Encyclopedia of

146 Cranberry (Vaccinium macrocarpon) Aiton
endothelium-dependent vasodilation; and 4) increase
of reverse cholesterol transport and decrease of total
and LDL-cholesterol. Data supporting these methods
are preliminary. Evidence to support other ways by
which cranberry or its constituents may decrease the
risk of atherosclerosis is not available in the literature.
Cancer
The antioxidant capacity alone of cranberry constituents
may not account for the observed effects. [38,41]
A soluble-free extract had the highest antiproliferative
activity and maximum calculated bioactivity index
for dietary cancer prevention compared to ten other
fruits. [10] Given the diversity of molecular structures
and bioactivity among the classes of phytochemicals
in cranberry, it is likely that they may fight cancer by
several different mechanisms. These include: 1) induction
of apoptosis; 2) slow initiation, promotion, and
progression of tumors [35,38,41] ; and 3) inhibition of
the inflammatory response. [41] In vivo carcinogenesis
studies will need to be performed to further confirm
antitumor promotion activity and identify individual
components and mixtures responsible for activity.
Cytotoxicity of cranberry or its constituents toward
tumor cells has not been reported.
Safety Studies
No animal toxicology studies have been reported, nor
have serious adverse events in humans consuming
cranberry products for long periods been reported.
CLINICAL STUDIES
Efficacy
Urinary tract infection
The use of cranberry to prevent or treat UTI is
common. The accumulating evidence from small, noncontrolled
and controlled clinical trials suggests that
the berry may relieve symptoms associated with UTI
and may reduce the need for antibiotics. The Cochrane
Library [42,43] conducted separate reviews of the fruit
for the prevention and treatment of UTI. Each review
used similar search strategies and selection criteria.
These included all randomized or quasirandomized
controlled trials. Trials of at least 1 mo to at least
5 days were included for prevention and treatment,
respectively. For prevention, seven trials met the inclusion
criteria. Meta-analysis performed using data from
the two better trials found that when consumed over
a year, cranberry juice decreased the number of
symptomatic UTIs in women. For the five trials not
included in the meta-analysis, one reported a significant
result for symptomatic UTIs in women and
another reported a significant result for asymptomatic
UTIs in elderly women. For treatment, no trials meeting
the inclusion criteria were found; only a few uncontrolled
trials were found. The Cochrane Library
concluded that there was no good quality or reliable
evidence of the effectiveness of cranberry juice or other
cranberry products for the treatment of UTI. For both
prevention and treatment, the review authors concluded
that more research was needed.
Two other studies not included in the Cochrane
reviews reported apparently contradictory results.
The first was a study of adults with spinal cord injury
who demonstrated a reduction in biofilm load, [44] but
the importance of this effect for frank UTI was not
determined. A small study of urostomy patients also
found equivocal results. [45]
Many of the clinical study reports available in the
literature suffer from major limitations. Many trials
have not been controlled or randomized, and randomization
procedures have not always been described.
Crossover designs used in some research may not be
appropriate for studies of UTI. Other limitations
include no blinding or failed blinding, lack of controlled
diets or dietary assessment, use of convenience
samples, and small numbers of subjects. Trials have
been faulted for the large number of withdrawals.
Intention-to-treat analyses were not often applied.
Most studies have been conducted in older or elderly
patients. Very few have been conducted in younger
patients, with or without comorbidities, or in men.
Primary outcomes have differed from study to study
and have often included urinary pH, as well as rate
of bacteriuria, biofilm a load, and urinary white and
red blood cell counts, rather than UTI. It is also not
clear what is the optimum dosage or type of product.
There is limited evidence of efficacy or safety for forms
of cranberry product other than juice or juice cocktail.
Finally, the published articles do not describe the
quality and composition of the products tested.
Adverse Effects
The U.S. Food and Drug Administration granted
generally recognized as safe (GRAS) status to cranberry
foods and beverages. This means that their safety
is well established. The few clinical studies assessing the
adverse effects of cranberry juice cocktail have
a Biofilms are collection of proteinaceous material that cover the
bacterial populations and often render them resistant to sterilization
and antimicrobial treatments.