While we often speak of omega-3s collectively, the 3 key omega-3 fatty acids—ALA, DHA, and EPA—fall under two umbrellas. ALA, the most frequently consumed omega-3 fatty acid, is found in many plants and seed oils. However, DHA and EPA are only produced by marine microalgae. When krill and fish eat these microalgae, the DHA and EPA bioaccumulates in their bodies, meaning it is stored and builds up over time.
Until a few years ago, DHA and EPA could only be sourced from ocean-dwelling oily fish—such as salmon, mackerel, and anchovies—in the form of fish oil, which is used in human nutritional products, aquaculture feeds, and pet foods.
In recent years, the supply of fish for fish oil production has been impacted by global warming and El Niño events, with these challenges compounded by many fish stocks reaching or exceeding maximum harvest capacity. In addition, fish oil yields have been declining. Fish oil yields were 5% by weight a decade ago. More recently, 3% to 4% has been typical. During 2023’s El Niño-impacted anchovy harvest off the coast of Peru, fish oil yields from those catches were 0.45%.
This has pushed industry stakeholders and startups alike in human nutrition and aquaculture to look to novel sources of omega-3s, most notably ocean-harvested krill and microalgae grown in onshore fermentation tanks.
However, both options have limitations. Only so many krill can be pulled out of the ocean without impacting species that feed on them, and krill populations can also be impacted by environmental factors. On the other hand, while on-land microalgae production doesn’t impact marine ecosystems and is resilient against environmental factors, it is costly and slow to scale up. Neither of these alternatives can ensure a supply of DHA and EPA that is sufficient, sustainable, and predictable enough to feed the demands of an omega-3 market that is expected to grow at a CAGR as high as 10%+ over the next decade.
Nuseed and Australian researchers opted to take a plant-based approach to closing the gap in the supply of DHA.
The potential of producing DHA and other omega-3s in seed oil crops has been recognized for more than a quarter century. In the 1990s and 2000s, several attempts were made at introducing genetics into plants to induce them to produce DHA, EPA, and other long-chain polyunsaturated fatty acids (LC-PUFAs). They were successful at doing so, with the caveat that DHA and EPA were only produced in amounts that were too small to be commercially viable.
Beginning in 1997, Australian researchers at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and Grains Research Development Council (GRDC) collaborated to pioneer a process for developing seed oil crops which produced DHA in amounts comparable to those found in fish oils as a proof of concept. After the founding of Nuseed in 2006, Nuseed’s plant geneticists and crop scientists joined the endeavor.
Focusing on DHA was both a lofty goal, and a practical one, as DHA is the longest and most complex of the key omega-3s. A plant that could produce DHA could be modified to produce shorter omega-3s, such as EPA.
The scientists at CSIRO, GRDC and Nuseed aimed to take a seed oil crop which naturally produced oleic acid, linoleic acid, and alpha-linoleic acid, and insert genes which would enable the enzyme production necessary to convert those fatty acids into increasingly longer-chained fatty acids.
For a plant-based source of DHA to make practical sense, it ideally had to satisfy three objectives amongst a longer list of necessities:
- The concentration of DHA had to be comparable to that of fish oil.
- The oil had to have a low ratio of omega-6s to omega-3s, as the ratio of omega-6s to omega-3s in Western diets is already high, and delivering the anti-inflammatory benefits of omega-3s requires a low omega-6 to omega-3 ratio.
- The plant used to produce LC-PUFAs had to be commonly grown throughout the world to mitigate the need for changing agricultural or seed oil production processes.
The production of high levels of LC-PUFAs was first achieved in Arabidopsis thaliana, a plant in the mustard family commonly known as thale cress. A. thaliana is one of the most heavily researched plant species in the world, as it’s small, hardy, easy to cultivate. It also has a small genome, which is why it was the first plant to have its genome fully sequenced. These qualities made it an ideal model organism for demonstrating that LC-PUFAs could be produced in high levels in a genetically modified plant. Ultimately, DHA levels up to 15% were produced in these pioneering efforts using A. thaliana, exceeding the 12% typically found in fish oil.
The next step was to modify a conventional seed oil crop to produce LC-PUFAs.
From the initial test bed of A. thaliana, the scientists at Nuseed, CSIRO, and GRDC shifted their attention to Camelina sativa, commonly known as camelina, which:
- Is an existing seed oil crop,
- Produces high levels (35% to 40%) of ALA, a necessary precursor to DHA and EPA, and,
- Has a low ratio of omega-6s to omega-3s (roughly 1:2).
These qualities made camelina an ideal next step in the process of developing a desirable DHA seed oil. The process that had been pioneered with A. thaliana was applied to C. sativa, with modifications intended to fix bottlenecks identified in the original process.
These efforts resulted in a genetically modified camelina which produced oil that was 12% DHA, comparable to the DHA content of fish oil. This omega-3 camelina oil also contained EPA, DPA, ETA, ETE, and SDA, all omega-3s not found in conventional camelina oil or other seed or plant-derived oils.
This knowledge was then applied to a more difficult, yet more commercially promising challenge—producing a high-DHA canola oil.
Camelina was a useful test case for producing DHA seed oil, and camelina may prove to have applications for commercial production in the near future. However, introducing LC-PUFA-producing modifications into rapeseed, more specifically the commercially developed varieties collectively known as “canola,” was an attractive, shorter-term goal because of the crop’s global distribution.
While rapeseed has been cultivated for several thousand years, its utility in the human diet was limited due to the toxicity of the erucic acid that rapeseed oil contains. Between the 1940s and 1970s, growers and researchers in Canada began to work on developing non-toxic cultivars of rapeseed low in erucic acid. These efforts produced cultivars of Brassica napus, B. rapa, and B. juncea which were suitable for human consumption and collectively dubbed “canola,” for “Canadian oil.”
Today, canola is grown on every inhabited continent on Earth, with the top-producing countries being Canada, China, India, Germany, France, Australia, Russia, and Ukraine. More than 80 million metric tonnes are commercially grown each year, making it the second-largest seed oil crop in the world, second only to soybean.
Canola’s global presence made it an attractive platform for DHA oil production. However, conventional canola posed challenging limitations. While camelina oil is 35% to 40% ALA, canola oil is only 10% ALA, and contains 20% linoleic acid, an omega-6. The omega-6:omega-3 ratio of canola oil is 2:1, the reverse of camelina. Nuseed, CSIRO, and GRDC would have to turn one of the world’s most significant sources of omega-6s into a high-quality source of omega-3 nutrition.
In 2020, researchers at Nuseed and CSIRO collaborated on a paper, “Development of a Brassica napus (Canola) Crop Containing Fish Oil-Like Levels of DHA in the Seed Oil,” describing how they successfully developed a canola variety that produced high levels of omega-3s.
The researchers applied the processes they had utilized with A. thaliana and C. sativa, with improvements derived from the lessons learned along the way. They had realized that when modified plants produced DHA and EPA, such plants favored one of the two over the other. The team opted to focus on the production of DHA for two reasons:
- “Commodity fish oil (e.g., anchovy) contains a higher level of EPA compared to DHA (16–18% vs 12%) so from a purely source-oriented perspective DHA is the rarer molecule.”
- DHA is effectively the last stop on a linear, multi-step journey that involves the synthesis of other omega-3s of interest, such as EPA and DPA. Successfully producing DHA was the most challenging option, and with modifications, any other long-chain omega-3 could be produced as desired.
The researchers collaborating in this effort succeeded, producing Nuseed Total Omega-3 Canola, a canola variety that married the best aspects of canola oil and conventional sources of omega-3. Oil made from this Omega-3 Canola has twice the ALA of conventional canola oil (20% vs. 10%), DHA content of roughly 9% to 14%, and small amounts of EPA, DPA, and other long-chain omega-3s. The omega-6 to omega-3 ratio is about 1:4, compared to the 2:1 of conventional canola oil.
Nuseed Total Omega-3 Canola has been approved for cultivation in Australia, the United States, and Canada, has been shown to be safe for human and animal consumption, and offers complete omega-3 nutrition with the bioavailability of fish oils and algal oils.
Nuseed’s Omega-3 Canola is used to produce Nutriterra® Total Omega-3 Canola oil for use in supplements and conventional foods, and Aquaterra® Advanced Omega-3 Canola oil, which has been used to feed more than 300,000 metric tonnes of fish in Chile, Canada, and the United States.
These are just the first chapters in the story of the development and commercialization of the world’s first plant-based source of complete omega-3 nutrition. We are continuing to innovate and improve upon Total Omega-3 Canola, and to identify new applications and opportunities where it can be an ideal complement to conventional omega-3 sources.