Fish Out Of Water

HEART DISEASE. Macular degeneration. Neuropathy. Rheumatoid arthritis. It's hard to find an illness or syndrome that doesn't claim some relief from omega-3 fatty acid supplements. Given their ability to lower triglyceride levels and blood pressure, reduce the risk for heart attack, and possibly decrease inflammation, "omega-3 fatty acids" have become some of the most popular medical buzzwords.

Fatty fish, such as salmon and albacore tuna, are considered the optimal dietary source of these "heart healthy" omega-3s. But most Americans don't eat nearly the amount recommended by the American Heart Association. For a person without any coronary heart disease, the association recommends two servings of fatty fish each week, or 4 to 6 g of omega-3s. To meet these levels, Americans would have to quadruple their fish intake. This has caused many people to turn instead to fish oil nutritional supplements to boost their intake of omega-3 fatty acids.

As demand for omega-3-rich fish oil supplements continues to increase, wild salmon populations—the primary source of this precious oil—are plunging as a result of overfishing, disease, and pollution (C&EN, June 16, page 14). Because of the limited supply and increasing demand, economists fear a dramatic rise in the price of omega-3-rich fish oil supplements. So some scientists have begun to wonder: Is it possible to get the benefits of fish oil without any fish?

In fact, fish don't make these omega-3 fatty acids themselves; the compounds come from the algae the fish consume. Armed with that knowledge, scientists have begun to transplant into plants the genes that allow algae to synthesize omega-3 fatty acids. Oceans can't support our current level of fish consumption, so land-based plants may be more sustainable sources of these valuable fatty acids.

Omega-3 fatty acids are a class of polyunsaturated fatty acids in which the first double bond is located at the third carbon from the methyl group at the end of the carbon chain. Because humans cannot synthesize omega-3s from scratch and they are needed nutritionally, they are classified as essential fatty acids.

The core omega-3 fatty acid for humans—and the one most frequently consumed in the average American diet—is α-linolenic acid (ALA), which contains 18 carbons and three double bonds. Many plant oils, such as canola, soybean, and flaxseed, contain large quantities of ALA. Our bodies can make a variety of other longer chain omega-3 fatty acids from ALA on a limited basis through condensation reactions via an acetyl-coenzyme A intermediate.

Longer chain omega-3 fatty acids include eicosapentaenoic acid (EPA; 20 carbons and five double bonds) and docosahexaenoic acid (DHA; 22 carbons and six double bonds). Although both EPA and DHA have received the moniker "heart healthy," the majority of health benefits appear to come from DHA. Both of these fatty acids are only found naturally in fatty fish and the algae they consume.

RESEARCHERS AT Dow AgroSciences, in collaboration with Martek Biosciences, have turned to algae as a potential new source of EPA and DHA for the human diet. Rather than extracting the EPA and DHA from the algae to make supplements, researchers at Dow have inserted the algae genes required to make DHA into canola seeds. The enzymes these algae genes produce allow the canola plant to synthesize DHA from arachidonic acid via a condensation-desaturation pathway. Such plants produce canola oil that is enriched with DHA.

David Dzisiak, commercial leader in oils at Dow AgroSciences, says that his company ultimately chose to focus solely on DHA because the compound provides so many health benefits to consumers. "The best thing is to make the component of omega-3 fatty acids that is most beneficial," he says.

Besides their strong odor, omega-3 fatty acids such as DHA are very unstable and oxidize rapidly because they contain a large number of carbon atoms and double bonds. To prevent oxidation, these compounds must be kept away from light, heat, and oxygen. By combining reactive DHA with more stable canola oil, researchers at Dow AgroSciences hope to combine the best of both products to create an affordable, shelf-stable product for use throughout the food industry.

Monsanto is taking a slightly different approach to creating a plant-based substitute for marine-based omega-3 fatty acids. Rather than enriching plant oil with EPA or DHA, researchers at Monsanto genetically engineered a soybean plant enriched in stearidonic acid (SDA). SDA is a short-chain omega-3 fatty acid, one humans can use as a precursor to make longer chain omega-3 fatty acids such as EPA and DHA. Researchers at Monsanto searched their proprietary library of plant and fungal genes and found two that code for enzymes that enable soybeans to produce SDA. Ernie Sanders, director of the omega-3 collaboration at Monsanto, says the company decided to target SDA because it is "more stable than fish oil and has an excellent taste profile."

FOR MONSANTO, soybean plants were an obvious choice for enrichment. Besides being one of the three major plants in the company's portfolio (the others are corn and cotton), soybeans are one-fifth oil—an oil that borders on ubiquitous in foods on supermarket shelves. By working with Solae Co.—an alliance between DuPont and Bunge Ltd.???Monsanto hopes to put the SDA—enriched soybean oil in items such as salad dressings, yogurt smoothies, and granola bars.

But look on any supermarket shelf and you may already find products enriched in omega-3 fatty acids (C&EN, July 28, page 30). Although products from the Dow and Monsanto ventures aren't likely to appear in stores for several years, Martek Biosciences has developed a DHA additive that's already used in foods from infant formula to Crisco.

Martek isolates DHA from two species of microalgae that produce very large amounts of the fatty acid. Scientists grow them in large vats, using a fermentation process similar to beer-making. After fermentation, the oil is extracted. "What we end up with is a very highly concentrated omega-3 vegetarian oil," says Joseph Pfeifer, associate director of fermentation sciences at Martek.

Although this oil can be added to foods directly, Martek has engineered a microencapsulated DHA compound that protects the DHA from oxidation and degradation. Using a proprietary process, scientists at Martek suspend the DHA in a matrix. The final product, a powder that is dry to the touch, can be added directly to food during processing.

With all of the engineering and processing that goes into producing these plant-based sources of omega-3 fatty acids, it might seem like it would be easier to synthesize them in the lab. Not so, says Ruben Abril, director of ingredient formulation and technical support at Martek. Synthesizing these fatty acids from scratch is possible, he says, but to make a long-chain fatty acid with double bonds in specific positions would be "extremely expensive and inefficient."

That leaves researchers to rely on Mother Nature for omega-3s. Whether from canola, soybeans, or microalgae, the distance between salmon and their heart-healthy omega-3 fatty acids is likely to only get larger.