?' was presented at the BASF "Beyond Basic Nutrition - For Today and Tomorrow' symposium 9th October 2018, Singapore. The audience included senior staff from BASF and from several food manufacturers and academics. The purpose of the talk, which was accompanied by distribution of a project progress newsletter was to raise awareness of the initial findings of the project in the food industry.
Year(s) Of Engagement Activity 2018
 
Description STEM for Britain (Early career researcher event at the House of Commons, Westminster) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact After taking part in a competitive process, Dr Annette West (PDRA) was selcted to present a poster on the project and to take part on dicussions with MPs and other delegates.
Year(s) Of Engagement Activity 2019
 
Description Transgenic oil Facebook page 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The purpose of the Facebook page is to foster awareness among the general public of the nature and outcomes of the project. The page currently has ten followers and has generated a number of questions and queries.
Year(s) Of Engagement Activity 2017,2018,2019,2020