NBT Jan 2012

www.nutraceuticalmag.com

Volume 8 Number 1 January/February 2012

BONE & JOINT HEALTH Walking on eggshells A holistic approach

NATURAL SWEETENERS Welcoming a new era A sweet escape

ESSENTIAL FATTY ACIDS Taking the flax Protecting the platform

EXAMINING ECHINACEA FROM FARMER TO PHARMA

• ingredients • functional foods • nutraceuticals • supplements • raw materials •

Volume8 Issue1

contents

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January/February2012Contents

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18

22 20

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Guest Editorial

04 Nutraceuticals: How Pharma Can Get a Share of the Market Leonard M. Fuld

News

06 The Latest News and Updates

GOED Report

10 Oxidation of EPA and DHA Oils: The Controversy Continues

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30

Adam Ismail and Harry Rice

32 Building Bones Stronger, for Longer

Herbals and Botanicals

36 A Holistic Approach to Joint Health

12 Examining Echinacea Part I Dr Nancy J. Szabo

Essential Fatty Acids 18 The Alpha to Omega of Krill Henrik Traaholt

20 Protecting the Platform Dr Kevin Robinson with Dr Wael Massrieh

21 Taking the Flax Eric Bochardt

Natural Sweeteners 24 A Sweet Escape Rony Van Den Abbeele

28 Welcoming a New Era Henry Hussel

Kimberly J. Dekker

Dr Joosang Park

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40 Bone Boom Lu Ann Williams

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42 A Joint Effort Charlotte Frederiksen

Weight Management 44 Intuitive Nutrition Vladimir Shkolnikov

Industry Issues 46 Without a Safety Net George Pontiakos

Last Word

48 From Farmer to Pharma Tim Jones and Caroline Dewing

Bone and Joint Health Regulatory Review 30 Walking on Eggshells

50 Finding the Needle in the Haystack

Heather Thompson

Dr Cheri Turman

January/February 2012 www.nutraceuticalmag.com

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guest editorial

Nutraceuticals

How Pharma Can Get a Share of the Market … and Avoid Being Blindsided by CPGs

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he pharmaceutical industry is in danger of ceding the large and growing nutraceutical market to the consumer packaged goods (CPG) companies. Thus predicts The Battle for Designer Foods, a public war game in which four teams from top business schools were tasked with stress-testing the nutraceutical strategies of Abbott Labs, Danone, GlaxoSmithKline and Nestlé.

The global market for nutraceuticals — foods that, owing to addition or enhancement, provide health benefits beyond nutrition — is projected to be close to $250 billion by 2015, according to a report from Global Industry Analysts. The change in landscape that appears to signal the end of the era of the blockbuster drug and bring pharmaceutical companies face to face with expiring patents and slim pipelines means that the nutraceutical market could provide an alternative revenue stream — and a welcome one at that. Rather than posing the question of “can pharma compete here?” companies should instead ask what changes should be implemented by pharma to compete, and refuse to allow the obvious advantages of CPGs — such as strong track records in marketing foods directly to consumers — and the inherent obstacles of pharma companies — particularly a risk-averse culture borne of strict US Food and Drug Administration (FDA) regulations — to prevent them from carving out a piece of this market.

This is not to overlook the challenge that pharmaceutical companies must overcome to succeed; strict FDA regulations prevent them from simply putting their drugs into consumer products (although nutraceuticals are regulated by the FDA, they are subject to different restrictions). Their traditional route to success, which encompasses a high reliance on science, clinical trials, the protection of intellectual property and reaping the benefits of years of patent protection, may have to be upended if pharma is to succeed in the adjacent nutraceutical market. This hesitancy could well be a classic case of what Clay Christensen describes as The Innovator’s Dilemma, in which the high revenue-and-returns bar set by large companies, and their reluctance to accept anything less, hinders innovation — pharma companies are accustomed to much higher product margins than packaged food companies. Having invested billions in researching drugs that treat or prevent diseases, will pharma companies be satisfied with something as apparently simple and relatively low-margin as probiotic yoghurts, scientifically engineered nutritional drinks or even heart-healthy breakfast spreads?

Solutions of this kind, promising profits that exceed typical packaged food products, are part of what makes the opportunity so appealing for the CPGs, who boast great expertise in creating and marketing mainstream products in addition to some experience in doing the same with less sophisticated enhanced food products, such as vitamin water.

Food giants are beginning to make significant investment in this space; October 2010 saw Nestlé announce its planned investment of more than half a billion dollars in creating a standalone health science business to pioneer a new industry between food and pharma.

www.nutraceuticalmag.com January/February 2012

Similarly, Danone has refocused its portfolio on nutrition during the last decade, a key example of which is its $17 billion purchase of Royal Numico, a leader in infant and clinical nutrition products. This deal, along with its blockbuster Activia probiotic yoghurt, provides Danone with a stronghold in the area of health and nutrition. The bottom line is that to compete successfully, it will be necessary for pharmaceutical companies to start thinking and acting like CPGs. The recent war game exercise gave rise to some specific strategies that the pharmas can usefully employ.

Lose the Blockbuster Mentality The extensive — and expensive — research, clinical trials and formulation required to obtain FDA approval for drugs have paid off for the pharmaceutical companies in the form of patent protection, IP and a ready made distribution network of hospitals, doctors, formularies and insurance systems. This has contributed greatly to the mentality of relying on blockbuster drugs. Instead of looking for blockbuster-equivalent nutraceutical products, the pharmaceutical companies should consider taking smaller, measured steps and building a portfolio of products that incorporate ingredients already approved by the FDA for use in foods such as fish oils, sterols and stanols.

Make the Public Health Case High cholesterol, diabetes, obesity and heart disease are among the most serious and prevalent health risks in the developed world — and are all conditions that can be affected by nutraceuticals. Making the public health case is about solving a problem that already exists with proven ingredients that don’t need drug-level approval.

Experiment Outside the Lab Pharmaceutical companies are accustomed to basing their experimentation in the lab; indeed, it is at the very heart of what they do. There is, however, an overarching need for this zeal to be redirected toward the marketplace; companies must be willing to trial different enhanced-food products, establish what customers will buy and realize that testing a food that may bomb with consumers in one version and moderately succeed in another is not the same as putting out a drug that is found to have severe sideeffects. The consumer marketplace for nutraceuticals may offer a different risk-reward equation when testing for a winning product. Food companies recognize this distinction and are constantly tinkering with packaging, ingredients and brand extensions — although this is not always successful (new Coke, anyone?). It is this flexibility and willingness to fail occasionally that constitutes a part of their success.

Educate Consumers Despite marketing directly to consumers, pharmaceutical companies lack expertise in creating and exploiting a broad, populist market need.

guest editorial

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Volume 8 Issue 1 January/February 2012 ISSN 1745-8307

Contributors

The key will be in raising consumer awareness about the efficacy of non-medicinal products to manage certain health conditions, conditions for which, in many cases, they are already deeply involved in treating or preventing. The nutraceutical product simply provides another approach to addressing the same problem.

Be Willing to Collaborate Although mergers will increase (Pfizer has recently announced its willingness to sell a portion of its nutrition business), collaborations with CPGs will likely be a key basis for success. This is also an area in which pharmaceutical companies tend to be wary, afraid that the marketing, packaging expertise and distribution channels of CPGs will put them at a disadvantage in any deal. In the short-term, however, collaboration may be the easiest and quickest way for them to enter the market.

All this should not suggest that the barriers to entry and potential success are too high for pharmaceutical companies — they may be better equipped than CPGs to endure the costly and time consuming R&D required for more sophisticated products that the market may eventually call for. There have been some limited Big Pharma success stories; Abbott Labs is a leader in both child and adult nutraceuticals with its high science Pedialyte and Ensure products. GSK Consumer Healthcare has successfully launched several of its nutritional beverage products in China and India, the revenue growth from which could motivate the company to take a more aggressive approach with these products in other markets, such as the US. The size of the opportunity presented by this sector and their need for fresh revenue streams are pressing reasons for pharmaceutical companies to assert themselves in the market. It is in collaboration that their best hope for success lies — borrowing strategy, and perhaps even talent, from the CPGs. A shift in attitude will also be needed; the risks may be greater, but so may the rewards. To ignore the potential of this market would be a mistake for an industry that can no longer rely on its former business model as its only means of success.

On 30 April 2012, this war game will be acted out in the UK between top business students from Oxford and Cambridge. It will take place at Said Business School, University of Oxford, where students from Cambridge Judge Business School, University of Cambridge, will compete for the prize. It will be interesting to compare the predictions made in the US in April 2011 with those resulting from this game.

For more information Leonard M. Fuld CEO Fuld & Company (www.fuld.com) To see excerpts of the Fuld & Company The Battle for Designer Foods war game, please visit www.fuld.com/Services/WarGames.html.

Editorial Director

General Manager

Kevin Robinson +44 (0) 1392 202 591 kevin.robinson@via-medialtd.com

Miranda Docherty +44 (0) 1372 364 122 miranda.docherty@via-medialtd.com

Assistant Editor

Sales

Charlotte Hodgson +44 (0) 1372 364 130 charlotte.hodgson@via-medialtd.com

Gill Healy +44 (0) 1372 364 128 gill.healy@via-medialtd.com

Art Director/Production

Financial Officer

Paul Andrews +44 (0) 1372 364 126 paul.andrews@via-medialtd.com

Cherelle Saunders +44 (0) 1372 364 123 cherelle.saunders@via-medialtd.com

Web Design/Marketing Claire Day +44 (0) 1372 364 129 claire.day@via-medialtd.com

Editorial Advisory Board Susanne Fässler Marketing Communication Manager Frutarom Switzerland Ltd Jörg Grünwald President Analyze & Realize ag Dr Michelle H. Jones Manager, Regulatory and Scientific Affairs Archer Daniels Midland Company John Kurstjens Marketing Manager Lipid Nutrition Chris Lee Event Director IIR Exhibitions Ulla Freitas Manager Scientific Affairs, Nutrition Lonza AG

Theodor Graser Head Pharma Industry DSM Nutritional Products Ltd Denzil Phillips Founder Denzil Phillips International Pedro Vieira Marketing Manager Kemin Health Europe Robin Ward Managing Director Excelsa Pharmaceuticals Sagl John Wilkinson Consultant Phytochemist and Director Herbal Sciences Int. Ltd Dr Paul Berryman Chief Executive Leatherhead Food International Norbert Weitkemper Managing Director Vital Solutions GmbH

To subscribe Professionals working within the industries we cover may purchase a year’s subscription by sending a cheque for £100.00 made payable to Via Media UK Ltd, Wesley House, Bull Hill, Leatherhead, Surrey, KT22 7AH No part of this magazine may be reproduced, stored in a retrieval system or transmitted in any form without permission.

Copyright © 2012, Via Media UK Ltd. All Rights Reserved The publisher endeavours to collect and include complete, correct and current information in Nutraceutical Business & Technology, but does not warrant that any or all such information is complete, correct or current.

The publisher does not assume, and hereby disclaims, any liability to any person or entity for any loss or damage caused by errors or omissions of any kind, whether resulting from negligence, accident or any other cause. Nutraceutical Business & Technology does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take any responsibility for any losses or other damages incurred by readers in reliance on such content.

January/February 2012 www.nutraceuticalmag.com

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news

The Next Generation of Texturizers FiE was the scene of Fiberstar Inc. (www.fiberstar.net) and Gum Technology’s announcement of their new partnership to create a revolutionary new line of texturizing ingredients. Combining the proven moisture management of Fiberstar’s Citri-Fi with highly functional hydrocolloid-based stabilizer blends from Gum Technology, the Hydro-Fi line presents a new generation of texturizers for baked goods, frozen desserts, meat products and sauces.

Designed to provide innovative, high performance solutions for specific food formulation challenges, the ingredient range also offers significant cost reductions and performance benefits for manufacturers, including increased moisture retention, extended shelf-life and improved yield and texture. Dale Lindquist, president and CEO of Fiberstar comments: “We’re really excited by today’s launch; the two companies’ combined expertise and ingredients have enabled the emergence of an entirely new line of texturizers. Amalgamating the textural benefits of hydrocolloids with the unique properties of citrus fibre presents a new generation of ingredients that provide advantages well beyond the proven performance of their individual constituents. He continued to emphasize the “almost limitless” potential of Hydro-Fi and Citri-Fi and claimed that the company is “keen to develop relationships with other ingredient manufacturers who would be interested in capitalizing on the ingredients’ unique water and oil retention performance in combination with their own ingredients.”

Positive Opinion on Reduchol Following an application by Slovenian functional ingredients producer Valens Int. (www.valens-health.com) submitted pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA has recently delivered an opinion on the scientific substantiation of a health claim related to barley beta-glucans and the lowering of blood cholesterol and reduced risk of heart disease, referring to disease risk reduction and including a request for the protection of proprietary data. A cause-and-effect relationship has been established between the consumption of barley beta-glucans and the lowering of blood LDL-cholesterol concentrations. Several pertinent studies were provided in the health claim application, showing first that at doses of at least 3 g/day the ingredient produced a decrease in total and LDL cholesterol concentrations in both normo- and hypercholesterolaemic subjects and, second, that there is evidence supporting the biological plausibility of the mechanism of the effect.

Based on this scientific data, at least 3 g of barley beta-glucans should be consumed per day to obtain the claimed effect; in practice, this could be divided into smaller portions.

Following huge investment, Valens Int. regards this as an important success, which will enable even stronger health claims for producers using Reduchol in a wide range of food products. Furthermore, this opinion gives the company a competitive advantage when it comes to marketing its product.

The health claim application was submitted in May 2011 and the prompt and supportive communication with EFSA should be noted. During the evaluation process, Valens Int. delivered all requisite data on time and no stop-the-clock procedures were called for, which the company believes to be owing to the high quality of the health claim application, prepared with scientific support from the Nutrition Institute (Ljubljana, Slovenia).

www.nutraceuticalmag.com January/February 2012

Investing for Evolution In 2011, PLANTEX, a French specialist in plant extracts, expended 15% of its turnover in its R&D department. According to its CEO, Mrs Debaisieux, the investment reflects the company’s “strong will to remain involved in emerging markets to improve and perfect the services offered to industrial partners,” and signals that it is “preparing for the future with a constant drive to anticipate each of our clients’ particular needs.” The company invests heavily in its organization, creating a clearly identified marketing service and enhancing its R&D to further improve its response to the high level of demand it is currently facing, particularly in the area of organic vegetal extracts.

Their production unit and laboratory are acquiring new and more efficient analysis and extracting equipment, including a third innovative spray drying tower and HPLC, which will increase production capacity. This will allow PLANTEX to address customers’ requests, some of which are urgent, with an even better flexibility and reliability, while maintaining the same quality and traceability (www.plantex.fr).

Natural Shelf-Life and Yield Management Solution Vitiva has recently introduced VFish, a new product line of natural solutions for increasing the shelf-life and yield management of processed fresh fish. VFish is a unique combination of natural, mineral-rich sea salt combined with Vitiva’s proprietary plant extract formulations. This ready-to-use new formula provides full antirancidity and yield increase and supports antimicrobial stability for prepared fish and fish products.

Water-binding capacity is one of the key parameters of processed fish and has a significant impact on the yield and juiciness of the final product; most physical properties, including the colour, texture and firmness of raw fish result from water this capacity. In addition, fish and fish products contain high amounts of healthy polyunsaturated fatty acids (PUFA) and thus are prone to rapid oxidation and rancidity.

Lipid oxidation, coupled with microbial proliferation, is a major cause of deterioration and spoilage for fish.

As it affects the succulence and tenderness of the finished products as well as economic aspects of the operation, monitoring water-binding capacity is priority for the fish industry. Ohad Cohen, CEO of Vitiva, commented: “VFish is an excellent choice for food processors desiring to improve seafood water-binding capacity without the addition of phosphates and still control rancidity and microbial instability. Moreover, this completely natural product line enables fish processors to employ clean-label solutions for their products, while gaining extensive shelf-life and avoiding synthetic ingredients that might have the potential for harm.” Fish producers may choose among different customized VFish formulations, which are applicable to both mainstream and organic-certified products. The new line is available as a dry mix complete solution that is customized to different batch sizes, various technological needs and processing operations. Vitiva is a leading, fast growing and innovative company that provides advanced, applicationspecific solutions based on natural extracts for all food, cosmetic, pharmaceutical and nutraceutical industries (www.vitiva.eu).

Thank you for noticing.

Nutrition Business Technology Award for Most Innovative Ingredient, presented at Vitafoods

The Frost & Sullivan 2011 Global Eye Health Ingredients (Lutein & Zeaxanthin) Product Differentiation Excellence Award

OmniActive Health Technologies continues to receive global recognition and acclaim. Recently, OmniActive received two awards for ingredient and technology innovation.

Capsimax™ and Lutemax 2020™ showcase OmniActive’s breakthrough technologies and formulations that enhance the body's ability to absorb omniactives.com

and utilize health promoting ingredients. By delivering nutrients in bioavailable, scientifically validated and stable forms we provide our valued customers with the innovative partnership they require to develop truly outstanding consumer products. ©2011 OmniActive Health Technologies

For more information on our award-winning ingredients, visit capsimax.com or lutemax2020.com.

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news

Natural Colours for Use in Oral Dosage Forms

Kaneka Wins Novel Food Approval

Manufacturers of nutraceutical oral dosage forms now have more coating choices, thanks to the launch of the Aquarius coatings natural colour palette from Ashland Specialty Ingredients, a commercial unit of Ashland Inc. (www.ashland.com). Label friendly and in compliance with food regulations, these coating systems use colourants based on natural ingredients that are colour stable under light and storage conditions.

Available in a spectrum of hues, the new palette increases Ashland’s nutraceutical offerings and clearly designates solutions that comply with regional and global regulations. This new range was developed in response to market demand for natural coatings that are in compliance with changing regional regulations for nutraceutical products. “Nutraceuticals are subject to food regulations, which are more restrictive than their pharmaceutical counterparts regarding the colorants permitted for use in tablet coating systems,” said Laurie Kronenberg, Ashland’s new product leader of pharmaceutical and nutrition specialties, “and we anticipate that more colourants may come under future use restrictions.”

Ashland has responded to differing compliance requirements for colourants in major markets by providing a broader colour palette for their tablet coating systems, which addresses regional regulatory requirements.

Iron oxides, for instance, are permitted in pharmaceutical and food applications in the EU, but only for inclusion in pharmaceuticals in the US. Dr Tom Durig, technical director of pharmaceutical and nutrition specialties, explained: “We have recognized that, historically, natural colourants have not generally been perceived as colour stable, especially with regards to light stability. Through comprehensive and quantitative light storage colour stability testing our scientists were able to eliminate these from our tablet coating systems.”

Following a thorough regulatory and safety inspection process by EFSA, Glavonoid — a functional ingredient that, thanks to its ability to activate the body’s fat metabolism and suppress fat synthesis, offers unique dual support in fighting visceral fat — has been granted novel food status by the European Commission.

Derived from liquorice root (Glycyrrhiza glabra L.) using an advanced patented process, Glavonoid is absolutely free from glycyrrhizinic acid, contains 30% liquorice glabra polyphenols and is standardized on 3% Glabridin, its major active component. Its power to support visceral fat reduction has been proven — in DNA microarray analysis, the ingredient exhibited a two way efficiency mechanism: on the one hand it increases the body’s own fat burning ability by up-regulating genes involved in fatty acid oxidation, and on the other it decreases fat synthesis by down-regulating genes that are involved in fatty acid synthesis.

The liquorice root extract can be used in supplements as a single ingredient or as part of a multicomponent system and is also suitable for use in beverages based on milk, yoghurt, fruit or vegetables. Its novel food status provides manufacturers with a new health ingredient for building slimming and weight management products, especially those that target visceral fat reduction.

Possible claims for such products would principally be aimed at slimming, a healthy BMI, boosting fat metabolism and supporting weight management, but could also target the sport and fitness and healthy ageing markets. A spokesperson from Kaneka commented: “After the complex EFSA regulatory process, we are very pleased that Glavonoid has received novel food status.

Weight management is now a major issue and, as visceral fat is a main risk factor for the development of metabolic syndrome, we see an extremely promising market here.” Glavonoid has been sold in Japan and the US for several years, having achieved NDI status in 2005 and FDA GRAS status in 2008. The new novel food status refers to the general adult population and a 120 mg daily consumption of Glavonoid in milk, yoghurt, fruit or vegetable based beverages or food supplements (www.kanekapharma.com).

Beta-Glucan Benchmark Norwegian life science company, ImmunoMedic, has announced that it is preparing to launch its ultra pure beta 1,3/1,6 glucan ingredient, Betox-93, in the North American market. Betox-93 yields one of the highest levels of purity in the market — 93% — in addition to the higher bioavailability that results from high purity and micronization of particles, making it suitable for a wide range of formulations.

Beta-glucan is a complex sugar molecule, or polysaccharide, primarily used to stimulate the immune system as well as to manage levels of blood cholesterol concentration.

The most common source of beta-glucans are higher fungi, baker’s yeast cell walls and grains of some cereals. Morten Sundsto, president and CEO of ImmunoMedic, described the company as “thrilled to bring this new, high purity and high bioavailability beta-glucan to he North American market,” which he claimed is “expected to grow rapidly in the coming years.” He continued: Beta-glucan is increasingly gaining attention as a natural and effective ingredient for a wide range of applications, including supplements, functional foods, skincare and wound care.”

Free from any proteins, fats, taste or odour, the patented ingredient is produced under strict quality control from its origin of certified organic oyster mushroom (Pleurotusostreatus, hiratake). Beta-glucan is the most studied natural immunostimulator there is, boasting more than 10,000 published studies. As the next development and commercialization phase, ImmunoMedic is identifying distribution partners and key customers in the North American market (www.immunomedic.com).

www.nutraceuticalmag.com January/February 2012

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GOED report

Oxidation of EPA and DHA Oils The Controversy Continues

I

n the last issue of nutraceutical business & technology, GOED reported on the

controversy associated with oxidation of the long-chain omega-3 oils. Admittedly, this is a contentious issue, but when GOED’s last column went to press, both the European Food Safety Authority (EFSA) and the Norwegian Scientific Committee for Food Safety (VKM) were of the opinion that there was insufficient information available to conclude qualitatively or quantitatively that rancid fish oil intended for human consumption was a hazard. In the absence of supporting data, how can a scientific opinion change? Although the how is unclear, what is clear is that the VKM’s opinion appears to have done just that: changed.

At the end of October, the VKM published the second of its three reports, in which the committee deployed a new tone. 1 The report focused on the risk assessment of decomposition substances and oxidation products in fish oils and, similar to its previous conclusion on oxidation found in the first report, the VKM noted a lack of knowledge and insufficient information upon which to base a thorough risk assessment. 2 What’s curious, not to mention disturbing, is that despite finding no supporting data, the VKM concluded that concerns related to the regular consumption of oxidized marine oils warranted changes in consumer behaviour. In remarks made on its website, the VKM adds insult to injury by stating: “Scientific Committee for Food (SCF) is somewhat concerned about the negative health effects that long-term intake of oxidation products of supplementation with fish oil may have.” 3 The concern stems from a small number of animal studies

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demonstrating a “potential” negative health effect from large doses of highly oxidized vegetable oils. In other words, their concerns about the safety of oxidized fish oils in humans stem from tests that were not performed on humans and that used completely different products, which are known to be burned in the body faster than the fats in fish oils.

Although the VKM’s report notes a lack of published scientific studies on the effects of oxidation products on human health, results from the first double-blind randomized controlled study in humans have just been published. They demonstrate no changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation after daily intake of 8 grams of oxidized fish oil (equivalent to 1.6 grams of omega-3/ day) for 3 or 7 weeks, indicating that intake of oxidized fish oil may not have unfavourable short-term effects in healthy human subjects.4 The VKM is a scientific body and as such must substantiate its opinions with the available scientific evidence: concern based on an absence of science is conjecture and only serves to confuse consumers.

In fact, after a recent report raised fears about the consumption of oxidized fish oils, Norwegian public health officials were forced to announce on television that consumers have no reason to worry and that the products they are taking are safe. GOED has also had to address these issues at a symposium of healthcare professionals in China! The third of VKM’s three reports, which is yet to be published, is a full risk and benefit assessment of marine oils — hopefully all conclusions will be scientifically substantiated.

We leave you with one last very important piece of information. Oxidation — both in general and as it relates to fat specifically — typically carries negative connotations.

Thus, it’s no surprise that consumers and many healthcare professionals believe that oxidation is a bad thing. Keep in mind that, first, oxidation of dietary fat is part of normal metabolic homeostasis, secondly, no study has ever shown that consumption of oxidized fish oils is harmful and, thirdly, that the omega-3 oils consumed around the world are generally nowhere near rancid anyway!

References 1. N orwegian Scientific Committee for Food Safety, Description of the processes in the value chain and risk assessment of decomposition substances and oxidation products in fish oils (http://www.vkm.no/ dav/4be9bee090.pdf).

2. Norwegian Scientific Committee for Food Safety.

Evaluation of negative and positive health effects of n-3 fatty acids as constituents of food supplements and fortified foods. (http://english.vkm.no/dav/031c000d1a.pdf).

3. http://vkm.no/eway/default.aspx?pi d=277&trg=Content_6553&Conten t_6553=6187:1662070::0:6655:1:::0:0 4. I. Ottestad, et al., “Oxidised Fish Oil Does Not Influence Established Markers of Oxidative Stress in Healthy Human Subjects: a Randomised Controlled Trial,” British Journal of Nutrition. DOI: 10.1017/S0007114511005484. (2011)

For more information Adam Ismail, Executive Director and Harry Rice, VP, Regulatory and Scientific Affairs Global Organization for EPA and DHA Omega-3s (GOED) 1075 East Hollywood Avenue Salt Lake City, Utah 84105, USA Tel. +1 801 746 1413 www.goedomega3.com

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January/February 2012 www.nutraceuticalmag.com

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herbals and botanicals

Pa r t 1

Examining Echinacea

Access to safe and efficacious dietary supplements is an important part of a personal health and wellness regimen that is pursued by many US and Canadian consumers. Of the dietary supplements available, Echinacea-containing preparations — the sixth best selling in the US — are among the most popular. Broadly viewed as an immunostimulant by consumers, Echinacea is primarily taken to decrease the risk of contracting colds, flu and generalized upper respiratory infections, to shorten the duration and severity of such illnesses and to otherwise boost the immune system prophylactically. To ensure that consumers have continued access to safe dietary supplements, manufacturers must periodically identify and assess the occurrence and severity of adverse events, which this article undertakes to do in relation to products containing the Echinacea extract Echinilin.

Adverse Events Adverse event reporting for drugs, medical devices and dietary supplement products is recognized as an important means of identifying signals that could have a direct clinical impact on consumers. The Food and Drug Administration (FDA) and Center for Food Safety and Nutrition (CFSAN) defines an adverse event as “any health-related event associated with the use of a dietary supplement that is adverse,” and a serious adverse effect as “an adverse event that results in death, a life-threatening experience, inpatient hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth defect; or requires, based on reasonable medical judgment, a medical or surgical intervention to prevent an outcome described above.”1,2 Identifying possible adverse events associated with the use of a dietary supplement product is accomplished by conducting safety evaluations in preclinical (namely, animal) testing, before monitoring for adverse events in human clinical studies and postmarketing surveillance. In the US, the primary aim of a clinical study is to determine efficacy — identifying adverse effects is a secondary goal. Because clinical trial data are obtained under strictly controlled

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conditions, this signal detection mechanism is very sensitive. Identifying and following evolving adverse events for supplement products may also be achieved through postmarketing surveillance, which has two significant advantages over clinical trials: it provides ongoing surveillance of all users (as opposed to the small sample size in a clinical trial) and is relatively inexpensive as a process.3

Echinacea Products The genus Echinacea (Family Asteraceae) comprises about a dozen species of herbaceous perennials, indigenous throughout the eastern and central US and southern Canada. The three most commonly used species in supplemental preparations are Echinacea angustifolia, E. purpurea and E. pallida. Fresh and dried roots and aerial parts, and fresh-pressed juice from flowering tops, are prepared into tinctures, teas, juices, powders, tablets or capsules that may also contain additional ingredients, some of which may be botanical. In the US and Canada, Echinacea-containing products are marketed as dietary supplements, which, by definition, are for oral administration only; intravenous (IV) products for use in medical settings are common in other countries,

including Germany.4 Regardless of final form, Echinacea-containing preparations are used by consumers primarily because they are perceived as having immunostimulant properties. Of all the dietary supplements currently available, Echinacea-containing preparations are among the most popular, being sixth in USA sales in 2008.5 Few safety studies for Echinacea preparations are available in scientific literature, possibly because the flowering herb has an exceptionally long history of safe use. Echinacea has been used since at least the eighteenth century by native North Americans to assist in wound healing, as a remedy for infection and toothache, as a means of alleviating joint pain and as an antidote for snakebite — and, until modern antibiotics replaced most herbal remedies, Echinacea preparations were also in regular use by the general US population, primarily as anti-infective agents. 5-10

PreClinical Study In one published safety evaluation, the toxicological effects of orally and intravenously administered fresh-pressed E. purpurea juice (also known as Echinacin or Echinaguard — 1 mL of the unpurified juice is equivalent to 1.5–2.5 g of crude Echinacea

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herbals and botanicals

herb) from the aerial parts of the plant were examined in rats and mice for periods of up to 4 weeks.11 Four mutagenicity assays and one cell-transformation assay were also performed with freeze-dried residues (lyophilizates) of the juice. Each study was conducted in accordance with the internationally accepted guidelines of the Organization for Economic Co-operation and Development (OECD) for “Good Laboratory Practice” and with the OECD or EC (European Commission) recommendations for technical methods.

In the acute studies, a single dose of 15,000 mg/kg bw E. purpurea juice was administered by gastric tube to 8 week old Wistar rats (eight males and eight females, approximately 200 g each) and 8 week old NMRI mice (eight males and eight females; approximately 20 g each), with each receiving 30,000 mg/kg bw in the same manner (consuming the equivalent of 5.1–7.5 g crude Echinacea per day).

Following administration, the animals were observed for 14 days before termination and necropsy. No deaths occurred during the observation period, nor were abnormalities in appearance or behaviour reported, and no changes attributable to E. purpurea juice were observed in any organ at necropsy.

The oral LD 50 for E. purpurea juice was >15,000 mg/kg bw and >30,000 mg/kg bw in the rat and mouse, respectively. In a parallel study by the same authors, single doses of E. purpurea juice were administered via IV to rats (5000 mg/kg bw) and mice (10,000 mg/kg bw). Although minor reactions (sedation and dyspnea) to the IV administration procedure occurred, no other effects were observed.

In the subacute study, E. purpurea juice was administered via gastric tube at levels of 0, 800, 2400 or 8000 mg/kg bw/day for 28 days to four groups of rats (18 males and 18 females per group, consuming the equivalent of 2.72–4 g crude Echinacea per day). During the study body weight, food consumption, ophthalmology, clinical chemistry, haematology and histopathology were evaluated for toxicological effects.

No mortalities occurred. At the end of the study, a statistically significant decrease in plasma alkaline phosphatase (AP) in male rats of the 2400 and 8000 mg/kg bw/ day dose groups (P <0.01 and P <0.05, respectively) and a statistically significant increase in prothrombin time (PTT) in female rats of the same groups (also P <0.01 and P <0.05, respectively) was reported.

Although statistically significant, neither the change in AP nor the change in PTT was considered to be toxicologically significant, as both changes fell within the accepted physiological variation for the strain and neither was proportional to dose. No significant differences in body weight or food consumption occurred among the groups at any time point and, in addition, there were no reported changes from control in ophthalmology, necropsy findings or histopathology. The reported no-observedadverse-effect level (NOAEL) for freshpressed E. purpurea juice was 8000 mg/kg bw/day (equivalent to 13.6–20 g/kg bw/day of the raw herb), which was the highest dose administered and approximates 30 times the maximum daily dose in humans.

In the first mutagenicity assay — the bacterial mutation (Ames) assay — the mutagenic potential of E. purpurea juice lyophilizate was evaluated at concentrations of up to 5000 μg/plate in five test strains of Salmonella typhimurium (TA 98, TA 100, TA 1535, TA 1537 and TA 1538); no evidence of toxicity or mutagenicity was observed, with or without metabolic activation. Metabolic activation was induced by using an S-9 mixture containing the liver homogenate from male Wistar rats that had been injected intraperitoneally with 500 mg/kg bw Aroclor 1254 and sacrificed 5 days afterwards. Similarly, in the in vitro mouse lymphoma cell gene mutation assay, no statistically significant increase in mutation frequency was found in mouse lymphoma cells treated with E. purpurea juice lyophilizate at concentrations of up to 5000 μg/mL, with or without metabolic activation. The third assay, in vitro human lymphocyte analysis, also showed no mutagenic effect of the juice lyophilizate at concentrations up to 5000 μg/mL with or without metabolic activation — aberration frequency in the human lymphocyte cells was consistent among treatment and controls.

In the micronucleus assay, femoral bone marrow smears from mice orally treated with E. purpurea juice (25,000 mg/kg bw) on one occasion and sacrificed 24, 48 or 72 hours afterwards, showed no increase in micronucleated polychromatic erythrocytes (PCE) compared with bone marrow smears from control animals. To evaluate the unscheduled DNA synthesis (UDS) potential of E. purpurea juice lyophilizate, a cell transformation assay

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herbals and botanicals

with lyophilizate concentrations of up to 55μg/mL was performed; no morphological transformations were induced in Syrian hamster embryo cells exposed to the lyophilizate. In each of these five supportive assays, cells exposed to E. purpurea juice lyophilizate and cells from animals dosed with E. purpurea juice responded similarly to assay negative controls and unlike the corresponding positive controls (statistical significance was not generally determined for the positive control compared with the negative control).

The results of these studies indicate that fresh-pressed E. purpurea juice was well tolerated in rats, with an oral NOAEL of 8000 mg/kg bw/day (equivalent to 13.6–20 g/kg bw/day of the raw herb), the highest dose level tested. No adverse effects were observed at dose levels approximately 30 times the maximum normal daily dose that a human would ingest. Furthermore, E. purpurea juice and its lyophilized residues were demonstrated to lack mutagenic potential and to not cause chromosomal aberration or cell transformation.

Clinical Trial Believed by the general population to possess unique immunostimulatory properties, Echinacea is included in many dietary supplement products. Because most Echinacea-containing preparations are not standardized, clinical trials studying the effectiveness of these products have often produced inconclusive results, most likely owing to insufficient quantities or deficiencies in the preparation quality of Echinacea materials. The need to evaluate a high quality standardized preparation of Echinacea such as Echinilin (sold in the US as Echinamide)

Because most Echinaceacontaining preparations are not standardized, clinical trials studying the effectiveness of these products have often produced inconclusive results.

— for effectiveness and for incidence of adverse reaction — thus led to a clinical trial evaluating the effect of Echinilin on the severity and duration of the common cold in otherwise healthy subjects.

Similar to the E. purpurea juice Echinacin used in the preclinical studies, Echinilin is prepared from freshly harvested E. purpurea. However, whereas Echinacin is the pressed juice, Echinilin is an extract purified to principally contain three active components: alkamides, cichoric acid and polysaccharides, at concentrations of 0.25, 2.5 and 25.5 mg/mL, respectively. Lacking many of the impurities present in the raw juice of the E. purpurea plant, Echinacin is also somewhat more concentrated than Echinilin; 1 mL is equivalent to 1.5–5 g of the crude Echinacea herb whereas 1 mL of Echinilin is equivalent to approximately 1 gram of the plant. The clinical trial, a randomized, double-blind, placebocontrolled study conducted at the University of Alberta, Edmonton, Canada, showed that Echinilin, a standardized formulation prepared from freshly harvested E. purpurea, administered orally for a total of 7 days to volunteers developing the initial symptoms of a cold, was well tolerated with only mild to moderate adverse effects, similar to those seen with placebo.10 The primary objective of the study was

www.nutraceuticalmag.com January/February 2012

to evaluate the effect of orally administered Echinilin on the duration and severity of the common cold, whereas the secondary objective was to evaluate adverse reactions to Echinilin in comparison to placebo.

Enrolled in the clinical trial were 282 male and female volunteers aged 18–65 years with a history of two or more colds in the past year but otherwise in good health, who were randomized to either the Echinilin or placebo group. Exclusionary criteria included, amongst others, recent vaccination against influenza and allergy to ragweed. At the onset of the first symptoms of a naturally acquired cold, subjects were to begin the 7 day treatment programme, which consisted of 10 doses per day on the first day and four doses per day on the 6 subsequent days.

Each dose consisted of 4 mL of Echinilin or placebo mixed into half a glass of water before drinking. Subjects consumed the equivalent of 40 g crude Echinacea on the first day of dosing (approximately 0.67 g/kg bw) and 16 g on each of the subsequent 6 days (approximately 0.27 g/kg bw/day). Echinacea and placebo extracts were prepared to look, taste and smell the same. Of the enrolled subjects, a total of 128 developed a cold (59 Echinilin, 69 placebo) and complied with at least the first 2 days of the protocol by taking 14 doses of the study formulation within 48 hours of symptom onset; these subjects were included in the ITT (intention to treat) population. The 17 individuals from the ITT population who failed to comply fully with the trial criteria were excluded from the more restrictive (most compliant) PP (per Protocol) population. A total of 111 subjects — 54 in the Echinilin (28 women, 26 men) and 57 in the placebo (41 women, 16 men) groups — developed colds and fully complied with trial criteria; these subjects were included in both the ITT and PP populations.

Dosing compliance was recorded daily into a log, as was a self-assessed severity of 13 cold symptoms (sore throat, runny nose, stuffy nose, watery eyes, chills, malaise, fever, headache, sore muscles, hoarseness, shortness of breath, sneezing and cough). Each symptom was scored on a ten point scale as ‘no symptom’ (0 points), ‘mild’ (1–3 points), ‘moderate’ (4–6 points) or ‘severe’ (7–9 points) in nature and a Total Daily Symptom Score (TDSS) was generated by adding all symptom scores for that day. Each subject that suffered from a cold was also examined by a nurse on days 3 (after 14 doses) and 8 (after the course of treatment), who assessed the severity of

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cold symptoms, screened the subjects for secondary complications such as sinusitis, bronchitis, pneumonia and otitis media and collected fasting blood samples for white blood cell differential counts. Subjects were contacted periodically during the 7 day treatment to assess compliance, ask whether they thought they were taking Echinilin or placebo and request that any adverse reaction be recorded in the log.

The parameters assessed during the clinical trial included: the evolution of the mean TDSS results for each day, the change in individual symptom scores, the duration of symptoms (indicated by the number of days a symptom was scored above three points), the treatment response rate (the number of subjects reporting a decrease of at least 50% in their maximum TDSS) and the incidence of adverse effects.

In the PP population, statistical analysis revealed that the average TDSS for self-assessed cold symptom severity was significantly lower in the Echinilin group ... than in the placebo group Efficacy and Adverse Events As the distribution was not normal, the data were logarithmically transformed prior to statistical analysis. To determine the effect of treatment and time on TDSS and individual symptom scores, Type III repeated-measures analysis of variance (ANOVA) was performed. To determine the effect of treatment on the duration of the individual symptoms, a one-way ANOVA was used. To evaluate the closeness of the self-assessed and nurse-assessed individual and total symptom scores, Pearson correlation coefficients were determined. 10

www.nutraceuticalmag.com January/February 2012

In the PP population, statistical analysis revealed that the average TDSS for self-assessed cold symptom severity was significantly lower in the Echinilin group (by 23.1%) than in the placebo group (P <0.01). In terms of symptoms, the 7 day mean severity of runny nose, sore throat, stuffy nose, fatigue, headache and chills were lower by 27%, 25%, 22%, 31%, 39% and 44% in the Echinilin group than in the placebo group, respectively (P <0.05 for all). Cough was the only symptom that scored higher in the Echinilin group than that of the placebo. Additionally, Pearson correlation coefficients were significantly high, indicating that self-assessed scores and nurse-assessed scores were extremely similar for cough, runny nose, stuffy nose, sore throat, fatigue and for total symptoms (P <0.0001 for all). Blinding was demonstrated to be adequate at the end of the study as approximately 50% of subjects incorrectly guessed which formulation they had received.

The results of the ITT population were similar, albeit less pronounced, than those of the PP. The average TDSS for self-assessed cold symptom severity was significantly lower in the Echinilin group (by 17.6%) than in the placebo group (P <0.05). In terms of symptoms, the mean severity of fatigue and headache decreased significantly during the 7 days in the Echinilin group compared with the placebo group (P <0.05 for both).

Cough was again the only symptom that scored higher in the Echinilin group than in the placebo group. Owing to a lack of compliance by 17 subjects in the ITT population, Pearson correlation coefficients were not determined.

In the PP population, the cold duration in individuals in the Echinilin group was reduced by approximately 1.5 days (27%) compared with the placebo group, with symptom severity dropping to 50% of maximum by day 4 for subjects receiving Echinilin but not until day 5.5 for placebo subjects. On day 7, 95% of the members of the Echinilin group exhibited symptoms at <50% of their reported maxima; 33% of the members of the placebo group still exhibited symptoms at this level. Again, the results of the ITT population were similar, although not as pronounced; all individual symptoms, except cough, were of shorter duration in both populations when treated with Echinilin than placebo. Among the ITT population, a secondary complication in

the form of bronchitis developed in seven participants â&#x20AC;&#x201D; two individuals from the Echinilin group and five from the placebo group. No significant differences were observed in the white blood cell differential counts in either group.

Several incidents of non-severe adverse effects were reported by both the treatment and placebo groups of the ITT population.

Gastrointestinal effects (such as nausea, heartburn and constipation) were reported in 8/59 (13%) of the Echinilin subjects and 6/69 (9%) of the placebo subjects taking at least 14 doses during a 2 day period.

Unpleasant tongue sensations (such as itching, burning and numbness) were reported in 8/59 (13%) of the Echinilin subjects and in 8/69 (11%) of the placebo subjects. No allergic events were reported for either group during the study. Differences between the treatment and placebo groups were not statistically significant â&#x20AC;&#x201D; results showed that both formulations were well tolerated and that side-effects, when they occurred, were not sufficient to cause any subjects to withdraw from the study.

This article will be continued in the next issue of nutraceutical business & technology, where it will explore the issue of postmarketing surveillance and fully discuss the benefits, limitations and potential applications of both the ingredient and the means used to evaluate it.

For more information Dr Nancy J. Szabo Burdock Group 801 N. Orange Ave., Ste. 710 Orlando, Florida 32828, USA. Tel. +1 4078 021 400 nszabo@burdockgroup.com

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Omega-3 Phospholipid EPA & DHA are important building blocks for healthy cell membranes. The ratio of EPA & DHA to other fatty acids in the membrane is called www.superbakrill.com superba@akerbiomarine.com Phone: +47 24 13 00 00

the Omega-3 Index – a strong indicator of cardiovascular health. In a recent human study, Superba™ Krill Phospholipid EPA & DHA had a significantly improved Omega-3 index compared to ordinary fish oil.

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essential fatty acids

THE Alpha to Omega of Krill

Dietary intake of the long-chain omega-3 polyunsaturated fatty acids, EPA and DHA, has been associated with many health benefits — from cardiovascular health and improved cognitive function to reduced levels of inflammation. Although various organizations have established recommended daily intakes for EPA and DHA, the typical western diet is known to fall short of these, requiring dietary supplementation to make up the shortfall.

O

ne novel source of phospholipid omega-3 PUFAs is krill oil extracted from Euphausia superba, an Antarctic krill species. Krill has a shrimp-like appearance with big black eyes and a reddish, semi-transparent shell. They live in huge swarms in the cold Antarctic waters of the Southern Ocean, feeding on microscopic marine algae rich in enzymes that can produce omega-3 fatty acids, which are then accumulated in the krill themselves and can subsequently be extracted in krill oil. Moreover, algae are capable of synthesizing the powerful antioxidant astaxanthin, which is taken up by krill and protects PUFAs from oxidation — it is also the reason for the characteristic deep red colour of krill oil.

Most importantly, the majority of the EPA and DHA in krill oil is bound to a particular type of fat — phospholipids — unlike other marine oils, which confine them to different chemical forms of fat, usually either triglycerides or ethyl esters. The differences are quite significant, particularly in the area of utilization by the body: dietary triglycerides and phospholipids differ in their physiological functions in the body; triglycerides are primarily used either as energy or as energy storage in fat tissues.

When delivered in triglyceride form, a portion of

the beneficial omega-3s are burned as energy or stored in the body’s fat reserves — as a result the dosage of triglyceride omega-3 oils

(phospholipid versus triglyceride) of omega-3 fatty acids is important for the bioavailability of EPA and DHA in blood plasma. The study,

must be large enough to compensate for that loss and ensure that sufficient omega-3s are available on a cellular level.

Recent human clinical studies have shown that phospholipid omega-3s may be a more desirable form. When compared with triglyceride omega-3s, a smaller amount of the phospholipid kind is required to achieve equal bioavailability in the body’s cells and organs, which results in krill oil capsules being smaller than their fish oil counterparts. There’s more good news that consumers will love: krill oil is dispersible in the stomach fluids, eradicating the repeating that fish oil capsules so commonly incur.

Studies have demonstrated that increased blood levels of EPA and DHA are accompanied by health benefits in humans, placing great importance on the bioavailability of these omega-3 fatty acids in the blood. The term ‘bioavailability’ refers to how much of a substance reaches the blood and describes absorption and survival rate of said substance in the body. Two recent human intervention studies investigated whether the molecular form

performed by Kevin C. Maki and his co-workers at the Provident Clinical Research and Meridien Research Centres, USA, was conducted as a randomized, double-blind, parallel arm trial.

Within this setup, 76 overweight and obese men and women were randomly distributed into three groups to take Superba Krill oil, fish oil, or olive oil for 4 weeks. To avoid any influence, the supplementation given was unknown to both the study subjects and researchers. Whereas the received daily amount of EPA was similar in the krill and fish oil groups, the DHA quantity was approximately half as much in the krill oil group as that in the fish oil group. Nevertheless, at the end of the study period, plasma analysis showed that the mean EPA concentrations were higher in the krill oil than the fish oil group and the mean DHA concentrations were similar in both groups. Both sources of omega-3 fatty acids were safe, generally well-tolerated and significantly increased EPA and DHA levels in plasma compared with the control group. Most importantly krill oil supplementation (2 g/day) resulted in increased plasma EPA bioavailability and, in the case of DHA, equal bioavailability but at half the dosage of fish oil. Overall, after dose adjustment, the total increase of EPA and DHA in the plasma of subjects who received Superba Krill oil for 4 weeks was 24% higher than that of the subjects who received fish oil (Figure 1).

The second study, performed by researchers at Akershus University College and University of Oslo, investigated whether a lower dose of EPA and DHA provided in phospholipids, compared with omega-3 fatty acids provided in triglycerides, shows equal bioavailability of these fatty acids in plasma. In this study, 113 subjects with normal or slightly increased total blood cholesterol and/or triglyceride levels were randomized into three groups and given

Figure 1: The plasma increase (%) in total EPA and DHA after either 4 or 7 weeks of Superba Krill oil, in comparison with fish oil supplementation (values have been dose adjusted).

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essential fatty acids

Superba Krill oil, fish oil or placebo for 7 weeks.

The daily supplementation of total EPA and DHA was approximately 37% less in the krill oil group than in the fish oil group. Results showed that dietary omega-3 administration led to a similar increase of plasma omega-3 fatty acids in both the krill and fish oil groups compared with the control group. These findings suggest that a lower dosage of EPA and DHA in phospholipid form is required to obtain comparable plasma EPA and DHA levels to the triglyceride form of omega-3 supplementation. After adjustment of EPA and DHA levels to the daily dose given, the results from the krill oil group suggest a total EPA and DHA plasma level that was 45% higher than in the fish oil group after 7 weeks of administration. Moreover, the subjects with the highest baseline values of triglycerides further benefited from krill oil supplementation and showed decreased plasma triglyceride levels.

Additionally, the HDL-cholesterol/triglyceride ratio, a risk predictor for heart disease, was significantly decreased after Superba Krill oil, but not fish oil, treatment.

These two human clinical studies demonstrate that intake of Superba Krill oil is more potent than fish oil in increasing total plasma EPA and DHA values and suggest that there is a higher bioavailability of omega-3 fatty acids bound to phospholipids than in the triglyceride bound omega-3s found in fish oil.

In the first study mentioned, in which 2 g of Superba Krill oil was administered for 4 weeks, the blood levels of endocannabinoids were also measured. The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese persons with respect to normalweight subjects. Superba Krill oil — but not menhaden oil or olive oil — was able to significantly decrease 2-AG in obese subjects,

which correlated with a decreased plasma phospholipid omega-6/omega-3 ratio. These data show for the first time that relatively low doses of omega-3 fatty acids such as Superba Krill oil can significantly decrease plasma 2-AG levels in obese human subjects and reveal that it presents a promising approach for counteracting elevated EC levels. By changing the balance between omega-6 and omega-3 fatty acids and reducing EC precursor availabilities, Superba Krill oil may provide therapeutic benefits such as lowered triglyceride blood levels and decreased fat deposition in and around organs. It could also alleviate metabolic dysfunctions such as dyslipidemia, visceral adiposity and the associated inflammatory states that play a role in atherogenesis and the subsequent increased cardiovascular risk.

Krill are an underexploited biomass — one that is more than double the size of that of all humans. Aker BioMarine has made a commitment to sustainability and maintaining the highest standards in all aspects of the krill fishing operations.

The company conforms to all CCAMLR requirements and has taken sustainability and environmental responsibility even further

19

by addressing all the issues on CCAMLR’s wish list of best practices, co-operating with WWF-Norway in conservation efforts and obtaining MSC certification for the sustainability and full traceability of Aker BioMarine’s krill products, from sea to shelf. Although krill’s health benefits have been explored in several studies, many of the potential areas of its health-promoting effects are as yet unknown. In addition, various interesting data have been obtained in preclinical studies that are yet to be confirmed in human trials; of particular interest will be the areas of joints, brain health and pet food. Krill oil supplements provide an excellent source of EPA and DHA — phospholipid omega-3s — and, owing to its increased bioefficiency, improved compliance and eminent sustainability, is arguably superior to others available.

For more information Henrik Traaholt Business Director and Brand Manager, Europe Aker BioMarine Tel. +44 241 300 00 henrik.traaholt@akerbiomarine.com www.akerbiomarine.com

January/February 2012 www.nutraceuticalmag.com

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Protecting the Platform

Following its recent issue of a of a US patent, nutraceutical business & technology spoke with Dr Wael Massrieh, VP of scientific affairs at Neptune Biotechnology, to discuss the protection of their innovative platform … and of the raw material itself.

NBT: Can you comment on Neptune’s recently issued US patent novel for omega-3 fatty acid phospholipid compositions suitable for human consumption and what message that sends to the EFA market?

WM: We are extremely proud of achieving both recently issued patents — ‘348 and ‘825 — both of which reaffirm Neptune’s position as pioneer and leader of the krill oil industry. The ‘348 patent provides Neptune with the right to exclude others from making, using, selling, offering for sale or importing the patented invention for the term of the patent, which is valid and has full force and effect regardless of any re-examination request made by a third party. The USPTO, the foremost reputable authority for awarding patents to their entitled inventors, concluded that the claims are novel and non-obvious — and thus patentable. We hope this sends the message that we are open for business and willing to discuss mutually beneficial agreements with all distributors interested in capitalizing on this rapidly growing krill oil market.

NBT: In a similar vein, one of your customers was recently awarded “Product of the Year 2011” in Denmark, which suggests positive consumer uptake. What factors do you think led to that success and how can you improve enduser market penetration?

WM: Although Neptune as a manufacturer does not directly market to end-users, we do offer technical, scientific and marketing support for those who require such assistance in their consumer approach. This is the second time in a year that NKO has been recognized as a best product, an achievement of which we are very proud. Consumers are aware that Neptune’s krill oils offer them the best quality krill oil that is supported by clinically proven health benefits.

NBT: Critics have recently questioned the sustainability of krill fishing in the Southern Oceans. How would you respond to these comments?

WM: To overcome this highly sensitive issue, Neptune only sources krill through CCAMLR licensed vessels. The Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) is the only official and reliable international organization involved

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in Antarctic krill fishery management and is unique in involving the governments of 25 state member nations — in addition to concerned stewardship organizations such as the Antarctic and Southern Ocean Coalition (ASOC), which counts Greenpeace as a member. CCAMLR establishes detailed precautionary measures to ensure and confirm the ecological sustainability of harvesting the Antarctic krill species (Euphausia superba) and has never forecasted a shortage of it. In 2009/10, 11 vessels, all of which acted within CCAMLR guidelines, were licensed to fish krill in the Antarctic. The total precautionary catch limit of 2009/2010 corresponded to 1.56 % of the total biomass figure of 420 million tonnes and the total catch of all CCAMLR certified vessels for 2009/2010 was only 5.54% of the established quota. Neptune only captured 0.006% of the total biomass and 0.04% of total precautionary catch limit.

NBT: Neptune’s chief scientific officer was recently quoted as stating that the patent (US No. 8,030,348) also “benefits our majority-owned subsidiaries, Acasti Pharma and NeuroBioPharm, as it protects the platform for our pharmaceutical products.” Is the convergence of the two sectors important to Neptune, and how do you see your nutra/pharma activities aligning in the future?

WM: Our nutra and pharma activities will always be aligned in the sense that Neptune will be the exclusive supplier of raw material to both its pharmaceutical subsidiaries (Acasti Pharma and NeuroBioPharm), which will always have the exclusive world license for Neptune’s patents in their respective sectors. On one hand, Acasti Pharma, Inc. is dedicated to the research, development and commercialization of its proprietary product portfolio for the management of cardiometabolic disorders — from prevention to treatment. Acasti develops first-in-class and best-in-class anti-dyslipidemic prescription drugs (Rx), medical foods (MF) and over-the-counter (OTC) products. Acasti’s lead product, CaPre, intended for use in the treatment of dyslipidemia, has demonstrated a superior efficacy and safety profile in established preclinical models. NeuroBioPharm, by contrast, is dedicated in the research, development and commercialization of its proprietary product

portfolio for the management of neurological disorders, also from prevention to treatment. By targeting the cardiovascular and neurological sectors, Neptune and its subsidiaries have the potential to play a major role in the management of the world’s most prevalent human diseases and disorders.

NBT: Perhaps driven by the convergence of the pharma/nutra industries, you’ve undertaken a large dietary supplement clinical study: what results do you hope to achieve and should this be a model for the whole functional food industry?

WM: Neptune has undertaken several clinical studies to meet the demands of the changing market. Regulatory requirements in Europe, Asia and even the US are becoming stricter and more demanding in terms of the criteria required to obtain and use health claims. With all these clinical studies we are confident of achieving significant results that will provide us with the necessary tools to submit and obtain approved health claims. The design of clinical studies is more critical than ever before and we have accumulated much knowledge of what each international regulatory body requires for approving health claim submissions.

NBT: Finally, like Big Pharma, the nutraceutical industry is becoming more litigious: can we expect to see more IP/patent disputes or are there steps that can be put in place to avoid such issues?

WM: Is Nutra Industry really becoming more litigious? I see the industry becoming a little more structured now that the FDA has decided to play a bigger role in enforcing regulation.

However, from an IP point of view, I think there will always be companies that decide to operate regardless of the IP in the market they are targeting. Unfortunately this leads to unnecessary lawsuits for the IP holders who simply wish to protect what has been rightfully granted to them by the USPTO.

For more information Dr Wael Massrieh VP of Scientific Affairs w.massrieh@neptunebiotech.com www.neptunebiotech.com

January/February 2012 www.nutraceuticalmag.com

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Taking the Flax

A focus on healthier lifestyles has led to a surge in the popularity of foods enriched with essential fatty acids (EFAs) — such as omega-3s — which offer a variety of health benefits, including those associated with cardiovascular health. These benefits are increasingly being delivered through the use of ingredients that contain high levels of omega-3s. With their growing market potential and consumer preference, omega-3s are expected to continue to penetrate the functional foods and dietary supplements arena in coming years.1

T

he wealth of clinical research on omega-3s has rapidly translated into rising consumer recognition of their health benefits.2 As such, the global omega-3 ingredients market is estimated to reach $3.21 billion in 2016, compared with $1.48 billion in 2010. Europe’s current sociodemographical trend of eating foods with known physiological benefits and taking precautionary health measures makes it the fastest growing segment — the omega-3 market in this region alone is set to rise from $311.2 million in 2010 to $771.8 million in 2016. This increased market penetration can be attributed largely to technological advancements that have widened its available sources and enabled its incorporation into a broader range of food and beverage applications.

Essential Sources Omega-3 fatty acids are derived from two main dietary sources: seafood and certain nut and plant oils. Marine-derived omega-3 fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in particularly high concentrations in deep water oily fish, such as anchovies and sardines. These EFAs, which play an important role in human health and are a vital component of a healthy diet, have recently attracted the media spotlight, resulting in broad consumer recognition of the benefits of oily fish. Another source of omega-3 EFAs that is growing in popularity is flaxseed: it

was flaxseed and other foods rich in alpha-linolenic acid (ALA) that earned a reputation for healthy living in the past — and this recognition is being reawakened. Flaxseed provides the richest vegetarian source of ALA available, containing more than five times the ALA content of most other common plant oils (Table I).

The ‘True’ Essential Fatty Acid

ALA is the only essential omega-3 fatty acid that is actually required in the diet, as it cannot be synthesized by the body but is critical to human health — particularly for normal growth, development, reproduction and vision. Previous attempts at parenteral nutrition without EFA content has led to individuals exhibiting negative physiological symptoms including eczema, neuropathy or an impaired immune system.3 One aspect that is yet to be recognized or Plant Oil ALA Content fully comprehended by consumers is that ALA Flaxseed oil 50.8% can be converted into EPA and DHA through metabolic pathways. Several studies have Soy oil 7% attempted to identify the conversion rate of ALA into EPA and DHA but the results have varied Canola oil 9.3% widely. A recent study provided evidence for the Corn oil 1% in vivo conversion of ALA into EPA and DHA and may help to explain variations that have occurred Olive oil .06% in previous studies.4 This cohort study helped Table I: Alpha-linolenic acid content in plant-derived oils. to answer a burning question within the food

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technology community: whether plasma levels of EPA and DHA depend solely on dietary intake, or if ALA omega-3 sources provide an adequate dietary substitute via in vivo conversion to EPA and DHA. The study analysed the dietary consumption of 14,422 men and women (aged 39–78), subdivided into four groups (fish eaters, non-fish eating meat eaters, vegetarians and vegans).

Circulating levels of omega-3 fatty acids were measured in a subgroup of 4902 individuals, the results were compared with dietary habits and inferences were made regarding conversion rates of ALA to EPA and DHA. The results of the study showed that circulating levels of DHA and EPA were very similar in the fish eaters and non-fish eaters. The authors concluded that the conversion rate of ALA to EPA and DHA was significantly higher in those who did not consume fish; in other words, not consuming fish appears to increase the rate of conversion of ALA to EPA and DHA. This could mean that ALA is a key component in the modulation of circulating levels of ALA, EPA and DHA. As described above, the key observation is that the consumption of fish provides significant dietary sources of EPA and DHA. Despite this, however, circulating levels of EPA and DHA are very similar among the various cohort groups,

essential fatty acids

including those that did not consume fish.

Furthermore, this similarity between circulating levels of the fatty acids of fish eaters and nonfish eaters, despite the large difference in dietary consumption, suggests an important role for ALA as a precursor for in vivo synthesis of the fatty acids. This emphasizes the importance of ALA as a truly essential fatty acid.

need for refrigeration or special handling. The benefits of these flax ingredients reach beyond enhanced nutritional value; for example, their inherent functional components such as fibre allow them to be used as formulation enhancers or to improve moisture in breads, replace fats, provide allergen-free options and enhance shelf-life and texture.

The Heart of the Matter

Banish Formulation Challenges

ALA performs some of the same functions as other omega-3 fatty acids such as EPA and DHA long-chain fatty acids, which is logical considering the in vivo conversion of ALA into EPA and DHA — for example, research shows that ALA helps to protect against cardiovascular disease.5 Diets rich in ALA lower the risk of coronary heart disease (CHD), ischemic heart disease, nonfatal myocardial infarction and stroke; in fact, a meta-analysis of prospective studies suggested that increasing the intake of ALA by 1.2 g/day decreases the risk of fatal CHD by at least 20%.6 Additionally, ALA is linked with helping to decrease body inflammation, which is a key feature of many chronic conditions such as coronary heart disease, stroke and cancer.7 ALA-rich diets reduce the concentrations of pro-inflammatory compounds such as cytokines, along with indicators of whole-body inflammation, for example C-reactive protein, by as much as 18–75%.8,9,10 ALA also helps to reduce arrhythmia (infrequent heart beats).11

The ‘nutty’ and ‘toasted’ sensory profile of high performance flaxseed-derived omega-3 ingredients provides manufacturers with a great tasting way of adding wholegrain-style healthy functionality to baked goods, cereals and bars, in addition to dough applications such as pizza and tortillas. Critically, flax does not adversely affect the taste of many foods and is particularly suited to, for example, fortifying baked goods. In addition, the omega-3-rich oil in flaxseed is more stable than in fish oil and less prone to oxidation, offering manufacturers a stable approach to omega-3 fortification.

A unique property of flaxseed is that it contains a gum matrix, known as ‘gum mucilage.’ OptiSol 5000 functional flaxseed products have now been developed using a proprietary milling and processing system; a range of ingredient solutions that can be used to replace hydrocolloid systems in food applications, including gluten-free baked goods, where they can improve both texture and shelf-life in tortillas, sheeted doughs, batters, breadings, sweet baked goods and fresh breads.

Furthermore, the flax-based omega-3 ingredients can be easily incorporated into a wider variety of foods including beverages, pasta, cereals, dressings and sauces — as well as certain processed meat applications. Another benefit is its clean-label advantage; it can be listed simply as “flaxseed,” while contributing to omega-3 and fibre health claims. A patented cleaning and stabilization process known as MeadowPure guarantees a highly stable end product, with a shelf life of up to 2 years.

Flax-ing Lyrical The European guideline daily allowance (GDA) for ALA intake is 2 g/day.12 As a result of these GDA guidelines, consumers are looking for new ways to add omega-3 to their diets; products formulated with flax are rich in omega-3 ALA and offer the benefits of a clean label. When comparing the supplements market with functional foods and beverage applications, the main difference in omega-3 ingredients is the form of the products used. Milled flaxseed omega-3 is traditionally used in functional foods and beverages, taking advantage of the many health promoting properties of flaxseed, including antioxidants, lignans and fibre. Supplement manufacturers, in contrast, tend to prefer omega-3 in its oil form for obtaining the purest form of omega-3 possible and positioning their supplements with a clear, simple label and direct messaging.

A range of flax ingredients is now available to help manufacturers to provide nutritious solutions for their formulations. Some flaxbased products offer all three forms of omega-3 in a dry powder format, which benefit from a naturally long shelf-life of 12 months without the

Conclusion The proven health benefits of ALA omega-3 — and the corresponding consumer interest — has led to the further development of high performance flax-derived omega-3 functional ingredients. As with most food and beverage products, consumers want to improve their health in the way that is most convenient for their lifestyle. As such, flaxseed-derived ALA omega-3s provide the dual benefits of a high ALA content and an excellent sensory and functional profile.

In this way, manufacturers benefit from the ease of formulating omega-3 into their products, while consumers can gain significant health benefits.

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References 1. Market to Market, “Omega-3 & 6 Market by Source, Geography Trends & Global Forecasts,” August 2011 (http://www.marketsandmarkets.com/ Market-Reports/omega-3-omega-6-227.html).

2. Frost & Sullivan, “Consumers Becoming Increasingly Savvy About Marine and Algae Oil Omega-3 Ingredients,” 20 July 2010 (http://www.frost.com/ prod/servlet/press-release.pag?docid=207388177).

3. R.T. Holman, “The Slow Discovery of the Importance of Omega 3 Essential Fatty Acids in Human Health,” J. Nutr. 128(2), 427–433S (1998).

4. A.A. Welsh, et al., “Dietary Intake and Status of n-3 Polyunsaturated Fatty Acids in a Population of Fish-Eating and Non-Fish-Eating Meat-Eaters, Vegetarians and Vegans and the Precursor-Product Ratio of {alpha}-Linolenic Acid to Long-Chain n-3 Polyunsaturated Fatty Acids: Results from the EPICNorfolk Cohort,” Am. J. Clin. Nutr. 93(3), 676 (2010).

5. C.R. Harper, et al., “Flaxseed Oil Increases the Plasma Concentrations of Cardioprotective (n-3) Fatty Acids in Humans,” J. Nutr. 136, 83–87 (2006).

6. I.A. Brouwer, et al., “Dietary α-Linolenic Acid is Associated with Reduced Risk of Fatal Coronary Heart Disease, but Increased Prostate Cancer Risk: a MetaAnalysis,” J. Nutr. 134, 919–922 (2004).

7. G. Zhao, et al., “Dietary α-Linolenic Acid Inhibits Proinflammatory Cytokine Production by Peripheral Blood Mononuclear Cells in Hypercholesterolemic Subjects,” Am. J. Clin. Nutr. 85, 385–391 (2007).

8. G. Barcelo-Coblijin, et al., “ALA and its Conversion to Longer Chain n-3 Fatty Acids: Benefits for Human Health and a Role in Maintaining Tissue n-3 Fatty Acid Levels,” Prog. Lipid Res. 48(6), 355 (2009).

9. G. Zhao, et al., “Dietary Alpha-Linolenic Acid Reduces Inflammatory and Lipid Cardiovascular Risk Factors in Hypercholesterolemic Men and Women,” J. Nutr.

134, 2991–2997 (2004).

10. G. Zhao, et al., “Dietary α-Linolenic Acid Inhibits Proinflammatory Cytokine Production by Peripheral Blood Mononuclear Cells in Hypercholesterolemic Subjects,” Am. J. Clin. Nutr. 85, 385–391 (2007).

11. B.C. Davis, et al., “Achieving Optimal Essential Fatty Acid Status in Vegetarians: Current Knowledge and Practical Implications,” Am. J. Clin. Nutr. 78, 640S–660S (2003).

12. Guideline Daily Amounts: http://gda.ciaa.eu/asp2/ gdas_portions_rationale.asp?doc_id=129.

For more information Eric Bochardt Director of Marketing Glanbia Nutritionals Tel. +1 608 316 8521 www.glanbianutritionals.com

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natural sweeteners

A Sweet Escape Sweetness, one of the five basic tastes, is generally accepted as being pleasurable.

For many years sugar (sucrose) and honey (fructose and glucose) were its main sources but, more recently, there has been an increase in both the number and use of alternative, high potency sweeteners that work to lower the calorie content of foods and beverages. This capacity is given particular relevance by the increasing importance of issues surrounding calorie intake and weight management to customers; according to Tate & Lyle studies, 60% of European adults say that they limit high sugar content and calories within their diet.

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ugar reduced products offer a way for consumers to moderate their calorie intake: replacing all or some of a product’s sugars with high potency sweeteners is an effective and cost-efficient approach to reducing its sugar content. One of the more recent high-potency sweeteners to be approved for use in Europe is sucralose, which was developed by Tate & Lyle, following an intensive research programme.

SPLENDA Sucralose is a zero calorie sweetener that is made from cane sugar — but is not sugar. Its sweetening power is approximately 600 times that of sugar and its sugar-like taste gives it the benefit of helping to moderate calorie intake while providing an intensely sweet taste. It is suitable for use in a diverse range of products including carbonated beverages, ice cream, dairy desserts, salad dressing, hard boiled candies and many more. Now, with more than 5000 of the world’s leading consumer products relying on its great-tasting, zero-calorie sweetness, SPLENDA Sucralose has set the bar for being the consumers’ sweetener of choice.

Unmatched Taste Taste is vital to any food or beverage product and, to be successful, sugar-reduced offerings must be as appealing to consumers as their full-sugar alternatives.

Consumers refuse to compromise on taste, with most only repeatedly purchasing reduced-sugar alternatives when they are convinced of the high sensory profile of

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the product. Thanks to its sugar-like sweetness and flavour profile, SPLENDA Sucralose offers a solution for replacing the sweetness provided by sugar in virtually all food products, while maintaining the great taste and premium image.

Its sweetness profile is very similar to that of sugar, as demonstrated in time intensity measurements. At 5% sugar equivalence, typical of sweetened tea and coffee, SPLENDA Sucralose displays a rapid onset of sweetness and similar sweetness duration to sugar.

In addition to their sweetness, sweeteners possess a number of other tastes that contribute to an overall flavour. The flavour profiles of SPLENDA Sucralose and sugar are very similar. To compare them, a 12 member taste panel evaluated equally sweet solutions of SPLENDA Sucralose and sugar, equivalent to 9% sugar and prepared in water with a neutral pH. The key taste attributes were assigned a score rating by each individual member, which were then averaged and found to demonstrate the similarities between the two flavour profiles.

Unbeatable Stability In addition to assisting consumers to moderate their calorie intake with great tasting products, SPLENDA Sucralose also has a number of other qualities that make it appealing to food and drink manufacturers; for example its technical advantage of stability during processing and long-term storage, even when incorporated in low pH products. SPLENDA Sucralose

strap

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natural sweeteners

Figure 1: Comparative onsets of sweetness perception of fructose and sucralose.

is extremely heat stable, even when exposed to high temperature food processing such as pasteurization, sterilization, UHT and baking.

This stability during food manufacture has been confirmed by a series of processing trials, which cover the main processes used in the food industry; regardless of the application investigated — from a low pH pasteurized juice drink to a UHT yoghurt — the analysis of samples confirmed that no measurable loss of the ingredient had occurred during processing.

The product also maintains its sweetness and flavour during storage, avoiding the development of off-flavours, even at a low pH; shelf-life studies have demonstrated that products sweetened with SPLENDA Sucralose retain their sweetness throughout extended periods of storage and independent investigations have also shown that the flavour characteristics of products in which it is the predominant sweetener will age in a similar manner to a full sugar product. Its excellent stability means that the sweetness profile is maintained throughout its shelf-life and the true flavour of the product is delivered more consistently, irrespective of the challenging conditions in some distribution channels.

Sweet Combinations for Increased Competitiveness In addition to the consumer desire for products with less sugar and fewer calories, cost is a further factor that determines demand — sugar prices are expected to remain volatile for the foreseeable future, making costs more difficult to manage and profitability more challenging to maintain.

Replacing sugar with SPLENDA Sucralose provides an effective method of combining a reduction in costs with meeting consumer demand for products with fewer calories.

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The regulatory cut off point for making ‘sugar reduced’ claims is 30%, which has traditionally led companies to aim to reduce calories by 30%. SPLENDA Sucralose has been successfully used alone, reducing sugar levels by 30% and achieving significant cost savings on sweeteners. However, when reducing sugars to meet economic objectives, a light positioning is not inevitable; reformulated products can also be intended to sit on the shelf beside the full calorie versions.

Although in the interests of cost reduction it makes sense to extend sugar reduction beyond this 30% cut off, this creates a formulation challenge, as products must retain their original taste.

To this end, Tate & Lyle has developed innovative new concepts to help its customers to get ahead of the competition. For example,

it recently developed an orange carbonated soft drink that delivers a sugar reduction of 50% compared with the full sugar version and a significant sweetener cost saving of up to 40%, while still providing the great taste, sweetness and mouthfeel consumers look for. The combination of fructose and SPLENDA, which have complementary sweetness profiles, used in this case provides a sweetness synergy that allows a greater sweetener and calorie reduction. Fructose has a faster onset of sweetness perception, which boosts fruity tones and spice flavours and helps to deliver a more balanced sweetness and taste profile (Figure 1).

This combination gives manufacturers the opportunity to replace traditional fullsugar drinks with a lower cost alternative that has fewer calories. Sucralose works well in combination with many other nutritive sweeteners; it has been shown that blending it with nutritive carbohydrate sweeteners creates an excellent sweetness quality and, in most cases, a degree of sweetness synergy that results in incremental cost savings. Studies have demonstrated that partial replacement of the nutritive sweetener with SPLENDA Sucralose can be achieved without detrimentally impacting the flavour or sweetness in various food and beverage systems. Furthermore, the combination is sometimes sweeter than the sum of the individual sweeteners — as is the case when formulated with fructose. The ingredient can also be used in combination with any other high potency sweeteners; an experienced product developer will be able to customize the sweetness and flavour profile of the sweetening system to meet particular taste or budget requirements by blending high potency sweeteners; SPLENDA Sucralose will exhibit its cost saving advantages when combined with most of these.

Tate & Lyle has gained more than 30 years of experience working with sucralose and has pioneered the development of the most sophisticated manufacturing and testing processes used today. The company states that it is committed to delivering a consistent, reliable supply of the sweetener — manufactured to the highest standards of purity and hygiene.

For more information Rony Van Den Abbeele Product Manager, Sucralose, Tate & Lyle Speciality Food Ingredients Rony.vandenabbeele@tateandlyle.com www.tateandlyle.com

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natural sweeteners

Welcoming a New Era

The 11th of November 2011 was a very special day … and this was not only because it could be written 11.11.11! It was also the publication date of the EU Regulation marking the formal opening of the whole European market to stevia-based sweeteners.

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tevia is currently successfully used as a sweetener in Asia, North America and South America and products made from it have been on the French market for 2 years, under temporary approval. Only now, however, are food and drink manufacturers able to take an EU-wide perspective on developing new food and beverage formulations that include naturally-sourced, calorie-free sweetness.

Popular interest exists, but expectations are high; consumers are watching their calorie intake more carefully, but still resist compromising on taste and eating experience in the products they buy.

Furthermore, they increasingly prefer ingredients and products to be as natural as possible and demonstrate high ethical standards on the part of the companies behind them.

This presents a huge opportunity — and a significant challenge — to manufacturers. First, there’s the question of working out how to formulate successfully. Second, the vital issue of how to position stevia-based products and finally, how best to ensure consistent ingredient quality and availability to support roll-out on a pan-European scale. Cargill has been addressing these questions since 2004, when the decision was made to build a brand new Truvia business standing for quality, consistency and sustainability in stevia. Since then it has conducted almost 60,000 hours of food and applications work to bring Truvia stevia leaf extract to market, establishing three crucial success factors in the process.

Capability Stevia is not a ‘single ingredient’ solution. To reduce calories without reducing taste and enjoyment, you can’t simply replace sugar with Truvia stevia leaf extract. The whole food matrix needs to be rebalanced to suit precise requirements. Cargill is in a strong position to undertake this reformulation effectively with its range of sweeteners, texturizing ingredients and other ingredients such as cocoa and chocolate. This interconnected in-house capability has driven the creation of Truvia stevia leaf extract and is now inspiring the creation of successful products.

Working with more than 100 food and beverage companies, Cargill has helped to launch great tasting stevia-sweetened products across four continents. In the US, Truvia stevia leaf extract is present in Glaceau Vitaminwater zero and Powerade beverages and YoCrunch yoghurt, among many other products. In France, the extract is used in Coca-Cola’s Fanta Still and Eckes-Granini’s Joker and Réa brands.

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natural sweeteners

Brand Activation On pack branding can make consumers aware of reformulated products and promote trust in an ingredient — but how is awareness of an ingredient brand generated?

Cargill’s Truvia brand tabletop sweetener, containing Truvia stevia leaf extract has been extremely successful in the US, becoming the number one natural sweetener brand and recognized by 57% of consumers. Following partnership agreements signed with leading sugar brands Silver Spoon in the UK, CristalCo (Daddy) in France, Eridania in Italy A5 quer-4c-D-F-E:Layout 1 07.09.2010 and Azucarera Ebro in Spain, the sweetener

is being launched in Europe as from now, with a £5 million consumer advertising spend in the UK alone. Truvia branding works: in the US, a leading powdered beverage brand has moved from being a reluctant user of the brand to whole-hearted endorsement after capturing the benefits of the Truvia consumer campaigns and awareness building.

Sustainability Cargill has drawn substantial experience of agricultural supply chains in mature and developing agricultural businesses 15:23 Uhr Seite 3 from its 146 year history and the supply

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chain for Truvia stevia leaf extract has been in development for the past 7 years.

The company manages every step of the production process, incorporating strong environmental, economic and social standards and working to the vision of a sustainable product that supports growers. Comprehensive standards, targets and processes, such as working with the Carbon Trust towards a goal of becoming carbon neutral in 2020, have been developed and, as part of its desire to be measurable in this area, Cargill has invited inspection and scrutiny of its processes and results. Stevia offers great potential for reformulation in a wide range of food categories, such as dairy, beverages and even confectionery. The promise of naturally sourced, calorie-free sweetness is incredibly attractive to consumers, although manufacturing to meet their needs and negotiating a market of many options and myriad claims is a complex challenge.

For more information Henry Hussell Head of Marketing, Cargill Sweetness EMEA Tel. +32 154 00 411 www.cargill.com

www.stolz-concept.de

We’re taking a (super)critical look at extract quality

FLAVEX ® Naturextrakte GmbH · info@flavex.com · www.flavex.com

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bone and joint health

Walking on Egg Shells

There is no doubt that an optimally functioning skeletal system is crucial for overall health and vitality: strong bones, flexible joints and healthy soft tissue work together to support movement and facilitate an active lifestyle. Most of us recognize the tremendous benefits of staying active and for many this includes doing what we can to strengthen our skeletal system, with the goal of avoiding the disease and injury that can detrimentally affect our bones and joints and disrupt our way of life.

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or those who desire a natural approach to maintaining healthy bones and joints, there are numerous products designed to address the challenges that compromise skeletal health, making this category of products one of the largest within the dietary supplement industry. As a result, the consumer may face a difficult task in selecting the best products. Fortunately, there are bone and joint health products that do stand out from the plethora of products on the shelves — and they contain ingredients that exhibit impressive efficacy, are extensively researched and are derived from a renewable US food source: the humble hen’s egg.

Natural Eggshell Membrane Joint comfort is important to all of us; even the basic movements required to engage in normal activities depend upon joint flexibility without pain. Unfortunately, there are many diverse factors that can place stress on our joints, including an active lifestyle, excess weight, family history and the ageing process.

Most dietary supplement products designed to support joint health contain glucosamine or chondroitin, or both, frequently in combination with other dietary ingredients, such as MSM, hyaluronic acid and various anti-inflammatories.

Research support demonstrating the benefits offered by these products has been mixed, but generally positive in the long-term. However, the required dosage is relatively high, it takes several months for the positive effects to be experienced; for some, the benefits are less than remarkable.

Natural eggshell membrane (NEM) is an alternative choice for supporting joint health.

NEM is derived from the inner membrane of hen eggshell that is situated between the portion typically consumed as food (the egg white and yolk) and the hard outershell. It is a unique,

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naturally occurring source of several noteworthy glycosaminoglycans (GAGs), including chondroitin and hyaluronic acid, as well as collagen, other beneficial proteins and amino acids that are integral to joint health.

NEM is unique in other ways as well. Not only does it provide important building blocks for healthy joints, but it may also help to facilitate a healthy inflammatory response. In vitro data has shown that NEM decreases pro-inflammatory biomarkers, including IL-1α, IL-1, MIP-1α, MIP-1β, TNF-α and VEGF. More importantly, the research support for NEM is impressive, not only demonstrating that it works as well as or better than other therapeutic ingredients in this category, but also because it offers some distinct additional advantages.

The results from two open-label studies demonstrated the positive effects of natural eggshell membrane in enhancing joint comfort and flexibility.1 Each study evaluated levels of pain, with one also evaluating improvements in range of motion and in both a single daily 500 mg dose of NEM resulted in a significant response at the end of the 7 day treatment. In a separate randomized, multicentre, double-blind, placebo-controlled clinical study, 500 mg of NEM was found to statistically reduce both pain and stiffness in patients with knee osteoarthritis in as little as 10 days.2 This positive benefit continued throughout the duration of the study (60 days).

This clinical study also revealed that NEM showed clinically meaningful results from a brief responder analysis, the NNT (Number Needed to Treat), a widely accepted and statistically valid measurement used in clinical practice to determine the effectiveness of a healthcare intervention — in this study the parameter measured was pain reduction. For a treatment to be deemed effective, one out of every five

patients should experience at least a 50% reduction in pain within 30–60 days. The lower the NNT, the better the treatment modality is judged to be. The NNT for NEM was 5.0 (60 days), which was much better than the NNT for a combination of glucosamine/chondroitin or for celecoxib (Celebrex), an NSAID commonly used to treat the symptoms of arthritis and other joint disorders. The NNT values for stiffness, measured at 10, 30 and 60 days, were equally as striking, particularly at the 60 day point, when the NNT was 2.4.

No participants experienced the gastric or cardiovascular side-effects often associated with NSAIDS, an important result not only for individuals with arthritis, but also for those who regularly engage in sports or other athletic activities and experience the joint discomfort, inflammation and stiffness resulting from frequent joint motion. It is notable that all these studies utilized the relatively small single 500 mg dose of NEM, compared with the 1500 mg recommended dose for glucosamine products, which is typically split into three 500 mg doses. The recommended dosing for chondroitin is 1200 mg, also split between three 400 mg or two 600 mg doses.3 In terms of convenience, NEM provides a preferable alternative.

The safety profile for NEM is also significant; with the exception of those with known egg allergies, there are no known adverse effects associated with the use of NEM, even after long-term use. This is especially important for individuals suffering from conditions that warrant extended use, in addition to those who want to remain active into middle age and beyond. NEM is self-affirmed GRAS, produced in a GMP facility in the US and contains no lactose, gluten, MSG, salt, sugar, artificial colours, flavours, sweeteners or chemical preservatives, additives or fillers.

bone and joint health

Eggshell Calcium for Bone Health Osteoporosis and other disorders characterized by a weakening or loss of bone mass are increasing in prevalence — and the increase isn’t entirely a result of our ageing populations.

Most people under the age of 50 give little thought to their risk of hip fractures or developing osteoporosis; we tend to think of these issues as affecting the elderly, specifically post-menopausal, small-boned women.

(BMD). Eggshell calcium (ESC) provides these advantages and more; the calcium derived from eggshells is a natural food source, containing a high content of elemental calcium that is readily absorbed through the intestinal tract. It is a non-mined, environmentally friendly renewable source of calcium and doesn’t pose the risk of containing significant quantities of heavy metals such as arsenic, lead or mercury, found in many other calcium sources.

However, bone disorders don’t suddenly become an issue when we reach a certain age and definitely aren’t limited to a particular group of individuals. Bone loss may accelerate more rapidly in women, especially after menopause, but past the age of 20, most of us, both men and women, will start to lose more bone than we make.4 This natural bone loss is more pronounced in women and as a result of several environmental and lifestyle factors, physicians are beginning to report signs of low bone mass in women in their 20s, 30s, and 40s — this trend should be a concern for all of us.

We can’t control all the factors that can harm our bones, but we can control our diet, exercise plan and our choice of the right bone-support supplement to ensure that we are doing what we can to maintain the health of our skeletal structure. In selecting the best bone support product, it is important to consider several factors. Most importantly, an ideal bone support product should contain a source of calcium that has been researched and shown to not only be readily absorbed into circulation from the GI tract, but also functions to increase bone mineral density

contain calcium in the form of calcium carbonate. This has the advantage of containing considerably more elemental calcium than other forms, such as calcium citrate or calcium gluconate, so a smaller dose is needed to provide the recommended daily value. In many cases however, this advantage is offset by its poor absorbability. Most supplements containing calcium carbonate require gastric acid to properly dissolve (ionize) it to be readily absorbed through the intestinal wall into circulation. Therefore, it is recommended that calcium carbonate supplements be taken with food to increase the levels of gastric acid, which is in itself is somewhat problematic, as calcium carbonate is a gastric acid neutralizer. Individuals who frequently use acid neutralizing medications or who have low stomach acid are usually advised to select another form of calcium.5 Other calcium sources, such as calcium citrate, are more readily absorbed but contain less than 25% elemental calcium, necessitating a much larger dosage in either the number or size of tablets and capsules to achieve the recommended daily dose.

A significant number of calcium supplements

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ESC is unique; it has a high content of elemental calcium — approximately 40% — which is readily absorbed, whether taken with or without food. This is in part owing to the natural presence of transport proteins that facilitate intestinal absorption.6 In addition, ESC is better tolerated than other forms of calcium and is less likely to cause constipation or the other GI symptoms that are a common complaint of those taking calcium supplements. The benefits of ESC are supported by research that reveals its positive impact on bone mineral density.

Published results from several research studies demonstrated that supplementing with ESC, along with magnesium and vitamin D3, resulted in an improvement in BMD by up to 6% in a relatively short time (4–8 months) in patients with osteoporosis.7 Not only is ESC readily absorbed but also functions quickly and effectively to improve bone density.

Protecting the body’s skeletal system is a goal that can only be accomplished through high levels of dedication. Selecting the right joint and bone health supplements is integral to this process. If ingredient priorities include proven safety with GRAS status, a US supplied renewable and environmentally friendly source, well-researched efficacy substantiation and guaranteed testing for contaminants including heavy metals and microbes, then NEM and ESC are the obvious choices for supporting joint and bone health.

References 1. K.J. Ruff, et al., “Eggshell Membrane: A Possible New Natural Therapeutic for Joint and Connective Tissue Disorders. Results from Two Open-Label Human Clinical Studies,” Clin. Interv. Aging 4, 235–240 (2009).

2. K. J Ruff, et al., “Eggshell Membrane in the Treatment of Pain and Stiffness from Osteoarthritis of the Knee: a Randomized, Multicenter, Double-Blind, Placebo-Controlled Clinical Study,” Clin. Rheumatol.

28(8), 907-914 (2009).

3. http://www.mayoclinic.com/health/chondroitinsulfate/NS_patient-chondroitin/DSECTION=dosing 4. Natural Osteoporosis Foundation: http://www.nof. org/aboutosteoporosis/bonebasics/howbonesgrow 5. http://ods.od.nih.gov/factsheets/calcium 6. W. Daengprok, et al., “Chicken Eggshell Matrix Proteins Enhance Calcium Transport in the Human Intestinal Epithelial Cell, Caco-2,” J. Agric. Food.

Chem. 51(20), 6056–6061 (2003).

7. J. Rovensky, et al., “Eggshell Calcium in the Prevention and Treatment of Osteoporosis,” Int. J. Clin. Pharmacol. Res 23(2–3), 83–92 (2003).

For more information Heather Thompson Global Marketing Communications Stratum Nutrition heather.thompson@stratumnutrition.com www.stratumnutrition.com

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bone and joint health

Building Bones Stronger, for Longer

They say that 70 is the new 50 — and to watch senior citizens “going for the burn” at the local gym or doing battle on the tennis courts, they appear to be right. Adults entering their golden years today have more to look forward to than any previous generation. Medical science, improved preventive care and nutritional and pharmaceutical interventions for everything from high cholesterol to garden-variety fatigue not only help us to live longer, they also help us to live better. Yet even as today’s elderly remain active and independent well into their seventh or eighth decades, all it takes is one fall or fracture to rob them of their independence, bring their hard-earned vitality to a halt and remind us all that even this “new old age” is accompanied by osteoporosis and fragility that can still put us out of commission.

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his, however, does not have to be the case. Elderly consumers can take control of their health — and possibly stave off osteoporosis — by leveraging their diet’s role in preventing it. As scientists study the relationship between diet and osteoporosis, they’re learning that the antioxidant lycopene may help us reduce risk and improve our new old age.

Stealthy Condition What sets the new old age apart is that its characteristic health issues are no longer the acute diseases that put our grandparents in early graves.

Instead, chronic concerns — diabetes, heart disease, hypertension, arthritis and so on — follow us well into our golden years precisely because they’re not fatal. We’ve learned to manage them for the long-term, even if we can’t cure them outright. Such is the case with osteoporosis, a disease in which low bone mass and the progressive weakening of the bone’s architecture result in increased risk of fracture.

It is a stealthy condition and sufferers often don’t know that they have it until they experience their first bone break. In advanced cases, even a light bump of the furniture or a hearty cough can bring about fracture.

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Osteoporosis is of particular concern to menopausal women because the hormone oestrogen increases bone density, halting the natural process of bone breakdown known as resorption. As a result, when oestrogen levels drop during menopause, bones lose an important protector and strengthening agent. The increasing number of women now reaching menopausal age will be mirrored by an increasing number becoming susceptible to the fragility and fractures that make osteoporosis so incapacitating individually and so costly to society at large.

A Global Burden In fact, according to the International Osteoporosis Foundation (IOF), the disease already affects an estimated 75 million people in Europe, the US and Japan and its burden on healthcare systems will only increase in line with the global elderly population. In the US, the National Osteoporosis Foundation predicts that the cost of osteoporosis will reach $25.3 billion by 2025 and the IOF reports that, in Europe, levels of osteoporosisrelated disability already exceed those caused by cancers (with the

bone and joint health

exception of lung cancer) and are comparable with or greater than the disabling effects of chronic diseases such as rheumatoid arthritis, asthma and hypertension-related heart disease.

Although osteoporosis has entered the public consciousness as a “women’s disease,” neither gender is spared by the condition. The IOF estimates that osteoporotic fracture will strike one in five men who live past the age of 50, compared to one in three women of the same age group, and that by 2050 the worldwide incidence of hip fracture in men will increase by 310% and 240% in men and women, respectively.

More than Minerals It is no surprise that so much money and effort has gone into understanding the progression, treatment and prevention of osteoporosis. When that research has focused on nutritional factors, it has usually, and not without reason, turned its attention to calcium.

The body stores about 99% of its calcium in the bones, where it forms a critical component of hydroxyapatite, a calcium-phosphate complex that gives bone its structural rigidity. Calcium alone, however, can neither prevent nor cure osteoporosis.

Protein, which constitutes up to 22% of bone by weight and 50% by volume, is also involved, serving as a matrix in which minerals embed.

The body thus needs a steady supply of top-quality protein for bone maintenance, especially as we age. Despite some studies showing that high intakes of animal protein may trigger calciuria, or excess calcium in the urine, other research points out that a high-protein diet can actually increase intestinal calcium absorption. Then there’s vitamin D, which supports calcium metabolism and its incorporation into the skeletal structure. In children with severe vitamin D deficiency, bones inadequately mineralize, retarding growth and leading to the pain and deformity of rickets. Once a rare deficiency in the developed world owing to its presence in fortified foods and capacity to form in the skin when exposed to sunlight, public health efforts to discourage sun exposure have inadvertently reinstated vitamin D on the ‘vitamins of concern’ list.

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Oxidation Offensive Aside from vitamin D, protein and calcium, do other nutrients hold promise as a dietary check on osteoporosis? In fact, some do. Antioxidants have long attracted notice for stemming the progress of chronic, oxidationrelated diseases such as atherosclerosis, neurodegenerative disorders and some forms of cancer. Now researchers are investigating whether they can combat the oxidative component of osteoporosis. Scientific literature demonstrates such a component in the development of osteoporosis; oxidative stress induced by free radicals increases bone loss, with high concentrations of free radicals weakening and killing the osteoblast cells that promote bone synthesis, and promoting the formation of the osteoclasts responsible for bone resorption. Researchers have also found epidemiological evidence of an inverse relation between oxidative stress biomarkers and bone mineral density.

In examining the antioxidant concentrations of women with and without bone loss, several case-controlled studies have found there to be less antioxidant activity in those with osteopenia — a condition of low bone density that falls short of osteoporosis — than in their healthy postmenopausal counterparts. This may reflect the body’s endogenous antioxidant system kicking into overdrive in osteopenic women to “turn off” resorption-promoting osteoclasts.

The Lycopene Link As osteopenia progresses to osteoporosis, our internal defenses appear to become overwhelmed, allowing oxidation and subsequent bone loss to proceed. This raises the question of whether, when our endogenous antioxidants fall short, dietary antioxidants can step in — and researchers are optimistic that they can. Although the supporting science is still in its infancy, the carotenoid antioxidant lycopene, a pigment found in tomatoes, watermelon and other red foods, has been the subject of considerable excitement as a result of its potential to reduce the risk of osteoporosis.

Lycopene appears to inhibit osteoclast formation and subsequent free-radical production in vitro, reducing the rate of bone resorption.

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bone and joint health

Furthermore, in human and mouse models the carotenoid’s effect on osteoblasts appears to be stimulative, boosting growth, differentiation and activity. Researchers have observed a positive association between lycopene status and bone mineral density and postulate that the correlation may contribute to a reduced risk of osteoporotic frailty and fracture.

The State of the Science A US Department of Agriculture-funded longitudinal dietary study, published in 2009 in the Journal of Bone and Mineral Research, followed participants in the Framingham Osteoporosis Study for more than 15 years and found that those with a high lycopene intake — 12.7 mg/day — suffered significantly fewer non-vertebral osteoporotic fractures compared with participants who consumed only 2.7 mg of lycopene daily. When the researchers examined the relationship between hip fractures and consumption of lycopene-rich foods, they found that subjects who ate at least 4.4 servings of certain foods such as tomatoes, tomato juice and/ or sauce, grapefruit, pizza and watermelon per week had significantly fewer hip fractures than those who consumed such foods at a rate below 4.4 servings weekly.

Moreover, they observed no such associations for the antioxidants betacryptoxanthin, lutein, zeaxanthin or alpha- or beta-carotene, hinting that lycopene may be unique among carotenoids in its effect on osteoporosis risk reduction.

A more recent dietary study examined bone resorption rates, antioxidant activity and oxidative stress markers to measure the effect of dietary lycopene on osteoporosis risk. In the first month of the study, 60 postmenopausal women aged 50–60 years consumed no lycopene at all. Then the researchers randomly assigned the women to 4 month long, twice daily regimens of ordinary tomato juice, lycopeneenhanced tomato juice, a tomato lycopene Lyc-O-Mato capsule or a placebo. Following treatment, those on the lycopene regimens showed not only increased antioxidant activity relative to those taking the placebo, but decreased levels of markers for both oxidative stress and bone resorption. The study was published online in Osteoporosis International in June 2010.

An even more recent research abstract published in 2011 in the journal Bone followed 440 healthy, postmenopausal women, each of whom supplied the researchers with 4 day diet diaries and blood and urine samples. The researchers measured the women’s bone mineral density at five sites using dual-energy X-ray absorptiometry and found that women with higher dietary lycopene intakes not only exhibited higher serum lycopene levels, but that those levels translated into significant increases in bone mineral density and formation, and decreases in bone resorption biomarkers. Women in the higher dose lycopene groups also displayed improved oxidative stress parameters. The results led researchers to conclude that the dietary antioxidant lycopene may help to decrease the risk of bone loss and osteoporosis.

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Bones and Beyond Researchers are still trying to tease out the mechanisms by which lycopene achieves these benefits, but most proposed modes of action thus far focus on the carotenoid’s potent antioxidant capacity. This comes as no surprise to Dr Yoav Blatt, chief technology officer at LycoRed, who commented: “It just makes good sense; during the past few decades, what we’ve learned about disease prevention and antioxidants — and lycopene in particular — has been game-changing. When you look at how lycopene reduces the oxidative stress related to risk for cardiovascular disease, cancer, hypertension, diabetes and even male infertility, a role for lycopene in preventing bone loss and osteoporosis almost seems the next logical step.”

As the science surrounding lycopene and bone health matures, so will the public’s interest in the relationship grow. Why? Because, as Blatt points out, today’s seniors are a savvy lot when it comes to their personal health and arm themselves with information about conditions that concern them, whether that be by following medical websites, gleaning peers’ experiences from social media or simply quizzing their own medical professionals. “If news arises that links lycopene to improved bone health,” Blatt says, “you can bet they’ll be on it.”

This opens the door for product developers to design foods and beverages that directly target this educated, health-aware community.

Consider a beverage that bills itself as a ‘bone-health cocktail;’ in addition to soy or dairy protein and calcium, it might deliver natural, tomato-sourced Lyc-O-Mato, which is not only specially formulated for water-solubility but contains the full complement of naturally occurring carotenoids, in addition to lycopene. Blatt continues: “Then, for the beverage’s vitamin D component, you could use our CapsuDar D3 CWD ingredient — we designed it to dissolve instantly and, by encapsulating it, we protect it against light, oxidation and acid. What we really think is exciting about the ingredient, however, is that it goes into solution in beverages with crystal clarity, which means that this fat-soluble vitamin can now be invisible, even in flavoured waters.”

By formulating with nutrients that address seniors’ bone health concerns, you can reach a consumer base that’s eager to be addressed. Blatt has seen this firsthand: “Our research shows that today’s older consumers are hungry — or thirsty, if you like — for products that are relevant to them,” he says — “that means designing for bone health benefits.” In addition, they’re less price-sensitive when these products offer benefits backed by sound science, as well as the required great taste and texture. “It’s their health, after all,” Blatt points out, “if we in the food industry can help to improve it, and maybe even save consumers money relative to expensive medical treatments, I think we’re getting the ball rolling in a positive direction.”

For more information Karina Munch Bedrack Sales Manager LycoRed Bio Ltd Tel. +972 732 327 500 info@lycored.com www.lycored.com

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A Holistic Approach to Joint Health A

ffecting approximately 30 million people in the US alone, osteoarthritis (OA) is the most prevalent chronic joint disease, with a rising global incidence that is ensured by an ageing population and an obesity epidemic.

Diverse treatment options that include pharmacological, non-pharmacological and surgical approaches are available to manage the main clinical features, such as pain and loss of joint function â&#x20AC;&#x201D; they have, however, shown limited success. The pharmacological option in particular is accompanied by serious gastrointestinal and cardiologic sideeffects, which, aside from the heavy financial burden, make it unfit for a safe and long-term approach.

Despite some of their number displaying efficacy in human clinical trials, the outcome of non-pharmacological options, such as dietary supplements, remains inconclusive.

One reason for this disappointment is

www.nutraceuticalmag.com January/February 2012

that current OA treatment options fail to address the complexity of osteoarthritic pathogenesis, which involves abnormal signal transduction in various cells found in the cartilage, synovium and subchondral bones. At a molecular level, OA is accompanied by the disruptive turnover of extracellular matrix (ECM) in the cartilage; catabolic changes in ECM are mediated not only by the secretion of inflammatory mediators but by the disorganization, fragmentation and eventual loss of collagen fibres and proteoglycans such as aggrecans (a multi-molecular complex of glycoproteins and GAGs). Additionally, OA is associated with the reduced lubricating capability of the synovial fluid, which is likely to result from the breakdown of HA. Thus, any effective treatment should be able to address these multi-faceted aspects of OA to halt or modify its course, while providing relief from its debilitating symptoms.

Partial versus Comprehensive Dietary Approach

Dietary ingredients subjected to human clinical trials that have shown potential in managing OA-associated symptoms include glucosamine, chondroitin sulfate, avocado soybean unsaponifiables (ASU), pycnogenol and collagen (in both undenatured and hydrolysed forms). Although clinical relevance and biological mechanisms are yet to be established, the finished products that contain these ingredients appear at least to be safer than their pharmacological counterparts, in addition to reducing some of the debilitating OA symptoms. Among these ingredients, glucosamine and its combination with chondroitin sulfate lead the market. However, a recent meta-analysis of the ten largest clinical trials performed under high-standard clinical protocols demonstrated that its efficacy in reducing OA-associated pain was seriously called into question, as data

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37

Figure 1: Bioavailablity of LMW HA in hydrolysed chicken sternal cartilage extract.

obtained from more than 3000 OA patients failed to show a statistical significance of pain-reducing effect as compared to placebo.

A plausible explanation may be that the two ingredients act on the complex pathological process in the cartilage only by supplementing GAGs and fail to address the more important issue: the loss of the collagen fibre network.

As previously stated, OA is a dynamic and complex disease that involves the degradation of ECM in the cartilage that comprises both collagen (primarily type II) and non-proteinous molecules such as GAGs — and thus requires a more comprehensive approach to counteracting the degenerative process.

Chicken Sternal Cartilage Mirrors Human Cartilage OA is also termed a ‘wear and tear’ disease of the articular cartilage of the synovial joint; the most common and active joint in the human body. Aside from water, which comprises 70–80% of human cartilage, collagen and proteoglycans are its major components, each assuming 10–20% of the avascular glossy covering of the underlying subchondral bone, followed by the chondrocytes, which produce and maintain the cartilage ECM and comprise 1–5% of it. Proteoglycans are a multi-molecular complex of glycoproteins with GAGs such as HA, keratin sulfate and chondroitin sulfate, which are immobilized into the collagen fibre matrix. The nature of this complex network of diverse molecules implies that an ingredient made from the same type of cartilage can offer a more effective nutritional approach to OA than glucosamine or its combination with chondroitin sulfate.

Classified as an articular cartilage — and with a composition of collagen type II and GAGs that mirrors that of human articular cartilage — chicken sternum cartilage is a potential solution. Furthermore, recent research on hydrolysed collagen and GAGs has suggested that hydrolysed chicken sternal cartilage extract containing LMW GAGs, as well as hydrolysed collagen type II (MW of 1.5–2.5 kDa), appears to harbour diverse biological properties — in addition to enhanced bioavailability — that not only make it relevant to a comprehensive dietary support for OA-associated symptoms but offer a possible diseasemodifying effect through a potential regeneration of the cartilage.

Hydrolysis Enhances Bioavailability A number of collagen types have been found in the human body, with types I, II, and III being predominant. Collagen type II is specific to the articular cartilage, constituting more than 90% of collagen in the tissue, whereas types I and III are abundant in the skin dermis.

Most collagen is found as a macromolecular triple-helix form that is poorly soluble in its native or undenatured state. Hydrolysing this macromolecule sufficiently to reduce its MW substantially, depending upon manufacturing protocols, results in a collagen that becomes much more soluble.

The most direct effect of the hydrolysis process is to increase the collagen’s bioavailability — as demonstrated by a study using a mouse model, which revealed that more than 90% of hydrolysed collagen was absorbed into the small intestine. A separate study, which used human subjects,

demonstrated that hydrolysis of the chicken sternal cartilage not only reduced the MW of the collagen type II but also depolymerized the HA (a macromolecule with a native MW that ranges higher than 1x106 Da) into shorter chain LMW fragments. When hydrolysed chicken sternal cartilage extract containing the LMW HA is ingested, the latter greatly increases its levels in the human blood compared with its baseline, thus suggesting that LMW HA is also highly bioavailable (Figure 1). Several patents exist surrounding this invention and have been assigned to BioCell Technology, LLC.

Synergy of Multiple Biological Properties A neglected issue in the discussion of a dietary ingredient’s efficacy is its pharmacokinetics — its absorption, distribution and metabolism — which affects both its bioavailability at the target tissue and its eventual health benefits. Although a number of ingredients display their exciting potential in in vitro cell-based studies, most of these fail to demonstrate their presumed physiological effect as a result of their short half-life in vivo. The hydrolysed type II collagen and LMW HA contained in hydrolysed chicken cartilage extract is unique in that these important issues have been addressed relatively well by independent studies.

• First, in a mouse model, the majority of radiolabelled hydrolysed collagen was absorbed through the gastrointestinal tract and found to be accumulated in the cartilage in the long-term, suggesting that the metabolites of ingested hydrolysed collagen reach the target site of action.

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bone and joint health

• Second, human ingestion of hydrolysed chicken cartilage extract led to the appearance of many different forms of collagen-derived peptides, among which the dipeptide, Pro-Hyp, was predominant.

Studies suggested that this dipeptide was biologically active in vivo and exerted multiple physiological effects; for example, the articular cartilage of mice fed with Pro-Hyp in an OA-inducing, phosphoruscontaining diet showed a significantly lower degree of cartilage degradation than control mice. There was also a reduced level of death of the chondrocytes, suggesting that this dipeptide provided a chondroprotective effect. An alternative study revealed that the biosynthesis of HA was stimulated from the synovium cells and that, moreover, the collagen-derived Pro-Hyp stimulated the proliferation of the dermal fibroblasts.

This is particularly intriguing as the cells’ senescence is considered to be an important underlying cause of the dermal breakdown of collagen fibres in skin ageing.

• Third, hydrolysed collagen — not the native or undenatured form of collagen — was shown to stimulate the chondrocytes to produce and secrete collagen type II and proteoglycans, with hydrolysed collagen type II from chicken sternums displaying higher activity than hydrolysed collagen type I. This in vitro study suggests a possible positive feedback mechanism for the regulation of collagen turnover in the cartilage, which has significant ramifications for the use of the extract in rebuilding degraded cartilage.

• Fourth, hydrolyzed chicken sternal cartilage extract was shown to inhibit hyaluronidase in vitro, in a dose-dependent manner (Figure 2). Hyaluronidase contributes to ageing processes in the skin by degrading HA, which has its ability to bind water attenuated by a shortened chain length and decreased polyanionic charge. The loss of the amount and integrity of HA may lead to weakened joint lubrication and dampened resistance to compressive forces applied to the cartilage. Given the fact that hyaluronidase-mediated degradation of HA is implicated in ageing and inflammation, the ability of this extract to inhibit it may have profound implications for the ageing processes that take place in the joints and skin.

Figure 2: Inhibition of hyaluronidase.

however, was a study performed on a dietary ingredient containing both hydrolysed collagen and GAGs such as HA. The clinical trial of LMW hydrolysed chicken cartilage extract revealed its safety and significant efficacy in managing OA-associated conditions — and thereby its potential to enhance the quality of daily life. Its daily ingestion for 8 weeks led to a significant difference in the reduction of the WOMAC (Western Ontario McMaster University Osteoarthritis) score — the composite of the efficacy endpoints for pain, stiffness and physical difficulties — compared with placebo (Figure 3). At the end of the study, the difference between the two groups’ scores was approximately 40%, suggesting that this novel ingredient that provides a synergy between hydrolysed collagen type II and LMW HA is a strong candidate for a holistic solution to this complex and dynamic joint disease.

Figure 3: Improvement of OA-associated symptoms.

This dietary ingredient boasts multiple mechanisms of action that indicate a potential holistic approach to joint health.

Human Clinical Trials This dietary ingredient boasts multiple mechanisms of action that indicate a

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potential holistic approach to joint health. A randomized, controlled human clinical trial is the gold standard in investigating the clinical relevance of the bioavailability and biological properties of the LMW hydrolysed chicken sternal cartilage extract to the effective management of OA-associated symptoms.

There have previously been clinical studies demonstrating the safety and beneficial effects of hydrolysed collagen, in addition to GAGs, with respect to chronic arthritic joint conditions, including OA. Only recently,

A Holistic Approach and Beyond Collagen and GAGs are found in the ECM of virtually every connective tissue, including cartilage, tendon, ligament, blood vessel and skin dermis. Their efficacy for joint health has been well documented by clinical trials, as discussed above, and recent experimental and clinical skin studies have provided evidence for their positive effect on skin ageing. For example, in an animal model study, hydrolysed collagen led to an increase in the number of dermal fibroblasts and the diameter of collagen fibrils in the ECM of the skin dermis. Hydrolysed collagen can also protect the skin from UV damage such as epidermal hyperplasia and the loss of collagen type I. In addition, the Pro-Hyp dipeptide that appears in human blood after ingestion of hydrolysed chicken cartilage extract was shown to enhance the biosynthesis of HA from the dermal fibroblasts.

It can be hypothesized that ingredients containing both hydrolysed collagen and GAGs can be relevant to other connective tissues, such as tendons and ligaments, as these molecules are also essential for their structure and functions. Further studies are warranted to investigate their effect on these and other connective tissues, which will prove whether this unique ingredient can offer a holistic solution to ageing-associated joint, skin and connective tissue problems.

For more information Dr Joosang Park Vice President of Scientific Affairs BioCell Technology, LLC Tel. +41 7146 321 231 joosang@biocelltechnology.com www.BioCellTechnology.com

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bone and joint health

Bone Boom A

lthough gut and digestive health claims remain the most popular to be appended to functional dairy products, there is considerable ongoing interest in bone health. Bone health or added calcium claims (or both) featured in more than 17% of dairy launches on an active health platform in the 12 months to the end of June 2011, or 4% of dairy launches as a whole (as recorded on the Innova Database). The majority of bone health launches in the sector were in dairy drinks or dairy alternative (mainly soy) drinks, which accounted for more than twothirds of the total, well ahead of yoghurt, which accounted for slightly more than 15%.

Dairy products marketed on a bone health platform have become increasingly sophisticated in recent years. Originally their primary focus was a naturally high calcium content or calcium fortification and they largely relied on consumer awareness of the mineral’s benefits; recently, however, these products have made greater use of ingredient blends that go beyond calcium, including ingredients that help to boost calcium absorption and bone formation, such as vitamin D. Ingredients now promoted in bone health applications include vitamin K2, lysine, prebiotic fibres and soy isoflavones.

Functional drinking milks have traditionally focused on added ingredients (such as vitamins, minerals,

probiotics) and a general health positioning rather than using more specific health claims. As a result, they have not always been regarded as functional in the strictest sense of the word. However, the number of more specialist milks being launched is changing this, although the market remains fairly fragmented and highly regionalized, with countries such as the US and Spain having large markets that partially reflect large liquid milk consumption levels. Spain has one of the largest European markets

calcium and vitamin D. It was launched in Spain in 2009 and, unlike most added calcium products in the past that have been aimed at the children’s market, was targeted at older women. It met with some initial success in Spain and has since been launched in Portugal and Italy, where it is called Danaos. Testing of Densia in France, however, proved disappointing and it was not launched onto the French market. In 2011 it was introduced in Brazil, both in the more common spoonable format and

for vitamin and mineral enriched milks, with particular strength in calcium fortified products. The first of these was introduced to the Spanish market by Puleva in 1993 — this triggered a burst of activity in fortified milks that built the market to its current level (calcium-enriched lines accounted for more than 16% of the Spanish milk market in 2010). Product activity in calcium milk now focuses more specifically on bone health ingredients used in conjunction with calcium, as demonstrated

by Puleva’s introduction in late 2010 of its Calcio con Isoflavonas de Soja — a skimmed milk with calcium and soya isoflavones.

In the yoghurt market, meanwhile, specialist bone health products are starting to appear in Europe, with recent activity being led by Danone and its Densia yoghurt with added

as a dose-delivery drink.

Interestingly, General Mills — which has just purchased a 51% controlling share in Yoplait, the world’s number two yoghurt brand — announced in July 2011 that it was looking for new ingredients or technologies for fermented dairy products. The goal is to move “beyond the known impact of calcium and vitamin D” in boosting the bone formation process, in addition to looking at solutions to increase calcium absorption.

Lu Ann Williams, research manager at Innova Market Insights, contends that, despite some of the problems caused by the economic downturn, consumer confusion and ongoing regulatory issues, the potential for functional lines such as bone health dairy products remains as strong as ever. She explains: “This is being driven by ageing populations, rising interest in healthy lifestyles and a growing awareness of the link between diet and health, supported by significant investment by the food and drinks industry in innovative product activity.”

For more information Lu Ann Williams Innova Market Insights Tel. +31 263 192 000 contact@innovami.com www.InnovaDatabase.com

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BUSINESS & TECHNOLOGY

Where food and pharma meet

NBT is your musT-read source of News, updaTes aNd developmeNTs iN The fuNcTioNal food, NuTraceuTical, dieTary supplemeNT aNd iNgredieNT iNdusTry. www.nutraceuticalmag.com Probiotics Restoring the balance Claims under pressure

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Women’s HealtH EXCLUSIVE ROUNDTABLES Supplementing the fairer sex

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bone and joint health

A Joint Effort

T

he ageing process is said to bring maturity and a wealth of experience, but it can also lead to a decline in health and vitality — sufficient intake of essential nutrients, however, can help older people to stay physically active and get the most out of life. There is a rapidly growing portion of the population that falls into the over-65 age group, which is resulting in a commercial renaissance for nutritional products targeting the senior audience.

Osteoarthritis of the knee afflicts 40% of people above the age of 70 worldwide; 80% of sufferers are forced to limit their movements and 25% cannot perform basic daily activities.1 A burgeoning demand for products that provide effective joint relief is behind the projected growth of the the European and US joint health markets by 7–8% and 6%, respectively. 2 Joint relief products, mainly comprising dietary supplements and beverage applications, are targeted predominantly at two consumer groups: people above the age of 50 and sports enthusiasts. ­ A joint is the point at which two or more bones come together to facilitate movement — healthy joints move smoothly, without pain or swelling, owing to a complex system of lubrication and shock absorption that acts

www.nutraceuticalmag.com January/February 2012

like a cushion and prevents excessive bone friction. Products currently available on the market are predominantly glucosamine/ chondroitin (GC) based, but new research has revealed that they are not as effective as once thought.3 The search for new solutions, has led nutraceutical manufacturers to vitamins, minerals and omega-3 fatty acids; according

to a number of studies, vitamin E, which is found in the synovial fluid, helps to reduce joint discomfort and low levels of vitamin B6 are associated with pro-inflammatory conditions that negatively affect joint health.4–7 In addition, vitamin D deficiency has been linked to osteoarthritis and rheumatoid arthritis.8–11 Regular consumption of omega-3 long chain polyunsaturated fatty acids (PUFAs), primarily docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been shown to reduce joint discomfort as a result of their anti-inflammatory properties.12–14 A metaanalysis of 14 clinical trials in patients with rheumatoid arthritis or joint pain linked PUFA supplementation with a significant decrease in joint pain intensity, duration of morning stiffness and number of sensitive joints.15 In another study, a daily high dose of omega-3 supplements was found to decrease the severity of symptoms associated with ankylosing spondylitis, a chronic disease that mainly affects joints of the spine and hips.16 Equally, a high intake of vitamin C substantially reduces uric acid concentration in the blood and is associated with minimized risk of gout.17

Adding Life to Years The ability to move unhindered by pain is a fundamental part of maintaining quality

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of life. Strong joints help seniors to remain independent and continue doing the things they enjoy. DSM Nutritional Products offers a wide range of high-quality micronutrients, available in Quali Blends nutritional premixes, which address all major causes of joint discomfort and immobility. In one easy step, DSM’s dry or liquid premixes can be added to a vast range of food, beverage and nutraceutical applications, providing manufacturers with opportunities to tap into the lucrative market for joint health products. DSM’s nutritional solutions are protected by the Quality for Life seal — which ensures the ingredients come from a dependable, safe and sustainable source — giving manufacturers the confidence to go to market with new products.

For more information

1. World Health Organization, “Chronic Rheumatic Conditions,” 2009 (www.who.int/chp/topics/rheumatic/en/).

2. Frost & Sullivan, “European Bone and Joint Health Ingredients,” 31 March 2009 (www.frost.com/prod/servlet/reporttoc.pag?repid=M39C-01-00-00-00).

3. J.E. Silbert, et al., “Dietary Glucosamine Under Question,” Glycobiology 19(6), 564–567 (2009).

4. K. Fairburn, et al., “Alpha-Tocopherol, Lipids and Lipoproteins in Knee-Joint Synovial Fluid and Serum from Patients with Inflammatory Joint Disease,” Clin. Sci. 83(6), 657–664 (1992).

5. G. Blankenhorn, ”Clinical Effectiveness of Spondyvit (Vitamin E) in Activated Arthroses. A Multicenter Placebo-Controlled Double-Blind Study,” Z. Orthop. Ihre Grenzge. 124(3), 340–343 (1986).

6. N.H. Haflah, et al., “Palm Vitamin E and Glucosamine Sulphate in the Treatment of Osteoarthritis of the Knee,” Saudi Med. J. 30(11), 1432–1438 (2009).

7. Chiang EP, et al. “Pyridoxine Supplementation Corrects Vitamin B6 Deficiency but Does Not Improve Inflammation in Patients with Rheumatoid Arthritis,” Arthritis Res. Ther. 7(6), 1404–1411 (2005).

8. C. Ding, et al., “Serum Levels of Vitamin D, Sunlight Exposire, and Knee Cartilage Loss in Older Adults: the Tasmanian Older Adult Cohort Study,“ Arthritis Rheum. 60(5), 1381–1389 (2009).

9. S.K. Das, et al., “Osteoarthritis,“ Best Pract. Res. Clin. Rheumatol. 22(4) 657–675 (2008).

10. T.E. McAlindon, et al., ”Relation of Dietary Intake and Serum Levels of Vitamin D to Progression of Osteoarthritis of the Knee Among Participants in the Framingham Study,” Ann. Intern. Med. 125(5), 353–359 (1996).

11. M. Mouyis, et al., “Hypovitaminosis D Among Rheumatology Outpatients in Clinical Practice,” Rheumatology 47(9), 1348–1351 (2008).

12. D. S. Kelley, et al., “DHA Lowers Blood Triglycerides in Diet Study,” J. Nutr. 139(3), 495–501 (2009).

13. M. Troseid, et al., “Serum Levels of Interleukin-18 are Reduced by Diet and n-3 Fatty Acid Intervention in Elderly High-Risk Men Metabolism 58(11), 1543–1549 (2009).

14. R.J. Goldberg, et al., “A Meta-Analysis of the Analgesic Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation for Inflammatory Joint Pain,” Pain 129(1–2), 210–223 (2007).

15. B. Sundstrom, et al., “Supplementation of Omega-3 Fatty Acids in Patients with Ankylosing Spondylitis,” Scandinavian Journal of Rheumatology 35, 359–362 (2007).

16. H.B. Stein, et al., ”Ascorbic Acid-Induced Uricosuria: A Consequence of Megavitamin Therapy,” Ann. Intern. Med. 84(4), 385–388 (1976).

17. H.K. Choi, et al., “Vitamin C Intake and the Risk of Gout in Men: A Prospective Study,” Arch. Intern. Med. 169(5), 502–507 (2009).

O S pp pe or ak tu e ni r tie s

DSM Nutritional Products Charlotte Frederiksen Tel. +41 6181 583 54 charlotte.frederiksen@dsm.com www.dsm.com

References

The Executive Advisory Board of the Vitafoods Europe Conference is now accepting papers for consideration for the 2012 Event.

Key topic areas include: • Market

•

•

for Aging Consumers Gut Health • Mental Health • Joint Health

•

Physical Performance Food Allergy & Intolerance • Ingredients from Nature

In addition to traditional presentations, we would also like to receive: Scientific papers | commercial applications | new markets | business development case studies | latest research thinking | panel debates | new applications Q&A sessions | merger and acquisition strategy | growth strategies

For further details visit www.vitafoods.eu.com/nbtcall Or contact Lynne Evans at lynne.evans@informa.com

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weight management

Intuitive Nutrition D uring the past 20 years, there has been a dramatic increase in obesity and the incidence of being overweight. Evidence suggests that even without reaching an ideal weight, a moderate amount of weight loss can be beneficial in terms of reducing the levels of some risk factors, such as blood pressure.1 SANKOM-CanDiet is a dietary supplement that contains inulin and oligofructose enriched with vitamins, mineral salts, green tea and natural flavours. Inulin and oligofructose are dietary fibres known as fructans. Inulin is a linear fructose polymer belonging to the group of fructans known for its fermentability and bulking properties. Oligofructose, a short-chain fructan obtained from inulin, might enhance satiety, thereby resulting in greater reductions in energy intake.2,3 Green tea, by containing both tea catechins and caffeine, may act by inhibiting

were not included in the trial. A daily dose of 4–6 SANKOM-CanDiet supplement chews was recommended to each patient and the

Index in 25 randomly selected patients: at the beginning of the trial the average BMI was 29.44, which had decreased to an average

duration of the programme was 4 weeks.

We gave each patient the following intake recommendations: •1 –2 chews + 1 glass of water (or warm tea) 30–40 minutes before lunch •1 –2 chews + 1 glass of water (or warm tea) in between lunch and dinner to prevent hunger fluctuation •1 –2 chews + 1 glass of water (or warm tea) 30–40 minutes before dinner.

No hypocaloric diet was suggested to patients.

BMI of 28.20 by the end of the trial.3

Summary of Results The observational results of this trial show a total average weight loss of 3.1 kg (an average loss of 2.7 kg in women and 3.5 kg in

This open pilot trial presents a rationale to propose oligofructose supplements for the management of food intake in overweight and obese patients. catechol O-methyl-transferase, and by inhibiting phosphodiesterase, providing positive effects on body weight management.4 In an open pilot trial to evaluate body weight reduction during a period of 4 weeks using SANKOM-CanDiet supplement chews, we selected 51 overweight patients (23 men and 28 women), aged between 18 and 60 years. Patients suffering from obesity as a result of hormonal or metabolic diseases

www.nutraceuticalmag.com January/February 2012

men). Considering four ranges of weight loss: 4 men and 8 women had a weight loss in the 0–2 kg range, 11 men and 6 women were in the 2–4 kg range, 8 men and 6 women were in the 4-6 kg range and 2 women were in the 6–8 kg range. One woman had a weight gain of 0.1 kg and another woman experienced a gain of 0.2 kg. No change in bodyweight was observed in 1 man and 3 women.

Furthermore, we evaluated the Body Mass

Conclusions SANKOM-CanDiet was shown to be a useful supplement in the management of weight loss in overweight patients. This open pilot trial presents a rationale to propose oligofructose supplements for the management of food intake in overweight and obese patients. A double-blind controlled study might be useful to better evaluate the efficacy of SANKOM-CanDiet supplement chews in weight reduction.

Furthermore, a normal calorie regimen should be recommended and followed by each patient, to reduce any eventual dietrelated interference.

References 1. C.L. Ogden, et al., “The Epidemiology of Obesity,” Gastroenterology 132(6), 2087–2102 (2007).

2. P.D. Cani, et al., “Oligofructose Promotes Satiety in Healthy Humans: A Pilot Study,” Eur. J. Clin.

Nutr. 60, 567–572 (2006).

3. K. Whelan, et al., “Appetite During Consumption of Enteral Formula as a Sole Source of Nutrition: The Effect of Supplementing Pea-Fibre and Fructo-Oligosaccharides,” Br. J. Nutr. 96(2), 350–356 (2006).

4. M.S. Westerterp-Plantenga, “Green Tea Catechins, Caffeine and Body-Weight Regulation,” Physiol. Behav. 100(1), 42–46 (2010).

For more information Vladimir Shkolnikov SANKOM Switzerland Avenue de la Gare 49 CH-2800 Delemont, Switzerland Tel. +41 32 422 5000 info@sankom.com www.sankom.com

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46

industry issues

Without a Safety Net A

number of recent public recalls of food products that have occurred in the global consumer marketplace have caused significant turbulence in consumer confidence when it comes to the safety of food and beverage products.

Any loss of confidence within the consumer mindset is obviously a horrific situation for a brand and the company that proffers the product; consequences include millions of wasted marketing dollars — plus millions more reallocated to regaining confidence — destruction of mindshare and grossly impacted shareholder/ownership value. Most importantly, the safety of people who trust a brand enough to ingest it is, in many cases, placed at serious risk.

Safely manufacturing products — any products — within the food chain has two prime points of contact: raw material procurement and processing.

This short paper intends to provide an overview for both.

T=0 (time begins at 0) begins at the point of raw material procurement, but not the actual purchasing of the material. The primary point of failure in any supply chain is the company’s cultural focus on “how they buy;” a professionally managed organization will have clear and concise specifications, guidelines and processes to ensure that there can be no misinterpretation by the vendor, buyer or receiving organization.

Failure point number two occurs when the buyer is rated and incentivized; show me a purchase price incentivized buyer and I will show you a buyer singularly focused on price. Incentivize a buyer on the total cost of quality, including being penalized for rejections, and I will show you a buyer who is motivated to find the highest quality raw material at a market competitive price.

I always make the argument that no buyer in a commodity market is so good that they can negotiate a price more than 10% below the market value. If you are receiving a product significantly below this, then it’s guaranteed that you are also receiving a product below quality standards.

www.nutraceuticalmag.com January/February 2012

Once the procurement hygiene is calibrated, the process of finding specification compliant providers of raw materials can begin. When one or more is located, we find ourselves with the opportunity for failure point three: the qualification and continued surveillance of an approved supplier. Taking a Suppliers Certificate of Approval at face value only makes the litigator’s job easy, stopping by a supplier once a year for lunch or a ceremonial dinner does not qualify a supplier. It is imperative that your procurement funds are buying a vendor’s consistent process, internal safeguards and market compensated professionals who understand the deliverable that they are providing. The deliverable must be a specification compliant product harvested or manufactured within accepted and recognized agricultural or manufacturing practices. Continued surveillance means just that — continuous; a $2000 travel expense is nickel slots compared with a line down situation caused by a product rejection at month or quarter’s end. Garner your savings by operating efficiently because you can schedule with confidence, not by shortchanging your quality focus.

Now that the raw material has arrived at your dock, how squared away are you? The media is replete with stories about government inspected production facilities that were grossly mismanaged, poorly run and downright dangerous. The responsibility for safety is with you, not an industry or governmental audit.

Once again, the company’s cultural focus goes a long way to determine how professionally the company is managed. Incentive programmes, reviews and promotions must have a significant quality hygiene component that rewards (or is highly punitive) towards a professional manager. Senior leadership cannot physically be in every department, facility and supplier.

Nearly every case study of a recall begins at a level far removed from the boardroom.

Despite this, we, as senior leaders, are totally responsible for the actions of our colleagues and the safety of our products and processes. How one enforces and reinforces the standards of professional conduct does much to protect your business and ensure consumer safety.

For more information George Pontiakos President and CEO BI Nutraceuticals gpontiakos@botanicals.com www.botanicals.com

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48

pharma foods

From Farmer to Pharma

A

n increased awareness of advances in biotechnology has led to a growing interest in the use of foods for medical purposes, building on the long-standing tradition in many cultures of using natural herbs and foods to treat ailments. So-called ‘superfoods’ have been in receipt of increasing attention in recent years, particularly from the media — this interest is now rapidly expanding to foods with clinically enhanced properties.

Probiotics, prebiotics, functional foods, clinical foods and nutraceuticals are discussed and promoted in terms of offering general health benefits or specifically targeting a bodily function, such as improving digestion, bone density and so on. As technology evolves and more is understood about how to tailor food and drug combinations to better fit individual needs, the opportunity for tailored food that uses improved genetic profiling is burgeoning. Many in the pharmaceutical and food industries predict that, by 2020, biotechnical advances will allow us regularly to combine foods grown in the field with drugs developed in the lab; in the next decade, we can expect to see a shift in some of our basics from traditional ‘farmer foods’ to more sophisticated ‘pharma foods.’

The term nutraceutical, a combination of nutrition and pharmaceutical, is used to describe food, or a part of a food, that provides medical or health benefits, including the prevention and/or treatment of a disease: one person’s functional food can be another person’s nutraceutical. Given that they are cheaper than pharmaceutical products and may provide some of the benefits, the nutraceutical industry is an area of growth that is now attracting pharmaceutical and biotech companies; including the likes of Monsanto, DuPont, Abbott, Johnson & Johnson, Novartis and Genzyme Transgenic. Clinical — or medical — foods are by contrast specifically formulated to meet the particular nutritional requirements of individuals with specific illnesses. They are regulated and therefore prescribed by physicians. Nutraceuticals therefore, are not clinical foods.

These products have been entering the market during recent years — but the greatest potential now lies in foods created for medical benefit. The big change is the link between food preparation and nutrigenomics, which refers to applying the sciences of genomics, transcriptomics, proteomics and metabolomics to human nutrition. Nutrigenomics is a relatively new science and is the application of highthroughput genomic tools to nutrition

www.nutraceuticalmag.com January/February 2012

research: now that human genes have been sequenced and we understand more about our genetic make-up, we can use the science of nutrigenomics to tailor food to fit our genetic profiles. Pharma foods, biopharmaceuticals or ‘farmaceuticals,’ compounds produced from genetically modified crops or animals, are the result of this. They provide higher than usual amounts of various nutrients that can be consumed as foods but are distinguished from functional foods, nutraceuticals and the like in that they are not naturally occurring. They are engineered to provide specific health benefits; for instance, gene ‘pharming’ allows scientists to alter an animal’s DNA by combining it with DNA from another species. The resulting genetically modified animals — transgenic fish, cattle, sheep, goats and chickens — are tailored to provide embedded drugs and proteins for human consumption. Proponents, such as the Biotechnology Industry Organization, see that not only can transgenic animals be provided with traits that will improve disease resistance, but that they can also accelerate growth and increase proteins, provider leaner meats, increased muscle mass and improved nutritional quality.

So, for example, a salmon can be raised in half the normal time, have less fat, more meat and include extra nutrients. Although no products of this kind are currently on the market, the US National Academy of Science undertook a study that did not identify any food safety concerns. However, alongside the ethical issues of blurring the differences between separate species, issues around environmental impact and animal welfare are raised by those who oppose this type of development. Plant-made pharmaceuticals are produced using similar technology in plants: transgenic plants are engineered to have resistance to pests and harsh conditions in addition to improved shelf-life and nutritional value. Modified potatoes have been enhanced with protein and, in 2008, scientists altered a carrot so that it would produce calcium and become a possible cure for osteoporosis.

There has also been discussion of the benefits to vitamin A deficiency offered by the consumption of golden rice, which was developed by the International Rice Research Institute to alleviate micronutrient deficiencies in developing countries.

As a group, pharma foods of this kind have been a controversial issue. For example, back in 2007 several food companies lobbied the US Department of Agriculture against the introduction of pharma foods owing to “concerns about their negative impacts on food safety, on markets for food crops and on the integrity of the wider food

supply.” PepsiCo saw that “the significant risk of crop contamination that is present when plantmade pharmaceuticals are produced in food and/or feed crops leads us to the conclusion that the only way to prevent such a contamination is to prohibit their production.” In its 2008 corporate social responsibility report, which addressed concern surrounding the testing of plant-made pharmaceuticals, General Mills stated that “to fully ensure the safety of world production via plants and grains, General Mills currently opposes moving to production of any so-called ‘pharmafood’ that would use a food crop or food grain to grow or produce plant-made pharmaceuticals.”

Despite this reticence, however, and given the increasingly populous and hungry world, many companies are now proceeding with the development of pharma foods. In his initial perspective on the future of food, Jim Kirkwood highlighted the opportunities and challenges: “Pharma-food, the intersection between food and pharmaceuticals, is an area of growing opportunity for many in the food sector. As consumers demand more technologically sophisticated foods with unique, complex health benefits, food companies will need to respond. We now understand more about individuals’ disease propensities from the human genome. Therefore, nutrigenomic determination of diet becomes technically possible. Technology is advancing and as natural bioactive components are better understood, the line between pharma and food will blur: the challenge will be to find new ways to continue to provide natural, food-delivered preventive health benefits and begin to provide natural, food-delivered disease state improvement benefits without food becoming a drug.”

In a New York workshop this view gained clear support. Besides the wider recognition of the global need for more proteins and nutrients, participants perceived that “genetic profiling is advancing very quickly and is now accepted as a good thing,” “business models in the pharmaceuticals sector are encouraging significant investment in the area” and that “nutrigenomics will fundamentally change consumer healthcare, as nutritional screening becomes a standard part of health check-ups and consumers readily provide their genetic profile.” Although a controversial subject, given the benefits to be gained, the fast pace of technology development and a shift in government regulation on the horizon, the advent of widespread availability of pharma foods by 2020 looks increasingly likely. Customized foods that match medical benefit to your genetic profile will be in your shopping basket soon.

Many in the pharmaceutical and and food industries predict that, by 2020, biotechnical advances will allow us regularly to combine foods grown in the field with drugs developed in the labs

For more information Tim Jones and Caroline Dewing Infinite Ideas Limited 36 St Giles Oxford OX1 3LD UK This article was originally published in â&#x20AC;&#x153;Future Agenda: The World in 2020,â&#x20AC;? by Infinite Ideas Limited (www.infideas.com) and is reproduced with kind permission.

50

regulatory review

Finding the Needle in the Haystack

T

here is nothing more frustrating than being pressed for time to get an order filled — all you are waiting for are the analytical results to release a product … only the results are nothing like what is expected.

It is important to evaluate how a given method might affect the product by considering the analyte being tested in addition to everything else: the sample matrix. This is a simple task in relation to multivitamins or other products for which every compound is known. However, for botanical extracts — which are very complex mixtures that can contain hundreds of different chemical compounds, the chemical structure of which may be unknown— it poses major difficulties. Many of the USP assay methods for a specific analyte are designed for raw materials or a defined finished product and will not perform effectively for a finished product containing botanical extracts. A simple physical analysis or colourimetric method might be sufficient for a raw material because there are no other components to interfere, whereas one must assess all possible interfering components with a finished product.

The general progression for testing an analyte in a complex matrix involves sample preparation/extraction, separation and detection; each step must be considered in relation to each product, even if only one component is different. For example, in a finished product tested for individual bioflavanoids containing various fruit and vegetable sources including grape seed extract, the substitution of grape seed extract with green tea extract could drastically affect analytical results. For optimal method selection, one must consider the chemistry that occurs at each of the phases of analysis, keeping in mind that detector results rely heavily on the way in which the sample is prepared.

Extractions are of two main types: liquidliquid (also known as

www.nutraceuticalmag.com January/February 2012

Dr Cheri Turman

partitioning or solvent extraction) and solidliquid, including solid phase extraction (SPE) and, more recently, solid phase micro extraction (SPME). Liquid extractions are based on the chemical concept of immiscibility between two phases, as seen between oil and water. An anlayte has more affinity to dissolve with one or the other based on the chemistry concept of “like dissolves like.” There are many solvents available to the chemist, which possess various properties that allow the removal of the analyte from the matrix; properties to consider are polarity, dipole moment and hydrogen bonding capacity — sugars, for example, are polar and as a result readily dissolve in polar solvents such as water or alcohols. Super critical fluid extraction is gaining in popularity as another type of extraction technique, although the cost of equipment prevents it from becoming commonplace in most analytical laboratories.

The extraction fluid is neither a liquid nor a gas but it maintains the transport properties of a gas and the solvent-like characteristics of a liquid, with the advantages of good analyte selectivity, efficiency with repeat runs, suitability with thermally labile compounds and low solvent consumption. Only high throughput analysis can justify using this type of extraction.

For solid-liquid phase extractions, ionic and covalent interactions are also possibilities to consider when attempting to remove an analyte from the matrix. In the case of solid samples, a liquid extraction must be performed prior to solid-liquid phase extractions as liquid containing the analyte must pass over the solid support. This support provides a surface for

chemical interactions to occur between the solid and the different compounds in solution.

The solid can be used to selectively bind the analyte or bind unwanted compounds; either way, it is a method for trying to isolate the analyte being tested. Once the analyte or unwanted compounds bind to the solid support, the first solvent is removed and a second is added to break the bond formed between the solid and the analyte, which leaves the compound dissolved in the new solvent. The second solvent must have a higher affinity for the compound than the solid support — if the analyte of interest has no affinity for the solid, it will simply remain in the first solvent while many of the unwanted compounds stay bound to the solid support. Both processes help to clarify the mixture and make the next steps of separation and detection easier. SPE can also be used to concentrate the analyte in cases where it is present at very low concentrations (such as vitamin B12 in liquid products).

SPE solid supports include reverse phase, normal phase, ion exchange and adsorption.

However, it is constantly evolving and some of the new technologies, including molecularly imprinted polymers (MIPs), are selective for a single analyte or a group of structurally related analytes, thus reducing the amount of nonspecific binding of unwanted compounds.

Once the anlayte is drawn out of the matrix and into a suitable solvent, the next step is to separate it from other compounds also extracted into the solvent, using a highly controlled and repeatable process with sophisticated chromatographic instrumentation and identify/quantitate it with technologically advanced detectors. The ultimate goal is to make preparation simple with as few steps as possible, which reduces human error.

Nevertheless, the reality is that extraction and sample preparation are limited by the structure of the compounds in the matrix and complex samples will likely mean complex preparation.

For more information Dr Cheri Turman Director of Chemistry Analytical Food Laboratories Tel. +1 800 242 6494 cheri@afltexas.com

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