Chlorophylls: Can These Green Food Pigments Prevent Some Cancers?

George S. Bailey, Ph.D. Distinguished Professor of Food Toxicology OSU/LPI Affiliate Investigator

Chlorophyll, the natural plant pigment that lends its color to grass, leaves, and many of the vegetables we eat, may play an important role in prevention of certain cancers. Researchers in the early 1980s discovered that chlorophylls and related chemicals can inhibit the ability of certain DNA-damaging chemicals to cause mutations in bacteria. How might this kind of "anti-mutagenic" activity be important in cancer prevention? Molecular geneticists now know that most if not all human cancers carry mutations in one or more genes that control the rates at which individual cells divide, differentiate, or die. According to current thinking, various combinations of mutations that upset this delicate balance to favor uncontrolled cell growth can then enable this irreversibly damaged cell to form a primary cancer in the lung, liver, blood, bone, skin, or another body organ. Therefore, it seems at least theoretically possible that the anti-mutagenic power of the chlorophylls might allow them to inhibit or reduce the formation of cancers in humans. Recent progress in our laboratory and elsewhere has brought this promise closer to realization.

People in certain parts of Africa, China, and other developing countries with similarly warm, damp climates have the highest rates of liver cancer in the world. The two major risk factors are chronic hepatitis B viral infection, and exposure to aflatoxin B1 (AFB1) in the food supply. People exposed to both factors are at extremely high risk for liver cancer. Peanuts, corn, rice, and other grains and nuts stored under warm damp conditions can be infected with the mold Aspergillus flavus, which produces AFB1 as a secondary metabolite. AFB1 is one of the most potent cancer-causing chemicals, or carcinogens, ever discovered. Interestingly, AFB1 came to be recognized as a potential human liver carcinogen only after it was identified as the cause of outbreaks of liver cancer in rainbow trout hatcheries in the Pacific Northwest in the 1960s.

Much of that pioneering work was carried out at Oregon State University by Professor Russel Sinnhuber who immediately recognized the promise of the rainbow trout as a model of exquisite sensitivity for the study of liver cancer. Postdoctoral fellows and graduate students in my laboratory have been using this model for the past 12 years in a search for means to reduce AFB1-based liver cancer risk.

Dr. Roderick Dashwood, a postdoctoral associate who came to my lab in 1986, became interested in chlorophylls. Although their anti-mutagenic activity in bacterial assays was then well known, no one knew if chlorophylls could have a protective effect in animals. Rod discovered that rainbow trout fed AFB1 together with chlorophyll chlorophyllin, a simple water-soluble chlorophyll derivative, had greatly reduced damage to their liver DNA compared to trout receiving AFB1 alone. Would this reduce liver cancer development? That question was answered by a Ph.D. student, Vibeke Breinholt, who showed that even very modest dietary levels of chlorophyll chlorophyllin, roughly equivalent to the chlorophyll in one small helping of spinach, strongly reduced liver cancer in trout co-fed AFB1. Vibeke's results also showed clearly that this reduction could be directly attributed to reduced AFB1-DNA damage in the liver. These very exciting findings were the first ever to reveal a true cancer-protective effect by chlorophylls.

Several important questions now remained before these findings might be taken to human trials: Was the effect unique to trout or would chlorophyll chlorophyllin inhibit cancer in other animals? How did the cancer inhibition come about and would this mechanism likely apply to AFB1-exposed humans? Could chlorophyll chlorophyllin inhibit cancers other than liver or caused by carcinogens other than AFB1 -- that is, might it have a potentially broader applicability? Would native chlorophylls in the plants we eat be as effective as the chlorophyll chlorophyllin derivative? The answers to most of these questions are now known. Rod Dashwood, presently at University of Hawaii, found that chlorophyll chlorophyllin in the drinking water could strongly reduce colon cancer development in rats exposed to heterocyclic amines, which are potent carcinogens isolated from meats broiled at high temperature. Others found similar protection against skin tumors in mice painted with polyaromatic hydrocarbons, and we have shown protection against stomach and liver cancer in trout treated with a carcinogenic hydrocarbon found in tobacco smoke. Subsequent work by Vibeke, Michael Schimerlik, and Tetsu Hayashi showed that chlorophyll chlorophyllin associated tightly with AFB1, even in the acidic environment of the stomach and at the temperature of the human body, which most likely explained the ability of chlorophyll chlorophyllin to greatly reduce bioavailability or uptake of AFB1 from the diet. John Groopman and Tom Kensler two colleagues at Johns Hopkins University, found that dietary chlorophyll chlorophyllin was as effective at preventing AFB1-DNA damage in the liver of rats as it was in trout. Such a simple and safe protective mechanism was almost sure to apply to humans!

Based on these findings and the known safety of chlorophyll chlorophyllin, the National Institute of Environmental Health Sciences recently funded a research grant for Drs. Kensler, Groopman, and me to conduct a chlorophyll chlorophyllin intervention trial in a region of China where people are unavoidably exposed to high levels of AFB1 in their diet. In August I ventured to the little town of Daxin where Tom and I, with the help of local physicians from the Qidong Liver Cancer Institute, initiated the trial.

After screening 500 volunteers, over 200 people were identified with high levels of chronic AFB1 exposure. Of these, 90 people will receive a green sugar pill and 90 will receive a green chlorophyll chlorophyllin tablet with each meal for four months. (The samples are all coded and nobody knows who gets what until the code is revealed at the very end). Blood and urine samples are being collected every second week. By analysis of these samples we hope to tell if chlorophyll chlorophyllin alters AFB1 uptake and liver DNA damage in people as it does in trout and rats. The experiment can detect a reduction of 20% or greater, and, of course, this is what we hope to see. On a personal note, those of us trained in the basic sciences rarely have an opportunity to see our work applied directly to the reduction of human disease and misery. It would be rewarding indeed to see the trout model applied full circle from the discovery of a major form of human cancer risk, to the discovery of a simple means for its prevention. By this time next year I hope to be able to tell you how this turns out.

The Outcome Follows 11.28.01 chlorophyll chlorophyllin Reduces Aflatoxin Indicators Among People At Risk For Liver Cancer

A study conducted by researchers at the Johns Hopkins Bloomberg School of Public Health shows that taking chlorophyll chlorophyllin greatly reduces the levels of aflatoxin-DNA damage byproducts in the body, which are indicators of exposure to carcinogenic aflatoxins and increased risk of liver cancer. chlorophyll chlorophyllin is a derivative of chlorophyll and is used as an over-the-counter diet supplement and as a food colorant. The results appear in the November 27, 2001 edition of Proceedings of the National Academy of Sciences.

“Our study shows that taking chlorophyll chlorophyllin three times a day reduced the amounts of aflatoxin-DNA damage by 55 percent, compared with taking a placebo,” says Thomas Kensler, PhD, professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health. “Taking chlorophyll chlorophyllin or eating green vegetables, like spinach, that are rich in chlorophyll may be a practical way of reducing the risk of liver cancer and other cancers caused by environmental triggers,” explains Dr. Kensler.

Dr. Kensler and his colleagues conducted a double-blind study among residents of Qidong, China. The people of the region have an extraordinarily high rate of liver cancer, which is due in part from routinely eating foods contaminated with carcinogenic aflatoxins. The aflatoxin is produced by molds found in foods like corn, peanuts, soy sauce, and fermented soybeans.

For the study, researchers recruited 180 healthy adults. Half of the group was given 100 mg tablets of chlorophyll chlorophyllin to take three times a day with meals for four months. The other half was given a placebo. Urine and blood samples were taken over four months to determine the effects of chlorophyll chlorophyllin on excretion of aflatoxin-DNA damage products.

According to the study’s results, the people who took chlorophyll chlorophyllin showed a 55 percent reduction in aflatoxin-DNA damage, compared to the placebo group.

“Studies conducted by our co-author, George Bailey of Oregon State University, have suggested that chlorophyll chlorophyllin acts as an ‘interceptor molecule’ to block the absorption of aflatoxins and carcinogens in the diet,” explains John Groopman, PhD, professor and chairman of the Department of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. “Our study shows that chlorophyll chlorophyllin can effectively reduce aflatoxin levels, which should reduce the risk of liver cancer. Since chlorophyll chlorophyllin is found in many foods or can be easily added to the diet, it could be a safe and effective prevention method. The study adds to the evidence that green vegetables contain effective anticarcinogens,” adds Dr. Groopman.

Follow up studies are planned to determine whether this early protective action of chlorophyll chlorophyllin extends to either delay the onset or reduce the incidence of liver cancer.

Patricia Egner, Jin-Bing Wang, Yuan-Rong Zhu, Bao-Chu Zhang, Geng-Sun Qian, Shuang-Yuan Kuang, Stephen J. Gange, Lisa P. Jacobson, Kathy J. Helzlsouer, George S. Bailey, John D. Groopman, and Thomas W. Kensler assisted in the research and writing of the article “chlorophyll chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.”

The study was funded by grants from the U.S. Public Health Service, National Institute of Environmental Health Sciences.

Note: This story has been adapted from a news release issued for journalists and other members of the public. If you wish to quote any part of this story, please credit Johns Hopkins University Bloomberg School Of Public Health as the original source.

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