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Preview-9781466596429 A26657694
Handbook of Functional
Nutraceutical
11
Science
and
Technology
Nutraceutical Science
and Technology
Series Editor: Fereidoon Shahidi
11
Beverages and Human Health
Handbook of
Edited by
Fereidoon Shahidi
Cesarettin Alasalvar
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Contents
Preface....................................................................................................................................................... xi
Editors......................................................................................................................................................xiii
Contributors.............................................................................................................................................. xv
8. Apple Juice....................................................................................................................................... 93
H.P. Vasantha Rupasinghe and Surangi Thilakarathna
v
vi Contents
21. Golden Berry and Selected Tropical (Açai, Acerola, and Maqui) Juices.................................251
Coralia Osorio, Maria Elisa Schreckinger, Prerna Bhargava, Woo Young Bang,
Daniel A. Jacobo-Velázquez, and Luis Cisneros-Zevallos
52. Coffee...............................................................................................................................................661
Iziar A. Ludwig, Michael N. Clifford, Michael E.J. Lean, and Alan Crozier
61. Beverages Fortified with Omega-3 Fatty Acids, Dietary Fiber, Minerals, and Vitamins...... 801
Fereidoon Shahidi and Priyatharini Ambigaipalan
Index........................................................................................................................................................861
Preface
The market for functional beverages represents the largest and fastest growing segment of the functional
foods sector, with an annual growth rate of almost 20% in the United States. The production and consump-
tion of functional beverages has gained much importance due to their major contribution to health pro-
motion and disease risk reduction. They constitute an excellent delivery means for nutrients and bioactive
compounds, including vitamins, minerals, antioxidants, omega-3 fatty acids, plant extracts, sterols/stanols,
dietary fiber, amino acids and biopeptides, prebiotics, and probiotics, among others. There have been con-
tinuous innovations in functional beverages and their associated market over the last decade as consumers
seek novelty and health benefits from their beverages. The market for new functional beverages with added
bioactive ingredients with health benefits has grown rapidly with positioning strategies linked to energy, ath-
letic performance, digestion, aging, satiety, cognitive ability, hydration, weight management, cardiovascular
health, cancer, diabetes, bone and joint health, and fatigue and stamina, among others.
This handbook consists of 65 chapters divided into 7 sections. Section I includes six chapters on
market trends, global regulations, flavor challenges, chemistry, health with specific reference to cancer
chemoprevention, and the prevention of postprandial metabolic stress due to consumption of functional
beverages. Section II, by far the largest part of the book, has 39 chapters on the most popular fruit
juices (acerola juice, apple juice, apricot juice/nectar, aronia juice, blackberry juice, black currant juice,
blueberry juice, cherry juice, cherry laurel syrup [pekmez], coconut juice, cranberry juice, date syrup,
dragon fruit juice, goji berry juice, golden berry and selected tropical juices [açai, acerola, and maqui],
grape juice, grapefruit juice, guava juice, hawthorn juice, Indian gooseberry [amla] juice, kiwifruit juice,
lemon juice, lime juice, mango juice, mangosteen juice, melon juice, mulberry juice, noni fruit juice,
orange juice, papaya juice, passion fruit juice, peach juice, pear juice, pineapple juice, plum, prune, and
ume juices, pomegranate juice, raspberry juice, strawberry juice, and watermelon juice). Section III
reports on herbal and vegetable juices (carrot juice, Chinese medicinal herbs and root-based beverages,
tomato juice, and vegetable-containing juices [carrot, kale, and sprout]). Section IV details caffeinated
beverages, including different varieties of tea (green, black, oolong, and herbal teas), coffee (coffee
and beverages from green coffee beans), and cocoa and chocolate. Section V is on dairy and soy bever-
ages, while Section VI is on alcoholic beverage (wine) and water (maple water). Finally, Section VII
describes fermented (kefir, koumiss, and ayran) and fortified functional beverages (applications of plant
sterols and stanols in functional beverages, beverages fortified with omega-3 fatty acids, dietary fiber,
minerals, vitamins, probiotics, and prebiotics in functional beverages, functional beverages in weight
management, fortified sports drinks, and peptide-enriched functional beverages).
We are most grateful to the contributors to this handbook, who are internationally renowned research-
ers, for their comprehensive account of the global perspective on the issues of concern related to nutri-
tional characteristics, bioactive and antioxidant efficacy, phytochemicals, and health effects of beverages.
The book will serve as a major resource for those interested in the potential applications and new devel-
opments in functional beverages, nutraceuticals, and health foods. Biochemists, chemists, food scien-
tists/technologists, nutritionists, and health professionals from academia, government laboratories, and
beverage industries will find the contents of this handbook of much interest. Although this book serves
primarily as a reference manual, it also summarizes the current state of knowledge in key research areas
and contains novel ideas for future research and development. In addition, it provides easy-to-read text
suitable for teaching senior undergraduate and postgraduate students in the relevant areas. Finally, we
trust that this handbook paves the way for better appreciation of the concepts, products, and opportuni-
ties in the field for professionals, regulators, processors, and consumers.
Fereidoon Shahidi
Cesarettin Alasalvar
xi
Editors
Fereidoon Shahidi, Ph.D., FACS, FAGFD-ACS, FAOCS, FCIC, FCIFST, FIAoFST, FIFT, FRSC,
is a university research professor, the highest rank the university gives for research, in the Department
of Biochemistry at the Memorial University of Newfoundland (MUN) in Canada. He is cross-appointed
to the Department of Biology, the Department of Ocean Sciences, and the Aquaculture Program. He is a
chair professor at National Chung Hsing University in Taiwan, an honorary professor at the Chung Shan
Medical University, also in Taiwan, a visiting professor at Jiangnan University, and Dalian Polytechnic
University in P.R. China. He collaborates with many other universities in countries such as Brazil,
France, Korea, Japan, Poland, Thailand, Turkey, the United States, and elsewhere around the globe.
He is also an advisor to the Chinese Academy of Agricultural Sciences for special projects on cereals
and oilseeds. Dr. Shahidi has made numerous outstanding and innovative quality contributions to both
the basic and applied areas of food and nutraceutical science and technology and antioxidant phenolics
and omega-3 oils in health and disease. He is the only Canadian on the ISI list of top 10 (3rd to 8th)
most highly cited scientists in agricultural sciences, first recognized as the most highly cited (top 15)
individual and the most productive scientist in the area of food, nutrition, and agricultural science for
the 1991–2001 period and 3rd in citations for 2001–2011, and is now in 6th place. He has received
numerous awards from different societies and organizations for his pioneering scientific achievements.
Dr. Shahidi’s work has led to the publication of more than 760 research articles in the form of peer-
reviewed journals and book chapters. He is also the editor/author of some 64 books and holds 10 patents.
These publications, along with his extensive list of presentations, have led to the advancement of the
discipline of food science at both the national and international levels. Dr. Shahidi has trained more
than 100 Ph.D. and M.Sc. students and research assistants/associates, postdoctoral fellows, and visiting
professors and scholars, and has educated the future generation of scientists. His former students, now
his colleagues, occupy key positions as faculty members, government workers, and industry leaders in
more than a dozen countries on five continents.
Cesarettin Alasalvar, Ph.D., FIFT, is the director of the Food Institute at TÜBİTAK Marmara
Research Centre (MRC) in Turkey and is also an associate professor of food science and engineering.
He received his Ph.D. in food science and technology in 1994 from the University of Lincoln (United
Kingdom) and conducted postdoctoral research at the same university (1995–1997). Dr. Alasalvar is
a recipient of a fellowship award from the Japanese Science and Technology Agency (1997–1998).
He was then appointed as a senior research fellow/lecturer both at the Food Research Centre and the
Department of Food Science and Technology at the University of Lincoln (1998–2005). He has been
working at different positions (chief research scientist, deputy director, and director) at the Food Institute
of TÜBİTAK MRC since 2006. Dr. Alasalvar is a leading international researcher in bioactive compo-
nents from marine resources and plant materials, especially hazelnuts. He is recognized for his impact
in identifying bioactives and phytochemicals present in foods and plant-based products. He has coedited
5 books, published more than 60 scientific articles in peer-reviewed journals and 25 book chapters,
given more than 100 presentations at different international scientific conferences, and holds a patent.
He has delivered invited lectures, served as a session chairperson and poster-award chair for various
international congresses, and has organized international congresses, seminars, and brokerage events.
Dr. Alasalvar has been active in the Institute of Food Technologists (IFT) programs for many years
and has played a leadership role in the Nutraceuticals and Functional Foods Division. He served as a
past chair of the division and serves as an editorial board member of Food Chemistry and the Journal
of Functional Foods. He also served as local chair of the International Society for Nutraceuticals and
Functional Foods (ISNFF) 2014 Annual Conference and Exhibition and is currently the chair-elect of
xiii
xiv Editors
ISNFF (2014–2016). Dr. Alasalvar serves on the expert advisory board of the Turkish Goverment and
Higher Education on R&D projects and as a panelist for projects funded by the European Union (EU). He
coordinates two major EU-funded projects, EU-FP7 (NutraHEALTH) and EU-IPA (INNOFOOD), and
has received a number of international prestigious awards, including the IFT-Fellow Award (2012), the
TÜBİTAK MRC–Most Successful Researcher Award (2012), the ISNFF Merit Award for Outstanding
Contributions to the Nutraceuticals and Functional Foods Discipline and Service to the ISNFF (2014),
and the Sabri Ülker International Science Award on Public Health and Nutrition (2015) in recognition of
his pioneering scientific achievements.
Contributors
xv
xvi Contributors
Sami Fattouch
National Institute of Applied Sciences and İncinur Hasbay
Technology Food Institute
University of Carthage TÜBİTAK Marmara Research Center
Tunis, Tunisia Gebze-Kocaeli, Turkey
xviii Contributors
Chin-Lin Hsu
Nauman Khalid
School of Nutrition
Graduate School of Agricultural and Life
Chung Shan Medical University
Sciences
and
The University of Tokyo
Department of Nutrition
Tokyo, Japan
Chung Shan Medical University Hospital
Taichung, Taiwan, People’s Republic of China
Emine Aytunga Arık Kibar
Tzou-Chi Huang Food Institute
Department of Biological Sciences and TÜBİTAK Marmara Research Center
Technology Gebze-Kocaeli, Turkey
National Pingtung University of Science and
Technology Tamami Kiyono
Pingtung, Taiwan, People’s Republic of China Division of Applied Life Sciences
Graduate School of Life and Environmental
Yu Huang Sciences
School of Biomedical Sciences Kyoto Prefectural University
The Chinese University of Hong Kong Kyoto, Japan
Shatin, Hong Kong, People’s Republic of China
Daniel A. Jacobo-Velázquez
Mirela Kopjar
Biotechnology Center–FEMSA Monterrey
Department of Food Technologies
Institute of Technology
Josip Juraj Strossmayer University of Osijek
Monterrey, Mexico
Osijek, Croatia
Rui Jiao
Department of Food Science and Engineering Sarah Kranz
Jinan University Department of Nutritional Sciences
Guangzhou, Guangdong, People’s Republic University of Connecticut
of China Storrs, Connecticut
Contributors xix
CONTENTS
1.1 Introduction....................................................................................................................................... 3
1.2 Global Functional Beverage Market................................................................................................. 4
1.3 Consumer-Oriented New Product Development Case Study: Functional Beverages....................... 5
1.4 Semiotic Approach to Market-Oriented Product Concept Optimization......................................... 5
1.5 Consumer Insights on Functional Beverages.................................................................................... 6
1.6 Semiotics and Functional Beverages................................................................................................ 7
1.6.1 Stage 1: The Semiotic Sort................................................................................................... 8
1.6.2 Stage 2: Interpretation of Package Signs by Respondents................................................... 8
1.7 Semiotic Results................................................................................................................................ 9
1.7.1 Stage 1: Results..................................................................................................................... 9
1.7.2 Stage 2: Results....................................................................................................................11
1.8 Preferences and Purchase Habits toward Functional Beverages.....................................................11
1.9 Semiotics and New Product Development...................................................................................... 12
1.10 Lessons from the Case Study.......................................................................................................... 13
1.11 Conclusion........................................................................................................................................14
References..................................................................................................................................................14
1.1 Introduction
There have been many changes and innovations in the beverage market over the past years as consum-
ers seek new benefits from their beverages. One of the most important benefits sought by consumers
is health and wellness. The market for new functional beverages with added ingredients and related
health benefits has grown rapidly with positioning strategies linked to energy, digestion, aging, satiety,
cognitive ability, hydration, weight management, and fatigue, among others. While the opportunity for
developing functional beverages is high, manufacturers often struggle to achieve market success, and
the challenges new functional beverage developers face include the technological challenge of develop-
ing and marketing new products with new ingredients; differentiating brands in ultracompetitive mar-
kets; identifying the most appropriate positioning platforms of convenience; and marketing science and
technology to consumers, as well as health, natural, and legal obstacles. The high failure rates suggest
an inability to understand consumer preferences and choice motives in relation to the purchase of func-
tional beverages.
This chapter examines the main trends in the functional beverage market and identifies the key issues
related to the consumer and the functional beverage market. Following this, a case study is introduced
that focuses on developing market-oriented functional beverages based on consumer insights. It exam-
ines the importance of market-oriented approaches in developing new functional beverages and views
3
4 Handbook of Functional Beverages and Human Health
how firms can use the voice of the consumer information to design products that more closely meet con-
sumer needs. The case study examines utilizing qualitative research techniques to generate information
at the early stages of the new product development (NPD) process. In particular, it looks at using semiot-
ics to generate information on beverage packaging as it can greatly influence consumers’ first purchase
of a new product and repeat purchases.
Consumption of superfruit juice is also on the rise globally, and with increasing consumer awareness,
there are opportunities to appeal to more mass-market consumers [5]. China leads in the consumption of
superfruit juice at 1587 million liters per annum, followed by the United States and Japan. As superfruit
juices move to a wider range of beverage categories, more novel flavors and ingredients are likely to be
available to consumers. Blueberry, pomegranate, and aloe vera are consumer favorites worldwide, but
more unusual varieties will be used in future beverage manufacture such as acai berry, baobab, mango-
steen, goji berry, and sea buckthorn [5].
A key part of developing novel beverages with new ingredients will be consumer acceptance of new
ingredients, their knowledge of the potential health benefits of such ingredients, and how the specific
science and technology is marketed to consumers. In addition, consumers’ interest in health is related
to what health benefits are relevant to them and their lifestyles and, thus, are highly individualized [16].
This suggests that beverage developers need to generate deep insights into consumers’ perceptions and
how these beverages fit in with their lifestyles.
functional beverages. Semiotics is an abductive method of analyzing meanings by examining signs that
communicate information [24,25].
Research estimates that approximately 70% of purchase decisions are usually made at point of sale,
and that for approximately 40 weeks of the year, packaging is the main attribute that leads to the sale
of a product [26,27]. For low-involvement purchases, the package is the product, particularly because
impressions formed during initial contact can have lasting effects. Beyond providing pure information,
the emotional aspects of packaging graphics are more subliminal, which evolve from the styling of
various graphical elements, including logo styling, symbols, icons, colors, textures, photography, and
illustrations [28].
Semiotics can be used to understand the important role of packaging design in motivating consumer
purchase of functional beverages. This entails an analysis of consumer perceptions of all icons, colors,
and images on the package and how these combined might influence the purchase decision. Good pack-
aging can support a brand in highlighting its difference in the marketplace [16].
In the following case study, some key activities at the early design stages of the NPD process are out-
lined in terms of the use of qualitative techniques to understand consumer requirements for functional
beverages.
I think functional beverages are suitable for those who do not like dairy products or are allergic
to lactose. (Focus Group 1, male, 18–24 years)
I know that there are many probiotic beverages on the market and most of them are dairy-based.
I think a non-dairy probiotic beverage may be of interest to consumers. (Interviewee 9, male,
35–44 years)
Some young participants, across both focus groups and interviews, suggested that functional beverages
could be positioned as healthy meal replacements or, more particularly, breakfast meal replacements.
Functional Beverages 7
They felt that those with busy lifestyles could consume functional beverages at the breakfast meal occa-
sion as they were convenient and could be consumed on the go based on the method of delivery. These
products could contain the nutritional and vitamin profile of a healthy breakfast and be positioned as an
on-the-go beverage. Moreover, they suggested that functional beverages could also be marketed to dif-
ferent demographic groups as healthy alternatives to carbonated sports or energy beverages with a natu-
ral positioning strategy. However, these consumers were also concerned about the high calorie content
of functional beverages. They might not consume a functional beverage as a meal component due to its
perceived high calorie content. Examples of participants’ comments were as follows:
A meal replacement at breakfast is an option and would be welcomed by people with busy life-
styles. (Focus Group 1, male, 18–24 years)
I think it is a good idea that you can take one (functional beverage) in the morning instead of
breakfast, but I would not have it with a meal because of its high calorie content. (Interviewee
11, female, 45–54 years)
The health benefits of functional beverages were considered valuable marketing cues by both focus
group participants and interviewees. The most important health benefits that would encourage purchase
of functional beverages were enhancing the immune system, aiding the digestion, lowering cholesterol,
and having high fiber and reduced sugar. Older focus group participants were interested in disease-
preventing benefits, such as cholesterol reduction or cancer prevention. Generally, males were more
interested in the specific health claims of the product. However, female participants focused more on
their knowledge of functional ingredients and their health benefits. From a marketing perspective, this
illustrates the significance of correctly identifying a suitable target market and then positioning an opti-
mal functional beverage toward the target market.
Many participants also indicated that product information had a strong influence on their willingness
to purchase functional beverages. They suggested that product descriptions on functional beverage pack-
aging should contain information on the functional ingredients, the health benefits, the suggested daily
dosage, and the reference daily intake. The following was a typical comment:
I want to know whether I have to be careful of the dosage I consume daily. (Focus Group 1,
female, over 55 years)
These participants also mentioned that the brand name, logo, images, and color on the packaging would
influence their motivation to purchase functional beverages. In addition, many of the respondents per-
ceived that beverages that utilized a single-serve packaging format were healthier than other formats.
Fifteen product attributes were generated from consumer interviews that would strongly influence par-
ticipants’ purchase of functional beverages. It also revealed that consumers’ purchase decision in relation
to functional foods was complex and influenced by many intrinsic and extrinsic attributes such as taste,
the added ingredients to the products, health benefits, price, product volume, packaging (color, images,
typeface, and product shape), brand, and label information. Label information and packaging were seen
by many participants as being central to the purchase decision particularly with respect to reduced risk
in relation to new ingredients, new products, or new brands. Packaging has frequently been mentioned
as a direct aid for consumers for evaluating product quality and, therefore, should be carefully designed
to effectively convey product attributes to the consumer.
TABLE 1.1
Main Sign System for Semiotic Analysis of Functional Beverages
Main Sign
System Headings Examples
Brand Innocent, Actimel, and Red Bull.
Signifier Any material thing used to signify something: use of a wheat kernel and heart symbol to signify
health.
Signified The concept that the signifier refers to: healthy ingredients, energy, and naturalness.
Code A set of conventions understood in a given society: modern lifestyles, healthiness, and wellness.
Metaphor Expressing the unfamiliar in terms of the familiar: the use of phrases or images to imply that
something is healthy and natural such as the use of a halo to imply pure.
Connotation The cultural meaning of signs: the use of the color green to mean organic or natural.
Imagery The use of graphics to convey a meaning: a picture of an active person to convey the meaning that
the product is for active people.
Functional Beverages 9
that graphic elicitation, such as PowerPoint presentations, encouraged contributions from consumers that
were difficult to obtain by other means and this facilitated a more market-oriented methodology [35–37].
The semiotic interviews were transcribed from the audiotapes and analyzed using the software pack-
age QSR N6 [31]. Various codes were allocated and assigned to key segments of information within the
data [30]. A detailed analysis of the codes identified signs that when incorporated onto a product package
could motivate the purchase of new or existing functional beverages.
TABLE 1.2
Semiotic Analysis of Functional Beverage 1
Beverage Brand Innocent Pure Fruit Smoothie
Signifier Brand and image of a head with a halo.
Signified Healthy ingredients, no artificial ingredients.
Code Wellness, dietary behavior, convenience, and modern lifestyles.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that the beverage can easily be incorporated into the everyday diet to enhance
its healthiness.
Connotation The use of the white label, the brand name, and the image with a halo suggests that the beverage
is healthy to the consumer and does not contain negative ingredients.
Imagery Face with a halo to portray the perception of healthiness.
TABLE 1.3
Semiotic Analysis of Functional Beverage 2
Beverage Brand Naked Juice Smoothie
Signifier Brand and logo, dominant use of the ingredient color (green).
Signified Naturally healthy juice, energy giving.
Code Natural, organic, and healthy.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that the beverage is a natural product with natural health-enhancing benefits.
Connotation The dominant use of the color green offers a connotative relationship between the green
ingredients and the green color utilized in the packaging.
Imagery Fruit and vegetables to represent the ingredients used within the product and the use of leaves to
convey the perception of naturalness.
10 Handbook of Functional Beverages and Human Health
TABLE 1.4
Semiotic Analysis of Functional Beverage 3
Beverage Brand Actimel Original
Signifier Brand and image of rising sun.
Signified Fun, energy giving, and natural.
Code Wellness, naturalness, health, and convenience.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that consumption of this beverage would improve the healthiness of the diet.
Connotation The dominant use of the color white offers a connotative relationship between the dairy carrier used
and the perception of natural ingredients.
Imagery Rising sun over a green pasture offers the perception of energy, freshness, and naturalness.
TABLE 1.5
Semiotic Analysis of Functional Beverage 4
Beverage Brand Ribena Plus Summer Fruits
Signifier Brand and descriptor: plus.
Signified Rich in fruits, high in vitamins and antioxidants.
Code Healthy and thirst quenching.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that the juice is high in fruits and therefore high in vitamins.
Connotation The use of primary color in conjunction with the blue sky and clouds offers the perception of a
refreshing drink.
Imagery Medallion illustrating the calcium content and fruits reflecting the ingredients of the product.
TABLE 1.6
Semiotic Analysis of Functional Beverage 5
Beverage Brand Yakult
Signifier Brand: dominant use of transparent packaging with red typeface for the brand.
Signified Small and powerful.
Code Convenience, innovation, wellness, simple, and effective.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that the beverage is novel, healthy, and powerful.
Connotation The use of the red typeface for the brand on the transparent packaging offers the idea that the
beverage is simple and effective.
Imagery Not applicable.
TABLE 1.7
Semiotic Analysis of Functional Beverage 6
Beverage Brand Tropicana Essentials Orange Juice and Omega 3
Signifier Brand and descriptor (essentials) in green typeface.
Signified Necessary for healthy living and natural.
Code Convenience, health, and wellness.
Metaphor The signs transfer the qualities of the signified for another, thus creating a metaphorical sign that
offers the meaning that the beverage is essential to everyday health.
Connotation The use of the green typeface for the brand on the white packaging gives the perception of a
natural beverage with no artificial ingredients.
Imagery Faded image of male and female on the center of the package illustrating the product is essential
for every person. Iconic images of oranges reaffirming the flavor and content of the beverage.
Functional Beverages 11
I just get the Tesco orange juice with added calcium but I always buy Actimel to take to work.
(R2, male, 41–50 years)
A majority of interviewees gave significant consideration to the preferences of the overall family unit
in the purchase of healthy beverages. Interestingly, a large number of female consumers indicated they
12 Handbook of Functional Beverages and Human Health
would purchase additional single-serve beverages to meet their own specific health and wellness needs.
These beverages were nearly always a popular branded product that reflected a premium price.
I will buy a multi-vitamin juice for everyone so they are getting all the vitamins they need but I
will have my own shot every morning. My kids would not drink those. (R10, female, 31–40 years)
The packaging type was also of particular importance to consumers. The majority of respondents indi-
cated that a resealable package that was easy to open and close was essential, in addition to being light-
weight and rectangular in shape, so that it could easily fit on the refrigerator shelf. For products that were
positioned on the basis of single-serve portions, a number of consumers mentioned the need for compact
packaging so that a number of portions could fit in the fridge. A small number of female consumers
also mentioned how these products should also have durable packaging for on-the-go consumption. The
importance of on-the-go consumption to the purchase decision was evident across many of the demo-
graphic groups.
The font size of nutritional and labeling information on packaging was an important issue for respon-
dents. They noted that food firms used smaller font sizes on the back of pack labeling, and, in some cases,
the additional information provided to support a health claim or logo. Importantly, these respondents
were reluctant to try any new products that displayed difficult to read text.
I find that the writing explaining ingredients has become very small and I hate having to look for
my glasses. So I will just pick up another one [beverage] instead. (R11, male, 61+ years)
Most respondents believed that juice and dairy beverages they regularly purchased were healthy and
positively contributed to the overall wellness of their diet. In particular, dairy was perceived to be a
naturally healthy product category, and older consumers mentioned a number of health benefits including
calcium, phosphorus, and protein. However, younger respondents were more positive toward water and
juice-based beverages particularly with energy, hydration, and beauty benefits.
Respondents were unsure how cholesterol reduction could be effectively conveyed through an image.
The majority of respondents revealed that a heart image would contribute to the perception of reduced
cholesterol levels, while images that conveyed the idea of natural ingredients and active individuals were
also deemed appropriate. In addition, a smaller number of respondents emphasized the need for key
words to accompany the image in order to avoid confusion at the retail point of purchase for the con-
sumer. Similar responses were found for the health benefits of omega-3 fatty acids. Respondents identi-
fied the image of a heart as appropriate to describe the benefits of this ingredient, and they stressed the
need for text that clearly outlined omega-3 benefits. Typical comments included the following:
I would like to see an active person and the healthy heart. (R2, male, 41–50 years)
Natural ingredients and a heart like before, but I would have to see the words Omega-3 to know
for sure. (R3, female, 51–60 years)
The image of a wheat shaft or grain kernel was suggested as a symbol for fiber in functional beverages.
Respondents also associated these images with whole grain. The most common health benefit for this
type of product was gut health and digestion. The use of images of leaves and grass on a beverage were
associated with fresh organic products. Although not a specific health benefit, respondents indicated that
these images were successful in attracting their attention to products in the retail environment.
Moreover, opaque packaging was associated with very familiar beverages that made no specific health
and wellness claims. Transparent packaging has been associated with reduction of the uncertainty or
purchase risk associated with novel products [38].
Typographical elements are often used to intentionally signify specific things, namely, the subcultural
context, the strategy of the food manufacturer, and the target group of consumers [39]. This was evident
for a number of beverage packages that were examined in the semiotic analysis. It was clear the respon-
dents held a preference for typeface that was simple and clearly legible for beverages that claimed to
have a functional benefit or positioned as a healthier product. Overemphasis on the depth and curvature
of the type gave the perception of a cheaper quality product for the vast majority of respondents. For this
reason, functional beverage packaging needs to incorporate plain, possibly Antigua-style text, as this text
is mostly associated with healthier products [26].
The consumer interviews also provided an insight into how the presence of a claim could interact with
other aspects of packaging to influence consumers’ attitudes and purchase intentions. The strategic use of
color is regarded as a fundamental tool in corporate marketing strategies and provides a means of product
and brand differentiation [40,41]. Importantly, this case study revealed that color was the primary sign
that attracted consumers to a brand on the market that they were unfamiliar with. In addition, consumers
made assumptions about the taste of the product based on the primary color used in the packaging.
It was also evident that the use of certain colors in smaller amounts on product packaging, that is, other
than the main package color, encouraged the consumer to interpret metonymic relationships. The most
common of which was the use of the colors green, white, and yellow: green to portray the meanings of
natural, healthy, organic, and fresh; white to portray the meanings of natural, fresh, and free-from; and
yellow to portray the meanings of sunlight, morning, energy, and fresh. In addition, the use of pictures
and images also attracted consumer attention to brands they were unfamiliar with on the market [37].
optimization research technique that is used to measure consumer preferences, through utility trade-
offs, for product concepts to understand preferences for products [42]. It is premised on the idea that
consumers evaluate the value of an object by combining the separate amounts of value provided by each
attribute. This enables the development of an optimal functional beverage that creates the most value for
consumers.
1.11 Conclusion
The market for functional beverages continues to grow as consumer demand for traditional carbonated
beverages falls, in line with changing consumer health and wellness lifestyles. This market offers huge
opportunities for firms that develop market-oriented beverages, where the intrinsic and extrinsic attri-
butes are designed to closely meet consumer expectations, offering benefits as part of a healthy lifestyle.
A market-oriented approach to the development of new functional beverages incorporates the voice of
the consumer information at the early stages of the NPD process in order to increase the likelihood of
consumer acceptance of such beverages. This is particularly important in the very competitive func-
tional beverage sector where consumers are faced with new choices, innovations, and brands on a very
regular basis.
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euromonitor.com/health-and-wellness-in-ireland/report (accessed April 16, 2014).
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nutraceuticalsworld.com/blog/marketwatch/2012-08-15/stevia-going-from-strength-to-strength
(accessed April 16, 2014).
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com/blog/top-functional-beverage-trends-for-2013 (accessed April 16, 2014).
Functional Beverages 15
13. Lipp, M., Beverages at the forefront of innovation in booming functional food market, June–July 2012.
Published online at: http://www.foodsafetymagazine.com/magazine-archive1/junejuly-2012/regulatory-
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naturalproductsinsider.com/articles/2012/11/2012-trends-in-functional-foods-and-beverages.aspx
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18. Mattsson, J. and Helmersson, H., Food product development: A consumer-led text analytic approach to
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16 Handbook of Functional Beverages and Human Health
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Pearson International, Upper Saddle River, NJ, 2006.
2
Global Nutraceutical Regulations
for Functional Beverages
CONTENTS
2.1 Introduction......................................................................................................................................17
2.2 Beverages and Regulations..............................................................................................................18
2.3 Beverages versus Liquid Dietary Supplements................................................................................18
2.4 Powdered Premix Products and Liquid Concentrations................................................................. 19
2.5 Regulatory Requirements for Ingredients in Beverages and Dietary Supplements....................... 20
2.6 Regulatory Requirements for Labeling of Beverages..................................................................... 20
2.7 International Regulatory Norms..................................................................................................... 21
2.7.1 Japan................................................................................................................................... 21
2.7.2 European Union.................................................................................................................. 22
2.7.3 China.................................................................................................................................. 22
2.7.4 Canada................................................................................................................................ 22
2.7.5 South Korea........................................................................................................................ 23
2.7.6 India.................................................................................................................................... 23
2.7.7 Australia............................................................................................................................. 23
2.7.8 New Zealand....................................................................................................................... 23
2.7.9 Israel................................................................................................................................... 24
2.8 World Market.................................................................................................................................. 24
2.9 Conclusion....................................................................................................................................... 25
References................................................................................................................................................. 25
2.1 Introduction
Phytopharmaceuticals have been used for centuries as novel prophylactic agents for the prevention and
treatment of diseases and disorders in humans and animals as well as for the improvements of chronic
degenerative conditions. Approximately more than 2500 years ago, the father of modern medicine
“Hippocrates” proclaimed the association of food with health benefits and quoted “Let food be thy medi-
cine and medicine be thy food” (Hippocrates, 460–377 BC). Nutritionists and health professionals are
continuously unveiling the beneficial health effects of diverse functional foods and nutraceuticals. This
may range from isolated nutrients as dietary supplements, herbal products, and fortified diets that can
be used as soups, cereals, fortified juices, or beverages, among others. Functional beverages are specifi-
cally designed to quench thirst and maintain healthy fluid and water levels and nutrition. Some examples
include orange juice fortified with vitamin C, calcium, and phytosterols, berry drinks with anthocyanins,
and green tea fortified with epigallocatechin gallate. It is very important that functional beverages carry
appropriate labeling information for the benefit of the consumer. It is also essential that these functional
beverages strictly follow regulatory guidelines to attract consumer confidence in the marketplace [1].
Nutraceuticals and functional foods are becoming increasingly popular around the world, and
especially the demand for functional nutraceutical beverages is on the rise. A significant number of
17
18 Handbook of Functional Beverages and Human Health
nutraceutical beverages have been introduced in the United States over the last two to three decades and
become increasingly popular. In 2010, the diverse functional beverage market including energy drinks,
sports drinks, various functional drinks, yogurt drinks, smoothies, and ready-to-drink teas and coffees
reached US$23.4 billion, and the same trend is similar globally [2]. The growth of functional beverages
is quite obvious in developing nations because of increased awareness of maintaining good health, body,
and mind. Another reason may be affordability and convenience. This chapter focuses on the intricate
aspect of nutraceutical beverage regulation process in the United States and around the world.
• A major emphasis has been given on the safety and appropriate labeling claims, which can be
achieved partly through the good manufacturing practice (GMP) regulations and keeping track
of adverse event reporting.
• Increased enforcement of regulations will streamline the comparatively new and fragmented
companies for regulatory compliance.
• Beverages are conventional foods that may not be marketed as dietary supplements. Under sec-
tion 201(ff)(2)(B) of the Federal Food, Drug, & Cosmetic (FD&C) Act (21 U.S.C. 321(ff)(2)(B)),
“dietary supplement” means a product that, among other requirements, “is not represented for use
as a conventional food or as a sole item of a meal or diet. On the other hand, beverages are conven-
tional foods under the FD&C Act” [4]. Sometimes, when the label of a product characterizes it as a
dietary supplement, the product may not meet the requirements of a dietary supplement. Beverages
or products in liquid form can be represented as conventional foods as a result of factors such as
their products or brand name, packaging, serving size, and recommended daily intake (RDI) or
the volume that is specified to be consumed, composition, recommendations, directions for use,
statements or graphic representations in labeling or advertising, and other marketing requirements.
important determinants whether the product is represented as a conventional food and may not be mar-
keted as a dietary supplement. However, in special circumstances, a single factor may determine whether
the product can be termed as a “conventional food,” but, in most circumstances, a combination of factors
would determine whether the product is represented as a conventional food.
Labeling: It has been outlined by Food and Drug Administration (FDA) that statements, graphics dis-
played on product labels, labeling, and advertisement details including websites and social media should
be available when the agency evaluates the intended use and its appropriate representation. It is very
important to emphasize that a product that exhibits a supplement fact panel may still be a conventional
food if it contains statements that it is intended to “refresh” or “rehydrate,” in which statements indicate
that the intended use is as a beverage (which is a conventional food). Graphic representation in terms of
symbols, vignettes, schematic, or pictorial serving suggestions is another representation of a product as a
“conventional food.” In salad dressings, one can see the advertisement or label with a picture of a liquid
product being poured onto a salad would identify the product as a salad dressing.
Product identification: The brand name or product name uses the terms “beverage,” “bottled water,”
“iced tea,” “coffee,” “apple cider,” “juice,” “orange juice,” “soda,” or “drink” on the label to represent
the products as conventional foods because “bottled water” is a terminology identifying a specific cat-
egory of conventional food, which is defined in a “food standard regulation” (see 21 Code of Federal
Regulations [CFR] 165.100).
Packaging: Packaging is a modern art, which is a great marketing tool to contain, hold, preserve, and
exhibit the aesthetic appeal of the product as well as to provide directions as to how the product is to be
used. It should also include the size, volume of liquid, shape, storage conditions, color and design of the
container, and packaging details including whether it is reclosable or to be consumed in a single serving.
These types of packaging and labeling are extensively used for common beverages. A good example is a
Coca Cola pop-top aluminum can bearing a silver strip indicating “cola supplement” that shows that the
product is cola-flavored soft drink intended to be consumed in a single serving. It is very important to
indicate that containers indicate other specifics, including serving size and RDI that need to differenti-
ate the product from a conventional food, even if the container looks like a regular beverage container.
Composition and generally recognized as safe (GRAS) status: To overcome the regulatory hurdles, the
ingredients which can be incorporated in functional beverages must be safe as demonstrated by a bat-
tery of toxicological studies and follow all regulations that are imposed by the regulatory agencies in the
country of use. In the United States, it is expected that the ingredients used in beverages are self-affirmed
or FDA-notified GRAS and qualified for the requirement need for food additives.
Recommended use: The serving size and RDI are very important criteria. Average daily drinking fluid
intake is approximately 1.2 L/day. Liquid formulations that suggest on their labels serving size and/or
RDI to consume up to three 16 ounce bottles (~1.4 L)/day that they are intended to be consumed in
amounts that provide all or a significant part of the entire daily fluid intake of an average person in the
United States are effectively represented as conventional foods [5]. It is important to note that even if
a product is not expressly represented as an alternative to a beverage, when the practical result of the
labeled serving size and/or RDI is that the product is used as a beverage or replaces beverages that serve
as ordinary sources of drinking fluid, FDA would generally consider the representation of the product
for use as a conventional food.
Sales and marketing practices: Appropriate marketing practices should be used. Appropriate labeling,
advertising, and all promotional activities should comply with the regulatory norms.
their convenience or stability. The structural integrity of some or all of the active ingredients of these
powdered premixes may be unstable in aqueous solution and hence are not considered beverages for use.
Nutrient content claims: Both beverages and liquid dietary supplements, which identify the nutrient level
in a food according to 21 CFR 101.13(b). In addition, the following sections provide additional details:
1. Section 403(r)(1)(A), (r)(2), (r)(4), and (r)(5) of the FD&C Act (21 U.S.C. 343[r][1][A], [r][2],
[r][4], [r][5])
2. Section 21 CFR 101.13, 21 CFR 101.69, and 21 CFR 101.54–101.67
3. FDAMA claims [14]
4. Label claims [11]
Structure function claims for conventional foods: Conventional foods and beverages may bear certain
kinds of claims about effects on the structure or function of the body. “Food” is defined in Section
201(f) of the FD&C Act (21 U.S.C. 321[f]) as (1) articles used for food or drink for man or other animals,
(2) chewing gum, and (3) articles used for components of any such article. It is also recommended to
consult Section 201(g)(1)(C) of the FD&C Act (21 U.S.C. 321[g][1][C]).
Structure function claims for dietary supplements: Labeling of dietary supplements needs to comply
with Section 403(r)(6) of the FD&C Act (21 U.S.C. 343(r)(6) and 21 CFR 101.93). These claims are about
general well-being and benefits.
General food labeling requirements: FDA’s general food labeling requirements, including those that
apply to dietary supplements, are in 21 CFR Part 101. Labeling requirements for beverages and conven-
tional foods differ greatly from dietary supplements. Beverages need to exhibit nutrition information in
the nutrition facts format as shown in 21 CFR 101.9, while dietary supplements need to exhibit nutrition
information in the Supplement Facts format (21 CFR 101.36). A beverage or other conventional foods
should not be labeled with the FDA disclaimer, which is required for dietary supplements.
2.7.1 Japan
The terminology “foods with health claims” was first incorporated for nutraceuticals and functional
foods in Japan. It is worthwhile to mention that Japanese are extremely health conscious and the second
largest consumer of nutraceuticals. There are two basic categories:
1. Foods with Nutrient Function Claims: Basically, it satisfies the minimum and maximum daily
levels of selected vitamins and micronutrients.
2. Foods for Specified Health Uses: This requires premarketing approval. This needs evalua-
tion of effectiveness and approval by the Pharmaceutical Affairs and Food Sanitation Council
and the Ministry of Health, Labour and Welfare (MHLW). Japan also established Consumer
Affairs Agency, which assumed the MHLW responsibility [1,3,16].
The new Japanese regulation reformation process is in process and will be implemented soon.
22 Handbook of Functional Beverages and Human Health
2.7.3 China
The nutraceutical market in 2008 was US$6 billion in China [19] and China Health Care Association, a
government-appointed body that regulates the nutraceutical industries. Other agencies include State Food
and Drug Administration (SFDA) that regulates the nutraceutical supplements, Ministry of Health (MoH)
that oversees SFDA and monitors the approval of novel food ingredients, and Administration of Quality
Supervision Inspection and Quarantine that regulates imports and exports of nutraceuticals and func-
tional foods. However, the regulatory position for functional beverages are not transparent at all [1,3,19].
2.7.4 Canada
Vitamins, minerals, botanical herbs based on dietary supplements, traditional Chinese medicines, pro-
biotics, and enzymes are called natural health products (NHPs) and regulated under the Canadian Food
and Drugs Act. The Canadian Government Health Authority—Health Canada has approved more than
61,000 NHPs for sale in Canada since 2004. NHP has classified a three-class system based on risk,
namely, (1) Class 1, (2) Class 2, and (3) Class 3. The regulatory approval process requires evidence
requirements based on risk and health claims. Furthermore, NHP Directorate has outlined procedures for
the evaluation of multi-ingredient formulations. Postmarket activities and vigilance are also performed
by regulatory agencies [1,20]. However, nutraceutical beverage regulation has not been independently
classified.
Global Nutraceutical Regulations for Functional Beverages 23
2.7.6 India
Nutraceutical and functional foods are regulated by Food Safety and Standards Act. Manufacturers
follow the standards of Indian Pharmacopoeia. Federation of Indian Chambers of Commerce and
Industry is somewhat associated with the improvement of regulation on nutraceutical market and func-
tional beverage [1,21]. However, no detailed information is available.
2.7.7 Australia
Botanical herbs, vitamins, minerals, nutraceutical supplements, and homeopathic and aromatherapy
preparations are referred to as “complimentary medicines” and are regulated under the Therapeutic
Goods Act (TGA) 1989 [22,23]. A complimentary medicine, including a nutraceutical, is defined as
“a therapeutic good consisting principally of one or more designated active ingredients mentioned
in Schedule 14 of the Regulations, each of which has a clearly established identity and traditional
use,” which include an amino acid; charcoal; a choline salt; an essential oil; plant or herbal extract;
homeopathic preparation; a microorganism, whole or extracted, except a vaccine; mineral; mucopoly-
saccharide; nonhuman animal material; a lipid, phospholipid, or an essential fatty acid; royal jelly;
bee pollen; propolis; a sugar; polysaccharide or carbohydrate; and a vitamin or provitamin. Australia
has a two-tiered system for the regulation of complimentary medicines: (1) higher-risk products need
to be registered on the Australian Register of Therapeutic Goods (ARTG) [22–24], which requires the
evaluation of quality, safety, and efficacy and (2) lower-risk products that contains preapproved low-risk
ingredients and has limited claims listed in ARTG. TGA’s postmarket regulatory activity of complimen-
tary medicines and adverse event reporting are standard procedures. No clear directive is available on
nutraceutical beverage.
2.7.9 Israel
Israel has been termed as one of the key innovation hubs for the nutraceutical industries, and their major
revenue comes from the export of nutraceuticals and functional foods to the United States and Europe.
MoH regulates nutraceuticals and functional foods [1,3].
TABLE 2.1
Nutraceutical Supplements, Regulatory Authorities, and Estimated Annual Business
Estimated Annual
Country Regulatory Authorities Business (US$) References
United States Code of Federal Regulations ~75.9 billion in 2018 [22]
Food and Drug Administration
Federal Trade Commission
Generally Recognized as Safe
Good Manufacturing Practices
Japan Consumer Affairs Agency ~26 billion in 2006 [23]
Foods with Nutrient Function Claims
Foods for Special Dietary Uses
Food for Specified Health Use
Ministry of Health, Labour, and Welfare
European Union European Food Safety Authority ~35 billion in 2010 [17]
Foods for Particular Nutritional Use
China China Health Care Association ~6 billion in 2008 [25]
State Food and Drug Administration
Ministry of Health
Administration of Quality Supervision Inspection and
Quarantine
Canada Natural Health Products Directorate na —
Health Canada
South Korea Health/Functional Food Act na —
Ministry of Food and Drug Safety
India Food Safety and Standards Act ~4 billion in 2018 [24]
Federation of Indian Chambers of Commerce and Industry
Australia Australia New Zealand Therapeutic Products Authority ~1.5 billion each year [26]
Australian Register of Therapeutic Goods
Complementary and Alternative Medicine
Therapeutic Goods Act
New Zealand Australia New Zealand Therapeutic Products Authority ~1 billion in 2010 [20]
Medicines and Medical Devices Safety Authority
New Zealand Food Safety Authority
Israel Ministry of Health na —
Abbreviation: na, not available.
Global Nutraceutical Regulations for Functional Beverages 25
2.9 Conclusion
Innovations and marketing of nutraceuticals and functional foods are now the fastest-growing segments
for this industry. Currently, the rising costs and toxicity of some pharmaceuticals are driving the popu-
lation around the world to move forward with safe, efficacious, and less expensive nutraceuticals and
functional food supplements and beverages. Especially, there is a massive global upsurge of functional
beverages in its sales and consumption. Especially, the younger generation has a trend to using func-
tional beverages over conventional cola beverages. Although nutraceutical beverage regulation has been
defined, further clarification is required to make it more effective and safe. Functional beverages are very
popular and extensively used in Japan, South Korea, China, and Thailand. Health professionals, nutri-
tionists, and regulatory toxicologists should strategically work shoulder to shoulder to derive appropriate
regulatory standards and to provide the optimal health and therapeutic benefits to mankind globally.
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17. Nutraceuticalsworld, Nutraceuticals regulation back on European Commission Agenda for 2013.
Published online at: http://www.nutraceuticalsworld.com/issues/2012–11/view_features/nutraceuticals-
regulation-back-on-european-commission-agenda-for-2013/, November 1, 2012 (accessed April 25, 2015).
18. MyDrink Beverages, Trends of nutraceutical functional beverages in Europe. Published online at: http://
mydrinkbeverages.com/trends-of-nutraceutical-functional-beverages-in-europe, April 2015 (accessed
April 25, 2015).
19. China’s Nutraceutical Industry, China’s nutraceutical industry. Published online at: http://www.
nutraceuticalsworld.com/issues/2008–11/view_features/china-s-nutraceutical-industry/, November 1, 2008
(accessed April 25, 2015).
20. Nutraceuticals World, Canada stands at regulatory crossroads for nutraceutical products. Published
online at: http://www.nutraceuticalsworld.com/contents/view_features/1999–03–01/canada-stands-at-
regulatory-crossroads-for-nutrace/, March 1, 1999 (accessed April 25, 2015).
21. Indian Nutraceutical Market, Indian nutraceutical market is filled with promise. Published online at:
http://www.naturalproductsinsider.com/articles/2014/05/indian-nutraceutical-market-is-filled-with-
promis.aspx, May 20, 2014 (accessed April 25, 2015).
22. TGA, Therapeutic goods act 1989. Published online at: http://www.comlaw.gov.au/Series/C2004A03952,
August 14, 2015 (accessed August 25, 2015).
23. TGA, Australian register of therapeutic goods. Published online at: https://www.tga.gov.au/australian-
register-therapeutic-goods, July 5, 2013 (accessed April 25, 2015).
24. The Guardian, Vitamins take Australia. Published online at: http://www.theguardian.com/world/2013/
jun/11/vitamins-take-australia-hollywood-names, June 10, 2013 (accessed April 25, 2015).
25. Food & Beverage Information, Food & Beverage Information Project 2011, Depth sector stream—
Nutraceuticals & foods for health. Published online at: https://www.med.govt.nz/sectors-industries/food-
beverage/pdf-docs-library/information-project/nutraceuticals-2011.pdf and www.foodandbeverage.govt.
nz, February 2012 (accessed April 25, 2015).
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prnewswire/press_releases/2014/07/16/BR70682, April 22, 2014 (accessed April 25, 2015).
3
Flavor Challenges in Functional Beverages
Keith R. Cadwallader
CONTENTS
3.1 Introduction..................................................................................................................................... 27
3.2 Flavor Perception............................................................................................................................ 28
3.3 Off Flavors Associated with Functional Ingredients...................................................................... 28
3.3.1 Off Odors............................................................................................................................ 28
3.3.2 Bitter and Astringent Substances....................................................................................... 28
3.4 Flavor Modification Techniques..................................................................................................... 28
3.4.1 Traditional Approaches...................................................................................................... 28
3.4.1.1 Odor Masking by Mixture Suppression and Odor Synergy............................... 30
3.4.1.2 Bitterness Masking by Suppression.................................................................... 30
3.4.1.3 Taste Masking by Viscosity Modification.......................................................... 30
3.4.2 Advanced Approaches........................................................................................................ 30
3.4.2.1 Taste Masking by Inclusion Complexation......................................................... 30
3.4.2.2 Bitter-Blocking Agents........................................................................................31
3.5 Masking and Flavoring of Functional Beverages............................................................................31
3.5.1 Partnering with a Flavor Company.................................................................................... 32
3.5.2 In-House Product Development......................................................................................... 32
3.5.2.1 Flavor Considerations......................................................................................... 32
3.6 Conclusion....................................................................................................................................... 33
References................................................................................................................................................. 33
3.1 Introduction
Formulated functional beverages differ from traditional beverages in that they are produced using
ingredients with scientifically proven physiological and health benefits. These products are often based
on patents, industry trade secrets, or other type of proprietary knowledge. As with any food product, the
ultimate goal is to make a product with an acceptable flavor profile that is characterized by the imme-
diate impact of an identifying flavor (e.g., vanilla, chocolate, and strawberry), rapid development of a
balanced and full-bodied flavor, compatible mouthfeel and texture, lack of off flavors, and a minimal
(short) aftertaste. It is important that when consumers first open or taste a product, their first impression
is that of the intended, desirable flavor. Functional beverages face many of the same flavor challenges
encountered with pharmaceuticals due to the inherent off flavors associated with the ingredients used
in their formulation. Products highly fortified with vitamins, minerals, and intensely bitter functional
ingredients present a particularly difficult challenge.
Several excellent reviews provide an exhaustive overview of methods for masking off flavors in phar-
maceutical products [1–5], and techniques for reducing bitterness in functional foods have recently been
published [6]. This chapter highlights traditional and emerging technologies and discusses practical
approaches to improve the flavor characteristics of functional beverages.
27
28 Handbook of Functional Beverages and Human Health
OH
OH
O
HO O O
HO
O
O O
N N
N N
O OH O
N NH HO
O N N OH
O OH
Caffeine Theobromine Naringin
(bitter) (bitter) (bitter)
OH
HO OH
OH
O
OH
OH
Resveratrol
(bitter) OH
OH
OH OH
O
OH
OH OH
HO O HO O
OH OH
OH
OH OH OH
OH OH Dimeric procyanidin B8
(+)-Catechin (2R,3S) (–)-Epicatechin (2R,3R) (4α 6 catechin-epicatechin)
(bitter/astringent) (bitter/astringent) (astringent/bitter)
FIGURE 3.1 Chemical structures of some bitter and astringent constituents of functional ingredients.
TABLE 3.1
Traditional and Emerging Methods for Improving the Flavor Characteristics of Functional Beverages
Flavor Challenge Strategy Methods
Off odor reduction Odor masking Mixture suppression by addition of complex flavorings.
Assimilation masking by addition of flavorings that complement
the odors already present in base formulation.
Matrix modification Subdue or modulate odor release (availability) by addition of fat,
fat replacers, or bulking agents.
Bitterness and Congruent or assimilation Choose flavoring that complements lingering or persistent bitter
astringency masking of bitterness and and astringent tastes (e.g., coffee, tea, or dark chocolate).
reduction astringency
Mask bitterness by suppression Suppress bitterness perception by addition of NaCl, amino acids,
sugar, or high-intensity sweeteners.
Mask bitterness and astringency Addition of thickening agents (polysaccharides or gums).
by decreasing (oral) diffusion Addition of emulsifiers (lipids or lecithin).
Mask by physical separation of Encapsulation of bitter and astringent ingredients. Addition of
bitter and astringent compounds cyclodextrins.
Blocking of bitter receptors Addition of substances (bitter-blocking agents) that suppress
bitterness by interfering with bitter receptors and/or receptor
signaling pathways.
30 Handbook of Functional Beverages and Human Health
Complexation using various types of cyclodextrins has been shown to be effective in reducing or
eliminating bitterness in a variety of foods and beverages. These include the use of β-cyclodextrin to
reduce the bitterness of naringin and limonin in citrus juice [16] and use of either β- or γ-cyclodextrin
for the reduction of bitterness of ginseng solutions [17]. In addition to reducing bitterness, cyclodextrins
can alter the sensory profile through flavor encapsulation and could interfere with the action of masking
agents or bitter-blocking agents [18].
Use of a flavoring that complements residual or lingering or persistent aromatics and tastes is referred
to as congruent or assimilation masking. An example of this approach is the use of a coffee and dark
chocolate flavoring to complement the bitter taste and astringent mouthfeel and green, beany, and cereal
aromatics associated with soy-fortified beverages. Similarly, the earthy note of St. John’s wort blends or
assimilates well with chocolate or coffee.
3.6 Conclusion
It is the ultimate goal of the product developer to provide consumers with functional beverages that not
only deliver the intended health-promoting benefits but also taste great. Various strategies can be used
in functional beverages to decrease off odors, bitter tastes, and astringent mouthfeel characteristics.
Traditional methods can be effective, but recent advances in the development of bitter-blocking agents
offer new and potentially more effective ways to inhibit bitterness. These may have particular appeal for
the targeted blocking of intensely bitter functional ingredients, especially polyphenolics that are com-
monly used in functional beverages. The use of several approaches, for example, traditional masking
strategies combined with inclusion complexation and bitter binding agents, is the most effective option
for the effective flavoring functional beverages.
REFERENCES
1. Roy, G., Modifying Bitterness: Mechanism, Ingredients, and Applications, CRC Press LLC, Boca
Raton, FL, 1997.
2. Sohi, H., Sultana, Y., and Khar, R.K., Taste masking technologies in oral pharmaceuticals: Recent
developments and approaches. Drug Dev. Ind. Pharm., 30, 429–448, 2004.
3. Ley, J.P., Masking bitter taste by molecules. Chem. Percept., 1, 58–77, 2008.
4. Sharma, S. and Lewis, S., Taste masking technologies: A review. Int. J. Pharm. Pharm. Sci., 2, 6–13,
2010.
5. Deepak, S., Dinesh, K., Mankaran, S., Gurmeet, S., and Singh, R.M., Taste masking technologies:
A novel approach for the improvement of organoleptic property of pharmaceutical active substances.
Int. Res. J. Pharm., 3, 108–116, 2012.
6. Gaudette, N. and Pickering, G.J., Modifying bitterness in functional food systems. Crit. Rev. Food Sci.
Nutr., 53, 464–481, 2013.
7. Auvray, M. and Spence, C., The multisensory perception of flavor. Conscious. Cogn., 17, 1016–1031,
2008.
8. Chaudhari, N. and Roper, S.D., The cell biology of taste. J. Cell Biol., 190, 285–296, 2010.
9. Peleg, H., Gacon, K., Schlich, P., and Noble, A.C., Bitterness and astringency of flavon-3-ol monomers,
dimers and trimers. J. Sci. Food Agric., 79, 1123–1128, 1999.
10. Cain, W.S., Odor intensity: Mixtures and masking. Chem. Senses Flavor, 1, 339–352, 1975.
11. Liang, D.G., Perceptual odour interactions and objective mixture analyses. Food Qual. Pref., 5, 75–80,
1994.
12. Calviño, A.M., García-Medina, M.R., and Cometto-Muñiz, J.E., Interactions in caffeine-sucrose and
coffee-sucrose mixtures: Evidence of taste and flavor suppression. Chem. Senses, 15, 505–519, 1990.
13. Keast, R.S.J., Breslin, P.A.S., and Beauchamp, G.K., Suppression of bitterness with sodium salts.
Chimia, 55, 441–447, 2001.
14. Szente, L. and Szejtli, J., Cyclodextrins as food ingredients. Trends Food Sci. Technol., 15, 137–142,
2004.
15. Astray, G., Gonzalez-Barreiro, C., Mejuto, J.C., Rial-Otero, R., and Simal-Gándara, J., A review on the
use of cyclodextrins in foods. Food Hydrocolloid., 23, 1631–1640, 2009.
16. Konno, A., Misaki, M., Toda, J., Wada, T., and Yasumatsu, K., Bitterness reduction of naringin and
limonin by β-cyclodextrin. Agric. Biol. Chem., 46, 2203–2208, 1982.
17. Tamamoto, L.C., Schmidt, S.J., and Lee, S.-Y., Sensory properties of ginseng solutions modified by
masking agents. J. Food Sci., 75, S341–S347, 2010.
34 Handbook of Functional Beverages and Human Health
18. Gaudette, N.J. and Pinkering, G.J., Modifying bitterness in functional food systems. Crit. Rev. Food
Sci. Nutr., 53, 464–491, 2013.
19. Nakamura, T., Tanigake, A., Miyanaga, Y., Ogawa, T., Akiyoshi, T., Matsuyama, K., and Uchida, T.,
The effect of various substances on the suppression of the bitterness of quinine-human gustatory sensa-
tion, binding, and taste sensor studies. Chem. Pharm. Bull. (Tokyo), 50, 1589–1593, 2002.
20. Maehashi, K., Matano, M., Nonaka, M., Udaka, S., and Yamamoto, Y., Riboflavin-binding protein is a
novel bitter inhibitor. Chem. Senses, 33, 57–63, 2008.
21. Green, T.A., Alarcon, S., Thomas, A., Berdougo, E., Doranz, B.J., Breslin, P.A.S., and Rucker, J.B.,
Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin.
PLoS One, 6, e201232011, 2011.
22. Suppavorasatit, I. and Cadwallader, K.R., Flavor-soy protein interactions, in Chemistry, Texture and
Flavor of Soy, Cadwallader, K.R. and Chang, S.K.C., eds., ACS Symposium Series 1059, American
Chemical Society, Washington, DC, 2010, pp. 339–359.
23. Brantd, L.A., Flavor masking: Strategies for success. Prepared Foods, 170, 63–66, 2001.
24. Labbe, D., Damevin, L., Vaccher, C., Morgenegg, C., and Martin, N., Modulation of perceived taste by
olfaction in familiar and unfamiliar beverages. Food Qual. Prefer., 17, 582–589, 2006.
4
Chemistry of Functional Beverages
CONTENTS
4.1 Introduction..................................................................................................................................... 35
4.2 Chemistry and Bioactivities of Phytochemicals............................................................................. 36
4.2.1 Polyphenols......................................................................................................................... 36
4.2.2 Flavonoids........................................................................................................................... 36
4.2.3 Terpenoids and Carotenoids............................................................................................... 36
4.2.4 Saponins............................................................................................................................. 38
4.2.5 Phytosterols........................................................................................................................ 39
4.2.6 Polysaccharides.................................................................................................................. 39
4.2.7 Alkaloids.............................................................................................................................41
4.3 Selected Functional Beverages........................................................................................................41
4.3.1 Tea...................................................................................................................................... 42
4.3.2 Coffee................................................................................................................................. 42
4.3.3 Fruit and Vegetable Beverages........................................................................................... 43
4.3.4 Energy Drinks.................................................................................................................... 44
4.4 Conclusion....................................................................................................................................... 44
References................................................................................................................................................. 45
4.1 Introduction
Functional beverages, a subsector of the functional food industry and the fastest-growing sector of the
functional food market, have become increasingly popular among conscientious consumers due to their
perceived health benefits. Convenience and health benefits are two of the most important factors when
consumers make decisions about purchasing foods and beverages. Functional beverages claim to improve
athletic endurance, energy, and hydration, and are associated with various health benefits such as gen-
eral wellness, antioxidant activity, healthy cardiovascular system, cancer prevention, healthy digestive
system, immune defense, body weight reduction, and joint health improvement, among others [1].
Apart from water, the most popular and traditional functional beverages worldwide are tea, coffee,
and fruit juices [2]. Newly developed functional drinks sometimes contain vitamins and minerals, but in
most cases they contain functional ingredients from fruits or other parts of medicinal plants, such as açai,
pomegranate, cranberry, blueberry, and monk fruits, to name a few. Hence, the phytochemical ingredi-
ents that are the building blocks of functional beverages, which provide targeted health functionality
need to be investigated and their content summarized. Bioactive phytochemicals in functional beverages
can be classified based on their chemical structures as polyphenols, including flavonoids, terpenoids,
carotenoids, saponins, phytosterols, polysaccharides, and alkaloids, among others, even though there
are some overlaps among the aforementioned classifications. This chapter highlights the most popular
beverages and their major ingredients from an array of chemical profiles.
35
36 Handbook of Functional Beverages and Human Health
4.2.2 Flavonoids
Flavonoids, a particular class of polyphenols, have a C6–C3–C6 skeleton structure and consist of several
subgroups: flavones, flavonols, flavanones, flavanols, isoflavones, chalcones, anthocyanidins, and procy-
anidins. Chalcones are the only subgroup in the flavonoid category that has two phenyl groups connected
by an acryl bond, whereas the majority of other flavonoids form a C-ring with a C3 skeleton (Figure 4.1).
Flavonoids are widely distributed in fruits and vegetables such as apples, citrus, berries, and soybeans;
in grains; and in beverages such as tea, coffee, and wine. They not only show strong antioxidant activity
but also exhibit bioactivities related to anti-inflammation, risk-lowering effect of cardiovascular disease
(CVD), cancer prevention, and antiobesity. The bioactivity of flavonoids is also assumed to originate
from their perceived antioxidant property owing to multiple phenolic groups and the hydrogen bonding
interaction between proteins and functional groups on flavonoids, such as carbonyl as hydrogen acceptor
and hydroxyl groups as hydrogen donor. Examples of flavonoids are quercetins, hesperidins, luteolins,
naringins, and tannins [4].
Hydroxybenzoic
Polyphenols acids:
Simple OH Stilbenes:
polyphenols:
HO R RO
OH
OH HO R
HO OH
R CO2H RO
R—
— H: Catechol R—
—OH: Gallic acid R—
—H: Resveratrol
Polyphenol R—
—OH: Pyrogallol R—
—H: Procatechuic acid R—
—Me: Pterostilbene
FIGURE 4.1 Chemical structures of polyphenols and flavonoids found in tea, coffee, soy, and fruit beverages.
38 Handbook of Functional Beverages and Human Health
Terpenoids
Monoterpene:
OH Diterpene:
OH
Isoprene
trans-retinol
Linalool Limonene
Carotenoids
β–Carotene
OH
Lutein
HO
OH
Zeaxanthin
HO
Lycopene
FIGURE 4.2 Chemical structures of terpenoids and carotenoids found in some fruit beverages.
our daily dietary intake. Carotenoids act as antioxidants and are reported to have the ability of prevent-
ing chronic diseases. β-Carotene is the most common carotenoid in food matrices and exists in carrots,
apricots, tomatoes, and pumpkins, among others. The antioxidant activity of carotenoids is believed to
be responsible for the health-promoting properties of fruits and vegetables. Furthermore, the function of
carotenoids with provitamin A activity is very important for a healthy vision [5,6]. Low-dose lycopene
intake has been reported to assist cardiovascular health [6,7] and intake in high doses has been reported
to reduce symptoms of benign prostatic hyperplasia [8].
4.2.4 Saponins
Saponin, whose name is gained from its soap foaming characteristic when suspended in water, consists
of a lipophilic triterpene (C30) or steroid (C27) and hydrophilic glycosides (Figure 4.3). The foam-
ing ability of saponins is due to the combination of a hydrophobic sapogenin and a hydrophilic sugar
portion. Sapogenin is the aglycone part of a saponin. They are a class of amphipathic compounds and
abundant in various plant species. For instance, saponins can be found in most vegetables, beans, and
herbs. Daily dietary intake of saponins is estimated at 15–240 mg. Saponins have many health benefits,
such as reduction of blood cholesterol, cancer prevention, and stimulation of the immune system. Studies
have illustrated that saponins cause cholesterol reduction by preventing their reabsorption [9]. They also
exhibit antitumor activity and can lower the risk of human cancers by inhibiting the growth of cancer
cells and may also help the immune system by protecting against viruses and bacteria; some saponins
have protective effects on bone loss. Reported examples include alfalfa saponins for decreasing lipid
Chemistry of Functional Beverages 39
Saponins
Aglycones of steroidal saponins:
O OH
OH HO
O O
OH
HO HO
H H HO
Spirostanol Furostanol Cholesterol
O
OH
H
β–D-Glc1-β–D-2Glc—O
Ginenoside Rb1
FIGURE 4.3 Chemical structures of major saponins (except cholesterol) found in some fruit beverages.
and cholesterol concentration in mouse liver; ginseng saponins for reducing hypertension by blocking
the calcium channel; and Panax notoginseng saponins for inhibiting inflammation, decreasing bleeding
time, and providing protection against cancer [9].
4.2.5 Phytosterols
Phytosterols are steroid compounds naturally occurring in plants and are structurally similar to choles-
terol. They exist widely in fruits, vegetables, berries, and nuts and are rich in vegetable oils. Good food
sources include whole grains, unrefined vegetable oils, nuts, seeds, and legumes. The daily intake of
phytosterols ranges from 150 to 450 mg or even higher in some vegetarian diet. In the human diet, the
common phytosterols are β-sitosterol, campesterol, stigmasterol, sitostanol, and campestanol [10,11].
Two major classes of phytosterols are sterols and stanols. Stanols are saturated sterols and have no double
bonds in their structural ring (Figure 4.4). Major health claims of phytosterols include reduction of
plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and perhaps triacylglycerols (TAG).
Between 1954 and 1982, phytosterol was originally used as a cholesterol-lowering drug (Cytellin) in
high doses. As a functional food additive to margarine, orange juice, and others, it was introduced to the
Finnish market in 1995 for its cholesterol-lowering functionality [11] and in 2000 with the introduction
of sterol esters under the Novel Food regulation in the EU.
4.2.6 Polysaccharides
Saccharides, also called carbohydrates, are a group of biological molecules consisting of hydrogen (H),
carbon (C), and oxygen (O) atoms. The ratio of the three atoms (H–C–O) is usually 2:1:1, but the oxygen
atom could be different. Saccharides include sugar, starch, and cellulose, whereas they can also be divided
into monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Monosaccharides are simple
sugars and disaccharides consist of two monosaccharides covalently linked. Polysaccharides have polymeric
carbohydrate structures, consisting of repeating units of mono- or disaccharides covalently linked by glyco-
sidic bonds (Figure 4.5). These structures are often linear, but may be branched. Polysaccharides are often
40 Handbook of Functional Beverages and Human Health
Phytosterols
Sterols:
H H H
H H H
H H H H H H
HO HO HO
β-Sitosterol Campesterol Stigmasterol
Stanols:
Cholesterol:
H H
HO
H H
H H H H OH
HO HO
H H
β-Sitostanol Campestanol HO
FIGURE 4.4 Major phytosterols (except cholesterol) found in some fruit beverages.
Polysaccharides
Monosaccharrides: Disaccharrides:
OH OH
HO O HO O
O HO O
HO HO HO
HO
HO OH OH O OH
OH HO
OH OH OH
Glucose Fructose Sucrose
OH
O
O OH
HO
OH O OH
O
HO
OH O O
OH
HO
OH O
O
HO
OH
O
n
Starch
Alkaloids
Purine derivatives: Imidazole derivatives:
O O O
H
N N HN N N N N NH2
O N N O N N O N N HN
heterogeneous, containing slight modifications of the repeating unit. Depending on the specific structures
of these macromolecules, they can have distinct properties depending on their monosaccharide building
blocks. They may be amorphous or insoluble in water. Natural saccharides often contributing to sweetness
are monosaccharides or disaccharides in general, such as glucose, fructose, and sucrose [12].
Digestible polysaccharides such as starch are a common source of energy. Polysaccharides that are
indigestible may have other functionalities that affect human health. For example, cellulose, chitin, and
pectin polysaccharides cannot be broken down to monosaccharides by many organisms including human
microorganisms. However, they provide a good source of dietary fiber having the functions of enhancing
digestion and reducing the absorption of cholesterol and sugars [13,14].
4.2.7 Alkaloids
Alkaloids, a class of naturally occurring organic nitrogen-containing compounds, are produced primar-
ily in plants, which can also be found in bacteria, fungi, and animals. The name alkaloid in fact came
from alkali. More than 27,000 different types of alkaloids have, so far, been identified, with 21,000 of
them are from plants [15]. They contain one or more nitrogen atoms and can be primary, secondary, and
tertiary amines. Alkaloids are usually classified based on their nitrogen-containing structures, such as
pyrrolidines, piperidines, quinolines, isoquinolines, and indoles. Traditionally, in the structure of alka-
loids, the nitrogen atom is part of the ring system, but this is not necessarily true. When the nitrogen is in
the exocyclic position in naturally occurring nitrogen compounds, they are usually classified as amines
[15,16]. Figure 4.6 lists some examples of alkaloids.
Many alkaloids possess pharmacologic effects. Most commonly used as drugs are often alkaloids from
natural sources, such as the anticancer drug taxol. Alkaloids with biological activity in humans mostly
affect the nervous system. Popular alkaloids in beverages are often purine derivatives, particularly caf-
feine, which is a stimulant of the human central nervous system, slowing down sleepiness and restoring
alertness. It is the world’s most widely used psychoactive drug. Caffeine achieves most of its effects by
blocking the activity of adenosine, a neurotransmitter affecting almost the entire body system. It also has
other reported beneficial health properties. For instance, it is a weak bronchodilator and at low doses it
is shown to provide some improvement in lung function. It is postulated that caffeine’s regulation of the
body’s neurotransmitters may also provide health benefits such as cognitive improvement, effectiveness,
and physical activity improvement and some specific therapeutic benefits such as pain relief [16].
4.3.1 Tea
Tea (Camellia sinensis) is cultivated worldwide, particularly in China, Sri Lanka, India, Kenya, Turkey,
and some other Asian countries. It is the most consumed flavored functional beverage in the world. As a
result of tea plant variety and different delicate manufacturing processes, there are numerous tea prod-
ucts commercially available in the global market. Generally, tea has three major types: green tea, oolong
tea, and black tea. Black tea accounts for about 78% of the total worldwide tea consumption and green
tea about 20%, whereas approximately 2% belongs to oolong tea [17]. Although all types of tea have been
gaining popularity worldwide, in regional preference, green, white, and oolong tea is dominant in China
and Japan while black tea occupies the majority of the market in Western countries.
Original tea consumption was mainly for its central nerve stimulating and soothing effects, but tea
drinking has been linked to health-promoting effects for centuries. Tea consumption is associated
with many health benefits such as antioxidant and anti-inflammatory activities, cancer prevention, and
reduced risk of coronary heart disease (CHD), among others [18]. Scientific data have demonstrated that
the health effects of tea are mainly attributed to its polyphenolic compounds (Table 4.1). Tea contains
different polyphenols in terms of content and variety [17]. Green tea polyphenols, that is, catechins, are
the most abundant polyphenols in green, white, and oolong tea, and even in most of the black tea bever-
ages on the market. Polyphenols in black tea also include theaflavins, thearubigins, and other catechin
polymeric pigments that exist in higher amounts than catechins. However, the latter are still present in
black tea and its extracts in relatively large percentages because the conversion of green tea catechins to
black tea polyphenols is always incomplete [17]. Tea polyphenols in oolong tea consist chiefly of green
tea catechins and a small percentage of black tea theaflavins and thearubigins due to limited fermenta-
tion process. The polyphenolic composition of pu-erh tea or raw pu-erh tea is the same as that of oolong
tea, whereas the fully fermented pu-erh tea mainly contains gallic acid and does not contain both green
and black tea polyphenols [17]. Epidemiological evidence shows that the intake of tea polyphenols has
a myriad of beneficial health effects including antioxidant, anticancer, anti-inflammatory, antidiabetic,
antiatherosclerotic, antihyperlipidemic, antibacterial, and antiviral activities, among others [2,18].
4.3.2 Coffee
Consumption of coffee has been reported to be positively associated with reduced risk of chronic and
degenerative diseases such as cancer, diabetes, Parkinson’s disease, inflammation, and CVD [19,20].
Coffee consumption is also associated with a lower risk of a variety of liver diseases, including liver
cirrhosis and liver cancer. Coffee is brewed by infusion and/or percolation of roasted ground coffee with
boiled water. Similar to tea, coffee contains a wide range of phytochemicals represented by caffeine and
chlorogenic acids with many potential beneficial bioactivity [19,21]. Although the biological effects of
coffee are highly dependent on plant variety and processing conditions such as in blending and brewing,
which can produce wide variations in the phytochemical compositions of the resulting beverage, the
basic fingerprint profile of coffee phytochemicals remains similar [22]. It is easy to construe that caffeine
TABLE 4.1
Major Tea Polyphenols
Polyphenols No. Name Acronym R R′
Catechins I Epicatechin EC H H
II Epigallocatechin EGC H OH
III Epicatechin gallate ECG Galloyl H
IV Epigallocatechin gallate EGCG Galloyl OH
Theaflavins V Theaflavin TF1 H H
VI Theaflavin-3-monogallate TF2a Galloyl H
VII Theaflavin-3′-monogallate TF2b H Galloyl
VIII Theaflavin-3,3′-digallate TF3 Galloyl Galloyl
Chemistry of Functional Beverages 43
is the most extensively studied compound in coffee and its bioactivity has been stated in the last section.
Less abundant alkaloids theobromine and theophylline are also present in coffee [19].
The most abundant polyphenols in coffee are chlorogenic acids and the major variant is 5-caffeoylquinic
acid [21]. The concentration of chlorogenic acids in coffee can reach as high as 840 mg/L. Apart from chlo-
rogenic acids, hydroxycinnamates, including caffeic acid, ferulic acid, and p-coumaric acid (Figure 4.1),
are some of the major polyphenols found in coffee [19,23]. The antioxidant activity of chlorogenic acids
allows them to inhibit the formation or scavenging of reactive oxygen species. Thus, they may play impor-
tant roles in the prevention of certain diseases caused by oxidative stress, such as CVD. It has been
reported that chlorogenic acids exert inhibitory effects on carcinogenesis in the large intestine, liver, and
tongue and a protective action on oxidative stress in vivo. Chlorogenic acids may also have neuropro-
tective effects. An animal feeding study with chlorogenic acids and caffeic acids found the absorption
of phenolic acids and the suppressed expression of P-selectin on mouse platelets, indicating significant
protective effect against CVD by the two phenolic acids in coffee. Chlorogenic acids were also found to
improve glucose tolerance and decrease the levels of cholesterol and TAG in rat plasma and liver [19,21].
Chlorogenic acids are one of the most abundant polyphenols in the human diet with coffee, fruits, and
vegetables as its major sources. For instance, they are an important group of nonvolatile compounds
in green coffee beans. Although 30 different species of chlorogenic acids have now been identified in
green beans, the vast majority of the compounds found belong to three classes: monocaffeoylquinic
acids at 3-, 4-, or 5-position of quinic acids, dicaffeoylquinic acids, and feruloylquinic acids. In addi-
tion to coffee, these compounds are also found at significant levels in plant foods such as apples, pears,
tomatoes, potatoes, eggplants, strawberries, pineapples, sunflowers, and blueberries. A small quantity
of free quinic acid occurs in green coffee beans. A greater quantity of quinic acid occurs as a series
of chlorogenic acids esters. They are a family of esters formed between trans-cinnamic acids (caffeic,
coumaric, and ferulic acids) and (−)-quinic acid. Chlorogenic acids are also found as a significant
component in some commonly used medicinal herbs, including chrysanthemum flower, hawthorn fruit,
artemisia leaves, epimedium leaves, artichoke leaves, burdock root, dandelion root, and echinacea root,
among others.
TABLE 4.2
Phytonutrients in Food Sources and Claimed Health Benefits
Phytonutrients Health Benefits Claimed Fruits and Vegetables
Allicin and allylic sulfides Antibacterial, antifungal, antiviral, and Chives, garlic, leeks, and onions
antioxidant activities; lowering the risk
of stomach and colon cancers.
Anthocyanidins and Strong antioxidants; maintaining Dark grapes, berries, cherries, and red wines
proanthocyanidins elasticity of capillary walls; anti-
inflammatory; inhibiting cancer cell
formation and proliferation.
Flavonoids (quercetin, Potent antioxidants; anticarcinogenic; Teas, citrus fruits, berries, cherries, apples,
kaempferol, hesperidin, anti-inflammatory; lowering the risk of grapes, papayas, cantaloupes, plums,
naringinin, CVD; decreasing fat absorption; tomatoes, apricots, beans, cocoa beans,
neohesperidin, and their increasing energy expenditure; broccolis, parsleys, celeries, onions, and soy
glycoside) neuroprotective effects. products
Carotenoids (α- and Important antiaging and antioxidants; Carrots, sweet potatoes, all berries, citrus peels,
β-carotenes, lycopene, enhancing immune function; balancing watercress, pumpkins, tomatoes, watermelons,
and lutein) blood sugars; reducing the risk of and dark green leafy vegetables
CVD and cancer.
Coumarins Antioxidant, anti-inflammatory, Blackberries, cranberries, raspberries,
antitumor, antimicrobial, and antiviral strawberries, cherries, grapes, black currants,
activities; neuroprotective effects. and apricots
Glucosinolates Reducing the risk of breast, colorectal, Cabbage family vegetables, such as broccolies,
lung, and stomach cancers. Brussels sprouts, collards, and kales
Phytosterols Blocking cholesterol uptake and thereby Most plants
preventing CHD.
Abbreviations: CVD, cardiovascular disease; CHD, coronary heart disease.
apple juice and the number is even higher for fresh apple juice. Flavonoid concentration is between 27
and 593 mg/L with fresh juice having higher values. The total polyphenols in commercial apple juice and
fresh apple juice are 110–459 mg/L and 154–970 mg/L, respectively [26,27].
Many reports about the health benefits of soy and soy products including soy milk and soy drinks
have emerged. Soy and its products are protein rich and have a high content of fat with moderate car-
bohydrates. They are rich in isoflavones (genistein, daidzein, and glycitein), saponins, β-sitosterol, and
lecithin [28,29]. Soy product consumption is associated with a reduction of TAG and LDL cholesterol,
reducing the risk of CVD [30]. Soy isoflavones help to ease menopause symptoms and reduce certain
cancer risks, including those of the breast and prostate [29]. There are many other phytochemicals in soy
products that are associated with certain health benefits [28,30].
4.4 Conclusion
Functional beverages have been dramatically gaining consumer interests and market shares. Due to
the extensive research and product exploration, vast scientific data for the correlation between phyto-
chemicals and biological activities have been gathered from the combined fields of natural products,
biochemistry, molecular biology, and nutrigenomics. Phytochemicals and their beneficial health effects
Chemistry of Functional Beverages 45
have rapidly changed traditional consumption patterns. For example, ready-to-drink teas, exotic blends
of fruit juices, antioxidant-rich “superfruits,” combinations of fruit and vegetable juices, and smoothies
continue to expand market territories and to gain impressive sales. Another nontraditional trend is that
many companies are harnessing the power and potency of vegetables due to their phytochemical-rich
and less-carbohydrate contents. In addition, the evolution of drinks with vitamins, minerals, and other
functional ingredients, particularly non-water-soluble nutrients, has led to the application of nanoemul-
sion and microencapsulation, which enables the introduction of hydrophobic ingredients into the aqueous
media and hence the development of water-soluble beverages rich in vitamins A, D, and E, omega-3 fatty
acids, and CoQ10, among others. The concepts of clear protein beverage and sports drinks have also led
to the discovery of whey protein and its extraction technology.
Developing functional beverages with effective health benefits such as disease risk reduction should be
the top priority among many aspects as appearance, flavor, and stability, which are also practical chal-
lenges to satisfy health conscientious customers. Biofunctionality of functional beverages with health-
promoting properties has been focused on preventing oxidation, maintaining cardiovascular health,
improving cognitive function and nutrition, lowering LDL cholesterol, decreasing insulin resistance and
preventing diabetes, reducing body fat, nurturing healthy bone and joints, and preventing cancer. With
the unequivocal and strong science-based data support, functional beverages will certainly grow sub-
stantially in the near future.
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5
Cancer Chemopreventive Effects
of Selected Fruit Juices
CONTENTS
5.1 Introduction..................................................................................................................................... 47
5.2 Combination Approach of Cancer Chemoprevention: Fruit Juice as a Gold Standard.................. 48
5.3 Cancer Chemopreventive Effects of Selected Fruit Juices............................................................. 50
5.3.1 Apple Juice..........................................................................................................................51
5.3.2 Berry Juices........................................................................................................................ 55
5.3.2.1 Chokeberry......................................................................................................... 56
5.3.2.2 Cranberry............................................................................................................ 56
5.3.2.3 Other Berry Juices.............................................................................................. 57
5.3.3 Cherry Juice........................................................................................................................ 57
5.3.4 Pomegranate Juice.............................................................................................................. 57
5.3.5 Mango Juice........................................................................................................................ 58
5.3.6 Noni Juice........................................................................................................................... 58
5.3.7 Tomato Juice....................................................................................................................... 59
5.3.8 Citrus Juices........................................................................................................................ 59
5.3.9 Miscellaneous Fruit Juices................................................................................................. 60
5.4 Conclusion........................................................................................................................................61
Acknowledgments......................................................................................................................................61
References..................................................................................................................................................61
5.1 Introduction
Despite the remarkable progress in developing a wide spectrum of anticancer therapies, cancer still
remains as one of the major global health challenges. Cancer develops through a multistep process
involving multiple gene mutations caused by various lifestyle factors, such as exposure to dietary
carcinogens and solar radiation, smoking, and increased alcohol intake, among others. The multistage
carcinogenesis apparently involves three distinct phases: initiation, promotion, and progression [1,2].
The tumor initiation phase is characterized by irreversible changes in cellular DNA by genotoxic
carcinogens that lead to the neoplastic cell transformation. Tumor promotion is a reversible process
when the initiated tumor cells undergo clonal expansion to form a benign tumor. During the promotion
stage, aberrant alterations in cellular biochemical networks result in the increased proliferation and
neovascularization of the growing tumor. The final stage of carcinogenesis is the tumor progression
phase, when cells from the localized solid tumor lose their adhesion properties and attain migratory
properties. At this stage, cancer cells gain motility and invade through the host stromal tissue and
disseminate to distant organs to form metastatic tumors [1,2]. It is now well accepted that cancer
is a preventable disease because many of the cancer-causing lifestyle factors are simply modifiable
and the biochemical changes occurring during tumor promotion are reversible. About 30%–40% of
47
48 Handbook of Functional Beverages and Human Health
cancers can be prevented by appropriate dietary habits and lifestyle modifications. Because oxidative
stress and inflammation play key roles in all phases of carcinogenesis by causing oxidative or covalent
modification of cellular macromolecules, and activation of oncogenic signal transduction pathways,
substances with antioxidative and anti-inflammatory properties are considered to be effective in pre-
venting cancer. Since the introduction of the concept of cancer prevention, termed as “chemopreven-
tion” in the 1970s [3], numerous studies have demonstrated that antioxidant and anti-inflammatory
plant constituents are effective in preventing carcinogenesis [4,5]. The biochemical basis of cancer
chemoprevention with a wide variety of structurally diverse plant metabolites, also known as phyto-
chemicals, includes inhibition of carcinogen activation and oxidative damage of cellular macromol-
ecules, suppression of inflammatory responses, induction of growth arrest and apoptosis in cancer
cells, inhibition of tumor growth by blocking angiogenesis, and the blockade of invasion, migration,
and metastasis of cancer [4,5]. This chapter highlights the potential of selected fruit juices in cancer
chemoprevention.
Since cancer is caused by mutations of multiple genes and involves perturbation of diverse oncogenic
signaling pathways, the use of a combination of multitargeted naturally occurring antioxidant and anti-
inflammatory phytochemicals would be a rational approach for chemoprevention [23]. The approach
of “combination chemoprevention” proposed by Sporn [23] has gained the experimental proof through
several studies where simultaneous administration of different chemopreventive phytochemicals showed
better anticancer effects than the individual compounds. For example, treatment of mouse skin with a
combination of pomegranate fruit extract with diallyl sulfide derived from garlic showed the most potent
inhibitory effects on the inhibition of chemically induced mouse skin tumorigenesis as compared to that
elicited by treatment with pomegranate fruit extract or diallyl sulfide alone [24]. Likewise, a pomegran-
ate fruit juice component, ellagic acid, when co-treated with grape seed extract or resveratrol exhibited
maximum inhibition of chemically induced skin inflammation and tumorigenesis [25]. Zessner et al. [26]
reported the differential antioxidant and anti-inflammatory effects of apple juice constituents. According
to their study, low molecular weight (LMW) polyphenols (chlorogenic acid, flavan-3-ols, and flavonols)
and procyanidins showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging potential, whereas
peroxyl radical was more effectively scavenged by LMW polyphenols than procyanidins. This study
also demonstrated that among the juice constituents, quercetin aglycone was an inhibitor of carcinogen
metabolizing enzyme, cytochrome p450 (CYP)-1A, whereas phloretin and (−)-epicatechin were the most
potent inhibitors of cyclooxygenase (COX)-1. These findings suggest that fruit juices enriched with a
wide variety of polyphenolic compounds, which often work in synergy, would be the appropriate natural
formulations for multitarget-based chemoprevention of cancer.
O OH
OH HO O OH
HO
O O
HO OH
HO O OH
OH O
HO OH
OH O OH OH
Garcinone Gartanin Mangiferin
O
β-D-glucose
COO–
HO
H3C
H3C CH3 CH3 CH3
HOOC N COOH
CH3 CH3 H3C CH3
HO CH3 H
β-Cryptoxanthin Betanin
H3C CH3
OH O
CH3 CH3 CH3 O CH3
H3C CH3 HO O OH
Lycopene Mangostin
FIGURE 5.1 Chemical structures of selected chemopreventive phytochemicals present in fruit juices. (Continued)
50 Handbook of Functional Beverages and Human Health
OH
OH OH
+
O O
OH
HO OH
OH OH
O OH
HO O OH OH OH O
OH O HO OH
OH OH OH
OH OH OH OH
Epicatechin Cyanidin-3-glucoside Procyanidin B2
OH O
OH HO CO2H
HO
O O
HO O OH
HO O HO
OH OH O
OH OH
OH O OH O
Quercetin Chlorogenic acid Ellagic acid
OH
HO O
O
O O O
HO O
OH HO OH
OH OH O
Hespiridin
FIGURE 5.1 (Continued) Chemical structures of selected chemopreventive phytochemicals present in fruit juices.
Antiproliferative
effects Apoptosis-
Antimutagenic/
Antigenotoxic effects inducing effects
Antioxidant Antiangiogenic
effects and
Antimetastatic
effects
Fruit
juices
suppression, whereas sour cherry, grapefruit, red currant, and pineapple juices were only weakly active
in blocking IQ-mediated genotoxic effects. On the other hand, the inhibition of PhIP-mediated genotox-
icity by these fruit juices was less prominent than their suppressive effect on the IQ-induced genotoxicity
[27]. Administration of several fruit juices has been shown to inhibit experimentally induced carcinogen-
esis in various animal models (Table 5.1). For example, drinking of pomegranate juice, cranberry juice,
and watermelon juice as 20% fruit juice preparation significantly diminished azoxymethane (AOM)-
induced ACF formation and increased the total glutathione-S-transferase (GST) activity in male Fischer
344 rats [28]. The following section will shed light on the antioxidant, anti-inflammatory, and cancer
chemopreventive effects of fruit juices and their underlying molecular mechanisms.
TABLE 5.1
Anticancer Effects of Fruit Juices
Fruit Juices Experimental Model Dose and Route Experimental Findings References
Apple Juice
Cloudy apple juice (21.5 mL/ DMH-induced ACF formation Drinking for 8 weeks; 1 week after Decreases genotoxicity, colonic epithelial cell proliferation, [13]
animal/day) and clear apple in male Fischer 344 rats juice intake, DMH was given i.p. and ACF formation; reduced COX-2 mRNA expression;
juice (22.9 mL/animal/day) once per week for 4 times and rats and increases antioxidant activity.
were sacrificed 3 weeks after the last
dose of DMH.
Cloudy apple juice, PF, or CF DMH-induced ACF formation Drinking for 8 weeks; 1 week after Only cloud juice, but not CF or PF, reduces DMH [22]
of apple juice in male Fischer 344 rats start of cloudy juice, PF, and CF, genotoxicity and DMH-induced colonic cell proliferation,
DMH was given i.p. once per week and increases antioxidant activity.
for 4 times and rats were sacrificed 3
weeks after the last AOM dose.
Procyanidin-rich fraction of SW620 colon cancer cells Incubation of cells at a concentration Inhibits cell proliferation, induces G2/M phase cell cycle [33]
apple juice of 50 μg/mL. arrest, increases caspase-3 activity, and reduces the
activity of ODC and PKC.
Rats challenged with AOM Daily drinking for 6 weeks post-AOM. Decreases AOM-induced colonic ACF formation. [33]
Berry Juices
Fruit juice plus pulp of black Rats treated with aminopyrene Daily for 3 days by gavage; AN Reduces formation of nitrosamine and inhibits liver [40]
chokeberry (AN) plus sodium nitrite in the (1 mL/100 g body weight). dystrophy.
presence or absence of AN
Polyphenol-rich chokeberry Caco-2 colon cancer cells Incubation of cells with 2% or 5% Decreases cell proliferation, and induces G2/M phase cell [41]
juice juice. cycle arrest, increases gene expression of CEACAM1 and
integrin-α2, and reduces S100A4 mRNA.
Cranberry juice concentrate Rats treated with bladder Juice concentrate (0.5 or 1 mL/rat/day) Inhibits urinary bladder hyperplasia, papilloma, and [48]
carcinogen OH-BBN given by gavage for 37 days, started carcinoma formation.
1 week after OH-BBN challenge.
Pure cranberry juice AOM-treated rats Juice (20%) in drinking water daily for Reduces the number of ACF in proximal and distal colon, [28]
17 weeks. decreases the number of crypts per ACF, and increases
liver GST activity.
(Continued)
Handbook of Functional Beverages and Human Health
TABLE 5.1 (Continued)
Anticancer Effects of Fruit Juices
Fruit Juices Experimental Model Dose and Route Experimental Findings References
Freshly prepared juices of Colon cancer (Caco-2), prostate Incubation of cells, with juice 50 μL/mL Inhibits cell proliferation, increases caspase-3 activity, and [14]
raspberry, black currant, red cancer (PC3), gastric cancer for 48 h. reduces the constitutive level of cyclin-D1 and cyclin-D3
currant, white currant, goose (AGS), and breast cancer and Cdk-4 and Cdk-6.
berry, cranberry, blueberry, (MCF-7, MDA-MB-231) cells PC3 cells stimulated with or without Inhibits TNFα-induced COX-2 expression and NF-κB
and sea buckthorn TNFα were treated with juice activity.
(25 μL/mL).
Black currant juice Ehrlich tumor–bearing mice Daily for 21 days at a dose of 10 mL/kg. Inhibits tumor weight by 45%. [55]
Tart cherry fruit juice Breast cancer (MCF-7) cells Incubation with 10% or 30% (v/v) Inhibits cell proliferation and decreases bromodeoxyuridine [57]
juice. incorporation by 20%.
Pomegranate Juice
Pure pomegranate juice AOM-treated rats Juice (20%) in drinking water daily for Reduces the number of ACF in proximal and distal colon, [28]
17 weeks. decreases the number of crypts per ACF, and increases
liver GST activity.
Fresh pomegranate juice AOM-treated rats Drinking daily for 9 weeks at a dose of Decreases the number of colonic ACF; reduces [12]
57.21 mL/day (438.95 mg GAE/kg/ proliferation of colon epithelial cells; suppresses iNOS
Cancer Chemopreventive Effects of Selected Fruit Juices
Nrf2 target genes [29]. These findings suggest that apple juice can fortify cellular antioxidant defense
by inducing Nrf2-dependent gene expression, which appears as a plausible mechanism of its cancer
chemopreventive activity.
Polyphenolic constituents of apple juice also exhibited anti-inflammatory effects. A phenolic apple
juice extract (AE04), prepared from juices of different apple varieties, significantly inhibited the expres-
sion of various inflammatory genes, such as tumor necrosis factor-α (TNFα), interleukin (IL)-β, chemo-
kine C-X-C motif ligand (CXCL)-9, CXCL-10, and COX-2 in lipopolysaccharide (LPS) plus interferon-γ
(IFNγ)-stimulated human monocytic (monoMac6) cells. AE04 was shown to contain diverse poly-
phenolic compounds, of which flavan-3-ol dimer procyanidin B2 was found to be responsible for
the anti-inflammatory activity of AE04. In addition, AE04 components dihydrochalcone aglycone
(phloretin) and the dimeric flavan-3-ol (procyanidin B1) significantly inhibited proinflammatory gene
expression and repressed NF-κB-, IFNγ-inducible protein-10 (IP-10)-, and IL-8-promoter activity in a
concentration-dependent manner [31]. Thus, the antioxidant and anti-inflammatory effects of apple juice
and/or its active constituents suggest the potential of apple juice for cancer chemoprevention.
In a pilot study, lymphocytes from female volunteers who consumed a quercetin-rich mixture of
blueberry and apple juice for 4 weeks were treated ex vivo with H2O2 or benzo(α)pyrene (B[α]P). The
juice consumption led to a decrease in H2O2-induced oxidative DNA damage and B[α]P-diol epixode
(BPDE)-DNA adduct formation. Moreover, treatment of human lymphocytes, preincubated with quer-
cetin in vitro, with H2O2 or B[α]P significantly decreased the oxidative DNA damage and BPDE-DNA
adduct formation [32]. Barth et al. [13] demonstrated that intervention with daily consumption of clear
apple juice or cloudy apple juice for 7 weeks starting 1 week prior to challenge with DMH significantly
reduced the proliferation index of colon epithelial cells. However, the cloudy apple juice, but not the clear
apple juice, reduced the number and mean size of large ACF in distal colon. A subsequent study by these
authors showed that daily consumption of cloudy apple juice itself, but not its fractions, was effective
in preventing DMH-induced genotoxicity, colonocyte proliferation, and large ACF formation [22]. The
cloudy apple juice contains a high concentration of procyanidins. Gosse et al. [33] examined the effect of
a procyanidin-rich fraction of fresh apple extract. According to their study, the procyanidin-rich extract
attenuated the proliferation of human colon cancer (SW620) cells in culture by blocking the activities of
protein kinase C (PKC) and ornithine decarboxylase (ODC). This study also demonstrated that a 6-week
intervention with procyanidin-rich apple extract significantly inhibited AOM-induced ACF formation in
rat colon [33].
The polyphenol-rich extract of commercially available apple juice inhibited the growth of human
colon cancer (HT29) cells by blocking the tyrosine kinase activity of epidermal growth factor receptor
(EGFR) and attenuating the activation of downstream mitogen-activated protein (MAP) kinases [34].
Chemical analysis of this polyphenol-rich apple juice extract revealed the presence of major phyto-
chemicals, such as proanthocyanidins B1 and B2, isoquercitrin (quercetin-3-glucoside), and hyperoside
(quercetin-3-galactoside) with substantial EGFR-inhibitory properties. However, a mixture of these
apple juice constituents showed only a marginal inhibitory effect on EGFR activation, suggesting that
the apple juice extract may contain additional chemopreventive agents and that the juice as a whole is
more effective than the isolated constituents [34]. Teller et al. [35] recently reported that the concentra-
tion of quercetin or its glycosides was too low to inhibit the EGFR activity and that the dihydrochalcones
and their glycosides diminished EGFR activity only in a cell-free system, but not in human cancer cells.
However, the fractions comprising more than 86% oligomeric procyanidins obtained from apple juice
extract inhibited the activities of EGFR and ErbB3 in cultured cancer cells [35].
berry juices in a wide range of human cancer cells. The juices of raspberry, black currant, white cur-
rant, gooseberry, velvet leaf blueberry, low-bush blueberry, sea buckthorn, and cranberry juice sig-
nificantly inhibited the growth of various cancer cells, including those of stomach, prostate, intestine,
and breast carcinomas. The antiproliferative effect of berry juices resulted from cell cycle arrest, but
not through caspase-dependent apoptosis, as evidenced by the downregulation of the expression of
cell cycle regulatory proteins, such as cyclin-dependent kinase (Cdk)-4, and Cdk-6 and cyclin-D1 and
cyclin-D3. Of the 13 berries tested, the juice of raspberry, black currant, gooseberry, sea buckthorn,
cranberry, and blackberry significantly inhibited TNFα-induced expression of COX-2 and the activa-
tion of NF-κB [14].
5.3.2.1 Chokeberry
Fruits of Aronia melanocarpa [Michx] Elliot and Aronia arbutifolia [L] Elliot are commonly known as
black choke berry and red chokeberry, respectively [37]. Because of the high content of anthocyanins,
chokeberries have long been used as a food colorant. The astringent taste of chokeberry limits the con-
sumption of this fruit, but recent advances in fruit juice blending technology improve the taste of the
juice by mixing with other fruit juices, such as that of apple, pear, or black currant [37]. Phytochemicals
present in chokeberry include anthocyanins (cyanidin-glycosides), phenolic acids (chlorogenic acid,
cryptochlorogenic acid, and neochlorogenic acid), and carotenoids (β-carotene, β-cryptoxanthin, and
violaxanthin) [37]. Anthocyanins, which represent about 25% of total polyphenols in chokeberry juice
[38], showed inhibitory effects on the mutagenicity of B[α]P and 2-aminoflourene [39]. Administration
of chokeberry juice inhibited the endogenous formation of N-nitrosamine in rats challenged with ami-
nopyrene and sodium nitrite and protected against liver damage [40]. Since N-nitrosamine is a potent
hepatocellular carcinogen, this study suggests the potential of chokeberry juice in preventing liver can-
cer. Treatment with chokeberry juice inhibited the proliferation of colon cancer (Caco2) cells in culture
by inducing G2/M phase cell cycle arrest and restoring the expression of a tumor suppressor protein
carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is diminished in early
adenomas and carcinomas [41]. Moreover, the anthocyanin-rich extract of chokeberry induced apoptosis
in human colon cancer (HT29 cells) without affecting the growth of normal colon epithelial (NCM460)
cells [42]. The colon cancer-preventive effect of chokeberry juice extract can be attributed to its antioxi-
dant effect [43]. Moreover, the chokeberry juice constituents, such as β-cryptoxanthin [44], chlorogenic
acid [45], and cyanidin-3-glucosides [46], exhibited colon cancer chemopreventive effects.
5.3.2.2 Cranberry
Cranberry juice is well known for its beneficial effects in urinary tract infections [47]. The a ntiproliferative
activity of cranberry juice in various human cancer cells has been reported [14]. Prasain et al. [48] demon-
strated that intervention with cranberry juice concentrate prevented chemically induced urinary bladder
carcinogenesis in rats. According to this study, rats were first treated with N-butyl-N-(4-hydroxybutyl)-
nitrosamine (OH-BBN) for 8 weeks and feeding with cranberry juice concentrate was started 1 week
after the final dose of OH-BBN and continued for 6 months. Consumption of cranberry juice inhibited
OH-BBN-induced urinary bladder papilloma and carcinoma formation in rats by 51% and 38%, respec-
tively. The study also identified the major chemopreventive constituent of cranberry juice as quercetin
and its methylated derivatives [48]. These findings were supported by a previous study demonstrating
that rats receiving a 5% quercetin diet were protected against chemically induced rat urinary bladder
carcinomas [49]. In another study, rats receiving 20% cranberry juice decreased the total number of
AOM-induced ACF formation and showed enhanced GST activity in the colon [28]. One of the major
causes of gastric cancer is Helicobacter pylori infection. In a prospective, randomized, double-blind, and
placebo-controlled human intervention trial, consumption of cranberry juice (500 mL/day) for 90 days
inhibited the H. pylori infection [50], suggesting the potential of cranberry juice in gastric cancer pre-
vention. A nondialyzable fraction derived from cranberry juice inhibited the growth of cultured murine
lymphoma (Rev-2-T-6) cells and attenuated the invasion of these cells through the extracellular matrix
[51]. Moreover, intraperitoneal administration of this fraction diminished the growth of Rev-2-T-6 cell
Cancer Chemopreventive Effects of Selected Fruit Juices 57
xenograft tumors in mice and enhanced the generation of antilymphoma antibodies [51]. Cranberry
juice was reported to be one of the effective fruit juices in inducing cell cycle arrest in various cancer
cells through the downregulation of the expression of D series cyclins and Cdk-4 and Cdk-6. In addi-
tion, cranberry juice inhibited TNFα-induced NF-κB activation and COX-2 expression in different
cancer cells [14].
colon cancer (HT-29) cells with pomegranate juice extract containing polyphenols decreased the cell
viability, which was associated with elevated expression of miR-126, activation of casapse-3 and cleav-
age of poly (ADP-ribose) polymerase (PARP), and diminished mRNA and protein expression of vari-
ous inflammatory markers, such as NF-κB p65, VCAM-1, intercellular adhesion molecule-1 (ICAM-1),
COX-2, and phosphorylated-Akt [12]. Transfecting cells with antagomiR-126 abrogated the antiprolif-
erative and anti-inflammatory effects of pomegranate juice in HT-29 cells. This study also revealed that
incubation with pomegranate juice polyphenols reduced the expression of vascular endothelial growth
factor (VEGF) in HT-29 cells, indicating the antiangiogenic potential of this fruit juice [12]. Adams et al.
[62] reported that treatment of HT-29 cells with pomegranate juice or its total tannin content attenuated
TNFα-induced expression of COX-2, phosphorylation p65, and DNA binding of NF-κB. In another study,
rats treated with pomegranate juice instead of drinking water ameliorated dextran sulfate sodium (DSS)-
induced colitis by blocking the activation of p70S6K, mitogen-activated protein kinase kinase (MEK),
and extracellular signal-regulated kinase (ERK1/2) and inducing the expression of miR145 in colonic
epithelial tissue [63].
and 5-fluorouracil [75,76]. The latter study further demonstrated that noni juice induced cytotoxicity in
LLC cells when co-cultured with murine peritoneal cells exudate which increased the release of cytokines
and NO upon treatment with noni juice [76]. These findings suggest that noni juice stimulates host immune
responses and holds the cancer immunotherapeutic potential. Other glycosides present in noni juice
diminished 12-O-tetradecanoyl phorbol-13-acetate (TPA)- or extracellular growth factor (EGF)-induced
transformation of mouse epidermal JB6 cells by blocking the activation of activator protein-1 (AP-1) [77].
Hornick et al. [78] suggested that noni juice disrupted newly formed human vascular networks, indicating
its antiangiogenic activity. A recent study reported that treatment of human lung adenocarcinoma (A549)
cells with noni juice inhibited manganese-induced expression of hypoxia-inducible factor-1α (HIF-1α), an
angiogenic switch in cancer, by blocking the activation of ERK1/2, c-Jun-N-terminal kinase-1 (JNK1),
protein kinase B (PKB), and ribosomal protein S6 kinase. This study also suggested that noni juice attenu-
ated HIF-1α protein expression in A549 cells stimulated with IL-1β [79].
activity [89]. Drinking of freshly prepared orange juice (20 fluid ounce [equivalent to 592 mL] daily) for
90 days significantly increased the total plasma antioxidant capacity and inhibited lipid peroxidation in
subjects with hyperlipidemia [90]. Juices prepared by hand-squeezing peeled Moro fruits (Citrus sinen-
sis L. Osbeck) contained a variety of C- and O-glycosylated flavonoids, such as lucenin-2, vicenin-2,
stellarin-2, lucenin-2 4′-methyl ether, scoparin, chrysoeriol 7-O-neohesperidoside, narirutin, and hes-
peridin [21]. Stella et al. [91] demonstrated that total polyphenol content in commercially available
ready-to-drink orange juice and nectar ranged from 18.7 to 54.2 mg GAE/100 mL and the total antioxi-
dant activity varied between 57.88 and 349.32 μmol trolox equivalents (TE)/100 mL. The antioxidant
capacity was more strongly correlated with the total polyphenol rather than vitamin C alone. Intake of
orange juice with a diet rich in high fat–high carbohydrate (HFHC) reduced the oxidative and inflamma-
tory markers, such as the gene expression of Toll-like receptor (TLR)-2, TLR4, nicotinamide-adenine
dinucleotide phosphate oxidase (NOX), and matrix metalloproteinase (MMP)-9 in blood mononuclear
cells of healthy volunteers [92]. Moreover, orange juice component α-terpineol reduced IL-6 production
in buccal epithelial cells [88].
Because of its antioxidant and anti-inflammatory properties, orange juice holds the promise of can-
cer chemopreventive activity. Consumption of orange juice has been shown to prevent experimentally
induced colon and mammary carcinogenesis [93,94]. Administration of orange juice delayed the devel-
opment of mammary tumors in rats challenged with DMBA or high-fat diet [94]. Orange juice supple-
mentation for 28 weeks after AOM administration also reduced the incidence of colon tumors in rats.
Hesperidin flavonoid and limonoid glucosides were identified as the major bioactive principles in orange
juice that could contribute to the chemopreventive effect of orange juice [93]. In fact, the proliferation of
human mammary carcinoma (MDA-MB-435) cells was markedly inhibited by treatment with hesperitin
in combination with grape fruit juice component quercetin or naringenin [94].
Drinking of juice prepared from Satsuma mandarin or its juice enriched with β-cryptoxanthin or
hesperidin for 36 weeks starting 1 week after AOM administration significantly decreased the incidence
and multiplicity of colonic adenocarcinomas in rats [95]. Mandarin juice rich in hesperidin showed the
strongest inhibitory effects. Moreover, mandarin juice consumption increased the apoptotic index and
inhibited the expression of cell proliferation markers PCNA and cyclin D1 in colonic adenocarcinomas
[95]. Likewise, administration of mandarin juices in drinking water starting at 1 week after challenge
with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) attenuated the incidence and multiplicity
of lung tumorigenesis in male A/J mice [96]. Treatment with juice prepared by squeezing fresh bergamot
fruit (Citrus bergamia) inhibited the proliferation and invasion of neuroblastoma (SK-N-SH and LAN1)
cells in vitro without altering the weight of LAN1 cell xenograft tumors in vivo. However, bergamot juice
inhibited lung metastasis of LAN1 neuroblastoma cells in severe combined immunodeficiency (SCID)
mice [97]. Zhu et al. [98] isolated 7-O-neohesperidoside of isosakuranetin (poncirin) from different parts
including the juice sac of Ougan fruit (Citrus reticulata cv. Suavissima) and reported the antiproliferative
effect of the compound in human gastric cancer (SGC-7901) cells.
yellow-orange pear, exhibited DPPH radical scavenging activity with red-purple pear juices being the
most active. When the juice of red-purple pear was given by gavage to mice treated with a mutagen
methyl methanesulfonate, the number of micronucleated polychromatic erythrocytes was significantly
decreased, suggesting the antioxidant and antimutagenic effects of red-purple pear juice [104]. In another
study, juices of nine different varieties of prickly pears were analyzed for their phenolic content, anti-
oxidant potential, and anticancer activity. Flavonoids, betaxanthins, and betacyanins were identified as
major constituents of these pear juices, which exhibited strong antioxidant activity and inhibited the
proliferation of human cancer cells. Among the nine varieties, juice of the Rastrero pear exhibited anti-
proliferative effects against prostate, colon, mammary, and liver cancer cells in vitro, while Moradillo
pear juice had the highest flavonoid content and diminished the growth of only prostate and colon cancer
cells. Interestingly, none of the pear juices reduced the viability of normal human fibroblasts, suggesting
that the prickly pear juices induce cytotoxicity selectively in cancer cells [105].
5.4 Conclusion
Over the last several decades, dietary cancer chemoprevention has received immense interest as a ratio-
nal strategy to reduce the incidence of and mortality from cancer. Numerous dietary phytochemicals,
especially those present in edible fruits, vegetables, and spices, have been identified as promising candi-
dates for cancer chemoprevention. Accumulating evidence from epidemiological and laboratory-based
studies has shown that regular intake of fruits can reduce the risk of various cancers. In addition to their
nutritional value, fruits are rich sources of a large number of chemical compounds, which have been
reported to possess anticancer activity. There is now increasing trend in consuming a wide variety of
ready-made fruit juices available in supermarkets. Since fruit juices contain a whole bunch of chemo-
preventive phytochemicals, it is considered that consumption of fruit juices may prevent carcinogenesis.
Since cancer is a heterogeneous disease, the combination of chemopreventive agents present in fruit
juices makes them a good choice for achieving multitargeted cancer chemoprevention. Although the
experimental findings accumulated to date strongly suggest the chemopreventive potential of fruit juices,
additional studies are warranted to evaluate the anticancer efficacy of fruit juices in an expanded area
covering many different types of cancer. Moreover, further studies are necessary to elucidate the phyto-
chemical and pharmacokinetic profiling of fruit juices and understanding their molecular mechanisms of
anticancer activity. Whereas the majority of chemoprevention research with fruit juices was performed
with freshly prepared juices, practically commercial fruit juices are consumed by humans. Thus, focus
should be given on assessing the chemopreventive potential and safety of commercially available fruit
juices. Nonetheless, fruit juices as a natural blend of anticancer principles are promising dietary measure
for cancer chemoprevention and a large variety of functional foods can be developed to help prevent
carcinogenesis.
Acknowledgments
This work has been supported by the Settlement Research Grant #2012-0195 of Keimyung University
allocated to Joydeb Kumar Kundu.
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