Diet, serum levels of fatty acids, and risk for prostate cancer


An article just published on-line in the American Journal of Epidemiology has suggested that a diet high in at least one of the omega-3 fatty acids may be good for your heart but less good for your prostate.

Brasky et al. used data from nearly 3,500 of the original participants in the Prostate Cancer Prevention Trial (PCPT) to study whether there was any association between risk for prostate cancer and the levels of omega-3, omega-6, and trans-fatty acids (TFAs) in the patients’ serum. Elevated levels of these types of fatty acids are known to be associated with prostate inflammation, and inflammation of the prostate may be one element of importance in the development and progression of some types of prostate cancer. Information about this study is also available in a media release issued by the Fred Hutchinson Cancer Research Center.

According to Dr. Brasky, “”We wanted to test the hypothesis that the concentrations of these fats in blood would be associated with prostate cancer risk. Specifically, we thought that omega-3 fatty acids would reduce and omega-6 and trans-fatty acids would increase prostate cancer risk.”

Things seem to have turned out a little differently.

The study used a case-control methodology in which data from 1,658 participants in the PCPT who were known to have prostate cancer (the “cases”) were compared to data from 1,803 PCPT participants who did not get a diagnosis of prostate cancer (the “controls”). The cases and the controls were carefully matched to each other on the basis of age, treatment, and family history of prostate cancer. For all cases and controls, phospholipid fatty acids were extracted from stored serum samples, and concentrations of omega-3, omega-6, and TFAs were assessed and reported as proportions of the total amount of phospholipid fatty acid.

The results of the study were as follows:

  • There was no apparent association at all between fatty acid levels and risk for low-grade prostate cancer.
  • There was a positive association between levels of docosahexaenoic acid (DHA, an omega-3 fatty acid) and risk for high-grade disease.
    • Men with the highest serum levels of  DHA were 2.50 times more likely to be diagnosed with high-grade prostate cancer than men with the lowest DHA levels.
  • Conversely, there was a negative association between levels of TFAs  and risk for high-grade disease.
    • Men with the highest serum levels of TFA 18:1 were 1.82 times less likely to be diagnosed with high-grade prostate cancer than men with the lowest TFA 18:2 levels.
    • Men with the highest serum levels of TFA 18:2 were 2.08 times less likely to be diagnosed with high-grade prostate cancer than men with the lowest TFA 18:2 levels.

These findings are exactly the reverse of the originally projected findings of the study. To quote Dr. Brasky again, “”We were stunned to see these results and we spent a lot of time making sure the analyses were correct. Our findings turn what we know — or rather what we think we know — about diet, inflammation and the development of prostate cancer on its head and shine a light on the complexity of studying the association between nutrition and the risk of various chronic diseases.”

Omega-3 fatty acids are a common component of a diet high in oily fish like salmon. The omega-3 fatty acids are known to be good for heart health, and the average American is about 20 times as likely to die of a heart problem than he is of prostate cancer. It would probably be a serious mistake for people to start taking radical action on the basis of this single study. Indeed, Dr. Brasky is very specific in stating that, “Overall, the beneficial effects of eating fish to prevent heart disease outweigh any harm related to prostate cancer risk,”

The (not entirely surprising) message from this study is that the relationships between diet, nutrition, levels of particular metabolites in serum, and risks for specific disorders like heart disease and prostate cancer are probably a great deal more complex than most of us would like to think. There is little doubt, however, that this study is going to stimulate some rather more sophisticated attempts to understand the relationships between diet, serum levels of the phospholipids, and risk for a number of different disorders — including high-grade prostate cancer.

15 Responses

  1. I have family history of prostate cancer. One of the things I have done to try to reduce my risk of prostate cancer is to take omega-3 supplements in an effort to achieve a ratio of omega-3:omega-6 fatty acids near 1:1 (or at least 2:1). I am doing this based on a suggestion from Dr. Strum on P2P.

    I wonder whether I should stop the omega-3 supplements (while continuing to eat a healthy diet)?

  2. Dear Chamorgadol:

    Rather than taking immediate action, I think the sensible thing is to bring the paper by Brasky et al. to the attention of your doctors and ask them what they think. Clearly, whatever else you do, you want to maintain a heart healthy diet. As Dr. Brasky himself notes, the benefit of omega-3 fatty acids on heart health probably far outweighs the possible risks associated with aggressive forms of prostate cancer.

  3. I’m wondering if the omega-3 source (plant versus animal) is accounting for the unexpected finding of a higher risk associated with omega-3 fatty acids. For many years Dr. Charles “Snuffy” Myers, with his background not only as a medical oncologist specializing in prostate cancer but also as one-time lead pharmacologist at the NIH, has been drawing a sharp distinction between these sources.

    He has advised that fish-based omega-3s are healthy for us for both prostate cancer and our hearts, but that plant-based omega-3s, which are not well processed by human males, are dangerous. He has even published a booklet that explains these points in detail (“Flaxseed: Panacea or Poison?”). He cites research showing that the alpha-linolenic acid (ALA) in flaxseed oil, canola oil, and certain other high ALA sources looks dangerous for prostate cancer patients.

    What I’ve noticed from Sitemaster’s article and the linked abstract and news release is that the serum samples were all from participants in the Prostate Cancer Prevention Trial, which was reported in 2003 after a median follow-up of about seven years, as I recall it — may be off a bit there. That means that the samples almost certainly were taken in the mid to late 1990s. Back in that period, flaxseed oil was a popular supplement, and some brands touted its value for the prostate. It’s possible that some of the men in the trial were consuming flaxseed oil supplements. If so, according to Dr. Myers, they would have been fueling any existing prostate cancer.

    The sources reporting this study note that not many men in the study were taking fish oil supplements but instead were eating fish. I’m curious whether the researchers looked at plant versus animal sources of omega-3s. Does anyone know whether omega-3s found in serum samples can be distinguished as to their source? Does anyone know if fish-based Omega 3s would be absorbed and metabolized quickly, so that they would be less likely to show up in a serum sample; would the reverse be true for plant-based omega-3s?

    I take about 3,600 units of fish-oil daily as well as herring at lunch daily and fish at least a couple of dinners each week. I’ll be following this research with interest and poking around PubMed for complementary research.

    Thanks for posting this thought-provoking research.

  4. I’m curious why this study is not available to the public for free because it was funded by the NCI. Any insight about that?

  5. Thanks Sitemaster. Is the full-text paper available on line? I found only abstract and a press release. (I will run this by my doctor, though my guess is he will not have the specific expertise necessary to give me a well-informed answer — he is a nice guy and a good doctor, but as a generalist internal medicine doctor it is impossible to be an expert in everything.)

  6. Jim:

    The fact that a study was funded by the NCI does not require publishers to report the results for free. After all, the publisher didn’t get a grant from the NCI! Even the Journal of the National Cancer Institute doesn’t make all of it’s content available gratis.

  7. Chamorgadol:

    Your best bet would be to contact the named author (whose e-mail address is clearly provided on the abstract) and ask him if he could provide you with a PDF copy of the full paper for your personal use.

  8. Jim:

    As an addendum, I would be amazed if anyone was collecting detailed information on the sources of supplements being used by participants in the PCPT. I therefore would be most surprised to hear that anyone could tell you what subtypes of supplements were being used by the study participants.

    After all, most men wouldn’t even be able to tell you what type of fish they had been eating either. They would just know that they ate a significant amount of fish.

    I also doubt if most of the men in the PCPT were using flaxseed oil supplements. That sort of careful and selective use of supplements (whether wise or not) is something being carried out by a relatively small percentage of prostate cancer patients.

    Finally, please remember that the men enrolled into the PCPT were all cancer-free at the time of initial enrollment, so very few of them would have been doing anything sophisticated to try to prevent prostate cancer (except for taking the finasteride or the placebo they were given as part of the trial).

  9. Hi Sitemaster:

    I’m taking your suggestion and have sent an email to Dr. Brasky.

    Regarding your post of 3:17 pm, I suspect too that there are no detailed records on supplements, but one can hope.

    However, I see a possibility for exposure to flaxseed oil (as a source of omega-3s among other nutrients) and subsequent disproportionate development of advanced cancer in the PCPT. Back in the 90s flaxseed oil was widely promoted for both men and women, including frequent mentions in magazines such as Prevention. Flaxseed oil was touted for all kinds of benefits. If the link between flaxseed oil and advanced prostate cancer is strong, which is at least plausible, it might only take a small percentage of patients in the PCPT taking flaxseed to show up as a relatively high proportion of the patients with advanced cases. I realize this is conjecture, but it might be testable, at least in a tentative way.

  10. THE COMPLETE BRASKY PAPER

    I’ve looked at the complete paper, which Dr. Brasky kindly provided, and, like the authors, I find the results “disconcerting.” The research looks well-done to me.

    Regarding DHA risk, I found the findings in the complete paper even more striking than the average reported in the abstract. Here’s the key statement from the full paper:

    “Compared with the lowest quartile, each quartile of percent serum DHA was associated with an approximate doubling of high-grade disease. In a post-hoc analysis contrasting quartiles 2–4 with quartile 1, the odds ratio for high-grade prostate cancer was 2.32 (95% confidence interval (CI): 1.33, 4.05).”

    I was also surprised with what appeared to be a lack of association of alpha-linolenic acid with low-risk or high-risk disease.

    Supplement use was not addressed in the study. I’m still thinking their might be a difference due to plant versus animal sources of omega-3 fatty acids.

    It would be helpful to have Dr. Myers’ review of this study.

    Once again, I’m impressed with the complexity of cancer.

  11. Jim,

    Can you e-mail me the paper?

    I think if this study holds water we will be seeing a lot of new book editions from the “experts” soon enough. We have already seen selenium, vitamin E, and now fish oil take a hit, not to mention that I’m saving $50.00 a month right there. … I guess that offsets the POM tab (which BTW I am not taking …).

  12. I think we need to be very clear that the “hits” against selenium and vitamin E were based on data from a large, randomized, double-blind, placebo-controlled clinical trial. Before we toss out the fish oil too, please remember that this may be doing a lot of good for your heart (as also noted by Dr. Brasky), and that despite your prostate cancer you are some 20 times more likely to die of a heart-related condition than a prostate-related one.

  13. Mike I agree.

    However, I think that supplementing comes with many unstudied risks. While it may show a good in one sense, it may also be bad in other areas including being counterproductive to to conventional therapies we are on for prostate cancer.

    When people start to exponentially increase such things through unstudied supplementation for anything, they are introducing more risk than if they ate a properly balanced heart healthy diet. People with heart risks need to talk to their cardiologists about supplementation with the same caution that we prostate cancer survivors would use to discuss supplementation with our oncologists. Perhaps it’s as simple as if you can prove that your body is deficient with a needed vitamin or mineral, then supplement first with dietary habit changes. Then if that is not effective enough consider sufficient supplementation ~ only enough to bring in safe levels in the blood that are acceptable.

    I know guys spending well over $100.00 per month on supplements. We are a study away from debunking the claims by well-known oncologists on fish oils. And if that study is true to this retrospective view, we could be doing more harm than good by excusing that it’s still good for the heart. If you are not experiencing heart problems and have good lipid panels, why take high doses of fish oil at all? And if you are experiencing issues with the heart, don’t do your own prescribing of supplements, talk to your doctor …

  14. Ah … Now that’s a whole different issue … As far as I am concerned most of the money being spent on supplements by the majority of people would be much better spent on a good diet and a gym club membership. Furthermore, I don’t believe that anyone should use significant amounts of supplements (fish oils included) without a careful discussion of the risks and benefits with a clinician who has some significant education in this topic.

    Supplements have their place in the grand scheme of things for some people, but self medication with these products can be dangerous, and the primary beneficiary is usually the person selling these products as opposed to the person buying them.

  15. PERSPECTIVE ON NEGATIVE (AND POSITIVE) RESEARCH ON OMEGA-3, SELENIUM, VITAMIN E, AND POMEGRANATE

    I’m still confidently taking fish oil and the other three as well. Of course we all have to make our own call on these issues, but here’s why I have not stopped.

    First, Sitemaster’s point about other health effects for greater threats is vital, especially for fish oil! Fish oil daily greatly reduces the risk for sudden death from heart attack, as well as having other cardiovascular benefits, and heart trouble is a far greater threat to our health and survival than prostate cancer. Yes, prostate cancer is a serious attack on our flanks, to use a military analogy, but we must not forget about the main force frontal assault!

    Second, you can find studies for and against virtually all of the nutrients. Some of us tend to see the world in black and white terms, instead of the shades of gray that is true reality, and the lack of absolute consistency may urge some of us to throw up our hands and damn the whole enterprise. But that’s not what we should do; the gray situations are a call to put our minds in gear! Some studies deserve far more weight than others, but almost all studies have limitations. Media reports are nearly useless, their chief value being to draw our attention to something that has happened and that may deserve our thought. Dr. Myers’ recent booklet “Flaxseed: Panacea or Poison?” is an excellent primer for laymen on separating the research wheat from the chaff; as you would guess from the title, he uses flaxseed and its oil as his main example. I look for the preponderance of quality evidence of various types in making my own decisions, keeping in mind important aspects of my individual situation. There is a lot of poor quality evidence in research papers that deserves no weight whatsoever (such as the PLCO screening trial results, and the need-to-treat statistic from the European ERSPC screening trial). On the other hand, well executed, randomized, placebo-controlled, and double-blinded Phase III clinical trials are strong evidence, especially if they are large with follow-up that is long-enough for to address the research question being investigated.

    I’ll add “lucky” to the list for a third point, as some clinical trials that looked well-conceived when launched run afoul of future developments that were hard to appreciate at the time of trial launch. The SELECT trial for selenium and vitamin E is a good example. When launched, the dose of 400 IU for vitamin E selected for the trial looked perfectly safe and was supported as a reasonable dose by such bodies as the Institute of Medicine. However, a few years into the trial, research indicated a low but serious risk of bleeding at that dose, a potential threat to life if a trial participant were in an accident or had surgery. Although a dose of 200 IU remains perfectly safe based on available evidence per expert opinion, the trialists had no way in their protocol to reduce the dose. Therefore, this problem alone would probably have been enough to derail the trial based on the “do no harm” principle (or at least, do less harm than you do good).

    However, the problem was compounded by a lack of effect from either vitamin E, selenium, or the combination, as seen by the review board that had access to the results prior to unblinding of results to the researchers. Most unfortunately, the forms of vitamin E and selenium selected for the trial were not good choices, in retrospect (actually in prospect too as some of us, including me, thought at the time that alpha-tocopherhol was a lousy choice for vitamin E). Even prior to trial launch the trialists were defending the choice for vitamin E as some research papers were suggesting that alpha-tocopherol alone was looking harmful in contrast to gamma- and other forms of vitamin E that appeared to be beneficial. I gained unsound reassurance from comments that gamma-tocopherol was not a good choice as it did not last long in the body and from my assumption that the tiralists must be making wise decisions in view of their thoughtful, formal, published consideration of clearly raised counter-arguments. The choice of the form of selenium was also unfortunate. My own solution was to reduce my own dose of vitamin E to 200 IU of high gamma- vitamin E daily and to keep taking a form of selenium that appeared to be beneficial. What the SELECT trial did a fine job in indicating was that the unfortunately chosen forms (selenium and vitamin E) and dose (vitamin E) were not beneficial and potentially harmful (the latter for vitamin E).

    A fourth point is that we need to be mindful of our individual health profile and biology. It now appears that vitamin E may interfere with statin drugs. Based on my test results, that does not seem to be a problem for me. My lipid results look fine, although perhaps they would be even better without the vitamin E, something I’m keeping in the back of my mind.

    Selenium may, per some far less than conclusive evidence from the finasteride prevention trial (the Prostate Cancer Prevention Trial — PCPT), slightly increase the risk of diabetes or insulin resistance in a few patients. I get tested at least annually for fasting glucose, and I’m fine; also, I have no signs of an insulin problem. Selenium’s value also now appears to have a genetic aspect, as Kantoff’s team is demonstrating. In considering whether to continue taking selenium, I considered that I was doing very well in dealing with a challenging case of prostate cancer, and I have been taking selenium from shortly after my diagnosis. Therefore, prior to a genetic test based on the Kantoff work that I may have someday, I’ll keep taking the supplement. (By the way, there is a toenail test that assesses the Se level versus an optimum level researched in dogs, but I don’t know what to make of a canine level as an indicator for men. While I’m glad the DoD’s CDMRP Prostate Cancer Research Program looked into this, I’ll pass on this one.)

    Quality pomegranate juice or extract is still looking like a hot prospect to me, and I’ve been taking an extract for a long time now. On the plus side, both the small UCLA trial (juice), which used a highly objective PSA doubling time endpoint and had very strong results, bolstered by results from extension of the trial for a few participants, and the Johns Hopkins trial (extract) had consistent and quite favorable results. Moreover, gene microarray testing has demonstrated likely favorable effects on many prostate cancer-related genes and signal pathways. On the possible negative side, the FDA slapped down POM Wonderful for overenthusiastic marketing. I’m with the FDA on that one, but the FDA’s action does not take away from the value of the well-done research. All this said, I’m not seeing a noticeable impact yet on my own PSA, especially at this point in my third off-therapy cycle. I attribute that lack of obvious impact to the facts that I started this journey with a challenging case (bPSA 113.6, Gleason 4 + 3 = 7, etc.) and still have an intact, functioning prostate, likely still with a lot of cancer (no radiation, no surgery, etc., just intermittent triple ADT for 11+ years). Still, I believe the extract is likely helping in important but subtle ways. Maybe the impact for me is to be able to continue to respond well on IADT3 at this point.

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