Vegetarian Alternative Shifts Industry Perspective

A SPECIAL ALL-DIGITAL ISSUE

VOLUME 4 ISSUE 2 February 2015

ALGAL-BASED OMEGA-3s Vegetarian Alternative Shifts Industry Perspective

• Ingredient Positioning • Market Overview A SPECIAL ALL-DIGITAL ISSUE Vol. 4, No. 2 February 2015 CONTENTS 5 4 VIEWPOINT ALGAL OMEGA-3S 5 by Gene Bruno, MS, MHS, RH (AHG) Manufacturers and consumers are taking notice of algal oil as the first viable vegetarian long-chain omega-3 alternative. Additional perks include nods to sustainability, bioavailability and clinical efficacy—as well as the absence of environmental contaminants. 12 2015 OUTLOOK: GLOBAL • • MICROALGAE OIL OMEGA-3 MARKET by Christopher Shanahan With continued investment, the growth opportunities in algae abound. However, a few challenges need to be overcome in order to truly contend in the marketplace.

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SupplySide Omega-3 Insights • February 2015 2 omega3insights.com Ask any fish where they get their Omega 3s?

algae algae

algae algae algae

Fish and krill don’t produce Omega-3s, algae does.

Since fish and krill derive their Omega-3s from the algae they eat, Almega PL makes it possible for your consumers to get their Omega-3s first-hand. Almega PL is grown in sunlit ponds, not fished from the sea, and does not endanger delicate marine ecosystems. And, as the only omega-3 containing both phospholipids and glycoplipids, Almega PL is as bioavailable as krill.

For your next Omega-3 product, don’t buy downstream. Go directly to the source for EPA-rich, polar-lipid, sustainably sourced Omega-3s.

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An ingredient from Qualitas Health © 2015 Qualitas Health VIEWPOINT

Exploring Algae

t has been said that the ocean is the source of all life, and certainly it has been a source of life- Igiving nutrients for creatures great and small. And wherever there is water, there is likely algae— plant-like organisms that are distributed worldwide and range from microscopic organisms to large seaweeds. The majority are photosynthetic, taking in carbon dioxide and sunlight, and releasing oxygen. And in addition to their beauty, many are rich sources of nutrients. Their special profile, adaptability and quick reproductive rate have made them a go-to source in different industries, particularly biofuel, but increasingly across the nutrition and pharmaceutical spaces. In the omega-3 industry, interest in algae as a source of long-chain omega-3s has been growing, as the algae sit at a sweet spot in terms of sustainability, adaptability and opportunity. In fact, algae are the source of the omega-3s that accumulate in marine organisms; without them, that fish oil wouldn’t be nearly the rich source it has been. This issue provides an overview of the opportunities around the algal-sourced omega-3 space, as well as the challenges that must be addressed to move it forward. And if you’re looking for more insights on algae and omega-3s, check out our documentary, “Quality, Sustainability Driving the Future of Omega-3s,” as we take a look at how one supplier is exploring new technology and production options. All in all, it may be time to give “pond scum” the respect it deserves.

Best regards,

Heather Granato VP Content, Health & Nutrition Network [email protected]

@heathergranato

SupplySide Omega-3 Insights • February 2015 4 omega3insights.com Algal Omega-3s by Gene Bruno, MS, MHS, RH (AHG)

he importance of omega-3 essential fatty acids (EFAs) to human health is very well established. Specifically, it is the long-chain omega-3s T eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that have been most extensively researched, and the value of which has been definitively demonstrated. For many years, the exclusive supplemental source of EPA and DHA was fish oils. Subsequently, krill oil and then calamari (squid) oil entered the market as additional sources, with various claims of better sustainability, a preferred EPA:DHA ratio and/or improved absorption as compared with fish oil. While flax seed, echium* and walnut oils have also been touted as vegetarian sources of omega-3 EFAs, they provide the shorter-chain alpha-linolenic acid (ALA), not EPA and DHA. As ALA is not always efficiently converted to EPA and DHA, it is not really a viable vegetarian alternative to these other sources of long-chain omega-3s.† With the availability of algae (or algal) oil, it can now be argued that a vegetarian alternative to fish, krill and calamari oils does indeed exist.

Algae as a Source of O3FA As part of the marine food-chain, algae actually serve as the original source of omega-3 fatty acids (O3FA). David Hart, vice president of marketing, Qualitas Health Ltd., said, “We tend to think of fish and krill as being sources of omega-3s, but these marine animals are just bioaccumulators of omega-3s that they get from their diet. Using one of the most primal reactions—photosynthesis— microalgae turn sunlight into omega-3s and other phytonutrients.” As fish and krill consume algae, they obtain omega-3s. Most significantly, the algae provide EPA and DHA.

Commercial sources of algal oil can provide EPA only, DHA only, or both EPA and DHA. Depending upon the supplier, algal oil can provide: EPA 23% to 25% DHA 10% to 35%

* Echium oil does provide the O3FA known as stearidonic acid, but it does not have IN THIS ISSUE the same body of research as EPA and DHA to support its value. Viewpoint p. 4 † That is not to say that ALA has no value. In fact, it is considered to be an essential nutrient and it plays various important roles in human health. However, it doesn’t 2015 Global Outlook p. 12 offer all of the same benefits as EPA and DHA, so therefore it does not function as Table of Contents p. 2 a true alternative to these O3FA.

SupplySide Omega-3 Insights • February 2015 5 omega3insights.com The Vegetarian Choice Previously, vegans had no options if they wanted to supplement their diets with EPA and DHA. They couldn’t use fish oil or krill oil. While flaxseed, echium and walnut oils were available as sources of ALA, there was no guarantee that their bodies would adequately convert the ALA to EPA and DHA. In fact, research on ALA metabolism in healthy young men indicated only approximately 8 percent of dietary ALA was converted to EPA and 4 percent or less was converted to DHA.1 The conversion was better in healthy young women, with about 21 percent of dietary ALA being converted to EPA and 9 percent being converted to DHA.2 Researchers have suggested the better conversion in young women is related to the effects of estrogen;3 4 but, that still means a significant amount of ALA is not converted to EPA and DHA in healthy young women. It also doesn’t account for young women who may not be particularly healthy or older women in any state of health.

The issue of reduced or non-conversion of ALA to EPA/DHA is solved for vegans when they use algal oil because it provides a direct source of EPA and/or DHA.

Even worse, a recent systematic review published in Critical Reviews in Food Science and Nutrition5 reported that data from seven intervention studies found ALA from nut and seed oils was not converted to DHA at all. This issue of reduced or non-conversion of ALA to EPA/DHA is solved for vegans when they use algal oil because it provides a direct source of EPA and/or DHA. This is an enormous advantage, especially if some vegan individuals need the EPA/DHA for therapeutic reasons, and they can’t afford to roll the dice with regard to these O3FA being converted from ALA.

Sustainability, Environmental Positioning Most EPA and DHA for human consumption is sourced from small fatty fish caught in coastal waters. Concerns about depleting these global fish stocks has led to research toward more sustainable sources, including marine microalgae.6 In Current Opinion in Biotechnology, Adarme-Vega et al predicted that, “large- scale cultivation of microalgae and plants is likely to become a reality with expected reductions in production costs, yield increases and the adequate addressing of genetically modified food acceptance issues.”7 Similarly, an article

SupplySide Omega-3 Insights • February 2015 6 omega3insights.com in the journal Marine Drugs8 indicated seafood sources of long-chain omega-3s are being “harvested beyond a sustainable capacity,” stating it is “imperative to develop alternative omega-3 long-chain polyunsaturated fatty acid sources for both EPA and DHA.” Algae oil was identified as the ideal candidate. The fact is, algae-derived oils are easy to grow on a large scale due to their small size. Leslie van der Meulen, general manager at BioProcess Algae, commented, “Algal cultivation, like any other land-based crop, can be scaled and adjusted to market needs and customer demand. Dependent on the method of cultivation—autotrophic (sunlight and carbon dioxide) or heterotrophic (sugar)—volumes of product can be accurately produced year round and volatility-free.” Furthermore, researchers have observed that lipid and protein byproducts during algal growth may be used as biodiesel and biomass for oil sources and animal feed, There is no need respectively.9 Hart summed it up with this statement: to exploit a fragile “The sustainability of algae as a source of omega-3s is marine eco-system pretty obvious—there is no need to exploit a fragile marine eco-system to obtain omega-3s.” to obtain omega-3s. Another potential environmental bonus is lower levels of environmental contaminants. “Just as omega-3s are concentrated in fish tissues as it moves up the food chain, environmental contaminants like heavy metals, dioxins and PCBs are also concentrated,” Hart said. “Algal sources of omega-3s do not have these environmental contaminants.” In fact, a study published in Journal of Agricultural and Food Chemistry 10 found that when analyzed, no heavy metals (such as mercury) were detected in DHA-producing algal biomass.

Efficacy and Availability Because algal oil is the “new kid on the block” with regard to being a supplemental source of long-chain omega-3s, the question arises as to whether its bioavailability is comparable to fish oil and krill oil, the latter of which is touted as having superior bioavailability as compared with fish oil. One recent human clinical study11 compared the bioavailability of krill oil with algal oil (as Almega PL, from Qualitas Health). The study showed there was no statistically significant difference between the bioavailability of algal and krill oils. Another “new kid on the block” question for algal oil is whether it offers clinical effectiveness as a source of long-chain omega-3s—especially where cardiovascular disease (CVD) risk factors are concerned. Again, the answer has been addressed in human studies. In Lipid Research, Jump et al reported that two CVD risk factors, fasting blood triglycerides and small dense low-density

SupplySide Omega-3 Insights • February 2015 7 omega3insights.com lipoprotein (LDL), were reduced in hypertriglyceridemic men consuming 3 g/d of algal-source DHA for 45 days.12 Likewise, a review from American Journal of Therapeutics13 examined data from 16 published clinical trials that tested the effects of algae-derived DHA on serum triglyceride levels and related parameters in normal subjects as well as patients with elevated triglycerides. The results showed that at doses of 1 to 2 g/d, algal-DHA significantly lowered triglyceride levels (up to 26 percent) either alone or in combination with statins— with reductions markedly greater in hypertriglyceridemic than in normal subjects. A similar meta-analysis14 examined the effects of algae-derived DHA on serum triglyceride levels in 485 healthy participants. The results were that a median dose of 1.68 g/d algal-DHA also reduced triglycerides. In addition, a single blind, randomized, placebo-controlled trial15 in 27 postmenopausal vegetarian women found that 2.14 g/d of algal-DHA for 42 days decreased plasma cholesterol levels (P=0.04), but did not influence the levels of plasma triglycerides. Furthermore, a double blind study16 in 24 healthy vegetarian subjects found that 1.62 g/d of algal-DHA lowered total and LDL-cholesterol:high-density lipoprotein (HDL)-cholesterol ratios.

Algal omega-3s especially open up the potential for fortification in functional foods, being in alignment with consumer trends such as vegetarian, “free-from” (i.e., allergen-free, GMO-free, gluten-free, etc.) and kosher.

Because DHA’s role in supporting normal infant brain and eye development is well established,17 18 19 this is another potential benefit of algal-DHA—assuming, of course, that alga-DHA can effectively enrich DHA levels of breast milk for infant consumption. To test this, a study20 was conducted in which breast-feeding mothers were supplemented with 170 to 260 mg/d of algal-DHA. The results were that DHA levels in breast milk increased by 32 to 91 percent, and plasma DHA in nursing infants correspondingly increased by 11 to 42 percent.

Future Possibilities “Algal omega-3s especially open up the potential for fortification in functional foods, being in alignment with consumer trends such as vegetarian, ‘free-from’ (i.e., allergen-free, GMO-free, gluten-free, etc.) and kosher,” Hart said. The food industry has even experimented with the production of healthy, reduced-fat Bologna sausages enriched with DHA from algae oil.21

SupplySide Omega-3 Insights • February 2015 8 omega3insights.com “Algae can be so nutrient-dense that their whole use is justified in many cases, which will lead to new product types and inclusions that we have seen with the likes of kale, Brussels sprouts and other ‘superfoods,’” van der Meulen said. “Their natural cleansing ability and their preference for liquid environments make them a perfect fit for the juice craze that we are witnessing, adding EPA and DHA to the healthy mix.” One potential limitation with algal oils is taste—although this is also a limitation with fish oil and krill. Algal oil has a distinct “ocean taste” that would require other strong-tasting foods to mask it. Of course this would not be an issue if the algal oil were delivered as a softgel, capsule or tablet.

Conclusion Algal oil sources of EPA and DHA provide a viable vegetarian alternative to fish, krill and calamari oils. Unlike flaxseed, echium and walnut oils that are vegetarian but provide ALA, algal oil provides EPA and/or DHA (depending upon the source). This is important because ALA is not always efficiently converted to EPA and DHA. Furthermore, algal oil has the advantage of sustainability and absence of environmental contaminants, while maintaining excellent bioavailability and clinical efficacy. q

Gene Bruno, MS, MHS, RH (AHG) is provost/chief academic officer for Huntington College of Health Sciences. With graduate degrees in both nutrition and herbal medicine, Bruno is a 35-year veteran of the dietary supplement industry.

References

1 Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*. Br J Nutr. 2002;88(4):355-364. 2 Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002;88(4):411-420. 3 Burdge G. Alpha-linolenic acid metabolism in men and women: nutritional and biological implications. Curr Opin Clin Nutr Metab Care. 2004;7(2):137-144. 4 Giltay EJ et al. Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects. Am J Clin Nutr. 2004;80(5):1167-1174. 5 Lane K et al. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Crit Rev Food Sci Nutr. 2014;54(5):572-9. 6 Barber MD. Omega 3 fatty acids and cardiovascular disease: Algae can be source of “fish” oil. BMJ. Feb 14, 2004; 328(7436): 406. 7 Adarme-Vega TC, Thomas-Hall SR, Schenk PM. Towards sustainable sources for omega-3 fatty acids production. Curr Opin Biotechnol. 2014 Apr;26:14-8.

SupplySide Omega-3 Insights • February 2015 9 omega3insights.com 8 Mühlroth A et al. Pathways of lipid metabolism in marine algae, co-expression network, bottlenecks and candidate genes for enhanced production of EPA and DHA in species of Chromista. Mar Drugs. 2013 Nov 22;11(11):4662-97. 9 Lenihan-Geels G, Bishop KS, Ferguson LR. Alternative Sources of Omega-3 Fats: Can We Find a Sustainable Substitute for Fish? Nutrients. 2013;5:1301-1315. 10 Pyle DJ, Garcia RA, Wen Z. Producing docosahexaenoic acid (DHA)-rich algae from biodiesel-derived crude glycerol: effects of impurities on DHA production and algal biomass composition. J Agric Food Chem. 2008 Jun 11;56(11):3933-9. 11 Kagan ML et al. Acute appearance of fatty acids in human plasma--a comparative study between polar-lipid rich oil from the microalgae Nannochloropsis oculata and krill oil in healthy young males. Lipids Health Dis. 2013 Jul 15;12:102. 12 Jump DB, Depner CM, Tripathy S. Omega-3 fatty acid supplementation and cardiovascular disease. J Lipid Res. 2012 Dec;53(12):2525-45. 13 Ryan AS et al. Clinical overview of algal-docosahexaenoic acid: effects on triglyceride levels and other cardiovascular risk factors. Am J Ther. 2009 Mar-Apr;16(2):183-92. 14 Bernstein AM et al. A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease. J Nutr. 2012 Jan;142(1):99-104. 15 Wu WH et al. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr. 2006 Mar;60(3):386-92. 16 Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr. 1996 Dec;126(12):3032-9. 17 Food and Nutrition Board, Institute of Medicine. Dietary Fats: Total Fat and Fatty Acids. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: National Academies Press; 2002:422-541. 18 Hart SL et al. Brief report: newborn behavior differs with decosahexaenoic acid levels in breast milk. J Pediatr Psychol. 2006 Mar;31(2):221-6. 19 Birch EE et al. Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula. Early Hum Dev. 2007 May;83(5):279-84. 20 Jensen CL et al. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. Am J Clin Nutr. 2000 Jan;71(1 Suppl):292S-9S. 21 Berasategi I et al. Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with Melissa officinalis extract. Meat Sci. 2014 Mar;96(3):1185-90.

SupplySide Omega-3 Insights • February 2015 10 omega3insights.com Questions?

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*Includes 2-day Expo Hall (April 8 & 9), Trends In Presentations, Keynote Address, Drinks on Us Reception. 2015 OUTLOOK: Global Microalgae Oil Omega-3 Market Focus on quality attributes beyond omega-3 marketing messages today will drive microalgae company revenue tomorrow by Christopher Shanahan

n 2014, the global market for microalgae-based omega-3 oils was US$375.5 million, corresponding to approximately 7,280 metric tons Iin unit shipment. Globally, the infant formula application represents the most important end application for microalgae omega-3 oils, followed by dietary supplements, food and beverage, and animal feed. Algal oil is an important and potentially disruptive feedstock within the omega-3 polyunsaturated fatty acid (PUFA) ingredients market, but it has yet to break through and dominate the market. The reason is quite simple—for total docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) content value, fish oil and vegetable feedstock remain more cost-effective compared with algae. To become more competitive, there have been signs of softening microalgae omega-3 prices—including a significant jump in microalgae production capacity capabilities across the world—but, absolute levels of microalgae oil production capacity are still not sufficient to address growing demand due to several key technology and business challenges facing this segment, including: • Scalability: Though various algae technologies have been developed across the globe, scalability of these technologies remains one of the biggest challenges in the industry. Today, there is no algae technology available that can produce omega-3 oils at commercial scale and substitute fish oil usage. • Lack of robust, stable cultures: Many algal strains have been developed for the production of various products, but most of these strains are developed in experimental setups IN THIS ISSUE in laboratorial controlled conditions. These strains are not Algal Omega-3s p. 5 very robust and stable in industrial conditions. This imposes Omega-3 Contacts p. 15 a big challenge for the industry and negatively influences the Table of Contents p. 2 commercial adoptability of the algae technologies.

SupplySide Omega-3 Insights • February 2015 12 omega3insights.com • Insufficient overall yield: Although oil yields from algae are significantly higher compared with other available feedstock, the efficiency of the algae system must be further enhanced to meet global demand for EPA/DHA omega-3 and completely substitute fish oils. • Environmental parameters affecting algal growth: Cultivation of algal strains depends on environmental conditions such as temperature. As such, not all algae can be cultivated everywhere in the world under normal environmental conditions. Specific strains for different climates and regions must be identified. • High cost of production: Cost is a major factor influencing the commercial adoptability of any technology. Unfortunately, there are few algae systems in place today through which EPA/DHA omega-3s can be produced in an economical manner. • Need for technology development and funding: To achieve more efficient algae technologies, further technology development is required. Funding support from various authorities and the government is crucial to make this a reality. Also, companies venturing into algae technology must be determined enough to forgo profits for the first few years of operation.

An increased focus on addressing technology and business challenges—and a gradual lowering of average prices—are key to drive growth in the microalgae segment of the omega-3 market.

As a consequence of these key technology and business challenges, the microalgae omega-3 oil subsegment has faced slower than expected market penetration of the food and dietary supplement end applications. However, algae oil suppliers understand that in order to grow market share, price competitiveness is the best option to motivate consumer switching. Based on Frost & Sullivan’s analysis, prices are expected to drop between 1 to 8 percent compound annual growth rate (CAGR), or an average of 4 percent, during the forecast period of 2015 to 2025. Of course, a drop in

SupplySide Omega-3 Insights • February 2015 13 omega3insights.com price will have a positive impact on the demand for microalgae omega-3 oils, and depending on the degree to which microalgae omega-3 suppliers choose to drop prices, the enhancement on unit shipment will vary. In summary, increased focus on addressing these technology and business challenges and a gradual lowering of average prices is key to drive growth in the microalgae segment of the omega-3 market. The total omega-3 market is still growing, but algae producers are looking at other food ingredient spaces to drive additional revenue contribution, including microalgae-sourced astaxanthin for aquaculture or eye health, algae protein ingredients, and other micronutrients. Thus, manufacturers are increasingly reaching a higher level of differentiation by investing more marketing and sales efforts to move microalgae beyond the confined and competitive omega-3 industry. q

Christopher Shanahan is Frost & Sullivan’s global program manager for the Food and Agriculture Practice. He leads a team of analysts who research and analyze market technologies, economics and applications within the food and beverage industry. For more information on the Food and Agriculture practice or the Chemical, Materials and Food research group, contact Ariel Brown, corporate communications, at [email protected] or (210)477-8427.

SupplySide Omega-3 Insights • February 2015 14 omega3insights.com OMEGA-3 CONTACTS supplysideomega3insights.com

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