CRANBERRY FOR A HEALTHY HEART

CRANBERRY FOR A HEALTHY HEART


Background


Atherosclerosis is the primary cause of cardiovascular disease (CVD), particularly heart disease and stroke,

and is the leading cause of death in the United States (1,2). Atherosclerosis is described as the deposition

of plaques containing lipids and cholesterol on the arterial wal s. A number of studies have shown that

flavonoids, phytonutrients found in fruits and vegetables, exhibit a number of CVD protective effects

primarily attributed to their antioxidant properties. A diet rich in antioxidants is associated with a reduced
risk of CVD and has been observed in studies with vitamin E (3) and total dietary flavonoid intake (4). Given

the rich and unique profile of cranberry flavonoids, recent studies have looked specifical y at the distinct

protective effects of this fruit.



The complex etiology of atherosclerosis is thought to begin with the oxidation of low-density liproprotein

(LDL) cholesterol and its subsequent aggregation in the vascular subendothelial space known as the intima.
Modified LDL trapped in the intima initiates an inflammatory response that ultimately causes more oxidation

to occur, leading to lipid laden foam cel s and lesions on the arteries known as fatty streaks. As lesions

progress, they grow to interfere with arterial endothelial function and ultimately block arteries to restrict

arterial blood flow. Total occlusion by atherosclerotic plaques can lead to ischemic heart disease, angina

and acute myocardial infarctions. Plaques can also rupture and cause thrombosis, leading to the complete

cessation of blood flow that causes the majority of CVD-related deaths (5,6).


Cranberry’s Flavonoid Rich Profile
Key Points:



•
A diet rich in antioxidants

There are several distinct classes of flavonoids found in cranberries,
such as those found in fruits
al with antioxidant properties and each having potential physiologic

and vegetables is associated
benefits in CVD. Cranberry flavonoids include anthocyanins, the
with a reduced risk of CVD

pigments that give cranberries their rich red color, flavonols, and
and has been observed in

proanthocyanidins (7). Of particular interest to researchers, proantho-
studies that measured total

cyanidins isolated from cranberries exhibit an antiadhesion effect on
dietary flavonoid intake.


certain bacteria. This antiadhesion effect is the mechanism by which
•
Compared with other
cranberries help maintain urinary tract health (8), and possibly even

common fruits, cranberries
help prevent periodontal disease (9) and the formation of certain

have one of the highest
ulcers (10).
concen-trations of antioxidant


polyphenols, which include

According to the research, the postabsorptive protective effects of the
flavonoids and related

many cranberry-specific flavonoids may act to: defend against
phenolic acids.
oxidation of low-density liproproteins (LDL), the first step in


atherogeneis; inhibit atherogenic inflammation; and, possibly enhance
•
While more research is

required to better understand
reverse cholesterol transport to lower LDL in hypercholesterolemic

cranberry’s unique
individuals (2). In an extensive review article of cranberry flavonoids
contribution to cardiovascular

and cardiovascular health, Reed (2) suggested that the similarities
health, many of the flavonoids

between the classes of flavonoids found in cranberry juice and the
found in this fruit are proven
more widely studied grape juice and red wine, may prove cranberries

to have potent antioxidant
wil have similar effects in promoting vasodilation and inhibiting the
protective effects.

formation of blood clots.



Antioxidant Effects


A number of studies have demonstrated that flavonoids and their related polyphenolic compounds inhibit

oxidation of LDL in vitro (11). Of the three classes of cranberry flavonoids, proanthocyanidins have shown

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the highest inhibitory effect on the copper-induced oxidation of LDL ex vivo (12,13). Wilson et al (14)

subsequently demonstrated the LDL protective effects of the antioxidants in cranberry are not due solely to

the mild metal binding capacity flavonoids display (15) but to the free radical scavenging abilities of

cranberry’s components. Findings indicated concentrations of pure cranberry juice as dilute as 1:10,000
exhibited significant LDL antioxidant activity when exposed to a non-metal initiated oxidizing agent. Another

study showed cranberry polyphenolic extracts could enrich LDL+VLDL in plasma and protect these isolated

lipoproteins from oxidation (16).



Quercetin, a flavonol found in high concentrations in cranberry (17), also has strong in vitro antioxidant

activity (18). As wel , quercetin is readily absorbed into the bloodstream of humans and approaches the in
vitro concentrations with proven antioxidant effects (19). Flavonols present in cranberries also spare the in

vitro oxidation of vitamin E, an important nutrient proven to inhibit LDL oxidation in vivo (20).. The

anthocyanins in cranberries have also demonstrated high antioxidant capacity in ex vivo studies (21) and

are also readily absorbed into the bloodstream of humans as shown in a human feeding study using

elderberry anthocyanins (22).


The exact mechanism by which flavonoids exhibit their antioxidant effects in vascular cel s has yet to be

determined. In a recent review article, Reed (2) hypothesized that, based on existing research, cranberry-

specific flavonoids may act to scavenge the free radicals within LDL that cause oxidation and/or inhibit the

endogenous oxidative enzymes (such as 15-lipoxygenase) present in the macrophages, endothelial cel s

and smooth muscle cel s involved in plaque formation.



Anti-inflammatory Effects


A number of flavonoids, such as those found in cranberries, inhibit the atherogenic inflammatory response

in the intima, induced by the presence of oxidized LDL (23), by blocking a number of key kinase enzymes

necessary for immune cel activation (24-26). Certain flavonoids can also inhibit cytokine-induced gene

expression, an important immune response modulator. Cel ular adhesion molecules on endothelial cel s,

aberrantly expressed in atheroscleratic lesions, are inhibited by flavonoids such as hydroxyl flavones and,

to a lesser extent, flavonols (27). These same flavonoids also inhibited the production of a number of
inflammatory intermediates (28) involved in the larger inflammatory response cascade.



Recently, a research team at Tufts University studied the antioxidant and inflammatory inhibition properties

of blueberry and cranberry polyphenol extracts, specifical y the anthocyanins and hydroxycinnamic acids

found in these fruits (29). Results demonstrated that these polyphenols were able to localize in human

microvascular endothelial cel s and effectively reduce oxidative stress in the cel s. These berry extracts also
suppressed the induction of various inflammatory mediators involved in recruiting leukocytes to damaged

areas of the endothelium. Researchers concluded the polyphenols in cranberries and blueberries protect

endothelial cel s from oxidative and inflammatory injury, providing benefits that may reduce the initiation and

development of vascular disease.



Enhanced Cholesterol Transport


A smal , preliminary animal study found cranberry juice powder (CJP) significantly decreased LDL in swine

with familial hypercholesterolemia (FH) (12). Blood was taken at weekly intervals for four weeks. At

baseline, FH sows had seven times the amount of total cholesterol versus normal sows and 11 times the

LDL of normal. Four weeks of feeding 150 g/day of CJP lowered total cholesterol and LDL levels in FH

sows, decreasing LDL levels 22 percent from the baseline measurement. Researchers hypothesized the

proanthocyanidins in CJP may be increasing reverse cholesterol transport and enhancing cholesterol
excretion by the liver. These researchers also concluded their results indicated humans with

hypercholesterolemia may benefit from adding cranberry juice to their diets.



Other Possible Protective Benefits



In a 2002 review article (2), Reed cited relevant research using flavonoids from different sources, primarily

grapes, but in the same class as those found in cranberries, suggesting the cranberry may offer other
cardiovascular benefits. Although cranberry-specific research is necessary, impaired arterial vasodilation

characteristic of CVD may also benefit from flavonoids present in cranberries. Nitric oxide (NO), produced

in the endothelial cel s, mediates vasodilation by acting on the adjacent smooth muscle cel s lining the

vascular membrane (30).. Research suggests the oligomeric proanthocyanidins found in wine improves

vasodilation by stimulating endothelial NO production in vitro (31,32). As wel , studies have shown that

proanthocyanidin oligomers in certain fruits interfered with the production of angiotensin II, a potent
vasoconstrictor that can aggravate atherosclerotic symptoms (33-35).

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Cranberry’s flavonoid arsenal may also prove to effect platelet activity in advanced atherosclerosis. The

damaged atherosclerotic endothelium can cause platelets to adhere to the wal s of the coronary arteries

and aorta and incorporate into the growing lesion (36). Thrombosis can occur when platelets aggregate in

the narrow areas of the coronary artery, stopping the flow of blood and inducing myocardial infarctions (37).

Researchers have studied the effects of drugs, notably aspirin, and food components, such as flavonoids,
in platelet downregulation in an effort to decrease the risk of heart attacks and strokes in atherosclerosis

(38). Not surprisingly, in vivo animal studies (39) and an ex vivo human study (40) found grape juice can

have beneficial effects on platelet aggregation. Flavonols, anthocyanidins and proanthocyanidins are the

flavonoids most common in grapes (2) and, notably, cranberries (41).



Conclusions


Epidemiological studies have long associated flavonoid rich diets with a decreased risk for many diseases,

including CVD (4). While more research is required to better understand cranberry’s unique contribution to

cardiovascular health, many of the flavonoids found in this fruit are proven to have potent antioxidant

protective effects. With the highest fresh-weight flavonoid content of 20 common fruits tested (16),

incorporating cranberries into a healthy diet can help protect cardiovascular health by providing a rich

source of dietary flavonoids and antioxidants.






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