CRANBERRY

Health Benefits

While familiar nutrients like vitamin C and fiber play a very important role in cranberry's health benefits, it's the amazing
array of phytonutrients in cranberries that has gotten the special attention of health researchers. There are at least 5 key
categories of health-supportive phytonutrients in cranberries, as summarized in the following chart:

Cranberry Phytonutrients

Type of
Specific Molecules
Phytonutrient
hydroxybenzoic acids including vanillic acids; hydroxycinnamic acids inculding caffeic, coumaric,
Phenolic Acids
cinnamic, and ferulic acids
Proanthocyanidins epicatechins
Anthocyanins cyanidins, malvidins, and peonidins
Flavonoids quercetin, myricetin, kaempferol
Triterpenoids ursolic acid

The vast majority of phytonutrients presented in this chart have been studied for their antioxidant, anti-inflammatory, and
anti-cancer properties, and in many cases the results have been impressive. Equally important in the cranberry research has
been the finding that isolated phytonutrients in cranberry do not account for the same degree of health benefit as
phytonutrients taken as a complete, synergistic group. What this research finding means is simple: it's the whole cranberry
that supports our health best.

When speaking in general terms about the health benefits of cranberries, it is also important to know that the most
commonly consumed form of this food is juice processed from the berries and typically produced by adding generous
amounts of sugar. This form of cranberry cannot provide you with cranberry's full phytonutrient benefits. The cranberry
"presscake"-or what is left behind in terms of skins and flesh after the juice has been processed out-typically contains the
bulk of the phytonutrients when evaluated in lab studies.

Protection against Urinary Tract Infection (UTI)

Long before researchers started investigating from the standpoint of science, cranberry has been used to help prevent and
treat urinary tract infections (UTIs). While the acidity of cranberries was at one time an important target of research, we now
know that cranberry's ability to provide UTI benefits is not primarily related to its acidity, but rather to its proanthocyanidin
(PAC) content. The PACs in cranberry have a special structure (called A-type linkages) that makes it more difficult for
certain types of bacteria to latch on to our urinary tract linings. Include in these types of bacteria are pathogenic (infection-
causing) strains of E. coli - one of the most common microorganisms involved in UTIs. By making it more difficult for
unwanted bacteria like E. coli to cling onto the urinary tract linings, cranberry's PACs help prevent the expansion of
bacterial populations that can result in outright infection. The age group in which researchers are least sure about this
process involves children-it's just not clear when cranberry's health benefits fully extend to this age group. The area where
benefits have been most pronounced are in middle-aged women who have experienced recurrent UTIs. In some studies,
UTIs in this age and gender group have been reduced by more than one- third through dietary consumption of cranberry.

The discovery that cranberries prevent UTIs by blocking adhesion of bacteria to the urinary tract lining is a discovery that
has allowed research on cranberry to expand out in other important directions. In our Digestive Benefits section below, we
will describe how prevention of stomach ulcer is one very intriguing new direction in the cranberry research, based on this
exact same principle of blocking bacterial adhesion to the lining of an organ system. (In the case of stomach ulcer, it's the
stomach lining that's at risk, and the bacteria involved are the Helicobacter pylori bacteria.)

Anti-Inflammatory Benefits

For the cardiovascular system and for many parts of the digestive tract (including the mouth and gums, stomach, and colon)
cranberry has been shown to provide important anti-inflammatory benefits. It's the phytonutrients in cranberry that are
especially effective in lowering our risk of unwanted inflammation, and virtually all of the phytonutrient categories
represented in cranberry are now known to play a role. These phytonutrient categories include proanthocyanidins (PACs),
anthocyanins (the flavonoid pigments that give cranberries their amazing shades of red), flavonols like quercetin, and
phenolic acid (like hydroxycinnamic acids).

In the case of our gums, the anti-inflammatory properties of cranberry can help us lower our risk of periodontal disease.
Chronic, excessive levels of inflammation around our gums can damage the tissues that support our teeth. It's exactly this
kind of inflammation that gets triggered by ongoing overproduction of certain cytokines. (Cytokines are messaging
molecules, and the pro-inflammatory cytokines tell our cells to mount an inflammatory response. As messages are sent more
frequently and more constantly, the inflammatory response becomes greater.) Phytonutrients in cranberry help reduce this
inflammatory cascade of events precisely at the cytokine level. Production of pro-inflammatory cytokines like interleukin 6
(IL-6) and RANTES (Regulated on

Activation Normal T-cell Expressed and Secreted) is lowered by the activity of cranberry phytonutrients. In addition,
cranberry phytonutrients inhibit the activity of the enzymes cyclo-oxygenase 1 (COX-1) and cyclo-oxygenase 2 (COX-2).
These COX-1 and COX-2 enzymes are key factors in the production of other pro-inflammatory messaging molecules, and
by inhibiting these enzymes, cranberry's phytonutrients significantly lower our risk of unwanted inflammation.

Dietary consumption of cranberry has also been shown to reduce the Rrisk of chronic, unwanted inflammation in the
stomach, large intestine (colon) and cardiovascular system (especially blood vessel linings). We'll discuss some of these
health benefits in more detail in the Digestive Benefits and Cardiovascular Benefits sections of this cranberry profile.

Mixed Findings for Kidney Stone Formation

Contrary to popular opinion, we believe that the latest research shows mixed results for cranberry with respect to kidney
stone formation. This area of the health research can be confusing. Kidney stones can be formed from several different
mineral-including combinations. The most common type of kidney stones formed in the United States involves a
combination of calcium-plus-oxalic acid and are called calcium-oxalate stones. Among U.S. adults who develop kidney
stones, about 75% develop calcium-oxalate stones. The other 25% develop a variety of different stones, including calcium-
phosphate stones (called brushite stones), magnesium-sulfate containing stones (called struvite stones), and uric acid-
containing stones (called urate stones). Since cranberries have the ability to increase the concentration of both calcium and
oxalate in the urine, they can increase the likelihood of calcium-oxalate stone formation in susceptible individuals. Urinary
uric acid, however, is typically decreased by intake of cranberry, and so risk of urate stones in susceptible individuals can be
decreased by intake of cranberry. With other types of kidney stones, mixed effects of cranberry intake have been
demonstrated. From our perspective, the bottom line at this point in the research process seems clear: individuals with
kidney stone problems of any kind, or known susceptibility to kidney stone formation, should talk with their healthcare
provider if considering inclusion of cranberry in their diet. Since 3 out of 4 U.S. adults experiencing kidney stone problems
develop calcium-oxalate stones, there's a good chance for cranberry to be a problematic addition to the diet in the case of
U.S. adults with a history of kidney stone formation.

Immune Support

While research in this area is somewhat limited, recent studies on the immune support benefits of cranberry are exciting. In
studies on very small numbers of human participants, intake of cranberry extracts has shown the ability to improve multiple
aspects of immune function, and to lower the frequency of cold and flu symptoms in the subjects. In several of these studies,
the cranberry extracts were standardized to contain a known, higher-end amount of proanthocyanidins (PACs)-somewhat
comparable to a double-strength cranberry juice. From our perspective, the doses of cranberry extract used in these studies
match up fairly well with generous intake of whole, raw cranberries, and we look forward to future studies focused on
precisely that: intake of whole, raw cranberries and resulting changes in cold and flu symptoms.

Cardiovascular Benefits

Following decreased risk of urinary tract infection (UTI), increased health of the cardiovascular system is perhaps the best-
researched area of cranberry health benefits. It's the combined impact of cranberry antioxidants and anti-inflammatory
phytonutrients in cranberry that's responsible here. Oxidative stress and chronic inflammation can place our blood vessel
walls at great risk of damage. Once damaged, our blood vessels walls can undergo a process of plaque formation, and our
risk of atherosclerosis (blood vessel wall thickening and blood vessel blocking) can be greatly increased. Dietary intake of
cranberries and cranberry juice (in normal everyday amounts, unchanged for research study purposes) has been shown to
prevent the triggering of two enyzmes that are pivotal in the atherosclerosis process (inducible nitric oxide synthase, or
iNOS, and cyclo-oxygenase 2, or COX-2). In both cases, cranberry has also been shown to prevent activation of these
enzymes by blocking activity of a pro-inflammatory cytokine- messaging molecule called tumor necrosis factor alpha (TNF-
alpha). These anti-inflammatory benefits of cranberry appear to be critical components in the cardiovascular protection
offered by this amazing fruit.

The antioxidant components of cranberries also appear to play a key role in cranberry's cardiovascular benefits. In animal
studies, these antioxidant benefits have been clearly associated with decreased risk of high blood pressure. By reducing
oxidative stress inside the blood vessels, cranberry extracts consumed by rats and mice have helped prevent overconstriction
of the blood vessels and unwanted increases in blood pressure.

Three related phytonutrient compounds- resveratrol, piceatannol, and pterostilbene-deserve special mention with respect to
cranberry's antioxidants. These unique phytonutrients may provide cranberry with some equally unique antioxidant
properties, and a special ability to support our cardiovascular system in this regard.

A final area of cardiovascular support provided by cranberry is its ability to help us lower our LDL-cholesterol and total
cholesterol, while simultaneously helping us increase our level of HDL-cholesterol. Cranberry most likely helps us achieve
these cholesterol-improving changes by helping to improve oxidative and inflammatory aspects of the everyday
environment in which our cholesterol-containing molecules must exist. This improved cholesterol control offered by
cranberry contributes even further to our decreased risk of blood vessel blocking problems, since excess accumulation of
LDL-cholesterol and insufficient amounts of HDL-cholesterol can increase the tendency of our blood vessels to become
blocked. All in all, it's quite amazing how a simple food like cranberry can provide us with cardiovascular benefits at so
many different levels, all rolled into one.

Antioxidant Protection

Although previously mentioned in this Health Benefits section, the antioxidants found in cranberry are especially important
contributors to its potential for health support. From a research perspective, there are two especially important points to
consider when thinking about the antioxidant benefits of cranberries. First is the amazing array of antioxidants that are
found exclusively in whole cranberries. Cranberry's special combination of phenolic antioxidants, proanthocyanidin
antioxidants, anthocyanin antioxidants, flavonoid antioxidants, and triterpenoid antioxidants is without a doubt unique. Also
unique is the particular combination of three antioxidant nutrients-resveratrol, piceatannol, and pterostilbene-found in
cranberry. Second are the research findings regarding the synergy between these nutrients. The phytonutrients in cranberry
provide maximal antioxidant benefits only when consumed in combination with each other, and also only when consumed
alongside of conventional antioxidant nutrients present in cranberry like manganese and vitamin C. When cranberry
processing disrupts this antioxidant combination, health benefits from cranberry are decreased. Multiple studies in multiple
health benefit areas point to this same conclusion-it's the overall blend of cranberry antioxidants that provides us with the
strongest health benefits.

One further point about cranberry antioxidant research seems worthy of mention. In several research studies, cranberries
were unable to provide significant antioxidant benefits when those benefits were measured in terms of blood values. In these
studies, it took a much closer look at activities going on inside of our cells to demonstrate the antioxidant benefits of
cranberries. The need to look inside of our cells to find cranberry antioxidant benefits may be telling us that the special
value of cranberries may often involve metabolic events that are taking place "behind the scenes." In other words, these
benefits may sometimes be missed in more broadly focused research studies, and cranberry may in fact have a stronger
research track record than previously assumed.

Anti-Cancer Benefits

No area of cranberry research has been more intriguing in the past 10 years than research on cranberry and cancer, even
though the majority of studies in this area have involved lab studies on human cancer cells or animal experiments. On a
virtual year-by-year basis, scientists continue to identify new mechanisms that establish cranberries as anti-cancer agents.
These mechanisms are now known to include: blocked expression of MMPs (matrix metalloproteinases); inhibition of ODC
(ornithine decarboxylase enzymes); stimulation of QRs (quinone reductase enzymes); inhibition of CYP2C9s (Phase I
detoxification enzymes); and triggering of apoptosis (programmed cell death) in tumor cells. It's important to point out that
this amazing list of anti-cancer properties in cranberry is not sufficient to establish cranberry as a food to be used in the
treatment of cancer. However, it is a list that appears consistent with other studies of cranberry and cancer showing dietary
intake of this food to help prevent cancer occurrence. These cancer-preventive benefits of cranberry are especially likely in
the case of breast, colon, lung, and prostate cancer.

None of the cancer-related benefits of cranberries should be surprising, since cranberry is loaded with antioxidant and anti-
inflammatory nutrients. Chronic excessive oxidative stress (from lack of sufficient antioxidant support) and chronic
excessive inflammation (from lack of sufficient anti-inflammatory compounds) are two key risk factors promoting increased
likelihood of cancer. With its unique array of antioxidant and anti-inflammatory nutrients, cranberry seems ideally
positioned to help us lower our risk of cancer development.

Digestive Tract Benefits

When you add up the health-related benefits of cranberry for our mouth and gums (decreased risk of periodontal disease),
stomach (decreased risk of stomach ulcer), and colon (decreased risk of colon cancer), it's impossible not to conclude that
cranberry is unique among fruits in its ability to provide us with digestive tract benefits. Every category of phytonutrient
known to be provided by cranberry is also known to play a role in digestive tract support. In the case of cranberry's
proanthocyanidins, it's decreased adherence of the bacterium Helicobacter pylori to our stomach wall that's made possible
by intake of cranberry. In the case of cranberry's flavonoids, anthocyanins and triterpenoids, provide antioxidant and anti-
inflammatory benefits that decrease our risk of colon cancer, and also our risk of periodontal disease.

Recent research has also shown that cranberry may be able to help optimize the balance of bacteria in our digestive tract.
Participants in one recent study involving cranberry juice intake (in amounts of approximately 2 ounces per day and over the
course of about 3 months) were able to increase the numbers of Bifidobacteria in their digestive tract while maintaining
other bacterial types (Bifidobacteria are typically considered to be a desirable and "friendly" type of bacteria). As a result,
the relative amount of Bifidobacteria was increased, and the bacterial environment of the digestive tract may have become
more favorable. Given the vast array of phytonutrients in cranberry and the known connection between so many of these
phytonutrients and digestive tract health, we expect to see the digestive benefits of cranberry becoming more and more
apparent in future research on this incredible berry.