Dr. David Levy is a Clinical Associate Professor in the Department of Urology at the Cleveland Clinic.
Dr. Levy spoke to Prostatepedia about his clinical trial looking at the impact of vitamin D, curcumin, and Omega-3 fatty acids on prostate cancer.
Can you explain the thinking behind your clinical trial on vitamin D, Omega-3 fatty acids and curcumin in prostate cancer?
Dr. David Levy: Well first let me say there are a number of people involved in this program without whom it would not be where it is today.
I was extremely fortunate. When I finished my residency in Cleveland, I went to MD Anderson Cancer Center in Houston, Texas to do a cancer fellowship.
At that time, we didn’t really understand why cancer occurs and how to treat it. The attitude was: “Cut it out. Radiate it. Give chemo.”
We’re now twenty years down the road and while medical knowledge has advanced tremendously, what are we still doing? Cut it out. Give radiation. Give chemo. People with cancer keep coming and coming. It’s like a conveyor belt. They don’t stop.
About five years ago, I bought an abandoned farm here in Northeast Ohio. The goal was to make it an organic certified produce farm, which I did over three years. In learning about the process to make our farm certified organic, I had to review all the pesticides and chemicals that had been put into the soil and what we had to avoid for over three years to gain the certification. With all these pesticides and chemicals come known side effects.
There is a journal called the Journal of Organic Sciences, which ran a 25-page article on the use of a very common weed killer. Going back to the 1970s, there is a direct correlation of the increased use of this weed killer in commercial agriculture with an increase in liver cancer, colon cancer, kidney cancer, kidney failure, lymphoma, leukemia, thyroid, and prostate cancers. Every cancer went up. They all paralleled the increased use of this common weed killer.
When I read that article, I started to think that there has to be some correlation between environmental exposure and cancers. I started to ask: If you change the environment in which the cells live, do you change their behavior? That has been studied a few times and the results published. Studies have shown the influence of vitamin D on prostate cancer behavior, the impact of Omega-3 and Omega-6 fatty acid ratios on prostate cancer behavior, and the impact of turmeric curcumin on biochemical pathways in the cells. I was thinking about all of that as I came to design the trial.
If you look at populations across the world, prostate cancer rates vary quite dramatically. India, China, and Japan have some of the lowest rates of anywhere in the world. The rate in India is 25 times less than that in the United States, England, France, Germany, Norway, Sweden, or Finland. Why is it that? Men in India all have testicles and testosterone and prostates, but they don’t have prostate cancer. The same goes for Japan and China.
There are pretty interesting differences in terms of the eating habits of these populations and the disease processes that are common in the societies.
It turns out, as far as we can tell, that meat and dairy feed prostate cancer. What do we see in this country on NFL Sunday? What do they serve? They serve hot dogs, French fries, chicken fingers, chicken nuggets, chicken wings, and hamburgers. All of these foods are very high in Omega-6 fats. No one goes to the ballpark to get a bag of broccoli. That doesn’t happen. No one goes there to eat apples.
When we look at our society in terms of the food choices, the foods that are heavily advertised are fast foods, pizzas, and sodas. High sugar loads, high glycemic index foods, and animal fats are all very well correlated with prostate, breast, pancreatic, and colon cancers.
I looked a little further into vitamin D and asked, “Is there a correlation with vitamin D and prostate cell behavior?”
It seems there is. One published study looked at 71,900 men—which is a pretty substantial population—for six and a half years. They found that the lower the vitamin D levels in the blood, the higher the patients’ PSAs, the higher the likelihood of a positive prostate biopsy, and the more aggressive their cancers.
Another vitamin D study published by the SEER committee, which is a national organization that correlates hospital reported statistics throughout the country, looked at 20,000 men. Again, they found low vitamin D, higher PSA, and higher odds of a positive prostate biopsy with significant disease.
Other studies correlate vitamin D levels with prostate cell behavior. It turns out that vitamin D binds on the prostate cell to the androgen receptor. That is where testosterone binds, and testosterone is the main food for prostate cells. Vitamin D binds to this receptor as well. As best we can tell, with low vitamin D levels, the prostate cell machinery churns along like a steel furnace. When the vitamin D levels go up, something happens to the cells’ metabolic rates
Across the country, almost all of the residents of the states north of South Carolina border and from East to West
Coasts are low in vitamin D. I haven’t tested anybody here in Cleveland in almost three years with a normal vitamin D level.
What about turmeric curcumin?
Dr. Levy: Tumeric is used in curry and it contains curcumin. Curcumin is a really good anti-inflammatory. It’s a naturally occurring COX-2 inhibitor. (Celebrex was a COX-2 inhibitor.) It turns out that curcumin has a far greater impact on the biochemistry of cells than just an anti-inflammatory. Curcumin impacts what is called the Hypoxia-inducible factor 1-alpha. This is a factor made in the cells that is involved in their ability to recruit new blood vessels to get more oxygen and more nutrients. Curcumin disrupts that cycle.
Curcumin disrupts the mesenchymalepithelial cell transformation. The mesenchymal-epithelial cell transformation is a process that allows cells to gain the ability to climb outside the prostate and spread to the lymph nodes and bones. Curcumin also impacts the diclofenac acid pathway, which is part of the cell’s Omega-6 metabolic pathway.
There are new publications that show curcumin increases cellular sensitivity to radiation treatment. There are some studies that show it increases the cell’s susceptibility to chemotherapy.
There are over 300 publications in the National Library of Medicine on curcumin and prostate cancer right now. When I started this work about 3. years ago, there were 13 publications on curcumin and prostate cancer. There were so few publications I couldn’t even include them in my suggested regimen to patients. Now, there’s no way we can ignore it.
In my opinion, to not include curcumin would be a disservice to patients because it has such a tremendous impact on cellular behavior without being toxic in any way to the kidneys, the liver, the intestinal system, or the cardiovascular system.
There are very few reported side effects of dosing curcumin. Patients have taken as much a 6 grams per day in capsule form in a study protocol to impact their prostate cancer. We give 2,000 milligrams per day, and in 27 months have not seen any side effects that would curtail our continued use of the supplement.
Are you giving men vitamin D, omega-3 fatty acids, and curcumin all at the same time and then measuring the outcome, or are you separating them out into different groups?
Dr. Levy: No. We’re giving them all together.
After you give patients a combination of the three supplements what kinds of measurements are you doing?
Dr. Levy: We measure the fatty acid ratios in the body. We measure the three individual components of the fish oil:
EPA, DHA, and DPA. We measure the Omega-3/Omega-6 ratios in the blood. We measure linoleic acid levels in the blood. We measure vitamin D levels, and then titrate their doses to get vitamin D levels up to our target range.
There is nothing you can do to measure curcumin except give the dose of the appropriate manufacturer’s preparation.
We spent a lot of time figuring out what was going to get to the cells most efficiently.
And of course, we change the diet.
But the end point of our study is genetics. We do a tissue biopsy at the time of diagnosis. Then the men go on nutrition modification and supplements for a minimum of nine months. After nine months, we repeat the prostate biopsy and do a side-by-side genetic comparison of the prostate tissue from before the diet and supplements regimen with the tissue from after the diet and supplements regimen. Then we see what kinds of changes we have caused by changing the environment in which the cells live.
What kind of patients are you looking for?
Dr. Levy: For the purposes of this genetic study, we are specifically looking at people with low-risk prostate cancer who are on active surveillance or who are candidates for active surveillance.
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