Black raspberries may protect against esophageal ca

PHILADELPHIA-Extracts of black raspberries might protect Barrett's esophagus patients against esophageal cancer and also might shift premalignant oral lesions from progression to squamous cell carcinoma (SCC) back toward normal differentiation, Ohio State researchers reported at the AACR's 6th Annual International Conference on Frontiers in Cancer Prevention Research.

Laura Kresty, PhD, assistant professor in the Ohio State University Cancer Chemoprevention Program, Columbus, reported that 58% of 20 Barrett's esophagus patients who ate a freeze-dried preparation of black raspberries daily for 26 weeks had a significant decline in mean urinary levels of 8-isoprostane, an indicator of global oxidative stress and DNA damage (abstract B34).

"Many of these patients had suffered from gastroesophageal reflux for a decade," Dr. Kresty said at a press briefing. "Injury from acids results in generation of reactive oxygen species, which then cause damage. We tested this preparation in an attempt to decrease the ongoing oxidative stress in these patients."

The take-home message, she said: "We need to increase fruit and vegetable consumption, and patients can do something to modify some pathways that lead to cancer."

She recommended that the lyophilized black raspberry formulation be further studied in a randomized, placebo-controlled phase II trial.

An oral gel

Susan Mallery PhD, DDS, and her colleagues took a different approach. Her group tested a highly concentrated, bioadhesive black raspberry gel as a topical treatment for precancerous oral lesions (abstract B35). Dr. Mallery is a professor in the Department of Oral Maxillofacial Surgery and Pathology at Ohio State University's College of Dentistry.

"The major problem with patients who have these premalignant lesions is recurrent disease that appears postop despite clear surgical margins," Dr. Mallery said. "Black raspberries are full of anthocyanins, potent antioxidants that give the berries their rich, dark color, and our findings show that these compounds may have a role in silencing precancerous cells."

This phase I/II trial included 20 patients with oral intraepithelial neoplasia (IEP) lesions and 10 normal controls. "There are lots of sugars and carbohydrates in black raspberries, and we wanted to control for risk of iatrogenic fungal infection," Dr. Mallery said.

The "very motivated" participants applied the 10% (by weight) dried black raspberry gel four times a day to the target sites. Each patient served as his or her own internal control. None were smokers. The study continued for 42 days, the approximate amount of time necessary for 1 cycles of surface epithelial turnover.

At the end of the study, Dr. Mallery said that comparison of pre- and post-treatment biopsies showed improvement (a decrease in lesion grade) in 35% of the patients, stable disease in 45%, and an apparent increase in lesion grade in 20%, but she suspects the latter is due to sampling bias.

More detailed examination showed decreased loss of heterozygosity (suggesting that cells were returning to a normal genetic state) and upregulation of cell differentiation markers.

Dr. Mallery said that the next step should be a longer (3-month), placebo-controlled, multicenter study. She also recommended further evaluation of berry gels for chemoprevention of oral IEP.

A more colorful diet

Navindra Seeram, PhD, MRSC, said that Dr. Mallery's method is "a great approach" to many of the problems of taking a food into drug use because it overcomes the problem of degeneration of active components during the digestive process.

"The active compounds need to be in surface contact with the oral epithelium. If you are eating this berry, it spends a miserably short time in contact with the oral mucosa. This bioadhesive topical appears to be much better," said Dr. Seeram, assistant professor in the Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston.

Dr. Seeram recently reviewed the cancer preventive potential of blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts (J Agric Food Chem 54:9329-9339, 2006).

A problem solved

Dr. Seeram also said that the lyophilized black raspberry preparation used in the study reported by Dr. Kresty solves another problem by permitting preparation of a large amount of standardized powdered extract that can be used in clinical trials.

He said that the studies reinforce the fact that "we should be eating more colors in our diet, particularly more berries."

Cranberries are effective against urinary tract infections, Dr. Seeram said, and blueberries have anti-neurodegenerative effects.

"And now we see that black raspberries seem to have some anticancer activity. We need a rainbow of colors in our diets," Dr. Seeram said.