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“Moving Beyond Antioxidants: Making Phytochemicals a Prescription for Health”
2013 Food and Nutrition Conference & Expo
October 21, 2013, 8:00 a.m. - 9:30 a.m.
Lenore Arab, Ph.D., M.Sc.
Professor, General Internal Medicine and Health Service Research & Department of Biological Chemistry
David Geffen School of Medicine, UCLA
Britt Burton-Freeman, Ph.D., M.S.
Director, Center for Nutrition Research, Institute for Food Safety and Health
Illinois Institute of Technology
Objectives. After this presentation, the attendee should be able to:
1. Explain the scientific rationale for the evolution of antioxidant claims and identify common dietary
phytochemical “active ingredients” in foods and their alternative mechanisms of action other than
antioxidant activity.
2. Describe the clinical evidence and epidemiologic foundation that support the health-promoting,
functional benefits of consuming polyphenol-rich foods and beverages, focusing on specific examples
of anthocyanidins in fruits and flavonols in tea.
3. Specify dietary guidelines and tailored recommendations for the choice of phytochemical-rich
foods and beverages that can help consumers eat and drink their way to better health.
When Greek physician Hippocrates said “Let food be thy medicine and medicine be thy food,” little did he
know that good health would continue to be inextricably linked to the types of foods we eat nearly 2,500
years later. The past decade has presented an explosion of clinical research to show specifically what health
benefits individual foods can offer, identifying the various nutrients and phytochemicals associated with
these benefits. No longer attributed to antioxidant activity, plant bioactive compounds have been shown
to exert biological effects in the body by interacting with cells, enzymes, hormones and DNA to positively
impact chronic disease risk. This session features two experts who will present emerging scientific and
epidemiological evidence that support the role of dietary flavonoids in disease prevention, and how meals
that include phytochemical-rich foods and beverages constitute a prescription for health.
The Evolution of Antioxidant Claims
The term “antioxidant” has become synonymous with overall good health and disease prevention. Despite
the label claims on a myriad of dietary supplements, foods and beverages, there is no standardized method
for measuring antioxidant status and no official definitions for antioxidant capacity, ability or activity. In fact,
any single numerical value greatly oversimplifies the complicated science and health-promoting significance
of these bioactives.
The end of antioxidant health claims in Europe came in 2010, when The European Food Safety Authority
(EFSA) issued a Scientific Opinion on the substantiation of health claims related to antioxidant properties.
EFSA found that “antioxidant activity” and “antioxidant properties” are not evidence based in the general
population, and that the evidence provided in animal and in vitro studies was not sufficient to predict
protection from oxidative damage in vivo in humans. In 2012, the USDA removed the ORAC (Oxygen Radical
Absorbance Capacity) database from its website, citing that these in vitro measures of antioxidant capacity
“have no relevance to the effects of specific bioactive compounds, including polyphenols, on human health,”
and that the ORAC values are “routinely misused by food and dietary supplement companies to promote
their products and by consumers to guide their food and dietary supplement choices.”
Industry and the scientific community are faced with a number of challenges to characterize these bioactive
compounds and their mechanisms of action, gain a better understanding of their metabolic fate during
digestion and absorption and develop a quantifiable reference for these health-promoting phytochemicals.
Common Dietary Flavonoids
Flavonoid Subclass
Dietary Flavonoids
Cyanidin, Delphinidin, Malvidin,
Pelargonidin, Peonidin, Petunidin
Monomers (Catechins):
Catechin, Epicatechin,
Epigallocatechin Epicatechin gallate,
Epigallocatechin gallate
Dimers and Polymers:
Theaflavins, Thearubigins,
Hesperidin, Naringenin, Eriodictyol
Quercetin, Kaempferol, Myricetin,
Apigenin, Luteolin
Daidzein, Genistein, Glycitein
Examples of Common Food Sources
Strawberries, blueberries, raspberries;
red and purple grapes; red wine
Catechins: Teas (particularly green and
white), chocolate, grapes, berries,
Theaflavins, Thearubigins: Teas
(particularly black and oolong)
Proanthocyanidins: Chocolate, apples,
berries, red grapes, red wine
Citrus fruits and juices (e.g., oranges,
grapefruits, lemons)
Widely distributed: yellow onions,
scallions, kale, broccoli, apples,
berries, teas
Parsley, thyme, celery, hot peppers,
Soybeans, soy foods, legumes
Tea Flavonols and Health
Flavonoids are a group of plant substances within the polyphenol family. They are not nutrients yet are
thought to support health due to special properties shown in vitro which enable them to reduce
inflammation, inhibit cancer cells, maintain vascular function and slow oxidation of LDL cholesterol. The
key dietary sources of flavanols in Western countries are tea, onions, red wine, chocolate and fruit.
The common flavanols in tea are catechins (particularly green and white tea) and theaflavins and
thearubigins (particularly black and oolong). Black tea, contributes 60-84% of dietary flavonoids in Western
populations, and the level and type of flavonoids in tea varies greatly depending on the type of tea (green or
black), variety, growing conditions, manufacturing process and tea preparation habits (e.g. brewing time).
There is strong evidence that tea flavonoids are associated with a lower risk of cardiovascular disease, and
emerging evidence points to a role for tea flavonoids in other chronic conditions, including obesity, diabetes
and declining cognitive function. The biological activities of flavonoids include effects on cell-signaling
pathways which could help prevent cardiovascular disease by:
 Decreasing inflammation
 Decreasing vascular cell adhesion molecule expression
 Increasing endothelial nitric oxide synthesis (eNOS) activity
 Decreasing platelet aggregation
The evidence linking flavonoids, and tea, with reduced risk of heart disease is very promising. Three types
of studies provide proof: (1) observational studies, where intakes of flavonoids or tea are associated with a
reduced risk of heart disease; (2) intervention studies, where beneficial changes in risk factors are seen in
subjects consuming flavonoids or tea under controlled conditions; (3) mechanistic studies, where flavonoids
are shown in the laboratory to have specific metabolic effects that explain how they work in practice. All of
these types of studies combine to prove that flavonoids have an impact on health.
A meta-analysis estimated that the risk of myocardial infarction was 11 percent lower when three cups of
tea per day were consumed, with a maximum reduction of 70 percent reported by two studies. (Peters,
et al, 2001)
A meta-analysis found that people with the highest intake of flavonols had a 20 percent lower risk of
developing coronary heart disease compared with people with the lowest intakes. (Huxley, 2003)
A meta-analysis of randomized controlled trials examined the impact of flavonoid-rich foods and drinks
on coronary risk factors. Flavonoids, especially from tea, improved vascular function by 3.4 percent, on
average, which would translate into a reduction in heart disease risk of around 2.5 percent. (Hooper, et
al, 2008)
Further intervention trials looked at the impact of two to three cups of tea per day on vascular function,
and have shown that it was beneficial to endothelial function. This benefit is most likely attributed to the
flavonoids in tea and may be at least partially responsible for any reduction in risk of cardiovascular
disease. (Schroeter, et al, 2006; Widlansky, et al, 2007; Loke, et al, 2008)
Evidence on tea or flavonoids and stroke is well established. Animal studies have shown that tea and/or
EGCG can reduce stroke-related brain damage. A meta-analysis of studies in five different countries, from
nine studies involving 4,378 strokes among 194,965 individuals, were pooled and associated regular tea
consumption with a 21 percent lower risk of developing or dying from stroke. (Arab, et al, 2009) People
drinking three or more cups of tea a day had a 21 percent lower risk of stroke compared with non-consumers
of tea. This study was supported by another meta-analysis which examined the evidence for flavonoid
intakes and risk of stroke. Using data from six large cohort studies, which reported that a high intake of
flavonols was significantly associated with a 20 percent lower risk of developing stroke. (Hollman, et al, 2010)
People of all ages can benefit from drinking tea on a regular basis, and unsweetened tea as a beverage may
be desirable for weight management, the elderly and those at risk of stroke and compromised endothelial
function. Studies suggest that physiologic effects are seen with the consumption of three or more cups of
tea per day.
Strawberry Anthocyanidins and Health
Anthocyanidins are a group of abundant and widely-consumed dietary flavonoids that occur ubiquitously in
plants, providing the bright red-orange to blue-violet colors present in many fruits and vegetables.
Strawberries are rich in phenolic compounds, the most abundant of which are anthocyanins, ellagic acid,
and the flavonols kaempferol and quercetin. These bioactive compounds continue to be the focus of intense
study due to their anti-inflammatory, anticarcinogenic and antimutagenic properties.
A growing body of research is revealing how chronic inflammation and obesity are related to the
development of a number of diseases, including heart disease, stroke, type 2 diabetes and cancer. Studies
continue to show a positive association between strawberry consumption and cardiovascular health, as well
as the fruit’s role in mediating inflammation.
Epidemiological studies have linked increased consumption of fruits and vegetables with lower risk for heart
disease, and dietary intake records of approximately 27,000 women who participated in the decade-long
Women's Health Study showed that women who had a higher intake of strawberries (two or more servings
per week) were more likely to follow a heart-healthy diet—eating about twice as many servings of fruits and
vegetables daily as women in the lowest intake group. (Sesso HD, et al, 2007)
In a study evaluating the effectiveness of strawberries in lowering cardiovascular risk factors in
individuals with metabolic syndrome, those receiving a diet supplemented with the equivalent of three
cups of fresh strawberries daily for eight weeks showed a significant decrease in total and low-density
lipoprotein cholesterol levels and a positive impact on other markers of atherosclerosis, including lipid
particle size and circulating levels of vascular cell adhesion molecules. (Basu A, et al, 2010)
A study conducted to determine the effect of strawberries on inflammatory mediators and blood lipid
profiles in obese individuals showed those who received a typical American diet which included the
equivalent of four servings of frozen strawberries daily had reduced blood cholesterol levels and positive
alterations in lipid subfractions after the three-week intervention. These observations suggest a role for
strawberries as a dietary strategy to reduce obesity-related disease risk. (Zunino SJ, et al, 2012)
Age-related declines in cognitive function have been related to both oxidative stress and inflammation.
Researchers at the USDA Human Nutrition Research Center on Aging at Tufts University have identified
phenolic compounds, particularly anthocyanins, found in strawberries and other berry fruits, to have potent
anti-inflammatory properties. Preclinical research in animal models has demonstrated the effects of these
phytochemicals on enhanced cognition and motor control. (Miller MG, et al, 2012)
An observational study of the association between the long-term dietary intakes of flavonoids, including
anthocyanidins, and cognitive decline was conducted in a sample of 16,010 women, age 70 years or
older, enrolled in the Nurses’ Health Study. Researchers found greater intakes of strawberries (two or
more servings per week) were associated with slower rates of cognitive decline, appearing to delay
cognitive aging by up to 2.5 years. (Devore EE, et al, 2012)
Dietary polyphenols are thought to exert their anticarcinogenic effects by offering protection against
inflammation and oxidative stress that can cause DNA damage, scavenging free radicals and protecting cell
membranes from lipid peroxidation.
In a study conducted in provinces in China where the population is at the highest risk for esophageal
cancers in the world, researchers assessed the effect of daily strawberry supplementation in adults with
premalignant lesions for a period of six months. Strawberry supplementation reduced the number of
people with mild dysplasia and significantly inhibited protein expression and cell proliferation, suggesting
that the strawberries played a role in down-regulating inflammation, oxidative stress and cell
proliferation associated with cancer promotion/progression. (Chen T, et al, 2012)
Fruits and vegetables make a significant contribution to overall health, and scientists are continuing to
associate groups of fruits and vegetables with specific health benefits based on their phytochemical
content. National consumer research shows that strawberries are one of America’s favorite fruits, and
scientific evidence supports their role in health and disease risk reduction, with the potential to provide
benefits related to cardiovascular disease, cancer, insulin resistance, diabetes and age-related declines in
cognitive function. A simple dietary recommendation to consume a serving of strawberries several days a
week or daily may have meaningful public health implications for children and adults of all ages.