Finding a Healthy Dietary Ratio for Prostate Cancer Prevention
Division of Cancer PreventionThe leading cause of mortality for the 10 percent of patients who develop recurrent or refractory (treatment resistant) prostate cancer is due to the progression of prostate cancer to androgen independence — the ability of the tumor to grow even in the absence of androgens, hormones that can stimulate the growth of prostate cancer cells. Strategies that prevent this progression are greatly needed, and early studies conducted by Linda A. deGraffenried, Ph.D., Associate Professor and Associate Chair of the Department of Nutritional Sciences at The University of Texas at Austin, demonstrate how the mammalian target of rapamycin (mTOR) — a protein regulator of cell growth — could play a role in controlling the progression of prostate cancer to androgen independence in animal models.
Several anti-cancer agents that target the mTOR pathway are currently in clinical development. “Because the mTOR pathway is regulated by growth factors and nutrients, this suggests that natural dietary interventions could also have protective effects against cancer through regulation of this pathway,” said Dr. deGraffenried. “We set out to examine the impact of a variety of dietary interventions that could prove beneficial for prostate cancer patients by targeting this pathway, including omega-3 and omega-6 fatty acids*.”
Omega-3 and omega-6 fatty acids are found naturally in the human diet through the consumption of cold water fish, and seeds and nuts and the oils extracted from them, respectively. In a preliminary study using an in vitro model of androgen suppression, Dr. deGraffenried and colleagues discovered that the balance between omega-3 and omega-6 fatty acids plays a role in affecting the progression of prostate cancer**. Specifically, the omega-3 fatty acid docosahexaenoic acid (DHA) effectively delayed the progression of prostate cancer cells to an androgen-independent state, whereas the omega-6 fatty acid arachidonic acid (AA) promoted disease progression. “Additionally, this delay in progression to hormone-refractory disease was mediated in part through inhibition of the mTOR signaling pathway,” said Dr. deGraffenried.
The American Heart Association (AHA) recommends an omega-6 to omega-3 ratio of 10:1; unfortunately, those on a Western diet eat too much omega-6 and not enough omega-3. “In men consuming a Western diet, the ratio is approximately 46:1 because omega-6 levels are high in processed foods; in the Asian diet, on the other hand, the ratio is 1.3:1 because omega-3 levels are high in fish,” said Dr. deGraffenried. “And if you look at the incidence of both breast and prostate cancer in the Asian population, it is very, very low.”
From a dietary perspective, Dr. deGraffenried and colleagues are trying to determine the best fatty acid ratio for preventing the progression of prostate cancer in patients. Specifically, does the AHA recommendation (10:1) provide the same benefit for prostate cancer as it does for cardiac protection? Or is the Asian diet ratio (1.3:1) required for maximal protection?
Early in vivo data suggest that the AHA recommendation of 10:1 provides the same protective benefit for prostate cancer as does an Asian diet. “In addition, our data shows that (blood) serum levels serve as effective surrogate markers as they closely reflect the levels of fatty acids that are getting into the tumors,” said Dr. deGraffenried.
The challenge, however, is getting patients to modify their fatty acid ratio from 46:1 to 10:1 through diet alone because eating patterns are notoriously difficult to overcome. “The strategy will be to provide fatty acid supplements to patients based on their serum levels, and to adjust the supplements as needed over time to maintain the proper ratios,” said Dr. deGraffenried.
NCI Division of Cancer Prevention Program Director Young Kim, Ph.D., commented, “Dr. deGraffenried’s group is revealing the mechanisms by which an omega-6 to omega-3 fatty acid ratio affects the outcome in prostate cancer patients. This information will be important for the development of effective dietary intervention strategies that improve overall survival.”
* Grant number: 5R01CA118962-05
** Friedrichs, W., Ruparel, S.B., Marciniak, R.A., & deGraffenried, L. (2011). Omega-3 fatty acid inhibition of prostate cancer progression to hormone independence is associated with suppression of mTOR signaling and androgen receptor expression. Nutrition and Cancer, 63(5), 771-777.