Growing interest in a forgotten long chain omega-3

Alex Byelashov, Director of New Product Development at Omega Protein Corp., discusses the shift in innovation in the omega-3 supplement market, recent advancements in DPA science and NPD

Fish oils offer an incredible platform for product and technological innovations

Omega-3 deficiency is reported to be one of the leading causes of preventable deaths in the US.1 In fact, epidemiologists estimate that 28 million life years are lost annually as a result of ill health, disability or early death from inadequate omega-3 intake.2 Therefore, US guidelines recommend the consumption of fatty fish two to three times per week to supply adequate amounts of omega-3 fatty acids.

However, owing to cost and dietary preferences, this recommended dietary intake is difficult for most consumers to achieve. Therefore, fish oils, which are generally derived from low trophic, sustainable fish populations, are an ideal alternative source of essential omega-3 fatty acids. In addition to being a cost-effective alternative to eating fatty fish, these oils typically have fewer environmental toxins compared with many commercial fish species that are traditionally eaten.

Initially, the omega-3 industry focused on supplying fish oil as an ingredient for food fortification and in supplement form for the purpose of helping consumers to reach their necessary dietary intake levels. However, innovations in the omega-3 industry have begun to shift the supplement market away from using fish oil for general health purposes and, instead, toward condition-specific and life-stage-specific fatty acid product offerings.

Indeed, many supplement producers are now focusing on product innovation, adopting proactive product strategies and differentiation strategies to create a unique omega-3 product, thereby reducing competitive rivalry. One way that supplement producers have begun to differentiate their omega-3 offerings is by capitalising on the value of docosapentaenoic acid (DPA).

DPA value

Currently, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) largely define the value of most natural triglyceride oils in the marketplace, from unrefined bulk oil to soft gel capsules.

Many consumers, largely because of their specific reference in dietary intake recommendations and numerous studies covering their health benefits, recognise EPA and DHA in terms of omega-3s. In contrast, DPA represents only approximately 2% of common fish oils and remains a 'diamond in the rough' from a commercialisation standpoint.

From a simplistic, big-picture perspective, given that approximately one million metric tons per year of fish oil is produced globally, approximately 20,000 tons of largely non-monetised DPA enters the food chain each year without market recognition.

The global value of this untapped resource is hard to quantify; but, under a conservative scenario, assuming that the DPA content is one tenth that of EPA and DHA combined, the value of oil should be approximately 10% higher than its normal selling price. Notably, this estimate does not include other opportunities for DPA, such as purified products for the drug and nutraceutical space.

DPA science

Evidence from mammalian, in vitro, epidemiological and human supplementation studies demonstrates that DPA may be at least as valuable to human health as EPA and DHA.3 In fact, a recent human clinical study reported that a novel investigational drug, MAT9001, containing predominantly EPA and DPA, was significantly more effective than Amarin’s Vascepa, an EPA-only drug.

The effectiveness was based on the drug’s ability to reduce blood triglycerides, very low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and other markers of hypertriglyceridemia, activities that highlight DPA’s potential for the treatment of dyslipidaemia.4

MAT9001 remains the lead product candidate of Matinas BioPharma, a publicly traded clinical stage biopharmaceutical company. The company considers DPA to be a key differentiation driver of the drug, perhaps because of its unique mechanism of action.

Alex Byelashov, PhD, MPH, is the director of new product development at Omega Protein Corp.

Additionally, a recent study by Harvard researchers published in Nature Scientific Reports demonstrated that DPA is converted into unique specialised proresolving lipid mediators that reduce systemic inflammation in humans.5 Inflammation is known to affect lipid metabolism and its association with heart health has long been recognised.6 Previous studies demonstrated that EPA exerts its anti-inflammatory effects indirectly through elongation to DPA. Therefore, DPA has been hypothesized to contribute to the anti-inflammatory effects of EPA.7

Product development

Typically, moderately concentrated omega-3 supplements contain 3–5% DPA, which is often referred to as the 'other' omega-3 on the Supplement Facts panel. However, mounting evidence illustrating the importance of DPA in recent years has prompted a shift wherein an increasing number of supplement manufacturers have begun to identify or specifically highlight DPA on their labels.

One such commercial product, Super DPA Fish Oil from Swanson Health Products, is derived from menhaden oil and contains around 10% DPA. Its market significance and innovation impact was recognised with the 2013 SupplySide Omega-3 Insights Award by Virgo Publishing, a health and nutrition information and distribution network.

Generally, concentrating DPA above 10% would require a significant use of capital-intensive and sophisticated technologies, such as industrial preparative chromatography. As the DPA content of starting materials is relatively low, an industrial installation of the necessary equipment would only make commercial sense if the manufacturers who invested in the equipment could cost-effectively split the pre-concentrated fish oil ethyl esters into ultra-concentrated EPA, DHA and DPA fractions, thereby spreading the costs across all the fractions.

A recent surge in patent applications reveals an increasing interest in DPA on the intellectual property side. In addition, a number of innovative and potentially less capital-intensive enzymatic and chemical processes for fractionation have been published. As a result of these innovations, some manufacturers are now providing concentrated DPA materials to researchers for supplementation trials, which will ultimately promote an increased body of scientific evidence to support DPA’s role in human health.

Summary

DPA is the third most prevalent marine omega-3 after EPA and DHA. Among other biologic functions, DPA serves as a precursor to anti-inflammatory and proresolving mediators. Numerous epidemiological studies have reported that the consumption of DPA and its levels in blood are associated with positive health outcomes. In vitro and in vivo models have further confirmed DPA’s biological role in mammals. A recent human clinical trial reinforced the totality of evidence of DPA’s value to omega-3 manufacturers, suppliers and consumers.

Fish oils contain more than forty fatty acids, all with distinct biological functions. However, 65–80% of a given fish oil, including the DPA component, is typically non-monetised, offering considerable potential in a developing market space. Thus, fish oils represent an incredible platform for technological and product innovations, and DPA could allow companies to surge forward, providing additional health benefits to their customers.

Finally, prescription omega-3s have, historically, had little impact on sales in the supplement market, and omega-3 supplement manufacturers are largely positive about pharmaceutical players promoting beneficial messaging about omega-3 as a category. Although at least three dozen companies are evaluating new omega-3 drugs or drug targets, omega-3 supplements continue to dominate the marketplace. The supplements may provide the same benefits as pharmaceutical omega-3s, but are available at a much lower cost. Therefore, a launch of new DPA drugs would only help to build the market for DPA-containing supplements.

References

1. G. Danaei, et al., 'The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle and Metabolic Risk Factors,' PLoS Med. 6(4): e1000058 (2009).

2. Institute for Health Metrics and Evaluation: http://ihmeuw.org/27t0.

3. O.A. Byelashov, A.J. Sinclair and G. Kaur, 'Dietary sources, Current Intakes and Nutritional Role of Omega-3 Docosapentaenoic Acid,' Lipid Technology 27(4), 79–82 (2015).

4. K.C. Maki, W.F. Keane and G. Bobotas, 'Effects of MAT9001, an Omega-3 Fatty Acid Drug, Compared with Eicosapentaenoic Acid Ethyl Esters, on Triglycerides, Lipoprotein Cholesterol and Related Variables in Hypertriglycemic Subjects,' http://content.stockpr.com/matinasbiopharma/media/e404abd123cfbccc0624879d8d8cef27.pdf (2015, Matinas BioPharma).

5. J. Dalli, R.A. Colas and C.N. Serhan, 'Novel n-3 Immunoresolvents: Structures and Actions,' Sci. Rep. 3, 1940 (2013).

6. J.A. van Diepen, et al., 'Interactions Between Inflammation and Lipid Metabolism: Relevance for Efficacy of Anti-Inflammatory Drugs in the Treatment of Atherosclerosis,' Atherosclerosis 228(2), 306–315 (2013).

7. P.C. Norris and E.A. Dennis, 'Omega-3 Fatty Acids Cause Dramatic Changes in TLR4 and Purinergic Eicosanoid Signaling,' Proceedings of the National Academy of Sciences of the United States of America 109(22), 8517–8522 (2012).

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