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?

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.

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.

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.