Heart health. Cognitive health. Joint health. Healthy skin. The list of benefits for omega 3 fatty acids goes on, and the body of science continues to expand rapidly. This sector has the unique distinction of being the most-researched nutraceutical ingredient with more than 20,000 published papers on omega 3s, according to Pubmed. The only substance—nutraceutical or pharmaceutical—we have found that is more widely researched is aspirin (see Figure 1). Yet experts believe the science behind omega 3s is still in its infancy, with more than 150 human clinical trials conducted in the last 12 months alone.
 
On the sales side, the numbers are equally impressive. According to a Frost & Sullivan report commissioned by the Global Organization for EPA and DHA Omega-3s (GOED), the global ingredient market grew to $1.89 billion in 2011, up from $1.68 billion in 2010. Double-digit growth is forecast from 2012 to 2016.
 
There are challenges, of course. The lack of recommended intakes in major countries like the U.S. and Canada still holds the industry back, and ongoing (but mostly unfounded) sustainability concerns and supply challenges will continue to be problematic. Obstacles also pop up in the form of regulatory challenges, lingering quality concerns and lack of education about dosages and benefits; but overall, the segment continues to be a shining star in the nutraceuticals industry.
 
The Regulatory Landscape
 
As with any ingredient that goes into a dietary supplement or functional food product, the regulatory world plays a role in the success of the business. Since 2004, omega 3s have been backed by a qualified health claim in the U.S. that states: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. One serving of [name of the food] provides [x] gram(s) of EPA and DHA omega-3 fatty acids.” Unfortunately, the unwieldy language and qualified nature of the claim does not allow for wide or successful use.
 
GOED believes the science is now in place to support an authorized health claim. In fact, currently the association is in the middle of a plan to “upgrade” it this year through the submission of a health claim petition, which will include an extensive literature review of all the relevant science.  
 
Connected to this effort are plans for a heart disease Article 14—or disease reduction—claim in Europe, which GOED also believes is supported by science. Approval of this claim would require a submission to the European Food Safety Authority (EFSA) and would include proposed claim language, conditions of use and target population. This claim application is also expected to be filed this year.
 
Despite the lack of an Article 14 heart disease claim, there was good news on the European health claim front in the past year. Omega 3s were approved for three Article 14 claims, while approval is pending for three Article 13 claims, which are similar to structure-function claims in the U.S. but require pre-approval.
 
Approved Article 14 claims include:
 
• DHA intake contributes to the normal visual development of infants up to 12 months of age (100 mg/day of DHA);
 
• DHA maternal intake contributes to the normal development of the eye of the fetus and breastfed infants (200 mg/day of DHA in addition to the recommended intake for omega 3 fatty acids for adults, i.e., 250 mg of EPA and DHA);
 
• DHA maternal intake contributes to the normal brain development of the fetus and breastfed infants (200 mg/day of DHA in addition to the recommended intake for omega 3 fatty acids for adults, i.e., 250 mg of EPA and DHA).
 
Article 13 claims, which have received a positive EFSA opinion, but are expected to be officially approved in June, are:
 
• Maintenance of normal cardiac function (250 mg/day of EPA+DHA);
 
• Maintenance of normal brain function (250 mg DHA/1 or more servings);
 
• Maintenance of normal vision (250 mg DHA/1 or more servings).
 
A regulatory challenge to the industry came late last year in the form of proposed legislation from the German government, suggesting that 1500 mg of EPA + DHA omega 3s per day should be the established upper limit. This is despite the fact that  Greenland Eskimos, which have basically no heart disease and live long, healthy lives, eat 13 grams of EPA + DHA daily, and the Norwegian Scientific Committee for Food Safety published a report stating: “Adverse effects of EPA + DHA up to 6.9 g/day could not be identified…” (“Evaluation of negative and positive health effects of n-3 fatty acids as constituents of food supplements and fortified foods,” Opinion of the Steering Committee of the Norwegian Scientific Committee on Food Safety, 28.01.2011; Doc: 08-707-final; ISBN: 978-82-8082-365-6). EFSA has been requested to comment on the safety; comments were due in March.
 
A related conversation centers around the fact that there is no DRI (dietary reference intake) for long-chain omega 3s in the U.S. or Canada, and dosage recommendations vary around the world (see Figure 2). The fact of the matter is that 84,000 heart disease deaths may be prevented annually by increasing EPA and DHA intake to only 250 mg per day (U.S. Centers for Disease Control and Prevention, 2009). However, until a DRI is in place, there is no mechanism to educate the general public about required intake levels.
 
To push the DRI process forward, GOED is undertaking a cost benefit analysis to provide the U.S. government with details on the financial and healthcare benefits of increasing omega 3 intake among Americans.
 
From the Science Side
 
The science on omega 3s continues to evolve and represents a large body of research, much of which is randomized human clinical trials. In 2011, more than 1000 peer-reviewed scientific articles about the benefits of EPA and DHA long-chain omega 3 fatty acids were published, with 165 human (i.e., clinical) studies alone. These studies cover a wide range of health areas, including cardiovascular, respiratory, cognitive, mental, immunity, respiratory and genetic conditions. Here is a sampling of current research in the past year.
 
Cardiovascular Benefits: Research corroborating a cardioprotective benefit for long-chain omega 3s continues to be published at explosive rates. Three articles are mentioned here, but there were many more that could have been included. 
 
1) Mozaffarian D, Lemaitre RN, King IB, Song X, Spiegelman D, Sacks FM, Rimm EB, Siscovick DS (2011). Circulating long-chain omega-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study: a cohort study. Ann Intern Med 155:160-170. In a prospective cohort study of almost 3000 U.S. adults without prevalent heart disease, long-chain omega 3 fatty acid concentrations were shown to be associated with a lower incidence of congestive heart failure, providing additional support to the importance of long-chain omega 3 intake in a healthy population.
 
2) Neubronner J, Schuchardt JP, Kressel G, Merkel M, von Schacky C, Hahn A. Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. Eur J Clin Nutr. 65:247-254. This study demonstrated that both long-chain omega 3 ethyl esters as well as long-chain omega 3 triglycerides increase the Omega-3 Index, which is the level of EPA + DHA in red blood cells. The Omega-3 Index is rapidly emerging as a measure of fatal and non-fatal cardiovascular events. The extensive data collected to date suggest that determination of the Omega-3 Index has a therapeutic benefit in that it allows for the rapid risk classification of individuals’ cardiovascular health.
 
3) Strøm M, Halldorsson TI, Mortensen EL, Torp-Pedersen C, Olsen SF (2011). Fish, n-3 Fatty Acids, and Cardiovascular Diseases in Women of Reproductive Age: A Prospective Study in a Large National Cohort. Hypertension 59:36-43. This study is noteworthy because of the historical underrepresentation of women in cardiovascular research. In this study, women who consumed the lowest amounts of fish and long-chain omega 3 fatty acids had a significantly increased risk of combined cardiovascular events.
 
Mental Health Benefits: While the cardiovascular benefits associated with EPA & DHA are well known, many people are not aware there is high quality research being published on the benefits (both primary and supplemental) of EPA & DHA for mental health. Additionally, according to ClinicalTrials.gov, research subjects are being recruited for new studies on long-chain omega 3s and many different aspects of mental health, including mania, social phobia, major depressive disorder, schizophrenia, post-menopausal depression, bipolar disorder and attention deficit hyperactivity disorder.
 
Data from one of the more noteworthy publications from last year in the area of long-chain omega 3s and mental health suggest that low serum DHA may be a risk factor for suicide in active-duty personnel. According to Capt. Joseph Hibbeln, MD, one of the co-investigators, “The findings add to an extensive body of research that points to a fundamental role for DHA and other omega 3 fatty acids in protecting against mental health problems and suicide risks.” While the results are nothing short of exciting, well-designed intervention trials are necessary in order to evaluate causality. (Lewis MD, Hibbeln JR, Johnson JE, Lin YH, Hyun DY, Loewke JD (2011). Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison. J Clin Psychiatry 72:1585-1590.)
 
Combating the “Negative” Science: While many positive clinical studies were published last year, success seems to invite criticism, and whenever there was a hint that long-chain omega 3s had failed to live up to their expectations, the popular press took the opportunity to embellish the facts. While long-chain omega 3s are not a panacea, the negative coverage is at best unnecessarily inflammatory, and at worst inaccurate and misleading. Following are several articles that required a little attention in order to set the record straight.
 
1) Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King IB, Albanes D, and Kristal AR (2011). Serum phospholipid fatty acids and prostate cancer risk: Results from the Prostate Cancer Prevention Trial. Am J Epidemiol 173:1429-1439. The popular press would have you believe that long-chain omega 3s cause prostate cancer. The reality is that based on the totality of the scientific evidence, the benefits associated with the long-chain omega 3s far outweigh the risks of developing high-grade prostate cancer.
 
2) Roodhart JM, Daenen LG, Stigter EC, Prins HJ, Gerrits J, Houthuijzen JM, Gerritsen MG, Schipper HS, Backer MJ, van Amersfoort M, Vermaat JS, Moerer P, Ishihara K, Kalkhoven E, Beijnen JH, Derksen PW, Medema RH, Martens AC, Brenkman AB, and Voest EE (2011). Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell 20:370-383. The popular press reported that fish oil reduces chemotherapy effectiveness, but GOED believed such reporting was premature. While the preclinical experiments reported in the publication were well designed and executed, the potential applicability of the results to clinical chemotherapy is dependent upon the outcome of additional research. The results can and should be used to design additional studies either to further the development of new chemotherapeutic agents and/or to identify strategies to enhance current chemotherapy effectiveness by decreasing drug resistance.
 
3) Vedtofte MS, Jakobsen MU, Lauritzen L, and Heitmann BL (2011). Dietary alpha–linolenic acid, linoleic acid, and n-3 long-chain PUFA and risk of ischemic heart disease. Am J Clin Nutr 94:1097-1103.  “Study Clouds Picture on Omega-3s and Heart Health” was carried as the headline in multiple articles and it couldn’t have been further from the truth. One study does not negate the demonstrated benefits beginning more than 40 years ago with the seminal investigations of Bang and Dyerberg. There is data for both sexes across a wide range of ages documenting the utility of the long-chain omega 3s in primary prevention of cardiovascular events. In addition, the already substantial list of long-chain omega 3 recommendations from professional organizations and government bodies continues to grow because the science is so compelling.
 
Technology Innovations & Sourcing
 
While it may be science that pushes the industry forward, technological innovations and new raw material sources are also playing a role in the evolution of the category. For three decades, the primary omega 3 product has been an 18:12 product, which represents the concentration of EPA (18%) to DHA (12%) found in the product. Recently, manufacturers have begun to develop higher concentration products that give consumers more EPA and DHA per dose. Consumers have responded in their purchasing decisions, “trading up” to higher end products and showing a deeper understanding of the nuances of the market. Now the market is full of medium-concentrate and high-concentrate products and consumers have a broad choice of EPA/DHA content, product forms and price points.
 
On the supply side, the vast majority of omega 3s are currently harvested from anchovy fisheries, primarily in Peru and Morocco. Yet this is a snapshot of the industry at this moment and will certainly be different 10 or 20 years from now. Additional sources of fish-based supply and choices beyond fish are rapidly becoming market changers. Krill has gained momentum and awareness in the past few years and, in the algal omega 3 market—dominated up to this point by one supplier—several producers are poised to come on-stream with production in the next year or two. The new algal products vary in EPA and DHA content and concentration amounts and will offer different product options for consumers.
 
There is also one omega 3 product on the market derived from yeast, a single cell organism similar to algae. Looking farther down the road, there are several genetically modified, plant-based products in the pipeline, all of which will provide additional sources of material as demand outstrips the sustainable supplies of marine sources.
 
In terms of product form, supplements still dominate the product landscape, but functional food formulations containing omega 3s are also gaining in popularity. Categories like fortified juices and dairy lead the way, but improvements in taste and smell as well as powder technology improvements and enteric coatings are opening up new roads into broader market segments.
 
Game-Changers Issues & Challenges
 
One of the game-changing developments in the omega 3 business is the potential entry of pharmaceutical players into the category. Currently, there are only two approved pharmaceuticals based on omega 3s—Lovaza from Pronova and Epadel sold only in Japan by Mochida Pharmaceutical—but this is expected to change very soon. There are more than 10 pharmaceutical players working in the omega 3 space and at least three or four companies are conducting Phase 2 or Phase 3 clinical trials with omega 3 products for a variety of indications. While Lovaza and Epadel are specifically for people with high triglycerides, additional yet-to-be-approved drugs target other heart conditions such as cholesterol reduction, as well as non-cardiac indications such as rheumatoid arthritis, asthma and ophthalmic conditions.
 
Sustainability and traceability are growing concerns in the omega 3 space, despite the fact this is more an issue of communication than a true environmental challenge. The vast majority of omega 3 manufacturers only work with sustainable sources and their processes are cleaner and more environmentally friendly than ever before. Many are already certified by organizations like the Marine Stewardship Council or Friend of the Sea, and many others are undergoing certification. Yet negative consumer media stories continue to surface and the industry continues to fight an uphill battle to educate media and the public about the situation. GOED has formed a Traceability Working Group to monitor the situation and develop traceability standards to alleviate some of these concerns.
 
Another area to watch is the growing influence of China. With 1.3 billion people and a growing middle class with more disposable income, the country is becoming a powerhouse of omega 3 consumers and manufacturers. The Chinese are interested in raising the quality level of their production and, reportedly, are working actively toward establishing a national recommended intake for EPA and DHA omega 3s.
 
Looking Ahead
 
For the future, expect to see ongoing growth and more and more science to support that growth. New sources of supply are a definite as the popularity of long-chain omega 3s grows and sustainable sources decrease in availability. If and when we get a DRI in the U.S. (and Canada), this will dramatically increase understanding and compliance, as well as improve public health tremendously.
 
Red flags include continued concerns about quality and overfishing as well as sourcing challenges that will surface inevitably as a result of increased omega 3 popularity. Regulatory developments and upper limits are an area of ongoing concern, but overall, the future looks bright for an already-robust business.                 
 
Ellen Schutt is the communications director at the Global Organization for EPA and DHA Omega-3s (GOED), Salt Lake City, UT. She can be reached at 973-983-1830 or ellen@goedomega3.com.