“We believe this is the first proof of principle that these substances have significant effects in patients with FAP,” said lead researcher Francis Giardiello, MD, from the Johns Hopkins University School of Medicine.
Familial adenomatous polyposis (FAP) is a hereditary disorder characterised by the development of hundreds of colorectal adenomas (polyps) and eventually colon cancer.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have recently been given to some patients with this condition, but these compounds, said Giardiello, frequently produce significant side effects, such as gastrointestinal ulcerations and bleeding.
Some epidemiological evidence and population studies link daily consumption of curcumin-containing turmeric, quercetin-rich vegetables such as onions, and green tea to lower incidence of gastrointestinal cancers. Bearing this in mind, the researchers undertook a small clinical trial with these compounds and humans with FAP.
How the research was done
The researchers recruited five patients with FAP and gave each patient 480mg of curcumin and 20mg of quercetin orally three times a day for six months.
“The amount of quercetin we administered was similar to what many people consume daily; however, the amount of curcumin is many times what a person might ingest in a typical diet, since turmeric only contains on average three to five percent curcumin by weight,” said Giardiello.
Because of this, Giardiello cautioned that simply consuming curry and onions might not have the same effect as observed for these patients - a comment that suggests that extracts in the form of supplements could be a better source.
This also suggests that the positive results could be due solely to curcumin, since the normal diet would provide similar amounts of quercetin, said Giardiello.
Drop in polyps
The results, published in the August issue of the journal Clinical Gastroenterology and Hepatology (Vol. 4, issue 8), show that the average number of polyps dropped 60,4 percent, and the average size dropped by 50,9 percent.
One patient dropped out after three months, while another patient was found to not have complied with the supplementation programme. Interestingly, this lack of compliance coincided with an increase in polyp numbers between the third and sixth months. After re-starting the supplements, the number of polyps is reported to have decreased.
“This study showed for the first time that curcumin was efficacious in decreasing the number of polyps in patients with FAP, similarly to what has been seen with the use of synthetic NSAID agents, but with minimal side effects. Furthermore, we saw that adenomas found in the small intestine of our patients also responded to curcumin,” said lead author Marcia Cruz-Correa.
Clues to the mechanism
While the researchers did not perform a mechanistic study to elucidate the possible mode of action of curcumin, previously proposed anti-cancer mechanisms include anti-oxidant activity, up-regulation of carcinogen-detoxifying enzymes such as glutathione S-transferases, and suppression of an enzyme called isoenzyme cyclooxygenase-2.
On the other hand, the possible anti-cancer mechanisms of quercetin are not well understood. Previously, flavonoid compounds such as quercetin have been implicated in the targeting of so-called ras gene products. Ras is the name given to a family of proteins, and the genes that code for these proteins, that play an important role in sending signals between cells. These ras genes are said to be de-activated in many cancers.
The authors concluded that “these findings need validation in a randomised, double-blind, placebo-controlled trial.”
Such a large, randomised clinical trial is planned as a collaboration between the John Hopkins and University of Puerto Rico Comprehensive Cancer Center. Cruz-Correa said that no date has yet been fixed for this trial.
Number of studies underway
Hazel Nunn, cancer information officer at Cancer Research UK, told NutraIngredients.com that the anti-cancer effects of curcumin are currently being investigated by a number of studies.
"Some laboratory studies have suggested that curcumin could be used to help prevent or treat bowel cancer, but there has been little research in humans.
"While this study shows that curcumin may be effective in humans, it only looks at five patients. Large-scale trials are needed before we know if this spice really has a role in treating cancer," she said.
Colorectal cancer accounts for nine percent of new cancer cases every year worldwide. The highest incidence rates are in the developed world, while Asia and Africa have the lowest incidence rates.
It remains one of the most curable cancers if diagnosis is made early. - (Decision News Media, August 2006)