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Cranberries: a multifunctional powerhouse

Urinary tract infections are old news. Emerging research from 2005 points to a rich range of therapeutic applications for this potent native American fruit. Mark Tallon, PhD, digs into the bumper crop

Cranberries (Vaccinium macrocarpon) are one of only three native American fruits. Used historically by Indians in the treatment of bladder and kidney ailments, the fruit was often called 'craneberry' because the stem and flower resembled the head, neck and beak of a crane.1 Therapeutic applications of cranberries have been documented as far back as the 17th century, including relief of blood disorders, stomach ailments, liver problems, vomiting, appetite loss, scurvy, urinary tract infections (UTIs) and cancer.2,3

All of that in a little berry. From the widely known aspects of cranberry uses in UTIs and cystitis to the previous list of medicinal applications, we can see that cranberries are a multifunctional nutrient with diverse marketing possibilities. Today, cranberries' recognised healthful mechanism is their antioxidants and bacterial anti-adhesion properties, which in addition to the growing list of human benefits is also opening up lucrative opportunities in the animal feed and nutrition market to replace antibiotics in order to keep E. coli from affecting chickens.

In 2005, a new selection of studies have been published about this rich source of phytochemicals, anthocyanins and other flavonoids.4,5 The US National Institutes of Health currently has 11 studies under way that will further hone in on cranberry bioactives.

As the average life expectancy increases, declining cognitive function and memory impairment have become an increasing concern in the medical community. In 2002, the proportion of people with moderate or severe memory impairment ranged from approximately five percent among those aged 65-69 to 32 percent for people over 85.6 These rapidly increasing numbers have driven the search for a natural remedy to slow or alleviate these symptoms.

One recent study looked at the short-term (ie, six weeks) efficacy of cranberry juice feeding on the neuropsychologic functioning of older adults.7 Fifty 60-year-old volunteers, who reported no history of dementia or significant neurocognitive impairments, were studied in a double-blind, placebo-controlled, randomised, parallel-group clinical trial. Participants were randomly assigned to either 32oz/day of a beverage containing 27 per cent per cent cranberry juice or placebo for six weeks, and administered a series of neuropsychologic tests at both pretreatment baseline and again after six weeks.

Statistical analysis revealed no significant interactions across all of the neuropsychologic tests and measures utilised in this study, including analyses of the groups' self-reported changes in their abilities to remember, thinking processes, moods, energy levels and overall health. However, more than twice as many participants in the cranberry group (37.5 per cent, n=9) rated their overall abilities to remember as 'improved' compared to placebo controls (17.4 per cent, n=4). This difference was considered statistically nonsignificant.

Although no significant interactions related to neuropsychologic assessments were noted on this subjective, self-report questionnaire, this could be interpreted as indicating a possible influence of cranberry juice on memory in those without loss of cognitive function.

While this is a preliminary study on healthy subjects, the positive trend reported gives rise to a real incentive to run a similar study on those suffering from neurodegenerative disease associated with ageing.

Gut health
Viruses cause 30 to 40 per cent of infectious diarrhoea cases in the United States, and viral gastroenteritis is the second most common illness, after upper respiratory infections.8 Rotaviruses cause enteric disease with symptoms characterised by diarrhoea, vomiting, abdominal discomfort and fever. The virus affects mainly infants and young children and is responsible for 50 percent of hospitalisations of children with diarrhoea. The naturally occurring anti-viral components of cranberry juice may be useful in preventing or treating these intestinal viral infections.

Results of a recent study, presented at the 105th general meeting of the American Society of Microbiology, suggest that cranberry juice may have naturally occurring anti-viral activity that may play a role in gut health.8 Researchers from St. Francis College in Brooklyn, New York, presented findings from an investigation designed to explore the occurrence and mechanism of cranberry juice cocktail on two mammalian enteric pathogens from the family Reoviridae. This family is divided into nine genera, four of which can infect humans and animals. The researchers used intestinal monkey rotavirus SA-11 and a pool of goat intestinal reoviruses. These models of intestinal virus systems share well-known similarities to human disease states.

Researchers used a variety of methods to measure time, dose and loss of viral infectivity comparing cranberry juice against a control of phosphate buffered saline. The results showed cranberry juice produced an almost instantaneous loss of reovirus infectivity and reduced reovirus infectivity to levels below the sensitivity of the infectivity assay.

In a study looking into yet another factor in optimal gut health, researchers have studied Helicobacter pylori — a major cause of peptic ulcers and gastric cancer. This study hypothesised that cranberry juice would effectively suppress H. pylori in a high-risk population for gastric cancer.9 A randomised, double-blind, placebo-controlled trial on 189 adults, mean age 489, with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants received two 250ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. After 90 days, 14 of the 97 subjects in the cranberry juice treatment group versus five of the 92 in the placebo group yielded negative test results for H. pylori infection. These results suggest that regular consumption of cranberry juice suppresses H. pylori infection.

The new anti-inflammatory?
In research carried out from the world-famous Rowett Research Institute in Scotland, researchers looked at the anti-inflammatory effects of cranberry juice in influencing cardiovascular disease states.10 The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (n=11) matched for age, weight and height, consumed 250ml of either cranberry juice or a placebo drink three times a day for two weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine. Concentrations of salicylic acid in plasma were also determined.

Regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound

The consumption of cranberry juice was associated with a marked increase of salicyluric and salicylic acids in urine within one week of the intervention. After two weeks, there was also a small but significant increase in salicylic acid in plasma. These results indicate that the regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may confer beneficial health effects on cardiovascular disease.

Dental care
In a recent study from the Institute of Dental Sciences in Jerusalem, researchers assessed the effects of a high molecular weight non-dialysable material (NDM) derived from cranberry juice on bacterial formation.11 Previously, NDM had been shown to inhibit the adhesion of Escherichia coli and the co-aggregation of a variety of oral bacteria in dental biofilm, which leads to dental cavities and disease.12

In the present study, researchers examined the anti-adhesion effect of NDM on S. sobrinus (attributable for a large percentage of dental cavities). NDM promoted desorption of S. sobrinus from biofilm. Therefore, pre-coating the bacteria with NDM reduced their ability to form biofilm. Thus, NDM could be exploited as an anti-biofilm agent and may have applications in mouthwashes or toothpaste.

Using unripe cranberries is one way to get beyond colour issues in the dental as well as cosmeceuticals markets. Further applied work and dose/extraction of actives from cranberries are needed before it can be fully exploited as a functional food source.

Berry bright future
Based on this research, a few areas should be addressed before we can take initial indications of efficacy to the market. The real issue is that of concentration and the type of active compounds found in cranberries. At present, most marketed drinks contain only 27-31 per cent cranberry extract; however, many of the studies would require rather larger doses to get a clinical effect from their concentration.

This begs the question: Why not use a powdered form of cranberry in capsule/tablet form? At this time there are very few studies on concentrated cranberry extracts in humans, with little data on the concentration and ratio of the actives within the product.

In a company that has clinical data to back up its cranberry extract, Michael Barnhart, director of quality control at Insure Your Health LLC, the worldwide license-holder of Cran-Max, commented on efficacy. "There have been numerous reports in a variety of publications describing the beneficial effects of cranberries," he says. "However, significantly more data needs to be accumulated and assessed before any definitive applications for the cranberry, beyond its known protective effects for urinary tract health, can be assured."

Beyond these initial issues of peer-review validation, environmental conditions such as light and soil conditions affect the concentration of the bioactives within cranberries.13 It is advisable to sift out the bioactive(s) that are the most efficient at bringing about beneficial influences to health and subsequently standardise products for these actives.

Why standardisation is required can be seen in recent work on different types of proanthocyanidins (PACs). These PACs are a major constituent of cranberries and are suggested as responsible for many beneficial effects. Type A PACs from cranberry shows higher anti-adhesion activities in comparison to the higher concentration of type Bs in other fruits.14 Therefore, future research work should aim to assess the commercial implication of isolating the type A PACs.

These issues are one of the key differentiators for Massachusetts-based Decas Botanical Synergies. "All cranberries are not alike," says Doug Klaiber, general manager at Decas. "For our nutraceutical ingredients, not only do we pick a specific cultivar which is higher in PACs — a variety called 'early black' — but we've also looked at farming practices, nighttime temperature, climate, sunlight, all these factors have impact on the actives."

At present, cranberry research is growing in fields such as influenza, cancer, drug interaction and heart disease.3,15 Studies scheduled for publication from the NIH in 2006 could cement the cranberry market as a profitable one for the foreseeable future.

Mark J Tallon, PhD, is chief science officer of OxygeniX, a London-based consultancy firm specialising in claims substantiation, product development and technical writing.
Dr Tallon is also co-founder of Cr-Technologies, a raw ingredients supplier.

Science drives European boom

The popularity of cranberries as a functional food can be seen in the rapid growth of national and international export markets. Recent figures show France alone had an increase in sales above 3,000 per cent in 2004 alone, primarily as a result of qualified health and label claims, which were spearheaded by Ocean Spray.

"The French market is really doing well right now," says Doug Klaiber, general manager for Massachusetts-based Decas Botanical Synergies. "Cranberries, because of the health claim, have had a real nice boost in sales opportunities in France, and it's spilling over into other parts of Europe."

The export market represents around 25 per cent of the total US cranberry production, which has grown substantially since 1996, according to US Department of Agriculture and NASS estimates. In 1996, 4.67 million barrels and in 2005 an estimated 6.5 million barrels of cranberries have been harvested, at a total value in excess of $230 million.1

This strong growth in internal and export markets is set to continue with greater public understanding of the health benefits of cranberries.

The need for science-driven claims was recently stressed by Michael Barnhart, director of quality control at Insure Your Health, the worldwide license-holder of Cran-Max, a brand leader in cranberry extracts.

"Scientific studies published in peer-reviewed journals indicate that the study design and data have passed the scientific scrutiny of experts in the field," Barnhart says. "They are important third-party proof sources that can substantiate the manufacturer's claims about their products." Klaiber agrees. "There's a lot of good science behind cranberries," he says, "and I think the NIH studies will validate it."

1. Siciliano AA. Cranberry. HerbalGram 1996; 38:51-4. Accessed online October 14, 2004, at
2. Duthie SJ, Jenkinson AM, et al. The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. Eur J Nutr 2005. (Ahead of publication).
3. Reed J. Cranberry flavonoids, atherosclerosis and cardiovascular health. Crit Rev Food Sci Nutr 2002; 42(3):301-16.
4. Vattem DA, Ghaedian R, et al. Enhancing health benefits of berries through phenolic antioxidant enrichment: focus on cranberry. Asia Pac J Clin Nutr 2005;14(2):120-30.
5. Leitao DP, Polizello AC, et al. Antibacterial screening of anthocyanic and proanthocyanic fractions from cranberry juice. J Med Food 2005; 8(1):36-40.
6. No Author. Older Americans 2004: Key indicators of well being. Federal interagency forum on ageing related statistics. Washington, DC; USA. Government Printing Office.
7. Crews WD, et al. A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings. J Alt Comp Med 2005; 11(2):305-9.
8. Cohen P. et al. Mechanism(s) of inactivation by the American cranberry of mammalian enteric viruses. 105th General Meeting, American Society for Microbiology, 2005.
9. Zhang L, et al. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind randomized placebo-controlled trial. Helicobacter 2005; 10:139-45.
10. Duthie GG, Kyle JA, et al. Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice. J Agric Food Chem 2005; 53(8):2897-900.
11. Steinberg D, et al. Cranberry high molecular weight constituents promote Streptococcus sorbrinus desorption from artificial biofilm. Int J Antimicrob Agents 2005; 25(3):247?51.
12. Weiss EL, et al. Inhibitory effect of a high-molecular-weight constituent of cranberry on adhesion of oral bacteria. Crit Rev Food Sci Nutr 2002; 42(3):285-92.
13. Zhou Yu, Singh BR. Effect of light on anthocyanin in submerged, harvested cranberry fruit. J Biomed Biotechnol 2004; (5):259-63.
14. Howell AB, et al. A-type cranberry proanthocyanidins and uropathogenic bacterial antiadhesion activity. Phytochemistry 2005 (Ahead of publication).
15. Weiss EI, et al. Cranberry juice constituents affect influenza virus adhesion and infectivity. Antiviral Res 2005; 66(1):9-12.

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