Acai juice, milk thistle, green tea, resveratrol, brown rice, grape seed extract, bitter melon and more
In April, 1971, ping pong player Glenn Cowan missed the U.S. team bus after a practice in Nagoya, Japan. A Chinese player waved him onto their waiting bus and the rest is history: In what has become known as Ping Pong Diplomacy, a delegation of America’s best players toured China, where they were treated like royalty and roundly thumped in exhibition matches against unseeded Chinese athletes. After the visit, relations between the countries thawed. Nixon visited the following year. And in the late 1970s, restrictions on emigration from China were eased and Chinese relocation to the United States skyrocketed.
Unfortunately, when Chinese women moved to the United States, their chance of developing breast cancer moved as well. Women in the United States have more than five times the breast cancer risk of women in China – 101 cases per every 100,000 people compared with only 18.7 per 100,000 in China. And here is the important part: when a woman of Chinese descent moves to the United States and adopts a Western lifestyle, she adopts a Western risk of breast cancer as well. It’s not genetics. Something in the difference between life in China and life in the U.S. affects breast cancer risk.
The question is, what is it? Is it something in the Chinese diet? A feature of traditional Chinese medicine? Is it air quality or social structure or the angle of the sun in China that protects Chinese women from breast cancer? More broadly, if something “natural” protects these Chinese women, could the same thing protect you against cancer…or even cure the disease?
GOOGLE SAYS YES
All it takes is a quick Google search to discover that the answer is a resounding yes… and that Western medicine has been hiding the truth for years. “Wasabi has powerful anti-cancer properties but can be difficult to fit into your diet,” says Dr. Oz. “Miracle cannabis oil may treat cancer,” writes SF Weekly. “Beat cancer with 35 percent hydrogen peroxide,” writes Natural News. “Carla received a death sentence in 1958, yet 54 years later she is in vibrant health, thanks to the Gerson Diet!” says the Gerson Diet website. “Frankincense oil shown to kill cancer and boost immunity,” writes someone called Dr. Eric Z, in an article that has been shared on Facebook more than 11,000 times.
“I was very excited back in the 1980s about the idea that we could find particularly potent ingredients or compounds in natural products that we could give to people as drugs and thereby reduce cancer risk. It hasn’t worked. And we have scores of failures,” says Tim Byers, MD, MPH, associate director for cancer prevention and control at University of Colorado Cancer Center. Byers recently chaired a major symposium at the annual meeting of the American Association for Cancer Research that he describes as “a post mortem on the first generation of chemo-prevention studies.”
Despite the internet’s hopeful claims, not one “natural” product has been definitively shown to treat cancer or decrease cancer risk. But Byers doesn’t see past failures as a reason to give up the search. Here are four ways researchers here and elsewhere are searching for natural products that could treat or prevent cancer:
1. GIVE A NATURAL PRODUCT TO CANCER PATIENTS AND SEE IF IT WORKS
Here’s an idea: what about giving a natural product to a group of cancer patients and seeing if it works? Believe it or not, this has been done in very controlled circumstances at the CU Cancer Center. See, in many slow-growing cases of prostate cancer, the best course of care is to watch and wait. And while watching and waiting, the reasoning went, it certainly couldn’t hurt to drink commercially available acai juice.
“Acai is a fruit rich in bioflavinoids shown to induce apoptosis in preclinical studies of prostate cancer, leukemia, and esophageal cancer,” write CU Cancer Center researchers Elizabeth Kessler, MD, Elaine Lam, MD, and colleagues. In other words, it worked in a dish and because it is not likely to do any harm, why not give it a try?
The researchers are planning a couple more experiments this spring. In early results, of the 21 patients treated on a clinical trial, all of whom had rising PSA (a measure of growing prostate cancer) prior to entering the study, 18 patients saw the rate at which their PSA was increasing slow down. One patient who entered the trial with a PSA of 12.57 had a PSA of 2.15 after 36 weeks of acai juice. In the world of cancer research, these early results are promising but still require additional validation before acai juice can be recommended broadly.
2. GIVE A NATURAL PRODUCT TO A HUGE POPULATION AND SEE HOW MANY LATER DEVELOP CANCER
In an ideal world, here’s how a cancer prevention trial would work: You would ask 100,000 people to drink acai juice and ask 100,000 people to drink an equal quantity of water, and you would note how many people in each group got cancer. Twenty years later, if the acai group had 2,300 cases of cancer while the water group had 2,400, you might have evidence that acai prevents cancer.
Unfortunately, that’s what it takes: It may require treating 100,000 people to prevent what would otherwise have been 100 additional cases of cancer. And if there is any chance at all that acai juice has even the mildest of side-effects, it wouldn’t be ethical to treat this massive number to prevent these few cases. Does the risk outweigh the reward?
“A great example is anti-inflammatory drugs and colon cancer risk. We did a trial and it was big enough to show beneficial effects on colon polyp development, but we also saw increases in heart attacks. Do you want to trade having fewer colon polyps for more heart attacks? Not me,” says Byers.
Many possible cancer preventions come with risk, and with human patients, the math doesn’t justify the chance. For this reason, the most successful cancer prevention trials have been trials of things that don’t actually go in your body, namely education. Or they are for things we already know are good for you, for example exercise, weight loss or a healthy diet.
3. ASK THE COMPUTERS
Imagine you have 100,000 women in the United States and 100,000 women in China. What are the lifestyle differences between these women? Which lifestyle differences affect cancer risk? This is a question not even a supercomputer can answer.
“You just can’t disentangle genetics from all the cultural factors. So far our weak, feeble attempts to pull out any single agent haven’t been successful. Is it the green tea? Or differences in obesity or physical activity? Or any one of thousands of other confounding factors?” Byers asks.
Instead, researchers are on the lookout for what are called “natural experiments” in which something specific and random happens to change a population’s behaviors. If a potato blight struck Idaho, forcing Americans to snack on fried grasshoppers instead of chips, and our rate of colorectal cancers declined immediately and dramatically, the natural experiment might tell us something about the health benefits of chips compared with grasshoppers. Or take natural experiments in cancer screening: Chance factors tied to health insurance access means that some people are screened and others are not, and cancer mortality tends to be lower in the screened populations (due in part to early detection).
These natural experiments can accidentally create situations in which research is possible. But to date, no convincing natural experiments have been uncovered to test the effectiveness of prevention or treatment with natural products; there has been no accidental shortage in green tea or ability for one community to eat bitter melon while a neighboring community cannot.
4. PICK APART THE BIOLOGY
Instead of restricting the use of natural products to watch-and-wait situations, or dreaming of the day we can run a 100,000-person prevention trial, or waiting for a natural experiment to divide a population into unintentional treatment and non-treatment groups, researchers at the CU Cancer Center and elsewhere are flipping the workflow of natural cure research: Instead of working from populations backward to find the product that might fight cancer, researchers at CU are starting with promising natural products and picking apart the chemistry just like a laboratory would treat any man-made pharmaceutical.
If there is a natural cure for cancer, it may come from the laboratory of Rajesh Agarwal, PhD, professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, and co-leader Cancer Prevention & Control Program at the CU Cancer Center. Agarwal has built a career dissecting the molecules inside natural products such as milk thistle, grape seed extract and bitter melon.
“The whole idea here is whether there are modalities people use in their life, for different reasons, that could be useful in slowing the growth of cancer,” Agarwal says. “If we try to do a study without knowing the mechanism of how a product works, you can spend many millions of dollars and you don’t know what you’re going to get out of it. We ask if these things are good in preclinical studies in test tubes and experimental animals, then go from there.”
For example, Agarwal writes papers with titles like, “Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells” and “Silibinin inhibits aberrant lipid metabolism, proliferation and emergence of androgen-independence in prostate cancer cells via primarily targeting the sterol response element binding protein 1.”
Don’t worry. You won’t be tested on comprehension. What these papers show is Agarwal’s appreciation that it will be impossible to prove that natural products treat cancer until we can show how they treat cancer. What does grape seed extract do? It messes up the mitochondria of head and neck cancer cells. What does the chemical silibinin, derived from milk thistle, do? It keeps prostate cancers from burning fat and also from losing their dependence on androgen.
Proving these mechanisms eventually helps to make the case for clinical trials in humans to actually test these treatments. Dr. Agarwal is currently building the case for clinical trials for grape seed extract to treat the watch-and-wait situations of prostate cancer with rising PSA and also colorectal cancer in which polyps have been surgically removed.
The science is solid. Time will tell if these chemicals that work so well in the lab also work in human cancer patients.
GREEN TEA FOR BREAST CANCER?
“The evidence regarding the potential benefits of tea consumption in relation to cancer is inconclusive at present,” writes the National Cancer Institute. But deep in the laboratories of the CU Cancer Center, a pair of researchers is unearthing a very different and quite compelling story. If you’ve stuck with this admittedly difficult science article so far, stick with it a bit further. Here’s the story:
Estrogen receptor-positive (ER+) breast cancer is commonly treated with the drug tamoxifen, which restricts the cancer cell’s access to the estrogen it needs to grow and survive. But 30 percent of ER+ breast cancers do not respond to tamoxifen. Why?
Hany Abdel-Hafiz, PhD, and Kathryn Horwitz, PhD, have part of the answer – an important difference between ER+ breast cancer cells that respond to tamoxifen and those that don’t. It’s not a genetic mutation; there’s no known difference in the genomes of resistant and sensitive cells. The answer is in something called the epigenome. The epigenome doesn’t change a cell’s genes, but it helps to decide which genes are turned on or off. If genes are blueprints, the epigenome is the general contractor that chooses how to use them. There are epigenetic changes that make ER+ breast cancers resistant to tamoxifen.
Importantly, changes in the epigenome are reversible.
“If epigenetic changes create tamoxifen resistance, then it is reasonable to suggest that reversing the epigenetic changes will restore tamoxifen sensitivity,” says Abdel-Hafiz.
Is there a switch? Could we flip breast tumors from estrogen-independent to estrogen-dependent and resensitize them to tamoxifen? We can in the lab. It takes about two cups of warm but not boiling green tea.
Abdel-Hafiz has isolated the active ingredient from a green tea extract and shown that in a tamoxifen-resistant ER+ breast cancer cell line, it resensitizes the cells to tamoxifen. In other words, a compound in green tea – comparable to drinking two cups – transforms breast cancer cells from treatment resistant to treatment sensitive ones.
“In Egypt, where I am from, people drink a great deal of dark tea. But it is prepared by five-to-ten minutes of boiling. This degrades the active ingredient,” says Abdel-Hafiz. “The Chinese and Japanese, possibly from centuries of folk knowledge, understand this. They know to prepare green tea in hot but not boiling water to maximize its health benefits. That is the way I prepared a green tea extract in the lab.”
Is 80-degree Celsius green tea the secret to the long-sought difference in breast cancer rates between the United States and China?
“There’s a long list of things that reduce risk in lab models of cancer that don’t appear to work in humans,” Byers says. “And there’s an even longer list of cancer drugs that seemed promising in the lab that didn’t pan out in people.”
But there are also reasons why many of these natural (and other) drugs haven’t proven effective.
“We discover that we have used the wrong product in the wrong population with the wrong cancer and have evaluated the wrong measure of success,” says Agarwal. He points out that after the CU Cancer Center wrote about his work with bitter melon juice last year, he has had more than 500 phone calls and emails from patients using or interested in using bitter melon with their cancers, “many of whom report their tumors are shrinking,” Agarwal says.
Chocolate is a drug. Coffee is a drug. Why not acai juice, milk thistle, green tea, resveratrol (from red wine), brown rice, grape seed extract, or bitter melon? There’s no solid science saying yes, but there’s also no absolute evidence saying no. And in the absence of answers, there is certainly hope that a natural product could prevent or treat cancer.
“For sure in my lifetime a natural substance will be proven to be a treatment or prevention for cancer,” Agarwal says.
For now, choosing to dose yourself with bitter melon or another natural product rather than following a doctor’s recommended course of cancer therapy is much more likely to be a death sentence than a cure. But in many cases, there is no harm in adding natural products in addition to your doctor’s prescribed course of therapy (consult your physician).
At the CU Cancer Center we will do more than hope – here, we continue to apply the best modern research techniques to analyze and test what are sometimes ancient medicines. The jury is still out on a natural treatment or prevention for cancer. And until there is a verdict, we will continue to gather evidence.